Carbon chain substance for regulating transmembrane transport and fluidity of cell membrane, and preparation and application thereof
Patent Information
- Application Number
- CN202380038380.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-05-05
- Publication Date
- 2025-04-18
AI Technical Summary
The existing technology lacks reagents that can widely kill and prevent microbial infections without toxic side effects, making it difficult to effectively treat and prevent microbial infections such as viruses, bacteria, and fungi.
A water-soluble carbon chain complex was developed, which affects the cell membrane structure and material transport across the membrane by combining with microbial lipid membranes, surface proteins or cell walls to achieve targeted killing and prevention of microorganisms. The complex, which includes a fat-soluble carbon chain and a water-soluble part, is capable of affecting microorganisms at therapeutic concentrations without harming human cells.
The complex can effectively prevent and treat microbial infections and is not easily cleared by the liver in the short term. It provides a stable antimicrobial infection dosage form suitable for intravenous injection, oral administration and topical application.
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Abstract
Description
Carbon chain substances regulating transmembrane transport and fluidity of cell membranes, their preparation and application Technical Field
[0001] The present invention relates to the pharmaceutical field, and relates to a group of water-soluble carbon chains that affect the structure and function of cell membranes and the transmembrane transport of substances; specifically, it relates to a group of carbon chain substances that can prevent and treat viral, bacterial and fungal infections and can resist aging and inflammation, including complexes and a preparation method of the complexes, and the use of the prepared complexes in preventing and treating viral, bacterial and fungal infectious diseases and in anti-aging and anti-inflammatory preparations. Background Art
[0002] 1. Structure and Function of Cell Membrane
[0003] The cell membrane is one of the most important structures in living organisms. It is primarily composed of a lipid bilayer and its embedded proteins, carbohydrates, and cholesterol. The lipid bilayer is composed of two parallel layers of phospholipid molecules. Each phospholipid molecule has a hydrophilic polar head at one end and a hydrophilic nonpolar tail at the other. Some phospholipid molecules also contain various groups, such as choline and glycerol, which make the arrangement and spatial structure of the phospholipid molecules complex and diverse. Numerous proteins are embedded in the lipid bilayer, extending throughout the membrane, spanning the membrane, or partially embedded within it. These proteins have diverse functions, including messenger receptors, ion channels, enzymes, and membrane structural proteins. In addition to lipids and proteins, the cell membrane also contains molecules such as carbohydrates and cholesterol, which bind to proteins or phospholipid molecules through chemical reactions such as glycosylation and esterification to form complex glycoproteins and lipoproteins.
[0004] Overall, the cell membrane is a semipermeable barrier that controls and regulates the flow of substances in and out of the cell, and transmits information between the inside and outside of the cell. The unique structure and function of the cell membrane make it play a vital role in life.
[0005] The cell membrane is the outer layer of all cells and has multiple functions, including: Cell boundary: The cell membrane forms the boundary between the cell and the external environment, isolating the cell's interior from the outside and maintaining the stability of the cell's internal environment. Material exchange: The cell membrane controls the entry and exit of substances, allowing the cell to obtain essential substances and eliminate waste and toxins. This is accomplished through channels and carrier proteins in the cell membrane. Signal transduction: Receptor proteins on the cell membrane can interact with external molecules and transmit information to the interior of the cell. This helps the cell respond appropriately to external stimuli. Cell adhesion: The cell membrane allows cells to adhere together to form tissues and organs. Membrane fluidity: The cell membrane is a dynamic structure whose composition and shape can be adjusted through internal transport and membrane fluidity to adapt to different environmental and physiological conditions. The cell membrane plays a vital role in maintaining cellular life activities and adapting to the environment.
[0006] 2. Cell Membrane Fluidity
[0007] Cell membrane fluidity refers to the flow properties of the cell membrane, namely, the ability of lipid molecules in the cell membrane to diffuse and rotate freely in a plane. Cell membrane fluidity is closely related to its function, as it influences the conformation and distribution of membrane proteins, thereby regulating cell signaling and the flow of substances into and out of the cell. Furthermore, cell membrane fluidity can affect cell morphology and motility, and participate in cell adhesion and motility. For example, cholesterol in the cell membrane can influence cell membrane fluidity, thereby regulating cell signaling and adhesion. Therefore, cell membrane fluidity is a key aspect of cell membrane function. This fluidity is caused by the dynamic interaction of the phospholipid bilayer structure and proteins within the cell membrane. Cell membrane fluidity is crucial for many cellular biological processes, such as cell signaling, cell motility, and phagocytosis. Because fluidity affects the order of the lipid bilayer within the cell membrane, it can affect the distribution and localization of enzymes within the membrane, thereby affecting their activity. Furthermore, changes in cell membrane structure and enzyme activity can affect processes such as cell growth and development, cell signaling, and other processes. These effects often depend on the specific function of the enzyme. For example, an enzyme may require a specific active site or rely on certain cofactors. Therefore, changes in cell membrane fluidity may directly or indirectly affect the activity of cell membrane enzymes, thereby affecting the physiological and biochemical processes of the cell.
[0008] The cell membrane is a crucial barrier between the cell's interior and the external environment. It is composed of a phospholipid bilayer and associated proteins. Reduced cell membrane fluidity can lead to the following consequences: Impaired intracellular transport of substances: Reduced cell membrane fluidity affects the activity and mobility of membrane transport proteins, thereby hindering transmembrane transport and reducing transport rates. Reduced cell signaling: The activity of many membrane receptors and signaling molecules is dependent on membrane fluidity. Reduced membrane fluidity can impair the efficiency of cell signaling. Alterations to the cytoskeleton: Reduced cell membrane fluidity can affect the interaction between membrane proteins and the cytoskeleton, potentially leading to cytoskeletal changes. Reduced cell adhesion and migration: Reduced cell membrane fluidity can impair cell adhesion and hinder the transport of substances: Proteins and lipids within the cell membrane can transfer substances from the outside to the inside of the cell through free diffusion and other methods. Reduced cell membrane fluidity hinders these processes, impacting normal cellular metabolism and function. Increased cell membrane fragility: Reduced cell membrane fluidity causes the phospholipid molecules in the cell membrane to become more tightly packed, making the cell membrane more fragile and easily damaged by substances in the external environment. Impacts on cell signal transduction: The cell membrane is a crucial component of cell signal transduction. Signaling molecules must bind to receptors on the cell membrane to transmit signals. When cell membrane fluidity decreases, the distribution and structure of these receptors may change, affecting the normal process of cell signal transduction. Increased cell membrane permeability: Reduced cell membrane fluidity may increase cell membrane permeability, disrupting the exchange of substances between the intracellular and extracellular environments and affecting normal cell function. Reduced cell membrane fluidity can affect the activity of membrane enzymes. Membrane enzymes are often embedded in the cell membrane, and cell membrane fluidity affects the conformation and spatial orientation of the enzymes, thereby affecting their activity. When cell membrane fluidity decreases, the activity of these enzymes may be reduced or completely stopped. Therefore, cell membrane fluidity is crucial for many biological processes in the cell.
[0009] Increased cell membrane fluidity may have several effects on cells, including: Increased cell membrane plasticity: Increased cell membrane fluidity means the cell membrane becomes more plastic. This allows cells to more easily adapt to environmental changes, such as cell migration and morphological changes. Increased cell membrane permeability: Increased cell membrane fluidity may lead to increased membrane permeability, making cells more susceptible to toxins, viruses, and other external factors. Enhanced membrane protein trafficking: Increased cell membrane fluidity can enhance the trafficking of membrane proteins. This can increase the absorption and excretion rates of certain substances, but may also increase the rate at which harmful substances enter the cell. Dysregulated signaling: Increased cell membrane fluidity may interfere with intercellular signaling, potentially leading to problems with cell growth, differentiation, and apoptosis. Increased membrane fluidity may affect the activity of cell membrane enzymes, as changes in the internal and external environments of the cell membrane can alter the structure and function of cell membrane proteins. Many enzymes in the cell membrane require the support of the lipid environment of the cell membrane to perform their enzymatic activities. Changes in cell membrane fluidity may affect the composition and structure of this lipid environment, thereby affecting the activity and specificity of cell membrane enzymes.
[0010] 3. Transmembrane transport
[0011] Transmembrane transport refers to the process by which substances enter or leave the cell through various mechanisms across the cell membrane. Transmembrane transport includes active transport, passive transport, and endocytosis and exocytosis. 1. Active transport: This transport requires cellular energy to move substances from areas of low concentration to areas of high concentration. Active transport can be divided into primary active transport and secondary active transport. Primary active transport involves the transfer of ions from areas of low concentration to areas of high concentration via ion pumps. For example, the sodium-potassium pump transports three sodium ions from the inside of the cell to the outside and two potassium ions from the outside to the inside. Secondary active transport utilizes the concentration gradient created by primary active transport to transport other substances. For example, the glucose transporter utilizes the intracellular ATPase to transport glucose from an area of low concentration to an area of high concentration. Passive transport: This transports substances from an area of high concentration to an area of low concentration without consuming cellular energy. Passive transport can be divided into simple diffusion and carrier-mediated diffusion. Simple diffusion allows small, non-polar or slightly polar molecules, such as oxygen and carbon dioxide, to pass freely through the lipid bilayer of the cell membrane. Carrier-mediated diffusion: The transport of specific substances from areas of high concentration to areas of low concentration by transmembrane proteins without consuming cellular energy. For example, water molecules are transported by aquaporins, and ions are transported by ion channels. Endocytosis and exocytosis: The process by which cells take in or expel substances through the formation of vesicles. Endocytosis and exocytosis occur through different mechanisms. Endocytosis: The process by which cells encapsulate substances within vesicles through membrane fusion or invagination, bringing them into the cell. An example is the process by which cells engulf bacteria.
[0012] Exocytosis refers to the process by which cells enclose substances within vesicles and then expel them from the cell through membrane separation or extrusion. An example is the process by which secretory cells release insulin. Transmembrane transport refers to the movement of biomolecules (such as proteins and nucleic acids) across the cell membrane into and out of the cell or into different organelles or regions within the cell.
[0013] Transmembrane transport refers to the process by which substances cross a cell membrane through the mediation of membrane proteins. The following factors influence transmembrane transport: 1. Concentration gradient: A concentration gradient refers to a difference in the concentration of a substance across a cell membrane, causing the higher concentration side to diffuse toward the lower concentration side. This concentration gradient promotes transmembrane transport, particularly passive transport that does not require energy. 2. Molecular size and shape: Molecular size and shape influence the ability of a substance to pass through membrane channels or carrier proteins. Small molecules can pass through membrane pores, while large molecules require carrier proteins for transmembrane transport. 3. Hydrophobicity: Membranes are composed of a lipid bilayer, and hydrophobic substances more easily pass through this barrier. Water-soluble substances require carrier proteins for transmembrane transport. 4. Electrochemical gradient: An electrochemical gradient refers to a difference in charge across a substance, causing charged substances to be affected by electric forces. This electrochemical gradient can influence transmembrane ion channels and electrokinetically driven passive transport. 5. The number and activity of carrier and channel proteins: Carrier and channel proteins are important factors in promoting transmembrane transport, and their number and activity can influence the rate of transmembrane transport. In summary, transmembrane transport is a complex process involving the interaction of multiple factors, and different substances and cell types may respond differently to these factors.
[0014] 4. Cell Membrane Fluidity and Transmembrane Transport
[0015] Cell membrane fluidity is a key characteristic of its structure and function. Cell membrane fluidity refers to the free movement of the phospholipid bilayer on the cell surface. This movement is caused by thermal motion between phospholipid molecules. Increased or decreased cell membrane fluidity can affect transmembrane transport. The cell membrane is primarily composed of a phospholipid bilayer, whose phospholipid molecules possess fluidity. The free movement of phospholipid molecules allows the cell membrane to change shape and size according to the needs of the cell, adapting to various physiological and biochemical activities. Increased cell membrane fluidity accelerates the movement of phospholipid molecules, increasing membrane fluidity. This can alter the conformation of membrane proteins (such as channel proteins and carrier proteins), affecting their function. Transmembrane transport requires passage through the cell membrane, and increased cell membrane fluidity can increase the movement of lipid molecules on the membrane surface, thereby increasing the diffusion rate of substances across the membrane and reducing friction between substances and the membrane surface, thereby facilitating transmembrane transport. Furthermore, many cell membrane proteins can facilitate transmembrane transport by changing their conformation, and increased membrane fluidity can also influence the conformational changes of these proteins. Therefore, increased cell membrane fluidity can facilitate transmembrane transport in a variety of ways. Reduced cell membrane fluidity may affect transmembrane transport because the functions of many transmembrane transport proteins depend on membrane fluidity. For example, the channels of some ion channel proteins are opened and closed by membrane fluidity, while some transport proteins also require membrane fluidity to transport substances from one side to the other. Therefore, if cell membrane fluidity decreases, the functions of these proteins may be affected, resulting in restricted transmembrane transport.
[0016] 5. Cell Membrane Fluidity and Cell Division and Proliferation
[0017] Cell division is one of the most important events in a cell's life cycle. It occurs when a single cell splits into two or more daughter cells. There are two types of cell division: mitosis and meiosis. During mitosis, the cell's chromosomes replicate and align within the cytoplasm in a structure called the spindle, where they are then separated into the two daughter cells. During meiosis, the number of chromosomes is halved, resulting in four cells for reproduction.
[0018] Cell membrane fluidity also plays a crucial role in cell division. Before cell division, the cell membrane needs to grow and expand to enclose the two new cells during the split. Cell membrane fluidity allows it to expand and change shape, thus assisting the cell in this process. Furthermore, cell membrane fluidity allows the cell to better sense its surroundings during division and adjust its behavior to the new environment. Therefore, cell membrane fluidity plays a crucial role in cell division.
[0019] Cell division is one of the most important events in a cell's life cycle. It refers to the division of a cell into two or more daughter cells. Cell division consists of two types: mitosis and meiosis. During mitosis, the cell's chromosomes replicate and arrange themselves in a structure called the spindle in the cytoplasm before being separated into the two daughter cells. During meiosis, the number of chromosomes is halved, resulting in four cells for reproductive processes. The fluidity of the cell membrane also plays a vital role in cell division. Before cell division, the cell membrane needs to grow and expand to enclose the two new cells during division. Cell membrane fluidity allows it to expand and change shape, thus assisting the cell in this process. Furthermore, cell membrane fluidity enables cells to better sense their surroundings during division and adjust their behavior to the new environment.
[0020] Increased cell membrane fluidity may play a role in cell division. Cell division is a complex biological process that includes various stages of the cell cycle, changes in the cytoskeleton, chromosome segregation, and cytoplasmic division. During this process, increased cell membrane fluidity may contribute to changes in cell morphology and the progression of cytoplasmic division. Furthermore, increased cell membrane fluidity may be associated with biological processes such as cell signal transduction and the reorganization of cell membrane proteins.
[0021] However, cell division and proliferation do not depend solely on the increase of cell membrane fluidity. Cell division and proliferation also involve many other biological factors, such as the regulation of cell cycle, DNA replication and repair, cell apoptosis, etc.
[0022] Reduced cell membrane fluidity may affect cell division and proliferation. The cell membrane is composed of a lipid bilayer, which contains many different lipid molecules, such as phospholipids and cholesterol. The fluidity of these lipid molecules can affect the structure and function of the cell membrane, thereby affecting various physiological processes of the cell.
[0023] Reduced cell membrane fluidity may affect cell division and proliferation, as the cell membrane plays a crucial role in these processes. For example, during cell division, the cell membrane undergoes significant changes to form two new cells. Reduced cell membrane fluidity may hinder this process, thereby affecting cell division. Furthermore, cell membrane fluidity is also linked to cellular signaling, and cell division and proliferation also rely on complex signaling pathways.
[0024] However, the exact relationship between reduced membrane fluidity and cell division and proliferation is not yet fully understood, as this process is very complex and influenced by many different factors. Therefore, more research is needed to determine the specific relationship between membrane fluidity and cell division and proliferation.
[0025] 6. Cell Membrane Fluidity and Cell Aging
[0026] The cell membrane is a critical barrier between the cell's interior and the external environment, and is also the primary site for intracellular molecular transmission and signal transduction. Cell membrane fluidity, which refers to the free movement and exchange of molecules within it, is crucial for maintaining cell membrane structure and function. Age-related changes in the cell membrane include decreased cell membrane fluidity and alterations in the content and types of lipid molecules within the membrane. These changes may contribute to decreased cell function and aging. Studies have shown that changes in the content and types of lipid molecules within the cell membrane are closely associated with cellular aging. For example, with aging, the content of saturated fatty acids in the cell membrane increases and that of unsaturated fatty acids decreases, reducing cell membrane fluidity and thus affecting cell function and lifespan. Furthermore, oxidative stress can lead to lipid peroxidation in the cell membrane, which compromises membrane integrity and fluidity, affecting cell function and lifespan. As cells age, the density and activity of membrane receptors and channels also change, leading to a decrease in the ability to transmit molecules and signal within the cell. Therefore, maintaining cell membrane fluidity may be a way to slow cell aging.
[0027] 7. Cell Membrane Fluidity and Cell Migration
[0028] Increased cell membrane fluidity may facilitate cell migration and movement. The cell membrane is composed of a lipid bilayer, whose lipid molecules possess fluidity. The movement of these lipid molecules is regulated by the cytoskeleton and other proteins. When a cell needs to move, it alters the structure of its cell membrane, increasing its fluidity. Increased cell membrane fluidity facilitates cell movement and migration. When white blood cells seek infection in the bloodstream, they increase membrane fluidity to expand their contact area and more easily pass through blood vessel walls. Overall, increased cell membrane fluidity increases the diffusion rate of proteins and other molecules across the cell membrane, thereby facilitating signaling and cell adhesion across the membrane and making it easier for cells to move through tissues. Furthermore, increased cell membrane fluidity may influence the remodeling of the cytoskeleton and cell membrane. The cytoskeleton is the scaffolding structure within the cell that helps cells maintain their shape and stability. Cell membrane remodeling involves the rearrangement of proteins and lipid molecules within the cell membrane to change cell shape. These processes are crucial for cell migration and movement. Increased cell membrane fluidity can facilitate cell migration and movement because membrane fluidity is required to support cell membrane deformation and movement. When cells need to navigate small pores or complex tissue structures, increased cell membrane fluidity helps them adapt to their environment and successfully migrate. As a cell expands outward, its membrane becomes more fluid, allowing it to more easily pass through narrow spaces and move within the extracellular matrix. Furthermore, increased cell membrane fluidity facilitates interactions between cells and their surroundings. Receptors and channels on the cell membrane can more easily interact with extracellular molecules, which can alter signaling and promote cell migration and locomotion. Therefore, increased cell membrane fluidity is crucial for cell migration and locomotion. Cell movement and migration require deformation and stretching of the cell membrane, processes that require membrane fluidity and flexibility. Reduced cell membrane fluidity can inhibit cell movement and migration. For example, phosphatidylinositol 3,4,5-triphosphate (PIP3) is a signaling molecule that plays a key role in cell polarity and motility. Studies have found that when cell membrane fluidity is reduced, PIP3 accumulates at the leading edge of the cell, inhibiting cell movement and migration.
[0029] 8. Methods and pathways of viral entry into cells
[0030] Transmembrane transport of viruses refers to the process by which, after a virus enters a cell, it uses a series of chemical and physical processes to transport its own genetic material or proteins and other substances from outside the cell across the cell membrane and into the interior of the cell. There are many ways for viruses to enter cells, the most common of which include: 1. Membrane fusion: The membrane proteins on the surface of the virus can bind to the corresponding proteins on the cell membrane, allowing the virus to fuse with the cell membrane and enter the cell. 2. Endocytosis: The virus recognizes and enters the cell by using receptor proteins on the cell surface. Once the virus binds to the cell receptor, the cell membrane will form a vesicle that encapsulates the virus, thereby internalizing the virus into the cell. 3. Direct penetration: Some viruses (such as poxviruses) can enter the cell by directly penetrating the cell membrane without the need for membrane fusion or endocytosis. Regardless of the method used, after the virus enters the cell, the viral genetic material will be released, allowing it to begin infecting the cell and replicating itself.
[0031] 9. Ways and pathways for bacteria and fungi to enter cells
[0032] Bacteria can enter cells in several ways: 1. Endocytosis: Some bacteria can enter cells through endocytosis. Endocytosis is the process by which cells encapsulate substances from the outside of the cell into vesicles through the cell membrane and then transport them into the cell interior. Bacteria can use this process to enter cells, the most common of which is through "triggered endocytosis." 2. Crossing the cell membrane: Some bacteria, such as Rickettsia and Mycoplasma, can enter cells directly through the cell membrane. 3. Active invasion: Some bacteria can actively invade cells using structures such as flagella, cilia, or pseudopodia. 4. Toxins: Some bacteria secrete toxins that enter cells by disrupting the cell membrane or other means. These toxins can enter cells through endocytosis or other means. It is important to note that different types of bacteria choose different invasion methods, and the method of invasion is also influenced by the interaction between the bacteria and the host cell.
[0033] There are two main ways fungi enter cells: 1. Direct penetration: Fungi secrete enzymes and toxins that penetrate the host cell membrane and cell wall, gaining entry. 2. Endocytosis: Fungi use specialized structures, such as hyphae and pseudopodia, to envelop host cells, forming a "food vacuole." Endocytosis then engulfs host cell contents into the fungal cell. Regardless of the method, once inside a host cell, fungi utilize its metabolic products and organelles for nutrient uptake and growth, leading to cell damage or death and disease.
[0034] 10. Chronic and recurrent viral infections can lead to a variety of chronic diseases, depending on the type of virus and the individual's immune status. The following are some common chronic diseases associated with viral infections: Hepatitis B and C viruses (HBV and HCV) are common chronic viral infections that can lead to hepatitis and cirrhosis. Respiratory viral infections, such as influenza virus and coronavirus, can cause chronic bronchitis and emphysema. Certain viral infections, such as coxsackievirus and German measles virus, are thought to cause pancreatic cell damage and insufficient insulin secretion, thereby increasing the risk of diabetes. Human immunodeficiency virus (HIV) infection may lead to acquired immunodeficiency syndrome (AIDS) and other immune system-related diseases. Herpes zoster virus (VZV) infection may cause shingles and sequelae, such as neuralgia. Parainfluenza virus infection may cause asthma and chronic obstructive pulmonary disease (COPD). Human cytomegalovirus (HCMV) infection may cause diseases in immunosuppressed patients, such as infection and reactivation after organ transplantation.
[0035] 11. Compounds that affect cell membranes
[0036] Many compounds affect cell membrane fluidity. Common compounds that can affect cell membrane fluidity include: Fatty acids: Phospholipid molecules in cell membranes are composed of two hydrophobic fatty acids and one hydrophobic molecule, either phosphatidylcholine or phosphatidylethanolamine. Fatty acids of varying length, degree of unsaturation, and distribution pattern affect membrane fluidity, with unsaturated fatty acids making the membrane more fluid. Cholesterol: Cholesterol is one of the most common lipids in cell membranes and contributes to membrane stability and rigidity. At low temperatures, cholesterol can reduce membrane fluidity, while at high temperatures it can increase it. Phosphatidylinositol: Phosphatidylinositol is a minor component of cell membranes that regulates cell signaling and membrane fluidity. In some cells, phosphatidylinositol is present. Phospholipids: Cell membranes are primarily composed of phospholipids, and different types of phospholipids can affect membrane fluidity. Alcohol: Alcohol can disrupt cell membrane structure, affecting membrane fluidity and stability. Squalene: Squalene, a substance similar to cholesterol, can increase cell membrane fluidity and improve membrane flexibility. Choline: Choline is a component of the B vitamins that can promote the fluidity of cell membranes and has antioxidant effects.
[0037] Tartaric acid: This is a naturally occurring organic acid that can reduce the fluidity of cell membranes, thus affecting cell function. Citric acid: This is another naturally occurring organic acid that can also reduce the fluidity of cell membranes. Surfactants: These compounds can interact with cell membranes and reduce their fluidity. Nonionic surfactants: These compounds have similar effects to surfactants but interact more gently with cell membranes.
[0038] Among the numerous microorganisms, pathogenic microorganisms that can directly cause human diseases are generally viruses, bacteria, and fungi. With the exception of a few non-enveloped viruses, the vast majority of microorganisms have lipid membranes, and the lipid membranes of microorganisms function in the same way as the cell membranes of other organisms. Structurally, they are all composed of a phospholipid bilayer, the basic scaffold of the membrane, with proteins penetrating, intercalated, and attached to the surface of the phospholipid bilayer. The outer surface of the membrane contains proteins, glycoproteins composed of a small amount of polysaccharides, and some sugars combined with lipids to form glycolipids. The lipid membrane of microorganisms is usually 7 to 8 nm in diameter and has a certain degree of fluidity. It not only acts as a barrier to create a stable internal environment for the life activities of microorganisms, but also has semipermeability or selective permeability, that is, it selectively allows substances to enter the cell through diffusion, osmosis, and active transport, thereby ensuring the normal metabolism of the cell. The present invention relates to a group of complexes and preparations that target and affect the structure and function of microbial lipid membranes or non-enveloped viral nucleocapsids.
[0039] 1. Viruses
[0040] 1.1 Enveloped and non-enveloped viruses
[0041] Viruses are the smallest infectious particles consisting of one or more nucleic acid (DNA or RNA) molecules encapsidated by a protein coat. They are non-cellular microorganisms that must replicate within susceptible living cells. Outside cells, viruses exist as particles. A structurally intact, infectious viral particle is called a virion. The viral genome is encapsidated by a protein coat called the nucleocapsid, while the protein coat is called the capsid. While the basic structure of the virion is the nucleocapsid, some viruses also possess a double lipid envelope surrounding the nucleocapsid. These viruses are called enveloped viruses, while viruses without an envelope are called naked viruses.
[0042] 1.2 Viral envelope structure and function
[0043] The envelope is the cytoplasmic membrane that a virus acquires upon release from a host cell. It can also be an intracellular organelle membrane or the nuclear membrane. Therefore, the viral envelope shares certain properties of the host cell membrane, allowing the virus to exhibit a specific "tropism" for host cell membranes. The envelope contains a lipid bilayer and several proteins encoded and synthesized by the viral gene, called envelope proteins. These proteins are virus-specific and often form glycoprotein subunits with polysaccharides. These subunits are embedded within the lipid layer and appear as spike-like projections on the surface, called "spikes" or "capsid particles." These spikes, located on the surface of the virion, are highly antigenic and can selectively bind to host cell receptors, promoting fusion of the viral envelope with the host cell membrane, allowing the infectious nucleocapsid to enter the cell and cause infection. Therefore, the envelope proteins of enveloped viruses determine the infectivity of the virus, while the nucleocapsid of an enveloped virus is the core of the virus and is non-infectious when isolated, without the envelope.
[0044] 1.3 Structure and function of non-enveloped viruses
[0045] Because naked viruses lack an envelope, their nucleocapsid is the mature virus, and their infectivity is determined by the capsid protein. The capsid protein is a product of viral genes, giving the virus its inherent shape and protecting the internal nucleic acid from damage by nucleases in the external environment (such as blood). The capsid protein also plays an auxiliary role in infection. The virus's surface-specific receptor-binding protein has a special affinity for the corresponding receptor on the cell surface, which is the first step for the virus to selectively attach to host cells and establish an infection focus. The capsid protein also exhibits virus-specific antigenicity, which can stimulate the body to produce an antigenic viral immune response.
[0046] 1.4 Types of enveloped viruses
[0047] Viruses containing envelopes include influenza virus, coronavirus, HIV, hepatitis B virus, hepatitis C virus, rabies virus, herpes virus, Ebola virus, hantavirus, dengue virus, Japanese encephalitis virus, Zika virus, etc.
[0048] The immune system relies on proteins on the cell membrane to distinguish friend from foe. Enveloped viruses, thanks to their additional lipid membrane, are recognized as friendly by the host immune system. Glycosylation of envelope proteins not only acts as an antigen shield, making vaccine development more difficult, but also spatially restructures the epitope structure.
[0049] 1.5 Coronavirus
[0050] Coronavirus: Currently, there are seven types of coronaviruses that can infect humans, namely HCoV-229E, HCoV-OC43, SARS-CoV, HCoV-NL63, HCoV-HKU1, MERS-CoV, and SARS-CoV-2. Coronaviruses are approximately 60-220nm in diameter. The virus has an envelope structure with three proteins: spike glycoprotein (S protein), small envelope glycoprotein, and membrane glycoprotein (M protein). A few species also have hemagglutinin glycoprotein (HE protein). The S protein plays a key role in recognizing and binding to host cell surface receptors and mediating the fusion of the viral envelope with the cell membrane; the M protein is involved in the formation and budding of the viral envelope; the HE protein is a short protrusion that constitutes the envelope and may be related to the early adsorption of coronaviruses. The HE protein of some coronaviruses can cause red blood cell agglutination and adsorption.
[0051] 1.6 Treatment of coronavirus
[0052] Currently, the COVID-19 vaccines and therapeutic drugs under clinical development are mainly divided into the following four categories:
[0053] First, small-molecule antiviral drugs: these include Merck's Molnupiravir, Pfizer's Paxlovid, Shionogi's Ensitrelvir, and the already marketed drugs remdesivir, lopinavir / ritonavir, and favipiravir. Although small-molecule drugs like lopinavir / ritonavir are widely used in antiviral treatments, they are not specific for treating COVID-19.
[0054] The second is anti-inflammatory drugs: multiple biological drugs are used to suppress inflammatory cytokine storms, such as Tocilizumab and Siltuximab; there are also clinical trials of some small molecule anti-inflammatory drugs, such as Baricitinib and Ruxolitinib.
[0055] Neutralizing antibodies are antibodies that bind to viruses and eliminate their ability to infect. Their mechanism of action is to alter the surface conformation of the virus, preventing it from adsorbing to susceptible cells and thus preventing it from penetrating and proliferating. The immune complexes formed by the virus and neutralizing antibodies are easily phagocytosed and cleared by macrophages.
[0056] Fourth, vaccines: including five types: recombinant protein vaccines, nucleic acid vaccines, viral vector vaccines, inactivated vaccines and live attenuated vaccines.
[0057] 1.7 Non-enveloped viruses
[0058] Non-enveloped naked viruses include hepatitis A virus, human papillomavirus, adenovirus, poliovirus, coxsackievirus, etc.
[0059] Human papillomavirus (HPV) belongs to the genus Papillomavirus in the family Papillomaviridae. It is a spherical, non-enveloped, double-stranded DNA virus with a diameter of 52 to 55 nm. The viral genome is a double-stranded circular DNA, approximately 7.8 to 8.0 kb, divided into an early region, a late region, and a regulatory region. The early region encodes proteins involved in viral replication, transcriptional regulation, and cellular transformation (such as E5, E6, and E7), while the late region encodes the major capsid protein L1 and the minor capsid protein L2. Over 130 types have been isolated, and different types cause different clinical manifestations. Based on the tissue site of invasion, they are divided into: low-risk cutaneous, high-risk cutaneous, low-risk mucosal, and high-risk mucosal types. Cutaneous HPV infection is very common in the human population, such as common warts, toe warts, and flat warts, but the specific infection rate is unknown.
[0060] 2 Bacteria
[0061] The basic structure of bacteria includes cell wall, cell membrane, cytoplasm, and nucleoplasm.
[0062] 2.1 Bacterial cell membrane
[0063] The bacterial cell membrane is a flexible, semipermeable membrane composed of a phospholipid bilayer intercalated with proteins. The membrane is 8 to 10 nm thick and adheres closely to the cell wall. The absence of cholesterol within the bacterial cell membrane distinguishes it from eukaryotic cell membranes. The bacterial cell membrane contains a rich system of enzymes that perform many important metabolic functions. The multifunctionality of the bacterial cell membrane is a significant characteristic that distinguishes it from other cell membranes. For example, the inner side of the cell membrane contains enzymes for electron transport and oxidative phosphorylation, performing some of the functions of eukaryotic mitochondria.
[0064] Structural characteristics of bacterial cell membranes: ① The main body of the membrane is the lipid bilayer ② The lipid bilayer has fluidity ③ Integrins can "dissolve" in the hydrophobic inner layer of the lipid bilayer because of their hydrophobic surface ④ Peripheral proteins contain hydrophilic groups on their surface, so they can be connected to the polar heads on the surface of the lipid bilayer through electrostatic attraction ⑤ There is no covalent bond between lipid molecules or between lipid and protein molecules ⑥ The lipid bilayer is like an "ocean", peripheral proteins can "float" on it, while integral proteins are like "icebergs" immersed in it and move laterally.
[0065] Physiological functions of bacterial cell membrane: ① It can selectively control the transport of nutrients and metabolic products inside and outside the cell; ② It is a structural barrier to maintain normal osmotic pressure in the cell; ③ It is an important place for synthesizing cell walls and sugar-related components (such as peptidoglycan, teichoic acid, LPS and capsular polysaccharides, etc.); ④ The membrane contains enzyme systems related to energy metabolism such as oxidative phosphorylation or photosynthetic phosphorylation, so it is the cell's energy production base; ⑤ It is the attachment site of the flagellar body and can provide the energy required for the flagella's rotational movement.
[0066] 2.2 Bacterial cell wall
[0067] The main component of the cell wall is peptidoglycan, also known as sticky peptide. Peptidoglycan is a polysaccharide scaffold composed of two amino sugars, N-acetylglucosamine and N-acetylmuramic acid, connected by β-1,4-glycosidic bonds and arranged in intervals. Tetrapeptide side chains are attached to the N-acetylmuramic acid molecules, and the peptide chains are linked by peptide bridges or peptide chains, forming a highly mechanically robust network structure.
[0068] 2.2.1 Gram-positive bacteria
[0069] The cell wall of Gram-positive bacteria is relatively thick, measuring approximately 20 to 80 mm. It is rich in peptidoglycan, comprising 15 to 50 layers, each 1 nm thick, which accounts for approximately 50 to 80% of the cell wall's dry weight. Furthermore, it contains a significant amount of the specialized component teichoic acid. Teichoic acid is highly antigenic and is a key surface antigen of Gram-positive bacteria. It plays a role in regulating the passage of ions through the mucopeptide layer and may also be involved in the activity of certain enzymes. The teichoic acid of some bacteria can adhere to the surface of human cells, acting similarly to pili and possibly contributing to pathogenicity.
[0070] 2.2.2 Gram-negative bacteria
[0071] The cell wall of Gram-negative bacteria has a multifaceted structure. The cell wall is relatively thin, approximately 10 to 15 nm, and contains one to two layers of peptidoglycan, which account for approximately 5 to 20% of the cell wall's dry weight. Beyond the cell wall lies an outer membrane composed of proteins, phospholipids, and lipopolysaccharides. The outer membrane contains lower phospholipids than the cytoplasmic membrane, but a higher lipopolysaccharide content. Unlike the cytoplasmic membrane, the proteins in the outer membrane are covalently linked to the tetrapeptide side chains of the peptidoglycan at one end through a protein moiety and to a phosphate group in the outer membrane at the other end through a lipid moiety. Their function is to stabilize the outer membrane and anchor it to the peptidoglycan layer. Lipopolysaccharides, known as bacterial endotoxins, are present in the outermost layer of the outer membrane. The outer membrane is the primary structure of the Gram-negative bacterial cell wall. Besides transporting nutrients, it also serves as a barrier, preventing the permeation of various substances and protecting against the effects of many chemical agents.
[0072] 2.3 Antibiotics
[0073] Antibiotics are mainly secondary metabolites produced by bacteria, fungi or other microorganisms or artificially synthesized analogues. They are mainly used to treat various bacterial infections or diseases caused by pathogenic microorganisms. Generally, they do not cause serious side effects on their hosts. The mechanism of action of antibiotics is generally to hinder the synthesis of bacterial cell walls, causing the bacteria to swell, rupture and die in a low osmotic pressure environment; interact with the bacterial cell membrane, increase the permeability of the bacterial cell membrane, open the ion channels on the membrane, and allow useful substances inside the bacteria to leak out of the bacteria or cause electrolyte imbalance and death; interact with bacterial ribosomes or their reaction substrates (such as tRNA, mRNA), inhibit protein synthesis, resulting in the inability to synthesize structural proteins and enzymes necessary for cell survival; hinder the replication and transcription of bacterial DNA, so that the process of bacterial cell division, reproduction and transcription and translation into protein is hindered.
[0074] 2.4 Antibiotic resistance
[0075] It's well known that excessive, high-dose, and prolonged use of antibiotics can lead to drug resistance. To combat pathogenic microorganisms, humans continuously develop new antibiotics. However, bacteria and other microorganisms, in order to survive, gradually adapt to these drug environments and mutate, evolving into new, more potent strains, perpetuating the cycle. Multidrug-resistant bacteria have even emerged—single bacteria resistant to three or more classes of antibiotics. Further research has revealed that bacterial resistance stems from the presence of resistance genes. NDM-1, a new super-resistance gene discovered by scientists, encodes a novel resistance enzyme, NDM-1 (full name: New Delhi Metallo-β-lactamase 1). This highly effective enzyme breaks down most antibiotics, rendering them ineffective. Resistance genes not only confer resistance to the bacteria themselves but can also spread through the environment, transferring to other bacteria and making them resistant to antibiotics. With few new antibiotics currently available and existing antibiotics ineffective against resistant bacteria, infection with resistant bacteria significantly increases the risk of death. The mortality rate for patients infected with resistant bacteria is approximately twice that of those infected with non-resistant bacteria. Therefore, the infection and spread of drug-resistant bacteria has become a major challenge in contemporary medicine.
[0076] 3. Fungi, Chlamydia, and Mycoplasma
[0077] The basic structures of fungal cells include the cell wall, cell membrane, nucleus, endoplasmic reticulum, and mitochondria. The main component of the fungal cell wall is chitin, and the fungal cell membrane is also composed of a phospholipid bilayer. However, the plasma membrane contains sterols, and ergosterol plays an important role in maintaining membrane permeability and fluidity. There are three types of antifungal drugs: polyenes (amphotericin B preparations), triazoles (voriconazole, itraconazole, and posaconazole), and echinocandins (caspofungin, micafungin, and anidulafungin).
[0078] Chlamydia are Gram-negative pathogens with a cell wall and membrane, but no peptidoglycan. Instead, their membrane is composed of disulfide-linked polypeptides. Mycoplasmas lack a cell wall, but instead have a cell membrane composed of a phospholipid bilayer, which plays a role in maintaining the integrity of the cell membrane.
[0079] 4. Targeting microbial lipid membrane components
[0080] The main structure of the microbial lipid membrane is the phospholipid bilayer, and its main components are phospholipids, proteins and polysaccharides. It can destroy the continuity and stability of the microbial lipid membrane, cause changes in the membrane's permeability, enhance permeability, and play an antimicrobial role.
[0081] 4.1 Structure and composition of microbial cell membranes
[0082] Microbial lipid membranes are typically 7 to 8 nm thick. Lipid membranes are primarily composed of lipids and proteins, with lipids accounting for 50%, proteins for 40%, and polysaccharides for approximately 1 to 10%. Membrane lipids primarily include phospholipids and glycolipids, with phospholipids comprising over 50% of membrane lipids. Phospholipids are primarily glycerophospholipids, which have a glycerol backbone bound to two fatty acid chains and a phosphate group. Molecules such as choline, ethanolamine, serine, or inositol are attached to the lipid molecules via the phosphate groups. The hydrophilic end of the phospholipid molecule is the phosphate group, known as the head; the hydrophobic end consists of two hydrocarbon chains of varying lengths, known as the tail, typically containing an even number of 14 to 24 carbon atoms. One of the hydrocarbon chains often contains one or more double bonds, which create a twist in the unsaturated chain. Glycolipids account for less than 5% of membrane lipids; the simplest glycolipid is galactocerebroside, which has only a single galactose group as its polar head. Glycolipids function as integral membrane proteins.
[0083] 4.2 Microbial membrane lipids
[0084] It is the basic skeleton of the membrane. Removing membrane lipids will cause the membrane to disintegrate. Membrane lipids are the solvents of membrane proteins. Some proteins interact with membrane lipids through their hydrophobic ends, allowing the proteins to be embedded in the membrane and perform special functions. Membrane lipids provide an environment for certain membrane proteases to maintain their conformation and express their activity. The activity of many enzymes on the membrane depends on the presence of membrane lipids.
[0085] 4.3 Microbial membrane proteins
[0086] Membrane proteins comprise 40% to 50% of the membrane. The more complex the membrane, the greater its protein content. Membrane proteins are categorized by their binding mechanism to membrane lipids and their location within the membrane: integral proteins, peripheral proteins, and lipid-anchored proteins. Integral proteins are proteins partially or completely embedded within the cell membrane or on both the inner and outer sides. They are so tightly bound to the membrane that they can only be removed from it using detergents, such as SDS and Triton-X100. Peripheral proteins, also known as extrinsic proteins, are water-soluble and distributed on the surface of the cell membrane. They bind to the hydrophilic portions of proteins or lipid molecules on the membrane surface through ionic bonds or other weaker bonds. Therefore, they can be separated from the membrane simply by changing the ionic strength of the solution or even increasing the temperature. Lipid-anchored proteins, also known as lipid-linked proteins, bind to lipids in two ways: indirectly through a sugar molecule or directly. Lipid-anchored proteins are covalently anchored to phospholipids or fatty acids. Membrane proteins function as transport proteins, catalyze metabolic reactions, connect proteins, and act as receptors.
[0087] 4.4 Microbial membrane sugars
[0088] They constitute 2% to 10% of the membrane composition and are primarily located on the outer surface of the lipid membrane. Seven main types of sugars are present in animal cell membranes: D-glucose, D-galactose, D-mannose, L-fucose, N-acetylgalactosamine, and N-acetylglucosamine. Sugars can be linked to amino acids in two main ways: N-linkages, where the sugar chain is attached to an asparagine residue in the peptide chain; and O-linkages, where the sugar chain is attached to a serine or threonine residue in the peptide chain.
[0089] 4.5 Asymmetry of microbial lipid membranes
[0090] The composition and functions of the inner and outer layers of the lipid membrane differ significantly, a phenomenon known as membrane asymmetry. The asymmetrical distribution of membrane lipids, proteins, and sugars within the membrane leads to asymmetric and directional membrane function. Specifically, the difference in fluidity between the inner and outer layers of the membrane results in directional transport of substances, as well as the reception and transmission of signals. This asymmetry and directional nature of membrane function ensures a high degree of order in life. Cell recognition, movement, transport of substances, and signal transmission all possess directional characteristics. This directional nature is maintained by the asymmetrical distribution of membrane proteins, lipids, and sugars.
[0091] 4.6 Fluidity of microbial lipid membranes
[0092] Microbial lipid membranes are fluid, allowing lipid molecules to diffuse laterally, rotate, oscillate, stretch, oscillate, flip, and undergo rotational isomerization. Membrane protein movement primarily involves lateral diffusion and rotational diffusion. Lipid membrane fluidity is essential for proper function. When membrane fluidity falls below a certain threshold, many enzyme activities and transmembrane transport cease. Conversely, excessive fluidity can lead to membrane dissolution.
[0093] 5. Methods and preparations for disrupting microbial cell membranes
[0094] 5.1 Physical damage
[0095] The simplest in vitro method is to place the microorganisms in distilled water. Using the principle of osmosis, the cells absorb water and swell, causing them to burst. Both low and high temperatures can destroy the lipid membranes of microorganisms. Direct differential centrifugation can also disrupt the lipid membrane structure.
[0096] 5.2 Protease and phospholipase destruction
[0097] Proteases can catalyze the hydrolysis of proteins in lipid membranes, thereby destroying the lipid membranes; while phospholipases also destroy lipid membranes by hydrolyzing phospholipids in lipid membranes.
[0098] 5.3 Ionic, nonionic, and zwitterionic detergents disrupt cell membranes
[0099] Detergents are amphiphilic molecules containing both hydrophilic and hydrophobic regions. They can disrupt protein, proteolipid, and lipid bonds, denaturing proteins and other macromolecules. Commonly used ionic detergents in experiments include sodium dodecyl sulfate (SDS), deoxycholate, cholate, and sarcosinate; commonly used nonionic detergents include Triton X-100, DDM, digitonin, tween 20, and tween 80. Detergents are amphiphilic organic compounds composed of a hydrophobic, nonpolar hydrocarbon portion and a hydrophilic, polar group. This molecular structure is very similar to the amphiphilic phospholipids that constitute lipid membranes. Phospholipids have two hydrophobic fatty acid tails attached to a hydrophilic group. At high concentrations, amphiphilic molecules self-assemble into structures that position their hydrophilic head groups on the outside and their hydrophobic tails on the inside, away from water. Due to their molecular differences, detergent molecules form spherical micelles. This similarity in molecular structure enables detergents to penetrate phospholipid bilayers, thereby disrupting lipid membranes.
[0100] 5.4. In vitro bactericidal effects of fatty acids
[0101] Fatty acids are a class of compounds composed of three elements: carbon, hydrogen, and oxygen. They are the main components of neutral fats, phospholipids, and glycolipids. Fatty acid metabolism: Fatty acids can be further divided into the following categories based on the length of their carbon chains: short-chain fatty acids, which have fewer than 6 carbon atoms (also known as volatile fatty acids); medium-chain fatty acids, which have 6-12 carbon atoms; and long-chain fatty acids, which have more than 12 carbon atoms. Fatty acids can be divided into three categories based on whether their carbon-hydrogen chains are saturated or unsaturated: saturated fatty acids, which have no unsaturated bonds; monounsaturated fatty acids, which have one unsaturated bond; and polyunsaturated fatty acids, which have two or more unsaturated bonds.
[0102] Fatty acids in food are re-esterified in intestinal cells, mixing with bile salts and monoglycerides to form 4-6 nm fat particles. These fat particles are directly absorbed by intestinal epithelial cells through pinocytosis and coated with a phosphatidylcholine and protein membrane, becoming chylomicrons that enter the lymphatic system. They then flow through the lymphatic vessels and thoracic duct and return to the bloodstream as an oil-in-water emulsion. While a small amount of medium-chain fatty acids remains in the peripheral blood for a short period of time, the majority are non-covalently bound to serum proteins and rapidly reach the liver via the portal vein. In the liver, medium-chain fatty acids rapidly cross the mitochondrial double membrane and are rapidly acylated by octanoyl CoA, with little to no conversion to fat. The excess acetyl CoA produced by acylation undergoes various metabolic processes in the mitochondrial cytoplasm, with the majority of this being converted to ketone bodies.
[0103] Research indicates that the antimicrobial effects of fatty acids are generally broad-spectrum. Although their antimicrobial mechanisms remain poorly understood, many studies hypothesize that the primary target of fatty acid action is the cell membrane, where they disrupt the electron transport chain and oxidative phosphorylation. In addition to interfering with cellular energy production, the effects of fatty acids may also be due to inhibition of enzyme activity, impairment of nutrient absorption, production of peroxidative and autooxidative degradation products, or direct decomposition of bacterial cells.
[0104] Because its mechanism of action is different from that of most traditional antibiotics, it has development potential. However, there are still some problems that have hindered progress so far. First, some free fatty acids taste bad. Second, free fatty acids are unstable, and they also tend to bind non-specifically to proteins. In the body, more fatty acids are transported in the form of stable lipids (such as triglycerides). Third, the fat solubility and rapid metabolism of fatty acids mean that they cannot be used directly in the body. Free fatty acids are insoluble in water, or have very low water solubility, and cannot be injected directly into the blood circulation. Direct injection into the vein can cause pulmonary embolism, and injection into the artery can cause arterial embolism and tissue necrosis.
[0105] The concentrations of in vitro antibacterial and bactericidal fatty acids used in research are often very high, and such high concentrations will definitely damage the cell membranes of human cells. Human cells are also composed of phospholipid bilayers and are also targets for attack by high concentrations of fatty acids. Therefore, the patent of the present invention relates to a group of stable water-soluble carbon chain complexes that can be injected intravenously or arterially, or taken orally. By covalently binding hydrophobic carbon chains with large, medium, and small water-soluble molecules and binding molecules, the fat-soluble hydrophobic carbon chains are converted into water-soluble complexes that can target and kill microorganisms in the body. At therapeutic concentrations, this group of complexes has the ability to target and kill pathogenic microorganisms, has no effect or damage to human cell tissues, and is not easily cleared and metabolized by the liver in the short term. The highly water-soluble and high-affinity complexes described in the present invention have the effect of resisting microbial infection. In addition to nasal sprays and dry powder inhalers, they can also be used in intravenous and oral dosage forms.
[0106] Summary of the Invention
[0107] In view of the lack of agents without toxic side effects in the prior art that cannot widely kill, prevent, block or treat microbial infections, the present invention provides a complex that can prevent, block or treat microbial infections.
[0108] During the process of studying substances for preventing, stopping or treating microbial infections, the present invention discovered after intensive research that the water-soluble carbon chain substance of the present invention can affect the structure and function of cell membranes and the transmembrane transport of substances. Furthermore, by studying and controlling the specific hydrophilicity and hydrophobicity of the carbon chain substance, and / or controlling the concentration of the carbon chain substance as needed, it is possible to destroy the cell membranes of microorganisms and thus achieve the effect of preventing, stopping or treating microbial infections; by controlling the concentration within a desired range, it is possible to affect the structure and function of the cell membrane and control the transmembrane transport of substances; by controlling the concentration within a desired range, it is possible to inhibit the fluidity of the cell membrane and improve the stability of the cell membrane, thereby making anti-aging or anti-inflammatory pharmaceutical preparations according to the place of use.
[0109] The present invention provides a group of water-soluble carbon chain substances that affect cell membrane structure and function and transmembrane transport of substances. Specifically, the inventors have discovered that, after contact with cells, the water-soluble carbon chains can partially insert into the cell membrane's phospholipid bilayer, altering or influencing the length, saturation, and arrangement of the fatty acid chains of cholesterol and phospholipid molecules, and altering or influencing the glycerophospholipid / sphingomyelin ratio, thereby changing the cell membrane structure. Alternatively, the water-soluble carbon chains can bind to membrane proteins, altering or influencing their structure, further affecting the cell membrane structure. These changes in cell membrane structure alter the asymmetry and directionality of membrane function, thereby affecting the directionality of substance transport and signal transmission across the cell membrane, and thus affecting the cell membrane's ability to transport drug molecules and micro-nanoparticles.
[0110] Specifically, in order to solve the problem that the existing technology lacks agents without toxic side effects, especially the inability to widely kill and prevent, inhibit or treat microbial infections, the present invention provides the following first set of technical solutions:
[0111] (1) The present invention provides a complex capable of preventing, inhibiting and / or treating microbial infection, comprising an active portion, a binding portion and a water-soluble portion.
[0112] The active part is a fat-soluble saturated and / or unsaturated carbon chain with a branched, cyclic and / or linear structure, the carbon chain is a molecule or a residue of a molecule, and the carbon chain is a carbon chain with 3-100 carbon atoms;
[0113] The water-soluble portion is a water-soluble molecule or a residue of a molecule, wherein the molecule contains one or more functional groups selected from an amide group, a phosphoryloxy group, a carboxylic acid group, a phosphoric acid group, a sulfonic acid group, a sulfonyloxy group, a hydroxyl group, a quaternary ammonium group, a thioether group, a disulfide bond, an ether group, a sulfhydryl group, an aldehyde group, an ester group, an amine group, an amino group, a urea group, and a guanidine group. The water-soluble portion may be one or more functional groups connected to the carbon chain serving as the active portion and / or the binding portion;
[0114] The binding portion is a molecule or a residue of a molecule that can bind to a microbial lipid membrane, a microbial surface protein, a microbial surface polysaccharide or a cell wall component, or can bind to a polysaccharide, protein or polypeptide in a microorganism. The binding portion can be the same as the water-soluble portion, i.e., a protein, polypeptide, amino acid, oligopeptide, oligosaccharide, monosaccharide and / or polysaccharide molecule or its residue that can bind to a microbial lipid membrane or surface domain;
[0115] The number of any one of the active part, the water-soluble part and the binding part can be 1 or more.
[0116] (2) The complex according to technical solution 1, wherein the active part is selected from saturated and / or unsaturated aliphatic hydrocarbons, saturated and / or unsaturated aliphatic alcohols or oxy-fatty alcohols, saturated and / or unsaturated fatty acids, hydrophobic amino acids, fat-soluble vitamins, steroid lipids, phospholipids, sphingomyelins, glycolipids, and surfactants, and the carbon chain or carbon chain residue has 3-100 carbon atoms, preferably 3-48 carbon atoms, and more preferably 3-26 carbon atoms; wherein the carbon chain has preferably 3-26 carbon atoms;
[0117] The water-soluble portion is a water-soluble molecule or a residue of a molecule containing one or more groups selected from the group consisting of a thiol group, an amino group, a phosphate group, a carboxylic acid group, a sulfonic acid group, a hydroxyl group, an amine group, a urea group, a guanidine group, and a disulfide group;
[0118] The binding portion has a group that plays a binding role, that is, it can bind to the microbial lipid membrane, microbial surface protein, microbial surface polysaccharide or cell wall component or can bind to the polysaccharide or protein or polypeptide in the microorganism, and the group is derived from the water-soluble portion or from one or more groups selected from thiol, amino, phosphate, carboxylic acid, sulfonic acid, hydroxyl, amine, urea, guanidine and disulfide as an independent binding portion, or from one or more groups selected from thiol, amino, phosphate, carboxylic acid, sulfonic acid, hydroxyl, amine, urea, guanidine and disulfide that provide carbon chain-to-carbon chain connection, so that the complex has one or more groups selected from thiol, amino, phosphate, carboxylic acid, sulfonic acid, hydroxyl, amine, urea, guanidine and disulfide;
[0119] That is, in the complex of the present invention, the binding portion may be the same as the water-soluble portion in some cases, and may also serve as the carbon chain function of the active portion.
[0120] Preferably, the binding moiety is selected from one or more of dibasic fatty acids or polybasic fatty acids, amino acids, targeting proteins, targeting polypeptides, and targeting polysaccharides;
[0121] More preferably, the complex is a complex formed by linking a fatty acid selected from a group having 3 to 100 carbon atoms, preferably 3 to 50 carbon atoms, and a water-soluble amino acid; or, the complex is a complex formed by linking a fatty acid selected from a group having 3 to 50 carbon atoms and a targeting polypeptide;
[0122] Alternatively, the complex is a complex formed by the reaction of a fatty acid having 3 to 100 carbon atoms, preferably 3 to 50 carbon atoms, a targeting polypeptide, and PEG;
[0123] Alternatively, the complex is a complex formed by the reaction of a surfactant and one or more selected from dibasic fatty acids or polybasic fatty acids, amino acids, targeting proteins, targeting polypeptides and targeting polysaccharides, wherein the surfactant is preferably selected from one or more selected from fatty alcohol polyoxyethylene ethers, fatty acid polyoxyethylene esters, alkyl glycosides, fatty acid sucrose esters, sorbitan fatty acid esters, sorbitan polyoxyethylene fatty acid esters, N-acyl-N-methylglucosamine, and mannose erythritol lipids.
[0124] (3) According to the complex described in Technical Solution 2, the saturated and / or unsaturated fatty acid is selected from saturated fatty acids or unsaturated fatty acids with a carbon number of 3-100, and the fatty acid is a fatty acid or amino acid containing a double bond, a triple bond, a hydroxyl group, an amino group and / or oxygenated, and can be a monobasic acid, a dibasic acid or a polybasic acid.
[0125] (4) The complex according to technical solution 3, wherein the saturated and / or unsaturated fatty acid is selected from saturated fatty acids with 3-46 carbon atoms, monoenoic acids with 3-34 carbon atoms, dienoic acids with 5-30 carbon atoms, trienoic acids with 7-30 carbon atoms, tetraenoic acids with 12-38 carbon atoms, pentaenoic acids with 12-38 carbon atoms, hexaenoic acids with 22-38 carbon atoms, ynoic acids with 6-22 carbon atoms, diynoic acids with 10-22 carbon atoms, triynoic acids with 12-22 carbon atoms, and enoic acids with 8-20 carbon atoms (preferably containing one or two C=C double bonds and one, two or three triple bonds), mainly Fatty acids with 3-30 carbon atoms and 1-10 alkyl groups and / or 1-3 hydroxyl groups on the branched chains (preferably saturated fatty acids with 1-3 methyl groups or fatty acids with C=C double bonds), saturated straight-chain and branched dicarboxylic acids and tricarboxylic acids with 3-38 carbon atoms, and unsaturated straight-chain or branched dicarboxylic acids and tricarboxylic acids with 4-18 carbon atoms that may be substituted with hydroxyl groups, amino-, hydroxyl-, oxo- and / or methyl-substituted carboxylic acids with 3-18 carbon atoms, N-acylamino acids with 6-30 carbon atoms, amino acids containing 2 or more acyl groups, and polycarboxylic acids linked by thioether bonds and amide bonds;
[0126] The saturated and / or unsaturated fatty alcohol is a saturated fatty straight-chain or branched alcohol with 3-33 carbon atoms; and / or an unsaturated fatty straight-chain or branched alcohol with 3-33 carbon atoms, 1-5 double bonds and 1-5 triple bonds, and 1-3 hydroxyl groups; the oxy-fatty alcohol is an alcohol ketone with 8-31 carbon atoms, 1-3 double bonds or triple bonds, and 1-3 hydroxyl groups, and the ketone is a monoketone or a diketone.
[0127] (5) According to the complex described in technical solution 4, the saturated / unsaturated fatty acid is one or more selected from fumaric acid, octanoic acid, glutaconic acid, hexanoic acid, nonanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid, octadecanoic acid, eicosanoic acid, oleic acid, linoleic acid, linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid, pentacosanoic acid, heptanoic acid, decanoic acid, dodecenoic acid, tetradecenoic acid, docosahexaenoic acid, and octacosanoic acid, or the carbon chain residues formed therefrom.
[0128] (6) The complex according to any one of technical solutions 1 to 5, wherein the water-soluble portion is a molecule or a residue of a molecule containing one or more groups selected from thiol, amino, carboxylic acid, hydroxyl and disulfide groups; the molecule is selected from one or more water-soluble macromolecules or their residues selected from proteins, polysaccharides, nucleic acids and synthetic water-soluble polymers;
[0129] and / or, one or more medium molecules or their residues selected from polypeptides, oligopeptides, oligosaccharides, oligonucleotides and synthetic water-soluble medium molecular weight polymers;
[0130] and / or, one or more water-soluble small molecules or their residues selected from amino acids, monosaccharides, disaccharides, nucleotides, water-soluble vitamins, and deoxynucleotides;
[0131] and / or, a molecule or a residue of a molecule connected to the carbon chain serving as the active part, wherein the molecule or the residue of a molecule contains one or more groups selected from the group consisting of a thiol group, an amino group, a carboxylic acid group, a hydroxyl group, and a disulfide group.
[0132] (7) According to the complex described in technical solution 6, the protein as the water-soluble macromolecule is one or more water-soluble macromolecules selected from serum albumin, immunoglobulin, water-soluble collagen, chaperone protein, water-soluble glycoprotein and CD14; the polysaccharide as the macromolecule is one or more water-soluble macromolecules selected from dextran, hyaluronic acid, sialic acid, heparin sulfate, heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, acetyl water-soluble cellulose derivatives, β-cyclodextrin and its derivatives and water-soluble chitosan derivatives; the water-soluble polymer as the macromolecule is one or more water-soluble macromolecules selected from polyethylene glycol and carboxylated or amino polyethylene glycol, polyvinyl alcohol and carboxylated or quaternized polyvinyl alcohol, polyacrylic acid and ammonium polyacrylate;
[0133] The water-soluble medium molecular weight polymer is selected from targeting polypeptides, oligopeptides, oligosaccharides, oligonucleotides and / or water-soluble polyamino acids; preferably, the targeting polypeptide includes proteins or neutralizing antibody fragments (including, for example, taurine transport peptide, SBP1) that specifically target microbial lipid membranes, bacterial and fungal cell walls, and viral surface protein domains; preferably, the water-soluble polyamino acids are selected from polyglutamic acid, polylysine and / or polyaspartic acid; as well as oligopeptides, oligosaccharides, and oligonucleotides;
[0134] The monosaccharides and / or disaccharides of the water-soluble small molecules are selected from one or more of glucose, fructose, rhamnose, sorbose, sucrose, maltose, lactose and trehalose; the nucleotides and / or deoxynucleotides as water-soluble small molecules are selected from one or more of adenylic acid, guanylic acid, uridine monophosphate, cytidylic acid, thymidylic acid, inosinic acid, deoxyadenylic acid, deoxyguanylic acid, deoxycytidylic acid and deoxythymidylic acid; the amino acids are selected from one or more of serine, threonine, cysteine, asparagine, glutamine, tyrosine, lysine, arginine, histidine, aspartic acid, glutamic acid, citrulline, ornithine, taurine and aminobutyric acid; the vitamins as the water-soluble small molecules are selected from one or more of vitamin B1, pantothenic acid, vitamin B6 and vitamin C.
[0135] (8) According to the complex described in any one of technical solutions 1 to 7, the binding portion and the water-soluble portion are the same, that is, proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, amino acids, nucleotides, vitamins, water-soluble polymers, water-soluble polyamino acids and / or polysaccharide molecules or residues of these molecules that can bind to the lipid membrane and surface domain of microorganisms, and the molecules or the residues of the molecules include one or more groups selected from thiol, amino, carboxylic acid, hydroxyl, and disulfide.
[0136] (9) The complex according to any one of technical solutions 1 to 8, which is a compound obtained by reacting a substance containing a carbon chain with 3 to 100 carbon atoms as an active part with one or more selected from proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, amino acids, nucleotides, vitamins, water-soluble polymers, water-soluble polyamino acids and / or polysaccharides; or it is a compound obtained by reacting a substance containing a carbon chain with 3 to 100 carbon atoms as an active part with one or more selected from proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, amino acids, nucleotides, vitamins, water-soluble polymers, water-soluble polyamino acids and / or polysaccharide molecules, and the unreacted The active part of the substance and / or the unreacted protein, polypeptide, oligopeptide, oligosaccharide, monosaccharide, disaccharide, amino acid, nucleotide, vitamin, water-soluble polymer, water-soluble polyamino acid and / or polysaccharide molecule mixture; wherein preferably, the active part of the substance is selected from saturated and / or unsaturated aliphatic hydrocarbons, saturated and / or unsaturated aliphatic alcohols or oxy-fatty alcohols, saturated and / or unsaturated fatty acids, hydrophobic amino acids, fat-soluble vitamins, steroid lipids, phospholipids, sphingomyelin, glycolipids and surfactants. One or more substances provide or have a carbon chain or a residue forming a carbon chain with a carbon number of 3-100, preferably 3-48, and more preferably 3-26.
[0137] That is, the complex for preventing, inhibiting or treating microbial infection includes the compound obtained by the reaction, the reaction mixture containing the compound obtained by the reaction (also referred to as "reaction product", "reaction mixture", "reaction product solution", "reaction mixture solution"), and the purified product after the reaction mixture is purified to remove unreacted starting materials and catalysts.
[0138] (10) The complex according to any one of technical solutions 1 to 8, which is a complex or a mixture obtained by direct physical mixing of a substance containing a carbon chain with 3 to 100 carbon atoms as an active part and one or more of the substances selected from proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, amino acids, nucleotides, vitamins, water-soluble polymers, water-soluble polyamino acids and / or polysaccharide molecules, wherein the physical and chemical action includes hydrogen bonding or van der Waals force or a combination of the two; wherein preferably, the substance as the active part is one or more of the substances selected from saturated and / or unsaturated aliphatic hydrocarbons, saturated and / or unsaturated aliphatic alcohols or oxy-fatty alcohols, saturated and / or unsaturated fatty acids, hydrophobic amino acids, fat-soluble vitamins, steroid lipids, phospholipids, sphingomyelins, glycolipids and surfactants, and these substances provide or have a carbon chain with 3 to 100 carbon atoms, preferably 3 to 48 carbon atoms, and more preferably 3 to 26 carbon atoms or a residue forming a carbon chain.
[0139] (11) The complex according to technical solution 9, which is a compound obtained by reacting a substance containing a carbon chain with 3 to 100 carbon atoms as an active part with at least one selected from proteins, polypeptides, oligopeptides and amino acids; or it is a compound obtained by reacting a substance containing a carbon chain with 3 to 100 carbon atoms as an active part with at least one selected from proteins, polypeptides, oligopeptides and amino acids, and a mixture of unreacted substance as the active part and / or unreacted at least one selected from proteins, polypeptides, oligopeptides and amino acids.
[0140] (12) The complex according to technical solution 9, which is a compound obtained by reacting a substance containing a carbon chain with 3 to 100 carbon atoms as an active part, PEG and at least one selected from proteins, polypeptides, oligopeptides and amino acids; or it is a compound obtained by reacting a substance containing a carbon chain with 3 to 100 carbon atoms as an active part, PEG and at least one selected from proteins, polypeptides, oligopeptides and amino acids, and a mixture of unreacted substance as the active part, unreacted PEG and / or unreacted at least one selected from proteins, polypeptides, oligopeptides and amino acids.
[0141] (13) The complex according to technical solution 9, which is a compound obtained by reacting a substance containing a carbon chain with 3 to 100 carbon atoms as an active part with one or more selected from polysaccharides, monosaccharides, disaccharides and / or oligosaccharides; or it is a compound obtained by reacting a substance containing a carbon chain with 3 to 100 carbon atoms as an active part with one or more selected from polysaccharides, monosaccharides, disaccharides and / or oligosaccharides, and a mixture of unreacted substance as active part and / or unreacted polysaccharides, monosaccharides, disaccharides and / or oligosaccharides.
[0142] (14) The complex according to technical solution 9 is a compound obtained by reacting a substance containing a carbon chain with 3 to 100 carbon atoms as an active part, PEG and one or more selected from polysaccharides, monosaccharides, disaccharides and / or oligosaccharides; or it is a compound obtained by reacting a saturated and / or unsaturated fatty acid with 3 to 100 carbon atoms, PEG and one or more selected from polysaccharides, monosaccharides, disaccharides and / or oligosaccharides, and a mixture of unreacted substance as the active part, unreacted PEG and / or unreacted polysaccharides, monosaccharides, disaccharides and / or oligosaccharides.
[0143] (15) According to any one of technical solutions 6 to 12, the protein is selected from one or more of serum albumin, immunoglobulin, water-soluble collagen, chaperone protein, water-soluble glycoprotein and CD14.
[0144] (16) According to the complex described in technical solution 13, the polysaccharide is selected from one or more of dextran and / or hyaluronic acid sialic acid, heparin sulfate, heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, acetyl water-soluble cellulose derivatives, β-cyclodextrin and its derivatives and water-soluble chitosan derivatives.
[0145] (17) The complex according to technical solution 11 or 12, which is a compound obtained by reacting a substance containing a carbon chain with 3 to 100 carbon atoms as an active part, a linker and a protein containing a thiol group; or a mixture of the compound obtained by the above reaction, unreacted substance as the active part, unreacted linker, and / or unreacted protein containing a thiol group; wherein the linker is one or more of amino acids, succinic acid, butadienoic acid, glutaric acid, hexamethylenediamine, carbamate, short peptide, N-hydroxybutyric imide, polyethylene glycol, and derivatives of the above compounds;
[0146] Preferably, the complex is a compound obtained by reacting a substance containing a carbon chain with 3-100 carbon atoms as the active part and N-hydroxybutyric acid imide with a protein containing a sulfhydryl group; or a mixture of the compound obtained by the above reaction, the unreacted substance as the active part, the unreacted N-hydroxybutyric acid imide and / or the unreacted protein containing a sulfhydryl group.
[0147] (18) The complex according to technical solution 13, which is a compound obtained by reacting a substance containing a carbon chain with 3 to 100 carbon atoms as an active part, cystamine and one or more selected from polysaccharides, monosaccharides, disaccharides and / or oligosaccharides; or a compound obtained by reacting a substance containing a carbon chain with 3 to 100 carbon atoms as an active part, cystamine and one or more selected from polysaccharides, monosaccharides, disaccharides and / or oligosaccharides, and a mixture of unreacted substance as the active part and unreacted polysaccharides, monosaccharides, disaccharides, oligosaccharides and / or unreacted cystamine.
[0148] (19) According to any one of technical solutions 8 to 17, the compound obtained by the reaction contains one or more of an amide group, an ester group, a thioether group or an ether group as a connecting portion between the water-soluble portion and the active portion.
[0149] (20) According to the complex described in any one of technical solutions 3-18, the substance that provides a carbon chain or a residue of a carbon chain as an active part is selected from one or more of saturated and / or unsaturated aliphatic hydrocarbons, saturated and / or unsaturated aliphatic alcohols or oxy-fatty alcohols, saturated and / or unsaturated fatty acids, hydrophobic amino acids, fat-soluble vitamins, steroid lipids, phospholipids, sphingomyelins, glycolipids and surfactants, and the number of carbon atoms in the carbon chain is 3-100, preferably 3-50, further preferably 3-48, and more preferably 3-26.
[0150] (21) According to the complex described in any one of technical solutions 3-18, the substance that provides a carbon chain or a carbon chain residue as an active part is selected from one or more of saturated and / or unsaturated aliphatic hydrocarbons, saturated and / or unsaturated aliphatic alcohols or oxy-fatty alcohols, saturated and / or unsaturated fatty acids, hydrophobic amino acids, fat-soluble vitamins, steroid lipids, phospholipids, sphingomyelins, glycolipids and surfactants, preferably saturated and / or unsaturated fatty acids; more preferably, the saturated and / or unsaturated fatty acids are fatty acids with 3-100 carbon atoms, preferably 3-50, also preferably 3-48, more preferably 3-40, containing 1-8 C=C double bonds, can be fatty acids containing 1-7 C=C double bonds, can be fatty acids containing 1-6 double bonds, can be fatty acids containing 1-5 double bonds, can be fatty acids containing 1-4 double bonds, can be fatty acids containing 1-3 double bonds, or can be fatty acids containing 1-2 double bonds.
[0151] (22) According to the complex described in any one of technical solutions 3 to 18, the substance that provides a carbon chain or a carbon chain residue as the active part is a saturated and / or unsaturated fatty acid, which can be a fatty acid with 1 to 6 double bonds and 2 to 30 carbon atoms, preferably 2 to 26, and more preferably 2 to 22.
[0152] (23) According to the complex described in any one of technical solutions 3-18, the saturated and / or unsaturated fatty acid has 3-30 carbon atoms, preferably 3-26, preferably 8-22, preferably 8-20, and preferably 8-18 carbon atoms.
[0153] (24) According to the complex described in any one of technical solutions 3 to 18, the saturated and / or unsaturated fatty acids are selected from one or more fatty acids selected from fumaric acid, octanoic acid, glutaric acid, hexanoic acid, nonanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid, octadecanoic acid, eicosanoic acid, oleic acid, linoleic acid, linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid, pentacosanoic acid, heptanoic acid, decanoic acid, dodecenoic acid, tetradecenoic acid, docosahexaenoic acid, and octacosanoic acid.
[0154] (25) According to any one of technical solutions 8 to 23, the protein is human serum albumin or bovine serum albumin, or CD14; or the polysaccharide is dextran and / or hyaluronic acid.
[0155] (26) The complex according to technical solution 11, wherein the compound obtained by the reaction is a fatty acid and albumin (Albumin) or SBP1 to obtain any one or more compounds having the following structural formula:
[0156] (27) According to the complex described in technical solution 12, the compound obtained by the reaction is a compound obtained by the reaction of a monobasic fatty acid with 3-10 carbon atoms, PEG and an amino acid, or a compound obtained by the reaction of a monobasic fatty acid with 3-10 carbon atoms, a saturated dibasic fatty acid with 5-8 carbon atoms, PEG and taurine; preferably, the compound has at least one of the following structural formulas:
[0157] Wherein n is an integer from 1 to 200.
[0158] (28) According to the complex of technical solution 13, the compound obtained by the reaction is any one or more compounds having the following structural formulas obtained by the reaction of fatty acid and glucan:
[0159] (29) According to the complex of technical solution 13, the compound obtained by the reaction is any one or more compounds having the following structural formulas obtained by the reaction of fatty acid and hyaluronic acid:
[0160] n is an integer from 1 to 2000.
[0161] (30) According to the complex described in technical solution 14, the compound obtained by the reaction is a compound obtained by reacting a fatty acid having 3 to 10 carbon atoms with PEG and glucose, preferably a compound having the following structural formula:
[0162] n is an integer from 1 to 200.
[0163] (31) According to the complex described in technical solution 17, the compound obtained by the reaction is a compound having a thioether bond and having any one or more of the following structural formulas obtained by reacting fatty acid, N-hydroxybutyromide and albumin:
[0164] (32) According to the complex of technical solution 18, the compound obtained by the reaction is any one or more compounds having the following structural formulas obtained by the reaction of fatty acid, cystamine and dextran:
[0165] (33) According to the complex of technical solution 18, the compound obtained by the reaction is any one or more compounds having the following structural formulas obtained by the reaction of fatty acid, cystamine and hyaluronic acid:
[0166] (34) The complex according to any one of technical solutions 1 to 8, which is a compound obtained by reacting a surfactant containing a carbon chain with 3 to 30 carbon atoms with a dibasic fatty acid or a polybasic fatty acid, an amino acid, a targeting protein, a targeting polypeptide, a targeting polysaccharide and / or a targeting polysaccharide; or it is a mixture of the compound obtained by the above reaction, the unreacted surfactant and / or the unreacted dibasic fatty acid or a polybasic fatty acid, an amino acid, a targeting protein, a targeting polypeptide, a targeting polysaccharide and / or a targeting polysaccharide.
[0167] (35) According to the complex described in technical solution 34, the surfactant is selected from one or more of fatty alcohol polyoxyethylene ether, fatty acid polyoxyethylene ester, alkyl glycoside, fatty acid sucrose ester, anhydrous sorbitan fatty acid ester, anhydrous sorbitan polyoxyethylene fatty acid ester, mannose erythritol ester and N-acyl-N-methyl glucosamine.
[0168] (36) According to the complex described in any one of technical solutions 1-35, the microbial infection includes infection caused by viruses.
[0169] (37) A preparation for preventing, inhibiting or treating microbial infection prepared by using the complex described in any one of technical solutions 1 to 35,
[0170] (38) The preparation according to technical solution 37 is a pharmaceutical preparation or an environmental disinfection preparation.
[0171] (39) According to the preparation described in technical solution 38, the pharmaceutical preparation is one selected from inhalation, nasal spray, injection, oral preparation and external skin preparation.
[0172] (40) Use of the complex described in any one of Technical Solutions 1 to 35 in the preparation of a pharmaceutical preparation for preventing, inhibiting and / or treating microbial infection.
[0173] (41) The application according to technical solution 40, wherein the microorganism is any one or more selected from viruses, bacteria, fungi, chlamydia or mycoplasma.
[0174] (42) The use according to technical solution 41, wherein the virus is an enveloped virus; and / or a non-enveloped virus.
[0175] (43) The application according to technical solution 42, wherein the enveloped virus is one or more of coronavirus, influenza virus, HIV, hepatitis B virus, hepatitis C virus, herpes virus, Zika virus, dengue virus, Japanese encephalitis virus, Ebola virus, rabies virus, and / or hantavirus; and the non-enveloped virus is two or more of hepatitis A virus, human papillomavirus, polio virus and / or coxsackie virus.
[0176] (44) The application according to technical solution 43, wherein the virus is any one or more of coronavirus, HIV, hepatitis B virus, hepatitis C virus, herpes virus, Japanese encephalitis virus, rabies virus, human papillomavirus and Ebola virus.
[0177] (45) The application according to technical solution 41, wherein the bacteria are Gram-positive bacteria and / or Gram-negative bacteria, the fungi are pathogenic fungi and / or conditionally pathogenic fungi; the Chlamydia are Chlamydia trachomatis, Chlamydia pneumoniae and / or Chlamydia psittaci; the Mycoplasma include Mycoplasma pneumoniae, Ureaplasma urealyticum, Mycoplasma hominis, and / or Mycoplasma genitalium.
[0178] (46) The application according to technical solution 41, wherein the bacteria are selected from one or more of Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae and Pseudomonas aeruginosa; and the fungi are selected from one or more of Candida albicans, Aspergillus niger, Actinomyces viscosus, Chaetomium sphaeroides, Aspergillus verrucosum and Microsporum canis.
[0179] (47) The application according to technical solution 41, wherein the virus is selected from one or more of H7N9 influenza virus, H5N1 influenza virus, HIV virus, new coronavirus, HPV virus and rabies virus.
[0180] (48) The method for preparing the complex described in any one of technical solutions 1 to 35 is to react a fat-soluble compound having a saturated and / or unsaturated carbon chain with a branched, cyclic and / or linear structure with a water-soluble molecule, and as needed, proteins, polypeptides, amino acids, oligopeptides, oligosaccharides, monosaccharides and / or polysaccharide molecules that can bind to the lipid membrane of a microorganism, the surface domain of a virus or the cell wall, and as needed, a linker molecule, in the presence of a catalyst to obtain the complex.
[0181] (49) According to the method for preparing the complex described in technical solution 48, the complex is the product of the compound obtained by the reaction after purification treatment.
[0182] (50) The method for preparing the complex described in any one of technical solutions 1 to 35 is to obtain the complex by physically mixing a fat-soluble compound having a saturated and / or unsaturated carbon chain with a branched, cyclic and / or linear structure with a water-soluble molecule, and a protein, polypeptide, amino acid, oligopeptide, oligosaccharide, monosaccharide and / or polysaccharide molecule that can bind to the microbial lipid membrane, microbial surface domain or cell wall as needed.
[0183] (51) A method for preparing the complex described in any one of technical solutions 1 to 35, wherein the complex is obtained by reacting a saturated and / or unsaturated fatty acid containing 3 to 100 carbon atoms with any one of proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, nucleotides, vitamins, water-soluble polymers, water-soluble polyamino acids and / or polysaccharides in the presence of a catalyst.
[0184] (52) According to the method for preparing the complex described in technical solution 51, the complex is the product of the compound obtained by the reaction after purification treatment.
[0185] (53) The method for preparing the complex described in any one of technical solutions 1 to 35 is to obtain the complex by physical and chemical compounding of saturated and / or unsaturated fatty acids with 3 to 100 carbon atoms with proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, nucleotides, vitamins, water-soluble polymers, water-soluble polyamino acids and / or polysaccharide molecules or by direct physical mixing.
[0186] Specifically, in order to solve the problem that the existing technology lacks agents without toxic side effects, especially the inability to widely kill and prevent, inhibit or treat microbial infections, the present invention provides the following second set of technical solutions:
[0187] ① A complex capable of preventing, inhibiting and / or treating microbial infection, comprising an active portion, a binding portion and a water-soluble portion,
[0188] The active part is a fat-soluble saturated and / or unsaturated carbon chain with a branched, cyclic and / or linear structure, wherein the carbon chain is a molecule or a residue of a molecule; wherein the active part is a carbon chain or a residue of a carbon chain with 3 to 100 carbon atoms formed by one or more substances selected from hydrophobic amino acids, fat-soluble vitamins, steroid lipids, phospholipids, sphingomyelins, glycolipids, surfactants, saturated and / or unsaturated aliphatic hydrocarbons and saturated and / or unsaturated fatty alcohols or oxy-fatty alcohols;
[0189] The water-soluble portion is a water-soluble molecule or a residue of a molecule, wherein the molecule contains one or more functional groups selected from amide groups, phosphoryloxy groups, carboxylic acid groups, phosphoric acid groups, sulfonic acid groups, sulfonyloxy groups, hydroxyl groups, quaternary ammonium groups, thioether groups, disulfide bonds, ether groups, sulfhydryl groups, aldehyde groups, ester groups, amine groups, amino groups, urea groups, and guanidine groups. The water-soluble portion may be one or more functional groups connected to the carbon chain serving as the active portion;
[0190] The binding portion is a molecule or a residue of a molecule that can bind to a microbial lipid membrane, a microbial surface protein, a microbial surface polysaccharide or a cell wall component, or can bind to a polysaccharide, protein or polypeptide in a microorganism. The binding portion can be the same as the water-soluble portion, i.e., a protein, polypeptide, amino acid, oligopeptide, oligosaccharide, monosaccharide and / or polysaccharide molecule or its residue that can bind to a microbial lipid membrane or surface domain;
[0191] The number of any one of the active part, the water-soluble part and the binding part can be 1 or more.
[0192] ② According to the complex described in technical solution 1, the number of carbon atoms is 3-48.
[0193] ③ According to the complex described in technical solution 1, the number of carbon atoms is 3-26.
[0194] ④ The complex according to any one of technical solutions 1 to 3, wherein the water-soluble portion is a water-soluble molecule or a residue of a molecule containing one or more groups selected from the group consisting of a thiol group, an amino group, a phosphate group, a carboxylic acid group, a sulfonic acid group, a hydroxyl group, an amine group, a urea group, a guanidine group, and a disulfide group;
[0195] The binding portion has a group that plays a binding role, that is, it can bind to the microbial lipid membrane, microbial surface protein, microbial surface polysaccharide or cell wall component or can bind to the polysaccharide or protein or polypeptide in the microorganism. The group is from the water-soluble part or from two or more groups selected from thiol, amino, phosphate, carboxylic acid, sulfonic acid, hydroxyl, amine, urea, guanidine and disulfide groups as an independent binding part, or from one or more groups selected from thiol, amino, phosphate, carboxylic acid, sulfonic acid, hydroxyl, amine, urea, guanidine and disulfide groups that provide carbon chain-to-carbon chain connection, so that the complex has one or more groups selected from thiol, amino, phosphate, carboxylic acid, sulfonic acid, hydroxyl, amine, urea, guanidine and disulfide groups.
[0196] ⑤ According to the complex described in technical solution 4, the binding part is selected from one or more of dibasic fatty acids or polybasic fatty acids, amino acids, targeting proteins, targeting polypeptides, and targeting polysaccharides.
[0197] ⑥ The complex according to any one of technical solutions 1-4, wherein the complex is a complex formed by the reaction of a surfactant and one or more selected from dibasic fatty acids or polybasic fatty acids, amino acids, targeting proteins, targeting polypeptides and targeting polysaccharides.
[0198] ⑥ According to the complex according to any one of technical solutions 1-6, the saturated and / or unsaturated fatty alcohol is a saturated fatty alcohol with a cyclic structure, a straight chain or a branched chain having 3-33 carbon atoms; and / or an unsaturated fatty alcohol with a straight chain or a branched chain having 1-3 hydroxyl groups and containing 1-5 double bonds and 1-5 triple bonds having 3-33 carbon atoms; the oxy-fatty alcohol is an alcohol ketone with a carbon number of 8-31, containing 1-3 double bonds or triple bonds and 1-3 hydroxyl groups, and the ketone is a monoketone or a diketone.
[0199] ⑧ The complex according to any one of technical solutions 1 to 5 and technical solution 7, wherein the water-soluble portion is a molecule or a residue of a molecule containing one or more groups selected from thiol, amino, carboxylic acid, hydroxyl and disulfide groups; the molecule is one or more water-soluble macromolecules or residues thereof selected from proteins, polysaccharides, nucleic acids and synthetic water-soluble polymers;
[0200] and / or, one or more medium molecules or their residues selected from polypeptides, oligopeptides, oligosaccharides, oligonucleotides and synthetic water-soluble medium molecular weight polymers;
[0201] and / or, one or more water-soluble small molecules or their residues selected from amino acids, monosaccharides, disaccharides, nucleotides, water-soluble vitamins and deoxynucleotides;
[0202] and / or, a molecule or a residue of a molecule connected to the carbon chain serving as the active part, wherein the molecule or the residue of a molecule contains one or more groups selected from the group consisting of a thiol group, an amino group, a carboxylic acid group, a hydroxyl group, and a disulfide group.
[0203] ⑨ The complex according to technical solution 8, wherein the protein serving as the water-soluble macromolecule is one or more water-soluble macromolecules selected from serum albumin, immunoglobulin, water-soluble collagen, chaperone protein, water-soluble glycoprotein and CD14; the polysaccharide serving as the macromolecule is one or more water-soluble macromolecules selected from dextran, hyaluronic acid, sialic acid, heparin sulfate, heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, acetyl water-soluble cellulose derivatives, β-cyclodextrin and its derivatives and water-soluble chitosan derivatives; the water-soluble polymer serving as the macromolecule is one or more water-soluble macromolecules selected from polyethylene glycol and carboxylated or amino polyethylene glycol, polyvinyl alcohol and carboxylated or quaternized polyvinyl alcohol, polyacrylic acid and ammonium polyacrylate;
[0204] The water-soluble medium molecular weight polymer is selected from one or more substances selected from targeting polypeptides, oligopeptides, oligosaccharides, oligonucleotides and / or water-soluble polyamino acids;
[0205] The monosaccharides and / or disaccharides of the water-soluble small molecules are selected from one or more of glucose, fructose, rhamnose, sorbose, sucrose, maltose, lactose and trehalose; the nucleotides and / or deoxynucleotides as water-soluble small molecules are selected from one or more of adenylic acid, guanylic acid, uridine monophosphate, cytidylic acid, thymidylic acid, inosinic acid, deoxyadenylic acid, deoxyguanylic acid, deoxycytidylic acid and deoxythymidylic acid; the amino acids are selected from one or more of serine, threonine, cysteine, asparagine, glutamine, tyrosine, lysine, arginine, histidine, aspartic acid, glutamic acid, citrulline, ornithine, taurine and aminobutyric acid; the vitamins as the water-soluble small molecules are selected from one or more of vitamin B1, pantothenic acid, vitamin B6 and vitamin C.
[0206] ⑩ According to the complex according to any one of technical solutions 5-9, the targeting polypeptide includes any one of a protein or a neutralizing antibody fragment that specifically targets a microbial lipid membrane, a bacterial and fungal cell wall, or a viral surface protein domain.
[0207] According to the complex described in Technical Solution 9, the water-soluble polyamino acid is selected from polyglutamic acid, polylysine and / or polyaspartic acid.
[0208] According to the complex described in any one of technical solutions 1-11, the binding portion and the water-soluble portion are the same, that is, proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, amino acids, nucleotides, vitamins, water-soluble polymers, water-soluble polyamino acids and / or polysaccharide molecules or residues of these molecules that can bind to microbial lipid membranes and surface domains, and the molecules or molecular residues include one or more groups selected from thiol, amino, carboxylic acid, hydroxyl, and disulfide groups.
[0209] The complex according to technical solutions 1-12, which is a compound obtained by reacting a substance containing a carbon chain with 3-100 carbon atoms as an active part with any one or more selected from proteins, polypeptides, oligopeptides, oligosaccharides, amino acids, monosaccharides, disaccharides, nucleotides, vitamins, water-soluble polymers, water-soluble polyamino acids and / or polysaccharide molecules; or it is a compound obtained by reacting a substance containing a carbon chain with 3-100 carbon atoms as an active part with any one or more selected from proteins, polypeptides, oligopeptides, oligosaccharides, amino acids, monosaccharides, disaccharides, nucleotides, vitamins, water-soluble polymers, water-soluble polyamino acids and / or polysaccharide molecules, and a mixture of unreacted substance as the active part and / or unreacted protein, polypeptide, oligopeptide, oligosaccharide, amino acid, monosaccharide, disaccharide, oligonucleotide, vitamin, water-soluble polymer, water-soluble polyamino acid and / or polysaccharide molecules;
[0210] The substance containing a carbon chain with 3 to 100 carbon atoms as the active part is selected from saturated and / or unsaturated aliphatic hydrocarbons, saturated and / or unsaturated aliphatic alcohols or oxy-fatty alcohols, hydrophobic amino acids, fat-soluble vitamins, steroid lipids, phospholipids, sphingomyelins, glycolipids and / or surfactants.
[0211] The complex according to any one of technical solutions 1 to 12, which is a complex formed by physical and chemical action of a substance containing a carbon chain having 3 to 100 carbon atoms as an active part and any one or two selected from proteins, polypeptides, oligopeptides, oligosaccharides, amino acids, monosaccharides, disaccharides, nucleotides, vitamins, water-soluble polymers, water-soluble polyamino acids and polysaccharide molecules, or a mixture obtained by direct physical mixing, wherein the physical and chemical action includes hydrogen bonding or van der Waals forces or a combination of the two;
[0212] The substance containing a carbon chain with 3 to 100 carbon atoms as the active part is a substance selected from saturated and / or unsaturated aliphatic hydrocarbons, saturated and / or unsaturated aliphatic alcohols or oxy-fatty alcohols, hydrophobic amino acids, fat-soluble vitamins, steroid lipids, phospholipids, sphingomyelins, glycolipids and / or surfactants.
[0213] The complex according to technical solution 13 is a compound obtained by reacting a substance containing a carbon chain with 3-100 carbon atoms as an active part with at least one selected from proteins, polypeptides, oligopeptides and amino acids; or it is a compound obtained by reacting a substance containing a carbon chain with 3-100 carbon atoms as an active part with at least one selected from proteins, polypeptides, oligopeptides and amino acids, and a mixture of unreacted substance as the active part and / or unreacted at least one selected from proteins, polypeptides, oligopeptides and amino acids.
[0214] The complex according to technical solution 13 is a compound obtained by reacting a substance containing a carbon chain with 3-100 carbon atoms as the active part, PEG and at least one selected from proteins, polypeptides, oligopeptides and amino acids; or it is a compound obtained by reacting a substance containing a carbon chain with 3-100 carbon atoms as the active part, PEG and at least one selected from proteins, polypeptides, oligopeptides and amino acids, and a mixture of unreacted substance as the active part, unreacted PEG and / or unreacted at least one selected from proteins, polypeptides, oligopeptides and amino acids.
[0215] The complex according to technical solution 13 is a compound obtained by reacting a substance containing a carbon chain with 3-100 carbon atoms as an active part with at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides; or it is a compound obtained by reacting a substance containing a carbon chain with 3-100 carbon atoms as an active part with at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides, and a mixture of unreacted substance as the active part and / or unreacted polysaccharides, monosaccharides, disaccharides and / or oligosaccharides.
[0216] The complex according to technical solution 13 is a compound obtained by reacting a substance containing a carbon chain with 3-100 carbon atoms as an active part, PEG and at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides; or it is a compound obtained by reacting a substance containing a carbon chain with 3-100 carbon atoms as an active part, PEG and at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides, and a mixture of unreacted substance as the active part, unreacted PEG and / or unreacted polysaccharides, monosaccharides, disaccharides and / or oligosaccharides.
[0217] According to the complex described in technical solution 13, the protein is one or more selected from serum albumin, immunoglobulin, water-soluble collagen, chaperone protein, water-soluble glycoprotein and CD14.
[0218] According to the complex described in any one of technical solutions 13-19, the polysaccharide is selected from one or more of dextran and / or hyaluronic acid, sialic acid, heparin sulfate, heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, acetyl water-soluble cellulose derivatives, β-cyclodextrin and its derivatives and water-soluble chitosan derivatives.
[0219] The complex according to technical solution 13 is a compound obtained by reacting a substance containing a carbon chain with 3-100 carbon atoms as an active part, a linker and a protein containing a thiol group; or a mixture of the compound obtained by the above reaction, unreacted substance as the active part, unreacted linker, and / or unreacted protein containing a thiol group; wherein the linker is one or more of amino acids, succinic acid, butadienoic acid, glutaric acid, hexamethylenediamine, carbamate, short peptide, N-hydroxybutyromide, polyethylene glycol and derivatives of the above compounds.
[0220] The complex according to technical solution 21 is a compound obtained by reacting a substance containing a carbon chain with 3-100 carbon atoms as an active part and N-hydroxybutyric acid imide with a protein containing a sulfhydryl group; or a mixture of the compound obtained by the above reaction, the unreacted substance as the active part, unreacted N-hydroxybutyric acid imide and / or unreacted protein containing a sulfhydryl group.
[0221] The compound according to technical solution 13 is a carbon compound containing 3 to 100 carbon atoms.
[0222] A compound obtained by reacting a substance containing a carbon chain as an active moiety, cystamine and at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides; or a compound obtained by reacting a substance containing a carbon chain with 3 to 50 carbon atoms as an active moiety, cystamine and at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides, and a mixture of unreacted substance as active moiety and unreacted polysaccharides, monosaccharides, disaccharides, oligosaccharides and / or unreacted cystamine.
[0223] According to the complex described in any one of technical solutions 13-23, the compound obtained by the reaction contains one or more of an amide group, an ester group, a thioether group or an ether group as the connecting part between the water-soluble part and the active part.
[0224] According to the complex described in any one of technical solutions 4 to 23, the number of carbon atoms of the saturated and / or unsaturated aliphatic hydrocarbon, saturated and / or unsaturated aliphatic alcohol or oxy-fatty alcohol is 3-50.
[0225] According to the complex described in technical solution 25, the number of carbon atoms is 3-48.
[0226] According to the complex described in technical solution 26, the carbon atoms are 3-26.
[0227] According to the complex described in any one of technical solutions 4 to 23, the protein is human serum albumin or bovine serum albumin, or CD14; or the polysaccharide is dextran, heparin and / or hyaluronic acid.
[0228] The complex according to any one of technical solutions 4-12 is a compound obtained by reacting a surfactant containing a carbon chain having 3-30 carbon atoms with at least one selected from dibasic fatty acids or polybasic fatty acids, amino acids, targeting proteins, targeting polypeptides and targeting polysaccharides; or it is a mixture of the compound obtained by the above reaction, the unreacted surfactant and / or the unreacted dibasic fatty acids or polybasic fatty acids, amino acids, targeting proteins, targeting polypeptides and / or targeting polysaccharides.
[0229] According to the complex described in any one of technical solutions 1-29, the surfactant is selected from one or more of fatty alcohol polyoxyethylene ether, fatty acid polyoxyethylene ester, alkyl glycoside, fatty acid sucrose ester, sorbitan fatty acid ester, sorbitan polyoxyethylene fatty acid ester, mannose erythritol ester and N-acyl-N-methyl glucosamine.
[0230] According to the complex described in any one of technical solutions 1-30, the microbial infection includes infection caused by any one or more of viruses, bacteria, fungi, chlamydia or mycoplasma.
[0231] A preparation for preventing, inhibiting or treating microbial infection prepared by the complex according to any one of technical solutions 1 to 31,
[0232] According to the preparation described in technical solution 32, the preparation is a pharmaceutical preparation or an environmental disinfection preparation.
[0233] According to the preparation described in technical solution 33, the pharmaceutical preparation is one selected from inhalation, nasal spray, injection, oral preparation and external skin preparation.
[0234] Use of the complex described in any one of technical solutions 1-31 in the preparation of pharmaceutical preparations for preventing, preventing and / or treating microbial infections or environmental microbial disinfection agents.
[0235] According to the application described in technical solution 35, the microorganism is any one or more selected from viruses, bacteria, fungi, chlamydia or mycoplasma.
[0236] According to the application described in Technical Solution 36, the virus is an enveloped virus; and / or a non-enveloped virus.
[0237] According to the application described in technical solution 37, the enveloped virus is one or more of coronavirus, influenza virus, HIV, hepatitis B virus, hepatitis C virus, herpes virus, Zika virus, dengue virus, Japanese encephalitis virus, Ebola virus, rabies virus, and hantavirus; the non-enveloped virus is one or more of hepatitis A virus, human papillomavirus, poliovirus and coxsackievirus.
[0238] According to the application described in technical solution 36, the virus is any one or more of coronavirus, HIV, hepatitis B virus, hepatitis C virus, herpes virus, Japanese encephalitis virus, rabies virus, human papillomavirus and Ebola virus.
[0239] According to the application described in technical solution 36, the bacteria are Gram-positive bacteria and / or Gram-negative bacteria, the fungi are pathogenic fungi and / or conditionally pathogenic fungi; the chlamydia are Chlamydia trachomatis, Chlamydia pneumoniae and / or Chlamydia psittaci; the mycoplasma include Mycoplasma pneumoniae, Ureaplasma urealyticum, Mycoplasma hominis, and / or Mycoplasma genitalium.
[0240] According to the application described in technical solution 36, the bacteria are selected from one or more of Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae and Pseudomonas aeruginosa; the fungi are selected from one or more of Candida albicans, Aspergillus niger, Actinomyces viscosus, Chaetomium sphaeroides, Aspergillus verrucosum and Microsporum canis.
[0241] According to the application described in technical solution 36, the virus is selected from one or more of H7N9 influenza virus, H5N1 influenza virus, HIV virus, new coronavirus, HPV virus and rabies virus.
[0242] The method for preparing the complex described in any one of technical solutions 1-32 is to react a fat-soluble compound with a saturated and / or unsaturated carbon chain having a branched, cyclic and / or linear structure with a water-soluble molecule, and proteins, polypeptides, amino acids, oligopeptides, oligosaccharides, monosaccharides and / or polysaccharide molecules that can bind to the microbial lipid membrane, microbial surface domain or cell wall as needed, as well as linker molecules added as needed, in the presence of a catalyst to obtain the complex.
[0243] According to the method for preparing the complex described in Technical Solution 44, the complex is the product of a purification treatment of the compound obtained by the reaction.
[0244] The method for preparing the complex described in any one of technical solutions 1-31 is to obtain the complex by physically mixing a fat-soluble compound having a saturated and / or unsaturated carbon chain with a branched, cyclic and / or linear structure with a water-soluble molecule, and at least one selected from proteins, polypeptides, amino acids, oligopeptides, oligosaccharides, monosaccharides and polysaccharide molecules that can bind to microbial lipid membranes, viral surface domains or cell walls as needed.
[0245] The method for preparing the complex described in any one of technical solutions 1-31 is obtained by reacting a substance having a carbon chain with 3 to 100 carbon atoms as the active part with at least one substance selected from proteins, polypeptides, oligopeptides, oligosaccharides, amino acids, monosaccharides, disaccharides, nucleotides, vitamins, water-soluble polymers, water-soluble polyamino acids and polysaccharides in the presence of a catalyst to obtain the complex.
[0246] The catalyst may be one or more of EDC, DCC, NHS, DMAP, HoBt and their derivatives and analogues, and the catalyst is preferably carbodiimide and succinimide, with a molar ratio of 0.1:1-10:1, preferably 1:1-1:10.
[0247] According to the method for preparing the complex described in Technical Solution 46, the complex is the product of a purification treatment of the compound obtained by the reaction.
[0248] The method for preparing the complex described in any one of technical solutions 1-31 is to obtain the complex by physically and chemically compounding a substance having a carbon chain with 3 to 100 carbon atoms as the active part with at least one selected from proteins, polypeptides, oligopeptides, polysaccharides, oligosaccharides, amino acids, monosaccharides, disaccharides, nucleotides, vitamins, water-soluble polymers, water-soluble polyamino acids and polysaccharide molecules or directly physically mixing the complex.
[0249] Specifically, in order to address the lack of agents in the prior art that are free of toxic side effects, and in particular, cannot widely kill and prevent, inhibit or treat microbial infections, the present invention provides the following third set of technical solutions:
[0250] ① A complex capable of preventing, inhibiting and / or treating viral or bacterial infection, comprising an active portion, a binding portion and a water-soluble portion;
[0251] The virus is one or more viruses selected from the group consisting of novel coronavirus, influenza virus, HIV, hepatitis B virus, human herpes virus, Ebola virus, rabies virus, and human papillomavirus; and the bacteria are one or more bacteria selected from the group consisting of Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa.
[0252] The active part is a fat-soluble saturated and / or unsaturated carbon chain with a branched, cyclic and / or linear structure, the carbon chain is a molecule or a residue of a molecule, and the carbon chain is a carbon chain with 3-100 carbon atoms; wherein the active part is a carbon chain or a residue of a carbon chain with 3-100 carbon atoms formed by a saturated and / or unsaturated fatty acid;
[0253] The water-soluble portion is a water-soluble molecule or a residue of a molecule, wherein the molecule contains one or more functional groups selected from amide groups, phosphoryloxy groups, carboxylic acid groups, phosphoric acid groups, sulfonic acid groups, sulfonyloxy groups, hydroxyl groups, quaternary ammonium groups, thioether groups, disulfide bonds, ether groups, sulfhydryl groups, aldehyde groups, ester groups, amine groups, amino groups, urea groups, and guanidine groups. The water-soluble portion may be one or more functional groups connected to the carbon chain serving as the active portion;
[0254] The binding part is a molecule or a residue of a molecule that can bind to a microbial lipid membrane, a microbial surface protein, a microbial surface polysaccharide or a cell wall component or can bind to a polysaccharide or protein or polypeptide in a microorganism. The binding part can bind to a water-soluble
[0255] Partially identical, i.e., proteins, polypeptides, amino acids, oligopeptides, oligosaccharides, monosaccharides and / or polysaccharide molecules or their residues that can bind to the lipid membrane or surface domain of microorganisms;
[0256] The number of any one of the active part, the water-soluble part and the binding part can be 1 or more.
[0257] ② According to the complex described in technical solution 1, the number of carbon atoms is 3-48.
[0258] ③ According to the complex described in technical solution 1, the number of carbon atoms is 3-26.
[0259] ④ The complex according to technical solution 1, wherein the water-soluble portion is a water-soluble molecule or a residue of a molecule containing one or more groups selected from the group consisting of a thiol group, an amino group, a phosphate group, a carboxylic acid group, a sulfonic acid group, a hydroxyl group, an amine group, a urea group, a guanidine group, and a disulfide group;
[0260] The binding portion has a group that plays a binding role, that is, it can bind to the microbial lipid membrane, microbial surface protein, microbial surface polysaccharide or cell wall component or can bind to the polysaccharide or protein or polypeptide in the microorganism. The group is from the water-soluble part or from two or more groups selected from thiol, amino, phosphate, carboxylic acid, sulfonic acid, hydroxyl, amine, urea, guanidine and disulfide groups as independent binding parts, or from one or more groups selected from thiol, amino, phosphate, carboxylic acid, sulfonic acid, hydroxyl, amine, urea, guanidine and disulfide groups that provide carbon chain-to-carbon chain connection, so that the complex has one or more groups selected from thiol, amino, phosphate, carboxylic acid, sulfonic acid, hydroxyl, amine, urea, guanidine and disulfide groups.
[0261] ⑤ According to the complex described in technical solution 4, the binding part is selected from one or more of dibasic fatty acids or polybasic fatty acids, amino acids, targeting proteins, targeting polypeptides, and targeting polysaccharides.
[0262] ⑥ The complex according to technical solution 4, wherein the complex is a complex formed by connecting a fatty acid with 3-50 carbon atoms and a water-soluble amino acid; or, the complex is a complex formed by connecting a fatty acid with 3-50 carbon atoms to a targeting polypeptide; or, the complex is a complex formed by reacting a fatty acid with 3-50 carbon atoms, a targeting polypeptide and PEG; or, the complex is a complex formed by reacting a surfactant and one or more selected from dibasic fatty acids or polybasic fatty acids, amino acids, targeting proteins, targeting polypeptides and targeting polysaccharides.
[0263] ⑦ According to the complex described in technical solution 4, the saturated and / or unsaturated fatty acid is selected from saturated fatty acids or unsaturated fatty acids with a carbon number of 3-50, and the fatty acid is a fatty acid or amino acid containing a double bond, a triple bond, a hydroxyl group, an amino group and / or oxygenated, and is a monobasic acid, a dibasic acid or a polybasic acid.
[0264] ⑧ According to the complex of technical solution 4, the saturated and / or unsaturated fatty acid is selected from saturated fatty acids with 3-46 carbon atoms, monoenoic acids with 3-34 carbon atoms, dienoic acids with 5-30 carbon atoms, trienoic acids with 7-30 carbon atoms, tetraenoic acids with 12-38 carbon atoms, pentaenoic acids with 12-38 carbon atoms, hexaenoic acids with 22-38 carbon atoms, ynoic acids with 6-22 carbon atoms, diynoic acids with 10-22 carbon atoms, triynoic acids with 12-22 carbon atoms, eneynoic acids with 8-20 carbon atoms, Fatty acids with 3-30 chain carbon atoms and 1-10 alkyl groups and / or 1-3 hydroxyl groups on the branches, saturated straight-chain and branched dicarboxylic acids and tricarboxylic acids with 3-38 carbon atoms, unsaturated straight-chain or branched dicarboxylic acids and tricarboxylic acids with 4-18 carbon atoms which may be substituted with hydroxyl groups, carboxylic acids with 3-18 carbon atoms substituted with amino, hydroxyl, oxo and / or methyl groups, N-acylamino acids with 6-30 carbon atoms, amino acids containing 2 or more acyl groups, and one or more polycarboxylic acids connected by thioether bonds and amide bonds.
[0265] ⑨ According to the complex described in technical solution 4, the saturated / unsaturated fatty acid is one or more selected from fumaric acid, octanoic acid, glutaconic acid, hexanoic acid, nonanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid, octadecanoic acid, eicosanoic acid, oleic acid, linoleic acid, linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid, pentacosanoic acid, heptanoic acid, decanoic acid, dodecenoic acid, tetradecenoic acid, docosahexaenoic acid, and octacosanoic acid, or the carbon chain residues formed therefrom.
[0266] ⑩ The complex according to claim 4, wherein the water-soluble portion is a molecule or a residue of a molecule containing one or more groups selected from the group consisting of sulfhydryl, amino, carboxylic acid, hydroxyl, and disulfide groups; the molecule is one or more water-soluble macromolecules or their residues selected from the group consisting of proteins, polysaccharides, nucleic acids, and synthetic water-soluble polymers;
[0267] and / or, one or more medium molecules or their residues selected from polypeptides, oligopeptides, oligosaccharides, oligonucleotides and synthetic water-soluble medium molecular weight polymers;
[0268] and / or, one or more water-soluble small molecules or their residues selected from amino acids, monosaccharides, disaccharides, nucleotides, water-soluble vitamins and deoxynucleotides;
[0269] and / or, a molecule or a residue of a molecule connected to the carbon chain serving as the active part, wherein the molecule or the residue of a molecule contains one or more groups selected from the group consisting of a thiol group, an amino group, a carboxylic acid group, a hydroxyl group, and a disulfide group.
[0270] According to the complex of technical solution 10, the protein as the water-soluble macromolecule is one or more water-soluble macromolecules selected from serum albumin, immunoglobulin, water-soluble collagen, chaperone protein, water-soluble glycoprotein and CD14; the polysaccharide as the macromolecule is one or more water-soluble macromolecules selected from dextran, hyaluronic acid, sialic acid, heparin sulfate, heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, acetyl water-soluble cellulose derivatives, β-cyclodextrin and its derivatives and water-soluble chitosan derivatives; the water-soluble polymer as the macromolecule is one or more water-soluble macromolecules selected from polyethylene glycol and carboxylated or amino polyethylene glycol, polyvinyl alcohol and carboxylated or quaternized polyvinyl alcohol, polyacrylic acid and ammonium polyacrylate;
[0271] The water-soluble medium molecular weight polymer is selected from one or more substances selected from targeting polypeptides, oligopeptides, oligosaccharides, oligonucleotides and / or water-soluble polyamino acids;
[0272] The monosaccharides and / or disaccharides of the water-soluble small molecules are selected from one or more of glucose, fructose, rhamnose, sorbose, sucrose, maltose, lactose and trehalose; the nucleotides and / or deoxynucleotides of the water-soluble small molecules are selected from one or more of adenylic acid, guanylic acid, uridine monophosphate, cytidylic acid, thymidylic acid, inosinic acid, deoxyadenylic acid, deoxyguanylic acid, deoxycytidylic acid and deoxythymidylic acid; the amino acids are selected from one or more of serine, threonine, cysteine, asparagine, glutamine, tyrosine, lysine, arginine, histidine, aspartic acid, glutamic acid, citrulline, ornithine, taurine and aminobutyric acid; the vitamins of the water-soluble small molecules are selected from one or more of vitamin B1, pantothenic acid, vitamin B6 and vitamin C.
[0273] According to the complex described in technical solution 11, the targeting polypeptide includes any one of a protein or a neutralizing antibody fragment that specifically targets a microbial lipid membrane, a bacterial and fungal cell wall, or a viral surface protein domain.
[0274] According to the complex described in technical solution 11, the water-soluble polyamino acid is selected from polyglutamic acid, polylysine and / or polyaspartic acid.
[0275] According to the complex described in technical solution 1, the binding portion and the water-soluble portion are the same, that is, proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, amino acids, nucleotides, vitamins, water-soluble polymers, water-soluble polyamino acids and / or polysaccharide molecules or residues of these molecules that can bind to microbial lipid membranes and surface domains, and the molecules or molecular residues include one or more groups selected from thiol, amino, carboxylic acid, hydroxyl, and disulfide groups.
[0276] The complex according to technical solution 1 is a compound obtained by reacting saturated and / or unsaturated fatty acids having 3 to 100 carbon atoms with proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, nucleotides, vitamins, amino acids, water-soluble polymers, water-soluble polyamino acids and / or polysaccharides; or it is a compound obtained by reacting saturated and / or unsaturated fatty acids having 3 to 50 carbon atoms with proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, nucleotides, vitamins, amino acids, water-soluble polymers, water-soluble polyamino acids and / or polysaccharide molecules, and a mixture of unreacted fatty acids and / or unreacted proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, nucleotides, vitamins, amino acids, water-soluble polymers, water-soluble polyamino acids and / or polysaccharide molecules.
[0277] The complex according to technical solution 1 is a complex containing saturated and / or unsaturated fatty acids with 3-100 carbon atoms and proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, nucleotides, vitamins, amino acids, water-soluble polymers, water-soluble polyamino acids and / or polysaccharide molecules, which are compounded by physical and chemical reactions or a mixture obtained by direct physical mixing, wherein the physical and chemical reactions include hydrogen bonds or van der Waals forces or a combination of the two.
[0278] The complex according to technical solution 15 is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3-100 carbon atoms with at least one selected from proteins, polypeptides, oligopeptides and amino acids; or it is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3-100 carbon atoms with at least one selected from proteins, polypeptides, oligopeptides and amino acids, and a mixture of unreacted fatty acids and / or unreacted at least one selected from proteins, polypeptides, oligopeptides and amino acids.
[0279] The complex according to technical solution 15 is a compound obtained by reacting a saturated and / or unsaturated fatty acid with a carbon number of 3-100, PEG and at least one selected from proteins, polypeptides, oligopeptides and amino acids; or it is a compound obtained by reacting a saturated and / or unsaturated fatty acid with a carbon number of 3-100, PEG and at least one selected from proteins, polypeptides, oligopeptides and amino acids, and a mixture of unreacted fatty acid, unreacted PEG and / or unreacted at least one selected from proteins, polypeptides, oligopeptides and amino acids.
[0280] The complex according to technical solution 15 is a compound obtained by reacting saturated and / or unsaturated fatty acids with 3-100 carbon atoms with polysaccharides, monosaccharides, disaccharides and / or oligosaccharides; or it is a compound obtained by reacting saturated and / or unsaturated fatty acids with 3-100 carbon atoms with polysaccharides, monosaccharides, disaccharides and / or oligosaccharides, and a mixture of unreacted fatty acids and / or unreacted polysaccharides, monosaccharides, disaccharides and / or oligosaccharides.
[0281] The complex according to technical solution 15 is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3-100 carbon atoms, PEG and at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides; or it is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3-100 carbon atoms, PEG and at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides, and a mixture of unreacted fatty acids, unreacted PEG and / or unreacted polysaccharides, monosaccharides, disaccharides and / or oligosaccharides.
[0282] According to the complex described in technical solution 15, the protein is one or more selected from serum albumin, immunoglobulin, water-soluble collagen, chaperone protein, water-soluble glycoprotein and CD14.
[0283] According to the complex described in technical solution 15, the polysaccharide is selected from one or more of dextran and / or hyaluronic acid, sialic acid, heparin sulfate, heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, acetyl water-soluble cellulose derivatives, β-cyclodextrin and its derivatives and water-soluble chitosan derivatives.
[0284] The complex according to technical solution 15 is a compound obtained by reacting a saturated and / or unsaturated fatty acid containing 3 to 100 carbon atoms, a linker and a protein containing a thiol group; or a mixture of the compound obtained by the above reaction, unreacted fatty acid, unreacted linker, and / or unreacted protein containing a thiol group; wherein the linker is one or more of amino acids, succinic acid, butadienoic acid, glutaric acid, hexamethylenediamine, carbamate, short peptide, N-hydroxybutyromide, polyethylene glycol and derivatives of the above compounds.
[0285] The complex according to technical solution 23 is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 100 carbon atoms, N-hydroxybuteneimide and a protein containing a sulfhydryl group; or a mixture of the compound obtained by the above reaction, unreacted fatty acid, unreacted N-hydroxybuteneimide and / or unreacted protein containing a sulfhydryl group.
[0286] The complex according to technical solution 15 is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 100 carbon atoms, cystamine and at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides; or a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 50 carbon atoms, cystamine and at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides, and a mixture of unreacted fatty acids and unreacted at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides, and / or unreacted cystamine.
[0287] According to the complex described in any one of technical solutions 15-25, the compound obtained by the reaction contains one or more of an amide group, an ester group, a thioether group or an ether group, and these groups serve as the connecting part between the water-soluble part and the active part.
[0288] According to the complex described in any one of technical solutions 4 to 25, the number of carbon atoms of the saturated and / or unsaturated fatty acid is 3-50.
[0289] According to the complex described in Technical Solution 27, the number of carbon atoms is 3-48.
[0290] According to the complex described in technical solution 27, the carbon atoms are 3-26.
[0291] According to the complex described in any one of technical solutions 4-25, the saturated and / or unsaturated fatty acid is a fatty acid with 3-40 carbon atoms and containing 1-8 C=C double bonds, a fatty acid containing 1-7 C=C double bonds, a fatty acid containing 1-6 double bonds, a fatty acid containing 1-5 double bonds, a fatty acid containing 1-4 double bonds, a fatty acid containing 1-3 double bonds, or a fatty acid containing 1-2 double bonds.
[0292] According to the complex described in any one of technical solutions 4 to 25, the saturated and / or unsaturated fatty acid is a fatty acid with 1 to 6 double bonds and 3 to 30 carbon atoms.
[0293] According to the complex described in any one of technical solutions 4-25, the saturated and / or unsaturated fatty acid has 3-30 carbon atoms.
[0294] According to the complex described in any one of technical solutions 4 to 25, the saturated and / or unsaturated fatty acids are selected from one or more fatty acids of fumaric acid, octanoic acid, glutaconic acid, hexanoic acid, nonanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid, octadecanoic acid, eicosanoic acid, oleic acid, linoleic acid, linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid, pentacosanoic acid, heptanoic acid, decanoic acid, dodecenoic acid, tetradecenoic acid, docosahexaenoic acid and octacosanoic acid.
[0295] According to the complex according to any one of technical solutions 4 to 25, the protein is human serum albumin or bovine serum albumin, or CD14; or the polysaccharide is dextran and / or hyaluronic acid.
[0296] The present invention also provides a preparation for preventing, inhibiting or treating microbial infection prepared from the above-mentioned complex.
[0297] The preparation according to the present invention is a pharmaceutical preparation or an environmental disinfection preparation.
[0298] According to the preparation of the present invention, the pharmaceutical preparation is one selected from the group consisting of inhalation, nasal spray, injection, oral preparation and external skin preparation.
[0299] The compound of the present invention is used in the preparation of a pharmaceutical preparation for preventing, preventing and / or treating microbial infection or an environmental microbial disinfection agent.
[0300] According to the use of the present invention, the microorganism is any one or two selected from viruses and bacteria.
[0301] According to the use of the present invention, the virus is an enveloped virus; and / or a non-enveloped virus.
[0302] According to the application of the present invention, the virus is one or more viruses selected from the group consisting of novel coronavirus, influenza virus, human immunodeficiency virus (HIV), hepatitis B virus, human herpes virus, Ebola virus, rabies virus and human papillomavirus (HPV), and the bacteria are one or more bacteria selected from the group consisting of Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae and Pseudomonas aeruginosa.
[0303] According to the application of the present invention, the virus is selected from one or more of H7N9 influenza virus, H5N1 influenza virus, HIV virus, new coronavirus, HPV virus and rabies virus.
[0304] The present invention also provides a method for preparing the complex, wherein the complex is obtained by reacting fat-soluble saturated and / or unsaturated carbon chains with branched, cyclic and / or linear structures, water-soluble molecules, and proteins, polypeptides, amino acids, oligopeptides, oligosaccharides, monosaccharides and / or polysaccharide molecules that can bind to microbial lipid membranes, microbial surface domains or cell walls as needed, as well as linker molecules as needed, in the presence of a catalyst.
[0305] Further preferably, according to the method for preparing the complex of the present invention, the complex is a product obtained by purifying the compound obtained by the reaction.
[0306] The present invention also provides a method for preparing the complex, which is obtained by physically mixing fat-soluble fatty acids with saturated and / or unsaturated carbon chains having branched, cyclic and / or linear structures with water-soluble molecules, and proteins, polypeptides, amino acids, oligopeptides, oligosaccharides, monosaccharides and / or polysaccharide molecules that can bind to microbial lipid membranes, viral surface domains or cell walls, as needed.
[0307] The present invention also provides a method for preparing the complex, wherein the complex is obtained by reacting a saturated and / or unsaturated fatty acid containing 3 to 100 carbon atoms with any one of proteins, polypeptides, oligopeptides, polysaccharides, oligosaccharides, monosaccharides, disaccharides, nucleotides, vitamins, amino acids, water-soluble polymers, water-soluble polyamino acids and / or polysaccharides in the presence of a catalyst.
[0308] More preferably, the complex is a product obtained by purifying the compound obtained by the reaction.
[0309] The present invention also provides a method for preparing the complex, which is obtained by physically and chemically compounding a saturated and / or unsaturated fatty acid containing 3 to 100 carbon atoms with a protein, polypeptide, oligopeptide, polysaccharide, oligosaccharide, monosaccharide, disaccharide, nucleotide, vitamin, amino acid, water-soluble polymer, water-soluble polyamino acid and / or polysaccharide molecule or directly physically mixing the complex.
[0310] The compound of the present invention can prevent and treat viral, bacterial, and fungal infections and its preparation can be used in preventing or treating various viral, bacterial, and fungal infections. Specific application methods include:
[0311] It can be used before infection to prevent viral, bacterial and fungal infections;
[0312] Can be used after infection to kill viruses, bacteria, and fungi in the body; and
[0313] The environment of items can be disinfected to prevent the spread of viruses, bacteria and fungi.
[0314] Compared with the prior art, the present invention has the following beneficial effects:
[0315] (1) The effect of the complex provided by the present invention on viruses is not affected by viral mutations
[0316] The complex provided by the present invention targets the basic structures of the virus - the envelope and nucleocapsid. For enveloped viruses, the complex destroys the viral envelope, making the virus lose the ability to infect cells; for non-enveloped viruses, the complex directly wraps the viral nucleocapsid for hydrophobic isolation, making the virus unable to infect cells; the complex will not become ineffective due to viral mutations.
[0317] (2) The complex provided by the present invention can kill drug-resistant microorganisms without causing the microorganisms to develop drug resistance.
[0318] Bacteria exhibit drug resistance because they harbor resistance genes that can express enzymes that break down antibiotics, rendering them ineffective. The complex of the present invention kills microorganisms through a mechanism distinct from that of antibiotics. It acts directly on the lipid membrane, the fundamental structure of microorganisms, by partially integrating into it, affecting its homeostasis and disrupting the cell wall and membrane. Therefore, it is unaffected by the enzymes that break down antibiotics in resistant bacteria.
[0319] (3) The complex provided by the present invention is safe for human cells
[0320] Viral particles, as well as bacterial and fungal cells, are significantly smaller than human cells. The complex, at therapeutic doses, preferentially binds to viruses, bacteria, and fungi. Cell-based experiments have confirmed that at therapeutic doses, the complex has no significant effect on cell membranes. The complex is safe for human cells.
[0321] (4) The complexes provided by the present invention can act in different areas depending on their molecular size. Large molecular complexes can be retained on the surface of the respiratory mucosa or in the blood circulation, immediately inactivating viruses, bacteria, or fungi and preventing them from spreading in the body. Large molecular complexes cannot enter normal tissues and can only enter the inflammatory sites after viral, bacterial, or fungal infection. Small molecular complexes, on the other hand, can penetrate the blood vessel wall into the interstitial space and interstitial fluid, targeting viruses, bacteria, or fungi for killing.
[0322] (5) Fatty acids, fatty alcohols, fat-soluble vitamins, and steroids are insoluble in water or have very low water solubility and cannot be directly injected into the human body. Direct injection into the vein can cause pulmonary embolism. Fatty acids in food are absorbed by the human body in the form of emulsions, and then flow back into the blood circulation in the form of chylomicrons through the lymphatic system, lymphatic vessels, and thoracic ducts. Moreover, fatty acids are encapsulated in the emulsion in the form of non-covalent bonds with proteins. In this form, the hydrophobic groups are encapsulated inside and cannot come into contact with infected viruses and bacteria, and thus cannot play a bactericidal and antiviral role. The above problems can be avoided by converting fat-soluble hydrophobic compounds into aqueous solution compounds with high affinity for pathogenic microorganisms.
[0323] Furthermore, based on an in-depth study of the mechanism of action, the present invention has discovered and provided the following fourth set of technical solutions.
[0324] 1. A water-soluble carbon chain substance for regulating transmembrane transport and / or fluidity of cell membranes, comprising an active portion, a binding portion, and a water-soluble portion, wherein the active portion is a fat-soluble saturated and / or unsaturated carbon chain with a branched, cyclic, and / or linear structure, wherein the carbon chain is a molecule or a residue of a molecule, and wherein the carbon chain is a carbon chain with 3-100 carbon atoms; wherein the active portion is a saturated and / or unsaturated fatty acid, aliphatic hydrocarbon, or cyclic hydrocarbon; or an aromatic ring compound or a heterocyclic compound; or a carbon chain with 3-100 carbon atoms or a residue of a carbon chain formed from any one or more of their salts, alcohols, ethers, esters, or other derivatives;
[0325] The water-soluble portion is a water-soluble molecule or a residue of a molecule, wherein the molecule contains one or more functional groups selected from amide groups, phosphoryloxy groups, carboxylic acid groups, phosphoric acid groups, sulfonic acid groups, sulfonyloxy groups, hydroxyl groups, quaternary ammonium groups, thioether groups, disulfide bonds, ether groups, sulfhydryl groups, aldehyde groups, ester groups, amine groups, amino groups, urea groups, and guanidine groups. The water-soluble portion may be one or more functional groups connected to the carbon chain serving as the active portion;
[0326] The binding portion is a molecule or a residue of a molecule that can bind to a microbial lipid membrane, a microbial surface protein, a microbial surface polysaccharide or a cell wall component, or can bind to a polysaccharide or protein or polypeptide in a microorganism, plant, animal or human organism, or a molecule or a residue of a molecule that can bind to a cell membrane or a polysaccharide or cell wall component on the cell membrane surface of a plant, animal or human organism tissue. The binding portion can be the same as the water-soluble portion, i.e., a protein, polypeptide, amino acid, oligopeptide, oligosaccharide, monosaccharide, disaccharide, amino acid, nucleotide, vitamin, water-soluble polymer, water-soluble polyamino acid and / or polysaccharide molecule or its residue that can bind to a surface domain of a microbial lipid membrane or a cell membrane of a plant, animal or human organism tissue;
[0327] The number of any one of the active part, the water-soluble part and the binding part can be 1 or more.
[0328] 2. According to the water-soluble carbon chain substance described in technical solution 1, the number of carbon atoms is 3-50, preferably 3-48, and more preferably 3-26.
[0329] 3. The water-soluble carbon chain substance according to technical solution 1, wherein the water-soluble portion is a water-soluble molecule or a residue of a molecule containing one or more groups selected from the group consisting of a thiol group, an amino group, a phosphate group, a carboxylic acid group, a sulfonic acid group, a hydroxyl group, an amine group, a urea group, a guanidine group, and a disulfide group;
[0330] The binding portion has a group that plays a binding role, that is, a molecule or a residue of a molecule that can bind to a microbial lipid membrane, a microbial surface protein, a microbial surface polysaccharide or a cell wall component, or can bind to a polysaccharide or protein or polypeptide in a microbial, plant, animal or human body, or a molecule or a residue of a molecule that can bind to a cell membrane or a polysaccharide or cell wall component on the cell membrane surface of a plant, animal or human body tissue. The group is derived from a water-soluble portion or from one or more groups selected from thiol, amino, phosphate, carboxylic acid, sulfonic acid, hydroxyl, amine, urea, guanidine and disulfide groups that serve as an independent binding portion, or from one or more groups selected from thiol, amino, phosphate, carboxylic acid, sulfonic acid, hydroxyl, amine, urea, guanidine and disulfide groups that provide a carbon chain-to-carbon chain connection, so that the complex has one or more groups selected from thiol, amino, phosphate, carboxylic acid, sulfonic acid, hydroxyl, amine, urea, guanidine and disulfide groups.
[0331] 4. According to any one of technical solutions 1-3, the water-soluble carbon chain substance, the binding part is selected from one or more of dibasic fatty acids or polybasic fatty acids, amino acids, targeting proteins, targeting polypeptides, and targeting polysaccharides.
[0332] 5. The water-soluble carbon chain substance according to any one of technical solutions 1-3, wherein the water-soluble carbon chain substance is a compound, a complex or a mixture.
[0333] 6. The water-soluble carbon chain substance according to technical solution 5 is a complex formed by connecting a fatty acid with 3-50 carbon atoms and a water-soluble amino acid; a complex formed by connecting a fatty acid with 3-50 carbon atoms to a targeting polypeptide; a complex formed by reacting a fatty acid with 3-50 carbon atoms, a targeting polypeptide and PEG; or a complex formed by reacting a surfactant and one or more selected from dibasic fatty acids or polybasic fatty acids, amino acids, targeting proteins, targeting polypeptides and targeting polysaccharides.
[0334] 7. According to the water-soluble carbon chain substance according to any one of technical solutions 1-4, the saturated and / or unsaturated fatty acid is selected from saturated fatty acids or unsaturated fatty acids with a carbon number of 3-50, and the fatty acid is a fatty acid or amino acid containing a double bond, a triple bond, a hydroxyl group, an amino group and / or is oxidized, and is a monobasic acid, a dibasic acid or a polybasic acid.
[0335] 8. The water-soluble carbon chain substance according to technical solution 7, wherein the saturated and / or unsaturated fatty acid is selected from saturated fatty acids having 3-46 carbon atoms, monoenoic acids having 3-34 carbon atoms, dienoic acids having 5-30 carbon atoms, trienoic acids having 7-30 carbon atoms, tetraenoic acids having 12-38 carbon atoms, pentaenoic acids having 12-38 carbon atoms, hexaenoic acids having 22-38 carbon atoms, ynoic acids having 6-22 carbon atoms, diynoic acids having 10-22 carbon atoms, triynoic acids having 12-22 carbon atoms, and eneynoic acids having 8-20 carbon atoms. , fatty acids with 3-30 carbon atoms in the main chain and 1-10 alkyl groups and / or 1-3 hydroxyl groups on the side chains, saturated straight-chain and branched dicarboxylic acids and tricarboxylic acids with 3-38 carbon atoms, and unsaturated straight-chain or branched dicarboxylic acids and tricarboxylic acids with 4-18 carbon atoms that may be substituted with hydroxyl groups, carboxylic acids with 3-18 carbon atoms substituted with amino, hydroxyl, oxo and / or methyl, N-acylamino acids with 6-30 carbon atoms, amino acids containing 2 or more acyl groups, and one or more polycarboxylic acids connected by thioether bonds and amide bonds.
[0336] 9. The water-soluble carbon chain substance according to technical solution 7, wherein the saturated / unsaturated fatty acid is one or more selected from fumaric acid, octanoic acid, octenic acid, glutaconic acid, hexanoic acid, suberic acid, nonanoic acid, dodecanoic acid, dodecanedioic acid, tridecanoic acid, tridecanedioic acid, tetradecanoic acid, hexadecanoic acid, hexadecanedioic acid, octadecanoic acid, eicosanoic acid, eicosandioic acid, oleic acid, linoleic acid, linolenic acid, eicosapentaenoic acid, docosenoic acid, docosapentaenoic acid, docosahexaenoic acid, pentacosanoic acid, heptanoic acid, decanoic acid, undecenoic acid, dodecenoic acid, tetradecenoic acid, hexadecenoic acid, triacontanedioic acid, docosahexaenoic acid, and octacosanoic acid, or a carbon chain residue formed thereof.
[0337] 10. The water-soluble carbon chain substance according to any one of technical solutions 1 to 4, wherein the water-soluble portion is a molecule or a residue of a molecule containing one or more groups selected from sulfhydryl, amino, carboxylic acid, hydroxyl and disulfide groups; the molecule is one or more water-soluble macromolecules or residues thereof selected from proteins, polysaccharides, nucleic acids and synthetic water-soluble polymers;
[0338] and / or, one or more medium molecules or their residues selected from polypeptides, oligopeptides, oligosaccharides, oligonucleotides and synthetic water-soluble medium molecular weight polymers;
[0339] and / or, one or more water-soluble small molecules or their residues selected from amino acids, monosaccharides, disaccharides, nucleotides, water-soluble vitamins and deoxynucleotides;
[0340] and / or, a molecule or a residue of a molecule connected to the carbon chain serving as the active part, wherein the molecule or the residue of a molecule contains one or more groups selected from the group consisting of a thiol group, an amino group, a carboxylic acid group, a hydroxyl group, and a disulfide group.
[0341] 11. The water-soluble carbon chain substance according to technical solution 10, wherein the protein as the water-soluble macromolecule is one or more water-soluble macromolecules selected from serum albumin, immunoglobulin, water-soluble collagen, chaperone protein, water-soluble glycoprotein and CD14; the polysaccharide as the macromolecule is one or more water-soluble macromolecules selected from dextran, hyaluronic acid, sialic acid, heparin sulfate, heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, acetyl water-soluble cellulose derivatives, β-cyclodextrin and its derivatives and water-soluble chitosan derivatives; the water-soluble polymer as the macromolecule is one or more water-soluble macromolecules selected from polyethylene glycol and carboxylated or amino polyethylene glycol, polyvinyl alcohol and carboxylated or quaternized polyvinyl alcohol, polyacrylic acid and ammonium polyacrylate;
[0342] The water-soluble medium molecular weight polymer is selected from one or more substances selected from targeting polypeptides, oligopeptides, oligosaccharides, oligonucleotides and / or water-soluble polyamino acids;
[0343] The monosaccharides and / or disaccharides of the water-soluble small molecules are selected from one or more of glucose, fructose, rhamnose, sorbose, sucrose, maltose, lactose and trehalose; the nucleotides and / or deoxynucleotides of the water-soluble small molecules are selected from one or more of adenylic acid, guanylic acid, uridine monophosphate, cytidylic acid, thymidylic acid, inosinic acid, deoxyadenylic acid, deoxyguanylic acid, deoxycytidylic acid and deoxythymidylic acid; the amino acids are selected from one or more of serine, threonine, cysteine, asparagine, glutamine, tyrosine, lysine, arginine, histidine, aspartic acid, glutamic acid, citrulline, ornithine, taurine and aminobutyric acid; the vitamins of the water-soluble small molecules are selected from one or more of vitamin B1, pantothenic acid, vitamin B6 and vitamin C.
[0344] 12. According to the water-soluble carbon chain substance described in technical solution 11, the targeting polypeptide includes any one of a protein or a neutralizing antibody fragment that specifically targets microbial lipid membranes, bacterial and fungal cell walls, and viral surface protein domains.
[0345] 13. According to the water-soluble carbon chain substance described in technical solution 11, the water-soluble polyamino acid is selected from polyglutamic acid, polylysine and / or polyaspartic acid.
[0346] 14. The water-soluble carbon chain substance according to technical solution 1, wherein the binding portion and the water-soluble portion are the same, that is, proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, amino acids, nucleotides, vitamins, water-soluble polymers, water-soluble polyamino acids and / or polysaccharide molecules or residues of these molecules that can bind to microbial lipid membranes, cell membranes or cell membrane surface domains of animal or human body tissues, and the molecules or molecular residues include one or more groups selected from thiol, amino, carboxylic acid, hydroxyl, and disulfide groups.
[0347] 15. The water-soluble carbon chain substance according to technical solution 1, which is a compound obtained by reacting a saturated and / or unsaturated fatty acid containing 3-100 carbon atoms with at least one selected from proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, nucleotides, vitamins, amino acids, water-soluble polymers, water-soluble polyamino acids and polysaccharide molecules; or it is a compound obtained by reacting a saturated and / or unsaturated fatty acid containing 3-100 carbon atoms with at least one selected from proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, nucleotides, vitamins, amino acids, water-soluble polymers, water-soluble polyamino acids and polysaccharide molecules, and a mixture of unreacted fatty acids and / or unreacted proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, nucleotides, vitamins, amino acids, water-soluble polymers, water-soluble polyamino acids and polysaccharide molecules.
[0348] 16. The water-soluble carbon chain substance according to technical solution 1 is a complex containing saturated and / or unsaturated fatty acids with 3-100 carbon atoms and at least one selected from proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, nucleotides, vitamins, amino acids, water-soluble polymers, water-soluble polyamino acids and polysaccharide molecules, which are complexed by physical and chemical action or a mixture obtained by direct physical mixing, wherein the physical and chemical action includes hydrogen bonding or van der Waals force or a combination of the two.
[0349] 17. The water-soluble carbon chain substance according to technical solution 15, which is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3-100 carbon atoms with at least one selected from proteins, polypeptides, oligopeptides and amino acids; or it is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3-100 carbon atoms with at least one selected from proteins, polypeptides, oligopeptides and amino acids, and a mixture of unreacted fatty acids and / or unreacted at least one selected from proteins, polypeptides, oligopeptides and amino acids.
[0350] 18. The water-soluble carbon chain substance according to technical solution 15, which is a compound obtained by reacting a saturated and / or unsaturated fatty acid with 3-100 carbon atoms, PEG and at least one selected from proteins, polypeptides, oligopeptides and amino acids; or it is a compound obtained by reacting a saturated and / or unsaturated fatty acid with 3-100 carbon atoms, PEG and at least one selected from proteins, polypeptides, oligopeptides and amino acids, and a mixture of unreacted fatty acids, unreacted PEG and / or unreacted at least one selected from proteins, polypeptides, oligopeptides and amino acids.
[0351] 19. The complex according to technical solution 15, which is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 100 carbon atoms with at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides; or it is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 100 carbon atoms with at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides, and a mixture of unreacted fatty acids and / or unreacted polysaccharides, monosaccharides, disaccharides and / or oligosaccharides.
[0352] 20. The water-soluble carbon chain substance according to technical solution 15, which is a compound obtained by reacting a saturated and / or unsaturated fatty acid with 3-100 carbon atoms, PEG and at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides; or it is a compound obtained by reacting a saturated and / or unsaturated fatty acid with 3-100 carbon atoms, PEG and at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides, and a mixture of unreacted fatty acids, unreacted PEG and / or unreacted polysaccharides, monosaccharides, disaccharides and / or oligosaccharides.
[0353] 21. The water-soluble carbon chain substance according to technical solution 15 or 16, wherein the protein is selected from one or more of serum albumin, immunoglobulin, water-soluble collagen, chaperone protein, water-soluble glycoprotein and CD14.
[0354] 22. According to the water-soluble carbon chain substance described in technical solution 15 or 16, the polysaccharide is selected from one or more of dextran and / or hyaluronic acid, sialic acid, heparin sulfate, heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, acetyl water-soluble cellulose derivatives, β-cyclodextrin and its derivatives and water-soluble chitosan derivatives.
[0355] 23. The water-soluble carbon chain substance according to technical solution 15 is a compound obtained by reacting a saturated and / or unsaturated fatty acid containing 3-100 carbon atoms, a linker and a protein containing a sulfhydryl group; or a mixture of the compound obtained by the above reaction, unreacted fatty acid, unreacted linker, and / or unreacted protein containing a sulfhydryl group; wherein the linker is one or more of amino acids, succinic acid, butadienoic acid, glutaric acid, hexamethylenediamine, carbamate, short peptide, N-hydroxybutyromide, polyethylene glycol and derivatives of the above compounds.
[0356] 24. The water-soluble carbon chain substance according to technical solution 23 is a compound obtained by reacting a saturated and / or unsaturated fatty acid containing 3 to 100 carbon atoms, N-hydroxybuteneimide and a protein containing a sulfhydryl group; or a mixture of the compound obtained by the above reaction, unreacted fatty acid, unreacted N-hydroxybuteneimide and / or unreacted protein containing a sulfhydryl group.
[0357] 25. The water-soluble carbon chain substance according to technical solution 15, which is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 100 carbon atoms, cystamine and at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides; or a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 50 carbon atoms, cystamine and at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides, and a mixture of unreacted fatty acid and unreacted at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides and / or unreacted cystamine.
[0358] 26. The water-soluble carbon chain substance according to any one of technical solutions 15-25, wherein the compound obtained by the reaction contains one or more of an amide group, an ester group, a thioether group or an ether group, and these groups serve as the connecting part between the water-soluble part and the active part.
[0359] 27. According to the water-soluble carbon chain substance according to any one of technical solutions 15-25, the number of carbon atoms of the saturated and / or unsaturated fatty acid is 3-50, preferably 3-48, more preferably 3-30, and more preferably 3-26.
[0360] 28. According to the water-soluble carbon chain substance described in any one of technical solutions 15-25, the saturated and / or unsaturated fatty acid is a fatty acid with 3-40 carbon atoms and 1-8 C=C double bonds, a fatty acid with 1-7 C=C double bonds, a fatty acid with 1-6 double bonds, a fatty acid with 1-5 double bonds, a fatty acid with 1-4 double bonds, a fatty acid with 1-3 double bonds, or a fatty acid with 1-2 double bonds; preferably, the saturated and / or unsaturated fatty acid is a fatty acid with 1-6 double bonds and 3-30 carbon atoms.
[0361] 29. The water-soluble carbon chain substance according to any one of technical solutions 15-25, wherein the saturated and / or unsaturated fatty acid has 3-30 carbon atoms.
[0362] 30. The water-soluble carbon chain substance according to any one of technical solutions 15 to 25, wherein the saturated and / or unsaturated fatty acids are selected from one or more of fumaric acid, octanoic acid, octenoic acid, glutaconic acid, hexanoic acid, suberic acid, nonanoic acid, dodecanoic acid, dodecanedioic acid, tridecanoic acid, tridecanedioic acid, tetradecanoic acid, hexadecanoic acid, hexadecanedioic acid, octadecanoic acid, eicosanoic acid, eicosandioic acid, oleic acid, linoleic acid, linolenic acid, eicosapentaenoic acid, docosenoic acid, docosapentaenoic acid, docosahexaenoic acid, pentacosanoic acid, heptanoic acid, decanoic acid, undecenoic acid, dodecenoic acid, tetradecenoic acid, hexadecenoic acid, triacontanedioic acid, docosahexaenoic acid, and octacosanoic acid.
[0363] 31. The water-soluble carbon chain substance according to any one of technical solutions 15-25, wherein the protein is human serum albumin or bovine serum albumin, or CD14; or the polysaccharide is dextran and / or hyaluronic acid.
[0364] 32. The water-soluble carbon chain substance according to technical solution 75, wherein the saturated and / or unsaturated fatty acid has 3-30 carbon atoms;
[0365] Preferably, the saturated and / or unsaturated fatty acids are selected from one or more fatty acids selected from fumaric acid, octanoic acid, octenoic acid, glutaconic acid, hexanoic acid, suberic acid, nonanoic acid, dodecanoic acid, dodecanedioic acid, tridecanoic acid, tridecanedioic acid, tetradecanoic acid, hexadecanoic acid, hexadecanedioic acid, octadecanoic acid, eicosanoic acid, eicosandioic acid, oleic acid, linoleic acid, linolenic acid, eicosapentaenoic acid, docosenoic acid, docosapentaenoic acid, docosahexaenoic acid, pentacosanoic acid, heptanoic acid, decanoic acid, undecenoic acid, dodecenoic acid, tetradecenoic acid, hexadecenoic acid, triacontanedioic acid, docosahexaenoic acid, and octacosanoic acid.
[0366] Also preferably, the protein is human serum albumin or bovine serum albumin, or CD14; or the polysaccharide is dextran and / or hyaluronic acid.
[0367] 1. According to the water-soluble carbon chain substance described in the previous technical solution, the compound obtained by the reaction is fatty acid and albumin
[0368] or SBP1 reaction, which has any one or more of the following structural formulas:
[0369] 33. According to the water-soluble carbon chain substance described in the previous technical solution, the compound obtained by the reaction is a compound obtained by the reaction of a monobasic fatty acid with 3-10 carbon atoms, PEG and an amino acid, or a compound obtained by the reaction of a monobasic fatty acid with 3-10 carbon atoms, a saturated dibasic fatty acid with 5-8 carbon atoms, PEG and taurine.
[0370] 34. The water-soluble carbon chain substance according to the above technical solution, wherein the compound obtained by the reaction is a compound having at least one of the following structural formulas:
[0371] Wherein n is an integer from 1 to 200.
[0372] 35. The water-soluble carbon chain substance according to the above technical solution, wherein the compound obtained by the reaction is any one or more compounds having the following structural formulas obtained by the reaction of fatty acids and dextran:
[0373] 36. The water-soluble carbon chain substance according to the above technical solution, wherein the compound obtained by the reaction is any one or more compounds having the following structural formulas obtained by the reaction of fatty acids and hyaluronic acid:
[0374] n is an integer from 1 to 2000.
[0375] 37. According to the water-soluble carbon chain substance described in the previous technical solution, the compound obtained by the reaction is a compound obtained by reacting a fatty acid with 3-10 carbon atoms with PEG and glucose.
[0376] 38. The water-soluble carbon chain substance according to the above technical solution, wherein the compound obtained by the reaction is a compound having the following structural formula:
[0377] n is an integer from 1 to 200.
[0378] 39. The water-soluble carbon chain substance according to the above technical solution, wherein the compound obtained by the reaction is a compound having a thioether bond and having any one or more of the following structural formulas obtained by reacting fatty acid, N-hydroxybutene imide and protein:
[0379] 40. The water-soluble carbon chain substance according to the above technical solution, wherein the compound obtained by the reaction is any one or more compounds having the following structural formulas obtained by the reaction of fatty acid, cystamine and dextran:
[0380] 41. The water-soluble carbon chain substance according to the above technical solution, wherein the compound obtained by the reaction is any one or more compounds having the following structural formula obtained by the reaction of fatty acid, cystamine and hyaluronic acid:
[0381] 42. The water-soluble carbon chain substance according to any one of the preceding technical solutions, comprising a small molecule compound containing a hydroxyl group and a benzene ring; preferably, comprising one, two, or more substances selected from the following group:
[0382] Flavonoids, isoflavones, anthocyanins, soy isoflavones, aloe-emodin, grape seed extract, green tea flavonoids, naringenin, tartrazine, baicalein, riboflavin, quercetin, graphite flavonoids, cinnamon, buxol, hawthorn flavonoids, morin, luteolin, melilotin, gypsum flavonoids, honeysuckle flavonoids, gentian flavonoids, platycodon flavonoids, violet flavonoids, perilla flavonoids, chrysanthemum flavonoids, artemisia annua flavonoids, red peony flavonoids, salvia miltiorrhiza flavonoids, safflower flavonoids, rhodiola rosea flavonoids, red date flavonoids, wolfberry flavonoids, rehmannia glutinosa flavonoids, ganoderma lucidum flavonoids, schisandra chinensis flavonoids, licorice flavonoids, panax flavonoids, curcumin, apigenin, carotene, anthocyanins, lutein, zeaxanthin, mustard flavonoids, rutin, coriander, pollen flavonoids, sand Echinoflavones, marigold flavonoids, cinnamon flavonoids, isoflavonoids and anthocyanins; rutin, emodin, fucoxanthin, gallic acid, kakirin, morin, echinacea glycosides, grape seed proanthocyanidins, phenolic acids, tea polyphenols, naringin, citric acid, flavonols, glycyrrhizic acid, cinnamic acid, flavonoid glycosides, silymarin, matrine, tanshinone, erythrocephalin, seabuckthorn acid, perillyl alcohol, anisic acid, phellodendron, hesperidin, punica granatum, morilin, naringin, rubellin, gentiopicroside, jasmonate, naringol, carotene, apigenin, umelin, morilin, honeysuckle glycoside, chrysanthemin, olive oleate, tea cyanidin, theanine, wine glycosides, platycodin, perillyl alcohol glycosides, morus alba, safflower glycosides, pinus needle glycosides, pachycocin, caffeic acid, chlorogenic acid;Resveratrol, white tea polyphenols, resveratrol disaccharide, banana lutein, anthocyanin, arachidonic acid, peanut flavonoids, pepper phenol, fennel, flavonoids, baicalein, flavonoid glycosides, flavanols, red wine polyphenols, rhodiola rosea, safflower phenol, black tea flavonoids, black sesame, rye phenol, trehalitol, seaweed polysaccharides, alginic acid, albizzia alkaloids, hemp phenol, polydatin, cucurbitacin, fenugreek, cucurbitacin, pollen phenol, pollen flavonoids, Pollen glycosides, pollen esters, arachidic acid, peanut flavonoid glycosides, peanut isoflavones, peanut isoflavone glycosides, peanut isoflavone disaccharides, peanut isoflavone trisaccharides, peanut resveratrol, peanut resveratrol disaccharides, peanut resveratrol trisaccharides, peanut resveratrol tetrasaccharides, peanut resveratrol pentasaccharides, peanut resveratrol hexasaccharides, peanut resveratrol heptasaccharides, peanut resveratrol octasaccharides, peanut resveratrol nonasaccharides, peanut resveratrol decasaccharides, peanut white quinoa Resveratrol undecanose, catechin, epicatechin, tea polyphenols, catechin, chlorophyll, protocatechin, hesperidin, anthocyanidin, anthocyanin, anthocyanin, anthocyanin, glucoside, glucoside, alfalfa, soy isoflavones, flavanols, quercetin, buckwheat glutenin, persimmon glutinin, persimmon glutinin, punicic acid, punica granatum, blueberry glutinin, resveratrol, lycopene, naringenin, morin, chlorogenic acid, chlorogenic acid triglucoside ... Chlorogenic acid diglucoside, methyl chlorogenic acid, ethyl chlorogenic acid, propyl chlorogenic acid, butyl chlorogenic acid, isopentyl chlorogenic acid, hexyl chlorogenic acid, octyl chlorogenic acid, benzyl chlorogenic acid, phenylethyl chlorogenic acid, phenylpropyl chlorogenic acid, phenylbutyl chlorogenic acid, isopentyl chlorogenic acid, phenylhexyl chlorogenic acid, phenyloctyl chlorogenic acid, phenylphenyl chlorogenic acid, benzyl alcohol chlorogenic acid, phenylethanol chlorogenic acid, anthocyanidins, proanthocyanidins and catechins.
[0383] 43. The water-soluble carbon chain substance according to any one of the preceding technical solutions, wherein the water-soluble carbon chain substance comprises a water-soluble medium- or short-chain fatty acid, or a fatty acid salt, or a fatty acid derivative, preferably comprising one, two, or more water-soluble medium- or short-chain fatty acid, or a fatty acid salt, or a fatty acid derivative selected from the following substance group:
[0384] Water-soluble medium and short-chain fatty acids such as butyric acid, succinic acid, fumaric acid, valeric acid, glutaric acid, hexanoic acid, adipic acid, heptanoic acid, pimelic acid, octanoic acid, octenic acid, suberic acid, capric acid, and sebacic acid; and any one or more of the following fatty acid derivatives including surfactants, etc.: fatty acid salts, alkyl sulfonates, alkyl sulfate esters, alkyl phosphate esters, alkylamine salts, alkyl quaternary ammonium salts, fatty acylamino acids, betaines, fatty alcohol polyoxyethylene ethers, alkylphenol polyoxyethylene ethers, fatty amine polyoxyethylene ethers, polyol fatty acid esters, polyol polyoxyethylene ether fatty acid esters, fatty acid polyoxyethylene esters, alkyl glycosides, and alcohol ether glycosides.
[0385] 44. The water-soluble carbon chain substance described in any of the above technical solutions is used to prepare a preparation for regulating transmembrane transport of cell membranes, regulating cell membrane structure or function, regulating cell division and proliferation or cell migration, regulating cell aging, and / or regulating cell membrane fluidity.
[0386] 45. The preparation according to the previous technical solution, wherein regulating cell membrane fluidity refers to increasing cell membrane fluidity.
[0387] 46. The preparation according to the previous technical solution, wherein regulating cell membrane fluidity refers to reducing cell membrane fluidity.
[0388] 47. The preparation according to the above technical solution, wherein the cell membrane includes a cytoplasmic membrane and an organelle membrane; the cell membrane or cell includes a cell membrane or cell of a microorganism, or a cell membrane or cell of a plant, animal or human body tissue; the regulation includes increasing or promoting, as well as inhibiting or reducing, wherein the cell membrane of a microorganism includes the cell membrane of bacteria and fungi, and the envelope of a virus;
[0389] The cell membrane structure includes a phospholipid bilayer, proteins and polysaccharides adsorbed on the surface of the phospholipid bilayer and embedded throughout the phospholipid bilayer; specifically, receptor proteins, transmembrane proteins, cytoskeleton proteins and enzymes;
[0390] Among them, transmembrane transport includes active transport, passive transport, endocytosis and exocytosis.
[0391] 48. The preparation according to the above technical solution, wherein the regulating transmembrane transport of cell membranes includes increasing and promoting the release of exosomes from cells to the extracellular space; also includes inhibiting or reducing the release of exosomes from cells to the extracellular space; and preventing viruses from entering cells; the inhibiting or reducing transmembrane transport of viruses means inhibiting or reducing the entry of viruses into cells through endocytosis; or inhibiting or reducing the entry of viruses into cells through fusion of viral envelopes with cell membranes; it is applied to the prevention of all viral infections, mycoplasma and chlamydia infections, and bacterial infections; substances transported across cell membranes include: small molecule compounds, medium molecule compounds, large molecule compounds, pathogenic microorganisms such as viruses, bacteria, mycoplasmas, chlamydias and fungi, and at least one or two or more of nanoparticles and nanomedicines.
[0392] 49. The preparation according to the above technical solution, wherein the preparation is used to improve cell membrane fluidity, including preparations for the prevention, suppression, improvement and / or treatment of drug delivery, gene transfection, cell therapy, diabetes, improvement of the nervous system, Alzheimer's disease, enhancement of the immune system, leukemia, hypercholesterolemia, and / or inflammatory bowel disease.
[0393] 50. The preparation according to the above technical solution, wherein the preparation is used to reduce cell membrane fluidity, including preparations for preventing, preventing, improving and / or treating cardiovascular diseases (including coronary heart disease, hypertension, myocardial infarction, heart failure), obesity, autism, osteoporosis, inflammatory diseases, autoimmune diseases, chronic fatigue syndrome, cell autolysis, viral infection and / or neurodegenerative diseases.
[0394] 51. A preparation for preventing, inhibiting or treating microbial infection made from the water-soluble carbon chain substance described in any of the above technical solutions.
[0395] 52. The preparation according to the above technical solution is a pharmaceutical preparation or an environmental disinfection preparation, and the pharmaceutical preparation is preferably one selected from inhalation, nasal spray, injection, oral preparation and external skin preparation.
[0396] 53. The use of the water-soluble carbon chain substance described in any of the above technical solutions in the preparation of pharmaceutical preparations or environmental disinfection agents for preventing, preventing and / or treating microbial infections; preferably, the microorganism is any one or two selected from viruses, bacteria and fungi; the virus is an enveloped virus; and / or a non-enveloped virus; more preferably, the virus is one or more selected from the group consisting of novel coronavirus, influenza virus, human immunodeficiency virus (HIV), hepatitis B virus, human herpes virus, Ebola virus, rabies virus and human papillomavirus (HPV), and the bacteria is one or more selected from the group consisting of Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae and Pseudomonas aeruginosa; further preferably, the virus is one or more selected from the group consisting of H7N9 influenza virus, H5N1 influenza virus, HIV virus, novel coronavirus, HPV virus and rabies virus.
[0397] 54. The use according to the above technical solution, wherein the water-soluble carbon chain substance according to any one of claims 59 to 99 is prepared into a solution with a concentration of 0.2 mM to 10 mM when acting on microorganisms.
[0398] 55. The use according to the above technical solution, wherein the solution is prepared into a concentration of 0.5 mM-10 mM.
[0399] 56. A preparation for preventing, inhibiting or treating inflammatory reactions and / or body aging prepared from the water-soluble carbon chain substance described in any of the above technical solutions.
[0400] 57. According to the preparation described in the previous technical solution, the body aging includes anti-skin aging, and the prevention, suppression or treatment of inflammatory response includes changing the conformation of inflammatory factors (proteins).
[0401] 58. The preparation according to the previous technical solution, wherein the carbon chain substance is combined with oxygen free radicals.
[0402] 59. The preparation according to the above technical solution, wherein the carbon chain substance is combined with one, two or more substances selected from the following substance group, or the carbon chain substance is one, two or more substances selected from the following substance group, or the carbon chain substance is mixed with one, two or more substances selected from the following substance group to form the preparation:
[0403] Flavonoids, isoflavones, anthocyanins, soy isoflavones, aloe-emodin, grape seed extract, green tea flavonoids, naringenin, tartrazine, baicalein, riboflavin, quercetin, graphite flavonoids, cinnamon, buxol, hawthorn flavonoids, morin, luteolin, melilotin, gypsum flavonoids, honeysuckle flavonoids, gentian flavonoids, platycodon flavonoids, violet flavonoids, perilla flavonoids, chrysanthemum flavonoids, artemisia annua flavonoids, red peony flavonoids, salvia miltiorrhiza flavonoids, safflower flavonoids, rhodiola rosea flavonoids, red date flavonoids, wolfberry flavonoids, rehmannia glutinosa flavonoids, ganoderma lucidum flavonoids, schisandra chinensis flavonoids, licorice flavonoids, panax flavonoids, curcumin, apigenin, carotene, anthocyanins, lutein, zeaxanthin, mustard flavonoids, rutin, coriander, pollen flavonoids, sand Echinoflavones, marigold flavonoids, cinnamon flavonoids, isoflavonoids and anthocyanins; rutin, emodin, fucoxanthin, gallic acid, kakirin, morin, echinacea glycosides, grape seed proanthocyanidins, phenolic acids, tea polyphenols, naringin, citric acid, flavonols, glycyrrhizic acid, cinnamic acid, flavonoid glycosides, silymarin, matrine, tanshinone, erythrocephalin, seabuckthorn acid, perillyl alcohol, anisic acid, phellodendron, hesperidin, punica granatum, morilin, naringin, rubellin, gentiopicroside, jasmonate, naringol, carotene, apigenin, umelin, morilin, honeysuckle glycoside, chrysanthemin, olive oleate, tea cyanidin, theanine, wine glycosides, platycodin, perillyl alcohol glycosides, morus alba, safflower glycosides, pinus needle glycosides, pachycocin, caffeic acid, chlorogenic acid;Resveratrol, white tea polyphenols, resveratrol disaccharide, banana lutein, anthocyanin, arachidonic acid, peanut flavonoids, pepper phenol, fennel, flavonoids, baicalein, flavonoid glycosides, flavanols, red wine polyphenols, rhodiola rosea, safflower phenol, black tea flavonoids, black sesame, rye phenol, trehalitol, seaweed polysaccharides, alginic acid, albizzia alkaloids, hemp phenol, polydatin, cucurbitacin, fenugreek, cucurbitacin, pollen phenol, pollen flavonoids, Pollen glycosides, pollen esters, arachidic acid, peanut flavonoid glycosides, peanut isoflavones, peanut isoflavone glycosides, peanut isoflavone disaccharides, peanut isoflavone trisaccharides, peanut resveratrol, peanut resveratrol disaccharides, peanut resveratrol trisaccharides, peanut resveratrol tetrasaccharides, peanut resveratrol pentasaccharides, peanut resveratrol hexasaccharides, peanut resveratrol heptasaccharides, peanut resveratrol octasaccharides, peanut resveratrol nonasaccharides, peanut resveratrol decasaccharides, peanut white quinoa Resveratrol undecanose, catechin, epicatechin, tea polyphenols, catechin, chlorophyll, protocatechin, hesperidin, anthocyanidin, anthocyanin, anthocyanin, anthocyanin, glucoside, glucoside, alfalfa, soy isoflavones, flavanols, quercetin, buckwheat glutenin, persimmon glutinin, persimmon glutinin, punicic acid, punica granatum, blueberry glutinin, resveratrol, lycopene, naringenin, morin, chlorogenic acid, chlorogenic acid triglucoside ... Chlorogenic acid diglucoside, methyl chlorogenic acid, ethyl chlorogenic acid, propyl chlorogenic acid, butyl chlorogenic acid, isopentyl chlorogenic acid, hexyl chlorogenic acid, octyl chlorogenic acid, benzyl chlorogenic acid, phenylethyl chlorogenic acid, phenylpropyl chlorogenic acid, phenylbutyl chlorogenic acid, isopentyl chlorogenic acid, phenylhexyl chlorogenic acid, phenyloctyl chlorogenic acid, phenylphenyl chlorogenic acid, benzyl alcohol chlorogenic acid, phenylethanol chlorogenic acid, anthocyanidins, proanthocyanidins and catechins.
[0404] 60. According to any one of the foregoing technical solutions, when the preparation is used to prevent, inhibit or treat inflammatory reactions and / or aging of the body, the water-soluble carbon chain substance is prepared into a solution with a concentration of 0.1nM-5mM. Preferably, the carbon chain substance is a complex formed by fatty acids and amino acids, more preferably, the concentration of the complex solution is 0.1nM-300uM, and more preferably 5nM-100uM.
[0405] 61. According to the preparation described in the previous technical solution, when the preparation is used to prevent, inhibit or treat inflammatory reactions and / or aging of the body, the water-soluble carbon chain substance is formulated into a solution with a concentration of 0.1nM-300uM, preferably 5nM-100uM.
[0406] 62. A pharmaceutical preparation for preventing, inhibiting, slowing down or treating neurodegenerative diseases prepared from the water-soluble carbon chain substance described in any of the above technical solutions.
[0407] 63. According to the pharmaceutical preparation described in the previous technical solution, the neurodegenerative diseases include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), senile dementia, amyotrophic lateral sclerosis (ALS), different types of spinocerebellar ataxia (SCA) or Pick's disease.
[0408] 64. According to the pharmaceutical preparation described in the previous technical solution, the water-soluble carbon chain substance is prepared into a solution with a concentration of 0.1nM-5mM to exert its effect.
[0409] 65. According to the pharmaceutical preparation described in the previous technical solution, the water-soluble carbon chain substance is formulated into a solution with a concentration of 0.1nM-300uM, preferably 5nM-100uM to exert its effect.
[0410] The preparation made from the carbon chain substance of the present invention is used to reduce the fluidity of cell membranes and can be applied to the following aspects and diseases:
[0411] 1) Cardiovascular diseases (including coronary heart disease, hypertension, myocardial infarction, and heart failure): Reducing the fluidity of cell membranes can reduce the risk of heart disease and stroke; moderately reducing the fluidity of cell membranes can reduce the heart load and relieve the symptoms of cardiovascular disease; moderately reducing the fluidity of cell membranes can reduce the activity of sodium channels and calcium channels on the cell membrane, thereby reducing the influx of calcium ions into cells, reducing the excitability of myocardial cells and the load on the heart, and relieving the symptoms of cardiovascular disease.
[0412] 2) Obesity: Reducing the fluidity of cell membranes can improve fat metabolism, reduce fat storage, and help alleviate obesity symptoms.
[0413] 3) Autism: Reducing the fluidity of cell membranes can improve the function of brain cells, thereby helping to alleviate the symptoms of autism.
[0414] 4) Osteoporosis: Reducing the fluidity of cell membranes can promote the growth of bone cells and increase bone density, thereby preventing and treating osteoporosis.
[0415] 5) Inflammatory diseases: Reducing the fluidity of cell membranes can alleviate inflammatory responses and help control the symptoms of inflammatory diseases.
[0416] 6) Autoimmune diseases: Moderately reducing cell membrane fluidity can reduce autoimmune reactions and alleviate the symptoms of autoimmune diseases.
[0417] 7) Chronic fatigue syndrome: Moderately reducing cell membrane fluidity can relieve fatigue symptoms.
[0418] 8) Cell autolysis: Reducing the fluidity of the cell membrane can prevent the loss of intracellular substances, thereby preventing cell autolysis.
[0419] 9) Neurodegenerative diseases: Reducing the fluidity of cell membranes can prevent the loss of useful substances in neurons, thereby preventing neurodegenerative diseases.
[0420] 10) Prevent viral infection, etc., by reducing the possibility of viruses entering cells and spreading to tumor cells by reducing cell membrane fluidity.
[0421] The preparations made from the carbon chain substances of the present invention can increase cell membrane permeability by moderately improving cell membrane fluidity, thereby promoting the passage of substances across the cell membrane, and are further applied in the following aspects and diseases:
[0422] Drug delivery: Drug molecules need to pass through the cell membrane to enter the cell, but due to the biological properties of the cell membrane, many drugs cannot cross the cell membrane. Therefore, by increasing the fluidity of the cell membrane, the rate and efficiency of drug molecules passing through the cell membrane can be increased, thereby improving the effectiveness of drug delivery.
[0423] Gene transfection: Similarly, by increasing the fluidity of the cell membrane, the rate and efficiency of exogenous genes passing through the cell membrane into the cell can be increased, thereby achieving gene transfection.
[0424] Cell therapy: Some cell therapies require the introduction of exogenous cells into the host body. Exogenous cells must pass through the host cell membrane to enter the host cell. Therefore, increasing the fluidity of the cell membrane can improve the efficiency of exogenous cells crossing the host cell membrane.
[0425] Tumor treatment: By increasing the fluidity of cell membranes, the rate and efficiency of chemotherapy drugs passing through the cell membrane into tumor cells can be increased, thereby improving the efficacy of chemotherapy drugs.
[0426] Diabetes: Diabetic patients often have lower cell membrane fluidity than healthy people. By reducing cell membrane fluidity, insulin sensitivity can be increased, thereby helping to control blood sugar levels.
[0427] Improve neurological diseases: Water-soluble fatty acid complexes can improve the symptoms of neurological diseases by increasing the fluidity of cell membranes and promoting neuronal cell regeneration.
[0428] Alzheimer's disease: Reduced cell membrane fluidity may lead to nerve cell death, which can be reduced by increasing cell membrane fluidity.
[0429] Boosts the immune system: Reduced cell membrane fluidity can lead to decreased immune system function. By increasing cell membrane fluidity, the immune system can be boosted, helping to prevent infection and disease.
[0430] Leukemia: Leukemia is a type of cancer caused by abnormal proliferation of white blood cells. Water-soluble fatty acid complexes that increase cell membrane fluidity may help chemotherapy drugs better enter the interior of white blood cells, thereby improving treatment efficacy.
[0431] Hypercholesterolemia: Hypercholesterolemia may lead to vascular sclerosis and cardiovascular disease. Water-soluble fatty acid complexes increase cell membrane fluidity, thereby helping to lower blood cholesterol levels.
[0432] Inflammatory bowel disease: Inflammatory bowel disease is a group of chronic inflammatory bowel diseases, including Crohn's disease and ulcerative colitis. Some studies have shown that water-soluble fatty acid complexes can increase the fluidity of intestinal epithelial cell membranes, thereby reducing intestinal inflammation.
[0433] By moderately increasing cell membrane fluidity, cell membrane permeability can be increased, thereby promoting the passage of substances across the cell membrane, which can be applied in the following areas and diseases:
[0434] Drug delivery: Drug molecules need to pass through the cell membrane to enter the cell, but due to the biological properties of the cell membrane, many drugs cannot cross the cell membrane. Therefore, by increasing the fluidity of the cell membrane, the rate and efficiency of drug molecules passing through the cell membrane can be increased, thereby improving the effectiveness of drug delivery.
[0435] Gene transfection: Similarly, by increasing the fluidity of the cell membrane, the rate and efficiency of exogenous genes passing through the cell membrane into the cell can be increased, thereby achieving gene transfection.
[0436] Cell therapy: Some cell therapies require the introduction of exogenous cells into the host body. Exogenous cells must pass through the host cell membrane to enter the host cell. Therefore, increasing the fluidity of the cell membrane can improve the efficiency of exogenous cells crossing the host cell membrane.
[0437] Tumor treatment: By increasing the fluidity of cell membranes, the rate and efficiency of chemotherapy drugs passing through the cell membrane into tumor cells can be increased, thereby improving the efficacy of chemotherapy drugs.
[0438] Diabetes: Diabetic patients often have lower cell membrane fluidity than healthy people. By reducing cell membrane fluidity, insulin sensitivity can be increased, thereby helping to control blood sugar levels.
[0439] Improve neurological diseases: Water-soluble fatty acid complexes can improve the symptoms of neurological diseases by increasing the fluidity of cell membranes and promoting neuronal cell regeneration.
[0440] Alzheimer's disease: Reduced cell membrane fluidity may lead to nerve cell death, which can be reduced by increasing cell membrane fluidity.
[0441] Boosts the immune system: Reduced cell membrane fluidity can lead to decreased immune system function. By increasing cell membrane fluidity, the immune system can be boosted, helping to prevent infection and disease.
[0442] Leukemia: Leukemia is a type of cancer caused by abnormal proliferation of white blood cells. Water-soluble fatty acid complexes that increase cell membrane fluidity may help chemotherapy drugs better enter the interior of white blood cells, thereby improving treatment efficacy.
[0443] Hypercholesterolemia: Hypercholesterolemia may lead to vascular sclerosis and cardiovascular disease. Water-soluble fatty acid complexes increase cell membrane fluidity, thereby helping to lower blood cholesterol levels.
[0444] Inflammatory bowel disease: Inflammatory bowel disease is a group of chronic inflammatory bowel diseases that includes Crohn's disease and ulcerative colitis. Some studies have shown that water-soluble fatty acid complexes can increase the fluidity of intestinal epithelial cell membranes, thereby reducing intestinal inflammation.
[0445] The carbon chain substance of the present invention can affect the structure and function of cell membranes, increase or inhibit transmembrane substance transport of cell membranes, increase or decrease the fluidity of cell membranes, increase or inhibit cell division, increase or inhibit cell migration, affect cell aging, etc.; the water-soluble carbon chain substance includes a carbon chain that originally has a certain water solubility, and its structure includes at least one or more hydrophobic carbon chain parts and one or more hydrophilic groups or residues; it also includes a highly hydrophilic complex formed by coupling the hydrophobic carbon chain part with a water-soluble molecule; the water-soluble carbon chain can be used to prevent and treat infections including viruses, bacteria and fungi; anti-aging; prevent and reduce the occurrence of neurodegenerative diseases such as Alzheimer's disease; by reducing the nonspecific phagocytosis of nanomedicines by cells, the effect of nanomedicines on target lesions is enhanced.
[0446] The present invention preliminarily shows through experiments that when the water-soluble fatty acid complex of the present invention functions as a water-soluble carbon chain substance, the concentration range thereof can be controlled by referring to the concentration and mechanism described below.
[0447] (1) The concentration range of the water-soluble fatty acid complex that acts on cells is: 0.1nM-5mM, preferably 1nM-0.3mM, and more preferably 5nM-0.1mM. Those skilled in the art can refer to this experimental concentration range to understand the blood drug concentration range that acts in animals or humans.
[0448] (2) Concentration range for inhibiting cell membrane fluidity: The range of action of each water-soluble fatty acid complex is different from that of another water-soluble fatty acid complex; for most water-soluble fatty acid complexes: the concentration range for inhibiting cell membrane fluidity is between 0.1nm-30 micromolar; reduced cell membrane fluidity may be related to the following diseases: 1) Hypertension: Reduced cell membrane fluidity in hypertensive patients may be related to abnormal vascular endothelial cell function. 2) Diabetes: Reduced cell membrane fluidity in diabetic patients may be related to oxidative stress and the production of glycation end products caused by high blood sugar. 3) Heart disease: Reduced cell membrane fluidity in heart disease patients may be related to abnormal structure and function of myocardial cell membranes. 4) Autoimmune disease: Reduced cell membrane fluidity in patients with autoimmune diseases may be related to abnormal activation of the immune system and inflammatory response. The above diseases can be treated by moderately increasing cell membrane fluidity.
[0449] (3) When the fluidity of the cell membrane decreases: the transmembrane transport of substances is restricted and inhibited, including the transmembrane transport of large and small molecules and particulate substances;
[0450] (4) Concentration range for increasing cell membrane fluidity: The range of action of each water-soluble fatty acid complex is different from that of another water-soluble fatty acid complex; generally speaking, the fluidity of the cell membrane increases at a concentration of 50 micromolar to 500 micromolar;
[0451] (5) The physiological and pathological processes corresponding to increased cell membrane fluidity include: When cell membrane fluidity increases, cells are more likely to divide and proliferate. One of the reasons is that their cell membrane fluidity is higher than that of normal cells.
[0452] Cell deformation and migration are also closely related to cell membrane fluidity. For example, leukocyte chemotaxis is also the reason for high fluidity; the ability of leukocytes to chemotaxis to inflamed areas will also be reduced.
[0453] (6) When the cell membrane fluidity increases to a certain extent, the cell membrane changes from a liquid crystal state to a liquid state, and the cell membrane ruptures. At this time, the concentration of water-soluble fatty acids is generally above 500 micromolar.
[0454] (7) Concentration range of water-soluble fatty acid complexes affecting transmembrane transport of substances: All water-soluble fatty acid complexes will affect transmembrane transport of substances, either increasing or inhibiting transmembrane transport;
[0455] For example, viruses entering cells belong to transmembrane transport; insulin secreted outside cells through exosomes also belongs to transmembrane transport;
[0456] (8) One of the major obstacles to the widespread application of nanomedicines is that, after being injected into the body, these nanomedicines are phagocytosed by the body's innate immune-related phagocytic system and reticuloendothelial system, which is a protective mechanism. However, this results in insufficient nanomedicines entering the target lesion area. Water-soluble fatty acid complexes inhibit the nonspecific endocytosis of nanomedicines by the reticuloendothelial system, allowing more nanomedicines to enter the target lesion area.
[0457] (9) The concentration range for inhibiting aging is between 5nM-100uM, while the concentration range for killing microorganisms is between 0.2mM-10mM.
[0458] Compared with the prior art, the present invention has the following beneficial effects:
[0459] 1) The present invention relates to a group of water-soluble carbon chain substances that affect the transport of substances across cell membranes, cell division and proliferation, cell movement and migration, and cell aging by affecting the fluidity of cell membranes;
[0460] 2) The group of water-soluble carbon chain substances disclosed herein increases the fluidity of cell membranes. When the fluidity of cell membranes increases to a certain level, the membranes transform from a liquid crystal state to a liquid state, causing the cell membranes to rupture. These substances can destroy the lipid envelopes of pathogenic microorganisms, including enveloped viruses, bacteria, and fungi, and are used to treat infections caused by these microorganisms, including enveloped viruses, bacteria, and fungi.
[0461] 3) The group of water-soluble carbon chain substances involved in the present invention affects the fluidity of cell membranes by changing the composition, function and structure of cell membranes.
[0462] 4) The group of water-soluble carbon chain substances involved in the present invention can bind to the proteins in the phospholipid bilayer of the cell membrane within a certain concentration range, change its conformation, and then affect the protein's deformability and its movement in the phospholipid bilayer, resulting in a decrease in the fluidity of the cell membrane.
[0463] 5.) The group of water-soluble carbon chain substances disclosed herein can bind to endocytosis-related proteins, receptor proteins, and scaffold proteins within the cell membrane phospholipid bilayer within a certain concentration range, altering their conformation and inhibiting protein deformation, thereby inhibiting the substance's transmembrane transport. For example, this can prevent viruses and nanomedicines from endocytosing into cells. This can prevent viral infection, inhibit nonspecific phagocytosis of nanomedicines, and enhance their ability to target lesions.
[0464] 6) The group of water-soluble carbon chain substances involved in the present invention can bind to endocytosis-related proteins, receptor proteins, and scaffold proteins in the cell membrane phospholipid bilayer within a certain concentration range, changing their conformation and inhibiting protein deformation, thereby inhibiting the substance's transmembrane transport properties. For example, they can prevent bacteria and fungi from endocytosing and entering cells, thereby preventing bacterial and fungal infections.
[0465] 7) The group of water-soluble carbon chain substances involved in the present invention can prevent viral infection by acting on host cells; it is not necessary to eliminate the virus in the host body to prevent viral infection.
[0466] 8) The group of water-soluble carbon chain substances involved in the present invention act on the skeleton protein within a certain concentration range, change its conformation, inhibit the protein's deformation ability, and thus inhibit the ability of cells to move and deform; and can be used for inflammatory response syndrome caused by leukocyte migration during severe inflammation.
[0467] 9) The group of water-soluble carbon chain substances involved in the present invention inhibit the ability of cells to move and deform by reducing the fluidity of cell membranes within a certain concentration range; they can be used to treat inflammatory response syndrome caused by leukocyte migration during severe inflammation.
[0468] 10) The group of water-soluble carbon chain substances involved in the present invention inhibit cell aging by increasing the fluidity of cell membranes within a certain concentration range; they can be used to resist body aging and skin aging.
[0469] 11) The group of water-soluble carbon chain substances involved in the present invention inhibits inflammatory responses by binding to oxygen free radicals and changing the conformation of inflammatory factors (proteins), thereby exerting anti-inflammatory and anti-aging effects. Furthermore, within a certain concentration range, the group of water-soluble carbon chain substances stabilizes cell membranes by reducing their fluidity, inhibiting their rupture under the influence of inflammatory factors, leading to the release of more inflammatory factors within the cells, thereby inhibiting the occurrence of inflammation. BRIEF DESCRIPTION OF THE DRAWINGS
[0470] FIG1 is a comparison diagram of infrared spectra of linolenic acid-serum albumin prepared in Example 1;
[0471] FIG2 is a Coomassie brilliant blue staining result of fumaric acid, linolenic acid, eicosapentaenoic acid, and docosahexaenoic acid-serum albumin obtained in Example 1;
[0472] FIG3A is a mass spectrometry analysis of linolenic acid-serum albumin prepared in Example 1;
[0473] FIG3B is a site analysis diagram of the linolenic acid-modified albumin prepared in Example 1;
[0474] FIG4A is a mass spectrometry analysis of docosahexaenoic acid-serum albumin prepared in Example 1;
[0475] FIG4B is a site analysis diagram of docosahexaenoic acid-modified albumin prepared in Example 1;
[0476] FIG5 is a mass spectrum of oleic acid-serum albumin prepared in Example 2;
[0477] FIG6 is a site analysis diagram of oleic acid-modified serum albumin in the compound prepared in Example 2;
[0478] FIG7 is a comparison diagram of infrared spectra of eicosapentaenoic acid-serum albumin prepared in Example 3;
[0479] FIG8 is a mass spectrum of eicosapentaenoic acid-serum albumin prepared in Example 4;
[0480] FIG9 is a site analysis diagram of eicosapentaenoic acid-modified serum albumin in the compound prepared in Example 4;
[0481] FIG10 is a mass spectrum of linoleic acid-serum albumin prepared in Example 5;
[0482] FIG11 is a site analysis diagram of linoleic acid-modified serum albumin in the compound prepared in Example 5;
[0483] FIG12 is a comparison diagram of infrared spectra of docosahexaenoic acid-serum albumin prepared in Example 6;
[0484] FIG13 is a mass spectrum of docosahexaenoic acid-serum albumin prepared in Example 6;
[0485] FIG14 is a site analysis diagram of docosahexaenoic acid-modified serum albumin in the compound prepared in Example 6;
[0486] FIG15 is a comparison diagram of infrared spectra of linoleic acid-hyaluronic acid prepared in Example 7;
[0487] FIG16 is a comparison of infrared spectra of docosahexaenoic acid-hyaluronic acid prepared in Example 8;
[0488] FIG17 is a comparison diagram of the infrared spectra of fatty acid-SBP1 prepared in Example 9;
[0489] FIG18 is a comparison diagram of the infrared spectra of 9-tetradecenoic acid-SBP1 prepared in Example 10;
[0490] FIG19 is an infrared spectrum of the eight-carbon saturated carbon chain-glucose complex prepared in Example 14;
[0491] FIG20 is a graph showing the antibacterial results of the eight-carbon saturated carbon chain-glucose complex prepared in Example 14;
[0492] FIG21 is an infrared spectrum of the eight-carbon saturated carbon chain-sucrose complex prepared in Example 15;
[0493] FIG22 is a graph showing the antibacterial results of the eight-carbon saturated carbon chain-sucrose complex prepared in Example 15;
[0494] FIG23 is an infrared spectrum of the fatty acid-adenosine monophosphate complex prepared in Example 16;
[0495] FIG24 is a graph showing the antibacterial results of the eight-carbon saturated carbon chain-adenosine monophosphate complex prepared in Example 16;
[0496] FIG25 is an infrared spectrum of the eight-carbon saturated carbon chain-ascorbic acid complex prepared in Example 17;
[0497] FIG26 is a graph showing the antibacterial results of the eight-carbon saturated carbon chain-ascorbic acid complex prepared in Example 17;
[0498] FIG27 is an infrared spectrum of the eight-carbon saturated carbon chain-polyethylene glycol 400-COOH complex prepared in Example 18;
[0499] FIG28 is a graph showing the antibacterial results of the eight-carbon saturated carbon chain-polyethylene glycol 400-COOH complex prepared in Example 18;
[0500] Figure 29 is a transmission electron microscopic image of ethyl oleate liposomes prepared in Example 19 (1);
[0501] Figure 30 is a transmission electron microscopic image of the linoleic acid liposomes prepared in Example 19 (2);
[0502] FIG31 is a linolenic acid-serum albumin injection prepared in Example 20;
[0503] FIG32 shows the particle size distribution of the linolenic acid-serum albumin prepared in Example 20 measured by a Malvern particle size analyzer;
[0504] FIG33 is a transmission electron microscope image of linolenic acid-serum albumin prepared in Example 20;
[0505] FIG34 is a freeze-dried powder injection of linoleic acid-hyaluronic acid prepared in Example 21;
[0506] FIG35 is a freeze-dried powder injection of docosahexaenoic acid-hyaluronic acid prepared in Example 21;
[0507] FIG36 is a transmission electron microscope image of the linoleic acid-hyaluronic acid freeze-dried powder prepared in Example 21 re-dissolved in water;
[0508] FIG37 shows the particle size distribution of the lyophilized linoleic acid-hyaluronic acid powder prepared in Example 21 after being re-dissolved in water and measured using a Malvern particle size analyzer;
[0509] FIG38 is a lyophilized powder preparation of lauryl aspartate complex liposomes prepared in Example 22;
[0510] FIG39 is a scanning electron micrograph of the lyophilized powder formulation of lauryl aspartate complex liposomes prepared in Example 22;
[0511] FIG40 is a graph showing the particle size distribution of the lyophilized powder of the lauryl aspartate complex liposome prepared in Example 22 after redissolution in water;
[0512] FIG41 is a potential distribution diagram of the lyophilized powder preparation of lauryl aspartate complex liposomes prepared in Example 22;
[0513] FIG42 is a transmission electron micrograph of the eicosapentaenoic acid ethyl ester injection prepared in Example 23;
[0514] FIG43 is a particle size distribution diagram of the icosapentaenoic acid ethyl ester injection prepared in Example 23;
[0515] FIG44 is a potential distribution diagram of the icosapentaenoic acid ethyl ester injection prepared in Example 23;
[0516] FIG45 is a transmission electron microscope image of docosahexaenoic acid-SBP1 prepared in Example 24;
[0517] FIG46 shows the particle size distribution of docosahexaenoic acid-SBP1 prepared in Example 24 measured using a Malvern particle size analyzer;
[0518] FIG47 is a picture of the product of the polypeptide SBP1 obtained in Example 24 grafted with different ω-3 fatty acids (ALA: linolenic acid, EPA: eicosapentaenoic acid, DHA: docosahexaenoic acid);
[0519] FIG48 is a transmission electron micrograph of the reconstituted product of the CD14 protein grafted dodecenoic acid lyophilized powder injection prepared in Example 25;
[0520] FIG49 is a transmission electron micrograph of the reconstituted product of the CD14 protein grafted tetradecenoic acid lyophilized powder injection prepared in Example 25;
[0521] FIG50 is a transmission electron micrograph of the reconstituted product of the CD14 protein grafted eicosapentaenoic acid lyophilized powder injection prepared in Example 25;
[0522] FIG51 shows the results of a VERO E6 cell safety experiment on the eight-carbon saturated carbon chain threonine prepared in Example 29;
[0523] FIG52 shows the results of a safety experiment on VERO E6 cells using the eight-carbon saturated carbon chain serine prepared in Example 29;
[0524] FIG53 shows the results of a safety test on VERO E6 cells using the 18-carbon monounsaturated carbon chain serine prepared in Example 29;
[0525] FIG54 shows the results of a VERO E6 cell safety test on the 18-carbon monounsaturated carbon chain - threonine prepared in Example 29;
[0526] FIG55 is a graph showing the results of a VERO E6 cell safety test on the twenty-two carbon polyunsaturated carbon chain - threonine prepared in Example 29;
[0527] FIG56 is a graph showing the results of a VERO E6 cell safety experiment on the twenty-carbon polyunsaturated carbon chain serine prepared in Example 29;
[0528] FIG57 is a graph showing the results of a VERO E6 cell safety experiment on the 18-carbon monounsaturated carbon chain lysine prepared in Example 29;
[0529] FIG58 is a graph showing the results of a VERO E6 cell safety experiment on the twenty-two carbon polyunsaturated carbon chain lysine prepared in Example 29;
[0530] FIG59 is a graph showing the results of a VERO E6 cell safety experiment on the 18-carbon polyunsaturated carbon chain - threonine prepared in Example 29;
[0531] FIG60 shows the results of a VERO E6 cell safety experiment of an eight-carbon saturated carbon chain-5'-adenosine monophosphate-four-carbon unsaturated carbon chain-carboxyl group prepared in Example 29;
[0532] FIG61 is a graph showing the results of a safety experiment on VERO E6 cells using N-octyl-N-methylglucamine in Example 29;
[0533] FIG62 is a graph showing the results of a VERO E6 cell safety experiment on N-nonyl-N-methylglucamine in Example 29;
[0534] FIG63 is a graph showing the antibacterial effect of threonine, an eight-carbon saturated carbon chain, on Staphylococcus aureus obtained in Example 30;
[0535] FIG64 is a graph showing the antibacterial effect of the eight-carbon saturated carbon chain serine prepared in Example 30 on Staphylococcus aureus;
[0536] FIG65 is a graph showing the antibacterial effect of 18-carbon monounsaturated carbon chain-serine prepared in Example 30 on Staphylococcus aureus;
[0537] FIG66 is a graph showing the antibacterial effect of threonine, an 18-carbon monounsaturated carbon chain, on Staphylococcus aureus obtained in Example 30;
[0538] FIG67 is a graph showing the antibacterial effect of threonine, a 22-carbon polyunsaturated carbon chain, on Staphylococcus aureus obtained in Example 30;
[0539] FIG68 is a graph showing the antibacterial effect of the twenty-two-carbon polyunsaturated carbon chain serine prepared in Example 30 on Staphylococcus aureus;
[0540] FIG69 is a graph showing the antibacterial effect of 18-carbon monounsaturated carbon chain-lysine prepared in Example 30 on Staphylococcus aureus;
[0541] FIG70 is a graph showing the antibacterial effect of the twenty-two-carbon polyunsaturated carbon chain lysine prepared in Example 30 on Staphylococcus aureus;
[0542] FIG71 is a graph showing the antibacterial effect of threonine, an 18-carbon polyunsaturated carbon chain, on Staphylococcus aureus obtained in Example 30;
[0543] FIG72 is a graph showing the antibacterial effect of the eight-carbon saturated carbon chain-5'-adenosine monophosphate-four-carbon unsaturated carbon chain-carboxyl group on Staphylococcus aureus prepared in Example 30;
[0544] FIG73 is a graph showing the antibacterial effect of N-octyl-N-methylglucamine on Staphylococcus aureus in Example 30;
[0545] FIG74 is a graph showing the antibacterial effect of N-nonyl-N-methylglucamine on Staphylococcus aureus in Example 30;
[0546] FIG75 shows the results of cytotoxicity test of ω-3 fatty acid-serum albumin complex on VERO E6 cells in Example 32;
[0547] FIG76 shows the results of the toxicity test of the fatty acid-serum albumin complex on hepatocytes in Example 33;
[0548] Figure 77 shows the results of cytotoxicity testing of carboxyl-eight-carbon unsaturated carbon chain-taurocholic acid on VERO-E6 cells in Example 34;
[0549] Figure 78 is a graph showing the results of liver and kidney function in the animal safety test in Example 35 (1);
[0550] Figure 79 is a graph showing the results of liver and kidney function in the animal safety test in Example 35 (2);
[0551] Figure 80 is a graph showing the results of liver and kidney function in the animal safety test in Example 35 (3);
[0552] Figure 81 is a graph showing the results of liver and kidney function in the animal safety test in Example 35 (4);
[0553] Figure 82 is a graph showing the results of liver and kidney function in the animal safety test in Example 35 (5);
[0554] Figure 83 is a graph showing the results of the hemolysis experiment in the animal safety test in Example 35 (6);
[0555] Figure 84 shows the neutralization inhibition rate of the fatty acid (ω-3 fatty acid)-serum albumin complex against the new coronavirus pseudovirus in Example 36;
[0556] FIG85 shows the neutralization inhibition rate of the hexacosenoic acid-cyclodextrin coating against rabies pseudovirus in Example 37;
[0557] FIG86 shows the neutralization inhibition rate of the docosahexaenoic acid-SBP1 complex against the novel coronavirus pseudovirus in Example 38;
[0558] FIG87 shows the neutralization inhibition rate of the hexanoic acid-hyaluronic acid complex against HIV pseudovirus HIV18A-41 in Example 39;
[0559] FIG88 shows the neutralization inhibition rate of the nonanoic acid-hyaluronic acid complex against influenza pseudovirus H7N9-Fluc in Example 40;
[0560] FIG89 shows the neutralization inhibition rate of the octadecanoic acid-serum albumin complex against HIV pseudovirus in Example 41;
[0561] FIG90 shows the neutralization inhibition rate of the eicosanoic acid-hyaluronic acid complex against H7N9-Fluc pseudovirus in Example 42;
[0562] FIG91 shows the neutralization inhibition rate of the octacosanoic acid-serum albumin complex against H5N1-Fluc pseudovirus in Example 43;
[0563] FIG92 shows the results of transfection of HIV-derived lentivirus into hepatocytes pretreated with fatty acid-serum albumin complexes in Example 44;
[0564] Figure 93 is a transmission electron micrograph of the treated novel coronavirus pseudovirus in Example 45;
[0565] FIG94 is a schematic diagram showing the hydrophobic isolation process of the "carbon chain interaction portion + small molecule water-soluble portion / binding portion" complex on human papillomavirus in Example 46;
[0566] FIG95 is an in vitro simulation of the process of encapsulating protein particles loaded with L1 protein with N-octyl-N-methylglucamine in Example 46;
[0567] Figure 96 shows the neutralization inhibition rate of docosahexaenoic acid-coupled serine against HPV pseudovirus in Example 47;
[0568] FIG97 is a graph showing the antibacterial effect (methicillin-resistant Staphylococcus aureus) of different concentrations of the docosahexaenoic acid-serum albumin complex prepared in Example 48;
[0569] FIG98 is a graph showing the antibacterial (E. coli) results of different concentrations of the docosahexaenoic acid-serum albumin complex prepared in Example 48;
[0570] FIG99 shows the structural changes of Escherichia coli observed under a scanning electron microscope after the action of the docosahexaenoic acid-serum albumin complex prepared in Example 48;
[0571] FIG100 shows the structural changes of Staphylococcus aureus observed under a scanning electron microscope after the action of the docosahexaenoic acid-serum albumin complex prepared in Example 48;
[0572] FIG101 shows the membrane detachment of Staphylococcus aureus observed under a transmission electron microscope after the docosahexaenoic acid-serum albumin complex prepared in Example 48 was applied;
[0573] FIG102 is a comparison of the binding rates of the novel coronavirus pseudovirus, Staphylococcus aureus, Escherichia coli, and hepatic stellate cells to the docosahexaenoic acid-serum albumin complex in Example 49;
[0574] FIG103 is a graph showing the residence time of the docosahexaenoic acid-serum albumin complex in the lungs in Example 50;
[0575] FIG104 is a graph showing the residence time of the eicosapentaenoic acid-hyaluronic acid complex in the lungs in Example 50;
[0576] FIG105 is a graph showing the results of animal experiments on docosahexaenoic acid-serum albumin complexes in Example 51;
[0577] FIG106 is a graph showing the results of the animal lung administration experiment of the eicosapentaenoic acid-hyaluronic acid complex in Example 51;
[0578] FIG107 is a graph showing the lung fluorescence results of an animal experiment in which the small molecule complex is orally administered in Example 52;
[0579] FIG108 is an ImageJ analysis result of the average fluorescence value of the lungs in the animal experiment of oral administration of the small molecule complex in Example 52;
[0580] Figure 109A is a diagram showing the binding sites between Ser-EPA and caveolin-1 in Example II-1.
[0581] Figure 109B is a diagram showing the binding sites between Ser-EPA and caveolin-2 in Example II-1.
[0582] Figure 109C is a diagram showing the binding sites between Ser-EPA and caveolin-3 in Example II-1.
[0583] Figure 110A is a diagram showing the binding sites between GA-DHA and caveolin-1 in Example II-2.
[0584] FIG110B is a diagram showing the binding sites between GA-DHA and caveolin-2 in Example II-2.
[0585] Figure 110C is a diagram showing the binding sites between GA-DHA and caveolin-3 in Example II-2.
[0586] Figure 111 is a diagram showing the binding sites between GA-DHA and dynamin in Example II-3.
[0587] Figure 112A is a diagram showing the binding sites between Ser-EPA and Dynamin in Example II-4.
[0588] Figure 112B is a diagram showing the binding sites between Ser-EPA and Dynamin in Example II-4.
[0589] Figure 113 is a diagram showing the binding sites between Ser-EPA and Rab protein in Example II-5.
[0590] Figure 114 is a diagram showing the binding sites between GA-DHA and Rab protein in Example II-6.
[0591] Figure 115 is a diagram showing the binding site between Ser-EPA and Trpv1 (transient receptor cation channel) in Example II-7.
[0592] FIG116 is a diagram showing the binding sites between cholyltaurine-C14 and SNAP-25 (synaptosome-associated protein-25) in Example II-8.
[0593] FIG117 is a diagram showing the binding sites between PEG-C18-2 and SNAP-25 (synaptosome-associated protein-25) in Example II-9.
[0594] Figure 118 is a diagram showing the binding sites between PEG-C7 and Arf (ADP-ribosylation factor) in Example II-10.
[0595] Figure 119 is a diagram showing the binding sites between PEG-C9 and AP180 (bridging protein) in Example II-11.
[0596] Figure 120 is a diagram showing the binding sites between PEG-C11 and α-actin in Example II-12.
[0597] Figure 121 is a diagram showing the binding sites between PEG-C18 and α-tubulin in Example II-13.
[0598] Figure 122 is a diagram showing the binding sites between RGD-2-OH-PA and muscle myosin in Example II-14.
[0599] Figure 123 is a diagram showing the binding sites between RGD-DA and Septin protein in Example II-15.
[0600] Figure 124 is a diagram showing the binding sites between RGD-FA and CD36 protein in Example II-16.
[0601] Figure 125 is a diagram showing the binding sites between RGD-C8 and TfR1 (transferrin receptor 1) in Example II-17.
[0602] Figure 126 is a diagram showing the binding sites between Thr-BA and TLR1 receptor in Example II-18.
[0603] Figure 127 is a diagram showing the binding site between Vitamin-C-OH and TLR7 receptor in Example II-19.
[0604] Figure 128 is a diagram showing the binding sites between THr-C24 and G protein-coupled receptors in Example II-20.
[0605] Figure 129 is a diagram showing the binding site between Chondroitin sulfate-2-C8 and Scavenger receptor in Example II-21.
[0606] Figure 130 is a diagram showing the binding sites between Heparin-SA and VLDL receptor in Example II-22.
[0607] Figure 131 is a diagram showing the binding sites between UDPGA-BA and chloride channel receptors in Example II-23.
[0608] Figure 132 is a diagram showing the binding sites between UDPGA-C12 and Endoglin receptor in Example II-24.
[0609] Figure 133 is a diagram showing the binding sites between Thr-n-CA and CD44 receptor in Example II-25.
[0610] Figure 134 is a diagram showing the binding sites between UDPGA-C25 and cathepsin in Example II-26.
[0611] Figure 135 is a diagram showing the binding sites between UDPGA-PA and TNF (tumor necrosis factor) in Example II-27.
[0612] Figure 136 is a diagram showing the binding sites between UDPGA-OA and VEGF (angiogenic factor) in Example II-28.
[0613] Figure 137 shows the binding site between Thr-C36 and glutathione S-transferases (GSTs) in Example II-29.
[0614] Figure 138 is a diagram showing the binding sites between HA-OH-1 and proteinase inhibitors (TIMPs) in Example II-30.
[0615] FIG139 is a diagram showing the binding sites between HA-SA and the protease inhibitor (α2-macroglobulin) in Example II-31.
[0616] Figure 140 is a diagram showing the binding sites between Vitamin-C-C30 and tyrosine kinase receptors (TKRs) in Example II-32.
[0617] Figure 141 is a diagram showing the binding sites between fat-soluble vitamins and Toll-like receptors (TLRs) in Example II-33.
[0618] Figure 142 is a diagram showing the binding sites between Adenosine-C22-1 and integrins in Example II-34.
[0619] Figure 143 is a diagram showing the binding sites between cholylglycine-C18-1-OH and Fibrillin in Example II-35.
[0620] Figure 144 is a diagram showing the binding sites between UDPGA-C12 and Collagen in Example II-36.
[0621] Figure 145 shows the results of Ser-EPA inhibiting the phagocytosis of nanomedicine in Example II-37.
[0622] Figure 146 is a graph showing the results of the water-soluble fatty acid complex Thr-DHA inhibiting cell membrane fluidity in Example II-40.
[0623] Figure 147 is a graph showing the results of the water-soluble fatty acid complex Thr-DHA promoting cell membrane fluidity in Example II-41.
[0624] Figure 148 shows the results of promoting the proliferation of human hair follicle stem cells by Lys-ALA, Ser-DHA, and Glu-oleic acid in Example II-42.
[0625] FIG149 shows the results of Thr-EPA inhibiting cell migration in Example II-43.
[0626] Figure 150 shows the results of Thr-EPA promoting cell migration in Example II-44.
[0627] Figure 151 is a diagram showing the results of the interaction between the water-soluble fatty acid complex and the cell membrane in Example II-52.
[0628] Figure 152 shows the results of the interaction between the water-soluble fatty acid complex and the alveolar epithelial cell membrane in Example II-53. Figure 153 shows the lung fluorescence results of the animal experiment of oral administration of the small molecule complex in Example 52;
[0629] FIG154 is an infrared spectrum of the heparin-oleic acid complex prepared in Example 53;
[0630] FIG155 is a graph showing the neutralization inhibition rate of heparin-oleic acid complex against hepatitis B pseudovirus in Example 53;
[0631] Figure 156 is a diagram showing HE staining results of mouse sinus mucosa sections in Example 54;
[0632] FIG157 is a graph showing the results of myeloperoxidase activity detection in mouse nasal mucosal tissues in Example 54;
[0633] FIG158 is an infrared spectrum of the Tween 80-threonine complex prepared in Example 55;
[0634] FIG159 is an infrared spectrum of the cholesterol-PEG400-fumaric acid complex prepared in Example 56;
[0635] FIG160 is an infrared spectrum of the phosphatidylethanolamine-PEG1000-suberic acid complex prepared in Example 57;
[0636] FIG161 is an infrared spectrum of the α-tocopherol-hyaluronic acid complex prepared in Example 58;
[0637] FIG162 is an infrared spectrum of the sodium cholate-hyaluronic acid complex prepared in Example 59;
[0638] Figure 163 is the infrared spectrum of the complex prepared in Example 60. DETAILED DESCRIPTION
[0639] The present invention aims to provide a group of water-soluble carbon chain substances that affect transmembrane transport of cell membrane substances, membrane fluidity, membrane structure and function. The carbon chain substances can be compounds, complexes or mixtures.
[0640] 1.1. The water-soluble carbon chain substances include: a) carbon chains that are inherently water-soluble, and whose structure includes at least one or more hydrophobic carbon chain portions and one or more hydrophilic groups or residues; b) highly hydrophilic complexes formed by covalently coupling the hydrophobic carbon chain portion to a water-soluble molecule;
[0641] 1.2. The water-soluble carbon chain substances affect the structure and function of cell membranes, the transport of substances across cell membranes, cell division and proliferation, cell migration, cell membrane fluidity, and cell aging;
[0642] 1.3. The effects described include increase and promotion, or inhibition and reduction;
[0643] 1.4. The water-soluble carbon chain substances described above may exhibit an increasing and promoting effect within a certain concentration range, and an inhibiting and reducing effect within another concentration range;
[0644] 1.5. The cell membrane includes the plasma membrane and organelle membrane; including the cell membranes of humans, animals, plants, bacteria and fungi, as well as the envelope of viruses;
[0645] 1.6. The cell membrane structure includes a phospholipid bilayer, proteins and polysaccharides adsorbed on the surface of the phospholipid bilayer, and embedded throughout the phospholipid bilayer; including receptor proteins, transmembrane proteins, cytoskeletal proteins, and enzymes;
[0646] 1.7. The effects on cell membrane function include effects on transmembrane transport, i.e., increasing and promoting, inhibiting or reducing transmembrane transport. Transmembrane transport includes active transport, passive transport, endocytosis and exocytosis.
[0647] Active transport as described in 1.7.1 includes: ATP-driven pump transport including Na+-K+ pumps and Ca2+ pumps, P-class, V-class, F-class and ABC superfamily classes, and cooperative transport;
[0648] The passive transport includes simple diffusion and facilitated diffusion;
[0649] The endocytosis includes: phagocytosis, pinocytosis, and receptor-mediated endocytosis;
[0650] 1.8. In the aforementioned function of inhibiting or reducing transmembrane transport, substances transported across cell membranes include: small molecule compounds, medium molecule compounds, macromolecular compounds, pathogenic microorganisms such as viruses, bacteria, mycoplasmas, chlamydia, and fungi, as well as nanoparticles and nanomedicines;
[0651] 1.9. The inhibition or reduction of viral transmembrane transport, i.e., the inhibition or reduction of viral entry into cells via endocytosis; or the inhibition or reduction of viral entry into cells via fusion of the viral envelope with the cell membrane, is applicable to the prevention of all viral infections;
[0652] The inhibition or reduction of transmembrane transport of mycoplasma, chlamydia, bacteria and fungi can prevent mycoplasma and chlamydia infections, and prevent bacterial and fungal infections;
[0653] 1.10. The aforementioned inhibition or reduction of transmembrane transport of nanoparticles or nanodrugs, i.e., inhibition or reduction of nanoparticles or nanodrugs entering cells via endocytosis, can prevent, inhibit, or reduce the nonspecific phagocytosis of nanoparticles or nanodrugs by cells, thereby allowing more nanodrugs to enter the target site and improving the effective utilization of nanodrugs.
[0654] 1.11. The effects on transmembrane transport of cell membranes include increasing and promoting the release of exosomes from cells to the extracellular space, as well as inhibiting or reducing the release of exosomes from cells to the extracellular space.
[0655] 1.12. The effects on the structure and function of the cell membrane include affecting the fluidity of the cell membrane; promoting cell proliferation and division by increasing the fluidity of the cell membrane;
[0656] 1.13. The aforementioned increase in cell membrane fluidity may also cause the phospholipid bilayer in the cell membrane to change from a liquid crystal state to a liquid state, thereby causing the cell membrane to rupture;
[0657] 1.14. The method of increasing cell membrane fluidity, which causes the phospholipid bilayer in the cell membrane to change from a liquid crystal state to a liquid state, leading to cell membrane rupture, is used to destroy the lipid envelopes of viruses, mycoplasmas, chlamydia, bacteria, and fungi, and is used to treat infections caused by viruses, mycoplasmas, chlamydia, bacteria, and fungi.
[0658] 1.15. The reduction in cell membrane fluidity can maintain membrane stability, reduce cell division and proliferation, and reduce and inhibit the release of intracellular inflammatory factors caused by cell membrane rupture, thereby reducing the inflammatory response and severity, thereby having anti-aging, life-prolonging, and anti-skin aging effects in humans and other animals.
[0659] 1.16. The inhibition or reduction of viral, bacterial, and mycoplasma entry into cells through endocytosis or membrane fusion can be used to prevent viral diseases and other pathogenic microbial infections; thereby preventing chronic diseases caused by viral, bacterial, and mycoplasma infections, including neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), senile dementia, amyotrophic lateral sclerosis (ALS), various types of spinocerebellar ataxia (SCA), Pick's disease, and degenerative neuropathy caused by herpes virus-induced intracranial nerve infections.
[0660] 1.17. The effects on cell membrane function also include effects on cell movement and migration, including promoting or inhibiting the movement of macrophages and immune cells, promoting or inhibiting the migration and movement of melanocytes, and promoting or inhibiting the migration and movement of hair follicle cells.
[0661] 1.18 The method of reducing the fluidity of cell membranes and inhibiting the ability of cells to move and deform can be used to treat inflammatory response syndrome caused by white blood cell migration during severe inflammation; reducing the fluidity of cell membranes can stabilize the cell membranes, inhibit the rupture of cell membranes under the action of inflammatory factors, and inhibit the occurrence of inflammation.
[0662] Increasing the fluidity of cell membranes as described in 1.19 can inhibit cell aging and can be used to resist body aging and skin aging.
[0663] The group of water-soluble carbon chain substances described in 1.20 inhibits the inflammatory response by combining with oxygen free radicals and changing the conformation of inflammatory factors (proteins), thereby having anti-inflammatory and anti-aging effects.
[0664] 2. Structural composition of water-soluble carbon chain substances
[0665] In the present invention, the "water-soluble carbon chain" or "carbon chain" includes two situations of substances or residues having a carbon chain. The "water-soluble carbon chain substance" or "carbon chain substance" includes a substance (which may be a molecule) containing a carbon chain or a carbon chain residue or a carbon chain portion, or a complex or physical mixture formed by the substance (which may be a molecule) and other molecules or residues containing hydrophilic groups. That is to say, in some cases, the water-soluble carbon chain substance in the present invention is itself a compound having both a hydrophilic group and a hydrophobic carbon chain portion or carbon chain residue; in some cases, the water-soluble carbon chain substance is a carbon chain residue of an aliphatic hydrocarbon, fatty acid, fatty alcohol or ether or ester or surfactant or various derivatives thereof having a carbon chain (preferably a carbon chain with 3-100 carbon atoms), or these carbon chain substances themselves and other substances such as at least one selected from proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, nucleotides, vitamins, amino acids, water-soluble polymers, water-soluble polyamino acids and polysaccharide molecules, or a mixture of unreacted carbon chain residues or carbon chain substances and / or unreacted proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, nucleotides, vitamins, amino acids, water-soluble polymers, water-soluble polyamino acids and / or polysaccharide molecules.
[0666] 2.1. The carbon chain portion with a certain degree of water solubility is a water-soluble polar group or residue in the molecule, such as a hydroxyl group, carboxyl group, amino group, amine group, quaternary ammonium group, guanidine group, sulfhydryl group, sulfonic acid group, sulfonyloxy group, or phosphate group, and the number of carbon atoms constituting the carbon chain is 3-100;
[0667] 2.1.1. Carbon chain substances with a certain degree of water solubility include medium- and short-chain fatty acids with relatively low water solubility, including acetic acid, oxalic acid, propionic acid, lactic acid, pyruvic acid, citric acid, butyric acid, succinic acid, malic acid, tartaric acid, fumaric acid, valeric acid, glutaric acid, hexanoic acid, adipic acid, heptanoic acid, pimelic acid, octanoic acid, octenoic acid, suberic acid, capric acid, and sebacic acid; and fatty acid derivatives, including surfactants: fatty acid salts, alkyl sulfonates, alkylbenzene sulfonates, alkyl sulfate esters, alkyl phosphate esters, alkylamine salts, alkyl quaternary ammonium salts, fatty acylamino acids, betaines, fatty alcohol polyoxyethylene ethers, alkylphenol polyoxyethylene ethers, fatty amine polyoxyethylene ethers, polyol fatty acid esters, polyol polyoxyethylene ether fatty acid esters, fatty acid polyoxyethylene esters, alkyl glycosides, and alcohol ether glycosides;
[0668] The water-soluble carbon chain substances of the present invention include some small molecular compounds containing hydroxyl groups and benzene rings:
[0669] Flavonoids, isoflavones, anthocyanins, soy isoflavones, aloe-emodin, grape seed extract, green tea flavonoids, naringenin, tartrazine, baicalein, riboflavin, quercetin, graphite flavonoids, cinnamon, buxol, hawthorn flavonoids, morin, luteolin, melilotin, gypsum flavonoids, honeysuckle flavonoids, gentian flavonoids, platycodon flavonoids, violet flavonoids, perilla flavonoids, chrysanthemum flavonoids, artemisia annua flavonoids, red peony flavonoids, salvia miltiorrhiza flavonoids, safflower flavonoids, rhodiola rosea flavonoids, red date flavonoids, wolfberry flavonoids, rehmannia glutinosa flavonoids, ganoderma lucidum flavonoids, schisandra chinensis flavonoids, licorice flavonoids, panax flavonoids, curcumin, apigenin, carotene, anthocyanins, lutein, zeaxanthin, mustard flavonoids, rutin, coriander, pollen flavonoids, sand Echinoflavones, marigold flavonoids, cinnamon flavonoids, isoflavonoids and anthocyanins; rutin, emodin, fucoxanthin, gallic acid, kakirin, morin, echinacea glycosides, grape seed proanthocyanidins, phenolic acids, tea polyphenols, naringin, citric acid, flavonols, glycyrrhizic acid, cinnamic acid, flavonoid glycosides, silymarin, matrine, tanshinone, erythrocephalin, seabuckthorn acid, perillyl alcohol, anisic acid, phellodendron, hesperidin, punica granatum, morilin, naringin, rubellin, gentiopicroside, jasmonate, naringol, carotene, apigenin, umelin, morilin, honeysuckle glycoside, chrysanthemin, olive oleate, tea cyanidin, theanine, wine glycosides, platycodin, perillyl alcohol glycosides, morus alba, safflower glycosides, pinus needle glycosides, pachycocin, caffeic acid, chlorogenic acid;Resveratrol, white tea polyphenols, resveratrol disaccharide, banana lutein, anthocyanin, arachidonic acid, peanut flavonoids, pepper phenol, fennel, flavonoids, baicalein, flavonoid glycosides, flavanols, red wine polyphenols, rhodiola rosea, safflower phenol, black tea flavonoids, black sesame, rye phenol, trehalitol, seaweed polysaccharides, alginic acid, albizzia alkaloids, hemp phenol, polydatin, cucurbitacin, fenugreek, cucurbitacin, pollen phenol, pollen flavonoids, Pollen glycosides, pollen esters, arachidic acid, peanut flavonoid glycosides, peanut isoflavones, peanut isoflavone glycosides, peanut isoflavone disaccharides, peanut isoflavone trisaccharides, peanut resveratrol, peanut resveratrol disaccharides, peanut resveratrol trisaccharides, peanut resveratrol tetrasaccharides, peanut resveratrol pentasaccharides, peanut resveratrol hexasaccharides, peanut resveratrol heptasaccharides, peanut resveratrol octasaccharides, peanut resveratrol nonasaccharides, peanut resveratrol decasaccharides, peanut white quinoa Resveratrol undecanose, catechin, epicatechin, tea polyphenols, catechin, chlorophyll, protocatechin, hesperidin, anthocyanidin, anthocyanin, anthocyanin, anthocyanin, glucoside, glucoside, alfalfa, soy isoflavones, flavanols, quercetin, buckwheat glutenin, persimmon glutinin, persimmon glutinin, punicic acid, punica granatum, blueberry glutinin, resveratrol, lycopene, naringenin, morin, chlorogenic acid, chlorogenic acid triglucoside ... Chlorogenic acid diglucoside, methyl chlorogenic acid, ethyl chlorogenic acid, propyl chlorogenic acid, butyl chlorogenic acid, isopentyl chlorogenic acid, hexyl chlorogenic acid, octyl chlorogenic acid, benzyl chlorogenic acid, phenylethyl chlorogenic acid, phenylpropyl chlorogenic acid, phenylbutyl chlorogenic acid, isopentyl chlorogenic acid, phenylhexyl chlorogenic acid, phenyloctyl chlorogenic acid, phenylphenyl chlorogenic acid, benzyl alcohol chlorogenic acid, phenylethanol chlorogenic acid, anthocyanidins, proanthocyanidins, catechins;
[0670] 2.2. The complex formed by the hydrophobic carbon chain substance or carbon chain portion and the water-soluble molecule refers to a complex formed by the hydrophobic carbon chain directly bonding to the water-soluble molecule through a chemical bond, or bonding to the water-soluble molecule through a linker;
[0671] 2.2.1. The hydrophobic carbon chain substance or carbon chain portion is a molecule or a residue of a molecule having 3 to 100 carbon atoms;
[0672] 2.2.2. The carbon chain is saturated or unsaturated, the unsaturated bond is a double bond or a triple bond, and the number of unsaturated bonds is one or more;
[0673] 2.2.3. The carbon chain substance or carbon chain portion is a linear or cyclic carbon chain, a linear carbon chain with branches, a linear carbon chain with a cyclic structure, or a linear or cyclic carbon chain containing oxygen, sulfur, or nitrogen;
[0674] 2.2.4. The cyclic carbon chain-water-soluble carbon chain substances include monocyclic and polycyclic carbon chains;
[0675] 2.3. The hydrophobic carbon chain substance or carbon chain portion is a carbon chain substance or carbon chain residue having 3 to 100 carbon atoms selected from saturated and / or unsaturated aliphatic hydrocarbons, saturated and / or unsaturated fatty alcohols or oxy-fatty alcohols, saturated and / or unsaturated fatty acids, saturated and / or unsaturated hydroxy fatty acids, saturated and / or unsaturated oxy-fatty acids, hydrophobic amino acids, fat-soluble vitamins, carotenoids, sterols and steroid lipids, fatty acid glycerides, phospholipids, sphingomyelins, glycolipids, and / or surfactants;
[0676] 2.3.1. The saturated and / or unsaturated fatty acid has 3 to 50 carbon atoms;
[0677] 2.3.2. The saturated and / or unsaturated fatty acids have 3 to 26 carbon atoms;
[0678] 2.3.3. The saturated and / or unsaturated fatty acids are selected from one or more of acetic acid, oxalic acid, propionic acid, lactic acid, pyruvic acid, citric acid, butyric acid, succinic acid, malic acid, tartaric acid, crotonic acid, fumaric acid, pentanoic acid, glutaric acid, hexanoic acid, hexenoic acid, adipic acid, heptanoic acid, heptenoic acid, pimelic acid, octanoic acid, octenoic acid, suberic acid, nonanoic acid, decanoic acid, decanedioic acid, undecanoic acid, undecenoic acid, dodecanoic acid, dodecenoic acid, dodecanedioic acid, tridecanoic acid, tridecanedioic acid, tetradecanoic acid, pentadecanoic acid, pentadecanedioic acid, hexadecanoic acid, hexadecenoic acid, hexadecanedioic acid, octadecanoic acid, octadecanoic acid, octadecadienoic acid, octadecatrienoic acid, octadecanedioic acid, eicosanoic acid, eicosapentaenoic acid, docosanoic acid, docosomonoenoic acid, docosahexaenoic acid, docosandioic acid, tetracosanoic acid, triacontanic acid, and hexatriacontanic acid.
[0679] 2.3.4. The hydrophobic carbon chain substances include fatty acid ozonation products: fatty acid peroxides, hydroxy fatty acids, oxy fatty acids, fatty acid dicarboxylic acids, fatty aldehydes, fatty alcohols, and fatty acid esters;
[0680] 2.4. The water-soluble portion is a molecule or a residue of a molecule that is soluble in water;
[0681] 2.4.1. The molecules of the water-soluble portion contain one or more functional groups selected from amide groups, phosphoryloxy groups, carboxylic acid groups, phosphoric acid groups, sulfonic acid groups, sulfonyloxy groups, hydroxyl groups, quaternary ammonium groups, thioether groups, disulfide bonds, ether groups, sulfhydryl groups, aldehyde groups, ester groups, amine groups, amino groups, urea groups, and guanidine groups;
[0682] 2.4.2. The water-soluble molecule is one or more water-soluble macromolecules or their residues selected from proteins, polysaccharides, nucleic acids, and synthetic water-soluble polymers;
[0683] and / or, one or more medium molecules or their residues selected from polypeptides, oligopeptides, oligosaccharides, oligonucleotides and synthetic water-soluble medium molecular weight polymers;
[0684] and / or, one or more water-soluble small molecules or their residues selected from amino acids, monosaccharides, disaccharides, nucleotides, deoxynucleotides and water-soluble vitamins;
[0685] 2.4.3. The protein serving as the water-soluble macromolecule is one or more water-soluble macromolecules selected from serum albumin, immunoglobulin, water-soluble collagen, chaperone protein, and water-soluble glycoprotein;
[0686] The polysaccharide as the water-soluble macromolecule is one or more water-soluble macromolecules selected from dextran, hyaluronic acid, sialic acid, heparin sulfate, heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, acetyl water-soluble cellulose derivatives, β-cyclodextrin and its derivatives and water-soluble chitosan derivatives;
[0687] The water-soluble polymer as the water-soluble macromolecule is one or more water-soluble macromolecules selected from polyethylene glycol and carboxylated or amino polyethylene glycol, polyvinyl alcohol and carboxylated or amino polyvinyl alcohol, polyacrylic acid and ammonium polyacrylate;
[0688] The water-soluble medium molecular weight polymer is selected from one or more substances selected from polypeptides, oligopeptides, oligosaccharides, oligonucleotides and / or water-soluble polyamino acids;
[0689] The water-soluble small molecule monosaccharide and / or disaccharide is selected from one or more of glucose, fructose, rhamnose, sorbose, sucrose, maltose, lactose and trehalose;
[0690] The nucleotides and / or deoxynucleotides as the water-soluble small molecules are selected from adenylic acid, guanylic acid, uridine monophosphate, cytidylic acid, thymidylic acid, inosinic acid, deoxyadenylic acid, deoxyguanylic acid, deoxycytidylic acid, deoxythymidylic acid; amino acids such as serine, threonine, cysteine, asparagine, glutamine, tyrosine, lysine, arginine, histidine, aspartic acid, glutamic acid, citrulline, ornithine, taurine and aminobutyric acid, or two or more thereof;
[0691] The vitamin as the water-soluble small molecule is selected from one or more of vitamin B1, folic acid, pantothenic acid, vitamin B6, vitamin C, and biotin;
[0692] The water-soluble proteins and polypeptides include any one of proteins or neutralizing antibody fragments that specifically target microbial lipid membranes, bacterial and fungal cell walls, and viral surface protein domains.
[0693] The water-soluble polyamino acid is selected from polyglutamic acid, polylysine and / or polyaspartic acid; and any one of oligopeptides, oligosaccharides and oligonucleotides.
[0694] 3. The water-soluble carbon chains affect the structure and function of cell membranes;
[0695] 3.1. The structure and composition of the cell membrane phospholipid bilayer: including a phospholipid bilayer composed of phosphatidylcholine, sphingomyelin, and cholesterol; also including lipid raft structures; including the inner and outer leaflets of the phospholipid bilayer;
[0696] 3.2. The cell membrane structure includes proteins related to endocytosis and exocytosis: cell membrane proteins, cell membrane transmembrane proteins, cell membrane receptors, and cytoskeleton proteins;
[0697] 3.3. The structure of the cell membrane includes glycoproteins and lipoproteins on the cell membrane surface; including polysaccharides on the cell membrane surface;
[0698] 3.4. Proteins related to endocytosis and exocytosis:
[0699] 3.4.1. Endocytic proteins:
[0700] 3.4.1.1. Clathrin protein: Clathrin Heavy Chain 1 (CHC1), Clathrin Heavy Chain 2 (CHC2), Clathrin Light Chain A (CLTA), Clathrin Light Chain B (CLTB);
[0701] 3.4.1.2.Caveolin protein: Caveolin-1(CAV1), Caveolin-2(CAV2), Caveolin-3(CAV3);
[0702] 3.4.1.3.Dynamin proteins: Dynamin1, Dynamin2, Dynamin3, Dynamin-like protein (DNM1L, also known as Drp1), Dynamin-like protein 2 (DNM2);
[0703] 3.4.1.4. Rab proteins: Rab1, Rab2, Rab5, Rab7, Rab11, Rab27, Rab35;
[0704] 3.4.1.5.SNARE proteins: SNARE proteins: VAMP2, VAMP3, VAMP4, Syntaxin, SNAP-25, Munc18, Munc13, SNAP23;
[0705] 3.4.1.6. Arf (ADP-ribosylation factor): Arf1, Arf2, Arf3, Arf6;
[0706] 3.4.1.7. Bridging integrators: AP180 / CALM, Epsin, EHD (Eps15 Homology Domain), Dab2 (Disabled-2);
[0707] 3.4.2. Endocytosis-related cytoskeletal proteins:
[0708] 3.4.2.1. Actin: α-actin, β-actin, and γ-actin;
[0709] 3.4.2.2. Tubulins: α-tubulin, β-tubulin, and γ-tubulin;
[0710] 3.4.2.3. Intermediate filament proteins: keratin, myosin, neurofilament, glutamine filament (GFAP), nuclear lamins;
[0711] 3.4.2.4. Myosin: Muscle Myosin, Non-muscle Myosin, Adhesion Myosin, Neural Myosin, Cardiac Myosin
[0712] 3.4.2.5. Septin protein: SEPT2 subtype, SEPT3 subtype, SEPT4 subtype, SEPT5 subtype, SEPT6 subtype, SEPT7 subtype, SEPT9 subtype, SEPT11 subtype;
[0713] 3.4.3. Cell membrane receptor proteins related to endocytosis:
[0714] 3.4.3.1. High-density lipoprotein receptor (HDL receptor): SR-BI, CD36, ABCA1, SR-BII, CLA-1, GPIHBP1;
[0715] 3.4.3.2.LDL receptor (LDLR): LDLR-A, LDLR-B, LDLR-related protein (LRP), LDLR-related protein 1B (LRP1B), sortilin;
[0716] 3.4.3.3. Transferrin receptor: transferrin receptor 1 (TfR1), transferrin receptor 2 (TfR2);
[0717] 3.4.3.4. EGF receptor (EGFR): EGFR (ErbB1), ErbB2 (HER2), ErbB3 (HER3), ErbB4 (HER4);
[0718] 3.4.3.5.TLR receptor (Toll-like receptor): TLR1, TLR2, TLR3, TLR4, TLR5, TLR6, TLR7, TLR8, TLR9, TLR10;
[0719] 3.4.3.6. G protein-coupled receptors (GPCRs): Rhodopsin-like GPCR family, Secretin-like GPCR family, Metabotropic glutamate GPCR family, Adhesion GPCR family, Frizzled / Smoothened GPCR family;
[0720] 3.4.3.7.Scavenger receptor: Class A Scavenger Receptor, Class B Scavenger Receptor, Class C Scavenger Receptor, Class D Scavenger Receptor;
[0721] 3.4.3.8.VLDL receptor: VLDLR, LRP8;
[0722] 3.4.3.9.LRP (Low-Density Lipoprotein Receptor-Related Protein) receptors: LRP1, LRP2, LRP4, LRP5;
[0723] 3.4.3.10. Chloride channel receptors: GABA-A receptor, GlyR receptor, CFTR (Cystic Fibrosis Transmembrane Conductance Regulator), CLC family, Bestrophin, Anoctamin;
[0724] 3.4.11.Endoglin receptors: CD105, CD105a;
[0725] 3.4.12.CD44 protein: CD44s, CD44v;
[0726] 3.5. Proteins related to cell extracellular transport: cathepsins, tumor necrosis factor (TNF), angiogenic factor (VEGF), glutathione S-transferases (GGSTs), tissue protease inhibitors (TIMPs), ovalbumin (α2-macroglobulin), tyrosine kinase receptors (TKRs), G protein-coupled receptors (GPCRs), toll-like receptors (TLRs), integrins, fibrillin, collagen, heparan sulfate proteoglycans, syndecan;
[0727] 4. Application of the water-soluble carbon chain in affecting the transmembrane transport function of cell membranes
[0728] 4.1. The substances transported across cell membranes in the function of inhibiting or reducing transmembrane transport include: small molecule compounds, medium molecule compounds, large molecule compounds, viruses, bacteria, mycoplasma, chlamydia and other pathogenic microorganisms, as well as nanoparticles and nanomedicines
[0729] 4.1.1. The small molecule compounds include: water, glucose, amino acids, ions, O2, CO2, N2;
[0730] 4.1.2. The middle molecular weight compounds include cholesterol, iron, and vitamin B12 polypeptides;
[0731] 4.1.3. The macromolecular compounds include: proteins, growth factors;
[0732] 4.1.4. The viruses mentioned include:
[0733] Influenza virus, Coronavirus, Hepatitis B virus, Hepatitis C virus, HIV (Human immunodeficiency virus), Varicella-zoster virus, Measles virus, Rubella virus, Adenovirus, Enterovirus, Yellow fever virus, Human papillomavirus, Human respiratory syncytial virus, Rotavirus, Adenovirus type 36 36), adenovirus type 6, adenovirus type 11, adenovirus type 7, adenovirus type 5, adenovirus type 4, adenovirus type 3, adenovirus type 2, adenovirus type 1, adenovirus type 40, adenovirus type 41, parainfluenza virus, Japanese encephalitis virus, human immunodeficiency virus (HIV)-2, human herpes simplex virus, respiratory syncytial virus type 1, respiratory syncytial virus type 2, respiratory syncytial virus type 3, herpes zoster virus, Lyme disease virus, HIV-1, porcine swine fever virus parvovirus, Picornaviridae, Norovirus, Parainfluenza virus, Influenza virus, Norovirus, Hepatitis A virus, Calicivirus;
[0734] Viruses that animals are susceptible to:
[0735] Feline infectious peritonitis virus (FIPV), feline distemper virus (FPV), feline coronavirus (FCoV), feline immunodeficiency virus (FIV), feline leukemia virus (FeLV), feline stomatitis virus (FHV), feline viral rhinotracheitis virus (FVRV), feline infectious anemia virus (Haemobartonella felis), feline herpesvirus 1, feline leptospirosis virus (Borrelia burgdorferi), rabies virus, canine distemper virus, canine coronavirus, canine infectious hepatitis virus, canine parvovirus, canine influenza virus, canine viral diarrhea virus, canine oral papillomavirus, canine herpesvirus, canine immunodeficiency virus virus), Foot-and-mouth disease virus, Bovine respiratory syncytial virus, Rinderpest virus, Bovine reproductive and respiratory syndrome virus, Ovine viral diarrhea virus, Bluetongue virus, Infectious bronchitis virus, Marek's disease virus, Newcastle disease virus, Duck plague virus, Duck hepatitis virus, Goose parvovirus, Infectious laryngotracheitis virus, Goose hepatitis B virus, Goose astrovirus,Equine foot-and-mouth disease virus, Porcine parvovirus, Swine influenza virus, Porcine reproductive and respiratory syndrome virus, Porcine epidemic diarrhea virus, Porcine viral diarrhea virus, Porcine paravirus, Mycoplasma hyopneumoniae, Porcine encephalitis virus, Porcine vesicular virus, Herpes virus, Bovine viral diarrhea virus (BVDV), Bovine papillomavirus, Bovine viral diarrhea virus, Bovine enterovirus, Bovine coronavirus coronavirus), goose plague virus, duck infectious hepatitis virus, duck infectious laryngotracheitis virus, duck infectious gastroenteritis virus, goose infectious gastroenteritis virus, avian influenza virus, Newcastle disease virus, infectious bronchitis virus, infectious bursal disease virus, infectious chicken anemia virus, infectious rhinitis virus, infectious laryngotracheitis virus, infectious chicken hepatitis virus, infectious diarrhea virus of chicken;
[0736] 4.1.5. The pathogenic microorganisms include:
[0737] Mycoplasma, Chlamydia, Bordetella pertussis, Candida, Actinomyces, Treponema pallidum; Escherichia coli, Staphylococcus aureus, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella, Proteus mirabilis, Bacillus, Streptococcus pneumoniae, Methicillin-resistant Staphylococcus aureus (MRSA), Vibrio cholerae, Clostridium difficile, Neisseria gonorrhoeae, Clostridium tetani, Listeria monocytogenes, Clostridium perfringens, Mycobacterium tuberculosis, Candida albicans, Aspergillus, Histoplasma, Trichophyton, Cryptococcus, Blastomyces, Pneumocystis, Clostridium, Phytophthora, Saccharomyces, Fusarium, Sporothrix, Malassezia, Coccidioides, Actinomyces, Bacillus anthracis), cell wall fungi (Rhizopus), pathogenic fungi Pneumocystis carinii, Zygomycetes;
[0738] 4.1.6. The nanomedicines include polymer, metal, semiconductor or ceramic nanomedicines, liposome drugs, nanotube drugs, and nucleic acid nanomedicines;
[0739] 4.1.7. The nanoparticles include metal nanoparticles, quantum dots, magnetic nanoparticles, and polymer nanoparticles;
[0740] 4.2. The method of preventing, inhibiting or reducing the entry of viruses, bacteria, chlamydia, mycoplasma and fungi into cells through endocytosis or transmembrane transport such as membrane fusion is used to prevent viral, bacterial, chlamydia, mycoplasma and fungal infections;
[0741] 4.3. The above method can prevent, inhibit or reduce the non-specific phagocytosis of nanoparticles or nanomedicines by cells, thereby allowing more nanomedicines to enter the target area and improving the effective utilization of nanomedicines;
[0742] 4.5. Effects of the Water-Soluble Carbon Chains on Exosomes
[0743] 4.5.1. A water-soluble carbon chain that, within a certain concentration range, increases and promotes the extracellular release of insulin from exosomes of pancreatic islet cells; and, within another concentration range, inhibits or reduces the extracellular release of insulin from exosomes of pancreatic islet cells;
[0744] 4.5.2. A water-soluble carbon chain that, within a certain concentration range, increases and promotes the extracellular release of exosomes from white blood cells, hepatocytes, mammary gland cells, and nerve cells; and, within another concentration range, inhibits or reduces the extracellular release of exosomes from white blood cells, hepatocytes, mammary gland cells, and nerve cells;
[0745] 5. Application of water-soluble carbon chains to increase cell membrane fluidity;
[0746] 5.1. Water-soluble carbon chains increase membrane fluidity at certain concentrations, promoting cell proliferation and division;
[0747] 5.2. It can increase cell membrane fluidity, causing the phospholipid bilayer in the cell membrane to change from a liquid crystal state to a liquid state, leading to cell membrane rupture. It is used to destroy the cell membranes of lipid-encapsulated viruses, mycoplasmas, chlamydia, bacteria, and fungi, and is used to treat infections caused by viruses, mycoplasmas, chlamydia, bacteria, and fungi.
[0748] 5.2.1. Enveloped viruses that are killed include: Enveloped viruses such as one or more of coronavirus, influenza virus, HIV, hepatitis B virus, hepatitis C virus, herpes simplex virus, Zika virus, dengue virus, Japanese encephalitis virus, Ebola virus, monkeypox virus, respiratory syncytial virus, and / or hantavirus;
[0749] 5.2.2. The bacteria, mycoplasmas, chlamydia, and fungi killed include: the bacteria are Gram-positive bacteria and / or Gram-negative bacteria, the fungi are pathogenic fungi and / or conditionally pathogenic fungi; the chlamydia are Chlamydia trachomatis, Chlamydia pneumoniae, and / or Chlamydia psittaci; the mycoplasmas include Mycoplasma pneumoniae, Ureaplasma urealyticum, Mycoplasma hominis, and / or Mycoplasma genitalium.
[0750] 5.2.3. The bacteria are selected from one or more of Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa; the fungi are selected from one or more of Candida albicans, Aspergillus niger, Actinomyces viscosus, Chaetomium globosum, Aspergillus verrucosum, and Microsporum canis.
[0751] 6. Application of the water-soluble carbon chain to reduce cell membrane fluidity within a certain concentration range;
[0752] 6.1. The water-soluble carbon chain maintains membrane stability by reducing cell membrane fluidity, thereby reducing cell division and proliferation;
[0753] 6.2. The water-soluble carbon chain reduces and inhibits the release of intracellular inflammatory factors caused by cell membrane rupture, thereby reducing the inflammatory response and degree;
[0754] 6.3. The water-soluble carbon chain has anti-aging effects on the body and skin by affecting the fluidity of cell membranes;
[0755] 6.4. The water-soluble carbon chain has the ability to neutralize inflammatory mediators and thus inhibit inflammation, thereby having anti-aging and anti-skin aging effects;
[0756] 7. The water-soluble carbon chain can prevent, inhibit or reduce the entry of viruses into host cells through endocytosis or membrane fusion within a certain concentration range, and can be used to prevent viral infection in humans or animals:
[0757] 7.1. The viruses include
[0758] 7.1.1. Enveloped and non-enveloped viruses;
[0759] 7.1.2. DNA viruses and RNA viruses: double-stranded DNA viruses, single-stranded DNA viruses, double-stranded RNA viruses, positive-sense single-stranded RNA viruses, negative-sense single-stranded RNA viruses, retroviruses, RNA retroviruses, DNA retroviruses;
[0760] 7.2. Prevention of infections caused by human viruses, animal viruses, and plant viruses;
[0761] 7.3. The viruses include: coronavirus, influenza virus, HIV, hepatitis B virus, hepatitis C virus, herpes virus, Zika virus, dengue virus, Japanese encephalitis virus, Ebola virus, Hantavirus, polio virus, adenovirus, herpes zoster virus (Herpes simplex virus (HSV), varicella-zoster virus (VZV), human papillomavirus (HPV), poxvirus (including variola virus and monkeypox virus), African swine fever virus (Asfarviridae), rotavirus, measles virus, Bunyavirus, flavivirus, reovirus, Arenaviridae, Filoviridae, Cannulaviridae, rabies virus, Paramyxoviridae, Nipah virus, prion virus;
[0762] 8. The water-soluble carbon chain can prevent chronic diseases caused by viral infection within a certain concentration range;
[0763] 8.1. It can prevent neurodegenerative diseases caused by bacterial infections, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), senile dementia, amyotrophic lateral sclerosis (ALS), different types of spinocerebellar ataxia (SCA), and Pick's disease;
[0764] 8.2. It can prevent acquired immune deficiency syndrome (AIDS) caused by human immunodeficiency virus (HIV);
[0765] It can prevent herpes simplex virus (HSV) infection that causes oral herpes, genital herpes and other skin lesions;
[0766] It can prevent infection with the herpes zoster virus (VZV), which causes shingles and postherpetic neuralgia;
[0767] It can prevent human cytomegalovirus (HCMV)-induced infection and disease after organ transplantation, congenital infection in newborns, and lesions in immunocompromised individuals;
[0768] It can prevent human T-cell lymphotropic virus (HTLV-1) infection leading to adult T-cell leukemia / lymphoma (ATL) and HTLV-1-associated myelopathy;
[0769] It can prevent human cytomegalovirus type 6 (HHV-6) infection that causes mumps, rosacea, and post-infectious fatigue syndrome;
[0770] 9. Application of the water-soluble carbon chain to influence cell movement and migration;
[0771] 9.1. Within a certain concentration range, it can promote the deformation and migration of macrophages, immune cells such as T lymphocytes, B lymphocytes, dendritic cells, and NK cells; it can be used as an adjuvant therapy in immunotherapy; within another concentration range, it can inhibit the deformation and migration of macrophages, immune cells such as T lymphocytes, B lymphocytes, dendritic cells, and NK cells.
[0772] 9.2. Within a certain concentration range, it can promote the deformation and migration of melanocytes; within another concentration range, it can inhibit the deformation and migration of melanocytes;
[0773] 9.3. Within a certain concentration range, it can promote the deformation and movement of hair follicle cells; within another concentration range, it can inhibit the deformation and movement of hair follicle cells;
[0774] 9.4. Within a certain concentration range, it can promote the deformation and migration of endothelial cells; within another concentration range, it can inhibit the deformation and migration of endothelial cells.
[0775] 9.5. Within a certain concentration range, it can promote the deformation and movement of epithelial cells; within another concentration range, it can inhibit the deformation and movement of epithelial cells.
[0776] 9.6. Within a certain concentration range, it can promote the deformation and movement of white blood cells; within another concentration range, it can inhibit the deformation and movement of white blood cells;
[0777] 10. The water-soluble carbon chain substance can neutralize inflammatory mediators
[0778] 10.1. Water-soluble carbon chain substances can neutralize small molecule inflammatory mediators: oxygen free radicals, nitrogen free radicals, prostaglandins, histamine, leukotrienes, 5-hydroxytryptamine and other neurotransmitters;
[0779] 10.2. Water-soluble carbon chains can neutralize macromolecular inflammatory mediators such as tumor necrosis factor (TNF), interleukins (IL-1, IL-6, IL-8, etc.), thromboxane, proteases, and angiotensin; they interact with these macromolecular inflammatory molecules to inhibit inflammatory responses;
[0780] 11. The water-soluble carbon chain substance can be used as pharmaceutical preparations, cosmetics, skin care products, health care products, and environmental disinfection preparations;
[0781] 11.1. The pharmaceutical preparation is selected from an inhaler, nasal spray, injection, oral formulation, liposome emulsion, ointment, oil, or topical skin formulation;
[0782] 11.2. Use of the water-soluble carbon chain substance in the preparation of a pharmaceutical preparation for preventing, inhibiting, and / or treating microbial infection or an environmental microbial disinfection agent;
[0783] The method for preparing the water-soluble carbon chain substance described in 11.3 is to react a fat-soluble compound having a saturated and / or unsaturated carbon chain with a branched, cyclic and / or linear structure with a water-soluble molecule, and as needed, proteins, polypeptides, amino acids, oligopeptides, oligosaccharides, monosaccharides and / or polysaccharide molecules that can bind to the lipid membrane surface or cell wall of microorganisms, as well as linker molecules added as needed, in the presence of a catalyst to obtain the complex.
[0784] 11.3.1. The method for preparing the water-soluble carbon chain substance, wherein the water-soluble carbon chain substance is a product obtained by purifying the compound obtained by the reaction.
[0785] 11.4. The method for preparing the water-soluble carbon chain substance is to obtain the complex by physically mixing a fat-soluble compound having a saturated and / or unsaturated carbon chain with a branched, cyclic and / or linear structure with a water-soluble molecule, and, as needed, proteins, polypeptides, amino acids, oligopeptides, oligosaccharides, monosaccharides and / or polysaccharide molecules that can bind to the lipid membrane surface or cell wall of microorganisms.
[0786] 11.5. The method for preparing the water-soluble carbon chain substance is to obtain the complex by reacting saturated and / or unsaturated fatty acids containing 3-100 carbon atoms with any one of proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, oligonucleotides, vitamins, water-soluble polymers, water-soluble polyamino acids and / or polysaccharides in the presence of a catalyst.
[0787] 11.5.1. The method for preparing the water-soluble carbon chain substance, wherein the complex is the product of a purified compound obtained by the reaction.
[0788] 11.6. The method for preparing the water-soluble carbon chain substance is to obtain the complex by physical and chemical compounding of saturated and / or unsaturated fatty acids containing 3-100 carbon atoms with proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, oligonucleotides, vitamins, water-soluble polymers, water-soluble polyamino acids and / or polysaccharide molecules or by direct physical mixing.
[0789] Specifically, in one embodiment, the present invention provides a complex for preventing, inhibiting or treating microbial infection. The complex of the present invention comprises an active part, a binding part and a water-soluble part.
[0790] The active part is a fat-soluble hydrophobic carbon chain, which can exist in the form of a molecule or a molecular residue, and is a saturated and / or unsaturated carbon chain with a branched and / or linear structure, which can be inserted into / integrated into the lipid membrane of the microorganism, thereby destroying the lipid membrane structure, or wrapping non-enveloped viruses so that the viruses are hydrophobically isolated;
[0791] The binding portion can be a molecule or a residue of a molecule that binds to the microbial lipid membrane, microbial surface protein, microbial surface polysaccharide or cell wall component (including polysaccharide or protein) or can bind to the polysaccharide or protein or polypeptide in the microorganism, so that the complex is connected to the microbial lipid membrane or virus surface.
[0792] The water-soluble part is a molecule or a residue of a molecule that is soluble in water and contains a water-soluble group, which can give the complex water solubility, so that the complex can be evenly dispersed in an aqueous solution and avoid the fat-soluble hydrophobic groups from aggregating into clusters, thereby preventing the fat-soluble hydrophobic groups of the complex from aggregating into clusters in an aqueous solution or in blood to form lipid droplets.
[0793] In further detail, the active part is a fat-soluble, hydrophobic, saturated and / or unsaturated carbon chain with a branched, cyclic and / or linear structure, the carbon chain is a molecule or a residue of a molecule, and the carbon chain is a carbon chain with 3-100 carbon atoms;
[0794] The water-soluble portion is a water-soluble molecule or a residue of a molecule, wherein the molecule contains one or more groups selected from an amide group, a phosphoryloxy group, a carboxylic acid group, a phosphoric acid group, a sulfonic acid group, a sulfonyloxy group, a hydroxyl group, a quaternary ammonium group, a thioether group, a disulfide bond, an ether group, a sulfhydryl group, an amine group, an amino group, a urea group, and a guanidine group, and the water-soluble portion may be a group connected to the carbon chain serving as the active portion;
[0795] The binding moiety is a molecule or residue of a molecule that can bind to the microbial lipid membrane, microbial surface protein, microbial surface polysaccharide, or cell wall component, or can bind to a polysaccharide, protein, or polypeptide in the microorganism. The binding moiety can be the same as the water-soluble moiety, i.e., a protein, polypeptide, oligopeptide, oligosaccharide, monosaccharide, and / or polysaccharide molecule or residue thereof that can bind to the microbial lipid membrane or surface domain. The binding moiety can also be the same as the water-soluble moiety, i.e., after forming a complex, one or more free carboxyl, phosphate, sulfonate, hydroxyl, sulfhydryl, amine, amino, urea, or guanidine groups are retained. In some cases, the binding moiety can be a dibasic fatty acid or polybasic fatty acid, or a fat-soluble amino acid molecule or residue thereof that binds to the microbial lipid membrane or surface domain. In this case, the carboxylic acid group and amino acid group in these dibasic fatty acid or polybasic fatty acid or fat-soluble amino acid molecule or residue essentially play a binding role.
[0796] Specifically, the active part is a fat-soluble carbon chain, including a saturated or unsaturated carbon chain with a branched or cyclic structure; preferably, the active part is selected from saturated and / or unsaturated aliphatic hydrocarbons, saturated and / or unsaturated aliphatic alcohols or oxy-fatty alcohols, saturated and / or unsaturated fatty acids, hydrophobic amino acids, fat-soluble vitamins, steroid lipids, phospholipids, sphingomyelins, glycolipids, and the carbon chain or carbon chain residue formed by the surfactant has 3-48 carbon atoms, more preferably 3-26 carbon atoms; preferably, the carbon chain has 3-26 carbon atoms;
[0797] The water-soluble portion is a water-soluble molecule or molecule residue containing one or more groups selected from sulfhydryl, amino, phosphate, carboxylic acid, sulfonic acid, hydroxyl, amine, urea, guanidine and disulfide groups; the group that plays a binding role in the binding portion (capable of binding to microbial lipid membranes, microbial surface proteins, microbial surface polysaccharides or cell wall components or capable of binding to polysaccharides, proteins or polypeptides in microorganisms) is one or more groups selected from sulfhydryl, amino, phosphate, carboxylic acid, sulfonic acid, hydroxyl, amine, urea, guanidine and disulfide groups from the water-soluble portion or one or more groups selected from sulfhydryl, amino, phosphate, carboxylic acid, sulfonic acid, hydroxyl, amine, urea, guanidine and disulfide groups that provide carbon chain-to-carbon chain connection.
[0798] Specifically, for the complex of the present invention, the water-soluble portion is a water-soluble molecule or molecule residue, including macromolecular proteins, polysaccharides, nucleic acids, synthetic water-soluble polymers, medium molecular polypeptides, oligopeptides, oligosaccharides, oligonucleotides, synthetic polymers with moderate water solubility, and small molecules including amino acids, monosaccharides or disaccharides, nucleotides, and water-soluble vitamins; it can also be a functional group directly bound to the carbon chain that can increase water solubility, such as an amide group, phosphoryloxy group, carboxylic acid group, phosphate group, sulfonic acid group, sulfonyloxy group, hydroxyl group, quaternary ammonium group, thioether group, disulfide bond, ether group, thiol group, aldehyde group, ester group, amine group, amino group, urea group, guanidine group, etc.; the water-soluble portion can be a group connected to the carbon chain serving as the active portion and / or binding portion;
[0799] The binding portion is a molecule or a residue of a molecule (comprising the functional group on the molecule) that can be combined with a microorganism lipid membrane, a microorganism surface protein, a microorganism surface polysaccharide or a cell wall component, can be the third part that constitutes the complex, can also be identical with the water-soluble part, or can be connected with the active part. When the binding portion and the water-soluble part are the same part such as a protein, polypeptide, a polysaccharide that can be combined with a microorganism lipid membrane, a microorganism surface protein, a microorganism surface polysaccharide, the water-soluble part is a kind of that contains and is selected from sulfhydryl, amino, urea group, guanidine group, carboxylic acid group, hydroxyl and disulfide ether group. When the binding portion is in some cases, the dibasic fatty acid or polybasic fatty acid, fat-soluble amino acid etc. that can be combined with a microorganism lipid membrane, a microorganism surface protein, a microorganism surface polysaccharide can be used.
[0800] Without being limited by the reaction mechanism, the functional groups in the binding part that play a binding role may be carboxyl, sulfonic acid, phosphoric acid, hydroxyl, aldehyde or hemiacetal hydroxyl (sugar), amino, urea, guanidine, sulfhydryl, etc.
[0801] 1. The following is further explained using fatty acids as carbon chain donors (i.e., functional part donors):
[0802] (1) Fatty acids are insoluble in water or have very low water solubility and cannot be directly injected into the blood circulation. Direct injection into the vein can cause pulmonary embolism, and injection into the artery can cause arterial embolism and tissue necrosis;
[0803] (2) Fatty acids are re-esterified in intestinal cells and mixed with bile salts and monoglycerides to form 4-6 nm fat particles. These fat particles are directly absorbed by intestinal epithelial cells through phagocytosis and coated with a layer of phosphatidylcholine and protein membrane. They become chylomicrons and enter the lymphatic system. They pass through the lymphatic vessels and thoracic duct and return to the blood circulation in the form of water-in-oil emulsions. Except for a small amount of medium-chain fatty acids that exist in the peripheral blood for a short period of time, most of them are non-covalently bound to serum proteins and reach the liver quickly through the portal vein system. In the liver, medium-chain fatty acids can quickly pass through the mitochondrial double membrane and are quickly acylated under the action of octanoyl CoA, and are almost not synthesized into fat. The excess acetyl CoA produced by acylation undergoes various metabolic reactions in the mitochondrial cytoplasm, most of which tend to synthesize ketone bodies.
[0804] (3) Fatty acids covalently bonded to large, medium and small molecules convert fat-soluble fatty acids into water-soluble fatty acids, which are not easily eliminated and metabolized by the liver.
[0805] (4) The highly water-soluble and high-affinity complex of the present invention has the effect of resisting microbial infection. In addition to the external skin dosage form, it can also be used in nasal spray, dry powder inhaler, and can also be used for intravenous injection and oral dosage form.
[0806] 2. Complexes formed by fatty acids and water-soluble amino acids, monosaccharides or disaccharides, nucleotides, and water-soluble vitamins
[0807] In this case, the carbon chain of the fatty acid is the active part, the water-soluble amino acid, monosaccharide or disaccharide, nucleotide, or water-soluble vitamin is the water-soluble part, and then the binding part is connected to form the complex with antimicrobial infection effect described in the present invention. The binding part can be selected from dibasic or polybasic fatty acids, amino acids, targeting proteins, targeting polypeptides, and targeting polysaccharides. Among them, dibasic or polybasic fatty acids and fat-soluble amino acids are both the binding part and the active part; water-soluble amino acids, targeting proteins, targeting polypeptides, and targeting polysaccharides are both the binding part and the water-soluble part.
[0808] In one embodiment, the complex of the present invention is selected from a complex formed by linking a fatty trienoic acid having 3 to 50 carbon atoms and a water-soluble amino acid, for example, the following compound is a complex formed by linking octadecatrienoic acid and asparagine:
[0809] The carbon chain of octadecatrienoic acid is the active part, and asparagine is both the water-soluble part and the binding part.
[0810] 3. Complexes formed by fatty acids with proteins, peptides and polysaccharides
[0811] At this time, the carbon chain of fatty acid is the active part, which can target the surface domain of the virus, the protein or polypeptide of the lipid membrane or cell wall, and the polysaccharide is the binding part, and it is also the water-soluble part.
[0812] In a specific embodiment, the complex of the present invention is selected from a complex formed by a fatty olefinic acid having 3-50 carbon atoms linked to a targeting polypeptide, for example, the structural formula shown below is a schematic structural formula of a complex formed by octadecenoic acid linked to a targeting polypeptide, wherein octadecenoic acid is linked to a lysine residue in the polypeptide by an amide bond.
[0813] The carbon chain of octadecenoic acid is the active part, and the targeting polypeptide is both the water-soluble part and the binding part.
[0814] 4. In the above three cases, if the water solubility of the complex is poor, or if the complex molecules need to be enlarged, a water-soluble polymer can be added, such as
[0815] Fatty acid+targeting polypeptide+PEG, that is, the complex is a complex formed by the reaction of a fatty acid with 3-50 carbon atoms, a targeting polypeptide and PEG.
[0816] At this time, the carbon chain of the fatty acid is the active part, the targeting polypeptide is the binding part, and PEG is the water-soluble part.
[0817] 5. Compounds such as fatty alcohol polyoxyethylene ethers, fatty acid polyoxyethylene esters, alkyl glycosides, fatty acid sucrose esters, sorbitan fatty acid esters, sorbitan polyoxyethylene fatty acid esters, mannose erythritol esters, and N-acyl-N-methylglucosamine have fatty alcohols or fatty acids as carbon chain donors and are highly water-soluble. However, they have weak binding to viral surface domains, lipid membranes, or cell wall components, requiring higher concentrations to kill microorganisms. At these concentrations, these compounds can also damage human cells and are unsuitable for use within the human body. When these compounds are linked to a binding moiety to form a new complex, they possess the ability to kill microorganisms at relatively low concentrations within the human body, exerting an antimicrobial infection effect. Furthermore, at this therapeutic concentration, the new complex comprising the active moiety + water-soluble moiety + binding moiety has no effect on human tissue cells and organs. The binding moiety can be selected from dibasic or polybasic fatty acids, amino acids, targeting proteins, targeting polypeptides, or targeting polysaccharides. That is, in this case, the complex of the present invention is a complex formed by the reaction of a surfactant and one or more selected from dibasic fatty acids or polybasic fatty acids, amino acids, targeting proteins, targeting polypeptides and targeting polysaccharides.
[0818] At this time, the carbon chain of fatty alcohol or fatty acid is the active part, polyoxyethylene ether (PEG), dextran, sucrose, anhydrous sorbitol, mannitol erythritol, and glucosamine are the water-soluble parts, the connected dibasic fatty acids or polybasic fatty acids and fat-soluble amino acids are both the binding part and the active part, and the water-soluble amino acids, targeting proteins, targeting polypeptides, and targeting polysaccharides are both the binding part and the water-soluble part.
[0819] Specifically, in one embodiment of the present invention, the present invention provides a group of complexes that can prevent and treat viral, bacterial and fungal infections, wherein the main structure is formed by an active portion, a binding portion and a water-soluble portion coupled by covalent bonds, hydrogen bonds or van der Waals forces;
[0820] The active part gives the complex the effect of destroying the lipid membrane of microorganisms or hydrophobically isolating non-enveloped viruses; the binding part gives the complex the effect of binding to the lipid membrane of microorganisms or the surface domain of viruses, and a specific binding part can also give the complex the effect of specifically targeting microorganisms; the water-soluble part gives the complex water solubility, so that the complex can be evenly dispersed in an aqueous solution and prevent hydrophobic groups from aggregating into clusters to form lipid droplets.
[0821] The lipid membrane refers to the envelope formed by the phospholipid bilayer of the microorganism;
[0822] The active part, binding part and water-soluble part of the complex can be a natural compound, an artificially synthesized compound or a natural compound coupled with an artificially synthesized compound;
[0823] The number of groups of the same type in the complex can be one or more; the arrangement and order of the groups are not fixed; the groups of the same or different types can be coupled linearly or in the form of side chains.
[0824] The complex can be used to prevent and treat infectious diseases caused by viruses, bacteria, fungi, chlamydia and mycoplasma.
[0825] Furthermore, the active part is a natural or synthetic hydrophobic group, including a straight carbon chain, a branched carbon chain, or a cyclic carbon chain; the carbon chain may be a saturated or unsaturated carbon chain, and the unsaturated carbon chain may have one or more unsaturated bonds, wherein the unsaturated bond may be a double bond or a triple bond;
[0826] For microorganisms with lipid membrane structures, such as enveloped viruses, bacteria, fungi, chlamydia and mycoplasma, the active part can penetrate, insert into, and integrate into the lipid membrane, destroying the structural stability of the lipid membrane and then destroying the integrity of the lipid membrane and cell wall, thereby achieving the effect of killing microorganisms;
[0827] For non-enveloped viruses, the binding portion binds to the viral surface protein domain, and the active portion is wrapped around the surface of the non-enveloped virus, causing the non-enveloped virus to be hydrophobically isolated and then cleared by immune cells, thereby achieving the effect of preventing and treating non-enveloped virus infection.
[0828] Furthermore, the binding portion has one or more functional groups that can bind to proteins, polysaccharides or binding domains, such as carboxyl groups, hydroxyl groups, amino groups, sulfhydryl groups, urea groups, and guanidinium groups, and can bind to proteins, polysaccharides or binding domains on the lipid membrane or virus surface, so that the complex is attached to the lipid membrane or virus surface;
[0829] The binding portion can also be designed to have a molecular structure that specifically targets lipid membranes, bacterial and fungal cell wall components, and viral surface protein domains, thereby giving the complex the function of targeting viruses, bacteria, and fungi;
[0830] The binding portion and the hydrophilic group can be the same group, which can bind to the lipid membrane, cell wall or virus surface protein domain, and can also impart water solubility to the complex.
[0831] Furthermore, the binding moiety that can specifically target microbial lipid membranes, bacterial and fungal cell wall components, and viral surface protein domains is a protein, polypeptide, or polysaccharide, including:
[0832] (1) Neutralizing antibodies targeting coronavirus envelope proteins including spike glycoprotein (S), small envelope glycoprotein (E), membrane glycoprotein (M), and hemagglutinin glycoprotein (HE), as well as amino acid sequences and small molecule peptides that can specifically bind to the above protein domains;
[0833] (2) Proteins targeting the human immunodeficiency virus envelope include: neutralizing antibodies against gp120 and gp41 proteins, as well as amino acid sequences and small molecule peptides that can specifically bind to the above protein domains;
[0834] (3) Neutralizing antibodies targeting hepatitis B virus envelope proteins including SHBs, MHBs, and LHBs, as well as amino acid sequences and small molecule peptides that can specifically bind to the above protein domains;
[0835] (4) Targeting HCV envelope proteins, including neutralizing antibodies against E1 and E2 proteins, as well as amino acid sequences and small molecule peptides that can specifically bind to the above protein domains;
[0836] (5) Targeting rabies virus envelope protein includes: neutralizing antibodies against envelope glycoprotein, as well as amino acid sequences and small molecule peptides that can specifically bind to the above protein domains;
[0837] (6) Neutralizing antibodies targeting herpes virus envelope proteins including gB, gC, gD, gE, gG, and gH glycoproteins, as well as amino acid sequences and small molecule peptides that can specifically bind to the above protein domains;
[0838] (7) neutralizing antibodies targeting Ebola virus envelope proteins, including envelope glycoproteins on the viral outer membrane, as well as amino acid sequences and small molecule peptides that can specifically bind to the above protein domains;
[0839] (8) Targeting Hantavirus envelope proteins include: neutralizing antibodies against G1 and G2 glycoproteins, as well as amino acid sequences and small molecule peptides that can specifically bind to the above protein domains;
[0840] (9) Targeting dengue virus envelope proteins including: neutralizing antibodies against protein E and protein M, as well as amino acid sequences and small molecule peptides that can specifically bind to the above protein domains;
[0841] (10) Neutralizing antibodies targeting the envelope proteins of Japanese encephalitis virus include: glycoprotein E (i.e., viral hemagglutinin) and protein M, as well as amino acid sequences and small molecule peptides that can specifically bind to the above protein domains;
[0842] (11) Targeting influenza virus envelope proteins include: neutralizing antibodies against hemagglutinin and neuraminidase, as well as amino acid sequences and small molecule peptides that can specifically bind to the above protein domains;
[0843] (12) Neutralizing antibodies targeting hepatitis A virus capsid proteins including VP1, VP2, VP3, and VP4, as well as amino acid sequences and small molecule peptides that can specifically bind to the above protein domains;
[0844] (13) Targeting human papillomavirus capsid proteins include: neutralizing antibodies against L1 and L2 proteins, as well as amino acid sequences and small molecule peptides that can specifically bind to the above protein domains;
[0845] (14) Neutralizing antibodies targeting adenovirus capsid proteins including PⅡ, PⅢ, PⅢa, PⅣ, PⅥ, PⅧ, and PⅨ, as well as amino acid sequences and small molecule peptides that can specifically bind to the above protein domains;
[0846] (15) Neutralizing antibodies targeting poliovirus capsid proteins including VP1, VP2, VP3, and VP4, as well as amino acid sequences and small molecule peptides that can specifically bind to the above protein domains;
[0847] (16) Neutralizing antibodies targeting Coxsackievirus capsid proteins including VP1, VP2, VP3, and VP4, as well as amino acid sequences and small molecule peptides that can specifically bind to the above protein domains;
[0848] (17) Proteins targeting bacterial or fungal cell walls include: CD14 and amino acid sequences and small molecule peptides that can specifically bind to its domains;
[0849] (18) Also included are ligands designed for low-affinity receptors (such as heparan sulfate, proteoglycans, etc.) targeting enveloped viruses, bacteria, or fungal cell walls.
[0850] That is, for the present invention, in order to prevent, inhibit or treat microbial infection diseases, the basic structure of the complex of the present invention includes any of the following components:
[0851] Binding part + water-soluble part + active part;
[0852] Binding part + action part + water-soluble part;
[0853] Water-soluble part + active part + binding part;
[0854] Water-soluble part + binding part + active part;
[0855] Binding part + water-soluble part + binding part + active part + … + XX part;
[0856] Binding part + water-soluble part + active part + water-soluble part + … + XX part;
[0857] Binding part + water-soluble part + active part + binding part + ... + XX part;
[0858] Water-soluble part + binding part + active part + binding part + ... + XX part; and
[0859] Water-soluble part + active part + binding part + active part + … + XX part.
[0860] Here, the term "XX moiety" refers to any one or more moieties of "water-soluble moiety", "binding moiety" and "action moiety".
[0861] The number of the same type of parts in the complex can be one or more, and the arrangement and order of the parts are not fixed.
[0862] Furthermore, in a more specific embodiment, the structure of the complex of the present invention includes the following structure.
[0863] The small molecule water-soluble portion / binding portion is covalently bound to the active portion of the medium- or short-chain carbon chain, wherein the medium- or short-chain carbon chain includes a saturated or unsaturated straight carbon chain, a branched carbon chain, and a carbon chain with a cyclic structure, and may be a carbon chain of 3 to 10 carbon atoms. The small molecule water-soluble portion / binding portion may be a small molecule, medium molecule, or macromolecule with a carboxyl group or a hydroxyl group, such as:
[0864] A complex formed by amino acids or monosaccharides, nucleotides and carbon chains with 3-10 carbon atoms with carboxyl / hydroxyl groups. This complex has significantly improved water solubility, is well dispersed, and does not aggregate into clumps.
[0865] In the complex formed by the macromolecular water-soluble part + the binding part + the long-chain carbon chain (more than 10 carbon atoms) interaction part, the long-chain carbon chain includes a saturated or unsaturated straight carbon chain, a branched carbon chain, and a carbon chain with a cyclic structure, for example, a complex with the following structure is formed:
[0866] Protein / target protein + binding part + linear, branched or saturated / unsaturated carbon chain with a ring structure,
[0867] Targeting small molecules + protein + binding part + straight chain, branched chain or saturated / unsaturated carbon chain with ring structure,
[0868] Polysaccharide + binding part + straight chain, branched chain or saturated / unsaturated carbon chain with ring structure,
[0869] Targeting small molecules + polysaccharides + binding moieties + linear, branched or saturated / unsaturated carbon chains with cyclic structures,
[0870] Water-soluble polymer + binding part + straight chain, branched chain or saturated / unsaturated carbon chain with ring structure,
[0871] Targeting small molecule + water-soluble high molecular polymer + binding part + straight chain, branched chain or saturated / unsaturated carbon chain with a ring structure.
[0872] Furthermore, the complex is a derivative of a water-soluble portion, a binding portion and a lipid covalently coupled, and the construction mode includes:
[0873] Macromolecular water-soluble part / binding part / targeted binding part + lipid,
[0874] Macromolecular water-soluble part + binding part / targeted binding part + lipid,
[0875] 2 or more small molecule water-soluble parts / binding parts / targeted binding parts + lipids,
[0876] 2 or more small molecule water-soluble parts + binding part / targeted binding part + lipid.
[0877] Furthermore, the lipids include fatty alcohols, fatty acids, phospholipids, fat-soluble vitamins and steroid lipids;
[0878] The fatty alcohols include saturated fatty ...
Claims
1. A complex capable of preventing, inhibiting and / or treating viral or bacterial infection, comprising an active portion, a binding portion and a water-soluble portion, wherein: The virus is one or more viruses selected from the group consisting of novel coronavirus, influenza virus, HIV, hepatitis B virus, human herpes virus, Ebola virus, rabies virus, and human papillomavirus; the bacteria are one or more bacteria selected from the group consisting of Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa; The active part is a fat-soluble saturated and / or unsaturated carbon chain with a branched, cyclic and / or linear structure, the carbon chain is a molecule or a residue of a molecule, and the carbon chain is a carbon chain with 3-100 carbon atoms; wherein the active part is a carbon chain or a residue of a carbon chain with 3-100 carbon atoms formed by a saturated and / or unsaturated fatty acid; The water-soluble portion is a water-soluble molecule or a residue of a molecule, wherein the molecule contains one or more functional groups selected from amide groups, phosphoryloxy groups, carboxylic acid groups, phosphoric acid groups, sulfonic acid groups, sulfonyloxy groups, hydroxyl groups, quaternary ammonium groups, thioether groups, disulfide bonds, ether groups, sulfhydryl groups, aldehyde groups, ester groups, amine groups, amino groups, urea groups, and guanidine groups. The water-soluble portion may be one or more functional groups connected to the carbon chain serving as the active portion; The binding portion is a molecule or a residue of a molecule that can bind to a microbial lipid membrane, a microbial surface protein, a microbial surface polysaccharide or a cell wall component, or can bind to a polysaccharide, protein or polypeptide in a microorganism. The binding portion can be the same as the water-soluble portion, i.e., a protein, polypeptide, amino acid, oligopeptide, oligosaccharide, monosaccharide and / or polysaccharide molecule or its residue that can bind to a microbial lipid membrane or surface domain; The number of any one of the active part, the water-soluble part and the binding part can be 1 or more. The complex according to claim 1 , wherein the number of carbon atoms is 3-48. The complex according to claim 1 , wherein the number of carbon atoms is 3-26.
4. The complex according to claim 1, wherein the water-soluble portion is a water-soluble molecule or a residue of a molecule containing one or more groups selected from the group consisting of a thiol group, an amino group, a phosphate group, a carboxylic acid group, a sulfonic acid group, a hydroxyl group, an amine group, a urea group, a guanidine group, and a disulfide group; The binding portion has a group that plays a binding role, that is, it can bind to the microbial lipid membrane, microbial surface protein, microbial surface polysaccharide or cell wall component or can bind to the polysaccharide or protein or polypeptide in the microorganism. The group is from the water-soluble part or from two or more groups selected from thiol, amino, phosphate, carboxylic acid, sulfonic acid, hydroxyl, amine, urea, guanidine and disulfide groups as independent binding parts, or from one or more groups selected from thiol, amino, phosphate, carboxylic acid, sulfonic acid, hydroxyl, amine, urea, guanidine and disulfide groups that provide carbon chain-to-carbon chain connection, so that the complex has one or more groups selected from thiol, amino, phosphate, carboxylic acid, sulfonic acid, hydroxyl, amine, urea, guanidine and disulfide groups.
5. The complex according to claim 4, wherein the binding moiety is one or more selected from dibasic fatty acids or polybasic fatty acids, amino acids, targeting proteins, targeting polypeptides, and targeting polysaccharides.
6. The complex according to claim 4, wherein the complex is a complex formed by linking a fatty acid with 3-50 carbon atoms and a water-soluble amino acid; or, the complex is a complex formed by linking a fatty acid with 3-50 carbon atoms and a targeting polypeptide; or, the complex is a complex formed by reacting a fatty acid with 3-50 carbon atoms, a targeting polypeptide, and PEG; or, the complex is a complex formed by reacting a surfactant and one or more selected from dibasic fatty acids or polybasic fatty acids, amino acids, targeting proteins, targeting polypeptides, and targeting polysaccharides.
7. The complex according to claim 4, wherein the saturated and / or unsaturated fatty acid is selected from saturated fatty acids or unsaturated fatty acids having 3 to 50 carbon atoms, and the fatty acid is a fatty acid or amino acid containing a double bond, a triple bond, a hydroxyl group, an amino group and / or oxygenated, and is a monobasic acid, a dibasic acid or a polybasic acid.
8. The complex according to claim 4, wherein the saturated and / or unsaturated fatty acid is selected from the group consisting of saturated fatty acids having 3 to 46 carbon atoms, monoenoic acids having 3 to 34 carbon atoms, dienoic acids having 5 to 30 carbon atoms, trienoic acids having 7 to 30 carbon atoms, tetraenoic acids having 12 to 38 carbon atoms, pentaenoic acids having 12 to 38 carbon atoms, hexaenoic acids having 22 to 38 carbon atoms, ynoic acids having 6 to 22 carbon atoms, diynoic acids having 10 to 22 carbon atoms, triynoic acids having 12 to 22 carbon atoms, enoic acids having 8 to 20 carbon atoms, fatty acids having 3 to 30 carbon atoms in the main chain and 1 to 10 alkyl groups and / or 1 to 3 hydroxyl groups on the side chains, One or more of saturated straight-chain and branched dicarboxylic acids and tricarboxylic acids having 3-38 carbon atoms, unsaturated straight-chain or branched dicarboxylic acids and tricarboxylic acids having 4-18 carbon atoms which may be substituted with hydroxyl groups, amino-, hydroxyl-, oxo- and / or methyl-substituted carboxylic acids having 3-18 carbon atoms, N-acylamino acids having 6-30 carbon atoms, amino acids containing 2 or more acyl groups, and polycarboxylic acids connected by thioether bonds and amide bonds.
9. The complex according to claim 4, wherein the saturated / unsaturated fatty acid is one or more selected from fumaric acid, octanoic acid, glutaconic acid, hexanoic acid, nonanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid, octadecanoic acid, eicosanoic acid, oleic acid, linoleic acid, linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid, pentacosanoic acid, heptanoic acid, decanoic acid, dodecenoic acid, tetradecenoic acid, docosahexaenoic acid, and octacosanoic acid, or carbon chain residues formed therefrom.
10. The complex according to claim 4, wherein the water-soluble portion is a molecule or a residue of a molecule containing one or more groups selected from the group consisting of sulfhydryl, amino, carboxylic acid, hydroxyl, and disulfide groups; the molecule is one or more water-soluble macromolecules or residues thereof selected from the group consisting of proteins, polysaccharides, nucleic acids, and synthetic water-soluble polymers; and / or, one or more medium molecules or their residues selected from polypeptides, oligopeptides, oligosaccharides, oligonucleotides and synthetic water-soluble medium molecular weight polymers; and / or, one or more water-soluble small molecules or their residues selected from amino acids, monosaccharides, disaccharides, nucleotides, water-soluble vitamins and deoxynucleotides; and / or, a molecule or a residue of a molecule connected to the carbon chain serving as the active part, wherein the molecule or the residue of a molecule contains one or more groups selected from the group consisting of a thiol group, an amino group, a carboxylic acid group, a hydroxyl group, and a disulfide group.
11. The complex according to claim 10, wherein the protein serving as the water-soluble macromolecule is one or more water-soluble macromolecules selected from serum albumin, immunoglobulin, water-soluble collagen, chaperone protein, water-soluble glycoprotein, and CD14; the polysaccharide serving as the macromolecule is one or more water-soluble macromolecules selected from dextran, hyaluronic acid, sialic acid, heparin sulfate, heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, acetyl water-soluble cellulose derivatives, β-cyclodextrin and its derivatives, and water-soluble chitosan derivatives; the water-soluble polymer serving as the macromolecule is one or more water-soluble macromolecules selected from polyethylene glycol and carboxylated or amino polyethylene glycol, polyvinyl alcohol and carboxylated or quaternized polyvinyl alcohol, polyacrylic acid, and ammonium polyacrylate; The water-soluble medium molecular weight polymer is selected from one or more substances selected from targeting polypeptides, oligopeptides, oligosaccharides, oligonucleotides and / or water-soluble polyamino acids; The monosaccharides and / or disaccharides of the water-soluble small molecules are selected from one or more of glucose, fructose, rhamnose, sorbose, sucrose, maltose, lactose and trehalose; the nucleotides and / or deoxynucleotides of the water-soluble small molecules are selected from one or more of adenylic acid, guanylic acid, uridine monophosphate, cytidylic acid, thymidylic acid, inosinic acid, deoxyadenylic acid, deoxyguanylic acid, deoxycytidylic acid and deoxythymidylic acid; the amino acids are selected from one or more of serine, threonine, cysteine, asparagine, glutamine, tyrosine, lysine, arginine, histidine, aspartic acid, glutamic acid, citrulline, ornithine, taurine and aminobutyric acid; the vitamins of the water-soluble small molecules are selected from one or more of vitamin B1, pantothenic acid, vitamin B6 and vitamin C. 12 . The complex according to claim 11 , wherein the targeting polypeptide comprises any one of a protein or a neutralizing antibody fragment that specifically targets a microbial lipid membrane, a bacterial or fungal cell wall, or a viral surface protein domain. The complex according to claim 11 , wherein the water-soluble polyamino acid is selected from polyglutamic acid, polylysine and / or polyaspartic acid.
14. The complex according to claim 1, wherein the binding portion and the water-soluble portion are the same, that is, proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, amino acids, nucleotides, vitamins, water-soluble polymers, water-soluble polyamino acids and / or polysaccharide molecules or residues of these molecules that can bind to microbial lipid membranes and surface domains, and the molecules or residues of these molecules include one or more groups selected from sulfhydryl, amino, carboxylic acid, hydroxyl and disulfide groups.
15. The complex according to claim 1, which is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 100 carbon atoms with at least one selected from proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, nucleotides, vitamins, amino acids, water-soluble polymers, water-soluble polyamino acids and polysaccharide molecules; or it is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 50 carbon atoms with at least one selected from proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, nucleotides, vitamins, amino acids, water-soluble polymers, water-soluble polyamino acids and polysaccharide molecules, and a mixture of unreacted fatty acids and / or unreacted proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, nucleotides, vitamins, amino acids, water-soluble polymers, water-soluble polyamino acids and polysaccharide molecules.
16. The complex according to claim 1, which is a complex formed by physical and chemical action of saturated and / or unsaturated fatty acids having 3 to 100 carbon atoms and at least one selected from proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, nucleotides, vitamins, amino acids, water-soluble polymers, water-soluble polyamino acids and polysaccharide molecules, or a mixture obtained by direct physical mixing, wherein the physical and chemical action includes hydrogen bonding or van der Waals forces or a combination of the two.
17. The complex according to claim 15, which is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 100 carbon atoms with at least one selected from proteins, polypeptides, oligopeptides and amino acids; or it is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 100 carbon atoms with at least one selected from proteins, polypeptides, oligopeptides and amino acids, and a mixture of unreacted fatty acids and / or unreacted at least one selected from proteins, polypeptides, oligopeptides and amino acids.
18. The complex according to claim 15, which is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 100 carbon atoms, PEG and at least one selected from proteins, polypeptides, oligopeptides and amino acids; or it is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 100 carbon atoms, PEG and at least one selected from proteins, polypeptides, oligopeptides and amino acids, and a mixture of unreacted fatty acid, unreacted PEG and / or unreacted at least one selected from proteins, polypeptides, oligopeptides and amino acids.
19. The complex according to claim 15, which is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 100 carbon atoms with at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides; or it is a mixture of a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 100 carbon atoms with at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides, and unreacted fatty acids and / or unreacted polysaccharides, monosaccharides, disaccharides and / or oligosaccharides.
20. The complex according to claim 15, which is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3-100 carbon atoms, PEG and at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides; or it is a mixture of a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3-100 carbon atoms, PEG and at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides, and unreacted fatty acid, unreacted PEG and / or unreacted polysaccharides, monosaccharides, disaccharides and / or oligosaccharides. The complex according to claim 15 , wherein the protein is one or more selected from the group consisting of serum albumin, immunoglobulin, water-soluble collagen, chaperone protein, water-soluble glycoprotein and CD14.
22. The complex according to claim 15, wherein the polysaccharide is one or more selected from the group consisting of dextran and / or hyaluronic acid, sialic acid, heparin sulfate, heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, acetyl water-soluble cellulose derivatives, β-cyclodextrin and its derivatives, and water-soluble chitosan derivatives.
23. The complex according to claim 15, which is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 100 carbon atoms, a linker, and a protein containing a sulfhydryl group; or a mixture of the compound obtained by the above reaction, unreacted fatty acid, unreacted linker, and / or unreacted protein containing a sulfhydryl group; wherein, The linker is one or more of amino acids, succinic acid, butadienoic acid, glutaconic acid, hexamethylenediamine, carbamate, short peptide, N-hydroxybuteneimide, polyethylene glycol and derivatives of the above compounds.
24. The complex according to claim 23, which is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 100 carbon atoms, N-hydroxybutyromide and a protein containing a sulfhydryl group; or a mixture of the compound obtained by the above reaction, unreacted fatty acid, unreacted N-hydroxybutyromide and / or unreacted protein containing a sulfhydryl group.
25. The complex according to claim 15, which is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 100 carbon atoms, cystamine and at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides; or a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 50 carbon atoms, cystamine and at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides, and a mixture of unreacted fatty acid, unreacted at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides and / or unreacted cystamine.
26. The complex according to any one of claims 15 to 25, wherein the compound obtained by the reaction contains one or more of amide groups, ester groups, thioether groups or ether groups, and these groups serve as the connecting portion between the water-soluble portion and the active portion.
27. The complex according to any one of claims 4 to 25, wherein the saturated and / or unsaturated fatty acid has 3 to 50 carbon atoms. The complex according to claim 27 , wherein the number of carbon atoms is 3-48. The complex according to claim 27 , wherein the carbon atoms are 3 to 26.
30. The complex according to any one of claims 4 to 25, wherein the saturated and / or unsaturated fatty acid is a fatty acid having 3 to 40 carbon atoms and containing 1 to 8 C=C double bonds, a fatty acid containing 1 to 7 C=C double bonds, a fatty acid containing 1 to 6 double bonds, a fatty acid containing 1 to 5 double bonds, a fatty acid containing 1 to 4 double bonds, a fatty acid containing 1 to 3 double bonds, or a fatty acid containing 1 to 2 double bonds. The complex according to any one of claims 4 to 25 , wherein the saturated and / or unsaturated fatty acid is a fatty acid having 1 to 6 double bonds and 3 to 30 carbon atoms.
32. The complex according to any one of claims 4 to 25, wherein the saturated and / or unsaturated fatty acid has 3 to 30 carbon atoms.
33. The complex according to any one of claims 4 to 25, wherein the saturated and / or unsaturated fatty acids are selected from one or more of fumaric acid, octanoic acid, glutaconic acid, hexanoic acid, nonanoic acid, dodecanoic acid, tetradecanoic acid, hexadecanoic acid, octadecanoic acid, eicosanoic acid, oleic acid, linoleic acid, linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid, pentacosanoic acid, heptanoic acid, decanoic acid, dodecenoic acid, tetradecenoic acid, docosahexaenoic acid and octacosanoic acid. 34 . The complex according to claim 4 , wherein the protein is human serum albumin or bovine serum albumin, or CD14; or the polysaccharide is dextran and / or hyaluronic acid.
35. The complex according to claim 17, wherein the compound obtained by the reaction is a compound obtained by the reaction of fatty acid and albumin or SBP1, and has any one or more of the following structural formulas:
36. The complex according to claim 18, wherein the compound obtained by the reaction is a compound obtained by the reaction of a monobasic fatty acid having 3 to 10 carbon atoms, PEG and an amino acid, or a compound obtained by the reaction of a monobasic fatty acid having 3 to 10 carbon atoms, a saturated dibasic fatty acid having 5 to 8 carbon atoms, PEG and taurine.
37. The complex according to claim 36, wherein the compound obtained by the reaction is a compound having at least one of the following structural formulas: Wherein n is an integer from 1 to 200.
38. The complex according to claim 19, wherein the compound obtained by the reaction is any one or more compounds obtained by the reaction of fatty acid and dextran having the following structural formulas:
39. The complex according to claim 19, wherein the compound obtained by the reaction is any one or more compounds obtained by the reaction of fatty acid and hyaluronic acid having the following structural formula: n is an integer from 1 to 2000.
40. The complex according to claim 20, wherein the compound obtained by the reaction is a compound obtained by reacting a fatty acid having 3 to 10 carbon atoms with PEG and glucose.
41. The complex according to claim 40, wherein the compound obtained by the reaction is a compound having the following structural formula: n is an integer from 1 to 200.
42. The complex according to claim 23, wherein the compound obtained by the reaction is a compound having a thioether bond and having any one or more of the following structural formulas obtained by reacting fatty acid, N-hydroxybutyromide and albumin:
43. The complex according to claim 25, wherein the compound obtained by the reaction is any one or more compounds having the following structural formulas obtained by reacting fatty acid, cystamine and dextran:
44. The complex according to claim 25, wherein the compound obtained by the reaction is any one or more compounds obtained by the reaction of fatty acid, cystamine and hyaluronic acid having the following structural formula:
45. A preparation for preventing, inhibiting or treating microbial infection prepared using the complex according to any one of claims 1 to 44.
46. The preparation according to claim 45, which is a pharmaceutical preparation or an environmental disinfection preparation.
47. The preparation according to claim 46, wherein the pharmaceutical preparation is one selected from the group consisting of an inhaler, a nasal spray, an injection, an oral preparation, and a topical skin preparation.
48. Use of the complex according to any one of claims 1 to 44 in the preparation of a pharmaceutical preparation for preventing, inhibiting and / or treating microbial infection or an environmental microbicidal agent.
49. The use according to claim 48, wherein the microorganism is any one or two selected from viruses and bacteria.
50. The use according to claim 49, wherein the virus is an enveloped virus; and / or a non-enveloped virus.
51. The use according to claim 49, wherein the virus is one or more viruses selected from the group consisting of novel coronavirus, influenza virus, human immunodeficiency virus (HIV), hepatitis B virus, human herpes virus, Ebola virus, rabies virus, and human papillomavirus (HPV), and the bacteria are one or more bacteria selected from the group consisting of Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa.
52. The use according to claim 49, wherein the virus is selected from one or more of H7N9 influenza virus, H5N1 influenza virus, HIV virus, new coronavirus, HPV virus and rabies virus.
53. A method for preparing the complex according to any one of claims 1 to 44, comprising reacting fat-soluble saturated and / or unsaturated carbon chains having branched, cyclic and / or linear structures with water-soluble molecules, and proteins, polypeptides, amino acids, oligopeptides, oligosaccharides, monosaccharides and / or polysaccharide molecules capable of binding to microbial lipid membranes, microbial surface domains or cell walls, as well as linker molecules added as needed, in the presence of a catalyst to obtain the complex.
54. The method for preparing the complex according to claim 53, wherein the complex is a product obtained by purifying the compound obtained by the reaction.
55. A method for preparing the complex according to any one of claims 1 to 44, comprising physically mixing fat-soluble fatty acids having saturated and / or unsaturated carbon chains with branched, cyclic and / or linear structures with water-soluble molecules, and proteins, polypeptides, amino acids, oligopeptides, oligosaccharides, monosaccharides and / or polysaccharide molecules that can bind to microbial lipid membranes, viral surface domains or cell walls, as needed, to obtain the complex.
56. A method for preparing the complex according to any one of claims 1 to 44, comprising reacting a saturated and / or unsaturated fatty acid containing 3 to 100 carbon atoms with any one of proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, nucleotides, vitamins, amino acids, water-soluble polymers, water-soluble polyamino acids and / or polysaccharides in the presence of a catalyst to obtain the complex.
57. The method for preparing the complex according to claim 56, wherein the complex is a product obtained by purifying the compound obtained by the reaction.
58. A method for preparing the complex according to any one of claims 1-44, wherein the complex is obtained by physical-chemical complexing or direct physical mixing of saturated and / or unsaturated fatty acids having 3-100 carbon atoms with proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, nucleotides, vitamins, amino acids, water-soluble polymers, water-soluble polyamino acids and / or polysaccharide molecules.
59. A water-soluble carbon chain substance for regulating transmembrane transport and / or fluidity of cell membranes, comprising an active portion, a binding portion and a water-soluble portion, wherein: The active part is a fat-soluble saturated and / or unsaturated carbon chain with a branched, cyclic and / or linear structure, wherein the carbon chain is a molecule or a residue of a molecule, and the carbon chain is a carbon chain with 3-100 carbon atoms; wherein the active part is a saturated and / or unsaturated fatty acid, aliphatic hydrocarbon or cyclic hydrocarbon; or an aromatic ring compound or a heterocyclic compound; or a carbon chain or a residue of a carbon chain with 3-100 carbon atoms formed by any one or more of their salts, alcohols, ethers, esters or other derivatives; The water-soluble portion is a water-soluble molecule or a residue of a molecule, wherein the molecule contains one or more functional groups selected from amide groups, phosphoryloxy groups, carboxylic acid groups, phosphoric acid groups, sulfonic acid groups, sulfonyloxy groups, hydroxyl groups, quaternary ammonium groups, thioether groups, disulfide bonds, ether groups, sulfhydryl groups, aldehyde groups, ester groups, amine groups, amino groups, urea groups, and guanidine groups. The water-soluble portion may be one or more functional groups connected to the carbon chain serving as the active portion; The binding portion is a molecule or a residue of a molecule that can bind to a microbial lipid membrane, a microbial surface protein, a microbial surface polysaccharide or a cell wall component, or can bind to a polysaccharide or protein or polypeptide in a microbial, plant, animal or human organism, or can bind to a cell membrane or a cell membrane surface polysaccharide or a cell wall component of a plant, animal or human organism. The binding portion may be the same as the water-soluble portion, i.e., a protein, polypeptide, amino acid, oligopeptide, oligosaccharide, monosaccharide, disaccharide, amino acid, nucleotide, vitamin, water-soluble polymer, water-soluble polyamino acid and / or polysaccharide molecule or its residue that can bind to the surface domain of the lipid membrane of a microorganism or the cell membrane of a plant, animal or human body tissue; The number of any one of the active part, the water-soluble part and the binding part can be 1 or more.
60. The water-soluble carbon chain substance according to claim 59, wherein the number of carbon atoms is 3-50, preferably 3-48, and more preferably 3-26.
61. The water-soluble carbon chain substance according to claim 59, wherein the water-soluble portion is a water-soluble molecule or a residue of a molecule containing one or more groups selected from the group consisting of sulfhydryl, amino, phosphate, carboxylic acid, sulfonic acid, hydroxyl, amine, urea, guanidine and disulfide groups; The binding portion has a group that plays a binding role, that is, a molecule or a residue of a molecule that can bind to a microbial lipid membrane, a microbial surface protein, a microbial surface polysaccharide or a cell wall component, or can bind to a polysaccharide or protein or polypeptide in a microbial, plant, animal or human body, or a molecule or a residue of a molecule that can bind to a cell membrane or a polysaccharide or cell wall component on the cell membrane surface of a plant, animal or human body tissue. The group is derived from a water-soluble portion or from one or more groups selected from thiol, amino, phosphate, carboxylic acid, sulfonic acid, hydroxyl, amine, urea, guanidine and disulfide groups that serve as an independent binding portion, or from one or more groups selected from thiol, amino, phosphate, carboxylic acid, sulfonic acid, hydroxyl, amine, urea, guanidine and disulfide groups that provide a carbon chain-to-carbon chain connection, so that the complex has one or more groups selected from thiol, amino, phosphate, carboxylic acid, sulfonic acid, hydroxyl, amine, urea, guanidine and disulfide groups.
62. The water-soluble carbon chain substance according to any one of claims 59 to 61, wherein the binding moiety is selected from one or more of dibasic fatty acids or polybasic fatty acids, amino acids, targeting proteins, targeting polypeptides, and targeting polysaccharides.
63. The water-soluble carbon chain substance according to any one of claims 59 to 62, wherein the water-soluble carbon chain substance is a compound, a complex or a mixture.
64. The water-soluble carbon chain substance according to claim 63, wherein the water-soluble carbon chain substance is a complex formed by connecting a fatty acid with a carbon number of 3-50 and a water-soluble amino acid; a complex formed by connecting a fatty acid with a carbon number of 3-50 and a targeting polypeptide; a complex formed by reacting a fatty acid with a carbon number of 3-50, a targeting polypeptide and PEG; or a complex formed by reacting a surfactant and one or more selected from dibasic fatty acids or polybasic fatty acids, amino acids, targeting proteins, targeting polypeptides and targeting polysaccharides.
65. The water-soluble carbon chain substance according to any one of claims 59 to 63, wherein the saturated and / or unsaturated fatty acid is selected from a saturated fatty acid or an unsaturated fatty acid having 3 to 50 carbon atoms, and the fatty acid is a fatty acid or an amino acid containing a double bond, a triple bond, a hydroxyl group, an amino group and / or being oxidized, and is a monoprotic acid, a diprotic acid or a polyprotic acid.
66. The water-soluble carbon chain substance according to claim 65, wherein the saturated and / or unsaturated fatty acid is selected from saturated fatty acids having 3 to 46 carbon atoms, monoenoic acids having 3 to 34 carbon atoms, dienoic acids having 5 to 30 carbon atoms, trienoic acids having 7 to 30 carbon atoms, tetraenoic acids having 12 to 38 carbon atoms, pentaenoic acids having 12 to 38 carbon atoms, hexaenoic acids having 22 to 38 carbon atoms, acetylenic acids having 6 to 22 carbon atoms, diacetylenic acids having 10 to 22 carbon atoms, triacetylenic acids having 12 to 22 carbon atoms, and ene-ynes having 8 to 20 carbon atoms. Acid, fatty acid with 3-30 carbon atoms in the main chain and 1-10 alkyl groups and / or 1-3 hydroxyl groups in the side chain, saturated straight-chain and branched dicarboxylic acids and tricarboxylic acids with 3-38 carbon atoms and unsaturated straight-chain or branched dicarboxylic acids and tricarboxylic acids with 4-18 carbon atoms which may be substituted with hydroxyl groups, carboxylic acids with 3-18 carbon atoms substituted with amino, hydroxyl, oxo and / or methyl, N-acylamino acids with 6-30 carbon atoms, amino acids containing 2 or more acyl groups, and one or more polycarboxylic acids connected by thioether bonds and amide bonds.
67. The water-soluble carbon chain substance according to claim 65, wherein the saturated and / or unsaturated fatty acids are selected from one or more of fumaric acid, octanoic acid, octenic acid, glutaconic acid, hexanoic acid, suberic acid, nonanoic acid, dodecanoic acid, dodecanedioic acid, tridecanoic acid, tridecanedioic acid, tetradecanoic acid, hexadecanoic acid, hexadecanedioic acid, octadecanoic acid, eicosanoic acid, eicosandioic acid, oleic acid, linoleic acid, linolenic acid, eicosapentaenoic acid, docosenoic acid, docosapentaenoic acid, docosahexaenoic acid, pentacosanoic acid, heptanoic acid, decanoic acid, undecenoic acid, dodecenoic acid, tetradecenoic acid, hexadecenoic acid, triacontanedioic acid, docosahexaenoic acid, and octacosanoic acid, or carbon chain residues formed therefrom.
68. The water-soluble carbon chain substance according to any one of claims 59 to 63, wherein the water-soluble portion is a molecule or a residue of a molecule containing one or more groups selected from the group consisting of sulfhydryl, amino, carboxylic acid, hydroxyl, and disulfide groups; the molecule is one or more water-soluble macromolecules or residues thereof selected from the group consisting of proteins, polysaccharides, nucleic acids, and synthetic water-soluble polymers; and / or, one or more medium molecules or their residues selected from polypeptides, oligopeptides, oligosaccharides, oligonucleotides and synthetic water-soluble medium molecular weight polymers; and / or, one or more water-soluble small molecules or their residues selected from amino acids, monosaccharides, disaccharides, nucleotides, water-soluble vitamins and deoxynucleotides; and / or, a molecule or a residue of a molecule connected to the carbon chain serving as the active part, wherein the molecule or the residue of a molecule contains one or more groups selected from the group consisting of a thiol group, an amino group, a carboxylic acid group, a hydroxyl group, and a disulfide group.
69. The water-soluble carbon chain substance according to claim 68, wherein the protein serving as the water-soluble macromolecule is one or more water-soluble macromolecules selected from serum albumin, immunoglobulin, water-soluble collagen, chaperone protein, water-soluble glycoprotein and CD14; the polysaccharide serving as the macromolecule is one or more water-soluble macromolecules selected from dextran, hyaluronic acid, sialic acid, heparin sulfate, heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, acetyl water-soluble cellulose derivatives, β-cyclodextrin and its derivatives and water-soluble chitosan derivatives; the water-soluble polymer serving as the macromolecule is one or more water-soluble macromolecules selected from polyethylene glycol and carboxylated or amino polyethylene glycol, polyvinyl alcohol and carboxylated or quaternized polyvinyl alcohol, polyacrylic acid and ammonium polyacrylate; The water-soluble medium molecular weight polymer is selected from one or more substances selected from targeting polypeptides, oligopeptides, oligosaccharides, oligonucleotides and / or water-soluble polyamino acids; The monosaccharides and / or disaccharides of the water-soluble small molecules are selected from one or more of glucose, fructose, rhamnose, sorbose, sucrose, maltose, lactose and trehalose; the nucleotides and / or deoxynucleotides of the water-soluble small molecules are selected from one or more of adenylic acid, guanylic acid, uridine monophosphate, cytidylic acid, thymidylic acid, inosinic acid, deoxyadenylic acid, deoxyguanylic acid, deoxycytidylic acid and deoxythymidylic acid; the amino acids are selected from one or more of serine, threonine, cysteine, asparagine, glutamine, tyrosine, lysine, arginine, histidine, aspartic acid, glutamic acid, citrulline, ornithine, taurine and aminobutyric acid; the vitamins of the water-soluble small molecules are selected from one or more of vitamin B1, pantothenic acid, vitamin B6 and vitamin C.
70. The water-soluble carbon chain substance according to claim 69, wherein the targeting polypeptide comprises any one of a protein or a neutralizing antibody fragment that specifically targets a microbial lipid membrane, a bacterial and fungal cell wall, or a viral surface protein domain.
71. The water-soluble carbon chain substance according to claim 69, wherein the water-soluble polyamino acid is selected from polyglutamic acid, polylysine and / or polyaspartic acid.
72. water-soluble carbochain substances according to claim 59, described bound fraction is identical with water-soluble part, be the albumen, polypeptide, oligopeptides, oligosaccharide, monose, disaccharide, amino acid, nucleotide, vitamin, water-soluble polymer, water-soluble polyamino acid and / or polysaccharide molecule or the residue of these molecules that can be combined with the cell membrane or cell membrane surface domain of microorganism lipid film, animal or human body tissue, described molecule or molecule residue comprise one or more groups selected from sulfhydryl, amino, carboxylic acid group, hydroxyl, disulfide.
73. The water-soluble carbochain material according to claim 59, wherein the compound is obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 100 carbon atoms with at least one selected from a protein, a polypeptide, an oligopeptide, an oligosaccharide, a monosaccharide, a disaccharide, a nucleotide, a vitamin, an amino acid, a water-soluble polymer, a water-soluble polyamino acid, and a polysaccharide molecule; or the compound is obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 100 carbon atoms with at least one selected from a protein, a polypeptide, an oligopeptide, an oligosaccharide, a monosaccharide, a disaccharide, a nucleotide, a vitamin, an amino acid, a water-soluble polymer, a water-soluble polyamino acid, and a polysaccharide molecule, and a mixture of unreacted said fatty acid and / or unreacted said protein, a polypeptide, an oligopeptide, an oligosaccharide, a monosaccharide, a disaccharide, a nucleotide, a vitamin, an amino acid, a water-soluble polymer, a water-soluble polyamino acid, and / or a polysaccharide molecule.
74. The water-soluble carbon chain substance according to claim 59, which is a complex formed by physical and chemical reactions of saturated and / or unsaturated fatty acids containing 3 to 100 carbon atoms and at least one selected from proteins, polypeptides, oligopeptides, oligosaccharides, monosaccharides, disaccharides, nucleotides, vitamins, amino acids, water-soluble polymers, water-soluble polyamino acids and polysaccharide molecules, or a mixture obtained by direct physical mixing, wherein the physical and chemical reactions include hydrogen bonds or van der Waals forces or a combination of the two.
75. The water-soluble carbon chain substance according to claim 73, which is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 100 carbon atoms with at least one selected from proteins, polypeptides, oligopeptides and amino acids; or it is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 100 carbon atoms with at least one selected from proteins, polypeptides, oligopeptides and amino acids, and a mixture of unreacted fatty acids and / or unreacted at least one selected from proteins, polypeptides, oligopeptides and amino acids.
76. The water-soluble carbon chain substance according to claim 73, which is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3-100 carbon atoms, PEG and at least one selected from proteins, polypeptides, oligopeptides and amino acids; or it is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3-100 carbon atoms, PEG and at least one selected from proteins, polypeptides, oligopeptides and amino acids, and a mixture of unreacted fatty acids, unreacted PEG and / or unreacted at least one selected from proteins, polypeptides, oligopeptides and amino acids.
77. The complex according to claim 73, which is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3-100 carbon atoms with at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides; or it is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3-100 carbon atoms with at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides, and a mixture of unreacted fatty acids and / or unreacted polysaccharides, monosaccharides, disaccharides and / or oligosaccharides.
78. The water-soluble carbon chain substance according to claim 73, which is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 100 carbon atoms, PEG and at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides; or it is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 100 carbon atoms, PEG and at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides, and a mixture of unreacted fatty acids, unreacted PEG and / or unreacted polysaccharides, monosaccharides, disaccharides and / or oligosaccharides.
79. The water-soluble carbon chain substance according to claim 73 or 74, wherein the protein is selected from one or more of serum albumin, immunoglobulin, water-soluble collagen, chaperone protein, water-soluble glycoprotein and CD14.
80. The water-soluble carbon chain substance according to claim 73 or 74, wherein the polysaccharide is selected from one or more of dextran and / or hyaluronic acid, sialic acid, heparin sulfate, heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, acetyl water-soluble cellulose derivatives, β-cyclodextrin and its derivatives and water-soluble chitosan derivatives.
81. The water-soluble carbon chain substance according to claim 73, which is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 100 carbon atoms, a linker, and a protein containing a sulfhydryl group; or a mixture of the compound obtained by the above reaction, unreacted fatty acid, unreacted linker, and / or unreacted protein containing a sulfhydryl group; wherein, The linker is one or more of amino acids, succinic acid, butadienoic acid, glutaconic acid, hexamethylenediamine, carbamate, short peptide, N-hydroxybuteneimide, polyethylene glycol and derivatives of the above compounds.
82. The water-soluble carbon chain substance according to claim 81, wherein the water-soluble carbon chain substance is a compound obtained by reacting saturated and / or unsaturated fatty acids containing 3 to 100 carbon atoms, N-hydroxybutene imide and a protein containing a sulfhydryl group; or a mixture of the compound obtained by the above reaction, unreacted fatty acids, unreacted N-hydroxybutene imide and / or unreacted protein containing a sulfhydryl group.
83. The water-soluble carbon chain substance according to claim 73, which is a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 100 carbon atoms, cystamine and at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides; or a compound obtained by reacting a saturated and / or unsaturated fatty acid having 3 to 50 carbon atoms, cystamine and at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides, and a mixture of unreacted fatty acid, unreacted at least one selected from polysaccharides, monosaccharides, disaccharides and oligosaccharides and / or unreacted cystamine.
84. The water-soluble carbon chain substance according to any one of claims 73 to 83, wherein the compound obtained by the reaction contains one or more of an amide group, an ester group, a thioether group or an ether group, and these groups serve as the connecting portion between the water-soluble portion and the active portion.
85. The water-soluble carbon chain substance according to any one of claims 59-84, wherein the number of carbon atoms of the saturated and / or unsaturated fatty acid is 3-50, preferably 3-48, more preferably 3-30, and more preferably 3-26.
86. According to the water-soluble carbon chain substance according to any one of claims 73-84, the saturated and / or unsaturated fatty acid is a fatty acid with 3-40 carbon atoms and 1-8 C=C double bonds, a fatty acid with 1-7 C=C double bonds, a fatty acid with 1-6 double bonds, a fatty acid with 1-5 double bonds, a fatty acid with 1-4 double bonds, a fatty acid with 1-3 double bonds, or a fatty acid with 1-2 double bonds; preferably, the saturated and / or unsaturated fatty acid is a fatty acid with 1-6 double bonds and 3-30 carbon atoms.
87. The water-soluble carbon chain substance according to any one of claims 59 to 84, wherein the saturated and / or unsaturated fatty acid has 3 to 30 carbon atoms.
88. The water-soluble carbon chain substance according to any one of claims 59 to 84, wherein the saturated and / or unsaturated fatty acids are selected from one or more fatty acids selected from fumaric acid, octanoic acid, octenoic acid, glutaconic acid, hexanoic acid, suberic acid, nonanoic acid, dodecanoic acid, dodecanedioic acid, tridecanoic acid, tridecanedioic acid, tetradecanoic acid, hexadecanoic acid, hexadecanedioic acid, octadecanoic acid, eicosanoic acid, eicosandioic acid, oleic acid, linoleic acid, linolenic acid, eicosapentaenoic acid, docosenoic acid, docosapentaenoic acid, docosahexaenoic acid, pentacosanoic acid, heptanoic acid, decanoic acid, undecenoic acid, dodecenoic acid, tetradecenoic acid, hexadecenoic acid, triacontanedioic acid, docosahexaenoic acid, and octacosanoic acid.
89. The water-soluble carbon chain substance according to any one of claims 59 to 84, wherein the protein is human serum albumin or bovine serum albumin, or CD14; or the polysaccharide is dextran and / or hyaluronic acid.
90. The water-soluble carbon chain substance according to claim 75, wherein the compound obtained by the reaction is a compound obtained by the reaction of fatty acid and albumin or SBP1, and has any one or more of the following structural formulas:
91. The water-soluble carbon chain substance according to claim 76, wherein the compound obtained by the reaction is a compound obtained by the reaction of a monobasic fatty acid with a carbon number of 3-10, PEG and an amino acid, or a compound obtained by the reaction of a monobasic fatty acid with a carbon number of 3-10, a saturated dibasic fatty acid with a carbon number of 5-8, PEG and taurine.
92. The water-soluble carbon chain substance according to claim 91, wherein the compound obtained by the reaction is a compound having at least one of the following structural formulas: Wherein n is an integer from 1 to 200.
93. The water-soluble carbon chain substance according to claim 77, wherein the compound obtained by the reaction is any one or more compounds having the following structural formulas obtained by reacting fatty acids with dextran:
94. The water-soluble carbon chain substance according to claim 77, wherein the compound obtained by the reaction is any one or more compounds having the following structural formulas obtained by reacting fatty acids with hyaluronic acid: n is an integer from 1 to 2000.
95. The water-soluble carbon chain substance according to claim 78, wherein the compound obtained by the reaction is a compound obtained by reacting a fatty acid having 3 to 10 carbon atoms with PEG and glucose.
96. The water-soluble carbon chain substance according to claim 95, wherein the compound obtained by the reaction is a compound having the following structural formula: n is an integer from 1 to 200.
97. The water-soluble carbon chain substance according to claim 82, wherein the compound obtained by the reaction is a compound having a thioether bond and having any one or more of the following structural formulas obtained by reacting fatty acid, N-hydroxybutene imide and protein:
98. The water-soluble carbon chain substance according to claim 83, wherein the compound obtained by the reaction is any one or more compounds having the following structural formulas obtained by reacting fatty acids, cystamine and dextran:
99. The water-soluble carbon chain substance according to claim 83, wherein the compound obtained by the reaction is any one or more compounds having the following structural formula obtained by the reaction of fatty acid, cystamine and hyaluronic acid:
100. The water-soluble carbon chain substance according to any one of claims 59 to 72, comprising a small molecule compound containing a hydroxyl group and a benzene ring; preferably, comprising one or two or more substances selected from the following group of substances: Flavonoids, isoflavones, anthocyanins, soy isoflavones, aloe-emodin, grape seed extract, green tea flavonoids, naringenin, tartrazine, baicalein, riboflavin, quercetin, graphite flavonoids, cinnamon, buxol, hawthorn flavonoids, morin, luteolin, melilotin, gypsum flavonoids, honeysuckle flavonoids, gentian flavonoids, platycodon flavonoids, violet flavonoids, perilla flavonoids, chrysanthemum flavonoids, artemisia annua flavonoids, red peony flavonoids, salvia miltiorrhiza flavonoids, safflower flavonoids, rhodiola rosea flavonoids, red date flavonoids, wolfberry flavonoids, rehmannia glutinosa flavonoids, ganoderma lucidum flavonoids, schisandra chinensis flavonoids, licorice flavonoids, panax flavonoids, curcumin, apigenin, carotene, anthocyanins, lutein, zeaxanthin, mustard flavonoids, rutin, coriander, pollen flavonoids, sand Echinoflavones, marigold flavonoids, cinnamon flavonoids, isoflavonoids and anthocyanins; rutin, emodin, fucoxanthin, gallic acid, kakirin, morin, echinacea glycosides, grape seed proanthocyanidins, phenolic acids, tea polyphenols, naringin, citric acid, flavonols, glycyrrhizic acid, cinnamic acid, flavonoid glycosides, silymarin, matrine, tanshinone, erythrocephalin, seabuckthorn acid, perillyl alcohol, anisic acid, phellodendron, hesperidin, punica granatum, morilin, naringin, rubellin, gentiopicroside, jasmonate, naringol, carotene, apigenin, umelin, morilin, honeysuckle glycoside, chrysanthemin, olive oleate, tea cyanidin, theanine, wine glycosides, platycodin, perillyl alcohol glycosides, morus alba, safflower glycosides, pinus needle glycosides, pachycocin, caffeic acid, chlorogenic acid;Resveratrol, white tea polyphenols, resveratrol disaccharide, banana lutein, anthocyanin, arachidonic acid, peanut flavonoids, pepper phenol, fennel, flavonoids, baicalein, flavonoid glycosides, flavanols, red wine polyphenols, rhodiola rosea, safflower phenol, black tea flavonoids, black sesame, rye phenol, trehalitol, seaweed polysaccharides, alginic acid, albizzia alkaloids, hemp phenol, polydatin, cucurbitacin, fenugreek, cucurbitacin, pollen phenol, pollen flavonoids, Pollen glycosides, pollen esters, arachidic acid, peanut flavonoid glycosides, peanut isoflavones, peanut isoflavone glycosides, peanut isoflavone disaccharides, peanut isoflavone trisaccharides, peanut resveratrol, peanut resveratrol disaccharides, peanut resveratrol trisaccharides, peanut resveratrol tetrasaccharides, peanut resveratrol pentasaccharides, peanut resveratrol hexasaccharides, peanut resveratrol heptasaccharides, peanut resveratrol octasaccharides, peanut resveratrol nonasaccharides, peanut resveratrol decasaccharides, peanut white quinoa Resveratrol undecanose, catechin, epicatechin, tea polyphenols, catechin, chlorophyll, protocatechin, hesperidin, anthocyanidin, anthocyanin, anthocyanin, anthocyanin, glucoside, glucoside, alfalfa, soy isoflavones, flavanols, quercetin, buckwheat glutenin, persimmon glutinin, persimmon glutinin, punicic acid, punica granatum, blueberry glutinin, resveratrol, lycopene, naringenin, morin, chlorogenic acid, chlorogenic acid triglucoside ... Chlorogenic acid diglucoside, methyl chlorogenic acid, ethyl chlorogenic acid, propyl chlorogenic acid, butyl chlorogenic acid, isopentyl chlorogenic acid, hexyl chlorogenic acid, octyl chlorogenic acid, benzyl chlorogenic acid, phenylethyl chlorogenic acid, phenylpropyl chlorogenic acid, phenylbutyl chlorogenic acid, isopentyl chlorogenic acid, phenylhexyl chlorogenic acid, phenyloctyl chlorogenic acid, phenylphenyl chlorogenic acid, benzyl alcohol chlorogenic acid, phenylethanol chlorogenic acid, anthocyanidins, proanthocyanidins and catechins.
101. The water-soluble carbon chain substance according to any one of claims 59 to 72, wherein the water-soluble carbon chain substance comprises a water-soluble medium- or short-chain fatty acid, or a fatty acid salt, or a fatty acid derivative, and preferably comprises one or two or more water-soluble medium- or short-chain fatty acids, or fatty acid salts, or fatty acid derivatives selected from the following substance groups: Such as butyric acid, succinic acid, fumaric acid, valeric acid, glutaric acid, hexanoic acid, adipic acid, heptanoic acid, pimelic acid, octanoic acid, octanoic acid, Water-soluble medium- and short-chain fatty acids such as oleic acid, suberic acid, capric acid, and sebacic acid; and any one or more of the following fatty acid derivatives including surfactants, etc.: fatty acid salts, alkyl sulfonates, alkyl sulfate ester salts, alkyl phosphate ester salts, alkylamine salts, alkyl quaternary ammonium salts, fatty acylamino acids, betaines, fatty alcohol polyoxyethylene ethers, alkylphenol polyoxyethylene ethers, fatty amine polyoxyethylene ethers, polyol fatty acid esters, polyol polyoxyethylene ether fatty acid esters, fatty acid polyoxyethylene esters, alkyl glycosides, and alcohol ether glycosides.
102. The water-soluble carbon chain substance according to any one of claims 59 to 101 is used to prepare a preparation for regulating transmembrane transport of cell membranes, regulating cell membrane structure or function, regulating cell division and proliferation or cell migration, regulating cell aging, and / or regulating cell membrane fluidity.
103. The formulation of claim 102, wherein The regulating cell membrane fluidity refers to increasing cell membrane fluidity.
104. The formulation of claim 102, wherein The regulating cell membrane fluidity refers to reducing cell membrane fluidity.
105. The formulation of claim 102, wherein The cell membrane includes the cytoplasmic membrane and the organelle membrane; the cell membrane or cell includes the cell membrane or cell of a microorganism, or the cell membrane or cell of a plant, animal or human body tissue; the regulation includes increasing or promoting, as well as inhibiting or reducing, wherein the cell membrane of a microorganism includes the cell membrane of bacteria and fungi and the envelope of a virus; The cell membrane structure includes a phospholipid bilayer, proteins and polysaccharides adsorbed on the surface of the phospholipid bilayer and embedded throughout the phospholipid bilayer; specifically, receptor proteins, transmembrane proteins, cytoskeleton proteins and enzymes; Among them, transmembrane transport includes active transport, passive transport, endocytosis and exocytosis.
106. The formulation of claim 102, wherein The regulation of transmembrane transport of the cell membrane includes increasing and promoting the release of exosomes from cells to the extracellular space; also includes inhibiting or reducing the release of exosomes from cells to the extracellular space; and preventing viruses from entering cells; the inhibition or reduction of transmembrane transport of viruses, namely, inhibiting or reducing the entry of viruses into cells through endocytosis; or inhibiting or reducing the entry of viruses into cells through the fusion of viral envelope and cell membrane; and is applicable to the prevention of all viral infections, the prevention of mycoplasma and chlamydia infections, and the prevention of bacterial infections; Substances transported across cell membranes include: small molecule compounds, medium molecule compounds, large molecule compounds, pathogenic microorganisms such as viruses, bacteria, mycoplasmas, chlamydia and fungi, as well as at least one or two or more of nanoparticles and nanomedicines.
107. The preparation according to claim 103, wherein the preparation is used for improving cell membrane fluidity, including preparations for drug delivery, gene transfection, cell therapy, diabetes, improvement of the nervous system, Alzheimer's disease, enhancement of the immune system, hypercholesterolemia, and / or inflammatory bowel disease prevention, suppression, improvement and / or treatment.
108. The preparation according to claim 104, wherein the preparation is used to reduce the fluidity of cell membranes, including preparations for preventing, suppressing, improving and / or treating cardiovascular diseases (including coronary heart disease, hypertension, myocardial infarction, heart failure), obesity, autism, osteoporosis, inflammatory diseases, autoimmune diseases, chronic fatigue syndrome, leukemia, cell autolysis, viral infection and / or neurodegenerative diseases.
109. A preparation for preventing, inhibiting or treating microbial infection prepared from the water-soluble carbon chain substance according to any one of claims 59 to 101.
110. The preparation according to claim 102, which is a pharmaceutical preparation or an environmental disinfection preparation, and the pharmaceutical preparation is preferably one selected from inhalation, nasal spray, injection, oral preparation and skin external preparation.
111. Use of the water-soluble carbon chain substance described in any one of claims 59-101 in the preparation of a pharmaceutical preparation or environmental disinfection agent for preventing, preventing and / or treating microbial infection; preferably, the microorganism is any one or two selected from viruses, bacteria and fungi; the virus is an enveloped virus; and / or a non-enveloped virus; more preferably, the virus is one or more selected from the group consisting of novel coronavirus, influenza virus, human immunodeficiency virus (HIV), hepatitis B virus, human herpes virus, Ebola virus, rabies virus and human papillomavirus (HPV), and the bacteria is one or more selected from the group consisting of Escherichia coli, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, Klebsiella pneumoniae and Pseudomonas aeruginosa; further preferably, the virus is one or more selected from the group consisting of H7N9 influenza virus, H5N1 influenza virus, HIV virus, novel coronavirus, HPV virus and rabies virus.
112. The use according to claim 111, wherein the water-soluble carbon chain substance according to any one of claims 59 to 99 is prepared into a solution with a concentration of 0.2 mM to 10 mM when acting on microorganisms.
113. The use according to claim 111, wherein the compound is prepared into a solution with a concentration of 0.5 mM to 10 mM.
114. A preparation for preventing, inhibiting or treating inflammatory response and / or body aging prepared from the water-soluble carbon chain substance according to any one of claims 59 to 101.
115. The preparation according to claim 114, wherein the body aging includes anti-skin aging, and the prevention, suppression or treatment of inflammatory response includes changing the conformation of inflammatory factors (proteins).
116. The formulation of claim 114, wherein The carbon chain substances bind oxygen free radicals.
117. The formulation of claim 114, wherein The carbon chain substance is combined with one or two or more substances selected from the following substance groups, or the carbon chain substance is one or two or more substances selected from the following substance groups, or the carbon chain substance is mixed with one or two or more substances selected from the following substance groups to form a preparation: Flavonoids, isoflavones, anthocyanins, soy isoflavones, aloe-emodin, grape seed extract, green tea flavonoids, naringenin, tartrazine, baicalein, riboflavin, quercetin, graphite flavonoids, cinnamon, buxol, hawthorn flavonoids, morin, luteolin, melilotin, gypsum flavonoids, honeysuckle flavonoids, gentian flavonoids, platycodon flavonoids, violet flavonoids, perilla flavonoids, chrysanthemum flavonoids, artemisia annua flavonoids, red peony flavonoids, salvia miltiorrhiza flavonoids, safflower flavonoids, rhodiola rosea flavonoids, red date flavonoids, wolfberry flavonoids, rehmannia glutinosa flavonoids, ganoderma lucidum flavonoids, schisandra chinensis flavonoids, licorice flavonoids, panax flavonoids, curcumin, apigenin, carotene, anthocyanins, lutein, zeaxanthin, mustard flavonoids, rutin, coriander, pollen flavonoids, sand Echinoflavones, marigold flavonoids, cinnamon flavonoids, isoflavonoids and anthocyanins; rutin, emodin, fucoxanthin, gallic acid, kakirin, morin, echinacea glycosides, grape seed proanthocyanidins, phenolic acids, tea polyphenols, naringin, citric acid, flavonols, glycyrrhizic acid, cinnamic acid, flavonoid glycosides, silymarin, matrine, tanshinone, erythrocephalin, seabuckthorn acid, perillyl alcohol, anisic acid, phellodendron, hesperidin, punica granatum, morilin, naringin, rubellin, gentiopicroside, jasmonate, naringol, carotene, apigenin, umelin, morilin, honeysuckle glycoside, chrysanthemin, olive oleate, tea cyanidin, theanine, wine glycosides, platycodin, perillyl alcohol glycosides, morus alba, safflower glycosides, pinus needle glycosides, pachycocin, caffeic acid, chlorogenic acid;Resveratrol, white tea polyphenols, resveratrol disaccharide, banana lutein, anthocyanin, arachidonic acid, peanut flavonoids, pepper phenol, fennel, flavonoids, baicalein, flavonoid glycosides, flavanols, red wine polyphenols, rhodiola rosea, safflower phenol, black tea flavonoids, black sesame, rye phenol, trehalitol, seaweed polysaccharides, alginic acid, albizzia alkaloids, hemp phenol, polydatin, cucurbitacin, fenugreek, cucurbitacin, pollen phenol, pollen flavonoids, Pollen glycosides, pollen esters, arachidic acid, peanut flavonoid glycosides, peanut isoflavones, peanut isoflavone glycosides, peanut isoflavone disaccharides, peanut isoflavone trisaccharides, peanut resveratrol, peanut resveratrol disaccharides, peanut resveratrol trisaccharides, peanut resveratrol tetrasaccharides, peanut resveratrol pentasaccharides, peanut resveratrol hexasaccharides, peanut resveratrol heptasaccharides, peanut resveratrol octasaccharides, peanut resveratrol nonasaccharides, peanut resveratrol decasaccharides, peanut white quinoa Resveratrol undecanose, catechin, epicatechin, tea polyphenols, catechin, chlorophyll, protocatechin, hesperidin, anthocyanidin, anthocyanin, anthocyanin, anthocyanin, glucoside, glucoside, alfalfa, soy isoflavones, flavanols, quercetin, buckwheat glutenin, persimmon glutinin, persimmon glutinin, punicic acid, punica granatum, blueberry glutinin, resveratrol, lycopene, naringenin, morin, chlorogenic acid, chlorogenic acid triglucoside ... Chlorogenic acid diglucoside, methyl chlorogenic acid, ethyl chlorogenic acid, propyl chlorogenic acid, butyl chlorogenic acid, isopentyl chlorogenic acid, hexyl chlorogenic acid, octyl chlorogenic acid, benzyl chlorogenic acid, phenylethyl chlorogenic acid, phenylpropyl chlorogenic acid, phenylbutyl chlorogenic acid, isopentyl chlorogenic acid, phenylhexyl chlorogenic acid, phenyloctyl chlorogenic acid, phenylphenyl chlorogenic acid, benzyl alcohol chlorogenic acid, phenylethanol chlorogenic acid, anthocyanidins, proanthocyanidins and catechins.
118. The preparation according to any one of claims 114-117, wherein when the preparation is used to prevent, inhibit or treat inflammatory reactions and / or aging of the body, the water-soluble carbon chain substance is formulated into a solution with a concentration of 0.1nM-5mM; preferably, the carbon chain substance is a complex formed by fatty acids and amino acids, more preferably, the concentration of the complex solution is 0.1nM-300uM, and more preferably 5nM-100uM.
119. The preparation according to claim 118, wherein when the preparation is used to prevent, inhibit or treat inflammatory response and / or aging of the body, the water-soluble carbon chain substance is formulated into a solution with a concentration of 0.1nM-300uM, preferably 5nM-100uM.
120. A pharmaceutical preparation for preventing, inhibiting, slowing down or treating neurodegenerative diseases prepared from the water-soluble carbon chain substance according to any one of claims 59 to 101.
121. The pharmaceutical formulation of claim 120, wherein the neurodegenerative disease comprises Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), senile dementia, amyotrophic lateral sclerosis (ALS), different types of spinocerebellar ataxia (SCA), or Pick's disease.
122. The pharmaceutical preparation according to claim 120, wherein the water-soluble carbon chain substance is formulated into a solution with a concentration of 0.1nM-5mM to exert its effect.
123. The pharmaceutical preparation according to claim 120, wherein the water-soluble carbon chain substance is formulated into a solution with a concentration of 0.1nM-300uM, preferably 5nM-100uM to exert its effect.
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