Broad-spectrum anti-infection and broad-spectrum anti-cancer pharmaceutical composition

Abstract

The invention relates to a pharmaceutical composition with broad-spectrum anti-infection and broad-spectrum anti-cancer effects, the action mechanism of the pharmaceutical composition is that the pharmaceutical composition comprises two parts A and B as main components, A can be metformin hydrochloride, isosorbide and the like, or a salt or derivative compound and a heterocomplex of A, and B can be one or more of metformin hydrochloride, isosorbide and the like. Therefore, the molecules can always maintain the active molecular characteristics of functional groups such as guanidyl, thiazolyl, imidazolyl, hydroxyl, imino or ether bonds, so that A can always act as a protonated compound. B can be vitamin C, vitamin E and the like, and can be used as hydrogen donors to provide help for protonation of A; the invention aims to prepare a combined medicine for treating infection of helicobacter pylori, new crown, hepatitis B, herpes zoster virus, human immunodeficiency virus, mycoplasma, chlamydia, toxoplasma gondii and the like; and prion infection diseases such as asymptotheca, senile dementia and the like can be treated; even targeted cancer resistance is achieved, and normal cell functions are not affected; and application of a broad-spectrum technical route is provided.

Description

Technical Field

[0001] The present invention relates to a pharmaceutical composition with broad-spectrum anti-infection and anti-cancer effects, the mechanism of which includes two parts A and B as main components, A can be metformin hydrochloride, isosorbide, etc., or a salt or derivative compound and a heterocomplex of A, so that the molecule can always maintain the active molecular characteristics of functional groups such as guanidine, thiazolyl, imidazole, hydroxyl, imino or ether bonds, so that A can always act as a protonated compound. B can be vitamin C, vitamin E, etc., which can act as a hydrogen donor to help A protonation. The present invention will provide the application of a broad-spectrum technical route for the preparation of a combination drug for the treatment of Helicobacter pylori, new crown, hepatitis B, herpes zoster virus, HIV, mycoplasma, chlamydia, toxoplasma and other infections; and the treatment of prion-type infectious diseases such as amyotrophic lateral sclerosis, Alzheimer's disease, etc.; even for targeted anti-cancer without affecting normal cell functions, etc. Background Art

[0002] Scientists all over the world are working very hard to find a specific drug to fight the virus. While scientists in technologically advanced countries such as the United States, Europe, and Japan are still looking for treatments at the nucleic acid and protein levels, people have forgotten this mechanism: in fact, the virus's preference for human tissue is mainly related to the phospholipid envelope structure on the virus surface, and the virus's lipid envelope is indeed a primitive but very reasonable target of attack. 【1】【2】【3】

[0003] When the virus passes through an intermediate host, it will mutate faster due to increased natural selection pressure, but even if it does not pass through an intermediate host, mutations still occur all the time. Viruses also understand the principle of survival of the fittest. Its bases mutate continuously during replication, with several bases mutating each time it replicates. Although most of them are ineffective or eliminated by the host's immune system, in the end there will always be some viral nucleic acid sequences that invade through the host and attack human organs and the immune system. They continue to mutate during the replication and spread of the human body. Therefore, vaccines prepared based on known viral nucleic acid sequences sometimes cannot keep up with the nucleic acid mutations of the virus, and the development of highly effective and broad-spectrum antiviral drugs is the best choice to fight the virus.

[0004] Therefore, from this perspective, the broad-spectrum antiviral drug combination of the present invention attacks the viral envelope structure, which is not only reasonable, but also more stable and durable. Almost all of the compounds claimed to be effective against viruses during treatment are of this type, such as phenol, ethanol, chloroquine phosphate, hydroxychloroquine sulfate, diammonium glycyrrhizinate, Chinese medicine Pneumonia No. 1 (containing unextracted original ecological diammonium glycyrrhizinate) and metformin hydrochloride.

[0005] Since the phospholipid envelopes of various bacteria and viruses are negatively charged, and drugs such as metformin hydrochloride have some positively charged functional groups, they can easily adsorb on the surface of bacteria and viruses and destroy the lipid layer of bacteria and viruses, thereby preventing the bacteria and viruses from dividing and multiplying, and losing their activity. Even if the bacteria and viruses mutate, it will not affect the inactivation effect of the drugs, so their bactericidal and antiviral abilities are often broad-spectrum. 【4】【5】【6】【7】【8】

[0006] The use of metformin to treat COVID-19 infection can help infected people recover. This was published in an editorial in the authoritative British medical journal The Lancet on February 5, 2020. 【9】

[0007] (I) Morphoguanidine, a former broad-spectrum antiviral drug Before discussing the antiviral ability of metformin hydrochloride, let us first examine a former broad-spectrum antiviral drug, morphoguanidine. The molecular formula of morphoguanidine is: C6H 13 N5O molecular weight: 171.20, CAS number: 3731-59-7 structural formula is as follows: see attached Figure 1 .

[0008] Morphoguanidine can effectively fight some common DNA and RNA viruses. It is cheap and easy to synthesize. In the era of lack of medical care and medicine, it was widely used to treat epidemic diseases such as influenza and mild viral infections. The chemical structure of morphoguanidine was first invented by Kabi Company in 1950. Clinical research reports show that morphoguanidine can shorten the course of influenza by at least one third. Most influenza patients recover within four days, while the usual treatment takes six days. In preventive drug trials, reports show that it can reduce the number of influenza cases by 80%. Therefore, morphoguanidine is a broad-spectrum antiviral drug. It has active inhibitory effects on various links of the proliferation period of various viruses such as viral influenza and respiratory viruses. In addition, it also has inhibitory effects on many potential RNA and DNA viruses.

[0009] However, due to its morpholine ring structure, morpholine biguanide can cause liver damage and allergic reactions in patients, especially in children. There have been cases of children dying from drug allergies. Since metformin hydrochloride lacks a morpholine ring, it rarely has the allergic defects of morpholine biguanide, while still having its powerful broad-spectrum antiviral ability.

[0010] Past research on the antiviral mechanism of the guanidine group only believed that it would inhibit the action of viral DNA or RNA synthetase, but missed the most important point: the guanidine cation can drill holes in the viral phospholipid envelope and directly kill the virus.

[10]

[0011] (II) Review of the anti-infection, anti-viral and anti-malarial effects of metformin hydrochloride

[0012] In fact, when metformin hydrochloride was first introduced, it was used as an anti-influenza drug. It has antiviral effects that can directly kill viruses in the human body. However, after it was discovered that it has a blood sugar-lowering effect, its original anti-influenza and anti-viral effects were abandoned.

[0013] In fact, in 1949, doctor Garcia believed that metformin had anti-infection, antiviral, antimalarial, antipyretic and analgesic effects, and used it to treat influenza. He also found that it could lower patients' blood sugar without causing other adverse reactions.

[11]

[0014] (III) Combination of metformin hydrochloride and vitamin C and its derived drug combination has the effect of fighting prions. Regarding the broad-spectrum anti-infective drug composition of the present invention, it is also necessary to emphasize that it is a rare drug combination that can fight prions, and prions are the causative factors of many difficult and complicated diseases in humans. Only by fighting prions can we truly achieve broad-spectrum anti-infection. The broad-spectrum anti-infective drug combination of the present invention can fight prions and also fight cancer broadly, and the anti-cancer mechanism of the present invention can have a certain targeting effect, and can also fundamentally achieve the closure of oncogenes.

[0015] 1. Prion definition

[0016] Prion virus, also known as prion, protein infection factor, prion or infectious protein, is a type of hydrophobic protein that can infect animals and humans and has no immunity in host cells. Prion is a protein with abnormal folding, which has a certain ability to self-replicate and amplify, but the mechanism is unknown.

[0017] 2. Prion properties

[0018] Prions are like conventional viruses in that they are filterable, infectious, pathogenic, and specific to the host range, but they are much smaller than the smallest known conventional viruses (about 30 to 50 nm), and do not exhibit immune effects or induce interferon production. The greatest threat of prions to humans is that they can cause central nervous system lesions in humans and livestock, including Alzheimer's disease, amyotrophic lateral sclerosis (ALS), Parkinson's disease, Huntington's disease, and cancer, and eventually lead to death. Therefore, the World Health Organization has listed prion disease and AIDS as the most serious diseases that endanger human health in the century.

[0019] Prions are small protein particles composed of about 250 amino acids, which are only 1% of the size of the smallest virus. Prions can penetrate all natural barriers of the human body, such as the skin and mucosal barrier, the blood-brain barrier, the placenta barrier (mother-to-child transmission barrier), and the blood-testis barrier (male). In short, all natural barriers of human beings have been completely broken through by prions.

[0020] Although we define prions (a very hard infectious protein) as inanimate material, its genetic material only has shape; it has no DNA, RNA, or membrane structure, but it can divide and infect cells. Mutations, inheritance, or infection of personal DNA can cause people to be infected with prions. The biggest feature of prions is that they can cause spongiform lesions in the human brain.

[12]

[13]

[0021] 3. Pathogenic mechanism of prions

[0022] Prions are pathogenic substances formed by the normal prion protein PrPC through conformational transformation into the abnormal prion protein PrPSC with protease resistance, that is, a pathogenic molecule first combines with a normal molecule, under the action of the pathogenic molecule, the normal molecule is transformed into a pathogenic molecule, and then the two pathogenic molecules respectively combine with two normal molecules, which then transform the latter into pathogenic molecules. This cycle repeats itself, multiplying the pathogenicity through the domino effect.

[0023] Proteins can only function when they are correctly folded into a specific three-dimensional structure. Misfolded proteins can cause many diseases, including cystic fibrosis, juvenile cataracts, Alzheimer's disease and various cancers. Prions cause a protein conformational disease. The concept of protein conformational disease means that if a protein folds incorrectly, although the order of amino acids in its primary structure remains unchanged, the conformation of the protein changes, which can still affect its function and cause disease in severe cases. Prions are very special proteins that can induce other proteins to make the same folding errors and achieve self-reproduction. Prions can form disruptive aggregates in cells (especially nerve cells), which are highly stable and can cause tissue damage and cell death. Prions released by dying cells can enter other cells and be reused repeatedly, destroying normal cells and tissues and causing infection. This protein can not only cause mad cow disease, but is also associated with a variety of neurodegenerative diseases, including Alzheimer's disease, amyotrophic lateral sclerosis (ALS, also known as motor neuron disease), Parkinson's disease and Huntington's disease, as well as cancer.

[0024] Normal human body can digest and utilize the energy of foreign proteins that enter the human body, but human protease cannot digest and utilize prions because they are abnormally folded protein particles, mainly β (beta) folds and β sheets and irregular curls. Human protease digestion and hydrolysis will stop when encountering prions. This will cause prion particles to accumulate in the lysosomes of human cells, and eventually rupture the lysosomes, which will cause the protease in the human lysosomes to come out, and digest and hydrolyze the body's own cells. Prions can cause aseptic inflammation of human tissues and organs.

[0025] Mechanism of protein conformational disease: Some proteins aggregate with each other after being misfolded, often forming amyloid fibril deposits that are resistant to proteolytic enzymes, which become toxic and pathogenic, manifesting as pathological changes of protein amyloid fibril deposits.

[0026] If this phenomenon occurs in the brain, it will cause mad cow disease and Alzheimer's disease, resulting in a decline in cognitive ability and perception ability (such as olfactory and taste disorders); in the cardiac nerve conduction pathway, it will damage the cardiac electrical neurons, causing heart conduction block, which will lead to cardiac arrest and sudden fainting while running; in the inner walls of the cardiovascular and cerebrovascular vessels, it will cause bulges, stimulate the formation of microthrombi, which will then expand and cause embolism, leading to myocardial infarction and cerebral infarction; in motor neurons it will cause amyotrophic lateral sclerosis and progressive muscular dystrophy, in the spinal cord it will cause transverse myelitis (causing paraplegia), in pancreatic islet cells it will cause diabetes, and so on.

[0027] In short, wherever prion particles go, they will cause harm. They kill human tissue cells in a hard way, causing infected tissue cells to be directly hollowed out, causing organic lesions in human tissues and organs, often causing irreversible damage.

[0028] 4. Inactivation of Prions

[0029] Prions are very difficult to kill, have strong resistance to adversity, and can withstand bactericides (formaldehyde) and high temperatures (still infectious after being treated at 120-130°C for 4 hours). Although general high-pressure sterilization processes can change the properties of almost all other proteins, prions can withstand various chemical treatments and high-pressure sterilization processes and are difficult to kill because they can return to their original form again. In the external environment, only strong alkalis such as sodium hydroxide, sodium hypochlorite and phenol can kill prions. As for prions that enter the human body, there is basically no effective drug to eliminate them.

[0030] Foreign literature has mentioned that low concentrations of phenol can inhibit prions. American literature says that phenol injected intramuscularly has the function of bidirectionally regulating immune cells, and trace low concentrations of phenol are harmless to the human body. People who have received phenol autologous plasma vaccines have excellent antibodies, 85% of which are still there after 3 months, and there are no sequelae after injection, because it does not contain any foreign protein at all, which can prevent the medical spread of prions. However, since phenol itself is a carcinogen and it cannot pass through the blood-brain barrier to completely kill prions, using phenol to treat prion diseases can only solve part of the problem.

[14]

[0031] 5. Symptoms of prion poisoning

[0032] In the past, there was no cure for diseases caused by prions, and the cause of their abnormal folding was unknown. In short, in the current medical community, this terrible protein that can cause human brain degeneration remains an unsolved mystery. This protein can not only cause mad cow disease, but is also related to a variety of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS, also known as motor neuron disease) and Huntington's disease. If medical instruments are not strictly sterilized, they may infect the next patient.

[0033] Prion infection can cause diarrhea because prions can invade not only the oral mucosa, but also the gastrointestinal mucosa, and break through the blood-brain barrier through the gastrointestinal vagus nerve; six months later, progressive brain nerve lesions will appear, and the first warning bell is the appearance of recent memory loss and other Alzheimer's disease-like symptoms. Muscle tremors, recent memory loss, weakness and fatigue are currently the only clinical characteristic indicators that can confirm that prions have entered the brain. Patients will feel obvious muscle weakness and recent memory loss, in addition to headaches, nausea, muscle pain, memory loss, hair loss, etc.

[0034] In addition, prions can also cause periodontitis and gum atrophy. The dental nerves are entangled by the heterofolded proteins of prions for a long time, and their nutrition is cut off, causing them to wither. The whole process is silent and painless. There are also symptoms of sinusitis and long-term pharyngitis, which cannot be cured by Chinese and Western medicines. It is also necessary to consider that prions attack the mucosa.

[0035] Prions accelerate Alzheimer's disease, which can be deduced to the following neuroses caused by prion-like diseases that have not yet been named in the medical community: 1. Amyotrophic lateral sclerosis (ALS, also known as motor neuron disease), 2. Chronic fatigue syndrome (CFS syndrome), 3. Dengue fever sequelae, 4. Rabies patients, 5. Rabies vaccine sequelae, 6. HPV vaccine sequelae, 7. Behcet's syndrome, 8. Myalgic encephalomyelitis, 9. Various spirochetal diseases, 10. Moregellons, 11. Type II atopic dermatitis, 12. Demyelination of neuronal cells. Syphilis is actually a protein conformational disease, and phenol is effective against syphilis.

[0036] Diseases caused by prions are divided into fast prions and slow prions. Mad cow disease is a fast prion, which causes illness and death quickly. The vast majority of diseases are slow prions. In other words, most diseases caused by prions are chronic toxins, and since prions cannot be killed easily, once they break out, they are terminal illnesses because organs are damaged and organic lesions are irreversible.

[0037] (IV) The novel coronavirus spike protein has a pseudovirus-like therapeutic effect

[0038] Researchers have found that the coronavirus spike protein is the main pathogenic factor of the coronavirus.

[15]

[16] On December 21, 2021, the research group of Guangxun Meng and Dimitri Lavillette from the Shanghai Pasteur Institute of the Chinese Academy of Sciences collaborated to publish a research paper titled "SARS-CoV-2 spike engagement of ACE2primes S2'site cleavage and fusion initiation" in the international academic journal "Proceedings of the National Academy of Sciences of the United States of America". The study discovered the molecular mechanism of viral infection and cell membrane fusion mediated by the Spike protein of the new coronavirus, indicating that the Shanghai Pasteur Institute of the Chinese Academy of Sciences also recognizes the Salk Institute's "S protein pathogenicity" theory.

[17]

[18]

[19]

[20]

[0039] The spike protein of the new coronavirus (SARS-CoV-2), namely the S protein monomer, consists of two fragments: S1 and S2. The S1 subunit at the amino terminus contains a receptor binding domain (RBD), which is responsible for recognizing the host ACE2 receptor and performing initial docking; while the S2 subunit at the carboxyl terminus is responsible for catalyzing the fusion of the virus and cell membranes, allowing the subsequent viral RNA genome to enter the infected cell for replication.

[0040] In the research conducted by the Shanghai Pasteur Institute of the Chinese Academy of Sciences, researchers found through the cell-cell fusion system and the "pseudovirus" model that after the spike (S) protein binds to the receptor, it will initiate a protease cleavage reaction in the cell, leading to the generation of S2' fragments and membrane fusion. If the S2 cleavage site of the spike protein is replaced, the cell membrane fusion reaction induced by the spike proteins of various epidemic strains (such as Alpha, Beta and Delta, etc.) can be effectively inhibited. Therefore, S2' cleavage during the infection process of the spike protein is one of the indispensable molecular events in the infection process of the new coronavirus.

[21]

[0041] These findings in themselves are not entirely surprising, as many scientists have previously believed that SARS-CoV-2 affects the vascular system, but the exact manner of action was unclear. Scientists studying other coronaviruses have long suspected that the spike protein damages the endothelial cells that line blood vessels, but this is the first time that this process has been documented in an experimental paper. The paper provides clear evidence and explains in detail for the first time the mechanism by which the spike protein damages vascular cells. The experiment accurately demonstrates how the new coronavirus (SARS-CoV-2) damages and attacks the vascular system at the cellular level.

[0042] The mutant strains currently prevalent around the world have multiple mutations in the spike protein, which poses a great challenge to the updating and design of vaccines. Although it has been found that the host angiotensin-converting enzyme 2 (ACE2) protein binds to the viral Spike protein, the molecular events and cellular mechanisms after the binding are still unclear.

[0043] In the binding domain of the new coronavirus spike protein and ACE2, there are 5 amino acids that are different from the Sars coronavirus (Sars' S460, T488, N480, Y485, T488 were replaced by Q474, N481, Q493, Q498 and N501, respectively). In this way, the receptor binding domain of the new coronavirus spike protein forms an area rich in asparagine (N) and glutamine (Q); and the Q / N-rich, as well as the altered hydrophobicity and net charge sequence areas, are the characteristics of abnormal protein folding.

[22]

[0044] Self-replicating proteins or their abnormal folding deviate from the central law of genetic replication. Studies on the spike protein domains in the new coronavirus have shown that they may play a very important role in viral evolution. Here, we need to further study and understand the functions of these viral self-replication protein-like domains, and they may become new targets for the development of effective antiviral drugs in the future.

[23]

[0045] 5. The relationship between prions and cancer

[0046] 1. Prions can cause sterile inflammation

[0047] Prions are also related to human cancer. Researchers from foreign universities have found that prions can cause sterile inflammation, which in turn shuts down the human DNA repair gene P53, causing errors in DNA base pairing during replication of human cells, thereby inducing cancer. Current studies have found that severe COVID-19 may be a sign of undiagnosed cancer. Artificial intelligence ChatGPT has also found that infectious proteins, or prions, are a substance that is positively correlated with carcinogenesis.

[24]

[0048] Long-term exposure to carcinogenic chemicals, long-term exposure to radiation, infection with certain viruses, etc. are all physical, chemical, and biological conditions that lead to cancer. In fact, in this process, there is also a very important link of protein denaturation, that is, protein denaturation first becomes prion, which can cause aseptic inflammation, and then cause the repair mechanism of human gene replication to fail, resulting in cancer. If the denaturation of prions can be completely prevented at the level of prions, the oncogene can be completely shut down fundamentally.

[25]

[26]

[0049] 2. Inflammation is an important cause of cancer

[0050] One of the mechanisms of cancer induction and enhancement is inflammation, which is the main cause of almost all cancers and increases cancer at every stage. Prions cause sterile inflammatory responses in human cells, and when a large number of spike proteins containing abnormally folded protein domains enter the human body, the degree and duration of inflammation produced increases significantly, which has never been seen before.

[0051] The interaction and regulation between the human nucleic acid genome and the proteome can maintain the stable inheritance of human DNA. Prions can cause aseptic inflammation, and the proteolytic enzymes released from the lysosomes of the cells themselves will hydrolyze and destroy the proteome. The key DNA repair proteins BRCA1 and 53BP1 in the human body will be completely lost, the DNA damage repair mechanism will be lost, and oncogenes will be turned on, which will cause cancer.

[27]

[28]

[0052] (VI) Mechanism of Metformin's Anti-Cancer Effect

[0053] The idea that metformin can fight cancer has been around for a long time. It was first inferred in the 1970s that biguanides might be an anti-cancer drug, and a series of animal studies were conducted. Since then, this idea has been basically forgotten due to the chain reaction caused by the withdrawal of phenformin from the market. The real anti-cancer effect of metformin attracted attention in 2005, when a large case-control study in the UK first found that metformin could reduce the risk of breast cancer.

[29]

[30]

[0054] A clinical report showed that the use of metformin was associated with a reduced risk of cancer in patients with type 2 diabetes, and this safe and inexpensive drug has attracted attention for its anti-tumor activity. The key to anti-cancer treatment is to kill malignant cells while minimizing the side effects on normal tissues, and metformin can protect normal cells from carcinogens and tumor growth and make cancer cells more sensitive to various types of anti-cancer drugs (such as radiotherapy and chemotherapy).

[31]

[32]

[0055] 1. Metformin has been shown to activate anti-tumor immune mechanisms

[0056] Metformin has been shown to activate anti-tumor immune mechanisms, increase the number of CD8+T lymphocytes, NK cells and anti-tumor cytokines in cancer patients, promote the release of pro-apoptotic cytokines (such as IFN-γ and TNF-α) and other pro-apoptotic molecules (such as FasL and TRAIL) in patients, and enhance the function of the immune system against cancer cells.

[33]

[34]

[35]

[0057] 2. Metformin inhibits the PI3K / Akt pathway

[0058] Experiments have shown that metformin can inhibit the PI3K / Akt pathway after AMPK activation, and the latter inhibition can further induce the activation of NK cells, thereby activating the immune system.

[36]

[37]

[0059] 3. Metformin can enhance the activation of the tumor suppressor gene p53

[0060] Metformin can induce upregulation and activation of tumor suppressor genes p53 and PTEN in cancer cells through upregulation of AMPK.

[38]

[0061] 4. Metformin activates AMPK signaling pathway

[0062] AMPK is one of the most important targets of metformin. By activating AMPK, it inhibits the phosphorylation of Akt and mTOR in cancer cells, thereby leading to decreased Bcl-2 expression and increased Bad phosphorylation and expression of pro-apoptotic markers.

[0063] 5. Metformin can trigger cellular autophagy

[0064] Metformin has been shown to prevent tumorigenesis by stimulating autophagy in premalignant cells.

[0065] 6. Metformin can cause cancer cells to age and die

[0066] In tumors, metformin may induce senescence, thereby reducing cancer cell survival.

[0067] 7. Metformin can induce cell pyroptosis

[0068] Pyroptosis is mediated by the activation of caspase proteins, including caspase 1, 4, 5, and 11, as well as the cleavage of gasdermin D. Metformin can stimulate the upregulation of gasdermin D in cancer cells and induce cell pyroptosis.

[39]

[40]

[41]

[0069] In the past, metformin's anti-cancer effects mostly came from cell or mouse experiments. The research published in the Cell journal was conducted on mice and has not been truly verified in humans. The results simply based on animal experiments are still a long way from being safely applied in clinical practice. The concentration of metformin required to achieve the purpose of anti-cancer treatment is far higher than the usual dose or concentration of metformin, and taking high doses of metformin means greater adverse reactions.

[0070] Although metformin is a hypoglycemic drug, it also has many adverse reactions, the most common of which are diarrhea, nausea, bloating, fatigue, indigestion, abdominal discomfort, and headache. Long-term use may also cause kidney damage. In addition, long-term high-dose use of metformin may affect vitamin B2 and vitamin B 12 , vitamin C and folic acid, causing anemia, capillary and peripheral nerve damage, and also has a certain impact on the absorption of trace elements calcium and phosphorus.

[42]

[0071] (VII) The most fundamental real mechanisms of several anticancer drugs

[0072] The publicly announced broad-spectrum anticancer drug AOH1996, the structural formula is attached Figure 2 .

[0073] As early as December 1, 2019, Long Gu, Min Li and others released a small molecule broad-spectrum targeted anticancer drug AOH1996 at an international symposium on molecular targeted anticancer therapy held in Boston, USA, announcing that it could kill 70% of solid tumors. Its molecular formula is C 26 H 22 The molecular weight of N2O4 is 426.472g / mol. The researchers tested AOH1996 in more than 70 cancer cell lines and several groups of normal cells. This investigational therapy prevented cells with damaged DNA from dividing in the G2 / M phase (G2 mitosis preparation phase, M phase, refers to the period after interphase, which refers to the period of nuclear division and cytoplasmic division in the cell cycle) and prevented the replication of erroneous DNA in the S phase (i.e. the gap phase, the DNA replication and synthesis phase).

[0074] What is the mechanism of AOH1996 in treating cancer? It is believed that AOH1996 has a mechanism of action at the molecular nucleic acid and protein levels. When the DNA double helix is ​​opened for DNA replication, RNA transcription is required to synthesize proteins at the same time. The seamless coordination of the two steps is the key to successfully completing cell division. The role of PCNA is to assist this process to proceed smoothly, otherwise errors will occur in this process. In the nucleus of the body, there is a protein called Proliferating Cell Nuclear Antigen (PCNA for short), with a molecular weight of 36KD. It is an auxiliary protein of DNA polymerase. A new cancer-related PCNA subtype (called caPCNA) has been reported before. It is mainly expressed in a wide range of cancer cells and tumor tissues, but not significantly in non-cancerous cells. AOH1996 inhibits the activity of caPCNA through a series of actions, resulting in the collapse and termination of transcription of DNA replication and cell apoptosis. Dr. Linda H. Malkas's research found that the PCNA of cancer cells is different from that of normal cells (caPCNA). AOH1996 can avoid attacking normal cell PCNA and specifically attack the PCNA of cancer cells. Therefore, it has good selectivity and will not harm normal cells in the human body. Long Gu, MinLi and others published their detailed mechanism online in the Journal of Cellular Biochemistry in August 2023.

[43]

[44]

[0075] Piper longum amide molecular formula C 17 H 19 NO5 molecular weight 317.126312CAS registration number 20069-09-4, see the attached structure of piperidine Figure 3 .

[0076] Piper longum is an alkaloid obtained from Piper longum, which has anti-inflammatory, antibacterial, anti-angiogenic, antioxidant, anti-tumor and anti-diabetic activities. In tumor cells, Piper longum can induce ROS and apoptosis. It also has anti-myocardial fibrosis effects and inhibits the transformation of myofibroblasts by inhibiting the ERK1 / 2 signaling pathway. Piper longum is an alkaloid compound isolated from the root of Piper longum, a plant of the Piperaceae family. Studies on Piper longum have shown that it has a variety of pharmacological effects, the most striking of which is its selective killing effect on tumor cells, which has made Piper longum a compound with great development potential in tumor treatment in recent years. However, to date, the targets and mechanisms of Piper longum in the specific killing of cancer cells are still highly controversial.

[45]

[0077] Artemisinin, also known as artemisinin, is an organic compound with a molecular formula of C15 H 22 O5, relative molecular mass 282.34, artemisinin structural formula is attached Figure 4 Artemisinin is a colorless needle-shaped crystal, easily soluble in chloroform and benzene, soluble in ethanol and ether, slightly soluble in cold petroleum ether, and almost insoluble in water. Because it has a special peroxide group, it is unstable to heat and is easily decomposed by moisture, heat and reducing substances.

[0078] Artemisinin is one of the most effective drugs for treating drug-resistant malaria. Combination therapy based on artemisinin is the most effective and important means of treating malaria. In recent years, with the continuous deepening of research, other effects of artemisinin have also been discovered. It has multiple pharmacological effects such as anti-tumor, treatment of pulmonary hypertension, anti-diabetes, embryotoxicity, anti-fungal, immunomodulatory, anti-viral, anti-inflammatory, anti-pulmonary fibrosis, antibacterial, and cardiovascular effects.

[46]

[47]

[0079] In 1995, researchers at the University of Washington found that artemisinin can inhibit pancreatic cancer, breast cancer and leukemia cells, and in the process of killing cancer cells, it will not have any effect on normal cells. After a number of experimental studies, it was found that artemisinin eliminated all breast cancer cells in the test tube in just 16 hours, and normal cells were intact. A domestic team published a paper confirming that artemisinin can inhibit liver metastasis of colorectal cancer and enhance the efficiency of anti-PD1 treatment.

[0080] Studies have confirmed that the main target of artemisinin attack is the tumor cell membrane. When the tumor cell membrane is destroyed, the permeability will not change, the cell will swell and die due to absorbing a large amount of water, and a large amount of calcium ions will enter the cell, leading to cell apoptosis.

[0081] Studies have also found that the effect of artemisinin combined with other chemotherapy drugs in treating tumors will be doubled. Artemisinin is also relatively safe, and the dose used for antimalarial activity is three times higher than that for anti-cancer activity.

[0082] Artemisinin has no antagonistic effect with other anti-cancer drugs and the possibility of producing drug resistance is relatively small, so artemisinin can also play a very important role in the treatment of tumors.

[48]

[49]

[0083] Fenbendazole molecular formula C 15 H 13 N3 O2S molecular weight 299.348 CAS registration number 43210-67-9, see attached Figure 5. Fenbendazole is a white or off-white powder, odorless and tasteless. This product is soluble in dimethyl sulfoxide, slightly soluble in methanol, insoluble in water, and soluble in glacial acetic acid. It is a broad-spectrum benzimidazole anthelmintic, effective against gastrointestinal parasites. As early as 2013, studies have shown that fenbendazole is a potential anticancer drug. Recently, it has been reported that fenbendazole combined with vitamin E can treat small cell lung cancer.

[50]

[51]

[52]

[0084] The broad-spectrum anticancer drug AOH1996 has a mechanism of action at the molecular nucleic acid and protein levels, but the most fundamental and real mechanism of these anticancer drugs is that they can directly kill cancer cells without exception. AOH1996 contains two ether bonds, piperlongumide has three ether bonds, and artemisinin has four ether bonds. Their anticancer mechanisms are the same, and they all have the function of directly killing cancer cells because the ether bonds can be protonated. Fenbendazole's imidazole ring, imino group and ether bonds can all be protonated, and vitamin E can help its protonation. Their common target is the cancer cell membrane structure. While killing cancer cells, they do not affect the metabolism and function of normal cells. Therefore, from a structural analysis, it can be seen that the effect of the broad-spectrum anticancer drug AOH1996 is not much stronger than piperlongumide, artemisinin and fenbendazole.

[0085] Because the glycolysis pathway of cancer cells is abnormally active, the amount of intracellular lactic acid increases significantly, and the amount of hydrogen ions increases, which lowers the pH value, causing the cancer cell surface to carry a large amount of negative charge. The charge potential of the cancer cell surface membrane is negatively charged. Protonated compounds such as metformin hydrochloride and vitamin C can use their positive charge opposite to that of the cancer cell surface to identify cancer cells and complete the killing process. This targeted killing function of cancer cells will not have any effect on normal cells. This targeted effect on cancer cells is achieved through the mutual attraction of positive and negative charges.

[0086] 8. Mycoplasma, Chlamydia and Toxoplasma infection

[0087] 1. Mycoplasma

[0088] Mycoplasma is a Gram-negative pathogen. It is a type of minimal prokaryotic cell-type microorganism that has no cell wall, is highly polymorphic, can pass through bacteria filters, and can be cultured and proliferated in artificial culture media. Its size is 0.1 to 0.3 microns. Because it can form filamentous and branched shapes, it is called mycoplasma. Mycoplasma is widely present in humans and animals. Most of them are non-pathogenic. The mycoplasmas that are pathogenic to humans mainly include Mycoplasma pneumoniae, Ureaplasma urealyticum, Mycoplasma hominis, and Mycoplasma genitalium.

[0089] Mycoplasma pneumoniae is the pathogen that causes mycoplasma pneumonia, and can also cause upper respiratory tract infections and chronic bronchitis. It is mainly transmitted through the respiratory tract and can occur all year round, but it is more common in late summer and early autumn, with a higher incidence in people aged 1 to 15 years old. The symptoms are mild, with irregular fever, headache, and irritating cough.

[0090] Ureaplasma urealyticum, Mycoplasma hominis, and Mycoplasma genitalium are pathogens that cause human urogenital tract infections. They are transmitted through sexual contact and cause urogenital tract infections such as urethritis and prostatitis. They can also cause fever after abortion and postpartum fever or puerperal fever, infertility, and infection through the birth canal can cause pneumonia or meningitis in newborns. Currently, the treatment of Mycoplasma pneumoniae infections mostly uses macrolide drugs such as roxithromycin, clarithromycin, azithromycin, etc., or quinolone drugs such as ofloxacin and sparfloxacin.

[53]

[0091] 2. Chlamydia

[0092] Chlamydia is a group of extremely small, non-motile microorganisms that grow exclusively inside cells. Chlamydia can be divided into four types, namely Chlamydia pneumoniae, Chlamydia psittaci, Chlamydia trachomatis and Chlamydia bovis. Chlamydia is also a Gram-negative pathogen, a type of prokaryotic microorganism that can pass through bacterial filters, parasitize inside cells, and has a unique development cycle. Chlamydia is an organism that is smaller than bacteria but larger than viruses. It is an obligate intracellular parasite that is similar to bacteria and viruses and has a two-phase life cycle. It does not have the ability to synthesize high-energy compounds ATP and GTP, which must be provided by host cells, thus becoming an energy parasite. It is mostly spherical or heap-shaped, has a cell wall and a cell membrane, is a prokaryotic cell, and generally parasitizes inside animal cells. It is divided into four types of Chlamydia: trachomatis, pneumonia, parrots and livestock.

[0093] Chlamydia pneumoniae is considered a common cause of pneumonia, bronchitis and other respiratory infections; Chlamydia bovis only exists in cattle and sheep; Chlamydia psittaci can cause psittacosis, which is caused by humans inhaling dry dust particles from infected bird excrement. When the disease occurs, there are often high fever, headache, muscle pain, chills and upper and lower respiratory tract discomfort. Some patients may have complications such as encephalitis, myocarditis or thrombophlebitis. In addition to causing trachoma, Chlamydia trachomatis is also a recognized source of infection for sexually transmitted diseases. In non-gonococcal urethritis, almost half is caused by Chlamydia trachomatis infection. It can also cause urethral syndrome and venereum lymphogranuloma, male urethritis, epididymitis, female infertility, cervicitis, pelvic inflammatory disease, etc. Infection in newborns through the birth canal can cause neonatal ophthalmia or neonatal pneumonia. Chlamydia trachomatis can also cause pneumonia in adults, and it is also very harmful to pregnant women, causing ectopic pregnancy, miscarriage, stillbirth, chorioamnionitis, premature birth, etc.

[0094] Currently, tetracycline, doxycycline, erythromycin, azithromycin, clarithromycin, quinolones, etc. are mostly used as first-line drugs for the treatment of Mycoplasma pneumoniae infection.

[54]

[55]

[0095] 3. Toxoplasma gondii

[0096] Toxoplasmosis is an infection of humans and animals caused by a parasite called Toxoplasma gondii. Toxoplasma belongs to a class of parasites called protozoa, which are the smallest and simplest in structure. Cats and other felines are the final hosts of Toxoplasma. It parasitizes in the epithelial cells of the small intestine of these animals, forming cysts that are excreted in the feces. Other mammals and birds are infected when they eat them, and they develop into cysts in their body tissues. Cysts and cysts are different developmental stages of Toxoplasma.

[0097] Toxoplasmosis is an intracellular parasitic protozoan with five forms in its life cycle, namely trophozoites (tachyzoites); cysts (which can survive in tissues for a long time), which are round or oval, with a diameter of 10 to 200 μm, and can release bradyzoites after rupture; schizonts; gametocytes and oocysts. The first three stages are asexual reproduction, and the last two stages are sexual reproduction. The completion of the life cycle of Toxoplasma requires two hosts: in the definitive host (cats and felines), the above five forms exist; in the intermediate host (including birds, mammals and humans), there is only asexual reproduction but no sexual reproduction. Asexual reproduction can often cause systemic infection, while sexual reproduction only develops in the intestinal epithelial cells of the definitive host, causing local infection.

[0098] Most patients with toxoplasmosis are asymptomatic, and about 10%-20% have symptoms. The main clinical manifestations include fever, general malaise, night sweats, muscle pain, sore throat, rash, hepatomegaly, splenomegaly, and systemic lymphadenopathy. Lymph node enlargement is more prominent. In addition to superficial lymph node enlargement, deep lymph nodes such as the mediastinum, mesentery, and retroperitoneum may also swell. Intra-abdominal lymph node enlargement may be accompanied by abdominal pain. The swollen lymph nodes are hard and may be accompanied by tenderness but not suppuration. Symptoms and signs generally disappear after 1-3 weeks. The course of a few cases can last up to 1 year. Some patients may experience persistent high fever, single cases of retinochoroiditis, transient pneumonia, pleural effusion, hepatitis, pericarditis, myocarditis, Guillain-Barré syndrome, intracranial space-occupying lesions, and meningoencephalitis.

[0099] Scientists have found that drugs that can inhibit Toxoplasma include: pyrimethamine, sulfonamides, tetracycline drugs, spiramycin, etc. These drugs can inhibit Toxoplasma trophozoites, but are ineffective against cysts. If used for a long time, they will produce drug toxicity and fail to achieve the purpose of curing Toxoplasma.

[56]

[0100] After careful study of the pathogenesis of the above-mentioned bacteria, viral infections and prions, as well as cancer, mycoplasma, chlamydia, and toxoplasma, it was found that metformin hydrochloride and isosorbide, etc., after protonation, can completely kill bacteria, viruses, prions and cancer cells. In addition, the composition of this patent application can also kill mycoplasma, chlamydia and toxoplasma. Summary of the invention

[0101] Although many anti-bacterial, anti-viral and anti-cancer drugs have been developed and used clinically, there is no good way to treat prion-like infectious diseases such as amyotrophic lateral sclerosis (ALS, also known as motor neuron disease). Therefore, the present invention can provide a treatment method with less toxic side effects for the above infectious diseases and cancer.

[0102] The present invention provides a pharmaceutical composition with broad-spectrum anti-infection and anti-cancer effects, so as to solve the difficulties in the prior art in the treatment of some drug-resistant bacterial infections, viruses, prion diseases and cancer. The present invention has a broad-spectrum anti-infection effect and a broad-spectrum anti-cancer effect, and the anti-cancer mechanism also has a targeted effect, which will not affect the function of normal cells while killing cancer cells.

[0103] The present invention discloses, claims and protects a pharmaceutical composition with broad-spectrum anti-infection and broad-spectrum anti-cancer effects, the mechanism of which comprises two parts A and B as main components, A can be metformin hydrochloride, arginine, isosorbide, isomannide, cimetidine, ranitidine, famotidine, or a salt or derivative compound and a heterocomplex of metformin hydrochloride, arginine, isosorbide, isomannide, cimetidine, ranitidine, famotidine, such as a salt, amidation, ester of arginine. Compounds such as esters of isosorbide and isomannide, monoesters or disesters of isosorbide, isomannide, cimetidine, ranitidine, famotidine, salts or derivatives thereof and heterocompounds, such as salts, esterifications, and ether compounds of isosorbide and isomannide, so that the molecules can always maintain the active molecular characteristics of functional groups such as guanidine, imidazole, hydroxyl, imine or ether bonds, so that they can always act as protonated compounds. B can be vitamin C, vitamin B1, vitamin B6, vitamin E, glutathione, N-acetylcysteine, etc., which can act as hydrogen donors and protonation donors to help A protonate. A or a salt of A or its derivatives and heterocompounds can be formed into effective compositions alone or in multiples with B or a salt of B or its derivatives and heterocompounds alone or in multiples, and the composition ratio can meet the molar ratio requirements, or the molar ratio of A and B can be more or less. The broad-spectrum anti-infection and broad-spectrum anti-cancer pharmaceutical compositions and the use of preparing these drugs, as well as animal feed, veterinary drugs, beverages, health products, compound preparations, etc. based on the compositions.

[0104] In short, the invention of this patent application discovered a completely new mechanism of broad-spectrum anti-infection and broad-spectrum anti-cancer, and on this basis invented a pharmaceutical composition with broad-spectrum anti-infection and broad-spectrum anti-cancer effects, which has broad-spectrum anti-bacterial and broad-spectrum anti-viral infection effects; it has anti-prion effects; it has broad-spectrum anti-cancer effects; it also has effects against mycoplasma, chlamydia, and toxoplasma infections.

[0105] Long-term exposure to carcinogenic chemicals, long-term exposure to radiation, infection with certain viruses, etc. are all physical, chemical, and biological conditions for the occurrence of cancer. In fact, in this process, there is also a very important link of protein denaturation, that is, the protein is first denatured into prions. These prions can cause aseptic inflammation, affect and shut down the human DNA repair gene P53, and then lead to the failure of the human gene replication mechanism. Long-term inflammation and the failure of human DNA repair genes are the root causes of cancer.

[0106] In animal experiments, if metformin hydrochloride is to have an anti-cancer effect, the dosage will often exceed the body's safe dosage limit in order to exert its anti-cancer effect. However, if vitamin C is added, metformin hydrochloride can be kept within the body's safe dosage range and exert its anti-cancer effect. By extension, due to the addition of hydrogen donor B, the protonated A can be kept within the safe dosage range and exert its anti-cancer effect, which will provide a new broad-spectrum technical route for curing cancer.

[57]

[58]

[59]

[0107] Since the membrane vesicle structures of mycoplasma, chlamydia and toxoplasma all carry a large amount of negative charges, the invention also has the effect of resisting mycoplasma, chlamydia and toxoplasma infection.

[0108] (I) Description of the compounds and technical principles of the present invention In order to facilitate the understanding of the present invention, the compounds and technical principles of the present invention are further described as follows: The structure of the main compound involved in this patent is as follows:

[0109] They are metformin hydrochloride, arginine, isosorbide, isomannide, cimetidine, ranitidine, famotidine, vitamin C, vitamin B1, vitamin B6, vitamin E, glutathione, N-acetylcysteine, etc.

[0110] Metformin hydrochloride: Molecular formula: C4H 11 N5·HCl; molecular weight: 165.63; CAS registration number: 1115-70-4, see attached Figure 6 .

[0111] Arginine: Chemical formula C6H 14 N4O2; molecular weight 174.20; DL type CAS registration number: 7200-25-1; L type CAS registration number 74-79-3; D type CAS registration number 157-06-2, see attached Figure 7 .

[0112] Isosorbide: Molecular formula C6H 10 O4; molecular weight 146.14; CAS registration number 652-67-5, isosorbide structural formula is attached Figure 8 .

[0113] Isomanitol: molecular formula C6H 10 O4; molecular weight 146.14; CAS registration number 641-74-7, isomannide and isosorbide are isomers, the structural formula of isomannide is attached Fig. 9 .

[0114] Vitamin C: molecular formula C6H8O6; molecular weight 176.13; CAS registration number: 50-81-7, vitamin C structural formula is attached Fig.10.

[0115] Common vitamin B1: molecular formula C 12 H 17 ClN4OS; molecular weight 300.81; CAS registration number: 59-43-8, vitamin B1 structural formula is attached Fig.11 .

[0116] Vitamin B6 includes three forms: pyridoxine, pyridoxal and pyridoxamine. Fig.12 .

[0117] Pyridoxine: molecular formula C8H 11 NO3 molecular weight 169.18, CAS registration number 65-23-6; 58-56-0 (HCl). Pyridoxal: molecular formula C8H9NO3 molecular weight 167.162, CAS registration number 66-72-8.

[0118] Pyridoxamine: molecular formula C8H 12 The molecular weight of N2O2 is 168.193, and its CAS registration number is 85-87-0.

[0119] The structural formula of common vitamin E (α-tocopherol) is attached. Fig.13 , it has three chiral centers and eight isomers.

[0120] Glutathione: also called reduced glutathione, molecular formula: C 10 H 17 N3O6S molecular weight: 307.32348CAS see attached Fig.14 .

[0121] N-acetylcysteine: Molecular formula: C5H9NO3S Molecular weight 163.20 CAS registration number 616-91-1, see attached Fig.15 .

[0122] Famotidine: molecular formula C8H 15 N7O2S3 molecular weight 337.445 CAS registration number 76824-35-6, see attached Fig.16 .

[0123] Ranitidine hydrochloride: Molecular formula C 13 H 23 ClN4O3S molecular weight 350.865 CAS registration number 66357-59-3, the molecular formula of ranitidine is attached Fig.17 .

[0124] Cimetidine: C 10 H 16 N6S molecular weight 252.339 CAS registration number 51481-61-9, see attached Fig.18CAS number (Chemical Abstracts Service)

[0125] 1. Protonation of Metformin Hydrochloride

[0126] In fact, when seeing the structural formula of metformin hydrochloride, it is easy to think of the benzene ring - the one written is alternating single and double bonds, which is actually a large planar π bond formed by a π electron cloud; and the planar peptide bond - the one written is a single bond, but is actually a non-rotatable CN bond.

[0127] The reason why ordinary ammonia molecules can easily bind protons is that they are sp3 hybridized, leaving a lone electron pair. This lone electron pair is very easy to attract protons.

[0128] The three nitrogen atoms and carbon atoms in the guanidine group, or guanidine and its derivatives, actually form a planar structure. All nitrogen atoms are sp2 hybridized.

[0129] The structure of guanidine, all atoms are in the same plane, Lp is a lone electron pair, see the attached Fig.19 In this structure, since there is a bare lone electron pair in the double-bonded N atom, it is very easy to capture a proton, forming the Lp lone pair of electrons of guanidine protonation, see attached Fig. 20 At this time, it is called a guanidine ion, which carries a positive charge as a whole. At the same time, three nitrogen atoms and one carbon atom have a total of 6 π electrons, forming a large π bond together. This structure no longer has exposed lone electron pairs and is very stable. There is no possibility of continuing to attract a proton.

[0130] The two guanidine Lp lone pairs of electrons of biguanide form two guanidine positive ions to form a protonated compound. The Lp lone pair of electrons of biguanide and the Lp lone pair of electrons of biguanide are protonated. See the attached Fig.21 and attached Fig. 22 .

[0131] Therefore, guanidine is very easy to attract protons, with a pKa of 13.6. Arginine also has a guanidinium group, and the alkalinity of arginine (R group pka = 12.5) is also stronger than that of another basic amino acid lysine (R group pka = 10.5). In addition to being able to form two guanidinium positive cations, metformin hydrochloride can also have its primary, secondary, and tertiary amines all protonated. It is simply a cationic thorn ball that can act on the viral phospholipid envelope and directly kill the virus. The protonation theory of the guanidinium group and its primary, secondary, and tertiary amine groups can also explain that the stronger the added Bronsted acidity, the easier it is to lose protons, and the easier it is for metformin hydrochloride to gain protons. Under the hypoxic metabolic conditions of coronavirus-infected people, the acidic body fluid environment is more conducive to the protonation of metformin hydrochloride to kill the virus.

[60]

[61]

[0132] 2. Protonation of isosorbide and isomannide

[0133] Isosorbide is a dehydrated derivative of sorbitol. The two ether bonds and two hydroxyl groups in its structure can form protonated forms. Fig.23 .

[0134] Isosorbide is currently a diuretic, an oral osmotic dehydration diuretic, and its mechanism of action is similar to that of intravenous mannitol and sorbitol. By increasing the plasma osmotic pressure, water in tissues (including eyes, brain, cerebrospinal fluid, etc.) enters the blood vessels, thereby reducing tissue edema, reducing intraocular pressure, intracranial pressure, and cerebrospinal fluid volume and pressure. Isosorbide is mainly used to treat cerebral edema and glaucoma. After oral administration of isosorbide, 98% of the drug is absorbed by the gastrointestinal tract, and 97% of the drug is excreted in the urine in its original form, without any metabolic effect or caloric value. The half-life t1 / 2 is 8 hours.

[0135] Isosorbide is contraindicated in patients with active intracranial bleeding and intracranial hematoma, as volume expansion aggravates bleeding. It should be used with caution in patients with dehydration, anuria caused by renal dysfunction, hemorrhagic glaucoma, and congestive heart failure. Adequate balance of body fluids and electrolytes should be maintained during multiple doses. Elderly patients are more likely to suffer from renal damage after using this product. The chance of renal damage increases with age, so the dosage should be appropriately controlled.

[0136] Isomanitol is an isomer of isosorbide, and its protonated structure is shown in the figure below. Fig.24 .

[0137] 3. H2 receptor blockers

[0138] Famotidine, ranitidine and cimetidine are all histamine H2 receptor antagonists, see attached Fig.16 , 17 18. It can inhibit gastric acid secretion and is suitable for gastric and duodenal ulcers, reflux esophagitis, upper gastrointestinal bleeding, Zollinger-Ellison syndrome, etc. It can significantly inhibit basal and nocturnal gastric acid secretion, as well as gastric acid secretion caused by stimulation such as histamine, gastrin peptide, insulin and food, and reduce its acidity. It has a preventive and protective effect on corrosive gastritis caused by chemical stimulation, and also has a significant therapeutic effect on stress-induced gastric ulcers and upper gastrointestinal bleeding.

[0139] The guanidine group, thiazole ring, imine group, imidazole ring, ether bond, etc. in the structure of famotidine, ranitidine and cimetidine can be protonated, which further plays a broad-spectrum anti-infection and anti-cancer role. As H2 receptor blockers, they can widely prevent inflammatory exudation and relieve pain by blocking histamine-like effects. Long-term inflammation is also the main factor in tissue cell carcinogenesis, so they also have anti-cancer function to prevent cancer.

[62]

[63]

[64]

[0140] 4. Compounds that assist in protonation

[0141] Broad-spectrum anti-infective and anti-cancer drugs must be protonated to work. Therefore, while giving patients anti-infective treatment against bacteria, viruses, etc., they should also be supplemented with hydrogen-donating drugs such as vitamin C or vitamin B1, vitamin B6, vitamin E, glutathione, N-cysteine, etc., which is beneficial to the body's anti-infection mechanism.

[0142] (1) Vitamin C

[0143] Since the aqueous solution of vitamin C mainly exists in the enol form, the hydroxyl group on C2 forms a hydrogen bond with the adjacent carbonyl group, and the acidity of the hydroxyl group at C3 is stronger than that at C2. Fig.10 . In the process of mutual transformation between the hydroxyl and enol forms at the C2 and C3 positions, vitamin C can act as a hydrogen donor to provide protonation assistance for metformin hydrochloride, and then be further oxidized. The aqueous solution of vitamin C will gradually turn slightly yellow after being left for a long time, because it is easily oxidized by oxygen in the air. The oxidation rate is determined by pH and oxygen concentration, and is catalyzed by metal ions. Vitamin C has strong reducing properties, not oxidizing properties.

[65]

[0144] (2) Vitamin B1

[0145] Vitamin B1 is also known as thiamine or anti-neuritis factor, see attached Fig.11 , is the first vitamin to be discovered. It is synthesized by fungi, microorganisms and plants, while animals and humans can only obtain it from food. Vitamin B1 is mainly found in the outer skin and germ of seeds, such as rice bran and bran, which are very rich in it. It is also extremely rich in yeast. Thiamine is composed of a pyrimidine ring and a thiazole ring, and participates in sugar metabolism in the body. It can provide protonation with the help of enzymes in the process of biochemical reactions in the body. Thiamine often appears in the form of its hydrochloride, with the molecular formula C 12 H 17 ClN4OS·HCl, molecular weight 337.29. See attached Fig.11 . White crystalline powder. Slightly odorous, bitter, and deliquescent. Melting point 248°C. Easily soluble in water, slightly soluble in ethanol, insoluble in ether and benzene. Vitamin B1 has the function of maintaining normal sugar metabolism and nerve conduction. The highest content of vitamin B1 in nature is in yeast.

[0146] Vitamin B1 is involved in the metabolism of pyruvate and α-ketoglutaric acid in glucose metabolism. Its deficiency can cause the accumulation of pyruvate and lactic acid, thereby affecting the body's energy metabolism and causing cardiovascular and nervous system manifestations. Patients may experience palpitations, shortness of breath, chest tightness, cardiac hypertrophy and sensory-motor peripheral neuropathy.

[66]

[67]

[0147] (3) Vitamin B6

[0148] Vitamin B6 (VitaminB6), also known as pyridoxine, includes pyridoxine, pyridoxal and pyridoxamine. It exists in the body in the form of phosphate ester and is a water-soluble vitamin. It is easily destroyed by light or alkali and is not resistant to high temperatures. It is easily soluble in water and ethanol, stable in acid, and easily destroyed in alkali. Pyridoxine is heat-resistant, while pyridoxal and pyridoxamine are not resistant to high temperatures. Vitamin B6 is found in high levels in yeast, liver, grains, meat, fish, eggs, beans and peanuts. Vitamin B6 is a component of certain coenzymes in the human body and is involved in a variety of metabolic reactions, especially closely related to amino acid metabolism. Vitamin B6 preparations are used clinically to prevent and treat vomiting during pregnancy and vomiting caused by radiation sickness. The structural formula of vitamin B6 is as follows: Vitamin B6 includes three forms: pyridoxine, pyridoxal and pyridoxamine, see attached. Fig.12 In the process of pyridoxine dehydrogenation and oxidation to pyridoxal, vitamin B6 can act as a hydrogen donor to provide protonation assistance for compound A such as metformin hydrochloride.

[68]

[0149] (4) Vitamin E

[0150] Vitamin E is a general term for tocopherols. It is a golden or light yellow oily substance with a mild special smell. Usually, vitamin E is easily oxidized when exposed to light and air and becomes dark red. It is an essential fat-soluble vitamin for the human body. As an excellent antioxidant and nutrient, it is widely used in clinical, pharmaceutical, food, feed, health products and cosmetics industries.

[0151] There are eight structures of natural vitamin E, namely α, β, γ, δ tocopherol and α, β, γ, δ tocotrienol. The structural formula of vitamin E (α-tocopherol) has three chiral centers and eight isomers, see the attached Fig.13 .

[0152] The structural formula of vitamin E (α-tocopherol) is attached. Fig.13 Vitamin E has antioxidant properties. Free radicals are active groups that are widely present in various chemical reactions and play an important role in the normal physiological metabolism of the human body. If they are produced in excess, they will trigger a free radical chain reaction (oxidation reaction), which will lead to lipid oxidation of polyunsaturated fatty acids in the cell membrane. The large amount of lipid peroxides produced will damage the cell membrane and the macromolecular proteins and nucleic acids in the cell, causing damage to the body.

[0153] Tocopherol has an active hydroxyl group on the benzene ring, so it has reducing properties and can provide a single electron. When free radicals enter the lipid phase and a chain reaction occurs, tocopherol can capture the free radicals, thereby blocking the chain reaction of free radicals and playing an antioxidant protective role for the body. The reaction of tocopherol capturing free radicals is shown in the attached Fig.25In this process, vitamin E can act as a hydrogen donor to provide protonation assistance for compound A such as metformin hydrochloride. In addition, vitamin E can also help glutathione to always remain in a reduced state and indirectly act as a hydrogen donor.

[0154] The structure-activity relationship study of vitamin E shows that the hydroxyl group in the molecule is the active group and must be in a para position with the heterocyclic oxygen atom. The more methyl groups on the benzene ring, the stronger the activity. Shortening or removing the side chain in the molecule will reduce or eliminate the activity. The three-dimensional structure of vitamin E also affects the activity. Dextrorotatory vitamin E has the strongest activity. The antioxidant properties of various vitamin E are opposite to the strength of physiological activity. The antioxidant properties are from strong to weak:

[0155] δ-tocopherol>γ-tocopherol>β-tocopherol>α-tocopherol, and tocotrienol is greater than the corresponding tocopherol. When vitamin E is used as a fat antioxidant, it is often used in combination with ascorbyl palmitate (AP) to have a synergistic effect. Ascorbyl palmitate can replace the vitamin E reactant after capturing free radicals with vitamin E, restoring its antioxidant activity.

[69]

[0156] (5) Glutathione

[0157] Glutathione (GSH) is a tripeptide compound. Fig.14 It is generally formed by the condensation of glutamic acid, cysteine ​​and glycine through peptide bonds, and it is called glutamylcysteinylglycine.

[0158] GSH is an important low-molecular carbon alcohol among the antioxidant substances in animal cells. It is easily soluble in water, dilute alcohol, liquid ammonia and dimethylacetamide, but not easily soluble in alcohol, ether and acetone. The chemical properties of solid substances are basically stable. Ordinary aqueous solutions in the atmosphere are particularly easy to be oxidized into redox reaction glutathione, which has high antioxidant activity and has the functions of scavenging free radicals, regulating immunity, improving resistance, wrinkle removal and anti-aging, cancer treatment, and preventing adverse effects of radiation. On the other hand, it can also help white blood cells kill harmful bacteria, reduce and reduce the redox reaction of vitamins C and E, and also reduce and reduce the formation of cerebral infarction and cataracts. It can be tied to some primary carcinogens and can excrete toxins through urine. It also helps to promote the metabolic rate of sugar, fat and protein, eliminate hormone secretion, etc., and plays a role in protecting the liver.

[0159] The sulfhydryl group on cysteine ​​of glutathione is its active group (so glutathione is generally called G-SH). Glutathione is divided into two forms: reduced type (G-SH) and oxidized type (GSSG). Under physiological conditions, reduced glutathione accounts for the vast majority. The active sulfhydryl group of the reduced product glutathione shrinks into a disulfide bond through redox reaction, resulting in oxidized glutathione (GSSH), which can serve as an important hydrogen donor to help the protonation of compounds A such as metformin hydrochloride and isosorbide.

[0160] Glutathione is widely used as a drug in clinic. In addition to using its sulfhydryl group to chelate heavy metals, fluoride, mustard gas and other toxins, it is also used as a drug for treatment or auxiliary treatment of hepatitis, hemolytic diseases, keratitis, cataracts and retinal diseases. In recent years, Western scientists, especially Japanese scholars, have discovered that glutathione has the function of inhibiting HIV.

[70]

[0161] (6) N-acetylcysteine

[0162] N-Acetylcysteine, chemical formula is C5H9NO3S, see attached Fig.15 Acetylcysteine, also known as N-acetylcysteine ​​(NAC), is an N-acetylated derivative of cysteine ​​and a precursor of glutathione (GSH). It has pharmacological effects such as antioxidant, anti-inflammatory, microvascular dilation, and protection of DNA molecules.

[0163] NAC is a thiol-containing amino acid, mainly used as a mucolytic agent, with a strong mucolytic effect. The thiol contained in its molecules can break the disulfide bonds in the glycoprotein polypeptide chains in the sputum through interchange with the disulfide bonds of mucin, thereby reducing the viscosity of the sputum, and making the sputum liquid and easier to cough up. It can also break the DNA fibers in purulent sputum. Therefore, it can dissolve not only white sticky sputum, but also purulent sputum. For patients who are not responding to general expectorants, this product can still be effective.

[0164] NAC is used in many dosage forms in clinical practice, such as tablets, capsules, granules, injections, etc. It can be used for a variety of clinical indications, including dissolving sticky phlegm, protecting the liver, rescuing acetaminophen poisoning, treating eye diseases, etc. Acetylcysteine ​​shrinks from the reduction product to a disulfide bond through an active sulfhydryl redox reaction to obtain oxidized N-acetylcysteine, which can then serve as an important hydrogen donor to help the protonation of metformin and isosorbide.

[71]

[0165] 5. Choice of antipyretic drugs

[0166] If a high fever occurs during the human body's anti-infection process, antipyretics are inevitable. When the fever exceeds 38.5 degrees and needs to be reduced, please take acetaminophen (paracetamol), which can be protonated and has antiviral properties, to reduce the fever.

[0167] Paracetamol, formerly known as paracetamol. Molecular formula C8H9NO2 Molecular weight 151.163 CAS registration number 103-90-2, the molecular structure of paracetamol is attached Fig.26 .

[0168] The amide group is a medium-strength electron-donating group (-NHCOR), which can help the phenolic hydroxyl group on the benzene ring to be protonated. Therefore, among antipyretic and analgesic drugs, acetaminophen (paracetamol) can be protonated and have antiviral function.

[0169] 6. Mechanism of anti-infection action of metformin hydrochloride and vitamin C combination

[0170] The anti-infection mechanism of the combination of metformin hydrochloride and vitamin C is fivefold:

[0171] (1) Metformin, two guanidine groups, can form two strong cationic groups in the human body. In addition to forming two guanidine positive cations, its primary, secondary, and tertiary amines can all be protonated. They can act on the viral phospholipid envelope and directly kill the virus. Patients infected with viruses often have hypoxic metabolic mechanisms and acidic constitutions, which are also conducive to the protonation of metformin. With the help of vitamin C, the guanidine primary, secondary, and tertiary amine groups of metformin can form highly hydrophilic strong cationic heads, which can make holes in the viral phospholipid membrane layer, making the virus full of holes, allowing the RNA nucleic acid in its content to flow out and die.

[0172] (2) Metformin has the function of blocking more than 740 proteins, and it is possible that it blocks the surface proteins of the new coronavirus or the surface proteins of the host's susceptible cells.

[0173] (3) Various immunogenic proteins and nucleic acid components of killed bacteria and viruses remain in human blood vessels and can serve as antigenic components of the virus, stimulating the human body to produce an immune response against the virus and generate immunity.

[0174] (4) Metformin hydrochloride and killed viral phospholipids can also form a guanidine-containing surfactant, which can promote the expansion of the infected alveoli, prevent lung collapse, slow down the hyaline membrane lesions of the lungs, and help patients enhance their ventilation function.

[0175] 7. Mechanism research on the combination of metformin hydrochloride and vitamin C for the treatment of prion diseases found that phenol and sodium hypochlorite NaClO can kill prions in vitro. Phenol kills prions because it carries its own charge due to the conjugation effect of the benzene ring, forming protonation. Sodium hypochlorite can be hydrolyzed into hypochlorous acid HClO and chlorine dioxide ClO2. Hypochlorous acid HCLO carries positive +1 chlorine, while chlorine dioxide ClO2 carries positive +4 chlorine, which is also a strongly protonated substance, and can kill prions.

[0176] Phenol and sodium hypochlorite can kill prions, and metformin can do so even better. The two guanidine groups of metformin can form a conjugation effect similar to that of a benzene ring. The alkalinity strength PKa value of phenol is 10, while the alkalinity strength PKa value of metformin can reach 11, which is stronger than phenol. It can also be protonated, thereby killing prions.

[0177] Vitamin C can help the protonation of metformin in the human body. Two guanidine groups can form two strong cationic groups in the human body. Its primary, secondary and tertiary amines can also all be protonated. It can interfere with and destroy the intermolecular forces formed by prion proteins, such as hydrogen bonds, van der Waals forces, etc., making it impossible for it to form β (beta) folds and β sheets and random curling, which are the secondary and tertiary spatial structures of prions. In this way, the prion cleavage site can be exposed, helping the proteolytic enzymes in the human body to completely decompose the prion into harmless polypeptide fragments or amino acids.

[0178] In other words, prions are a type of protein that is abnormally folded due to hydrophobicity. At this time, the guanidine group of metformin can form a strong cationic head with strong hydrophilicity. Its primary, secondary, and tertiary amines can also be protonated. It has strong hydrophilicity and can completely break the hydrophobic structure of prion proteins, so that proteolytic enzymes can further hydrolyze and destroy them. Among them, vitamin C is indispensable.

[0179] That is to say, the most basic principle of phenol, sodium hypochlorite NaClO and metformin in fighting prions is that they carry electric charges after protonation, which can interfere with and destroy the intermolecular forces formed by prion proteins, such as hydrogen bonds, van der Waals forces, etc., making it impossible for them to form β (beta) folds and β (beta) sheets and random curling, which are the secondary and tertiary spatial structures of prions, and then help the proteolytic enzymes in the body to decompose them.

[0180] The main disadvantage of phenol in treating prions is that it is a carcinogen itself and it cannot penetrate the blood-brain barrier to completely kill prions. If prions have already invaded the human central nervous system, then micro-phenol injection therapy will be ineffective. Sodium hypochlorite is generally an environmental disinfectant that cannot directly enter the human body, and chlorine dioxide ClO2 also has the problem of not being able to penetrate the human body's natural barrier - the blood-brain barrier.

[0181] Therefore, only metformin is a safe and efficient strong alkaline substance that can enter the human body, and it can play the role of a scavenger in the human body. Among them, vitamin C is indispensable, which facilitates the protonation of metformin in the human body. If metformin is likened to a gun, then vitamin C can provide it with bullets. The combination of gun and bullet can kill bacteria, viruses and prions. The principle of the combination of metformin hydrochloride and vitamin C drugs to fight bacteria, viruses and prions is to disassemble them and disassemble them into parts.

[0182] 8. Treatment of prions

[0183] Diseases caused by prion proteins are currently difficult to cure, and the cause of their abnormal folding is unknown. In short, in the current medical community, this terrible protein that can cause human brain degeneration remains an unsolved mystery.

[0184] In addition to biological immunity, there are also charge immunity methods for pathogen immunity. Prions are non-living things, so biological immunity methods are obviously ineffective against them. Therefore, charge immunity methods must be used to be effective. Therefore, the search for drugs to treat prions must start from this idea, which involves quantum electrochemistry of protein spatial structure and prion growth, which is also driven by micro-charges. Currently, there are three treatment options that are believed to be effective against prions. One is a traditional Chinese medicine recipe containing ginger, the second is micro-injection of phenol, and the third is a drug combination of metformin hydrochloride and vitamin C.

[0185] (1) How to use ginger in traditional Chinese medicine

[0186] TCM methods that contain ginger include licorice and dried ginger soup, and ginger and brown sugar tea. In short, TCM prescriptions containing ginger are the right choice. TCM prescriptions that contain ginger are the correct prescriptions that can kill prions. More than half of the prescriptions in "Treatise on Febrile Diseases" contain ginger, which shows that our ancestors have long proved that ginger can resist infection. Ginger contains gingerol, a polyphenol that can kill prions through the blood-brain barrier. Ginger also contains gingerene, which can fight cancer. In order to eliminate sequelae, more ginger should be added to TCM treatment prescriptions, including in future life and eating habits, and patients should be advised to eat more ginger.

[0187] (2) Microinjection of phenol

[0188] Studies have found that phenol can kill prions in both in vitro and in vivo environments. The mechanism by which phenol kills prions is that due to the conjugation effect of the benzene ring, it carries its own charge, which can interfere with and destroy the intermolecular forces formed by prion proteins, such as hydrogen bonds, van der Waals forces, etc., making it impossible for it to form β (beta) folds and β sheets and irregular curls, which are the secondary and tertiary spatial structures of prions, and help the proteolytic enzymes in the body to decompose them. The main disadvantage of phenol in treating prions is that it is a carcinogen itself, and it cannot completely kill prions through the blood-brain barrier. If prions have invaded the human central nervous system, then the micro-phenol injection therapy will fail.

[0189] (3) Metformin hydrochloride plus vitamin C drug combination

[0190] Phenol can kill prions, so the combination of metformin hydrochloride and vitamin C can do it even better. The mechanism is as described above. The combination of metformin hydrochloride and vitamin C can penetrate the body's natural barriers - the blood-brain barrier, the blood-testis barrier, and the placenta barrier to completely and thoroughly kill prions, so patients will not have sequelae.

[0191] To summarize the three treatment options for prions, traditional Chinese medicine includes ginger prescriptions, trace phenol injections, and a drug combination of metformin hydrochloride and vitamin C. Among them, the most efficient and optimal one is the drug combination of metformin hydrochloride and vitamin C, as well as the patented method of the present invention derived therefrom.

[0192] Vitamin C is generally harmless, and a daily intake of more than 1 gram is not considered large. Drink plenty of boiled water during medication to prevent obstruction of the renal tubules. The combination of metformin hydrochloride and vitamin C can treat COVID-19. Isosorbide plus vitamin C is non-toxic and harmless, and is beneficial for pregnant women, infants, young children (less than 4 years old), and elderly people with liver and kidney diseases.

[0193] 9. Mechanism of anti-cancer effect of metformin hydrochloride plus vitamin C drug combination

[0194] (1) Targeted killing of cancer cells by taking advantage of the large amount of negative charges on the surface of cancer cells

[0195] Granulocytes play an important role in the body's anti-cancer immune monitoring system. Studies have found that the surfaces of various cancer cells, bacteria, and fungi that are the target cells of granulocytes carry a large amount of surface negative charge, while normal cells are neutral or not positively charged. Comparative tests of multifunctional nanoparticles (NPs) and multifunctional nanoparticles capturing cell efficiency, Diff's fast staining test, and laser confocal microscopy observations show that the surface of cancer cells is strongly negatively charged, the surface of granulocytes is weakly positively charged, and the surface of monocytes is neutrally charged. The mechanism by which granulocytes recognize the above-mentioned pathogenic cells is not any special molecule on the cell surface, but the cell surface charge.

[0196] The experiment of inhibiting the glycolytic pathway with 3-bromopyruvate further showed that the glycolytic pathway of cancer cells is the basis for granulocytes to recognize cancer cells. The abnormally vigorous glycolytic pathway of cancer cells causes the cancer cells to carry a large amount of negative charge on their surface. Granulocytes can use the opposite positive charge on their cell surface to identify cancer cells and complete the killing process. All forms of cancer cells show excessive negative membrane charge potential at low pH values ​​and excessive positive membrane charge potential at high pH values. The glycolytic pathway of cancer cells is abnormally vigorous, and their intracellular lactic acid and hydrogen ions increase significantly, which lowers their pH value and makes the surface membrane charge potential of cancer cells negatively charged.

[72]

[73]

[74]

[0197] This is also the theoretical basis for the anti-cancer effect of the combination of metformin hydrochloride and vitamin C. Moreover, its anti-cancer properties also show a certain targeted effect. They will not damage normal cells in the process of killing cancer cells. Metformin, with two guanidine groups, can form two strong cationic groups in the human body, which can make holes in the lipid membrane of cancer cells, causing the RNA nucleic acid in the cancer cells to flow out and die, directly killing the cancer cells. This targeted effect on cancer cells is achieved through the mutual attraction of positive and negative charges.

[0198] (2) The broad-spectrum anticancer combination of metformin hydrochloride and vitamin C can shut down cancer genes

[0199] The novel coronavirus spike protein will invade the cell nucleus and inhibit DNA damage repair by preventing the key DNA repair proteins BRCA1 and 53BP1 in the human body from gathering at the site of gene damage. The broad-spectrum anti-cancer combination of metformin hydrochloride and vitamin C can kill prions, eliminate factors that damage DNA repair proteins, and completely shut down oncogenes at the DNA repair level to treat cancer.

[0200] (3) Metformin has the function of protein blocking and can block more than 740 proteins. It can block the functional proteins of cancer cells and further interfere with their metabolic function.

[75]

[0201] (4) Metformin can mobilize the body's T cell immune function and kill cancer cells through signal transduction and synergistically with interferon-γ in the human body.

[0202] (5) Metformin can induce cancer cell death by activating cell apoptosis and pyroptosis mechanisms in the human body through signal transduction, thereby exerting an anti-cancer effect.

[76]

[0203] (6) Metformin mainly increases peripheral glucose utilization by delaying glucose uptake from the gastrointestinal tract, improving insulin sensitivity, and inhibiting excessive gluconeogenesis in the liver and kidneys. Metformin can specifically slow tumor growth by preventing cancer cells from metabolizing glucose, preventing cell respiration, and inhibiting the production of aspartate.

[0204] (7) The anti-cancer drug combination of metformin hydrochloride and vitamin C can kill prion-like nano-scale infectious particles and further prevent them from interfering with and damaging the human DNA repair gene P53.

[77]

[78]

[0205] (8) In animal experiments, if metformin hydrochloride is to have an anti-cancer effect, the dosage must often exceed the body's safe dosage limit in order to exert its anti-cancer effect. However, if vitamin C is added, metformin hydrochloride can be kept within the body's safe dosage range and exert its anti-cancer effect. By extension, the addition of hydrogen donor B can keep protonated A within the safe dosage range and exert its anti-cancer effect.

[0206] (9) Various immunogenic proteins and nucleic acid components of the killed cancer cells remain in the human blood vessels and can serve as antigen components of the cancer cells, stimulating the human body to produce an immune response against the cancer cells and generate immunity.

[79]

[0207] In short, if metformin hydrochloride is to play an anti-cancer role during animal experiments, the dosage will often exceed the safe dosage limit of the body to play an anti-cancer role. Since the simple use of metformin for anti-cancer still has great uncertainty, however, if metformin hydrochloride and vitamin C combination drugs are used for anti-cancer, then, both the anti-cancer signal regulation effect of metformin can be played, and cancer cells can be directly killed after protonation, and the anti-cancer effect can be played within the safe dosage range, without increasing the dosage of metformin and putting the patient in danger. By extension, due to the addition of B hydrogen donors, it is possible to keep the protonated A within the safe dosage range and play its anti-cancer effect. This is also a major innovative discovery of the present invention, which will provide a new technical route for curing cancer.

[0208] The combination of metformin hydrochloride and vitamin C has a broad-spectrum anti-cancer effect with low cost, low side effects and positive effects. It is very worthy of promotion to benefit the people.

[0209] In addition, since the various nodules produced in human tissues and organs are often precancerous lesions, the combination of metformin hydrochloride and vitamin C and the drugs derived from them can also help eliminate nodules.

[0210] 10. Metformin hydrochloride plus vitamin C drug combination to combat mycoplasma, chlamydia, and toxoplasma infection Mechanism Mycoplasma and chlamydia are both gram-negative pathogens. The isoelectric point of gram-positive bacteria is low, while the isoelectric point of gram-negative bacteria is high. Under the same pH conditions, gram-positive bacteria carry more negative charges than gram-negative bacteria, and are more firmly bound to the positively charged crystal violet dye and are not easy to decolorize. The isoelectric point of gram-positive bacteria is pH2-3, and the isoelectric point of gram-negative bacteria is pH4-5. When the pH is lower than its isoelectric point, these bacteria will carry a net positive charge, and when the pH is higher than its isoelectric point, these bacteria will carry a net negative charge. Under normal physiological conditions of the human body, the pH value is 7.35-7.45, so gram-negative mycoplasma and chlamydia are all negatively charged under human physiological conditions. This is also the theoretical basis for metformin hydrochloride and vitamin C to completely kill them.

[0211] During the process of inventing the Toxoplasma vaccine, Huang Siyang and others used a Malvern zeta potential meter to measure the surface of Toxoplasma tachyzoites and found that the surface of Toxoplasma tachyzoites carried a negative charge. This is also the theoretical basis for metformin hydrochloride, vitamin C and the drugs derived from them to completely kill it.

[80]

[0213] (II) The present invention includes the following inventions

[0214] 1. A pharmaceutical composition with broad-spectrum anti-infection and anti-cancer effects described in the present invention comprises two parts A and B as main components, wherein A can be metformin hydrochloride, arginine, isosorbide, isomannide, cimetidine, ranitidine, famotidine, or salts or derivative compounds and heterocomplexes of metformin hydrochloride, arginine, isosorbide, isomannide, cimetidine, ranitidine, famotidine, such as salts, amidated, esterified compounds of arginine, monoesters or disesters of isosorbide and isomannide, salts or derivative compounds and heterocomplexes of isosorbide, isomannide, cimetidine, ranitidine, famotidine, such as salts, esterified, etherified compounds of isosorbide and isomannide, so that the molecules can always maintain the active molecular characteristics of functional groups such as guanidine, thiazolyl, imidazolyl, hydroxyl, imino or ether bonds, so that they can always act as protonated compounds. B can be vitamin C, vitamin B1, vitamin B6, vitamin E, glutathione, N-acetylcysteine, etc., which can act as hydrogen donors and protonation donors to help the protonation of A. A or its salt or derivative compound and heterocomplex, which can be used alone or in combination with B or B's salt or derivative compound and heterocomplex alone or in combination to form an effective composition, and the composition ratio can meet the molar ratio requirements, or the molar ratio of A and B can be different, so as to play a broad-spectrum anti-infection and broad-spectrum anti-cancer drug effect.

[0215] 2. All the pharmaceutically acceptable salts of A and B described in the present invention may be hydrochlorides, phosphates, sulfates, acetates, etc.

[0216] 3. Use of A and B and their solvates or pharmaceutically acceptable salts described in the present invention in the preparation of broad-spectrum anti-infection and broad-spectrum anti-cancer drugs.

[0217] 4. A and B described in the present invention can form solvates, such as hydrates, alcoholates, etc. Generally speaking, solvates and non-solvates formed with pharmaceutically acceptable solvents such as water, ethanol, etc. are used in the preparation of broad-spectrum anti-infective and broad-spectrum anti-cancer drugs.

[0218] 5. The A and B compounds or their pharmaceutically acceptable salts described in the present invention may also exist as crystals. The present invention includes any crystalline form of metformin or its pharmaceutically acceptable salt shown in Formula 1, and its use in the preparation of broad-spectrum anti-infection and broad-spectrum anti-cancer drugs.

[0219] 6. The compounds A and B described in the present invention and their solvates or pharmaceutically acceptable salts can be administered by the following routes: parenteral, topical, intravenous, oral, subcutaneous, intraarterial, intradermal, transdermal, rectal, intracranial, intraperitoneal, intranasal, intramuscular or as an inhalant, and used in the preparation of broad-spectrum anti-infective and broad-spectrum anti-cancer drugs.

[0220] 7. The compounds A and B described in the present invention and their solvates or pharmaceutically acceptable salts can be administered in the form of pharmaceutical preparations. The pharmaceutical composition comprises A and B and their solvates or pharmaceutically acceptable salts and pharmaceutically acceptable carriers or excipients, etc., and is used in the preparation of broad-spectrum anti-infection and broad-spectrum anti-cancer drugs.

[0221] 8. The compounds A and B described in the present invention and their solvates or pharmaceutically acceptable salts can be formulated into various suitable dosage forms according to the route of administration, and used in the preparation of broad-spectrum anti-infection and broad-spectrum anti-cancer drugs.

[0222] 9. When applied topically to the skin, the A and B compounds of the present invention can be prepared into suitable ointment, lotion or cream preparations, wherein the active ingredients are suspended or dissolved in one or more carriers. The carriers that can be used for ointment preparations include, but are not limited to: mineral oil, liquid petrolatum, white petrolatum, propylene glycol, polyethylene oxide, polypropylene oxide, emulsifying wax and water; the carriers that can be used for lotions or creams include, but are not limited to: mineral oil, sorbitan monostearate, Tween 60, hexadecyl ester wax, hexadecene aromatic alcohol, 2-octyldodecanol, benzyl alcohol and water, etc., and are used in the preparation of broad-spectrum anti-infective and broad-spectrum anti-cancer drugs.

[0223] 10. The pharmaceutical preparations A and B of the present invention include any pharmaceutically feasible preparations, such as oral preparations, parenteral preparations, etc., used in the preparation of broad-spectrum anti-infection and broad-spectrum anti-cancer drugs.

[0224] 11. When administered orally, the compounds A and B of the present invention can be prepared into any oral acceptable preparation form, including but not limited to tablets, capsules, aqueous solutions or aqueous suspensions. Among them, the carriers used in tablets generally include lactose and corn starch, and lubricants such as magnesium stearate may also be added. The diluents used in capsule preparations generally include lactose and dry corn starch. Aqueous suspension preparations are usually prepared by mixing the active ingredients with suitable emulsifiers and suspending agents. Optionally, some sweeteners, aromatics or colorants, etc., may be added to the above oral preparation forms for use in the preparation of broad-spectrum anti-infective and broad-spectrum anti-cancer drugs.

[0225] 12. The A and B compounds and their solvates or pharmaceutically acceptable salts described in the present invention can also be used in the form of sterile injection preparations, including sterile injection water or oil suspension or sterile injection solution, or in lyophilized form. Among them, the carriers and solvents that can be used include water, Ringer's solution and isotonic sodium chloride solution. In addition, sterilized non-volatile oils can also be used as solvents or suspension media, such as monoglycerides or diglycerides, etc., in the preparation of broad-spectrum anti-infective and broad-spectrum anti-cancer drugs.

[0226] 13. Since the present invention is a new use of old drugs, the two drugs A and B can also be used separately, but their respective half-lives overlap and cross in the body, and can also play a synergistic role in broad-spectrum anti-infection and broad-spectrum anti-cancer, that is, they are used as a combination to prepare drugs for preventing and treating broad-spectrum infections or for broad-spectrum anti-cancer, etc., which are all within the scope of the protection requirements of this patent application. The more the peak areas of the half-lives of the two drugs A and B overlap, the greater the synergistic effect they play.

[0227] 14. Since the present invention relates to new uses of old drugs, drugs A and B can also be used separately, but their respective half-lives overlap and cross in the body, and can also play a synergistic role in broad-spectrum anti-infection and broad-spectrum anti-cancer. That is, they are used as a combination to prepare drugs for preventing and treating broad-spectrum infections or for broad-spectrum anti-cancer, such as their use in drugs for preventing and treating mycoplasma, chlamydia and toxoplasma.

[0228] 15. Since the present invention relates to new uses for old drugs, drugs A and B can also be used separately, but their respective half-lives overlap and cross in the body, and can also play a synergistic role in broad-spectrum anti-infection and broad-spectrum anti-cancer. That is, they are used as a combination to prepare drugs for preventing and treating broad-spectrum infections or for broad-spectrum anti-cancer, etc., such as their use in preventing and treating various nodules, polyps and other precancerous lesions.

[0229] 16. Since the present invention relates to new uses of old drugs, drugs A and B can also be used separately, but their respective half-lives overlap and cross in the body, and can also play a synergistic role in broad-spectrum anti-infection and broad-spectrum anti-cancer. That is, they are used as a combination to prepare drugs for preventing and treating prion infection diseases, etc., such as their use in preventing and treating amyotrophic lateral sclerosis (ALS, also called motor neuron disease).

[0230] 17. Since the present invention relates to new uses of old drugs, drugs A and B can also be used separately, but their respective half-lives overlap and cross in the body, and can also play a synergistic role in broad-spectrum anti-infection and broad-spectrum anti-cancer. That is, they are used as a combination to prepare drugs for the prevention and treatment of protein amyloid deposition diseases, such as drugs for the prevention and treatment of Alzheimer's disease.

[0231] 18. Since the present invention belongs to the new use of old drugs, the two types of drugs A and B can also be used separately. A is a compound that can be protonated, and B is a hydrogen donor. The two can exert the greatest synergistic effect within the safe dosage range, and play a broad-spectrum killing effect on bacteria, viruses, prions, cancer cells, mycoplasmas, chlamydia, toxoplasma, etc. This has broken through the various limitations of the previous single use of Class A compounds for broad-spectrum anti-infection and broad-spectrum anti-cancer. The larger the safe dosage of the two types of drugs A and B, the more the peak area of ​​the half-life overlaps, and the greater the synergistic effect it plays. For example, metformin hydrochloride plus vitamin C is used for anti-cancer, and its daily dosage can reach the upper limit of 2.55 grams / day of metformin hydrochloride, and the oral dose of vitamin C can reach 3 grams per day, or even more (three times a day, taken after meals). In actual use, 1.5 grams / day of metformin hydrochloride and 1.8 grams of oral dose of vitamin C per day have achieved a good anti-cancer effect (three times a day, taken after meals). The two types of drugs A and B are used in the preparation of drugs for preventing and treating broad-spectrum anti-infection and broad-spectrum anti-cancer within their respective maximum safety limits.

[0232] 19. The A and B described in the present invention may be in the form of prodrugs or in the form of active ingredients that can be released after metabolic changes in the body. The selection and preparation of appropriate prodrug derivatives are well known to those skilled in the art, and the present invention does not limit this. DETAILED DESCRIPTION

[0233] 1. Metformin hydrochloride and vitamin C pharmaceutical composition for treating novel coronavirus infection

[0234] Wu Moumou, female, 95 years old, had a healthy past and no underlying diseases. The patient developed symptoms such as cough and fever on May 20, 2023, with a maximum body temperature of about 38.1℃, which gradually worsened and she developed shortness of breath. After taking medicine (specific details are unknown), there was no obvious relief. She was admitted to a local tertiary hospital for treatment and was given intravenous infusion of moxifloxacin. After 3 days, her body temperature returned to normal. A reexamination of the lung CT on May 25 showed that the lung infection had improved slightly compared with before. On May 26, she developed shortness of breath after activity and went to the local tertiary hospital again. The pharyngeal swab nucleic acid test for the new coronavirus was positive. A reexamination of the lung CT showed diffuse infectious lesions in both lungs and was diagnosed with new coronavirus infection. Chest CT examination showed bilateral pneumonia (increased and blurred texture in both lungs, and multiple large patchy blurred shadows diffusely distributed in both lungs). Fig. 27 . Indicates severe lung infection, see Fig.28 .

[0235] On the same day, he was admitted to a local tertiary hospital for treatment. The blood routine test on admission showed that the white blood cell count was 9.60x10^9 / L, the absolute value of lymphocytes was 1.53x 10^9 / L, and the absolute value of neutrophils was 7.60x10^9 / L. The new coronavirus nucleic acid test was positive. However, his condition worsened, RR ≥ 37 times / min, and his blood oxygen saturation was low, once below 90, and dropped to 88. Fig.29 On June 1, the attending physician issued a critical illness notice to the family.

[0236] At 8 pm on June 1, he started taking a combination of metformin hydrochloride and vitamin C. Considering the patient's serious condition, he was given 0.5 grams of metformin hydrochloride each time and 6 tablets of 0.1 grams of vitamin C each time. Take it three times a day (immediately after meals). By June 4, the patient's condition had improved significantly, RR ≥ 34 times / min, and the blood oxygen saturation returned to above 90, reaching 91-92. Fig.30 , 31 .

[0237] A reexamination of the lung CT showed that the infectious lesions in both lungs still existed, and multiple patchy and blurred shadows in the left lung were still obvious. Fig.32 However, the right lung gradually became clear, and the patchy shadows were significantly reduced. The patient's symptoms were improving, indicating that the lung infection was being alleviated. Fig.33 .

[0238] As of June 5, the patient continued to take metformin hydrochloride and vitamin C, RR ≥ 34 times / min, blood oxygen saturation remained above 93 for a long time, and was no longer in danger of death. Fig.34 . However, the throat swab novel coronavirus nucleic acid test was still positive.

[0239] The patient continued to take metformin hydrochloride and vitamin C in combination. As of June 9, the nucleic acid test for the new coronavirus in the throat swab had turned negative, and the patient's condition was stable.

[0240] As of June 11, the patient continued to take metformin hydrochloride and vitamin C. He still had shortness of breath (RR) of 39 times / min, but his blood oxygen saturation remained stable above 96 for a long time. Fig.35 .

[0241] As of June 16, the patient's condition has improved significantly, with RR ≥ 30 times / min, and blood oxygen saturation can be stabilized above 96 for a long time. Reexamination of lung CT showed that infectious lesions in both lungs still existed, and multiple patchy fuzzy shadows in the left lung were still obvious, but they also gradually became clearer. The right lung was clearer than the previous few days, and the patchy fuzzy shadows were significantly reduced, and no longer presented large blurred images. Multiple patchy fuzzy shadows in the left lung were still obvious, but they also gradually became clearer. Fig.36The right lung is clearer than the previous few days, and the flake-like blurred shadows have been significantly reduced, and there is no longer a large area of ​​blurred images. Fig.37 The patient's symptoms are improving significantly, indicating that the lung infection is continuing to ease. The patient's symptoms are improving significantly, indicating that the lung infection is continuing to ease.

[0242] The CT diagnosis report concluded that there were still multiple inflammations in both lungs, but the patient's symptoms were obviously improving. Considering that the patient was 95 years old, it was normal for the inflammation to be absorbed slowly. However, most of the right lung was clear, and the infection shadow in the left lung was also obviously shrinking. The lung infection was easing. Fig.38 In addition, the blood oxygen saturation remained stable above 96, indicating that the patient's condition had stabilized.

[0243] As of June 19, the patient had basically recovered. Although there was still a little inflammation in the lungs, he had met the discharge criteria and was allowed to be discharged. After discharge, he still needed to continue taking medication. The combination of metformin hydrochloride and vitamin C was changed to be taken twice a day in the morning and at noon after meals. The dosage was changed to 0.25 grams of metformin hydrochloride each time plus 4 tablets of 0.1 grams of vitamin C each time, and continued to take it for one week.

[0244] The combination of metformin hydrochloride and vitamin C has been used to treat more than 100 patients infected with various types of novel coronavirus, achieving satisfactory results. In the clinical data of more than 100 cases, they were treated with a combination of metformin hydrochloride and vitamin C. If the body temperature did not exceed 38°C and there were no other complications, no other treatment was needed. If the body temperature exceeded 38°C, the antipyretic drug acetaminophen could be taken. When the body temperature returned to normal, stop taking the antipyretic drug immediately, and no other treatment was needed.

[0245] There were more than 80-90 patients, including those with one positive infection, two positive infections, and even three positive infections, who tested positive for the new coronavirus antigen. Fig.39 , confirmed as a COVID-19 infected patient. The combination of metformin hydrochloride and vitamin C has achieved satisfactory results. Fig.40. Treatment method: Metformin hydrochloride 0.25g / tablet / time, plus 4 tablets of vitamin C 0.1g / tablet / time, taken orally 3 times a day, for 2 to 4 consecutive days. If the body temperature does not exceed 38°C and there are no other complications, no other treatment is required. For patients with severe conditions, the dosage can be increased to 0.5g / tablet / time of metformin hydrochloride, plus 0.1g / tablet / time of vitamin C for a total of 6 tablets, taken orally 3 times a day, for 2 to 4 consecutive days. If the body temperature does not exceed 38°C and there are no other complications, no other treatment is required. If the body temperature exceeds 38°C, you can take the antipyretic drug acetaminophen. Stop taking the antipyretic drug immediately after the body temperature returns to normal, and no other treatment is required. To give another example, Zhang XX, male, 3 years and 10 months old, weighing 15 kg, had a persistent high fever from March 8 to March 14, 2022, and the new crown antigen test was positive. At 7 pm on the 14th, the body temperature was measured at 38.6 degrees. No antipyretics were taken. At more than 8 pm, he was told to take half a tablet of metformin hydrochloride at 0.25 plus a tablet of vitamin C at 0.1g / tablet, 150mL of warm water. When the body temperature began to drop at 12 o'clock in the evening, the body temperature was measured at 36.7 degrees at 7 o'clock the next morning, and it returned to normal. After getting up the next morning, take the remaining half tablet of metformin hydrochloride plus a tablet of vitamin C at 0.1g / tablet to consolidate the effect. Then change to pear juice and take a tablet of vitamin C at 0.1g / tablet, three times a day. The condition has not relapsed since then. On March 18, 2022, the new crown antigen test turned negative, and the child was considered to have fully recovered.

[0246] 2. Metformin hydrochloride and vitamin C pharmaceutical composition for treating hepatitis B virus infection

[0247] Zhu, male, 52 years old, was found to be HBsAga positive for ten years, with occasional right upper abdominal distension and pain, abnormal liver function, no special discomfort, and generally good condition. He was diagnosed and treated in the infectious disease departments of major hospitals in Shanghai, Jiangsu and other places. Since then, he has taken traditional Chinese medicine for liver protection treatment intermittently (the details are unknown). On October 23, 2021, the test found that hepatitis B surface antibody, hepatitis B core antibody and hepatitis B e antibody were positive, and he was still in the small three positive stage, indicating that he still had the possibility of latent hepatitis B infection. See Fig.41 .

[0248] On October 25, 2021, he started to receive treatment with a combination of metformin hydrochloride and vitamin C. The combination of metformin hydrochloride and vitamin C was taken three times a day after meals in the morning, noon, and evening. The dosage was 0.25 grams of metformin hydrochloride each time plus 4 tablets of 0.1 grams / tablet of vitamin C each time, and it was taken continuously for one month.

[0249] On November 27, 2021, I went to the hospital for testing again and found that except for the hepatitis B surface antibody which was still positive, the other indicators including hepatitis B surface antigen, hepatitis B e antigen, hepatitis B core antibody and hepatitis B e antibody were all negative, especially the hepatitis B core antibody and hepatitis B e antibody, which were originally positive and all turned negative. This shows that the patient has fully recovered and has developed immunity to hepatitis B. Fig.42 .

[0250] On September 27, 2023, and November 27, 2021, he went to the hospital for testing again and found that except for the hepatitis B surface antibody which was still strongly positive, all other indicators were negative. This once again shows that the patient has fully recovered, has stood the test of time, and has developed immunity to hepatitis B. Fig.43 .

[0251] 3. Treatment of herpes zoster virus infection with a pharmaceutical composition of metformin hydrochloride and vitamin C

[0252] Acute herpetic skin disease caused by herpes zoster virus is prone to occur in the distribution areas of the intercostal nerves, cervical nerves and trigeminal nerves. Its clinical characteristics are burning sensation or neuralgia in the affected skin. The lesions are clustered blisters ranging in size from millet to mung bean on red spots, and the skin between each group of rashes is normal. The lesions are distributed in a band-like manner along the unilateral cutaneous nerve, generally not exceeding the midline of the body surface, and the course of the disease is 2-3 weeks.

[0253] From March 2020 to August 2023, the present invention cured 10 cases of herpes zoster by combining the metformin hydrochloride and vitamin C pharmaceutical composition with famotidine.

[0254] General data, 10 patients, including 6 males and 4 females, the oldest was 5-9 years old and the youngest was 15, the shortest course of disease was 12 hours and the longest was 2 days. Herpes was mostly distributed on the chest, back, and waist, with the back being more common.

[0255] Efficacy judgment criteria: cured: skin lesions disappear, neuralgia disappears; improved: skin lesions partially disappear, no new rash occurs, and neuralgia is relieved; uncured: skin lesions do not disappear, or new rash occurs, and neuralgia does not alleviate.

[0256] Treatment method: All three drugs are taken orally, 0.25g of metformin hydrochloride plus 4 tablets of 0.1g / tablet vitamin C each time, 3 times / day. Take 10mg / tablet / time of famotidine every night. Results: After treatment, all 10 patients were cured, the pain relief time was 1-2.5 days, the herpes healing time was 2-4 days, and the herpes scabs completely healed in about 7 days. Mild cases generally healed in 3-5 days, and severe cases healed in 5-10 days.

[0257] After 2-4 days of medication, the itching disappeared on the first day, the herpes scabs formed on the 2-3 days, and the scabs fell off and healed on the 4-6 days. All 10 cases were cured, and no complications occurred in any case, with a cure rate of 100%.

[0258] Famotidine, cimetidine and ranitidine all belong to H2 receptor antagonists, and famotidine is a new generation of H2 receptor antagonists, which can treat digestive diseases such as peptic ulcer, reflux esophagitis, gastrinoma, and can also prevent upper gastrointestinal bleeding caused by invasive stress reactions such as cerebrovascular disorders. H2 receptors are also distributed in large quantities in the skin. From the perspective of its structure, famotidine can also be protonated. In recent years, it has been found that the drug has a broad-spectrum antiviral effect, enhances immunity, shortens the course of treatment for certain diseases, consolidates the therapeutic effect, and prevents the effect of recurrence. Metformin and vitamin C pharmaceutical composition are used together with famotidine to treat herpes zoster virus infection, which can prevent and treat inflammatory exudation and pain.

[0259] The onset of herpes zoster is related to the host's reduced cellular immune function. Famotidine can antagonize the production of histamine-induced inhibitory factors, thereby enhancing the body's cellular immune function and shortening the infection process of herpes virus. Virulin is a broad-spectrum antiviral drug. The combination of three drugs has a definite effect. It is both economical and safe, and is worthy of clinical promotion. Precautions: It is contraindicated for people with severe renal insufficiency, lactating women, pregnant women, people who are allergic to metformin hydrochloride, the product ingredients in famotidine, and people who are allergic to other H2 receptor antagonists; people with heart disease and liver and kidney dysfunction should use it with caution. Adverse reactions may occur after use, such as dizziness, insomnia, abdominal pain, severe diarrhea, etc., and relevant symptoms should be observed. If serious adverse reactions occur, the drug should be discontinued immediately.

[0260] 4. Metformin hydrochloride and vitamin C pharmaceutical composition for treating Helicobacter pylori infection

[0261] Gu, male, 56 years old, has often felt bloating, stomach pain, belching, acid reflux, heartburn, bad breath and other symptoms after meals since February 2021. In April 2021, he underwent a C14 breath test for Helicobacter pylori at a local tertiary hospital. The HP value reached 1368dbp / mmol, and he was diagnosed with Helicobacter pylori positive infection. The doctor gave a quadruple prescription for treatment. The prescription and dosage are as follows: Colloidal bismuth tartrate capsules 220mg (4 capsules) twice a day before meals, pantoprazole sodium enteric-coated capsules 80mg (2 capsules) twice a day before meals, clarithromycin capsules 500mg (2 capsules) twice a day after meals, and metronidazole benzoate dispersible tablets 640mg (2 capsules) twice a day after meals. Take them at breakfast and dinner respectively, proton pump inhibitors and bismuth agents half an hour before meals; antibiotics are taken half an hour after meals. A course of treatment is 14 days. One month after stopping the medication, I went for another C14 test in July 2021, and the HP value reached 56dbp / mmol, which had turned negative. Since January 2022, I often feel bloating, belching, bad breath and other symptoms after meals. In the routine physical examination in April 2022, the C14 breath test for Helicobacter pylori was found again, and the HP value reached 1089dbp / mmol, which should be a recurrence of Helicobacter pylori positive infection.

[0262] On October 25, 2022, he began to receive treatment with a combination of metformin hydrochloride and vitamin C. The combination of metformin hydrochloride and vitamin C was taken three times a day in the morning, noon, and evening after meals. The dosage was 0.25 grams of metformin hydrochloride each time plus 4 tablets of 0.1 grams / tablet vitamin C each time. It was taken for 14 consecutive days as a course of treatment. One month after stopping the medication, he went for another C14 test at the end of December 2022. The HP value reached 42dbp / mmol, which had turned negative again. In the routine physical examination in April 2023, the C14 breath test detected Helicobacter pylori, and the HP value reached 46dbp / mmol. The C14 breath test for Helicobacter pylori was still negative, and there was no recurrence.

[0263] Ten patients with Helicobacter pylori infection were treated with the combination of metformin hydrochloride and vitamin C, including 8 males and 2 females, aged 5-6 years old and 18 years old. The efficacy was judged as cure: symptoms such as postprandial bloating, stomach pain, belching, acid reflux, heartburn, and bad breath disappeared, and the HP value of Helicobacter pylori detected by C14 breath test reached <100dbp / mmol and remained negative.

[0264] 5. Metformin hydrochloride and vitamin C pharmaceutical composition for the treatment of ALS

[0265] Ms. Wang, 49 years old, felt weakness in her left arm, occasional muscle twitching in both arms, tingling in the index fingers and thumbs of her left and right hands, unstable movements, frequent insomnia at night, chest tightness and shortness of breath. She felt particularly excited. Although she had insomnia, she was not tired. In early and mid-March 2021, the symptoms worsened and occurred more frequently. She went to the hospital for examination accompanied by her family. The electromyography showed neurogenic damage and was diagnosed with motor neuron disease.

[0266] On April 2, 2021, he started to receive treatment with a combination of metformin hydrochloride and vitamin C. The combination of metformin hydrochloride and vitamin C was taken three times a day after meals in the morning, noon, and evening. The dosage was 0.25 grams of metformin hydrochloride each time plus 4 tablets of 0.1 grams per tablet of vitamin C each time. A course of treatment was 30 consecutive days.

[0267] During a follow-up visit one month after medication, the patient's mental state improved significantly compared to before, weakness in both arms disappeared, muscles no longer twitched, tingling in the index fingers and thumbs of both hands disappeared, there was no more unsteady movement, sleep quality improved significantly, insomnia symptoms disappeared, chest tightness was completely relieved, and electromyography returned to normal. During follow-up visits, there has been no recurrence of the disease since the medication was stopped on May 4, 2021.

[0268] Two cases of ALS were treated with a combination of metformin hydrochloride and vitamin C, and the other case was a 22-year-old male college student. Efficacy evaluation, cure criteria: the weakness of both arms disappeared, the muscles no longer throbbed and throbbed, the tingling sensation in both fingers disappeared, there was no unsteady movement, the sleep quality was significantly improved, the insomnia symptoms disappeared, the chest tightness was completely relieved, and the electromyography returned to normal.

[0269] 6. Treatment of lung cancer with a pharmaceutical composition of metformin hydrochloride and vitamin C

[0270] Lung cancer is a common malignant tumor. In recent years, the incidence of lung cancer has continued to rise, bringing misfortune to many families. With the continuous advancement of medicine, there are more and more cancer treatment methods. There are clinical cases of cancer recovery, but there are also cases where the treatment effect is not good. For lung cancer, only active treatment can increase the cure rate of lung cancer.

[0271] The cure rate of lung cancer is indeed not optimistic. It is often discovered late and the opportunity for surgical treatment has been lost. The cure rate of the first stage is 60%-80%. The second stage is relatively rare and the effect is slightly worse, with a cure rate of 40%-50%. The third stage patients account for about 30%-35%, and the five-year survival rate is about 15%-40%. The fourth stage patients have distant metastasis, and the cure rate is less than 5%. In terms of statistical probability, it is a very small probability, which is almost impossible to cure. Patients with advanced lung cancer often lose the opportunity for surgery. At the same time, they are not sensitive to radiotherapy and chemotherapy, and targeted drugs cannot be used. In addition, the patients are physically weak at this time and often cannot accept any treatment methods. The present invention provides a brand new treatment plan for the treatment of lung cancer.

[0272] The patient, Niu Moumou, male, 64 years old, had a history of COPD for more than ten years. His typical symptoms are: daily chronic cough, obvious cough in the morning, and coughing or expectoration at night. Generally, it is white mucus or serous foamy sputum, occasionally with blood, and more sputum is discharged in the early morning. During the acute attack period, the amount of sputum increases, and there may be purulent sputum. In the early stage, shortness of breath or difficulty breathing occurred during more intense activities, and then gradually worsened, especially after January 2020, the aggravation was obvious, so that shortness of breath was felt during daily activities or even rest. By the end of March 2020, severe wheezing sometimes occurred, and the patient had weight loss and loss of appetite. A chest CT scan in April 2020 showed an enlarged shadow at the right hilum, and bronchoscopy showed a growth in the dorsal segment of the right lower lung. The biopsy pathological diagnosis was lung adenocarcinoma, and the definite diagnosis was "right lower lung adenocarcinoma", stage IV, poorly differentiated, ps1 point (T1N3M1a central type), right pleural metastasis, lymph node metastasis, large pleural effusion, and facial edema.

[0273] Chest CT scan showed an increase in the shadow of the right hilum. Fig.44 . Bronchoscopy showed a tumor in the dorsal segment of the right lower lobe. Because of weak lung function, surgical treatment is not suitable. Pemetrexed + platinum drugs (also known as PC or PP regimen) were given for four phases of chemotherapy, during which bronchoscopic intracavitary interventional treatment was performed twice. CT in October 2020 showed: inflammatory lesions of the lungs, no significant reduction in the tumor, and effusion in the chest cavity. Since October 2020, the patient has been taking metformin hydrochloride and vitamin C drug combination to treat lung cancer. The metformin hydrochloride and vitamin C drug combination is taken three times a day in the morning, noon, and evening after meals. The dosage is 0.25 grams of metformin hydrochloride each time plus 4 tablets of 0.1 grams / tablet of vitamin C each time, and it is taken continuously for 30 days as a course of treatment. After stopping the medication for one month, a chest CT scan in January 2022 showed that the range of the lesions was significantly reduced.

[0274] During this period, the patient had no obvious cough, sputum, hemoptysis, chest tightness, dyspnea, headache, dizziness, bone and joint pain, abdominal distension, abdominal pain, etc. Diet and bowel movements were normal. The spirit improved significantly and sleep was good. In February 2022, metformin hydrochloride and vitamin C pharmaceutical combination was taken again to treat lung cancer, and it was taken for 30 consecutive days as a course of treatment. After that, metformin hydrochloride and vitamin C pharmaceutical combination was taken for 7 days a month to treat lung cancer. Chest CT and bronchoscopy reexamination in July 2022 showed that the lesion range was basically absorbed, see Fig.45 The patient gained nearly 10 kg and the treatment effect was excellent. The patient is still alive and in good health.

[0275] 7. Metformin hydrochloride and vitamin C pharmaceutical composition for the treatment of myeloproliferative neoplasms essential thrombocythemia Essential thrombocythemia, also known as hemorrhagic thrombocythemia, is a hematopoietic stem cell clonal disease with megakaryocyte hyperplasia as the main feature, and the main clinical manifestations are persistent platelet increase, splenomegaly, hemorrhage or thrombosis. Various viral infections lead to higher white blood cell counts and more active bone marrow hyperplasia. Long-acting interferon treatment is usually given, and its purpose is also mainly for antiviral purposes.

[0276] Patient: Ji Moumou, female, 54 years old, was admitted to the hospital on February 7, 2021 due to palpitations and fatigue for half a month. Physical examination: anemia, no enlargement of superficial lymph nodes throughout the body. There are no bleeding spots and ecchymoses on the skin, negative heart and lungs, liver and spleen, and slight edema in both lower limbs. The patient also has hypotension, blood pressure 118 / 56mmHg. Past: ⑶ Imaging: peritoneal tumor metastasis at the right posterior edge of the liver, pancytopenia, and continued increase in tumor markers; bone marrow images during the consultation, bone marrow smears: nuclear heterogeneous cells, suspected tumor cells. Re-examination of bone marrow pathology: immunohistochemistry: CK (-), ER (-), Pax-9 (-), GATA-3 (-), CD3 (scattered +), CD20 (scattered +), CD5 (scattered +), Pax-5 (-), Ki-67 (10%). It was found that the platelet count reached more than 1350, and then the doctor arranged a bone marrow puncture.

[0277] Related test data: high-sensitivity C-reactive protein 39.02mg / L↑, CA126.32U / ml↑, vitamin B12910.81pg / mL↑, CA154:41.32U / mL↑, ferritin 548.52ng / mL↑, folic acid: 4.98ug / L↑. Antinuclear antibody spectrum: anti-SS-A antibody positive, the rest negative.

[0278] Bone marrow biopsy showed highly proliferative megakaryocytes, an increase in the number of mature megakaryocytes with large cell bodies and hyperlobated nuclei, morbid hematopoiesis of the megakaryocyte system, no significant proliferation or left shift of the granulocyte and erythroid systems, and a slight increase in reticular fibers (grade 1), accompanied by an increase in ring sideroblasts.

[0279] Bone marrow biopsy showed highly hyperplastic megakaryocytes, an increase in the number of mature megakaryocytes with large cell bodies and hyperlobed nuclei, morbid hematopoiesis of the megakaryocyte system, no significant hyperplasia or left shift of the granulocyte and erythroid systems, and a slight increase in reticular fibers (grade 1), accompanied by an increase in ring sideroblasts. The patient was eventually diagnosed with essential thrombocythemia.

[0280] During this period, oral metformin hydrochloride and vitamin C drug combination was taken three times a day in the morning, noon, and evening after meals. The dosage was 0.25 grams of metformin hydrochloride each time plus 4 tablets of 0.1 grams / tablet vitamin C each time, and it was taken for 30 consecutive days as a course of treatment. On April 18, 2021, the patient's platelet count fell back and was controlled at 350×109 / L (the normal range is (100-300)×109 / L). In June 2021, metformin hydrochloride and vitamin C drug combination were taken again for treatment, and it was taken for 14 consecutive days as a course of treatment. After that, metformin hydrochloride and vitamin C drug combination were taken for 7 days a month to treat myeloproliferative neoplasm primary thrombocythemia. The patient's platelet count returned to normal in November 2021, which was 187×109 / L. Bone marrow smear. The patient is still alive and in good health.

[0281] 8. Treatment of thyroid cancer with a pharmaceutical composition of metformin hydrochloride and vitamin C

[0282] Thyroid cancer can be divided into: 1. Papillary adenocarcinoma, 2. Follicular adenocarcinoma, 3. Undifferentiated cancer, 4. Medullary cancer. Its clinical manifestations are a hard and uneven mass in the thyroid tissue, which gradually increases in size. When swallowing, the mass moves less up and down. If these two symptoms appear quickly in a short period of time, it is mostly undifferentiated cancer. In the late stage, it often compresses the laryngeal nerve, trachea, and esophagus, causing hoarseness, dyspnea or dysphagia. If the cervical sympathetic ganglion is compressed, it can cause constriction of the pupil on the same side. The patient may have small thyroid gland, drooping upper eye cavity, enophthalmos, and no sweating on the same side of the head and face. During the invasion period of the superficial branches of the cervical plexus, the patient may have pain in the ears, occipital bone, shoulders, etc. Local metastasis is often in the skull, with hard and fixed lymph nodes. Distant metastasis is more common in flat bones, such as the cervical bones, vertebrae, pelvis, and lungs. Some people's thyroid tumors are not obvious, but metastatic cancer in the neck and lung bones is a prominent symptom. Therefore, when there is metastatic cancer in the neck, lungs, and bones with unclear primary lesions, the thyroid gland should be carefully examined.

[0283] Zhang, female, 74 years old, from Suqian, Jiangsu Province. Interview and diagnosis: Around 2020, the patient began to feel uncomfortable in the neck, tired of breathing, unable to sleep, unable to eat, and thinner day by day. Current medical history: a thyroid lump was felt, and the right thyroid lymph node was enlarged. The lump was hard like a stone and could not be moved. It was higher than the skin, and the skin color did not change. The blood pressure was normal at 120 / 70.

[0284] In May 2020, I went to the hospital for examination. The ultrasound diagnosis content was: thyroid scan, a 0.78x0.67 x0.83cm solid nodule was seen in the shallow inner layer of the lower pole of the right lobe of the thyroid gland, with clear boundaries, irregular, extremely low echo, uneven internal echo, and point-like strong echoes. CDFI: the internal blood flow signal was not rich. The signal of the left lobe of the thyroid gland was uniform. There was no obvious enlargement and abnormal echo lymph node shadows in the submandibular gland, parotid gland, and the rest of the neck. Diagnosis result: solid nodule in the right lobe of the thyroid gland - considered malignant grade 5.

[0285] The biopsy and images showed papillary hyperplasia of thyroid cells, some of which were obviously abnormal. Diagnosis: papillary thyroid carcinoma. After further biopsy, the patient did not receive any treatment because he did not want surgery.

[0286] Then he started taking oral metformin hydrochloride and vitamin C three times a day, morning, noon, and evening after meals. The dosage was 0.25 grams of metformin hydrochloride each time plus 4 tablets of 0.1 grams of vitamin C each time. One course of treatment was 30 days of continuous use. After that, he took metformin hydrochloride and vitamin C for 7 days a month.

[0287] After 30 days of treatment, the enlarged thyroid nodules softened significantly, and the condition improved significantly after one course of treatment. No enlarged lymph nodes were found in both necks during follow-up visits. The patient was very worried about recurrence and is now continuing consolidation treatment. The patient is still alive and in good health.

[0288] (IV) Effects of the Invention

[0289] According to the present invention, an application of a broad-spectrum anti-infection and broad-spectrum anti-cancer technology route can be provided.

[0290] It has significant therapeutic effects in the treatment of new coronavirus infection, especially in June 2023, the application of the present invention to treat a 95-year-old female patient diagnosed with new coronavirus white lung, allowing her to fully recover, which is of great significance; the treatment of hepatitis B according to the present invention has also achieved good therapeutic effects; in the treatment of herpes zoster virus infection according to the present invention, obvious therapeutic effects of short time, quick effect, rapid pain relief and rapid scabbing have been achieved; the use of the present invention to treat Helicobacter pylori infection is generally effective and not prone to recurrence; at the same time, the present invention can also provide a possible medical solution for the treatment of amyotrophic lateral sclerosis (ALS, also called motor neuron disease); the use of the present invention to treat cancer has also achieved significant therapeutic effects.

[0291] Some drugs in the present invention, such as isosorbide and isomannide, are non-toxic and harmless. They can provide practical treatment options for groups with difficulty in taking medicine, such as pregnant women, infants, young children (less than 4 years old), and the elderly with liver and kidney diseases. BRIEF DESCRIPTION OF THE DRAWINGS

[0292] Attached Figure 1 : Molecular structure of morpholine biguanide;

[0293] Attached Figure 2 : Molecular structure of broad-spectrum anticancer drug AOH1996;

[0294] Attached Figure 3 : Piper longum amide molecular structure formula;

[0295] Attached Figure 4 : Artemisinin molecular structure;

[0296] Attached Figure 5 : Fenbendazole molecular structure formula;

[0297] Attached Figure 6 : Metformin hydrochloride molecular structure formula;

[0298] Attached Figure 7 : Arginine molecular structure formula;

[0299] Attached Figure 8 : Isosorbide molecular structure formula;

[0300] Attached Fig. 9 : Molecular structure of isomannide;

[0301] Attached Fig.10 : Molecular structure of vitamin C;

[0302] Attached Fig.11 : Molecular structure of vitamin B1;

[0303] Attached Fig.12 : Vitamin B6 includes three forms: pyridoxine, pyridoxal and pyridoxamine;

[0304] Attached Fig.13 : The molecular structure of vitamin E (α-tocopherol);

[0305] Attached Fig.14 : Glutathione molecular structure;

[0306] Attached Fig.15 : N-acetylcysteine ​​molecular structure;

[0307] Attached Fig.16 : Famotidine molecular structure;

[0308] Attached Fig.17 : Ranitidine molecular structure;

[0309] Attached Fig.18 : Molecular structure of cimetidine;

[0310] Attached Fig.19 : Lp lone pair electrons of guanidine;

[0311] Attached Fig. 20 : Lp lone pair electrons of guanidine are protonated;

[0312] Attached Fig.21 : Lp lone pair electrons of biguanide;

[0313] Attached Fig. 22 : Lp lone pair electron protonation of biguanide;

[0314] Attached Fig.23 : Isosorbide protonation;

[0315] Attached Fig.24 : Isomannol protonation;

[0316] Attached Fig.25 : Vitamin E (α-tocopherol) captures free radical reactions;

[0317] Attached Fig.26 :Molecular structure of acetaminophen

[0318] Attached Fig. 27 : Chest CT examination showed bilateral pneumonia, increased and blurred texture in both lungs, and diffusely distributed multiple large patchy blurred shadows in both lungs;

[0319] Attached Fig.28 : CT showed severe lung infection;

[0320] Attached Fig.29 : The condition is still getting worse, RR ≥ 37 times / min, blood oxygen saturation is low, once below 90, dropped to 88; attached Fig.30 : As of June 4, 2023, the patient's condition has improved significantly, with RR ≥ 34 times / min, and blood oxygen saturation returning to above 90, reaching 91;

[0321] Attached Fig.31 : The patient's condition improved significantly, with blood oxygen saturation reaching 92;

[0322] Attached Fig.32 : A reexamination of the lung CT showed that the infectious lesions in both lungs still existed, and the multiple patchy and blurred shadows in the left lung were still obvious;

[0323] Attached Fig.33 : The right lung gradually became clearer, the flake-like blurred shadows were significantly reduced, and the patient's symptoms were improving, indicating that the lung infection was alleviating.

[0324] Attached Fig.34 : RR ≥ 34 times / min, blood oxygen saturation is stable above 93 for a long time, and the patient is out of danger;

[0325] Attached Fig.35: The patient still had shortness of breath (RR reached 39 times / min), but the blood oxygen saturation remained stable above 96 for a long time;

[0326] Attached Fig.36 : A reexamination of the lung CT showed that the infectious lesions in both lungs still existed, and the multiple patchy and blurred shadows in the left lung were still obvious, but gradually became clearer;

[0327] Attached Fig.37 : The right lung is clearer than a few days ago, and the flake-like blurry shadows have been significantly reduced, and there is no longer a large blurry image. The patient's symptoms are significantly improved, indicating that the lung infection is continuing to ease;

[0328] Attached Fig.38 : The CT conclusion was that there were still multiple inflammations in both lungs, but the patient's symptoms were obviously improving. Most of the right lung was clear, and the infection shadow in the left lung was also obviously shrinking gradually, and the lung infection was alleviating.

[0329] Attached Fig.39 : The patient tested positive for the coronavirus antigen and was confirmed to be infected with the coronavirus;

[0330] Attached Fig.40 :The combination of metformin hydrochloride and vitamin C has achieved satisfactory results. Fig.41 : The test found that the hepatitis B surface antibody, hepatitis B core antibody and hepatitis B e antibody were positive, and it was still in the small three positive stage, indicating that it was still possible to have latent hepatitis B infection;

[0331] Attached Fig.42 : After taking metformin hydrochloride and vitamin C, it was found that except for the hepatitis B surface antibody which was still positive, the other indicators including hepatitis B surface antigen, hepatitis B e antigen, hepatitis B core antibody and hepatitis B e antibody were all negative, especially the hepatitis B core antibody and hepatitis B e antibody, which were originally positive, all turned negative. This shows that the patient has fully recovered and has developed immunity to hepatitis B.

[0332] Attached Fig.43 : Except for the hepatitis B surface antibody which is still strongly positive, all other indicators are negative, which once again shows that the patient has fully recovered and has become immune to hepatitis B;

[0333] Attached Fig.44 : Chest CT scan showed an increase in the shadow of the right hilum

[0334] Attached Fig.45 : Chest CT scan showed that the lesion area was basically absorbed.

[0335] The drawings described herein are used to provide a further understanding of the present invention, constitute a part of this application, and do not constitute an improper limitation of the present invention.

[0336] The present invention is described in detail above with reference to the accompanying drawings and specific embodiments, which are merely illustrative embodiments and descriptions of the present invention and are used to explain the present invention, but cannot be used as limitations of the present invention.

[0337] In summary, the discovery that protonated metformin hydrochloride and isosorbide, etc. can completely kill viruses and bacteria after protonation is the most important discovery and invention of this patent application; the discovery that protonated metformin hydrochloride and isosorbide, etc. can directly kill cancer cells after protonation is also the most important discovery and invention of this patent application. The discovery that protonated metformin hydrochloride and isosorbide, etc. can disassemble the abnormal folding of proteins after protonation is also the most important discovery and invention of this patent application. The broad-spectrum anti-infection and broad-spectrum anti-cancer composition of the present invention can also resist mycoplasma, chlamydia and toxoplasma infection.

[0338] The broad-spectrum anti-infection and broad-spectrum anti-cancer composition of the present invention can kill viruses, bacteria, and cancer cells while causing the proteins, nucleic acids, and other contents of the viruses, bacteria, and cancer cells to flow out, thereby stimulating the human body to produce immunity against these viruses, bacteria, and cancer cells. In other words, the present invention can help the human body rebuild its immunity.

[0339] The present invention will provide a new pharmaceutical composition and preparation method for treating bacterial infections such as Helicobacter pylori, drug-resistant conjugated bacilli, Legionella, Brucella, etc.; it can also provide a new broad-spectrum pharmaceutical composition and preparation method for preventing and treating viral infectious diseases such as coronavirus, hepatitis B virus, hepatitis C virus, herpes zoster virus, HIV, Zika virus, dengue virus, West Nile virus, Nipah virus, monkeypox virus, etc.; it will also provide a new broad-spectrum pharmaceutical composition and preparation method for preventing and treating mycoplasma, chlamydia, and toxoplasma infections; it can also provide a new broad-spectrum pharmaceutical composition and preparation method for targeted killing of cancer cells without affecting normal cell functions. The method of the present invention can also provide a new broad-spectrum pharmaceutical composition and preparation method for treating mycoplasma, chlamydia, and toxoplasma infections.

[0340] The present invention relates to multiple drugs such as metformin hydrochloride and isosorbide, which are "old drugs with new uses". Since the present invention discovers a new mechanism of broad-spectrum anti-infection and broad-spectrum anti-cancer, it is found that they have new uses in addition to their original pharmacological effects. Since they have been widely used in clinical practice, their safety, drug metabolism characteristics, and toxic and side effects have long been very clear. The present invention can quickly apply them to the clinical treatment of various new related diseases under the condition of ensuring their safety.

[0341] The present invention is a composition selected by the inventors after years of unremitting concentration and hard work from hundreds of natural and synthetic compounds through exploratory mechanism analysis and scientific experiments. The above-mentioned experiments are only exemplary embodiments of the present invention, but the protection scope of the present invention is not limited thereto. Any technician familiar with the technical field can easily think of adding or subtracting several chemical groups from the chemical structure of the above-mentioned compound monomers, changing, replacing, or deriving, and all other corresponding composition embodiments obtained thereby should fall within the protection scope of the present invention.

[0342] (VI) References

[0343] 【1】Laporte, M. et al. Airway proteases: an emerging drug target for influenza and other respiratory virus infections. Curr Opin Virol. 2017; 24:16-24.

[0344] 【2】AFA B, RT C, KSD, KD E, HHFG H, Antivirals for COVID-19: A critical review, Clinical Epidemiology and Global Health, Volume 9, January-March 2021, Pages 90-98

[0345] 【3】Hoffmann, M. et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2and is blocked by a clinically proven protease inhibitor. Cell. 2020; 181:271-80.

[0346] 【4】Chaudhuri, S. et al. Innovation and trends in the development and approval of antiviral medicines:1987-2017and beyond. Antiviral Res. 2018; 155:76-88.

[0347] 【5】Mercuro,N.J.et al.Risk of QT interval prolongation associated withuse of hydroxychloroquine with or without concomitant azithromycin amonghospitalized patients testing positive for coronavirus disease 2019(COVID-19).JAMACardiol.2019.

[0348] 【6】García-Serradilla,M.et al.Drug repurposing for new,efficient,broadspectrum antivirals.Virus Research.2019,264:22-31.

[0349] 【7】Vipul C.Chitalia,V.C.et al.A painful lesson from the COVID-19pandemic:the need for broad-spectrum,host-directed antivirals.J TranslMed.2020,18,390.

[0350] 【8】Monk,P.The Need—And Opportunity—To Develop Broad-SpectrumAntivirals.Pharmaceutical Online.03,01,2023.

[0351] 【9】Alimuddin Zumla,David S Hui,Esam I Azhar,Ziad A Memish,MarkusMaeurer.Reducing mortality from 2019-nCoV:host-directed therapies should bean optionThe LancetIn press,corrected proofAvailable online 5February2020.DOI:https: / / doi.org / 10.1016 / S014-6736(20)30305-6.

[0352]

[10] Fan Kuncheng, Shen Haifeng, Li Jun, Guo Shijian, Dai Jingui. Bactericidal composition containing zinc thiazole and morpholino hydrochloride, and its preparation and application. Application number CN201610445195.X. Application date 2016.06.20.

[0353] 0213.

[11] Bailey C J.Metformin: historical overview[J].Diabetologia, 2017,60(9):1566-1576.

[0354]

[12] Stanley Prusiner, Novel proteinaceous infectious particles causes crappie.Science,09Apr 1982, Vol216, issue4542

[0355] pp136-144.Dol10.1126 / science6801762

[0356]

[13] Stanley Prusiner, Molecular biology of prion diseases. Science, 14Jun 1991, Vol252, issue5012 pp1515-1522.Dol10.1126 / science1675487.

[0357]

[14] Liu Quanguo, Ma Guiping, Li Yanxin, Shi Xiju, Li Bingling, Si Peipei. A method for disinfecting prions. CN2011110339459. Application date: November 1, 2011.

[0358] 0214.

[15] Weiqi Hong, Min Wu, Xiaowei Wei, Pulmonary vascular system: Avulnerable target for COVID-19, MedComm 2021 / 12 / 01Review MedComm Volume2Issue4.doi:10.1002 / mco2.94.eCollection 2021Dec.

[0359]

[16] Hasan K.Siddiqi,Peter Libby,Paul M Ridker.COVID-19-A vasculardisease.Trends in Cardiovascular Medicine.Volume 31,Issue 1,January 2021,Pages 1-5.

[0360]

[17] Shi Yu,Xu Zheng,Bingjie Zhou,Juan Li,Mengdan Chen,Rong Deng,GaryWong,Dimitri Lavillette,Guangxun Meng,SARS-CoV-2spike engagement ofACE2primes S2’site cleavage and fusion initiation.Proceedings of the NationalAcademy of Sciences Jan 2022,119(1)e2111199119;DOI:10.1073 / pnas.2111199119.

[0361]

[18] Chung,Mina K.,Zidar,David A.,Bristow,Michael R.,Cameron,Scott J.,Chan,Timothy,Harding,Clifford V.,III,Kwon,Deborah H.,Singh,Tamanna,Tilton,John C.,Tsai,Emily J.,Tucker,Nathan R.,Barnard,John,Loscalzo,Joseph.COVID-19and Cardiovascular Disease From Bench to Bedside.《Circulation research:ajournal of the American Heart Association》128(8)2021,1214-1236.ISSN:0009-7330NSTL Me.

[0362]

[19] Sofie 1,Per 1 Amyloidogenesis of SARS-CoV-2 Spike Protein. J. Am. Chem. Soc. 2022, 144, 20, 8945 - 8950.

[0363]

[20] Mirren Charnley, Saba Islam, Guneet K. Bindra, Jeremy Engwirda, Julian Ratcliffe, Jiangtao Zhou, Raffaele Mezzenga, Mark D. Hulett, Kyunghoon Han, Joshua T. Berryman & Nicholas P. Reynolds Neurotoxic amyloidogenic peptides in the proteome of SARS-COV2: potential implications for neurological symptoms in COVID-19. Nature Communications volume 13, 3387 (2022).

[0364] https: / / doi.org / 10.1038 / s41467-022-30932-1.

[0365]

[21] Authors: George Tetz, Victor Tetz,SARS-CoV-2 Prion-Like Domains in Spike Proteins Enables Higher Affinity to ACE2,online published on 29 March 2020, preprints (www.preprints.org) DOI: 10.20944 / preprints202003.0422.v1

[0366]

[22] Wu Shang, Zhang Limin, Wang Weizhi. Screened α-Helix Peptide Inhibitor toward SARS-CoV 2 by Blocking a Prion-like Domain in the Receptor Binding Domain,《Analytical chemistry》,94(33) 2022, 11464 - 11469.

[0367]

[23] Shahzad,Shakeel,Willcox,Mark,Univ New South Wales Sydney,ThePossible Role of Prion-Like Viral Protein Domains on the Emergence of NovelViruses as SARS-CoV-2.Journal of Molecular Evolution 90(3 / 4)2022 / 08 / 01227-230.

[0368]

[24] Baslan T,Morris JP 4th,Zhao Z,et al.Ordered and deterministiccancer genome evolution after p53 loss.Nature.2022;608(7924):795-802.

[0369] doi:10.1038 / s41586-022-05082-5

[0370]

[25] Hui Jiang 1 2,Ya-Fang Mei SARS-CoV-2 Spike Impairs DNA DamageRepair and Inhibits V(D)J Recombination In Vitro Viruses2021 Oct 13;13(10):2056.

[0371]

[26] Gerstung M,Jolly C,Leshchiner I,et al.The evolutionary history of2,658 cancers.Nature.2020;578(7793):122-128.doi:10.1038 / s41586-019-1907-7

[0372]

[27] Kristófi R,Eriksson JW.Metformin as an anti-inflammatory agent:ashort review.J Endocrinol2021;251:R11-22.doi:10.1530 / JOE-21-0194pmid:http: / / www.ncbi.nlm.nih.gov / pubm ed / 34463292

[0373]

[28] Timour Baslan, John P. Morris, Zhen Zhao, Jose Reyes, Yu-Jui Ho, Kaloyan M. Tsanov, Jonathan Bermeo, Sha Tian, Sean Zhang, Gokce Askan, Aslihan Yavas, Nicolas Lecomte, Amanda Erakky, Anna, "Ordered and deterministic cancer genome evolution after p53 loss," Nature, August 2022, vol. 608(7924), pages 795 - 802.

[0374]

[29] Evans JMM, Donnelly LA, Emslie-Smith AM, et al. Metformin and reduced risk of cancer in diabetic patients[J]. BMJ (Clinical research ed.), 2005, 330(7503): 1304 - 1305.

[0375]

[30] Deng X - S, Wang S, Deng A, et al. Metformin targets STAT3 to inhibit cell growth and induce apoptosis in triple - negative breast cancers. Cell Cycle 2012; 11: 367 - 76. doi:10.4161 / cc.11.2.18813 pmid:http: / / www.ncbi.nlm.nih.gov / pubmed / 22189713

[0376]

[31] Chae YK, Arya A, Malecek M - K, et al. Repurposing metformin for cancer treatment: current clinical studies. Oncotarget 2016; 7: 40767 - 80. doi:10.18632 / oncotarget.8194 pmid:http: / / www.ncbi.nlm.nih.gov / pubmed / 27004404

[0377]

[32] Gulati S,Desai J,Palackdharry SM,et alPhase 1dose-finding studyof metformin in combination with concurrent cisplatin and radiotherapy inpatients with locally advanced head and neck squamous cell cancer.Cancer2020;126:354-62.doi:10.1002 / cncr.32539pmid:http: / / www.ncbi.nlm.nih.gov / pubmed / 31626727

[0378]

[33] Curry J,Johnson J,Tassone P,et al.Metformin effects on head andneck squamous carcinoma microenvironment:window of opportunitytrial.Laryngoscope 2017;127:1808-15.doi:10.1002 / lary.26489pmid:http: / / www.ncbi.nlm.nih.gov / pubme d / 28185288

[0379]

[34] Amin D,Richa T,Mollaee M,et al.Metformin effects on FOXP3+and CD8+T cell infiltrates of head and neck squamous cell carcinoma.Laryngoscope2020;130:E490-8.doi:10.1002 / lary.28336pmid:http: / / www.ncbi.nlm.nih.gov / pubmed / 31593308

[0380]

[35] Murad R.Mamedov,Shane Vedova,Jacob W.Freimer,Avinash Das Sahu,Amrita Ramesh,Maya M.Arce,Angelo D.Meringa,Mineto Ota,Peixin Amy Chen,Kristina Hanspers,Vinh Q.Nguyen,Kirsten A.Takeshima,Anne C.Rios,JonathanK.Pritchard,Jürgen Kuball,Zsolt Sebestyen,Erin J.Adams&AlexanderMarson.CRISPR screens decode cancer cell pathways that triggerγδT celldetection[J].Nature volume 621,2023(8):188-195.

[0381]

[36] He L,Zhu H-Y,Qin S-C,et al.Low natural killer(NK)cell counts inperipheral blood adversely affect clinical outcome of patients withfollicular lymphoma.Blood Cancer J 2016;6:e45.doi:10.1038 / bcj.2016.67pmid:http: / / www.ncbi.nlm.nih.gov / pubmed / 27518240

[0382]

[37] Besson L,Mery B,Morelle M,et al.Cutting edge:mTORC1 inhibition inmetastatic breast cancer patients negatively affects peripheral NK cellmaturation and number.J Immunol 2021;206:2265-70.doi:10.4049 / jimmunol.2001215pmid:http: / / www.ncbi.nlm.nih.gov / pubmed / 33931486

[0383]

[38] Sak A, Wurm R, Elo B, et al. Increased radiation-induced apoptosis and altered cell cycle progression of human lung cancer cell lines by antisense oligodeoxynucleotides targeting p53 and p21(WAF1 / CIP1)[J]. Cancer Gene Therapy, 2003, 10(12):926-934.

[0384]

[39] Scharping NE, Menk AV, Whetstone RD, et al. Efficacy of PD-1 blockade is potentiated by metformin-induced reduction of tumor hypoxia. Cancer Immunol Res 2017;5:9-16.doi:10.1158 / 2326-6066.CIR-16-0103 pmid:http: / / www.ncbi.nlm.nih.gov / pubmed / 27941003

[0385]

[40] Zhang H H, Guo X L. Combinational strategies of metformin and chemotherapy in cancers[J]. Cancer Chemotherapy and Pharmacology, 2016, 78(1):13-26.

[0386]

[41] Li M, Li X, Zhang H, et al. Molecular Mechanisms of Metformin for Diabetes and Cancer Treatment[J]. Frontiers in Physiology, 2018, 9:1039.

[0387]

[42] Ugwueze C V,Ogamba O J,Young E E,et al..Metformin:A PossibleOption in Cancer Chemotherapy[J].Analytical Cellular Pathology(Amsterdam),2020,2020:7180923.

[0388]

[43] Long Gu,Min Li,R Lingeman,Robert J.Hickey,Linda H.Malkas.AbstractC067:Mechanistic study of the superior anti-cancer properties of a first-in-class small molecule targeting PCNA.AACR-NCI-EORTC International Conferenceon Molecular Targets and Cancer Therapeutics;October 26-30,2019;Boston,MA.Conference Date 2019 / 12 / 01.

[0389]

[44] Long Gu 1,Min Li 2,Caroline M.Li 1,Pouya Haratipour 3,RobertLingeman 1,Jennifer Jossart 1,Margarita Gutova 4,Linda Flores 4,Caitlyn Hyde4,Nikola Haiqing Li 6,Vincent Chung 7,Hongzhi Li 8,Brett Lomenick 9,Daniel D.Von Hoff 10,Timothy W.Synold 11,Karen.S.Aboody 4,Yilun Liu 2,DavidHorne3,Robert J.Hickey 3…Linda H.Malkas 1 12.Small molecule targeting of transcription-replication conflict for selective chemotherapy.Cell ChemicalBiology.Available online 1 August 2023.https: / / www.sciencedirect.com / science / article / pii / S2451945623002210#abs0010

[0390]

[45] Hua Zichun, Zhang Peng, Huang Qilai, References Application number CN201310360539.3 Application date 20130819 for the use of piperidine in the preparation of tumor drug metastasis drugs.

[0391]

[46] Qian Ruisheng, Li Zhuliang, Yu Jianliang, Ma Daojun. Immune and antiviral effects of artemisinin[J]. Journal of Traditional Chinese Medicine, 1981, (06): 63-66.

[0392]

[47] Wang Zijian, Li Yirui, Wu Wencheng, et al. Research progress on the pharmacological effects of artemisinin and its derivatives[J]. Guangxi Medical Journal, 2018, 40(10): 1222-1224.

[0393]

[48] SILVIA SLEZAKOVA and JANA RUDA-KUCEROVA, Anticancer Activity of Artemisinin and its Derivatives, ANTICANCER RESEARCH2017,37:5995-6003.

[0394]

[49] Guangshun Sun, Siqi Zhao, Zhongguo Fan, Yuliang Wang, Hanyuan Liu, Hengsong Cao, Guoqiang Sun, Tian Huang, Hongzhou Cai, Hong Pan, Dawei Rong, YunGao, Weiwei Tang published a paper titled "CHSY1 promotes CD8 T cell exhaustion throughactivation of succinate metabolism pathway leading to colorectal cancer livermetastasis based on CRISPR / Cas9 screening+.《Journal of Experimental&ClinicalCancer Research》, 25.09.2023.Articale number248:399.

[0395]

[50] Zhou Zhongyong, Zhu Xueyong, Chen Yuxiu. Experiment on the effect of fenbendazole on expelling parasitic helminths from wild animals. Chinese Journal of Veterinary Parasitic Diseases, No. 2, 1997.

[0396]

[51] DING Yan. Determination of fenbendazole and praziquantel in compound fenbendazole tablets by HPLC. 2016.

[52] QIWEN DUAN, YANFENG LIU, SARA ROCKWELL, Fenbendazole as a Potential Anticancer Drug[J]. Anticancer Research: International Journal of Cancer Research and Treatment. 2013 Vol 2.

[0397]

[53] Chen Zhimin, Rethinking Mycoplasma pneumonia: From pathogenesis to clinical treatment, Chinese Journal of Practical Pediatrics, 2012, DOI: Vol. 27, No. 4, April 2012, pp. 253-257.

[0398]

[54] Qiao Hongmei, Lu Jirong, Liu Li, Cheng Huanji, Huang Ying. Clinical observation and follow-up study on chronic cough in children caused by Mycoplasma pneumoniae and Chlamydia pneumoniae infection. Journal of Clinical Pediatrics, Vol. 25, No. 6, July 2007, 451-452.

[0399]

[55] Xu Weihua, reviewed by Shen Huahao, Respiratory Tract Infection and Asthma, Foreign Medical Journal of Respiratory System, Vol. 24, No. 6, December 2004, pp. 381-387.

[0400]

[56] Zhang Juzuo, Chen Hanzhong, Xu Junfei, Advances in Veterinary Medicine, No. 179, 2008, 29(7):101-104.

[0401]

[57] Treatment of prion protein-related diseases CN200880110132.2 John Fergus M. Ivan, David Kallis-Hill, Martin Lindell Windsor 20080808.

[0402]

[58] Liao Qinping, Zhang Yan, Xie Yaya, Hu Qian, Yu Li, Chen Rui. Use of metformin, application number CN201310069025.2, application date 20130305.

[0403]

[59] Veronica Finisguerra, Tereza Dvorakova, Matteo Formenti, Pierre VanMeerbeeck, Lionel Mignion, Bernard Gallez, and Benoit J Van den Eynde. Metforminimproves cancer immunotherapy by directly rescuing tumor-infiltrating CD8 Tlymphocytes from hypoxia-induced immunosuppressionJ Immunother Cancer.2023;11(5):e005719.10.1136 / jitc-2022-005719PMC10163559PMID:37147018.

[0404]

[60] A.GOBBI,G.FRENKING,ChemInform Abstract: Y-Conjugated Compounds: The Equilibrium Geometries and Electronic Structures of Guanidine, Guanidinium Cation, Urea, and 1,1-Diaminoethylene,, Physical Organic Chemistry, First published: July 20, 1993 Volume 24, Issue 29 July 20, 1993 https: / / doi.org / 10.1002 / chin.199329042

[0405]

[61] Christine Trumm, Simone Stang, Benjamin Eberle, Elisabeth Kaifer, Norbert Wagner, Johannes Beck, Thomas Bredow, Nikolaus Michael Zharnikov, Olaf Hübner, Himmel Highly Oxidized Semiconducting Coordination Polymers - Coupled Oxidation and Coordination of Guanidine Electron Donors Volume 2012, Issue 19 July 2012 Pages 3156 - 3167 DOI:10.1002 / ejic.201101325.

[0406]

[62] ATMM Chowdhury,A Kamal,MKU Abbas,MR Karim,MA Ali,S Talukder,HMH Mehedi,H Hassan,Role of H2 receptor blocker famotidine over the clinical recovery of COVID-19 patients: A randomized controlled trial 《世界临床病例杂志》2022第010卷第023期8170 - 8185 ISSN:2307 - 8960

[0407]

[63] DC Garg, DJ Wiedler, N Baltodano, FN Eshelman Pharmacokinetics ofranitidine, a new histamine H2-receptor blocker Clinical Pharmacology&Therapeutics January 1981, Clinical Pharmacology&Therapeutics 29(2).1981 / 01 / 01

[0408]

[64] M Hermansson, CS Von Holstein, T Zilling, Peptic ulcer perforationbefore and after the introduction of H2-receptor blockers and proton pumpinhibitors.Scandinavian Journal of Gastroenterology.1997 Jun;32(6):523-9.doi:10.3109 / 00365529709025093.

[0409]

[65] Liu Bin, Yang Jinyue, Tian Xiaocong, Ma Haifeng, Gao Wei. The history of vitamin C: from conquering the "sea monster" to the Nobel Prize[J]. University Chemistry, 2019, 34(08): 96-101.

[0410]

[66] Wang Xiangpu, Wang Yingtong, Li Juesheng, eds. Dictionary of Hygiene. Qingdao: Qingdao Publishing House. 2000. p. 470.

[0411]

[67] Shen Xinfu et al. (eds.). Practical Chemistry Dictionary for Middle School Teachers. Beijing: Beijing Science and Technology Press. 2002. pp. 300-301.

[0412]

[68] Wu Meixiang and Wu Boyan (eds.). Practical Handbook of Occupational Disease Prevention and Control. Tianjin. Tianjin Science and Technology Press. 2007.81.

[0413]

[69] Hu Li, Current status and application prospects of natural vitamin E production, Pharmaceutical Chemistry, Vol. 7, 2004. 24-27.

[70] Cong Fengsong. Magical small molecule active peptides: Shanghai Jiaotong University Press, 2015: 18.

[0414]

[71] Li Yimin, Zhao Shuyi. Research progress of N-acetylcysteine. Tianjin Pharmacy, Vol. 015, No. 002, 2003, pp. 50-53

[0415]

[72] Reference: Study on the surface charge characteristics of cancer cells and their recognition mechanism by granulocytes, a general project funded by Tongji University and headed by Cui Zheng. National Natural Science Foundation of China, cited on 2021-08-02.

[0416]

[73] Wang Sheng, Lu Yin, Qian Wenhui, Zhao Yang, Wang Yingyu, Zheng Shizhong, Wang Aiyun. Cellular charge: a potential important target for anti-tumor research. Chinese Pharmacological Bulletin, 2010 Dec 26(12): 1541-4.

[0417]

[74] Chen Bingdi, Liu Zhongmin, Le Wenjun, Cui Zheng, Chen Jingyao. A method for assessing tumor malignancy based on the surface charge intensity of cancer cells. Application number: 202111021345.1. Application date: 2021.09.01.

[0418]

[75] Dowling RJO, Zakikhani M, Fantus IG, et al. Metformin inhibitsmammalian target of rapamycin-dependent translation initiation in breastcancer cells[J]. Cancer Research, 2007, 67(22):10804-10812.

[0419]

[76] Foretz M, Guigas B, Bertrand L, et al. Metformin: from mechanisms of action to therapies[J]. Cell Metabolism, 2014, 20(6):953-966.

[0420]

[77] Nishant Singh and Anuradha Bharara Singh S2 Subunit of SARS-nCoV-2 Interacts with Tumor Suppressor Protein p53 and BRCA:an In Silico Study2020 Oct;13(10):100814.NIH(National Institutes of Health)NLM(national library of medicine)Published online 2020 Jun 30.doi:10.1016 / j.tranon.2020.100814PMCID:PMC7324311PMID:32619819

[0421]

[78] Morale MG, Tamura RE, Rubio IG S. Metformin and Cancer Hallmarks: Molecular Mechanisms in Thyroid, Prostate and Head and Neck Cancer Models[J]. Biomolecules, 2022, 12(3):357.

[0422]

[79] Braun, E. et al. Furin-mediated protein processing in infectious diseases and cancer. Clin Transl Immunology. 2019; 8: e1073.

[0423]

[80] Huang Siyang, Li Ling, Gong Jingzhi, Pan Ming, Jin Qiwang, Bai Shaoyuan, Fan Yimin, Mineralized Toxoplasma gondii tachyzoite particles and preparation method and application thereof, application number CN202211373635.7, application date: 2022-11-03.

Claims

1. A pharmaceutical composition with broad-spectrum anti-infection and anti-cancer effects, the mechanism of which comprises two parts A and B as main components, A can be metformin hydrochloride, arginine, isosorbide, isomannide, cimetidine, ranitidine, famotidine, or a salt or derivative compound and a heterocomplex of metformin hydrochloride, arginine, isosorbide, isomannide, cimetidine, ranitidine, famotidine, such as a salt, amidated, esterified compound of arginine, etc. , monoesters or disesters of isosorbide and isomannide, salts or derivatives of isosorbide, isomannide, cimetidine, ranitidine, famotidine, and heterocompounds, such as salts, esterification, and ether compounds of isosorbide and isomannide, so that the molecules can always maintain the active molecular characteristics of functional groups such as guanidine, thiazolyl, imidazole, hydroxyl, imine, or ether bonds, so that they can always act as protonated compounds. B can be vitamin C, vitamin B1, vitamin B6, vitamin E, glutathione, N-acetylcysteine, etc., which can act as hydrogen donors and protonation donors to help A protonate. A or its salt or its derivative compounds and heterocomplexes can be formed alone or in combination with B or B's salt or its derivative compounds and heterocomplexes alone or in combination to form an effective composition, and the composition ratio can meet the molar ratio requirements, or the molar ratio of A and B can be determined separately to form a broad-spectrum anti-infection and broad-spectrum anti-cancer pharmaceutical composition, animal feed, veterinary medicine, food, beverage, health care product, compound preparation, etc. based on this composition.

2. According to claim 1, A and B form an effective composition, and the composition ratio can meet the molar ratio requirements, or the molar ratio of the protonated donors of A and B can be different, to form a broad-spectrum anti-infection and broad-spectrum anti-cancer drug combination, and the animal feed, veterinary drugs, food, beverages, health products, compound preparations, etc. of this composition are used as a broad-spectrum anti-bacterial infection composition and for the preparation of drugs for preventing and treating bacterial infections such as Helicobacter pylori, drug-resistant conjugated bacilli, Legionella, Brucella, etc.

3. According to claim 1, A and B form an effective composition, and the composition ratio can meet the molar ratio requirements, or the molar ratio of the protonated donors of A and B can be different, to form a broad-spectrum anti-infection and broad-spectrum anti-cancer drug combination, and the animal feed, veterinary drugs, food, beverages, health products, compound preparations, etc. of this composition are used as a broad-spectrum antiviral infection composition and for the preparation of drugs for preventing and treating viral infections such as coronavirus, hepatitis B virus, hepatitis C virus, herpes zoster virus, HIV, Zika virus, dengue virus, West Nile virus, Nipah virus, monkeypox virus, etc.

4. According to claim 1, A and B form an effective composition, and the composition ratio can meet the molar ratio requirements, or the molar ratio of the protonated donors of A and B can be different, to form a broad-spectrum anti-infection and broad-spectrum anti-cancer drug combination, and the animal feed, veterinary drugs, food, beverages, health products, compound preparations, etc. of this composition are used as a broad-spectrum anti-cancer composition and for the preparation of drugs for preventing and treating various solid tumors and non-solid tumor cancer diseases, etc.

5. According to claim 1, A and B form an effective composition, and the composition ratio can meet the molar ratio requirements, or the molar ratio of the protonated donors of A and B can be different, to form a broad-spectrum anti-infection and broad-spectrum anti-cancer pharmaceutical composition, and the composition can be used in animal feed, veterinary drugs, food, beverages, health products, compound preparations, etc. as a broad-spectrum anti-cancer composition and in the preparation of drugs for preventing and treating various nodules, etc.

6. According to claim 1, A and B form an effective composition, and the composition ratio can meet the molar ratio requirements, or the molar ratio of the protonated donors of A and B can be different, to form a broad-spectrum anti-infection and broad-spectrum anti-cancer pharmaceutical composition, and the animal feed, veterinary drugs, food, beverages, health products, compound preparations, etc. of this composition can be used as a broad-spectrum anti-cancer composition and for the preparation of drugs for preventing and treating various intestinal polyps, etc.

7. According to claim 1, A and B form an effective composition, and the composition ratio can meet the molar ratio requirements, or the molar ratio of the protonated donors of A and B can be different, to form a broad-spectrum anti-infection and broad-spectrum anti-cancer drug combination, and the animal feed, veterinary drugs, food, beverages, health products, compound preparations, etc. of this composition are used as a broad-spectrum anti-prion infection composition and for the preparation of drugs for preventing and treating Alzheimer's disease, Parkinson's syndrome, amyotrophic lateral sclerosis (ALS, also called motor neuron disease), mad cow disease, etc.

8. According to claim 1, A and B form an effective composition, and its composition ratio can meet the molar ratio requirement, or the molar ratio of A and B protonated donors can account for a certain proportion, forming a broad-spectrum anti-infection and broad-spectrum anti-cancer drug combination, for the animal feed, veterinary drugs, food, beverages, health products, compound preparations, etc. composed of this composition, as a broad-spectrum antiviral infection composition, for the preparation of drugs for preventing and treating feline infectious peritonitis caused by animal feline coronavirus infection, etc.

9. According to claim 1, A and B form an effective composition, and the composition ratio can meet the molar ratio requirements, or the molar ratio of the protonated donors of A and B can be different, to form a broad-spectrum anti-infective and broad-spectrum anti-cancer drug combination, and the animal feed, veterinary drugs, food, beverages, health products, compound preparations, etc. of this composition are used as a broad-spectrum anti-infective composition and in the preparation of drugs for preventing and treating mycoplasma and chlamydia infections, etc.

10. According to claim 1, A and B form an effective composition, and the composition ratio can meet the molar ratio requirements, or the molar ratio of the protonated donors of A and B can be different, to form a broad-spectrum anti-infective and broad-spectrum anti-cancer drug combination, and the animal feed, veterinary drugs, food, beverages, health products, compound preparations, etc. of this composition are used as a broad-spectrum anti-infective composition and in the preparation of drugs for preventing and treating Toxoplasma infection, etc.

11. According to claim 1, since the present invention belongs to the new use of old drugs, the two types of drugs A and B can also be used separately, but their respective half-lives overlap and cross in the body, and can also play a synergistic role in broad-spectrum anti-infection and broad-spectrum anti-cancer, that is, they are used as a combination to prepare drugs for preventing and treating broad-spectrum infections or for broad-spectrum anti-cancer, etc.

12. According to claims 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, it is composed of animal feed, veterinary drugs, food, beverages, nasal sprays, throat sprays, mouth rinses, eye drops, or ear drops, buccal dosage forms, injections and or freeze-dried powders, external dosage forms such as skin mucosal patches or smears, oral dosage forms, compound preparations, etc.

Images