53 results about "Lipotropic" patented technology

The invention belongs to the technical field of nuclear medicine molecular diagnosis and treatment, and discloses a modified CAIX targeting cyclic peptide, a nuclide marker and application of the modified CAIX targeting cyclic peptide in tumor diagnosis and treatment. According to the CAIX targeted cyclic peptide, a rigid bifunctional chelating agent RESCA is introduced to replace a traditional chelating agent, and a sulfonated or alkylated amino acid connector is combined, so that the enzymolysis resistance and in-vivo stability of the probe are remarkably improved. By optimizing the structure of the connector, the lipophilicity is reduced, liver and gall metabolism and non-specific uptake are reduced, and the high uptake rate of tumor target tissues is maintained. The therapeutic nuclide marker of the cyclopeptide can be used for intratumoral irradiation therapy using DOTA or NOTA in combination with an alkylated amino acid linker or an albumin ligand. Experiments show that the marker has high radiochemical purity, excellent pharmacokinetic characteristics and low kidney retention, and is suitable for precise diagnosis and targeted therapy of CAIX high expression tumors such as kidney cancer, colorectal cancer and brain glioma.

Provided is a dual-target nucleic acid molecule for inhibiting the expression of the vegfa gene and ang-2 gene. A linker contains 2-10 nucleotides or abasic nucleotides, and is used for linking two independent oligonucleotides. One or more nucleotides or abasic nucleotides in the linker contain a lipophilic moiety, and the lipophilic moiety is a C12-26 saturated or unsaturated hydrocarbon chain. Compared to a situation where a specific lipophilic modification is located inside the two linked moieties of a dual-nucleic acid molecule structure, the nucleic acid molecule exhibits better efficacy and a longer-lasting therapeutic effect when the specific lipophilic modification is located on the linker.

Preparation of cannabinoid formulations containing: Δ9-tetrahydrocannabinol (Δ9-THC), Δ8-tetrahydrocannabinol (Δ8-THC), Δ9-tetrahydrocannabinolic acid (THCa), cannabidiol (CBD), cannabidiolic acid (CBDa), cannabigero (CBG), cannabichromene (CBC) and cannabinol (CBN), either alone or in combinations henceforth known as cannabis, have been created using an emulsification process to encapsulate cannabinoids. The aqueous-based method involves micellular encapsulation of cannabinoids, a method that has been used to increase the bioavailability of poorly permeable, lipophilic drugs. The present invention demonstrates the viability of transdermal delivery with gels and patches for consistent and sustained cannabinoid dosing.

The invention relates to application of a topoisomerase inhibitor and a conjugate thereof. Specifically, the inventor provides a class of camptothecin derivatives, linker conjugates and antibody-drug conjugates with novel structures, and the camptothecin derivatives, linker conjugates and antibody-drug conjugates have excellent anti-tumor activity and good lipophilicity. In-vitro and in-vivo experiments show that the drug conjugate containing the camptothecin derivative disclosed by the invention has an improved anti-tumor curative effect and high safety, and has an application prospect in the field of cancer treatment.

The invention relates to the technical field of cytobiology and biomedicine detection, and discloses a time sequence fluorescence tracing system based on a coupling detection lipid probe. Comprising an imaging detection module which is used for adding FM lipophilic styrene fluorescent dye in a culture environment, forming a membrane probe to observe the morphological change of a membrane and detect the formation of vesicles, and completing the complete time sequence tracing of the cell endocytosis process by adopting a content dyeing method; the deep learning module is used for carrying out deep learning on the obtained time sequence image, establishing a living cell imaging screening and image analysis system, and identifying protein molecules related to the target external vesicles; carrying out image description on the generation, transportation and fusion processes of the vesicles generated by the proteins in different stages before fusion of the outer vesicles and the cell membranes and after fusion and shearing; and the knock-down operation module is used for exploring the generation mode of the vesicle contents in the early endosome in combination with knockout and knock-down operations of the specific drug compound.

Double-stranded ribonucleic acid (dsRNAi) agents that target exon 1 of the huntingtin (HTT) gene are provided.SOLUTION: A double-stranded ribonucleic acid (dsRNA) agent for inhibiting the expression of huntingtin (HTT), the agent comprising a sense strand and an antisense strand forming a double-stranded region, wherein the sense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from a certain specific nucleotide sequence, and the antisense strand comprises at least 15 contiguous nucleotides differing by no more than 3 nucleotides from another certain specific nucleotide sequence, provided are dsRNA agents wherein one or more lipophilic moieties are conjugated to one or more internal positions on at least one of the sense or antisense strands.SELECTED DRAWING: None

The present application provides an oligonucleotide conjugate and a pharmaceutical composition comprising the oligonucleotide conjugate. The oligonucleotide conjugate comprises a functional double-stranded oligonucleotide, a lipophilic moiety, and a peptide chain, wherein the functional double-stranded oligonucleotide, the lipophilic moiety, and the peptide chain are connected by means of linkers. The oligonucleotide conjugate and the pharmaceutical composition provided in the present application can effectively regulate the expression level of a target gene in vivo or in vitro, and have excellent tissue specificity. Therefore, the oligonucleotide conjugate and the pharmaceutical composition can effectively treat and / or prevent disease symptoms related to the level of mRNA expressed by the target gene. The present application holds promise.

The present disclosure provides a double-stranded siRNA with lipophilic modification. The modified siRNA molecules exhibit excellent in vivo distribution and delivery efficiency via intrathecal injection, intradermal injection, or other administration routes. The molecules effectively knock down target gene expression while maintaining good tolerability and safety. The present disclosure further provides a preparation method of siRNA with lipophilical modification, a pharmaceutical composition, and application of the same in the preparation of a medicament for treating a TNF-α-mediated disease or disorder.

One aspect of the present invention relates to a double-stranded RNA (dsRNA) agent for modulating the expression of a target gene in the central nervous system (CNS), comprising: an antisense strand complementary to the target gene in the CNS; a sense strand complementary to the antisense strand; and one or more saturated or unsaturated C RNAs conjugated onto at least one strand via a linker or carrier as appropriate. 22 The present invention relates to a dsRNA agent comprising one or more lipophilic moieties containing a hydrocarbon chain. Another aspect of the present invention relates to a pharmaceutical composition comprising a dsRNA agent. Another aspect of the present invention relates to a method for modulating the expression of a target gene in CNS cell genes and a method for treating or preventing CNS damage in a subject, comprising administering a therapeutically effective amount of a dsRNA agent to cells or a subject.

This invention provides RNAi agents, such as dsRNA agents, that target the G protein-coupled receptor 75 (GPR75) gene. It also provides methods for using such RNAi agents to inhibit the expression of the GPR75 gene in a subject, and methods for treating or preventing GPR75-related diseases such as weight disorders, e.g., obesity. [Solution] A double-stranded ribonucleic acid (dsRNA) agent for inhibiting the expression of the GPR75 gene in cells is provided, comprising a sense strand and an antisense strand that form a double-stranded region, wherein the antisense strand comprises a region complementary to a portion of the mRNA encoding the GPR75 gene, each strand is independently 14 to 30 nucleotides long, and the sense strand or antisense strand is conjugated to one or more lipophilic portions.

The invention provides novel compounds of formula (I), stereoisomers and pharmaceutically acceptable salts thereof: (wherein: Q is a lipophilic, zinc chelating moiety which is selective for Zn2+ ions; L1 is a covalent bond or a C1-6 alkylene chain in which one or more -CH2- groups of the alkylene chain are optionally replaced by a group independently selected from -CO- and -NR4- (where R4 is H or C1-3 alkyl); Y is selected from the following groups: (II) and (III) (where each R5 is independently H or C1-3 alkyl; and R6 is H or C1-3 alkyl); L2 is a covalent bond or a C1-6 alkylene chain in which one or more -CH2- groups of the alkylene chain are optionally replaced by a group independently selected from -CO- and -NR7- (where R7 is H or C1-3 alkyl); R is -OH, -O-C1-6 alkyl, -O-(CH2)p-O-CO-C1-6 alkyl (where p is an integer of 1 or 2) or -O-CH(CH3)-O- CO-C1-6 alkyl; each R1 is independently selected from halogen and C1-3 alkyl; each R2 is independently selected from halogen and C1-3 alkyl; R3 is H or C1-3 alkyl; n is an integer of 0 or 1; and m is an integer of 0 or 1). The compounds according to the invention are selective zinc chelators that find use as adjuvants in the treatment of bacterial infections and / or bacterial biofilms that harbour such infections. For use in such treatment, the compounds are used in combination with an antibacterial agent, for example a β-lactam antibiotic. The invention further provides a triple combination therapy for use in the treatment of bacterial infections and / or bacterial biofilms which comprises co-administration of the compounds to a subject in combination with a β-lactam antibiotic and a serine β-lactamase inhibitor.

The invention discloses a lipophilic modified nucleic acid medicine composition and application thereof, the lipophilic modification is saturated or unsaturated C4-C30 alkyl, the composition comprises an absorption enhancer, and the method is that the lipophilic modified nucleic acid medicine is delivered to the brain through the nasal mucosa. Nucleic acid drugs are transmitted into the olfactory bulb region through a neural pathway, namely, cross-olfactory mucosa, bypass BBB and directly enter the brain, the drug concentration content of the olfactory bulb is far higher than that of other tissues of the brain, and the tissues except the olfactory bulb are uniformly distributed, so that the olfactory bulb can be used as a drug reservoir and gradually and slowly spread to the other tissues of the brain; the long-time drug effect can be maintained by one-time drug administration, so that the drug administration frequency can be reduced. Compared with intrathecal injection, by adopting the composition disclosed by the invention for nasal administration and using 1 / 2 of intrathecal administration dosage, the same intrathecal steady-state distribution as intrathecal distribution can be achieved, so that the method disclosed by the invention is safer, noninvasive and efficient.

This invention discloses a lipopeptide HIV membrane fusion inhibitor and its pharmaceutical use. The lipopeptide of this invention is of formula I: X1-EMTWEEWEK KVEELEKKIEELLK-X2-X3-X4-X5; or formula II: X1-ELTWEEWEKKVEELEKKIEELLK-X6-X7-X4-X5; wherein, X1 is an amino-terminal protecting group; X2 is a polypeptide sequence (EAAAK)n, A[(EAAAK)n]A, or (EP)n, where n represents the number of repetitions; X3 is Lys, Cys, Dap, Orn, Dab, Dah, or absent; X4 is a lipophilic compound group used to modify the C-terminus; X5 is a carboxyl-terminal protecting group; X6 is a polypeptide sequence KAEEQQKKNE; and X7 is Lys, Cys, Dap, Orn, Dab, or Dah. The lipopeptide of this invention has higher antiviral activity.

The present disclosure relates to oligonucleotides comprising lipophilic monomers and their use in non-hepatic delivery. Specifically, the present disclosure relates to an oligonucleotide comprising an antisense strand complementary to a target mRNA, a sense strand complementary to the antisense strand, and one or more nucleotides represented by Formula (I-1) or (I-2). The disclosure also relates to a pharmaceutical composition comprising the oligonucleotide, and a medical use of the oligonucleotide and / or the pharmaceutical composition.

Lanthanide complexing molecules having the following structure:wherein: R1, R2, R4, and R5 are independently selected from hydrogen atom, alkyl groups containing 1-3 carbon atoms, and hydrophilic groups containing at least one oxygen atom; R3 and R6 are independently selected from hydrogen atom, alkyl groups containing 1-3 carbon atoms, and hydrophilic groups containing at least one oxygen atom; and Ra and Rb are independently selected from hydrogen atom, methyl group, halogen atoms, and hydrophilic groups containing at least one oxygen atom; wherein at least two of R1, R2, R3, R4, R5, R6, Ra, and Rb are said hydrophilic groups. Also described is a method of separating adjacent lanthanides by use of a two-phase extractant system that includes (i) an acidic aqueous solution containing the lanthanide complexing molecule (1) along with a mixture of at least two lanthanides, and (ii) an aqueous-insoluble hydrophobic solution containing a lipophilic lanthanide extractant compound.

The invention discloses an orange fluorescent silicon nanodot, a preparation method thereof and an application of the orange fluorescent silicon nanodot in mitochondrial imaging in living cells, the method comprises the following steps: S1, dissolving tetramethyl rhodamine methyl ester in ultrapure water, then adding N-(2-aminoethyl)-3-aminopropyltrimethoxysilane, uniformly stirring, and carrying out hydrothermal reaction on the obtained mixture; and S2, cooling after the reaction is finished, purifying the product by using a chromatographic column, eluting by using an eluent, collecting the eluent, and drying to obtain the orange fluorescent silicon nanodot. The silicon nanodot provided by the invention has the advantages of good light stability, high quantum yield and the like, and can be successfully applied to positioning imaging of mitochondria in living cells; compared with common blue-green fluorescence, orange fluorescence has better tissue penetrating ability and background interference resistance; the O-SiNDs prepared by the invention also has the property similar to that of lipophilic cations, and can realize high-specificity targeted marking on mitochondria of living cells.

Preparation of cannabinoid formulations containing: Δ9-tetrahydrocannabinol (Δ9-THC), Δ8-tetrahydrocannabinol (Δ8-THC), Δ9-tetrahydrocannabinolic acid (THCa), cannabidiol (CBD), cannabidiolic acid (CBDa), cannabigerol (CBG), cannabichromene (CBC) and cannabinol (CBN), either alone or in combinations henceforth known as cannabis, have been created using an emulsification process to encapsulate cannabinoids. The aqueous-based method involves micellular encapsulation of cannabinoids, a method that has been used to increase the bioavailability of poorly permeable, lipophilic drugs. The present invention demonstrates the viability of transdermal delivery with gels and patches for consistent and sustained cannabinoid dosing.

The invention relates to the field of pharmaceutical preparations and pharmaceutical chemistry, belongs to the technical field of oral delivery of antitumor drugs, and particularly relates to an abiraterone lipophilic prodrug and application thereof. The prodrug meets the following general formula: AB-O-C (= O)-(CH2) m-S-S-(CH2) m-C (= O)-O-R, the prodrug significantly improves the fat solubility and intestinal absorption capacity of abiraterone, can be absorbed through a chylomicron-mediated lymph transport pathway, and releases a parent drug in a tumor cell high-reducibility environment. The SNEDDS preparation containing the prodrug can form a particle size of 1t in vivo; the O / W type nano emulsion droplet with the size of 100 nm can significantly improve the oral bioavailability of abiraterone and inhibit the growth of prostatic cancer tumors, and has a good application prospect.

The invention provides a novel amino acid cationic lipid, the structure is shown as a general formula (3-17), and the definition of each symbol is consistent with that described in the specification. The amino acid cationic lipid is a pharmaceutically acceptable, biodegradable or high-biocompatibility lipid, and has the advantages of low toxicity, low immunogenicity and high biocompatibility. The amino acid or the amino acid derivative used in the preparation process is simple and easy to obtain, can be naturally obtained or simply synthesized, and has the advantages of simplicity, convenience, safety and production cost saving. Degradable groups can further be contained between amino acid residues and lipophilic tail chains of the novel amino acid cationic lipid, due to existence of the degradable groups, lipid nanoparticles LNP prepared from the novel amino acid cationic lipid can be degraded in vivo in good time, and the problems that in the prior art, LNP prepared from lipid which cannot be degraded can be stored in vivo, the endosome environment is acidified, and the lipid nanoparticles LNP cannot be degraded in vivo are solved. Endosome escape of drug molecules (such as nucleic acid) is blocked, and the problem that drugs delivered into cells cannot play a role is solved.

Described are techniques, systems, and methods include those employing pneumatic, pressure assisted, extrusion-based 3D printing and emulsion evaporation, emulsion diffusion, nanoprecipitation, desolvation, gelation, spray-based atomization, etc. for fabricating loaded microparticles or nanoparticles that encapsulate an active pharmaceutical ingredient or live cells into a biocompatible polymer or pharmaceutical excipients. The techniques provide for encapsulation of a variety of substances including proteins, plasmid DNA, lipophilic pharmaceutical compositions, hydrophilic pharmaceutical compositions, live cells, and / or cellular components into polymeric microparticles or nanoparticles. The particles loaded with active pharmaceutical ingredients can be used for the treatment of different diseases or conditions. The particles loaded with live cells can be used for disease treatment, but can also be used for securely storing the live cells in a stable condition for transport and later use in inoculating fermentation systems, for example, to generate recombinant proteins.

The application discloses a two-photon fluorescent probe and uses the same for tumor microenvironment monitoring. The application opens the two-photon fluorescent characteristics of the material by responding to the overexpression of SO2 and H2O2 at the tumor site in stages, monitors and indicates the changes of cell oxidative stress and homeostasis balance, and is further used for early diagnosis of diseases caused by internal environment homeostasis imbalance. The application regulates the cancer cell uptake capacity of the molecule by introducing suitable lipophilic and hydrophilic groups, increases the recognition site of biological thiols by introducing conjugated olefin bonds, and further realizes the step-by-step recognition of endogenous signal molecules by using the easiness of substitution reaction, enhances the fidelity of the signal, and is expected to realize the in-situ activated two-photon fluorescence, early and accurate diagnosis of a series of diseases such as cardiovascular diseases, Alzheimer's disease and the like induced by internal environment homeostasis imbalance.

The present invention provides lipid nanoparticles that encapsulate nucleic acid and have at least 30mol% of neutral lipid, sterol or its derivative, and targeting moiety fixed to lipid layer via lipophilic moiety.Furthermore, the method of using lipid nanoparticles for in vivo targeted delivery is also provided.Such lipid nanoparticles can show significantly improved delivery and targeting to extrahepatic tissues and / or organs.

The invention provides a novel amino acid cationic lipid, the structure is shown as a general formula (3-9), and the definition of each symbol is consistent with that described in the specification. The amino acid cationic lipid is a pharmaceutically acceptable, biodegradable or high-biocompatibility lipid, and has the advantages of low toxicity, low immunogenicity and high biocompatibility. The amino acid or the amino acid derivative used in the preparation process is simple and easy to obtain, can be naturally obtained or simply synthesized, and has the advantages of simplicity, convenience, safety and production cost saving. Degradable groups can further be contained between amino acid residues and lipophilic tail chains of the novel amino acid cationic lipid, due to existence of the degradable groups, lipid nanoparticles LNP prepared from the novel amino acid cationic lipid can be degraded in vivo in good time, and the problems that in the prior art, LNP prepared from lipid which cannot be degraded can be stored in vivo, the endosome environment is acidified, and the lipid nanoparticles LNP cannot be degraded in vivo are solved. Endosome escape of drug molecules (such as nucleic acid) is blocked, and the problem that drugs delivered into cells cannot play a role is solved.

There is provided herein a copolymer comprising a ligand moiety that binds to a cell surface receptor, one or two lipophilic polymer blocks and a poly(alpha aminoester) block for the delivery of therapeutic, diagnostic and imaging agents, including small molecules therapeutic agents and nucleic acids, into a cell.

The present invention provides benzodiazepine derivatives, radioactive probes and their applications, belonging to the field of biomedicine technology. The present invention modifies the benzodiazepine derivatives and introduces hydrophilic or lipophilic side chains. The prepared benzodiazepine derivatives can be used as precursors targeting V2R, which can achieve specific targeting of V2R and provide new molecular tools for the subsequent diagnosis and treatment of V2R-positive tumors. 68 The Ga-labeled radioactive probe of the present invention exhibits good tumor imaging effects and can achieve PET imaging of V2R-positive tumors, which helps to improve the accuracy of tumor diagnosis. It can also be used to evaluate treatment effects, has a high "target / non-target" ratio, and can better display the distribution of V2R receptors throughout the body. It has many applications in the diagnosis and treatment of cancer.

Disclosed in the present invention is a double-stranded siRNA having a lipophilic modification. The modified siRNA molecule, via intrathecal injection, intradermal injection and other administration modes, achieves an excellent in-vivo distribution performance and delivery efficiency, and has a good tolerability and safety while effectively knocking down the expression of a target gene. Further disclosed in the present invention are a method for preparing the siRNA having a lipophilic modification, a pharmaceutical composition, and the use thereof in the preparation of a drug for treating a TNF-α-mediated disease or condition.

The application belongs to the technical field of biological diagnosis, and relates to a subcellular organelle active targeting imaging probe and a preparation method thereof. The subcellular organelle active targeting imaging probe of the application is formed into nanoparticles (NPs) by coupling a fluorescent imaging probe with a special sequence of bombesin peptide and a derivative thereof; on one hand, the NPs can be surface-functionalized with lipophilic cations related to the NPs; on the other hand, the NPs can be passively targeted to tumor sites, and have high permeability and retention effect for solid tumors.

The invention discloses a floxuridine phosphamide ester prodrug and application thereof in preparation of a medicine for treating liver cancer, and belongs to the technical field of medicine. The invention designs and synthesizes a series of 5-FdU phosphamide ester derivatives which are subjected to specific esterification modification at 3 '-site. Different aromatic acyl, fatty acyl or amino acid residues are introduced to the 3 '-site, so that the lipophilicity of molecules is further adjusted to enhance liver tissue distribution, and the enrichment and activation process of the medicine in the liver is optimized by utilizing the steric hindrance or metabolic lysis characteristic of the 3'-site. Experiments prove that the series of compounds show excellent anti-hepatoma cell proliferation activity and good pharmacokinetic characteristics, and a new choice is provided for clinical treatment of liver cancer.

The invention provides a novel amino acid cationic lipid, the structure is shown as a general formula (3-26), and the definition of each symbol is consistent with that described in the specification. The amino acid cationic lipid is a pharmaceutically acceptable, biodegradable or high-biocompatibility lipid, and has the advantages of low toxicity, low immunogenicity and high biocompatibility. The amino acid or the amino acid derivative used in the preparation process is simple and easy to obtain, can be naturally obtained or simply synthesized, and has the advantages of simplicity, convenience, safety and production cost saving. Degradable groups can further be contained between amino acid residues and lipophilic tail chains of the novel amino acid cationic lipid, due to existence of the degradable groups, lipid nanoparticles LNP prepared from the novel amino acid cationic lipid can be degraded in vivo in good time, and the problems that in the prior art, LNP prepared from lipid which cannot be degraded can be stored in vivo, the endosome environment is acidified, and the lipid nanoparticles LNP cannot be degraded in vivo are solved. Endosome escape of drug molecules (such as nucleic acid) is blocked, and the problem that drugs delivered into cells cannot play a role is solved.