55 results about "Liver targeting" patented technology

The invention relates to the field of biomedicine, particularly provides a copper-based nano-enzyme as well as a preparation method and application thereof, and aims to solve the problems that in the prior art, clinical treatment on primary sclerosing cholangitis (PSC) is difficult in diagnosis and lacks of effective treatment drugs. The copper-based nano-enzyme comprises a nano-enzyme carrier and a copper-based nano-enzyme, wherein the nano-enzyme carrier is a two-dimensional nanosheet formed by copper ions, gallic acid and ursodesoxycholic acid through coordinate bonds; the probe molecule is a cyanine dye molecule connected to the surface of the nano-enzyme carrier through a covalent bond; wherein the fluorescence intensity of the copper-based nano enzyme is enhanced after the action of the alkaline phosphatase. The three functions of alkaline phosphatase responsive diagnosis, nano-enzyme catalytic treatment and ursodesoxycholic acid hepatic targeting are innovatively and synergistically integrated into one nano platform, the treatment function can be executed while specific imaging diagnosis is performed on diseases, and a new strategy is provided for diagnosis and treatment of diseases such as PSC.

The invention provides curcumin composite particles for improving alcohol-related liver diseases and a preparation method of the curcumin composite particles, and belongs to the technical field of nutritional active ingredient delivery systems. According to the preparation method, zein is taken as a core carrier, curcumin encapsulation is realized through an anti-solvent precipitation method, a compact gel middle layer is constructed by further adopting the protection performance of carrageenan and combining calcium ion mediated ionic crosslinking, and then the outer layer is coated with galactosylated chitosan with liver targeting property through electrostatic adsorption, so that the curcumin-containing hydrogel is prepared. And the curcumin-zein-carrageenan-galactosylated chitosan composite particle with a core-shell-shell structure is innovatively constructed. Compared with free curcumin, the composite particle has obviously improved light and heat stability, realizes controlled release of curcumin in a gastrointestinal tract environment, exerts an effect of obviously improving the alcohol-related liver disease, and has a good application prospect in the aspect of development of functional products for preventing and treating the alcohol-related liver disease.

The application discloses a liver-targeted gene editing system based on endogenous promoter hijacking and application, and belongs to the field of biological medicine. The system is composed of an LNP-wrapped modified Cas nuclease mRNA (first component) and a promoter-free viral vector carrying a therapeutic transgene donor (second component). The system uses LNP to realize the transient burst expression of Cas nuclease in the liver, mediates the generation of double-strand breaks at the site of endogenous high-expression genes, induces the site-specific integration of therapeutic transgenes without exogenous promoters, and hijacks the expression driven by endogenous promoters by using the splice acceptor (SA) mechanism. The application solves the risk of carcinogenesis caused by random integration of exogenous strong promoters and the immunotoxicity of long-term expression of nucleases through a "double safety lock" design. Experimental results prove that the system has high editing efficiency, long-term stability and no off-target, and can be used for various liver-derived metabolic diseases such as hemophilia, hypercholesterolemia and the like.

The invention belongs to the technical field of traditional Chinese medicines, and discloses an immature bitter orange-derived extracellular vesicle-like nanoparticle, which is characterized in that the immature bitter orange-derived extracellular vesicle-like nanoparticle is prepared by the steps of crushing immature bitter orange, filtering, centrifuging and resuspending, the average particle size is 60-120 nm, and the particle size of the immature bitter orange-derived extracellular vesicle-like nanoparticle is 20-30 nm. The extracellular vesicle-like nanoparticles are used for entrapment of at least one of naringin, neohesperidin, naringenin and hesperidin. The extracellular vesicle-like nanoparticles derived from immature bitter oranges are simple in preparation method, have liver targeting and good stability, and can be used for preparing medicines for preventing and / or treating liver injury, depression and breast cancer.

The invention belongs to the field of medicines, and particularly relates to a hepatic targeting self-assembly liver protection peptide and application thereof in preparation of a medicine for treating alcoholic liver injury. According to the present invention, the prepared liver targeting self-assembly liver protection peptide FFGGHKDYNDLLDR can be formed through the formation of nanoparticles; the nanoparticles can be orally administered, maintain a stable sequence and structure in a gastric acid environment with a pH value of 2, prevent the influence of a complex enzyme environment in intestinal tracts, are released in a body fluid system after being absorbed by the intestinal tracts, and are enriched in the liver under the action of a liver targeting module in the liver targeting self-assembly liver protection peptide, so that the alcoholic liver injury is effectively inhibited.

The invention provides multivalent glycopeptide as well as a preparation method and application thereof, and belongs to the field of polypeptide drugs. The structure of the multivalent glycopeptide is shown as a formula I. A polycysteine peptide chain is used as a main chain, glycosyl sulfinate is used as a raw material to carry out multivalent glycosylation modification, the novel multivalent glycopeptide is obtained, the multivalent glycopeptide has multiple potential application values, and when acetylamino galactose is used for multivalent glycosylation modification, the multivalent glycopeptide can be used for preparing the novel multivalent glycopeptide. The obtained acetamino galactose multivalent glycopeptide has excellent liver targeting ability which is higher than that of traditional commercial trisaccharide of the Alnalym company, and the design can meet the requirements of biomedical research and drug development on multivalent glycopeptide. Formula I

The invention discloses a high-efficiency targeted anti-hepatic fibrosis oral nano drug delivery system and a preparation method thereof. According to the system, a sesquiterpene lactone component, namely lettuce lactone (LC), in Xinjiang traditional liver protection medicinal material cichorium glandulosum is used as a medicine core, and although the lettuce lactone has a good anti-fibrosis effect, the lettuce lactone (LC) has the problems of poor water solubility, high first-pass metabolism and the like. Therefore, 18 beta-glycyrrhetinic acid modified silicon-based hybrid micelles (LC-FS-G) are studied and constructed, the liver targeting property of glycyrrhetinic acid and a silicon-based cross-linked structure are utilized to enhance the stability, and drug release is responded in a glutathione (GSH) high expression environment by virtue of a disulfide bond. The particle size of the obtained micelle is uniform (27.83 nm), the encapsulation efficiency reaches 95.05%, and the drug loading rate is 10.62%. The system is slowly released in gastric juice (48h release lt); 50%), and the gt can be quickly released in a high GSH environment (36h release gt; 87%), and the liver fibrosis process can be reversed by regulating and controlling a TGF-beta / Smad pathway. According to the strategy, physicochemical and metabolic restrictions of LC are overcome, and a new way with high efficiency and low toxicity is provided for oral nano targeted therapy of hepatic fibrosis.

Provided are a GalNAc compound containing a ribose ring or its derivative structure and an oligonucleotide conjugate thereof. The oligonucleotide conjugate can achieve efficient liver-targeted delivery and improve the efficacy of the drug.

The invention discloses a liver-targeted therapeutic drug based on I-type photodynamic COF as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The preparation method comprises the following steps: firstly, synthesizing a novel I-type photosensitizer, modifying imine type COF with the photosensitizer to obtain a series of COF-E with I-type photodynamic capability, then loading a chemotherapeutic drug, and modifying a targeting molecule on the surface of a material through a pi-pi accumulation effect. The biocompatibility and cytotoxicity of the obtained liver tumor targeted nano therapeutic drug are evaluated through the cellular level. The liver tumor targeted therapeutic drug has good stability, can be triggered to release by a tumor microenvironment, and can play a synergistic therapeutic role of type I photodynamic therapy and chemotherapy; in addition, the compound has a good treatment effect in a subcutaneous hypoxia solid tumor model, and is expected to be applied to clinical research.

The invention relates to the field of medical biology, and discloses a lipid composition with improved liver targeting, a pharmaceutical composition containing the lipid composition and application of the lipid composition and the pharmaceutical composition. Aiming at the problems of complex synthesis process, low yield, poor targeting property, poor drug effect and the like of the existing liver targeting drug delivery system, the invention redesigns the formula of the LNP delivery system, and provides the drug targeting delivery system with good liver targeting property and low cytotoxicity by selecting specific types of lipids for matching. While side effects of liver injury and the like are reduced, a good curative effect is maintained, and a basis is provided for research, development and production of targeted biomolecular drugs.

The invention provides a liver-targeted protein degradation agent conjugate and an application of the liver-targeted protein degradation agent conjugate. Specifically, the invention provides a conjugate or a pharmaceutically acceptable salt thereof, and the protein binding conjugate is shown as a formula (A), wherein the variables are as defined herein.

The invention relates to the technical field of liver targeting compounds, in particular to a cyclic peptide ligand of a targeting asialoglycoprotein receptor, pharmaceutically acceptable salt of the cyclic peptide ligand, application of the pharmaceutically acceptable salt and a pharmaceutical composition. The invention provides a cyclic peptide ligand of a targeted asialoglycoprotein receptor, a pharmaceutically acceptable salt of the cyclic peptide ligand, an application of the pharmaceutically acceptable salt and a pharmaceutical composition. The cyclic peptide ligand has better endocytosis activity.

The invention belongs to the field of biological medicine, and particularly relates to siRNA for inhibiting XDH gene expression and a modifier and application thereof. Comprising a sense strand and an antisense strand; the positive-sense strand and / or the antisense strand has a length in the range of 19-25 nucleotides, and the antisense strand is reversely complementary to a segment on a target gene; the positive-sense strand has a nucleotide sequence as shown in SEQ ID NO.8, and the antisense strand has a nucleotide sequence as shown in SEQ ID NO.25. The siRNA molecules and the modified siRNA molecules have high stability and / or high inhibitory activity. The siRNA molecule conjugated with the ligand keeps high inhibitory activity and stability, and also has good liver targeting and cell endocytosis promotion capability, so that the influence on other tissues or organs can be reduced, the use amount of the siRNA molecule can be reduced, and the purposes of reducing toxicity and reducing cost can be achieved.

Provided in the present application are a GalNAc compound containing a triazole structure, and an oligonucleotide conjugate thereof, and specifically disclosed is a GalNAc compound shown in formula (I) or a pharmaceutically acceptable salt thereof. The GalNAc compound in the present application can form a conjugate with oligonucleotide, and the oligonucleotide can realize the efficient liver targeting delivery of the oligonucleotide, regulate gene expression, and can be used for preventing and / or treating diseases caused by expression of specific genes in liver cells.

The present application relates to the biomedical field, and specifically provides a copper-based nano-enzyme, a preparation method and application thereof, aiming to solve the problems of diagnosis difficulty and lack of effective treatment drugs in the prior art for the treatment of primary sclerosing cholangitis (PSC) in clinical practice. To this end, the copper-based nano-enzyme comprises: a nano-enzyme carrier, which is a two-dimensional nanosheet formed by coordination bonds between copper ions, gallic acid and ursodeoxycholic acid; and a probe molecule, which is a phycobilin dye molecule connected to the surface of the nano-enzyme carrier by a covalent bond; wherein the copper-based nano-enzyme has enhanced fluorescence intensity after the action of alkaline phosphatase. The present application innovatively integrates alkaline phosphatase-responsive diagnosis, nano-enzyme catalytic treatment and liver targeting of ursodeoxycholic acid into one nano-platform, can perform treatment functions while performing specific imaging diagnosis on diseases, and provides a new strategy for the diagnosis and treatment of PSC and other diseases.

The present application relates to the technical field of nanomedicine delivery system, and particularly relates to a liver-targeting, long-circulating and acid-responsive nanomedicine delivery system loaded with oleuropein and a preparation method and application thereof. The nanomedicine delivery system comprises a drug-loaded core and a functional surface modification layer; the drug-loaded core is a zeolitic imidazolate framework loaded with oleuropein; and the functional surface modification layer is a lactobionic acid-polyethylene glycol conjugate. The present application realizes the precise delivery and efficient release of oleuropein at the site of sepsis liver injury by constructing a liver-targeting, long-circulating and acid-responsive three-level modular nanomedicine delivery system. The technical scheme can solve the technical problems of low bioavailability of oleuropein and unsatisfactory targeting delivery efficiency at the site of sepsis liver injury. The technical scheme comprehensively improves the pharmacokinetic characteristics and targeted treatment efficiency of OLE, and provides an efficient and safe nanomedicine delivery system for the precise treatment of sepsis liver injury.

This application relates to the technical field of tumor treatment, disclosing a nucleic acid drug targeting lncSULT1C2 and its application in the treatment of liver cancer. This application discovered that lncSULT1C2 is specifically highly expressed in liver cancer cells and has significant pro-cancer activity. Therefore, an antisense oligonucleotide targeting lncSULT1C2 was designed and GalNAc was coupled to its 3' end to enhance its liver targeting and specificity. GalNAc-ASO-lncSULT1C2 can significantly inhibit the growth and metastasis of liver cancer cells, effectively inhibiting the progression of hepatocellular carcinoma, without causing damage to normal liver cells.

The invention belongs to the technical field of medicines, and particularly relates to lactylphenylalanine liposome with mitochondrial targeting and fluorescent tracing functions and application of the lactylphenylalanine liposome in treatment of metabolism-related fatty liver diseases. The preparation method comprises the following steps: firstly, preparing a bifunctional molecule Cy5-Lac Phe, and covalently linking a therapeutic active component with a mitochondrial targeting fluorescent tracing group through a chemical bond to form a single multifunctional entity; therefore, each therapeutic molecule is ensured to have targeting and tracing capabilities, and the problems of non-uniform targeting efficiency and in-vivo dissociation caused by simple physical mixing of different components are solved. According to the invention, the bifunctional molecules are prepared into liposome nanoparticles. According to the liposome, passive liver targeting is achieved through the nanometer size of the liposome, so that free Cy5-Lac Phe molecules are efficiently enriched and released in the liver, a Cy5 module plays a mitochondrial targeting function, and accurate drug delivery at the organelle level is achieved. Meanwhile, the fluorescent tracing function of Cy5 allows real-time visual monitoring of the medicine.

The present application relates to an exosome fusion liver-targeting liposome drug delivery system and its preparation method and application, and belongs to the field of polymer materials and pharmaceutical preparations. The present application discloses an exosome fusion liver-targeting liposome drug delivery system, which uses high-concentration PEG 8000 and Nycodenz in combination to synergistically improve the exosome and liposome fusion efficiency, form biomimetic vesicles with uniform size and high drug loading. The exosome not only can play the characteristics of anti-inflammatory and antioxidant, but also plays a role in resisting harsh gastrointestinal environment and crossing biological barriers. In addition, the liposome is modified by cholic acid derivative by using EDC / NHS mediated amidation reaction, which realizes precise targeting of liver and sufficient accumulation in liver. The above-mentioned effects synergistically realize the treatment of type II diabetes and non-alcoholic fatty liver disease.

This invention provides a liver-targeting glycoligand molecule modified with dual-antenna GalNAc and its drug delivery system. This liver-targeting glycoligand molecule and its drug delivery system, through ASGPR recognition, can maximize the concentration of therapeutic drugs in liver tumor parenchymal cells, thereby improving the targeting of drug distribution, increasing the therapeutic index, reducing systemic toxicity, and improving patient survival time and quality of life. The liver-targeting glycoligand molecule of this invention is synthesized using an enzymatic synthesis method, which involves fewer synthesis steps, mild enzymatic reaction conditions, high regioselectivity, high reaction efficiency, is environmentally friendly, and has low production costs, making it highly promising for industrialization.

The invention relates to preparation and application of an engineering virus with high tumor specificity and high killing efficiency. Specifically, the invention relates to a recombinant oncolytic virus based on HSV-1 transformation, which is mainly characterized in that a diphtheria toxin A subunit (DT-A) expression cassette driven by a tumor specific promoter (such as Survivin) is inserted into an ICP6 gene coding region of wild type HSV-1, so that specific recognition and efficient direct killing of tumor cells are realized, and the expression cassette is a recombinant oncolytic virus. And hepatic targeting delivery is realized by matching with red blood cells treated by cationic polymers.

Disclosed herein are identified compound fragments, compounds and their pharmaceutically acceptable salts, isotopes or solvates, useful as antiviral drug and / or as a hepatic-targeted drug, such as for the treatment of HBV, HDV and / or HIV. Formula (I).

The invention relates to the technical field of medical application, in particular to a liver-targeted chemotherapeutic drug nano-micelle preparation method, a chemotherapeutic drug and application, and the preparation method comprises the following steps: S100, preparing pluronic-succinimide formate; s200, preparing a pluronic-polyethyleneimine copolymer; s300, preparing divinyl sebacate; carrying out enzymatic synthesis on the Pluronic F127-SE; the preparation method comprises the following steps: preparing a Pluronic F127-C8-GalNAc nano micelle; and preparing the GalNAc (at) LFT-MMs / siCOP1 compound. The preparation method disclosed by the invention is beneficial to rapidly preparing the nano-micelle with multiple effects of active targeting, chemotherapy and gene therapy.

The invention discloses a fluorodeoxyuridine monophosphate prodrug as shown in a formula I, application of the prodrug in preparation of a medicine for treating liver cancer, a pharmaceutical composition containing the prodrug and pharmaceutically acceptable auxiliary materials or taraxasterol and application of the prodrug in preparation of the medicine for treating liver cancer, and belongs to the field of pharmacy. The compound is modified by specific natural amino acid residues and can be used for preparing medicines for treating liver cancer. The in-vitro and in-vivo anti-tumor activity of the compound is remarkably superior to that of the prior art, the compound has a synergistic effect when being combined with taraxasterol, the highest tumor inhibition rate reaches 91.72%, the compound is high in selectivity, good in safety and high in liver targeting performance, and a more effective new scheme is provided for liver cancer treatment.

The invention provides an application of terazosin or a pharmaceutically acceptable salt thereof in preparation of a medicine for preventing and / or treating hepatic fibrosis, relates to the technical field of biological medicines, and finds that the terazosin or the pharmaceutically acceptable salt thereof can be used for preventing and treating hepatic fibrosis for the first time. It is revealed that terazosin or a pharmaceutically acceptable salt thereof can improve the degree of hepatic fibrosis by improving the liver function, reducing the content of a marker alpha-SMA of activated hepatic stellate cells in liver tissue, reducing the content of Col1a1 in the liver tissue and reducing collagen deposition in the liver tissue. The liver-targeted sustained-release drug provided by the invention can reduce the peak value of the plasma concentration of terazosin and prolong the plasma half-life period of terazosin, has the same treatment effect as that of repeated low-dose injection of terazosin, and has a wide application prospect.

The invention belongs to the field of medicinal chemistry, and discloses synthesis of a novel dimeric ursodesoxycholic acid-ASO conjugate. In order to reduce the off-target effect of an ASO drug, ASO is often coupled with GalNAc to improve the liver targeting ability of GalNAc in an animal body. Clinical research finds that after an ASO drug for treating HBV infection is coupled with GalNAc, the activity of the ASO drug is reduced compared with that of uncoupled ASO, HBV viruses enter hepatocytes through NTCP, and an NTCP inhibitor dimeric ursodesoxycholic acid derivative may become a brand-new bullet for delivering ASO to the HBV infected hepatocytes. The dimeric ursodesoxycholic acid is used as a target head of ASO targeted HBV virus infected hepatocytes, the dimeric ursodesoxycholic acid derivative and ASO are efficiently coupled by using a click reaction without copper catalysis to obtain a target compound, and the compound can inhibit the content of HBsAg in an HBV mouse and possibly generate the same inhibitory activity in a human body.

The application belongs to the field of nanomedicine, and discloses a dual-target ROS-responsive nanomedicine for treating MASH and a preparation method thereof, which comprises the following steps: step 1, organic phase preparation, MCC950, Belzutifan and PEG-b-PPS are added into an organic solvent, and ultrasonic treatment is performed until complete dissolution to form an organic phase, the average molecular weight of the PEG block in PEG-b-PPS is 1000-5000, and the polymerization degree of the PPS block is 10-100; step 2, self-assembly wrapping, the organic phase is slowly added into an aqueous phase under constant magnetic stirring, and a primary micelle emulsion is obtained after self-assembly; step 3, dialysis purification and drying, the primary micelle emulsion is transferred into a dialysis bag for dialysis, and then freeze-drying is performed to obtain a dual-target nanomicelle powder. The dual-target ROS-responsive nanomedicine at least comprises the dual-target nanomicelle powder, the medicine breaks through the bottleneck of dissolution and delivery of extremely hydrophobic drugs, has excellent intravenous drug adaptability and stability, can realize long-acting and precise liver targeting enrichment, and greatly reduces the risk of systemic off-target toxicity.

This invention provides the use of terazosin or its pharmaceutically acceptable salts in the preparation of medicaments for the prevention and / or treatment of liver fibrosis, relating to the field of biomedical technology. This invention is the first to discover that terazosin or its pharmaceutically acceptable salts can be used to prevent and treat liver fibrosis. It reveals that terazosin or its pharmaceutically acceptable salts can improve the degree of liver fibrosis by improving liver function, reducing the content of α-SMA (a marker of activated hepatic stellate cells) in liver tissue, reducing the content of Col1a1 in liver tissue, and reducing collagen deposition in liver tissue. Furthermore, the liver-targeted sustained-release drug provided by this invention can reduce the peak plasma concentration of terazosin and prolong its plasma half-life, achieving therapeutic effects equivalent to multiple low-dose injections of terazosin, and has broad application prospects.

The application belongs to the technical field of biological medicine, and relates to a liver-targeting compound, a conjugate and application. The liver-targeting compound has a structure shown in formula I, T is a targeting group, B is a branch structure, L1 is a connecting group, L2 is a connecting part between the targeting group and the branch structure, and X is selected from integers between 2 and 6. The liver-targeting compound and the conjugate have clear structures, multiple galactose, galactosamine or galactosamine derivative molecules are linked into a three-cluster or four-cluster molecule to form a molecular cluster form, the affinity to ASGPR is obviously higher than the affinity of a single sugar, the drug liver-targeting delivery capacity can be improved, the delivery efficiency is high, and a long-acting inhibitory effect can be maintained; and the synthesis route is clear, and the preparation process is simple.

The invention discloses a high-enzyme-loading-amount liver targeted drug delivery system based on gradient biomimetic mineralization as well as a preparation method and application of the high-enzyme-loading-amount liver targeted drug delivery system. According to the system, protein serves as a nucleation site, zinc ions and a 2-methylimidazole framework are gradually assembled in a mild water phase environment by utilizing the coordination effect of histidine residues and metal ions in a protein structure, a protein-metal organic framework compound (Pmof) with high drug loading capacity is constructed, and small molecule drugs can be loaded at the same time. The delivery system has a remarkable liver targeting capability, can be efficiently enriched in liver tissues, and synchronously releases protein drugs and small molecule drugs. The problem that an existing carrier is low in enzyme loading amount is solved, the preparation process is mild, biocompatibility is good, and the carrier can be used for developing other drugs for treating liver diseases and has remarkable clinical transformation prospects.