102 results about "Liver targeting" patented technology

The invention discloses a preparation method of an oral liver protection composition containing ergothioneine, and relates to the technical field of ergothioneine application. The oral liver protection composition containing the ergothioneine is prepared from the following components in parts by mass: 0.5 to 5 parts of the ergothioneine, 10 to 30 parts of silibinin, 20 to 50 parts of a phospholipid complex, 5 to 15 parts of a liver targeting carrier, 2 to 8 parts of a disintegrating agent, 1 to 5 parts of an adhesive and 2 to 4 parts of an antioxidant. Free radicals are efficiently captured through a polycyclic conjugated pi electron system of the antioxidant, a hydrogen bond network is formed by a heteroatom bridging effect of the antioxidant, a galactose group of the liver targeting carrier and the disintegrating agent, and the stability of the system is synergistically improved; the phospholipid complex is embedded with a hydrophobic drug and a hydrophilic carrier, and the drug is accurately delivered to the liver by combining the specific recognition capability of the liver targeting carrier; the ergothioneine and the silybin form a bidirectional synergistic liver protection mechanism by removing reactive oxygen free radicals and regulating and controlling cell signal channels respectively.

Provided siRNA for inhibiting XDH gene expression and a modifier and use thereof. The siRNA comprises a sense strand and an antisense strand. The sense strand and / or the antisense strand have a length in the range of 19-25 nucleotides, and the antisense strand is reversely complementary to a segment on a target gene; and the sense strand has a nucleotide sequence as shown in SEQ ID NO: 1-14, and the antisense strand has a nucleotide sequence as shown in SEQ ID NO: 18-31. siRNA molecules and modified siRNA molecules have high stability and / or high inhibitory activity. Ligand-conjugated siRNA molecules have good liver targeting performance and the capability to promote cell endocytosis while maintaining high inhibitory activity and stability, can reduce the impact on other tissues or organs and reduce the amount of siRNA molecules used, and can achieve the purposes of reducing toxicity and reducing costs.

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 relates to an exosome fusion liver targeting liposome drug delivery system as well as a preparation method and application thereof, and belongs to the field of high polymer material science and pharmaceutical preparations. The invention discloses an exosome-fused liver-targeted liposome drug delivery system, which combines high-concentration PEG8000 and Nycodenz in a breakthrough manner, synergistically improves the fusion efficiency of exosome and liposome, and forms bionic vesicles with uniform size and high drug loading capacity. The exosome not only can exert the anti-inflammatory and anti-oxidation characteristics, but also plays a role in resisting a severe gastrointestinal environment and crossing a biological barrier. In addition, liposome is modified by cholic acid derivatives through EDC / NHS mediated amidation reaction, precise targeting of the liver is achieved, and the liposome is fully accumulated in the liver. The effects synergistically realize the treatment of type II diabetes and non-alcoholic steatohepatitis.

The invention relates to an ROS response type persulfide biomacromolecule nano prodrug, a nano preparation and a preparation method and application of the ROS response type persulfide biomacromolecule nano prodrug and the nano preparation, and belongs to the technical field of nano preparations. According to the invention, the hydrogen persulfide is protected by utilizing ROS to respond to a small molecule group, so that the defect that the existing hydrogen persulfide is unstable is overcome; meanwhile, biomacromolecules are used as a carrier of the hydrogen persulfide, so that the liver targeting property, the water solubility and the biological safety of the hydrogen persulfide are improved, and multi-site modification and adjustability of the drug loading capacity are realized; in addition, the nano preparation is simple in reaction process, mild in condition and beneficial to clinical transformation.

The invention relates to a GalNAc connexon precursor and a preparation method thereof, in particular to a preparation method of a liver targeting three-antenna GalNAc connexon precursor with a structure shown in a formula 13. The method provided by the invention has the advantages of few steps, simple purification, high yield and mild reaction conditions, and is suitable for industrial production.

The invention discloses a multilevel liver targeting drug delivery system based on ionizable amino lipid and a preparation method thereof, the system comprises the following components: target modified ionizable amino lipid, ionizable amino lipid, auxiliary lipid and structural lipid in a molar ratio of (10-30): (30-60): (5-40): (15-55), according to the system, nano lipid particles exist in a water-in-oil-in-water nano emulsion form; wherein the ionizable ammonia lipid is a compound with a structure as shown in a formula (I). The system is suitable for delivering nucleic acid, protein and other active pharmaceutical ingredients to the liver so as to improve the accuracy and treatment effect of drug delivery and reduce the side effects of non-target organs.

The invention discloses lipid nanoparticles targeting liver cells as well as a preparation method and application of the lipid nanoparticles. Raw materials of the lipid nanoparticles comprise lipid targeting dirty cells, and the lipid targeting dirty cells is selected from at least one of galactosyl lipid, N-acetyl galactosamino lipid, lactosyl lipid, mannose-based lipid, glycolipid, glycerol glycolipid, steroid glycolipid, glycerol cholic acid lipid or N-alkenyl lipid. The low-toxicity lipid nanoparticle for efficiently targeting the liver is high in delivery efficiency, has remarkable liver targeting, low immunogenicity and excellent biocompatibility, and is applicable to delivery of various drugs, gene therapy and vaccines needing liver targeting delivery.

The invention discloses a tandem double-locking liver targeting fluorescent probe as well as a preparation method and application thereof. The probe is a compound LDMTY. Through experiments, the applicant finds that the probe shows high sensitivity and selectivity to HClO and beta-gal, the lowest detection limits reach 0.046 mu M and 2.54 * 10 <-4 > U / mL respectively, overexpression of HClO and beta-gal in HCC can be recognized at the same time, the capacity of targeting and accumulating in the liver is achieved, hepatocellular carcinoma can be accurately detected, and the application prospect is wide. And promising potential and value are shown in the aspect of HCC detection.

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 invention discloses a liver targeting porous starch-luteolin compound and a preparation method and application thereof, and belongs to the technical field of drug delivery, corn porous starch is used as a carrier, and the compound with the liver targeting function is prepared through OSA hydrophobic modification, luteolin loading and epsilon-polylysine-galactoside targeting modification. The drug loading capacity and liver targeting property of luteolin are remarkably improved through triple modification, the production process is simple, the cost is low, and excellent blood sugar reducing and liver protecting effects are shown in diabetes liver injury treatment.

The invention discloses a pharmaceutical composition. The pharmaceutical composition is characterized in that the pharmaceutical composition comprises a carrier compound, the carrier compound is formed by an exosome and a lipid substance or a cationic polymer through positive and negative charge attraction, and the carrier compound further comprises an active pharmaceutical ingredient nucleic acid, the pharmaceutical composition also optionally comprises a pharmaceutically applicable carrier. The pharmaceutical composition enables delivery of nucleic acids. Therefore, hepatic targeting expression of nucleic acid is realized, and the survival rate of individuals suffering from hepatic diseases (such as an acute hepatic failure model and hepatic fibrosis) is improved.

The present invention provides a GalNAc compound containing a ribose ring or its derivative structure and an oligonucleotide conjugate thereof. With the oligonucleotide conjugate provided by the present invention, efficient liver-targeted delivery can be achieved, improving the drug efficacy.

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 discloses a pharmaceutical composition containing a hiHeps-derived exosome, an application of the pharmaceutical composition or the hiHeps-derived exosome in preparation of a medicine for treating liver diseases, and an application of the pharmaceutical composition or the hiHeps-derived exosome in preparation of a medicine for reducing inflammation. The pharmaceutical composition comprises an exosome, a liposome and a nucleic acid drug, wherein the exosome is derived from hiHeps. The pharmaceutical composition can realize better nucleic acid delivery, has lower immunotoxicity and better biocompatibility compared with single cationic liposome delivery, and can efficiently realize expression and functions in in-vitro cell lines, primary hepatocytes and in-vivo mice. Compared with other exosomes, the pharmaceutical composition constructed by the hiHeps exosome also has higher liver targeting property and parenchymal hepatic cell targeting property.

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 provides a preparation method of liver-targeted drug-loaded liposome, and belongs to the field of biological medicine. The hepatic targeting carbohydrate chain is constructed through a multi-step enzymatic reaction, and the accuracy of a modification site is ensured. The synthesized galactose ligand is connected to the surface of the liposome through a covalent bond, so that the targeting property and the stability are enhanced. The synthesis of the galactose ligand provides targeting functional groups with clear structures for the liposome, and the groups are integrated to the surface of the liposome through physical entrapment and chemical coupling in the preparation of the liposome, so that active targeting delivery is finally realized. The collaborative design of the two is based on an ASGPR-mediated liver targeting mechanism, and the delivery efficiency is optimized through enzymatic synthesis and a nanotechnology. In in vivo experiments, plasma and liver distributions of liposomes are determined. In an in-vitro experiment, the uptake efficiency of the lipidosome in liver cancer cells is determined. The experiments aim at verifying that the advantages of the lipidosome in liver cancer cell delivery are improved by optimizing the PEG chain length and the exposure of residues.

The application discloses a method for modifying phospholipids and application thereof in preparation of liver-targeted liposomes, relates to the field of drug delivery, and first utilizes cholate and mannose to modify phospholipid molecules DSPE-PEG 2000 respectively 2000 Two raw materials DSPE-PEG 2000 -CA and DSPE-PEG 2000 -MAN for synthesizing liposomes are synthesized, and then cholesterols, DSPC and DC-cholesterols are added in a certain proportion to obtain liposomes with liver targeting property, which have high cell safety and liver cell targeting property.

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 application discloses a liver-targeting lipid carrier as well as a preparation method and application thereof, relates to the field of drug delivery, and utilizes cholate and mannose to respectively modify a phospholipid molecule DSPE-PEG 2000 After two raw materials DSPE-PEG-CA and DSPE-PEG-MAN composed of synthetic liposomes are obtained, the liver-targeting lipid carrier is obtained according to a certain proportion of cholesterol, DSPC, DC-cholesterol and the like, and the liposome has high cell safety and liver targeting.

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.

The present invention provides a GalNAc compound-coupled nucleic acid lipid nanoparticle containing a ribose ring structure, and a preparation method and application thereof. The components of the lipid nanoparticle include: nucleic acid, lipid and anchor compound of GalNAc containing a ribose ring; the lipid includes: cationic lipid, neutral lipid, auxiliary lipid and long-circulating lipid; the anchor compound of GalNAc containing a ribose ring includes: a GalNAc part containing a ribose ring and a lipid chain group; the structural formula of the anchor compound is shown in Formula IX. The conjugate provided in the present invention can achieve efficient liver-targeted delivery and improve the efficacy of the drug.

The invention relates to the technical field of nano-drug delivery systems, in particular to a liver-targeting, long-circulating and acid-responsive nano-drug delivery system for loading oleuropein as well as a preparation method and application of the liver-targeting, long-circulating and acid-responsive nano-drug delivery system. The nano-drug delivery system comprises a drug-loading inner core and a functionalized surface modification layer, the medicine carrying inner core is a zeolite imidazate framework loaded with oleuropein; the functional surface modification layer is a lactobionic acid-polyethylene glycol conjugate. According to the invention, by constructing a three-stage modular nano-drug delivery system of liver targeting-long circulation-acid response, precise delivery and efficient release of oleuropein at a sepsis liver injury part are realized. According to the technical scheme, the technical problems that the bioavailability of the oleuropein is low, the targeted delivery efficiency of the oleuropein at the sepsis liver injury part is not ideal and the like can be solved. According to the technical scheme, the pharmacokinetic characteristics and targeted treatment efficiency of OLE are comprehensively improved, and an efficient and safe nano-drug delivery system is provided for precise treatment of sepsis liver injury.