151 results about "Acetylgalactosamine" patented technology

The invention discloses a composition for resisting porcine viral diarrhea and application of the composition. The composition for resisting porcine viral diarrhea is prepared from the following components in parts by mass: 2 parts of phloretin, 1 part of N-acetyl-D-galactosamine and 100 parts of proline. The composition can further comprise one or more auxiliary materials of absolute ethyl alcohol, propylene glycol, dimethyl sulfoxide, edible oil, water, tween-80, lactose, defatted rice bran, corncob powder, soluble starch, bran, silicon dioxide, montmorillonite, vermiculite, medical stone, zeolite powder, white carbon black and the like. The composition can significantly inhibit the proliferation of PEDV, TGEV and PoRV, and inhibit the infection of PEDV, TGEV and PoRV on cells, and further, the composition can be used for preparing drugs or feed additives for resisting porcine diarrhea diseases caused by viruses such as PEDV, TGEV and PoRV.

The present disclosure relates to delivery platforms that specifically and efficiently direct multimeric RNAi agent payloads to hepatocytes in a subject, in vivo. The delivery platforms disclosed herein include metabolically stabilized N-Acetylgalactosamine (NAG or GalNAc) targeting ligands conjugated to two or more RNAi agents, to facilitate the delivery of the oligonucleotide-based payloads to cells, including to hepatocytes. Pharmaceutical compositions that include the metabolically stabilized multimeric RNAi agent conjugate delivery platform are also described, as well as methods of use for the treatment of various diseases and disorders where delivery of a therapeutic payload to a hepatocyte is desirable.

The invention relates to the field of enzyme and protein structures, in particular to fusion protease as well as a construction method and application thereof. The construction method comprises the following steps: carrying out gene recombination on the FpGalNAcDeAc and the FpGalNase, and carrying out prokaryotic expression and purification, so as to obtain the FpGalNAcDeAc-FpGalNase or the FpGalNase-FpGalNAcDeAc. The construction method comprises the following steps: carrying out gene recombination on the FpGalNAcDeAc and the FpGalNase; the invention describes that under the conditions of specific buffer solution, incubation time and enzyme concentration, A type red blood cells can be converted into universal O type red blood cells with maximum efficiency. The structure of galactosaminase is analyzed by using a cryoelectron microscope, and acetylgalactosamine deacetylase and galactosaminase are subjected to fusion expression, so that more efficient erythrocyte type conversion is carried out. The method can be used for rapidly, efficiently and safely carrying out type-A erythrocyte type conversion, and has the advantages of high protease yield, low working concentration, simple and convenient conversion operation, universal conditions, low cost and the like.

The disclosure provides methods for synthesis of peracetylgalactosamine-1-pentanoic acid, also called peracetylated D-galactosamine C5 linker or GalNAc C5 linker, using a vegetal source as a starting material, such as vegetal-sourced D-glucosamine or D-glucosamine hydrochloride. Also provided are methods for purifying the peracetylgalactosamine-1-pentanoic acid, or GalNAc C5 linker, thus produced so that the end product comprises fewer impurities.

The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents such as small interfering RNA (siRNA) molecules, able to inhibit proprotein convertase subtilisin kexin 9 (PCSK9) gene expression. Also disclosed are pharmaceutical compositions that include PCSK9 RNAi agents and methods of use thereof. The PCSK9 RNAi agents disclosed herein may be conjugated to targeting ligands, including ligands that comprise N-acetyl-galactosamine, to facilitate the delivery to hepatocyte cells. Delivery of the PCSK9 RNAi agents in vivo provides for in vivo provides for inhibition of PCSK9 gene expression and thereby reduction of PCSK9 protein. The RNAi agents can be used in methods of treatment of diseases or disorders mediated at least in part by PCSK9 gene expression, including among others hypercholesterolemia, familial hypercholesterolemia including heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH), familial hypobetalipoproteinemia, hyperlipidemia, coronary artery disease, polygenic dyslipidemia, heart disease, cardiovascular disease (CVD) including clinical atherosclerotic cardiovascular disease (ASCVD).

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 relates to the technical field of medicines, and provides sea sodium polysaccharide, a preparation method and application thereof, and an anticoagulant and / or antithrombotic drug of a targeted endogenous coagulation pathway. The sea sodium polysaccharide provided by the invention is fucosylated chondroitin sulfate polysaccharide, the weight-average molecular weight is 90000-130000, the molar ratio of glucuronic acid to N-acetylgalactosamine to fucose is 1: (0.8-1.2): (0.5-0.8), and the mass percentage of sulfate group is 25-40%. The sea sodium polysaccharide provided by the invention can act on a terminal rate-limiting enzyme (iFXase) in an endogenous blood coagulation pathway in a targeting manner, is not obvious in effect on blood coagulation factors in other blood coagulation pathways, realizes the effects of anticoagulation and no bleeding, can be widely applied to acute-stage and recovery-stage treatment of cerebral arterial thrombosis, and has a wide application prospect. The problem of safety of anticoagulant and antithrombotic drugs used by clinical cerebral arterial thrombosis patients is solved, and a new field of research and development of targeted endogenous coagulation pathway rate-limiting enzyme anticoagulant drugs is developed.

Provided herein are oligomeric compounds with conjugate groups targeting apoplipoprotein C-III (ApoCIII). In certain embodiments, the ApoCIII targeting oligomeric compounds are conjugated to N-Acetylgalactosamine. Also disclosed herein are conjugated oligomeric compounds targeting ApoCIII for use in decreasing ApoCIII to treat, prevent, or ameliorate diseases, disorders or conditions related to ApoCIII. Certain diseases, disorders or conditions related to ApoCIII include inflammatory, cardiovascular and / or metabolic diseases, disorders or conditions. The conjugated oligomeric compounds disclosed herein can be used to treat such diseases, disorders or conditions in an individual in need thereof.

Embodiments of the present application relate to functionalized N-acetylgalactosamine-analogs, methods of making, and uses of the same. In particular, mono or trivalent N-acetylgalactosamine analogs may be prepared by utilizing a wide variety of linkers containing functional groups. These functionalized N-acetylgalactosamine-analogs may be used in the preparation of targeted delivery of oligonucleotide-based therapeutics.

The application discloses a preparation method of a liver-targeting drug delivery carrier, and comprises the following steps: synthesizing bromic acid N-acetylgalactosamine ester; and synthesizing the liver-targeting drug delivery carrier. x The liver-targeting drug delivery carrier GalNAc-C x CD is designed based on bromic acid N-acetylgalactosamine ester Br-C GalNAc and beta-cyclodextrin, which can include poorly soluble drugs to be delivered to the liver and released in a targeted manner, greatly improves the targeting efficiency on the liver, and the targeting delivery rate can reach more than 70%, while effectively improving the solubility and bioavailability of the poorly soluble drugs, improving the drug treatment effect, providing a new strategy for the delivery of other poorly soluble drugs for treating liver diseases, and laying a foundation for the development of drugs and functional foods for intervening NASH.

The present disclosure provides a combination comprising an antibody that specifically binds to C5 and a C5 iRNA, which is a glycoconjugate containing a ligand with a terminal N-acetylgalactosamine (GalNAc) residue and / or N-acetylglucosamine (GlcNAc) residue. A method for reducing degradation of glycoconjugate RNA by the beta-hexosaminidase enzyme is also provided. The present disclosure also includes a method for treating or preventing a C5-related disease or disorder by administering one or more doses of an anti-C5 antibody or antigen-binding fragment thereof in combination with one or more doses of a C5 iRNA; preferably, the anti-C5 antibody or fragment and the C5 iRNA are in a combination. The present disclosure also includes a dosing regimen for treating a C5-related disease or disorder with a combination of an anti-C5 antibody and a C5 iRNA in either a treatment-naive subject or a subject switching from a previous C5 inhibitor therapy.

The current invention concerns methods for the synthesis of 6-azido-6-deoxy-2-N-acetyl-monosaccharide-nucleoside diphosphate, in particular 6-azido-6-deoxy-2-N-acetyl-D-galactosamine-nucleoside diphosphate or 6-azido-6-deoxy-2-N-acetyl-D-glucosamine-nucleoside diphosphate. The synthesis method according to the invention is characterized by being highly efficient and high yielding. Also part of the present invention are key intermediates of this process.

This invention belongs to the field of biochemical analysis technology, and discloses a magnetic bead for enriching tyrosine N-acetylgalactosamine modification sites, its preparation method, and its application. Specifically, it discloses a recombinant antibody, including the Fab fragment of a G10C antibody, the Fc region of an immunoglobulin, and an AviTag tag. This invention provides a recombinant antibody capable of specifically targeting and enriching tyrosine-O-GalNAc glycosylated peptides. By coupling this recombinant antibody to magnetic beads, the enrichment of tyrosine-O-GalNAc glycosylated peptides can be effectively improved, and interference and signal masking by glycosylation modifications on serine and threonine can be avoided, enabling the identification of more tyrosine glycosylation sites in a single sample.

This disclosure relates to RNAi agents capable of inhibiting complement factor B (CFB) gene expression. Pharmaceutical compositions containing CFB RNAi agents and methods of use thereof are also disclosed. The CFB RNAi agents disclosed herein may be conjugated to a targeted ligand containing an N-acetyl-galactosamine ligand to facilitate in vivo delivery to hepatocytes. RNAi agents can be used in methods of treating diseases, disorders, or conditions partially mediated by CFB gene expression, including IgA nephropathy (IgAN), C3 glomerulopathy (C3G), immune complex-mediated membrane proliferative glomerulonephritis (IC-MPGN), lupus nephritis (LN), anti-glomerular basement membrane antibody disease (anti-GBM), ischemia-reperfusion injury and T-cell-mediated rejection in kidney transplantation (TCMR), anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, age-related macular degeneration (AMD) including early and / or intermediate-stage AMD, geographic atrophy (GA), glaucoma, Doyne honeycomb retinal dystrophy, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), pre-eclampsia, rheumatoid arthritis (RA), and / or other complement-mediated disorders.

This section presents oligomeric compounds with conjugate groups targeting apolipoprotein C-III (ApoCIII). In specific configurations, the oligomeric compounds targeting ApoCIII are conjugated to N-acetylgalactosamine. This section also describes conjugated oligomeric compounds targeting ApoCIII for use in reducing ApoCIII for the treatment, prevention, or amelioration of ApoCIII-related diseases, disorders, or conditions. Specific ApoCIII-related diseases, disorders, or conditions include inflammatory, cardiovascular, and / or metabolic diseases, disorders, or conditions. The conjugated oligomeric compounds described herein may be used to treat these diseases, disorders, or conditions in an individual who requires them.

The present disclosure relates to RNAi agents, e.g., double-stranded RNAi agents, capable of inhibiting the expression of a mitochondrial amidoxime reducing component 1 (MARC1) gene. Also disclosed are pharmaceutical compositions comprising the MARC1 RNAi agent and methods of using the same. In some embodiments, the MARC1 RNAi agents disclosed herein can be conjugated to targeting ligands, including ligands comprising N-acetyl-galactosamine, to facilitate delivery to hepatocytes. Delivery of the MARC1 RNAi agent in vivo provides inhibition of MARC1 gene expression. RNAi agents may be used in methods of treating diseases, disorders or conditions mediated in part by MARC1 gene expression, including non-alcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), alcoholic fatty liver disease, autoimmune hepatitis, hepatic fibrosis, cirrhosis, elevated blood cholesterol levels, hypertriglyceridemia, liver disease, and / or other MARC1 related diseases.

The invention belongs to the technical field of biochemical analysis, discloses a magnetic bead for enriching tyrosine N-acetylgalactosamine modification sites as well as a preparation method and application of the magnetic bead, and particularly discloses a recombinant antibody which comprises a Fab fragment of a G10C antibody, an immunoglobulin Fc region and an AviTag tag. The invention provides a recombinant antibody capable of enriching a tyrosine-O-GalNAc glycosylated peptide fragment in a specific targeting manner. By coupling the recombinant antibody to a magnetic bead, enrichment of tyrosine-O-GalNAc glycosylation peptide fragments can be effectively improved, interference and signal shielding of glycosylation modification on serine and threonine on site identification can be avoided, and more tyrosine glycosylation sites can be identified in a single sample.

The present disclosure relates to RNAi agents able to inhibit Complement Factor B (CFB) gene expression. Also disclosed are pharmaceutical compositions that include CFB RNAi agents and methods of use thereof. The CFB RNAi agents disclosed herein may be conjugated to targeting ligands, including ligands that comprise N-acetyl-galactosamine, to facilitate the in vivo delivery to hepatocyte cells. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms mediated in part by CFB gene expression, including IgA nephropathy (IgAN), C3 glomerulopathy (C3G), immune complex-mediated membranoproliferative glomerulonephritis (IC-MPGN), lupus nephritis (LN), Anti-Glomerular Basement Membrane disease (anti-GBM), ischemia reperfusion injury and T-cell mediated rejection (TCMR) in kidney transplantation, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, age-related macular degeneration (AMD), including early and / or intermediate AMD, geographic atrophy (GA), glaucoma, Doyne honeycomb retinal dystrophy, paroxysmal nocturnal hemoglobinuria (PNH), atypical hemolytic uremic syndrome (aHUS), pre-eclampsia, rheumatoid arthritis (RA), and / or other complement-mediated diseases.

The invention relates to the fields of biotechnology and molecular biology; specifically, to nucleic acid-based technologies. therapeutic agents, RNA interference (RNAi) technologies, oligonucleotides for gene silencing This relates to the design and targeted ligand conjugation of these ligands. More specifically... The invention, as described, provides hepatocyte-targeted gene silencing with N-acetylgalactosamine (GalNAc). conjugated, Seipin gene-specific oligonucleotide sequence (siSeipin) and abnormalities of this sequence It relates to its application in liver diseases associated with lipid accumulation.

The present invention relates to compositions and methods for regulating apolipoprotein (a) expression. Specifically, oligomeric compounds with conjugate groups targeting apolipoprotein (a) [apo (a)] are provided herein. In certain embodiments, the oligomeric compound targeting apo (a) is conjugated to N-acetylgalactosamine. Also disclosed herein are conjugated oligomeric compounds targeting apo (a) for reducing apo (a) to treat, prevent or improve diseases, conditions or symptoms associated with apo (a) and / or Lp (a). Certain diseases, conditions or symptoms associated with apo (a) and / or Lp (a) include inflammatory, cardiovascular and / or metabolic diseases, conditions or symptoms. The conjugated oligomeric compounds disclosed herein can be used to treat the diseases, conditions or symptoms in individuals in need thereof.

The invention discloses a preparation method and application of a hepatic parenchymal cell targeting gene delivery system, and relates to construction and preparation of a hepatic parenchymal cell targeting lipid material GalNAc-PEG2000-DSPE modified MKK4-siRNA (siMKK4) loaded lipid nanoparticle gene delivery system GalNAc-LNP-siMKK4, and the hepatic parenchymal cell targeting gene delivery system can be used for active targeting gene therapy of hepatic failure. The parenchymal hepatic cell targeted gene delivery system selects siMKK4 as a liver regeneration promoting gene therapy drug, has the advantages of clear target spot and capability of accurately silencing a target gene, and can protect siMKK4 from being degraded by extracellular nuclease as a gene delivery carrier, so that the targeted gene delivery system has a good application prospect. N-acetylgalactosamine (GalNAc) is selected as a target head, so that therapeutic genes can be precisely targeted and delivered to parenchymal hepatic cells, the risk of tumorigenesis of other parts of an organism can be reduced while liver regeneration is promoted, and a new thought and a new method are provided for liver regeneration treatment of hepatic failure patients.

The present invention relates to a novel compound and application thereof in the inhibition of HBV gene expression. The structure of the compound comprises an interfering nucleic acid for inhibiting HBV gene expression, transition points, and delivery chains of the interfering nucleic acid. By means of the delivery chains, two or three N-acetylgalactosamines can be introduced to an antisense strand 3′ end of such siRNA, and two or one N-acetylgalactosamine can be correspondingly introduced to a sense strand 5′ end, the total number of the introduced N-acetylgalactosamines being four. In vitro and in vivo pharmacological experiments prove that such a novel compound can continuously and efficiently inhibit HBV gene expression.

The present disclosure relates to RNAi agents, e.g., double stranded RNAi agents, able to inhibit Yellow Fever Virus (YFV) viral genome expression. Also disclosed are pharmaceutical compositions that include YFV RNAi agents and methods of use thereof. The YFV RNAi agents disclosed herein may be conjugated to targeting ligands, including ligands that comprise N-acetyl-galactosamine, to facilitate the delivery to hepatocyte cells. Delivery of the YFV RNAi agents in vivo provides for inhibition of YFV viral genome expression. The RNAi agents can be used in methods of treatment of diseases, disorders, or symptoms caused by YFV infection, such as liver failure.

The invention provides a novel FAPI trimer compound based on a GalNAc (N-acetylgalactosamine) link chain, a preparation method of the FAPI trimer compound, a developing agent based on the FAPI trimer compound and a preparation method of a developing agent. The trimerization structure in the FAPI trimer compound molecule provided by the invention can improve the in-vivo dynamic characteristics of the compound and prolong the residence time of the compound in tumors; the imaging agent based on the FAPI trimer compound can improve the uptake and imaging effects in tumors, and has good application prospects in PET / SPECT imaging, preparation of drugs for diagnosing tumors expressed by FAP-q and drugs for marking therapeutic nuclide (177Lu or 90Y) to treat tumors expressed by FAP-q in the future.

The present disclosure relates to delivery platforms that specifically and efficiently direct multimeric RNAi agent payloads to hepatocytes in a subject, in vivo. The delivery platforms disclosed herein include metabolically stabilized N-Acetylgalactosamine (NAG or GalNAc) targeting ligands conjugated to two or more RNAi agents, to facilitate the delivery of the oligonucleotide-based payloads to cells, including to hepatocytes. Pharmaceutical compositions that include the metabolically stabilized multimeric RNAi agent conjugate delivery platform are also described, as well as methods of use for the treatment of various diseases and disorders where delivery of a therapeutic payload to a hepatocyte is desirable.

Provided herein are oligomeric compounds with conjugate groups. In certain embodiments, the oligomeric compounds are conjugated to N-Acetylgalactosamine.

The invention relates to the technical field of anti-oxidation free radical eliminating drugs and anti-inflammatory activity, in particular to a preparation method of N-acetyl-D-galactosaminated astaxanthin / chitosan microspheres, a product and application of the N-acetyl-D-galactosaminated astaxanthin / chitosan microspheres. According to the preparation method, N-acetyl-D-galactosamine is taken as a ligand molecule, chitosan is taken as a microsphere carrier, chitosan coats astaxanthin to form chitosan microspheres, N-acetyl-D-galactosamine is used for modifying the chitosan microspheres on the outer layer, and finally the N-acetyl-D-galactosamine aminated astaxanthin / chitosan microspheres are formed. According to the invention, the biological limitation of the astaxanthin is improved, the water solubility of the astaxanthin is improved, and the bioavailability of the astaxanthin is improved. And the N-acetyl-D-galactosamine and the chitosan are natural materials which are non-toxic, degradable and easy to absorb by a human body, so that the safety is high.

The invention provides a liver targeting small nucleic acid drug carrier, a pharmaceutical composition and a preparation method and application thereof, and belongs to the technical field of biological drugs. The liver-targeted small nucleic acid drug carrier comprises N-acetylgalactosamine (GalNAc), a small nucleic acid drug for treating hepatocellular carcinoma and a cell-penetrating peptide which are connected in sequence, the cell-penetrating peptide comprises at least one of the following components: TP10 cell-penetrating peptide, iRGD polypeptide, cell-penetrating peptide TPP and cRGD polypeptide. The drug carrier has good nuclease stability and can protect nucleic acid from being degraded by enzyme. Experimental results show that compared with naked small nucleic acid and GalNAc-nucleic acid conjugates, the liver-targeted small nucleic acid drug carrier can be more ingested by HepG2 cells, has stronger capability of silencing tumor-related genes, and can realize efficient treatment of hepatocellular carcinoma (HCC).

We provide a technology that can activate NRF2. [Solution] An NRF2 activator comprising one or more chondroitin sulfate oligosaccharides selected from (a) to (c) below as an active ingredient: (a) a disaccharide having a chondroitin sulfate structure (a disaccharide of CS), (b) a trisaccharide having two N-acetyl-D-galactosamine residues and a chondroitin sulfate structure (a trisaccharide of CS having two GalNac residues), (c) a tetrasaccharide having a chondroitin sulfate structure (a tetrasaccharide of CS). According to the present invention, NRF2 can be activated. This is expected to promote homeostatic reactions in the body, such as antioxidant reactions, anti-inflammatory reactions, and detoxification reactions, and contribute to maintaining and improving health. It is also expected to contribute to the prevention and improvement of various unhealthy conditions and diseases caused by oxidative stress, inflammation, and toxic chemicals.