30 results about "Cholemia" patented technology

The present disclosure relates to methods of administering thyroid hormone receptor agonists. The present disclosure provides methods wherein the methods maintain the activity of a given thyroid receptor agonist in ameliorating or curing obesity, hyperlipidemia, hypercholesterolemia, diabetes, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, atherosclerosis, cardiovascular disease, hypothyroidism, and related conditions, meanwhile, thyroid-related and thyroid axis-related side effects are reduced or eliminated.

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.

Provided herein are anti-Activin E antibodies having specific complementarity determining regions (CDRs) for the heavy and light chains, heavy and light chains, antigen binding fragments thereof, polynucleotides that encode the same, vectors, and host cells, and methods for treating a metabolic disorder, type 2 diabetes, obesity, an elevated triglyceride level, lipodystrophy, liver inflammation, fatty liver disease, hypercholesterolemia, an elevated liver enzyme, nonalcoholic steatohepatitis (NASH), a cardiovascular disease, cardiomyopathy, high blood pressure, and / or heart failure with the anti-Activin E antibodies disclosed herein.

Compositions and methods are described herein for treating subjects having hypercholesterolemia and / or cardiovascular disease.

The present application provides a novel thyroid hormone β receptor agonist of formula (I) having better activity, selectivity or safety and the use thereof for preventing or treating diseases related to the action of β receptor agonists, including, for example, obesity, hyperlipidemia, hypercholesterolemia, diabetes, liver diseases (fatty liver, NASH, NAFLD, etc.), cardiovascular diseases (atherosclerosis, etc.), thyroid diseases (hypothyroidism, thyroid cancer, etc.), and the like.

Disclosed are compounds of Formula I as well as pharmaceutically acceptable salts, esters, and prodrugs thereof, which are DGAT2 inhibitors. Also provided are methods of making compounds of Formula I, pharmaceutical compositions comprising compounds of Formula I, and methods of using these compounds to treat hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, type-2 diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, cognitive decline, dementia, cardiorenal diseases such as chronic kidney diseases and heart failure and related diseases and conditions, comprising administering a compound of Formula I to a patient in need thereof.

Invented are compounds of formula I and the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are DGAT2 inhibitors. Also provided are methods of making compounds of Formula I, pharmaceutical compositions comprising compounds of Formula I, and methods of using these compounds to treat hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, type-2 diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, cognitive decline, dementia, cardiorenal diseases such as chronic kidney diseases and heart failure and related diseases and conditions, comprising administering a compound of Formula I to a patient in need thereof.

A method of reducing elevated plasma levels of cholesterol in a subject is disclosed. Also disclosed is a method of treating hypercholesterolemia in a subject. The method comprises administering to the subject an effective amount of Compound 1, or a pharmaceutically acceptable salt thereof, in the absence of a cholesterol-lowering drug.

A compound represented by structural formula (I) and a pharmaceutically acceptable salt thereof and a pharmaceutical composition comprising the compound or the pharmaceutically acceptable salt thereof, can be used for treating diseases such as obesity, hyperlipidemia, hypercholesterolemia, and diabetes and also for treating other diseases such as NASH, atherosclerosis, cardiovascular diseases, hypothyroidism, thyroid cancer and other related disorders and diseases

The invention discloses application of a substance for promoting an IDH3A level in preparation of related products for treating hypercholesterolemia. According to the present invention, the IDH3A overexpression adeno-associated virus 8 (IDH3A-AAV8) is constructed for the first time, and the IDH3A-AAV8 can specifically improve the expression level of the IDH3A gene in the liver so as to effectively reduce the plasma total cholesterol level of the hypercholesterolemia model mouse, improve the liver lipid deposition and finally achieve the effective treatment of the hypercholesterolemia; meanwhile, the correlation between the IDH3A and the hypercholesteremia is disclosed for the first time, and it is proved that the hypercholesteremia can be effectively treated by improving IDH3A gene expression or enhancing IDH3A protein activity.

Provided herein are anti-Activin E antibodies having specific complementarity determining regions (CDRs) for the heavy and light chains, heavy and light chains, antigen binding fragments thereof, polynucleotides that encode the same, vectors, and host cells, and methods for treating a metabolic disorder, type 2 diabetes, obesity, an elevated triglyceride level, lipodystrophy, liver inflammation, fatty liver disease, hypercholesterolemia, an elevated liver enzyme, nonalcoholic steatohepatitis (NASH), a cardiovascular disease, cardiomyopathy, high blood pressure, and / or heart failure with the anti-Activin E antibodies disclosed herein.

Provided are compounds of formula I and the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are DGAT2 inhibitors. Also provided are methods of making compounds of Formula I, pharmaceutical compositions comprising compounds of Formula I, and methods of using these compounds to treat hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, type-2 diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, cognitive decline, dementia, cardiorenal diseases such as chronic kidney diseases and heart failure and related diseases and conditions, comprising administering a compound of Formula I to a patient in need thereof.

This invention provides saponin derivatives with improved therapeutic concentration ranges. [Solution] The present invention relates to a saponin-based saponin derivative comprising a triterpene aglycone and a first glycan and / or a second glycan, wherein the saponin derivative comprises: an aglycone core structure containing a derivatized aldehyde group; and / or the first glycan, wherein the first glycan contains a derivatized carboxyl group; and / or the second glycan, wherein the second glycan contains at least one derivatized acetoxy group. The present invention also provides use in the treatment or prevention of cancer, infectious diseases, viral infections, hypercholesterolemia, primary hyperoxaluria, hemophilia A, hemophilia B, alpha-1 antitrypsin-related liver disease, acute hepatic porphyria, transthyretin-mediated amyloidosis, or autoimmune diseases.

Provided are compounds of Formula (I) and the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are DGAT2 inhibitors. Also provided are methods of making compounds of Formula I, pharmaceutical compositions comprising compounds of Formula I, and methods of using these compounds to treat hepatic steatosis, nonalcoholic steatohepatitis (NASH), metabolic dysfunction-associated steatohepatitis (MASH), hepatic fibrosis, type-2 diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, cognitive decline, dementia, cardiorenal diseases such as chronic kidney diseases and heart failure and related diseases and conditions, comprising administering a compound of Formula I and the pharmaceutically acceptable salts, esters, and prodrugs thereof, to a patient in need thereof.

This disclosure provides crystalline forms of a compound of Formula (I), as well as pharmaceutically acceptable compositions thereof, and methods for their preparation and use in methods of treating hypercholesterolemia and other conditions related to PCSK9 activity, e.g., atherosclerosis, atherosclerotic cardiovascular disease, peripheral arterial disease, cerebrovascular disease, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions.

The present disclosure relates to novel therapeutic compounds known as RNAi agents that reduce the expression of the HMGCR receptor (expressed by the HMGCR gene), thereby reducing mRNA expression and protein expression. Such RNAi agents are useful in the treatment of diseases and disorders involving the regulation of HMGCR expression and function, such as diseases and disorders that are risk factors for ASCVD (e.g., dyslipidemia, e.g., hypercholesterolemia).

The present invention provides a pH dependent antibody having an extended half-life. In particular, the invention relates to an anti-ANGPTL3 antibody which is engineered and has pH-dependent antigen binding. The compound can be used for treating lipid metabolism disorder diseases such as homozygous family hypercholesterolemia patients (HoFH), refractory hypercholesterolemia and serious hypertriglyceridemia.

The invention belongs to the technical field of medicines, and discloses a hydroxime compound derived from an aqueous extract of heads of angelica sinensis, a dehydrated furazan compound of the hydroxime compound, and preparation and application of the hydroxime compound and the dehydrated furazan compound. In particular discloses a hydroxime compound, a dehydrated furazan compound thereof, pharmaceutically acceptable salts of the dehydrated furazan compound and a pharmaceutical composition of the dehydrated furazan compound. The invention also discloses application of the compound in preparation of medicines for treating arthritis, asthma, chronic obstructive pneumonia, pneumonia, cystic fibrosis, diabetes, obesity, hypercholesterolemia, contact dermatitis, psoriasis, atopic dermatitis, stasis dermatitis, seborrheic dermatitis, neurodermatitis and the like, inflammatory enteritis, multiple sclerosis, Parkinson's disease, cardiovascular disease, autoimmune disease, gout and the like. The invention also relates to applications in medicines or health-care products for treating hyperuricemia and cancers. Activity evaluation of a cell model for starting reporter gene expression by using an NF-kappa B reaction element proves that the compound can significantly inhibit NF-kappa B induced transcriptional regulation and is expected to become a therapeutic drug for treating the various diseases.

The present invention discloses compounds of formula (I), as thyroid hormone receptor β subtype agonists or modulators for use in methods of treatment of obesity, hyperlipidemia, hypercholesterolemia, diabetes mellitus, nonalcoholic steatohepatitis (NASH), hepatic steatosis, arteriosclerosis, cardiovascular disease, hypothyroidism, overweight, fibrosis, thyroid cancer and alopecia, and in chronic weight management or weight management.

The invention relates to double-stranded nucleic acid molecules that interfere with or inhibit G Protein-Coupled Receptor 146 (GPR146) gene expression. It further relates to therapeutic uses of such inhibition such as for the treatment of GPR146-mediated diseases, disorders or syndromes, such as hyperlipidaemia, hypercholesterolaemia, Heterozygous familial hypercholesterolaemia (HeFH), Homozygous familial hypercholesterolaemia (HoFH), autosomal recessive hypercholesterolaemia, atherosclerosis, and / or atherosclerotic cardiovascular disease.

The invention discloses a construction method and application of a fetal-derived hypercholesterolemia animal model. The fetal-derived hypercholesteremia animal model is characterized in that 20 mg / kg of aspirin with a clinical dose is given to rodents (such as Kunming mice) through oral intragastric administration in the middle and late pregnancy periods (such as 9-18 pregnancy), and typical hypercholesteremia appears after high-fat diet is given to male filial generations 8-12 weeks after the male filial generations are born. Based on mice exposed by aspirin during pregnancy, ascorbic acid is externally supplemented to maternal bodies during pregnancy, so that the liver cholesterol synthesis function and the blood cholesterol level of offspring can be effectively reduced. Therefore, the established fetal hypercholesterolemia animal model has the characteristics of novelty, reliability and simplicity and convenience in operation, meanwhile, the effect of reversing the susceptibility of offspring hypercholesterolemia by supplementing ascorbic acid to the maternal body is found, and a new thought and a new technology are provided for early prevention and treatment of fetal hypercholesterolemia.

Disclosed are compounds of Formula (I), or a pharmaceutically acceptable salt thereof: (I) wherein A, A1, A2, R1, R2 and R3 are as defined herein, which compounds have properties for antagonizing PCSK9. Also described are pharmaceutical formulations comprising the compounds of Formula I or their salts, and methods of treating cardiovascular disease and conditions related to PCSK9 activity, e.g. atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular disease and cardiometabolic conditions.

Provided are compounds of formula (I) and the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are DGAT2 inhibitors. Also provided are methods of making compounds of Formula I, pharmaceutical compositions comprising compounds of Formula I, and methods of using these compounds to treat hepatic steatosis, nonalcoholic steatohepatitis (NASH), fibrosis, type-2 diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, cognitive decline, dementia, cardiorenal diseases such as chronic kidney diseases and heart failure and related diseases and conditions, comprising administering a compound of Formula I to a patient in need thereof.

Provided are compounds of Formula I, Formula Ib or Formula Ic and the pharmaceutically acceptable salts, esters, and prodrugs thereof, which are DGAT2 inhibitors. Also provided are methods of making compounds of Formula I, Formula Ib or Formula Ic, pharmaceutical compositions comprising compounds of Formula I, Formula Ib or Formula Ic, and methods of using these compounds to treat hepatic steatosis, non-alcoholic steatohepatitis (NASH), fibrosis, type-2 diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, atherosclerosis, cognitive decline, dementia, cardiorenal diseases such as chronic kidney diseases and heart failure and related diseases and conditions, comprising administering a compound of Formula I to a patient in need thereof.

25HC3S choline and crystalline 25HC3S choline are described herein.Further disclosed herein is the pharmaceutical preparation of 25HC3S choline, for example, using crystalline 25HC3S choline, and the method of using it to treat or prevent diseases, such as non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcoholic hepatitis, acute kidney injury (AKI), psoriasis, atherosclerosis, hypercholesterolemia, hypertriglyceridemia, alcoholic fatty liver disease (AFLD), alcoholic steatohepatitis (ASH), leptin resistance, leptin deficiency, diabetic condition, autoimmune condition, inflammatory condition, neurological condition, Epstein-Barr virus-related proliferation and the condition related to fat accumulation and inflammation.Also provided is the method of preparing 25HC3S, including crystalline 25HC3S choline.

The present invention relates to a saponin derivative based on a saponin, the saponin derivative comprising a triterpenoid aglycone and a first sugar chain and / or a second sugar chain, and comprising: an aglycone core structure comprising an aldehyde group which has been derivatized; and / or a first sugar chain, wherein the first sugar chain comprises a carboxyl group which has been derivatized; and / or a second sugar chain, wherein the second sugar chain comprises at least one acetoxy group which has been derivatized. The present invention further relates to a first pharmaceutical composition comprising the saponin derivative of the present invention. Furthermore, the present invention relates to a pharmaceutical combination comprising the first pharmaceutical composition of the present invention and a second pharmaceutical composition comprising any one or more of an antibody-toxin conjugate, a receptor-ligand-toxin conjugate, an antibody-drug conjugate, a receptor-ligand-drug conjugate, an antibody-oligonucleotide conjugate, or a receptor-ligand-oligonucleotide conjugate. The present invention further relates to the first pharmaceutical composition or the pharmaceutical combination of the present invention for use as a medicament or for use in the treatment or prevention of cancer, an infectious disease, a viral infection, hypercholesterolemia, primary hyperoxaluria, hemophilia A, hemophilia B, alpha-1 antitrypsin-related liver disease, acute hepatic porphyria, transthyretin-mediated amyloidosis, or an autoimmune disease. Furthermore, the present invention relates to an in vitro or ex vivo method for transferring a molecule from the outside of a cell to the inside of said cell, comprising contacting said cell with said molecule and the saponin derivative of the present invention.

Disclosed in the present invention are a targeting system and a use thereof. The system targets and modulates the expression of any one, two or more genes selected from the following: ANGPTL3, LPA, ASGR1, PNPLA3, TTR, APOC3, PCSK9, INHBE, AGT, HSD17B13, APOB, DLG4, SLC30A8, RALA, GPR75, AGTR1, XDH, SLC2A9, ALAS1, EDNRA, and EDNRB. The targeting system of the present invention can be used for prevention or treatment of diseases such as obesity, fatty liver, hypercholesterolemia, hyperlipidemia, diabetes, hypertension, hyperuricemia, and gout.

Several salts of 25HC3S are provided, including crystalline salts of 25HC3S. Pharmaceutical formulations of the disclosed salts and methods for using them to treat or prevent diseases, such as nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), alcoholic hepatitis, acute kidney injury (AKI), psoriasis, atherosclerosis, hypercholesterolemia, hypertriglyceridemia, alcoholic fatty liver disease (AFLD), alcoholic steatohepatitis (ASH), leptin resistance, leptin deficiency, diabetic conditions, autoimmune conditions, inflammatory conditions, neurological conditions, Epstein-Barr virus-associated proliferation, and conditions associated with fat accumulation and inflammation, are also provided. Methods for preparing the disclosed salts are also provided.

The invention discloses double-stranded siRNA (small interfering Ribonucleic Acid) targeting liver Sam68 and application of the double-stranded siRNA in metabolic syndrome related diseases, and relates to the field of biological medicines. The double-stranded siRNA comprises a positive-sense strand and an antisense strand complementary to the positive-sense strand, the positive-sense strand is a modified or unmodified sequence of which the nucleotide sequence is shown as SEQ ID NO.41; the antisense strand is a modified or unmodified sequence of which the nucleotide sequence is as shown in SEQ ID NO. 42. The double-chain siRNA designed and synthesized on the basis of Sam68 can realize potent, dose-dependent and liver-limited Sam68 knock-down in vivo, inhibits liver gluconeogenesis by down-regulating glucagon signals, can reduce fasting blood-glucose, improve insulin sensitivity and protect diabetic liver from being damaged, and can be used for treating diabetic liver diseases such as diabetes mellitus, diabetes mellitus, diabetes mellitus, diabetes mellitus, diabetes mellitus and diabetes mellitus. A novel long-acting nucleic acid medicine is provided for diabetes, obesity, hypercholesterolemia, atherosclerosis and other metabolic syndrome related diseases.