68 results about "Cholemia" patented technology

The present invention discloses a pharmaceutical composition comprising a circular RNA and a drug delivery carrier. Compared with traditional linear 1 * siRNA and annular 1 * siRNA, the number of repeated series connection of positive-sense strands is increased to include but not limited to two or more, it is accidentally found that the silence effect is remarkably enhanced, the expression level of the PCSK9 gene can be remarkably reduced, and degradation of mRNA of PCSK9 protein is mediated. The nano-particles are used for delivering oligonucleotide, so that the stability is improved, the immunogenicity is reduced, the effects of lowering cholesterol, reducing aortic plaque load and resisting atherosclerosis are improved, and the nano-particles are safe and free of obvious liver and kidney toxicity and have a wide application prospect in the aspect of preparing medicines for treating hypercholesterolemia and coronary heart disease.

Provided is a pharmaceutical composition, comprising a circular RNA and a drug delivery carrier. It is surprisingly found that compared with conventional linear 1 x siRNAs and circular 1 x siRNAs, increasing the number of tandem repeats in the sense strand to two or more significantly enhances the silencing effect, significantly reduces the expression level of the PCSK9 gene, and mediates the degradation of the PCSK9 protein mRNA. The use of nano-particles for delivering oligonucleotides features improved stability, reduced immunogenicity, improved cholesterol-lowering, aortic plaque load-reducing and anti-atherosclerotic effects, good safety, no significant liver and kidney toxicity, and therefore good prospects in preparing medicaments for treating hypercholesterolemia and a coronary heart disease.

A compound of formula (I) or (Ia), or a tautomer or a pharmaceutically acceptable salt thereof is provided. Compounds of formula (II) to (V), or a tautomer or a pharmaceutically acceptable salt thereof are also provided. These compounds and the pharmaceutical compositions containing them are useful for the treatment of diseases such as obesity, hyperlipidemia, hypercholesterolemia and diabetes and other related disorders and diseases, and may be useful for other diseases such as NASH, atherosclerosis, cardiovascular diseases, hypothyroidism, thyroid cancer and other disorders and diseases related thereto. (I), (Ia)

The present application provides a variety of salts of 25HC3S, including crystalline salts of 25HC3S. Provided herein are pharmaceutical formulations of the salts of the invention, and methods of treating or preventing diseases therewith, the 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 conditions, autoimmune conditions, inflammatory conditions, and the like. Nervous system disorders, EB virus related growth, and disorders associated with fat accumulation and inflammation. Methods of making the salts of the present application are also provided.

A method for improving gut microbiota population in a subject by administering a composition comprising allulose, erythritol or a combination thereof. A method for increasing one or more colonic bacterial populations from the families Lachnospiraceae or Eubacteriaceae by administering a composition comprising allulose, erythritol or a combination thereof. A method for preventing, treating or ameliorating a disease in a subject by administering a composition comprising allulose, erythritol or a combination thereof. The disease may be one or more of metabolic syndrome, obesity, type 2 diabetes, insulin resistance, hyperlipoproteinemia, hyperuricemia, hepatic steatosis, hypercholesterolemia, hypertriglyceridemia, irritable bowel syndrome (IBS), colon cancer, allergy, non-alcoholic fatty liver disease, inflammatory bowel disease, cardiovascular disease, or inflammation. The bacterial population may be the species Anaerostipes hadrus, Blautia obeum, Anaerobutyricum hallii, Eubacterium rectale (Agathobacter rectalis), Eubacterium callanderi, Eubacterium limosum and Eubacterium maltosivorans. A composition comprising allulose, erythritol or a combination thereof and one or more colonic bacterial populations from the families Lachnospiraceae or Eubacteriaceae is also provided. The composition may in the form of a food composition.

The present invention provides methods for treating patients suffering from familial hypercholesterolemia, including both HeFH and HoFH. The methods of the invention provide for lowering at least one lipid parameter in the patient by administering a therapeutically effective amount of an antibody or antigen-binding fragment thereof that specifically binds to ANGPTL3 in combination with a therapeutically effective amount of a statin, a first lipid lowering agent other than a statin, and a second lipid lowering agent other than a statin. The first non-statin lipid lowering agent is an agent that inhibits cholesterol uptake (e.g. ezetimibe) and the second non-statin lipid-lowering agent is an inhibitor of microsomal triglyceride transfer protein (e.g. lomitapide). The combination therapy is useful in treating hypercholesterolemia, as well as hyperlipidemia, hyperlipoproteinemia and dyslipidemia, including hypertriglyceridemia, chylomicronemia, and to prevent or treat diseases or disorders, for which abnormal lipid metabolism is a risk factor, such as cardiovascular diseases.

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 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.

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

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 relates to a conjugate for transferring an effector molecule from outside a cell into said cell, the conjugate comprising at least one effector molecule to be transferred into the cell, at least one saponin of the mono-desmosidic triterpene glycoside type or the bi-desmosidic triterpene glycoside type, and at least one single-domain antibody (sdAb), covalently bound to each other, wherein the sdAb is capable of binding to a cell-surface molecule of said cell. The invention also relates to a pharmaceutical composition comprising the conjugate of the invention. Furthermore, the invention relates to a pharmaceutical composition of the invention, for use as a medicament. In addition, the invention relates to a pharmaceutical composition of the invention, for use in the treatment or the prophylaxis of any one or more of: a cancer, an auto-immune disease such as rheumatoid arthritis, an enzyme deficiency, a disease related to an enzyme deficiency, a gene defect, a disease relating to a gene defect, an infection such as a viral infection, hypercholesterolemia, primary hyperoxaluria, haemophilia A, haemophilia B, alpha-1 antitrypsin related liver disease, acute hepatic porphyria, an amyloidosis and transthyretin-mediated amyloidosis. The invention also relates to an in vitro or ex vivo method for transferring the conjugate from outside a cell to inside said cell or for transferring the effector molecule comprised by the conjugate of the invention from outside a cell to inside said cell, preferably to the cytosol of said cell.

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.

This disclosure relates to a nucleic acid comprising a double stranded RNA molecule comprising sense and antisense strands and further comprising a single stranded DNA molecule covalently linked to at least the 5′ end of either the sense or antisense RNA part of the molecule wherein the double stranded inhibitory RNA targets genes associated with cardiovascular disease in the treatment hypercholesterolemia and diseases associated with hypercholesterolemia such as cardiovascular disease.

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 or salts thereof, wherein A, B, D, X, R1, R2, and R8 are as defined herein, and wherein the compounds have PCSK9 antagonistic properties. Also described are pharmaceutical formulations comprising the compounds of Formula I or salts thereof, and methods for treating cardiovascular diseases and conditions associated with PCSK9 activity, such as atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or related cardiovascular diseases and cardiometabolic conditions. #imgabs0#

The invention relates to application of guaiacol or a derivative thereof in preparation of a medicine for preventing or treating metabolic syndrome, and belongs to the technical field of medicines. The guaiacol and the derivative thereof provided by the invention have the advantages that by regulating a fat metabolism pathway, the insulin resistance condition is obviously improved, the inflammatory response and oxidative stress injury are relieved, and the prevention and treatment on the metabolism-related fatty liver disease (MASLD), hyperlipidemia, hypercholesteremia, obesity and diabetes mellitus are realized through the synergistic effect of multiple dimensions.

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.

Disclosed are compounds of Formula I: wherein A, B, D, X, R1, R2 and R8 are as defined herein, or salts thereof, which have the properties of antagonizing PCSK9. Also described are pharmaceutical formulations comprising the compounds of Formula I, or salts thereof, and methods of treating cardiovascular diseases and conditions associated with PCSK9 activity, such as atherosclerosis, hypercholesterolemia, coronary heart disease, metabolic syndrome, acute coronary syndrome, or associated cardiovascular diseases and cardiovascular metabolic conditions.

The present invention concerns multifunctional antibody construct containing at least one antibody Ab and two distinct payloads D1 and D2 of structure (1) or (2). Wherein L1, L2, L3, L4 and L5 are linkers; x1 and x2 are each individually an integer in the range of 1-8, wherein x1+x2=2-10; BM is a branching moiety; m and n are each independently 0 or 1; x3 is an integer in the range of 1-4; and D1 and D2 are two distinct payloads selected from the group consisting of polypeptides, small molecules, cytotoxins and oligonucleotides, wherein at least one of D1 and D2 is a polypeptide. The multifunctional antibody construct according to invention are suitable for use in medicine, such as for use in the treatment of cancer, a viral infection, a bacterial infection, a neurological disease, an autoimmune disease, an eye disease, hypercholesterolemia and amyloidosis.

The application relates to application of guaiacol or a derivative thereof in preparation of a medicine for preventing or treating metabolic syndrome, and belongs to the technical field of medicines. The guaiacol and the derivative thereof provided by the application can significantly improve insulin resistance conditions by regulating a fat metabolism channel, and can simultaneously reduce inflammatory reaction and oxidative stress damage, and can realize prevention and treatment of metabolic associated steatohepatitis (MASLD), hyperlipidemia, hypercholesterolemia, obesity and diabetes through synergistic action in multiple dimensions.

Prenylated tetrahydroquinolines and quinolines and pharmaceutical compositions comprising the same. Prenylated tetrahydroquinoline and quinolines and pharmaceutical compositions comprising the same, for use in the prevention and / or treatment of peroxisome proliferator-activated receptor (PPAR)-mediated diseases such as metabolic syndrome, type 2 diabetes mellitus, dyslipidemia, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, obesity, dyslipidemic atherosclerosis, metabolic dysfunction- associated fatty liver disease (MAFLD), cardiovascular disease, cardiometabolic disease, neurodegenerative disease, Friedreich's ataxia, Parkinson's disease, multiple sclerosis, Alzheimer's disease, autoimmune disease, rheumatoid arthritis, autoimmune thyroid disease, dermatological disease, and cancer.

Compounds of Formula I, Formula Ib, or Formula Ic, and pharmaceutically acceptable salts, esters, and prodrugs thereof are provided, which are DGAT2 inhibitors. Also provided are methods of preparing compounds of Formula I, Formula Ib, or Formula Ic, pHARMACEUTICAL COMPOSITIONS COMPRISING COMPOUNDS OF Formula I, Formula Ib OR Formula Ic AND USE OF THEIR FOR THE TREATMENT OF LIVER STEATIVE DEGENERATION, NON-ALCOHOLIC STEATIVE HEPATITIS (NASH), FIBROSIS, TYPE 2 DIABETES, OBESITY, HYPERLiPIA, HYPERCHROCHROLEASE, Atherosclerosis, DECIDERATION OF COGNITION, DEmentia, HEART-KITE DISEASES (e.g. And methods of treating diseases and conditions related thereto, comprising administering to a patient in need thereof a compound of Formula I, Formula Ib, or Formula Ic. # imgabs0 #

Methods of treating diseases and conditions in human subjects in need thereof using pharmaceutical compositions comprising an ANGPTL3 RNAi agent are described, the treatment being partially mediated by reducing expression of the ANGPTL3 gene. When administered to a human subject in need thereof according to the methods disclosed herein, the disclosed pharmaceutical compositions comprising an ANGPTL3RNAi agent treat diseases and conditions associated with elevated triglyceride (TG) levels and / or elevated low density lipoprotein cholesterol (LDL-C), such as hypertriglyceridemia (including severe hypertriglyceridemia (SHTG)), homozygous familial hypercholesterolemia (HoFH), hypertriglyceridemia-induced pancreatitis, metabolic syndrome, obesity, hyperlipidemia, mixed dyslipidemia, abnormal lipid and / or cholesterol metabolism, atherosclerosis, cardiovascular disease, type II diabetes, coronary artery disease, and the like. The present invention relates to compounds of formula (I), in particular to compounds of formula (I), such as non-alcoholic steatohepatitis, non-alcoholic fatty liver disease, heterozygous familial hypercholesterolemia (HeFH), statin-resistant hypercholesterolemia, other dyslipidemia, and other metabolism-related conditions and diseases.

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.

Provided herein are recombinant phage, probiotic vaccines and therapeutics comprising recombinant phage; and related methods of using same. In some embodiments, it includes recombinant phage (e.g., filamentous) and / or probiotic vaccines comprising a recombinant filamentous phage genome; and therapeutic methods of using the invention recombinant phage and / or probiotic vaccines. The invention recombinant filamentous phage: probiotic vaccines comprising said recombinant phage are useful wherein, for example, in therapeutic methods for preventing, treating, and / or reducing the risk of cancer, autoimmune diseases, respiratory diseases (e.g., asthma), neurological diseases, infectious diseases, among other diseases (osteoporosis, elevated cholesterol, among others).

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 belongs to the technical field of dermatan sulfate application, and particularly relates to application of dermatan sulfate in promotion of cholesterol excretion. The cholesterol excretion promoting effect of dermatan sulfate is discussed through in-vivo and in-vitro experiments, and results show that dermatan sulfate has the effect of promoting cholesterol excretion of liver cells, not only can reduce blood fat and liver lipid and promote excretion of cholesterol to excrement, but also can inhibit expression of ASGR1, further up-regulates LXR alpha, and has the effect of promoting cholesterol excretion of liver cells. The expression of ABCA1 and ABCG5 transporters is improved to promote cholesterol excretion and reduce the in-vivo lipid level. Therefore, dermatan sulfate is a potential medicine for promoting cholesterol excretion, a new thought is provided for development of a targeted ASGR1 medicine for promoting cholesterol excretion, and a theoretical basis is provided for treatment of cardiovascular diseases such as hypercholesterolemia and the like.

The invention relates to a pharmaceutical combination comprising: a first conjugate comprising at least one effector molecule and a single-domain antibody (sdAb) for binding to a first cell-surface molecule; and comprising a saponin, a derivative thereof, or a second conjugate comprising a binding molecule for binding to a second cell-surface molecule and the saponin and / or the derivative thereof, wherein the saponin or the derivative thereof is a monodesmosidic or bidesmosidic triterpene glycoside. The invention also relates to a composition comprising the first conjugate and the saponin (derivative) or the second conjugate comprising the saponin (derivative). In addition, the invention relates to a pharmaceutical combination or composition of the invention, for use as a medicament, and for use in the treatment or the prophylaxis of a cancer, an auto-immune disease such as rheumatoid arthritis, an enzyme deficiency, a gene defect, a disease relating to a gene defect, an amyloidosis, a disease related to an enzyme deficiency, an infection such as a viral infection, hypercholesterolemia, primary hyperoxaluria, haemophilia A, haemophilia B, alpha-1 antitrypsin related liver disease, acute hepatic porphyria, transthyretin-mediated amyloidosis. Furthermore, the invention relates to an in vitro or ex vivo method for transferring the first conjugate of the invention from outside a cell to inside said cell, preferably to the cytosol of said cell.