32 results about "Hypercholesteraemia" patented technology

The present invention relates to use of a GLP-1R / GLP-2R dual agonist, namely dapiglutide, for reducing cholesterol, in particular total cholesterol (TC) and low-density lipoprotein cholesterol (LDL cholesterol). The invention also relates to dapiglutide for treatment of hyperlipidaemia, in particular hypercholesterolaemia.

The present invention relates to the technical field of liver-protecting formula compositions, and in particular, to a liver-protecting milk thistle formula composition, and a preparation method thereof. Technical problems: the liver-protecting milk thistle formula composition, and a preparation method thereof are intended to solve the technical problems that most of existing liver-protecting compositions in the prior art are designed for the general liver protection needs of the general population and cannot specifically treat liver damage caused by excessive alcohol intake and liver diseases such as cirrhosis, acute hepatitis, hepatitis, fatty liver, cholangitis, cholelithiasis, psoriasis, and hypercholesterolemia. Technical solution: a liver-protecting milk thistle formula composition, including the following components: silymarin, puerarin, artichoke extract, glutathione, dandelion extract, and GABA. The liver-protecting formula composition has a good therapeutic effect on liver damage caused by excessive alcohol intake, and liver diseases such as cirrhosis, acute hepatitis, hepatitis, fatty liver, cholangitis, cholelithiasis, psoriasis, and hypercholesterolemia.

The application relates to the field of biological medicine, in particular to application of TDF in serum cholesterol regulation and a verification method. The application discloses that tenofovir disoproxil fumarate (TDF) can inhibit intestinal cholesterol absorption by specifically down-regulating the expression level of NPC1L1 protein in the intestinal tract, so as to reduce serum cholesterol. The regulation has tissue specificity, and TDF has no significant influence on the expression of key genes of liver cholesterol metabolism. The application also provides a method for verifying the regulation of TDF on serum cholesterol, which is evaluated by detecting blood lipid indexes and the gene and / or protein expression level of NPC1L1 in duodenal tissue. The application provides a treatment scheme with antiviral and cholesterol-lowering effects for patients with chronic hepatitis B combined with hypercholesterolemia, and provides a new idea for developing a lipid-lowering strategy targeting intestinal cholesterol absorption.

The invention relates to the technical field of biological medicine. The invention provides a PCSK9-targeted PROTAC oral drug as well as a preparation method and application thereof. The drug comprises the following structures: a PCSK9 binding peptide, an E3 ubiquitin ligase ligand, a cell penetrating peptide and a flexible linker. The medicine provided by the invention can be used for preparing products for treating lipid metabolism disorder diseases such as hypercholesteremia and atherosclerosis. In addition, the medicine disclosed by the invention can also be combined with statins to synergistically enhance the lipid-lowering curative effect.

The disclosure provides methods of treating heterozygous familial hypercholesterolemia (HeFH) and / or atherosclerotic cardiovascular disease (ASCVD), more particularly in subjects who require additional lowering of low-density lipoprotein cholesterol (LDL-C). The method comprises administering to the subject a therapeutically effective amount of a pharmaceutical composition comprising obicetrapib or a pharmaceutically acceptable salt, hydrate, or solvate thereof.

The invention discloses a preparation method of torreya grandis gel candies with an effect of reducing total cholesterol. The invention belongs to the technical field of functional food, the Chinese torreya oil and the flaxseed oil have a synergistic effect, and after the Chinese torreya oil and the flaxseed oil are compounded, the blood fat metabolism can be effectively regulated, the total cholesterol level can be reduced, and the content of high-density lipoprotein cholesterol can be increased; the Chinese torreya oil is extracted through a low-temperature pressing process, the linseed oil is prepared through a cold pressing process, active components in the raw materials are reserved to the maximum extent, and meanwhile, the stability and uniformity of functional components in the product are ensured by combining a feeding pump filtering process and a rolling die shaping process; by optimizing the formula and the preparation process of the gel matrix, the product has good elasticity and chewing feeling, is convenient to carry and take and is suitable for daily use. The health-care food does not contain artificially synthesized additives, all the raw materials are natural sources, and the health-care food is suitable for patients with hypercholesterolemia and crowds needing to regulate blood fat, and has relatively high safety and market promotion value.

The present disclosure relates to novel therapeutic compounds, known as RNAi agents, that decrease expression of the HMGCR receptor (expressed by the HMGCR gene), thereby decreasing expression of mRNA 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 (such as, dyslipidemia, such as hypercholesteremia).

This document describes the crystalline and liquid crystalline forms of sodium 25HC3S. This disclosure includes sodium 25HC3S in forms I, II, III, V, IX, XI, and XIII, and combinations thereof. Pharmaceutical formulations of the said forms or combinations thereof are further disclosed herein, as well as methods for treating or preventing diseases such as hypercholesterolemia, hypertriglyceridemia, and conditions associated with fat accumulation and inflammation (e.g., non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), alcoholic hepatitis, acute kidney injury (AKI), psoriasis, and atherosclerosis). Methods for preparing 25HC3S are also provided.

Aspects of the disclosure relate to compositions and methods for multiplexed gene silencing in a cell or subject. In some embodiments, the disclosure provides an isolated nucleic acid or an rAAV encoding a transgene comprising a RNA-guided nuclease (RGN) operably linked to a first promoter, and a second promoter operably linked to a multi guide-RNA (multi-gRNA) expression cassette encoding one or more gRNAs targeting a gene associated with hypercholesterolemia or dyslipidemia. In some embodiments, the disclosure provides methods of treating a subject having hypercholesterolemia or dyslipidemia by administering the compositions.

The present invention relates to methods of treating or preventing cholesterol related disorders, such as hypercholesterolemia, hyperlipidemia or dyslipidemia, using antibodies against proprotein convertase subtilisin / kexin type 9 (PCSK9). Formulations and methods of producing said formulations are also described.

This invention relates to a method for treating patients with heterozygous familial hypercholesterolemia (heFH), comprising administering a pharmaceutical composition containing a PCSK9 inhibitor to a patient with heterozygous familial hypercholesterolemia. In some embodiments, the PCSK9 inhibitor is an anti-PCSK9 antibody, such as the exemplary antibody referred to herein as mAb316P. The method of the present invention can be used to treat patients with heterozygous familial hypercholesterolemia whose cholesterol is poorly controlled with the maximum tolerated dose of statins, with or without other lipid-lowering therapy.

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.

The invention provides a double-layer tablet containing ezetimibe and fenofibrate. The double-layer tablet comprises an ezetimibe quick release layer and a fenofibrate slow release layer, the ezetimibe quick-release layer comprises ezetimibe, a quick-release layer filler, a quick-release layer surfactant, a quick-release layer adhesive, a quick-release layer disintegrating agent and a quick-release layer lubricant; the fenofibrate sustained-release layer comprises fenofibrate, a sustained-release layer filler, a sustained-release layer disintegrating agent, a sustained-release layer adhesive, a sustained-release layer solubilizer, a sustained-release layer sustained-release framework material and a sustained-release layer lubricant. The invention also provides a preparation method of the double-layer tablet. The double-layer tablet provided by the invention can be used for clinical treatment of hypercholesterolemia, hypertriglyceridemia and mixed dyslipidemia, the levels of triglyceride, total cholesterol and LDL-C are comprehensively reduced, the level of HDL-C is increased, and the occurrence rate of adverse reactions is relatively low.

The invention provides an oral pharmaceutical composition containing kidney bean kinase and application thereof.The pharmaceutical composition comprises kidney bean kinase serving as an active component and a pharmaceutically acceptable carrier, the activity of kidney bean kinase is not lower than 2000 U / mg, and the kidney bean kinase up-regulates the LDL-R expression level and promotes LDL uptake and degradation by hydrolyzing PCSK9 protein in liver cells, so that the activity of the kidney bean kinase is improved, and the activity of the kidney bean kinase is improved. The lipid-lowering effect is achieved. The pharmaceutical composition containing the kidney bean kinase can be taken orally, is natural in source and high in safety, can effectively reduce expression of PCSK9 protein, and is used for treating or preventing hypercholesteremia, atherosclerosis and complications thereof.

The invention discloses a parabacteroides gore DZ001 strain with a cholesterol sulfation function and application of the parabacteroides gore DZ001 strain. The preservation number of the parabacteroides gore DZ001 is GDMCC No: 67376, and the preservation number of the parabacteroides gore DZ001 is H. The strain is separated from faeces of healthy people, a genome carries a sequence for coding sulfotransferase, cholesterol can be specifically catalyzed to generate cholesterol sulfate with higher water solubility, intestinal epithelium reabsorption is blocked, and faeces excretion is promoted. In-vitro experiments show that the strain has excellent cholesterol degradation capacity, gastrointestinal tract tolerance and safe gamma-hemolysis characteristics; in-vivo experiments prove that the traditional Chinese medicine composition can remarkably reduce serum total cholesterol and triglyceride levels of high-fat diet mice, increase high-density lipoprotein cholesterol, improve liver fatty degeneration and regulate blood glucose metabolism. The strain and viable bacteria, supernate or cell-free extract thereof can be widely applied to preparation of cholesterol-reducing health-care foods, medicines and animal feeds, and a new way is provided for prevention and treatment of hypercholesterolemia and related cardiovascular and cerebrovascular diseases.

The present invention relates to methods of treating or preventing cholesterol related disorders, such as hypercholesterolemia, hyperlipidemia or dyslipidemia, using antibodies against proprotein convertase subtilisin / kexin type 9 (PCSK9). Formulations and methods of producing said formulations are also described.

An siRNA which inhibits proprotein convertase subtilisin / kexin type 9 (PCSK9) gene expression, a pharmaceutical composition containing the siRNA, and a conjugate. Each nucleotide in the siRNA is independently a modified or unmodified nucleotide. The siRNA contains a sense strand and an antisense strand. The sense strand contains nucleotide sequence I; nucleotide sequence I having the same length as the nucleotide sequence shown in SEQ ID NO: 1, with no more than three nucleotides differences. The antisense strand contains nucleotide sequence II, nucleotide sequence II having the same length as the nucleotide sequence shown in SEQ ID NO: 2, with no more than three nucleotides differences. The siRNA, pharmaceutical composition thereof and the conjugate can effectively treat and / or prevent hypercholesterolemia.

A bispecific nucleic acid molecule comprising at least two double stranded inhibitory ribonucleic acid (RNA) molecules that silence by RNA interference apolipoprotein B (ApoB) and diacylglycerol O acyltransferase 2 (DGAT2) wherein said at least two double stranded inhibitory RNA molecules are linked by a DNA linker molecule that has a melting temperature (TM) of approximately 73oC. The use of such dual siRNA constructs in treating cardiovascular related conditions including hypercholesterolemia is further claimed. [Fig. 2A]

The present invention provides methods for treating diseases and disorders associated with elevated lipid and lipoprotein levels. These methods consist of administering a pharmaceutical composition containing a PCSK9 inhibitor to a patient at high cardiovascular risk. In certain formulations, the PCSK9 inhibitor is an anti-PCSK9 antibody, such as the example antibody designated mAb316P or alirocumab. The methods of the present invention are useful for treating patients at high cardiovascular risk who have hypercholesterolemia and elevated levels of other atherogenic lipoproteins that are not adequately controlled with the maximum tolerated dose of statins.In particular, the methods of the present invention are useful for reducing cardiovascular risk and decreasing atherogenic lipoproteins in patients with high cardiovascular risk during the 12 months following an acute coronary syndrome event, despite treatment with the maximum tolerated dose of statins.

An siRNA which inhibits proprotein convertase subtilisin / kexin type 9 (PCSK9) gene expression, a pharmaceutical composition containing the siRNA, and a conjugate. Each nucleotide in the siRNA is independently a modified or unmodified nucleotide. The siRNA contains a sense strand and an antisense strand. The sense strand contains nucleotide sequence I; nucleotide sequence I having the same length as the nucleotide sequence shown in SEQ ID NO: 1, with no more than three nucleotides differences. The antisense strand contains nucleotide sequence II, nucleotide sequence II having the same length as the nucleotide sequence shown in SEQ ID NO: 2, with no more than three nucleotides differences. The siRNA, pharmaceutical composition thereof and the conjugate can effectively treat and / or prevent 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 experimental animal model construction, and particularly relates to a method for constructing an arteriosclerosis mouse model by using humanized flora. The technical problem to be solved by the invention is to establish an arteriosclerosis phenotype humanized mouse model taking intestinal flora of a patient with coronary artery disease as a donor source. According to the technical scheme, the method for constructing the arteriosclerosis mouse model by using the humanized flora comprises the following steps: collecting an excrement sample of a patient diagnosed as arteriosclerosis, and preparing a flora suspension; the sterile mouse is subjected to gavage, gavage is conducted once every other day, and gavage is conducted five times; lavage is carried out once a week; and the whole process lasts for 10-13 weeks from the beginning of gavage. The mouse model constructed by the method can systematically evaluate key pathological phenotypes of hypercholesteremia, vascular dysfunction, immune activation and the like of the mouse.

The present disclosure relates to RNAi agents, e.g., double-stranded RNAi agents, e.g., small interfering RNA (siRNA) molecules, capable of inhibiting the expression of the proprotein convertase subtilisin kexin 9 (PCSK9) gene. Pharmaceutical compositions comprising the PCSK9 RNAi agent and methods of using the same are also disclosed. In some embodiments, the PCSK9 RNAi agents disclosed herein can be conjugated to targeting ligands, including ligands comprising N-acetyl-galactosamine, to facilitate delivery to hepatocytes. In vivo delivery of the PCSK9 RNAi agent provides inhibition of expression of the PCSK9 gene, and thus reduction of the PCSK9 protein. RNAi agents may be used in methods of treating diseases or conditions mediated at least in part by PCSK9 gene expression, said diseases or conditions include, inter alia, hypercholesterolemia, familial hypercholesterolemia including heterozygous familial hypercholesterolemia (HeFH) and homozygous familial hypercholesterolemia (HoFH), familial low beta-lipoproteinemia, hyperlipidemia, coronary artery disease, polygene dyslipidemia, heart disease, cardiovascular disease (CVD) comprising clinical atherosclerotic cardiovascular diseases (ASCVD).

The present disclosure relates to genome editing systems and components for targeting, editing, and / or modulating the expression of a target nucleic acid sequence of interest, e.g., an LDLR target nucleic acid sequence in the 3' untranslated region (UTR) of the gene encoding the LDLR protein. The present disclosure is also directed to methods and applications thereof in connection with the treatment and / or management of hypercholesterolemia.

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.

The invention relates to the technical field of biological medicine. The invention provides a PCSK9-targeted PROTAC medicine as well as a preparation method and application thereof. The medicine comprises the following structures: a PCSK9 binding peptide, an E3 ubiquitin ligase ligand, a cell penetrating peptide and a flexible linker. The medicine provided by the invention can be used for preparing products for treating lipid metabolism disorder diseases such as hypercholesteremia and atherosclerosis. In addition, the medicine disclosed by the invention can also be combined with statins to synergistically enhance the lipid-lowering curative effect.

The present invention relates to a nucleic acid conjugate having a dual-target-gene inhibitory effect and the use thereof. Provided is a liver-targeting double-stranded nucleic acid conjugate capable of simultaneously inhibiting PCSK9 mRNA and LPA mRNA, which nucleic acid conjugate comprises a first nucleic acid single strand and a second nucleic acid single strand that are partially or completely complementary, each containing a region at least partially complementary to a sequence of PCSK9 mRNA or LPA mRNA. The double-stranded nucleic acid conjugate can be cleaved to form two independent siRNA conjugates, which respectively inhibit two target genes. The nucleic acid conjugate of the present invention has a therapeutic effect on hypercholesterolemia.