343 results about "Hepatic disorders" patented technology

The invention belongs to the technical field of biological medicines, and provides application of DRAM1 as a diagnosis and treatment target for resisting non-alcoholic fatty liver disease related hepatocellular carcinoma in preparation of a kit, a carrier and a medicine aiming at the problem of lack of effective treatment targets of NAFLD-related HCC. As a target spot for resisting the non-alcoholic fatty liver disease related hepatocellular carcinoma, the expression level of the DRAM1 in liver tissues of non-alcoholic fatty liver disease related hepatocellular carcinoma patients and mice is increased. According to the application disclosed by the invention, research is developed aiming at the effect of the DRAM1 in the generation and development of NAFLD-related HCC, the analysis of TCGA liver cancer queue data and a GSE164760 data set is taken as an entry point, the influence of the DRAM1 on the diagnosis and prognosis of the liver cancer is comprehensively analyzed, and verification is carried out through a mouse in-vivo experiment, so that a new thought and a new target spot are provided for clinical diagnosis and treatment of the liver cancer.

The invention relates to the field of biological medicine, in particular to application of hispidulin in preparation of a lipid de novo synthesis inhibitor or a metabolism-related fatty liver disease treatment or prevention product. The hispidulin disclosed by the invention has a chemical structure as shown in a formula (I). The hispidulin in the invention reverses liver cell lipid droplet excessive infiltration induced by high-dose fructose in a dose-dependent manner; furthermore, the hispidulin dose-dependent ameliorating obesity signs in HFD-induced MAFLD model mice, including liver weight, body weight, blood lipid level, liver fat content, and insulin resistance, without significantly reducing food intake.

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.

The invention belongs to the field of traditional Chinese medicines, and relates to a traditional Chinese medicine composition for treating liver depression and spleen deficiency syndrome metabolism-related fatty liver disease, which is prepared from the following raw materials in parts by weight: 8 to 10 parts of ginseng, 10 to 15 parts of radix bupleuri, 10 to 15 parts of radix curcumae, 6 to 9 parts of ginger processed pinellia, 6 to 10 parts of fructus amomi, 10 to 15 parts of rhizoma atractylodis, 10 to 15 parts of poria cocos, 10 to 15 parts of semen hoveniae, 10 to 15 parts of radix rehmanniae, 8 to 10 parts of rhizoma polygoni cuspidati and 6 to 9 parts of lignum dalbergiae odoriferae. The traditional Chinese medicine composition is used for treating the metabolism-related fatty liver diseases from the aspects of liver depression, spleen deficiency and phlegm-blood stasis, starts from the core pathological chain of liver depression, spleen deficiency, phlegm-dampness and blood stasis, has the functions of soothing the liver, tonifying the spleen, resolving dampness, reducing fat and promoting blood circulation to remove meridian obstruction, and is particularly suitable for patients with liver depression, spleen deficiency and metabolism-related fatty liver diseases. Clinical tests prove that the traditional Chinese medicine composition has a good treatment effect on patients with liver depression and spleen deficiency syndrome metabolism-related fatty liver diseases, the total effective rate reaches 94% or above, and the traditional Chinese medicine composition is mild in medicine property, good in safety, stable in curative effect, not prone to relapse and suitable for being taken for a long time.

The present invention relates to a composition for inducing liver disease in a mammal and a mammal with a liver disease induced using the same. The animal model of the present invention has been found to be an excellent animal model in which fatty liver, hepatic fibrosis, and insulin resistance are evenly induced, and which successfully reproduces the progression of a series of severe liver diseases, from hepatitis and excessive fibrogenesis in liver tissue through tissue hardening (cirrhosis) to liver cancer, and reflects the characteristics of each stage with high reliability. Accordingly, the present invention may be useful as a means for developing a therapeutic agent for chronic liver disease as well as studying the molecular and circulatory mechanisms of each stage of liver disease.

The present disclosure provides double stranded oligonucleotides, compositions, and methods relating thereto. The present disclosure encompasses the recognition that structural elements of double stranded oligonucleotides, such as base sequence, chemical modifications (e.g., modifications of sugar, base, and / or internucleotidic linkages) or patterns thereof, and / or stereochemistry (e.g., stereochemistry of backbone chiral centers (chiral internucleotidic linkages), and / or patterns thereof, can have significant impact on oligonucleotide properties and activities, e.g., RNA interference (RNAi) activity, Ago2 loading, thermal stability, in vivo stability, delivery to tissues and into cells, etc. The present disclosure also provides methods for treatment of diseases, e.g., hepatic diseases, central nervous system (CNS) diseases, etc., using provided double stranded oligonucleotide compositions, for example, in RNA interference.

The invention belongs to the technical field of biological pharmacy, and provides an application of jonquil glucoside in preparation of a medicine for treating a metabolism-related fatty liver disease, and the application is that the jonquil glucoside is applied to preparation of the medicine for treating the metabolism-related fatty liver disease. The treatment effect of the jonquil glycoside on MASLD is evaluated by adopting a method for establishing a fatty liver model through induction of HFD high-fat, high-fructose and high-cholesterol feed. Results show that the jonquil glucoside can reduce the liver weight by inhibiting weight gain, reduce the content of TC and TG in serum, improve the conditions of liver inflammation and fat change, reduce the oxidative stress level of liver tissue and restore SIRT1 protein expression of the liver tissue to achieve the purpose of treating MASLD.

The invention discloses a multi-classification risk prediction method and system for liver diseases based on machine learning, and relates to the technical field of biomedicine, and the method comprises the following steps: collecting fatty liver disease diagnosis results and biochemical indexes of a subject to form a training sample set, the method comprises the following steps: screening out biochemical indexes significantly related to fatty liver diseases through single-factor regression analysis, determining potential risk factors, carrying out multicollinearity test on the factors, screening out risk factors, constructing a plurality of machine learning classification models for training, and selecting a model with the best performance as a reference model. The contribution degree of each important risk factor is evaluated and sorted, classification significant factors are determined, the significant factors serve as classification metadata, a plurality of judgment models are trained, input factors are dynamically selected according to contribution values, and finally a fatty liver disease degree classification result is output, so that complex conditions under different sample features and clinical backgrounds are better handled; and the accuracy of prediction results is improved.

The invention discloses an application of costunolide in preparation of a medicine for treating and / or preventing a non-alcoholic fatty liver disease. It is found that costunolide can activate an Nrf2-ARE signal channel of a body, liver cell lipid metabolism abnormality is effectively improved from the molecular level, and meanwhile the pathological influence of oxidative damage on liver tissue is remarkably relieved. Experimental data show that the compound has a remarkable intervention effect on NAFLD, a scientific basis is provided for development of a novel liver disease treatment agent due to the unique dual regulation and control mechanism of the compound, particularly, the compound shows an important development prospect in the field of clinical intervention of metabolism-related liver injury, and an innovative solution is provided for NAFLD lacking a special-effect therapy at present.

The invention discloses an FAM20B protein and application of an FAM20B protein inhibitor in prevention or treatment of glucolipid metabolism related diseases. Specifically, the invention discloses an application of an FAM20B protein and / or an FAM20B gene in regulation and control of liver glycolipid metabolism. The invention also discloses application of the FAM20B inhibitor in improving, preventing or treating liver glycolipid metabolism disorder or glycolipid metabolism related diseases (such as diabetes, metabolism related fatty liver disease MAFLD, obesity and the like). Experiments show that the FAM20B inhibitor can reduce the liver gluconeogenesis level, relieve impairment of glucose tolerance, relieve hyperglycemia of diabetic patients, reduce the fat content of the whole body and the liver, relieve liver lipid deposition, promote energy consumption, reduce food intake, promote fat burning and reduce liver fat accumulation; the compound can be used for preparing medicines for preventing and treating glucose and lipid metabolism disorder or glucose and lipid metabolism related diseases, and has a wide application prospect in the fields of prevention and treatment of metabolism related diseases.

The present embodiments are directed to methods of using glycine transporter inhibitors, such as GlyT1 inhibitors, or pharmaceutically acceptable salts, solvates or prodrugs thereof, or pharmaceutical compositions thereof, for preventing or treating a hepatic porphyria, and related syndromes thereof.

25HC3S choline and crystalline 25HC3S choline are described in the present application. Further disclosed herein are pharmaceutical formulations of 25HC3S choline (e.g., containing crystalline 25HC3S choline) and methods of using the pharmaceutical formulations 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, hypercholesteremia, hypertriglyceridemia, and the like. Methods of treating fatty liver disease (AFLD), alcoholic steatohepatitis (ASH), leptin resistance, leptin deficiency, diabetic conditions, autoimmune conditions, inflammatory conditions, neurological conditions, Epstein-Barr virus associated growth, and conditions associated with fat accumulation and inflammation are provided. Also provided herein are methods of making 25HC3S, including crystalline 25HC3S choline.

The invention belongs to the field of traditional Chinese medicine compositions, and relates to a liver-clearing, spleen-enlivening and stasis-removing composition for treating non-alcoholic fatty liver disease, the liver-clearing, spleen-enlivening and stasis-removing composition comprises the following raw materials by weight: 10-25 g of oriental wormwood, 20-30 g of tea tree root, 20-30 g of adiantum capillus, 5-15 g of earthworm, 5-15 g of sophora flower, 5-10 g of bamboo shavings, 3-6 g of rhizoma nardostachyos, 3-6 g of lotus plumule, 6-12 g of lucid ganoderma, 10-15 g of roxburgh rose, and 5-15 g of honey-fried licorice root. The composition is used for treating the non-alcoholic fatty liver disease according to the idea of'stasis, phlegm, depression and deficiency 'and the viscera dredging theory, through a viscera connection treatment method of clearing liver and relieving depression, strengthening the spleen and clearing damp, and dredging intestines and removing stagnation, and through combination of medicines directly entering the liver channel for promoting blood circulation and dredging collaterals, breaking blood and removing stasis and medicines for caring healthy qi and strengthening the spleen and tonifying deficiency, the treatment effect is good, the effective rate is as high as 97.83%, and the curative effect is good. The traditional Chinese medicine composition is especially suitable for patients with phlegm-blood stasis type non-alcoholic fatty liver diseases.

The invention belongs to traditional Chinese medicine formula granules, and particularly relates to a preparation process of phlegm-eliminating and blood-activating granules and application of the phlegm-eliminating and blood-activating granules in metabolism-related fatty liver diseases. The granule comprises gynostemma pentaphylla and raw hawthorn which are used as monarch drugs, raw bighead atractylodes rhizome, rhodiola rosea and turmeric which are used as ministerial drugs, and auxiliary materials for preparing the granule. The granules with the formula for eliminating phlegm and activating blood, which are researched and developed by the invention, have the characteristics of stable property, convenience in transportation, carrying, storage and use and the like. The preparation technology is high in production efficiency and has good economic value, and the prepared granules can effectively exert the pesticide effect.

The invention discloses an application of isoquercitrin in preparation of a medicine for improving insulin resistance and diabetes-related liver diseases, and belongs to the technical field of medicines. According to the application, a high-glucose and high-fat diet and streptozotocin combined method is adopted to successfully construct a type 2 diabetes mouse model; experiments find that the isoquercitrin can effectively relieve the symptoms of weight loss and water intake increase of T2DM mice, significantly reduce the fasting blood-glucose level and improve abnormal glucose tolerance; the isoquercitrin can reduce the liver index of a T2DM mouse, relieve fatty degeneration of the liver and repair a liver cell structure; by activating a PI3K / AKT signal channel, the isoquercitrin up-regulates the expression levels of PI3K, p-AKT, p-GSK3 and GLUT4 and down-regulates the expressions of GSK3 and PEPCK at the same time, so that the insulin resistance of T2DM mice is effectively improved, the fatty degeneration of the liver is improved, and the isoquercitrin has a protection or repair effect on liver injury.

The invention discloses an application of corilagin in preparation of a medicine for treating and / or preventing a non-alcoholic fatty liver disease. It is proved for the first time that corilagin can reduce lipid accumulation and inhibit oxidative stress through an Nrf2-ARE endogenous antioxidant pathway, has an obvious improvement effect on the non-alcoholic fatty liver disease, and it is proved that corilagin is expected to serve as an alternative medicine for treating the NAFLD, and the corilagin can be used as a medicine for treating the NAFLD. The potential application value is realized on the improvement and treatment of the NAFLD disease.

This invention discloses a gRNA combination and its application in the preparation of drugs for the prevention of metabolic-associated fatty liver disease (MASLD). The gRNA combination, when mixed with Cas9 protein, yields an RNP complex, which, when microinjected into mouse zygotes, can breed a stable and heritable mouse strain with TMEM68 gene knockout. Combining lipidomics, transcriptomics, and primary hepatocyte functional verification, the core regulatory role of TMEM68 in hepatic lipid metabolism is revealed for the first time systematically. Experiments demonstrate that TMEM68 deficiency significantly reduces the storage of triglycerides (TAG) in the liver and hepatocytes, decreases lipid droplet formation, and reshapes the metabolic homeostasis of various lipids such as glycerophospholipids, cholesterol esters, and bile acids. Therefore, the gRNA combination of this invention, or the RNP complex obtained by mixing the gRNA combination with Cas9 protein, can be used to prepare drugs for the prevention of MASLD, providing a novel intervention strategy for MASLD prevention with broad application prospects.

The invention discloses a synthesis method of N-goose deoxycholyl-L-aspartic acid and application of the N-goose deoxycholyl-L-aspartic acid in preparation of a medicine for improving metabolism-related fatty liver diseases. According to the method provided by the invention, chenodeoxycholic acid and L-dimethyl aspartate hydrochloride are taken as raw materials, and a chenodeoxycholic acid-dimethyl aspartate intermediate is synthesized, so that a target compound-N-chenodeoxycholyl-L-aspartic acid with a brand new structure is efficiently prepared. The compound shows a treatment effect superior to that of obeticholic acid (OCA) in an animal model, and can effectively improve multiple indexes such as fatty degeneration, inflammation and fibrosis of the liver. The invention provides a brand new solution for major clinical challenges of insufficient curative effect, large side effect, drug withdrawal rebound and the like of the current MAFLD treatment drug, and provides a candidate compound with a wide prospect for developing a novel efficient MAFLD treatment drug.

The application provides a kind of prophylaxis and / or treatment of alcoholic liver disease, and belong to the technical field of traditional Chinese medicine.The application includes the following components by weight: turmeric extract 4.5~6 parts, radix puerariae extract 2~3 parts, raspberry extract 1~2 parts and sea buckthorn extract 0.5~1 part.The application provides a kind of prophylaxis and / or treatment of alcoholic liver disease, and belong to the technical field of traditional Chinese medicine.The application includes the following components by weight: turmeric extract 4.5~6 parts, radix puerariae extract 2~3 parts, raspberry extract 1~2 parts and sea buckthorn extract 0.5~1 part.The application provides a kind of prophylaxis and / or treatment of alcoholic liver disease, and belong to the technical field of traditional Chinese medicine.The application includes the following components by weight: turmeric extract 4.5~6 parts, radix puerariae extract 2~3 parts, raspberry extract 1~2 parts and sea buckthorn extract 0.5~1 part.

The application discloses application of aza-3 in resisting erythroleukemia, wherein the aza-3 is a compound obtained by modifying a ring of aza-3 with 3alpha-O-(Boc-proline); the application proves that the aza-3 can obviously inhibit HEL and K562 cell proliferation, reduce splenomegaly, improve anemia indexes (RBC, HGB and HCT) and splenic and hepatic pathological infiltration, and has no obvious toxic side effects on main organs such as heart, lung and kidney through in-vitro MTT experiment and a Friend virus-induced erythroleukemia mouse model.

The Applicant has discovered that the peptide of SEQUENCE ID NO: 1 (WKDEAGKPLVK) mediates changes in key biomarker activities associated with NASH (Table 1), and that the peptide is capable of penetrating HepG2 liver cells in a hepatic cell penetration assay (FIG. 1). In addition, the Applicant demonstrates that treatment with pep_260 (SEQ ID 1) for 44 days significantly relieves macro-vesicular steatosis in obese diabetic KKAy mice (FIG. 2) In a first aspect, the invention relates to the use of a peptide comprising SEQUENCE ID NO: 1, or a functional (or therapeutically effective) variant or functional fragment of SEQUENCE ID NO: 1 (hereafter “peptide active agent” or “peptide of the invention”), in a method for the treatment or prevention of non-alcoholic fatty liver disease (NAFLD), in particular non-alcoholic steatohepatitis (NASH), in a mammal.

The invention provides application of a xanthine derivative in preparation of a medicine for preventing and / or treating fatty liver diseases related to metabolic dysfunction, and belongs to the technical field of medicine preparation. The invention relates to an application of a xanthine derivative 8-[(2, 3-dihydroxy propyl) sulfo]-3-methyl-7-[(4-methylphenyl) methyl]-1H-purine-2, 6-diketone in preparation of a medicine for preventing and / or treating fatty liver diseases related to metabolic dysfunction. The xanthine derivative has dual efficacy of improving liver cell insulin sensitivity and / or reducing liver cell lipid accumulation, and provides a new way for treatment of metabolic dysfunction related fatty liver diseases and preparation of related clinical drugs.

The application belongs to the technical field of biological medicine, and particularly relates to a nano selenium compound with liver fibrosis prevention and treatment integration function and a preparation and application thereof. The preparation method is as follows: bovine serum albumin is mixed with sodium selenite, and under the reduction of glutathione, elemental selenium is generated, BSA-Se is obtained through dialysis ultrafiltration, and then the BSA-Se is reacted with dopamine hydrochloride in a Tris-HCl buffer solution in the dark to obtain a nano drug BSA-Se@PDA (BSP). The synthesis method is simple in process, convenient in operation and good in repeatability; the BSP is high in stability, good in biocompatibility, can effectively eliminate active oxygen, inhibit the activation of liver stellate cells, and thus significantly relieve liver fibrosis; meanwhile, the BSP also shows good protection in alcoholic liver injury in the fibrosis stage, realizes the dual treatment effects of'source intervention' and 'pathological process regulation' of liver fibrosis, and provides a new nano preparation and intervention strategy for the treatment of alcoholic liver disease and liver fibrosis.

The invention discloses application of auricularia auricula monomer polysaccharide ME-2 in preparation of drugs for preventing and treating fatty liver diseases related to metabolic dysfunction. The research of the invention systematically proves that ME-2 has a remarkable intervention effect on the whole course of MASLD for the first time. The invention discloses a breakthrough function of ME-2 as a liver metabolism regulator for the first time: by directly correcting liver lipid metabolism disorder (such as regulating core genes such as Srebp-1c, ACC1, FASN and the like), liver fatty degeneration can be relieved in a dose-dependent manner in the whole course of MASLD, and the serum transaminase level and dyslipidemia can be reduced. Importantly, the curative effect of the traditional Chinese medicine is derived from intervention on a metabolic root source, and is totally different from a known anti-inflammatory application mechanism. Meanwhile, ME-2 has the remarkable advantages of being clear in structure, taking metabolic regulation as a core, and being safe and non-toxic, and a brand new drug candidate is provided for prevention and treatment of MASLD.

The present invention relates to imidazo[1,2-a]pyridine and [1,2,4]triazolo[1, 5-a]pyridine derivatives of formula (I) or a salt thereof. The present compounds are inhibitors of TLR9 and useful in treating preventing, or slowing fibrotic diseases, such as e.g. liver fibrosis, renal fibrosis, biliary fibrosis or pancreatic fibrosis, nonalcoholic steatohepatitis (NASH), non-alcoholic fatty liver disease (NAFLD), chronic kidney disease, diabetic kidney disease, primary sclerosing cholangitis (PSC) or primary biliary cirrhosis (PBC), or idiopathic pulmonary fibrosis (IPF).

Metabolic dysfunction–associated steatotic liver disease (MASLD), previously known as non- alcoholic fatty liver disease (NAFLD), is a condition characterized by the accumulation of fat in the liver of individuals with no alcohol consumption, and at least one cardiometabolic risk factor (overweight / obesity, high blood pressure, high blood sugar, high triglycerides levels, low HDL-C levels). The inventors demonstrated that Rab30 silencing improve metabolic dysfunction–associated steatotic liver disease (MASLD). The present invention relates to a method for the treatment of metabolic dysfunction–associated steatotic liver disease (MASLD) in a subject in need thereof comprising the administration of a therapeutically effective amount of an inhibitor of Rab30.

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 present disclosure related to compounds that can be useful as inhibitors of PD-1, PD-Ll or the PD-1 / PD-Ll interaction. Also disclosed herein are pharmaceutical compositions of that can include a compound as described herein, or a pharmaceutically acceptable salt thereof, and uses of or methods of using a compound as described herein, or a pharmaceutically acceptable salt thereof, for the treatment of PD-L1 related diseases including, but not limited to, liver diseases, cancer, hepatocellular carcinoma, viral diseases, or hepatitis B.

The composition is prepared from humifuse euphorbia herb, exocarpium benincasae, herba asari, radix platycodonis, radix sophorae flavescentis, radix rehmanniae, leech, lumbricus, radix salviae miltiorrhizae, semen pharbitidis and radix glycyrrhizae, all the raw materials are natural medicinal raw materials, and chemical synthesis anti-hepatic fibrosis components are not contained. Through the synergistic effect of multiple components, the composition inhibits the liver fibrosis process at the molecule, cell and tissue levels, improves the liver structure and function, and can be used for preparing drugs for treating liver fibrosis caused by various causes. The invention has the advantages of naturalness, safety, multiple targets and integral regulation, and is suitable for long-term intervention of chronic liver diseases.

The invention relates to a traditional Chinese medicine composition for treating non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. The traditional Chinese medicine composition is prepared from the following raw material medicines in parts by weight: 30-90 parts of Chinese yam, 6-18 parts of pericarpium citri reticulatae, 8-24 parts of raw rhizoma atractylodis macrocephalae, 6-18 parts of fingered citron, 15-45 parts of sedum sarmentosum, 8-24 parts of penthorum chinense pursh, 8-24 parts of salvia miltiorrhiza and 8-24 parts of kudzu vine root. The invention also provides application of the traditional Chinese medicine composition in preparation of medicines for treating non-alcoholic fatty liver diseases and non-alcoholic steatohepatitis. According to the invention, the MCD-induced liver tissue injury and lipid deposition can be obviously improved. According to the invention, the mitochondrial injury caused by the non-alcoholic fatty liver injury can be improved.