451 results about "Nonalcoholic steatohepatitis" patented technology

Disclosed are: a safe and highly effective prophylactic/ameliorating or therapeutic agent for NASH; and a method for using the agent. The prophylactic/ameliorating or therapeutic agent for NASH comprises a combination of at least one component selected from the group consisting of ω3PUFAs, a pharmaceutically acceptable salt thereof and an ester thereof and a PDE4 inhibitor as active ingredients.

The disclosure provides for a method for treating a fatty liver disorder in a subject in need thereof, comprising selecting a subject having or suspected of having a fatty liver disease or disorder, wherein the subject is non diabetic, pre-diabetic, mildly diabetic, or has normal or substantially normal biliary tract function; and administering a therapeutically effective amount of a pharmaceutical composition comprising ethyl eicosapentanoate (EPA-E). In some cases EPA-E present may be at least 40% by weight in total of the fatty acids and their derivatives.

The invention relates generally to compositions comprising antioxidants useful for reducing oxidative stress and lipid peroxidation, and treating chronic liver disease, chronic hepatitis C virus infection and non-alcoholic steatohepatitis. In particular, the invention relates to the preparation and oral administration of compositions comprising glycyrrhizin, schisandra, ascorbic acid, L-glutathione, silymarin, lipoic acid, and d-alpha-tocopherol. The invention also relates to the preparation and parenteral administration of compositions comprising glycyrrhizin, ascorbic acid, L-glutathione, and vitamin B-complex, preferably by infusion or intravenous injection. The invention further relates to methods of using the antioxidants, oral compositions and parenteral compositions.

The object of the present invention is to provide PPAR (peroxisome proliferator-activated receptor) activity regulators, which can be widely used for improving insulin resistance and preventing/treating various diseases such as diabetes, metabolic syndromes, hyperlipemia, high-blood pressure, vascular disorders, inflammation, hepatitis, fatty liver, liver fibrosis, NASH (non-alcoholic steatohepatitis) and obesity.

The present invention provides PPAR activity regulators which comprise an acylamide compound having the specific structure, prodrugs thereof, or pharmaceutically acceptable salts thereof.

The invention relates to the discovery that farnesoid X receptor (FXR) agonists can be used in combination with peroxisome proliferation activated receptor gamma (PPARγ) agonists to reduce drug-induced adverse side effects in patients suffering from conditions such as insulin resistance, Type II diabetes, metabolic syndrome, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and heart disease. Particularly, the present invention encompasses methods for treating patients suffering from drug-induced adverse side effects with selective PPARγ, dual PPARα/γ and pan PPARα/γ/δ agonists in combination with FXR agonists.

The present invention provides methods of treating TNF-α-mediated disorders, the methods generally involving administering to an individual in need thereof effective amounts of pirfenidone or a pirfenidone analog and a second therapeutic agent that reduces TNF-α synthesis or that reduces TNF-α binding to a TNF receptor. The present invention further provides methods for treating non-alcoholic steatohepatitis, the method generally involving administering to an individual in need thereof an effective amount of pirfenidone. The present invention further provides methods of treating end-stage or advanced Type II diabetes, the methods generally involving administering to an individual in need thereof effective amounts of pirfenidone and insulin.

Disclosed is a novel NASH marker for use in a method for detecting NASH or evaluating the severity of NASH, which utilizes at least one factor selected from the group consisting of an IL-1 receptor antagonist, sCD40, HMGB1, sPLA2 group IIA and an sPLA2 activity as the marker. Also disclosed is a method for detecting NASH or evaluating the severity of NASH in a subject, which utilizes the marker.

The present invention provides markers and methods for determining whether a subject, particularly a human subject, has or is at risk of developing, a disease such as cardiovascular disease, diabetes mellitus, insulin resistance, metabolic syndrome, NAFLD (Nonalcoholic Fatty Liver Disease) or NASH (Nonalcoholic Steatohepatitis) (e.g., within the ensuing year, two years, and/or three years). The present application also relates to the use of such markers and methods for monitoring the status of such diseases in a subject or the effects of therapeutic agents on subjects with such diseases.

The present invention is directed toward the use of thyromimetic compounds that are thyroid receptor ligands, pharmaceutically acceptable salts thereof, and to prodrugs of these compounds for preventing, treating, or ameliorating fatty liver diseases such as steatosis, non-alcoholic fatty liver disease, and non-alcoholic steatohepatitis.

Disclosed is a method and composition for nutritional compositions containing -glucosidase inhibitors, and more specifically Touchi Extract and its uses in the treatment of many disorders. These disorders include diabetes, hyperlipidemia, obesity, Metabolic syndrome/Syndrome X, COPD, malabsorption, Crohn's disease, diarrhea, constipation, irritable bowel syndrome, human immunodeficiency virus, cystic fibrosis, non-alcoholic steatohepatitis, polycystic ovarian syndrome including associate infertility, and erectile dysfunction. Further, -glucosidase inhibitors, and more specifically Touchi Extract can be used to aid healing in critical care patients and for general wound healing. Additionally, -glucosidase inhibitors, including Touchi Extract can be used to enhance athletic performance.

The present invention is drawn to a new diagnosis method for detecting the extent of alcoholic or non-alcoholic steato-hepatitis in a patient, in particular in a patient suffering from a disease involving alcoholic or non-alcoholic steato-hepatitis or who already had a positive diagnosis test of liver fibrosis and/or presence of liver necroinflammatory lesions, by using the serum concentration of easily detectable biological markers. The invention is also drawn to diagnosis kits for the implementation of the method.

A method for reducing the likelihood of developing non-alcoholic steatohepatitis (NASH) in an individual diagnosed with non-alcoholic fatty liver disease involves providing in the gut of an individual a population of beneficial bacteria selected from the group consisting of Lactobacillus species, and at least 6 grams per day of fiber to the individual to maintain a therapeutically effective amount of the beneficial bacteria in the gut of the individual. In certain embodiments, monoacylglycerolacyltransferase-3 (MGAT3) synthesis is inhibited to lower triacylglycerol (TAG) production, while in others, expression of diacylglycerolacyltransferase-2 (DGAT-2) is inhibited. The beneficial bacteria are preferably modified to produce increased amounts of butyrate and are also encapsulated in a frangible enclosure. Levels of Roseburia are preferably increased while the levels of Akkermansia spp. in the individual's gut microbiome are reduced.

The present invention provides methods of treating a subject with non-alcoholic fatty liver disease (NAFLD), insulin resistance, obesity or hyperlipidemia, comprising administering to the subject an effective amount of a compound according to Formula I:

or a physiologically acceptable salt thereof.

Methods useful for reducing or preventing non-alcoholic steatohepatitis or hepatic steatosis are provided herein. Such methods may comprise administering to a subject in need thereof a sirtuin pathway activator and/or PDE5 inhibitor alone or in combination with an amount of a branched amino acid in free amino acid form, or a metabolite thereof. Also provided herein are compositions and kits for practicing any of the methods described herein.

The present invention discloses an application of pentacyclic triterpenoid saponin represented by formulas (I) to (XIII) for the preparation of a medicine for preventing or treating AMPK-mediated diseases including fatty liver disease, inflammatory bowel disease, respiratory disease, diabetic complications and polycystic kidney disease. The compounds of formula (I) to (XIII) are especially usefulfor nonalcoholic simple fatty liver, nonalcoholic steatohepatitis, non-alcoholic steatohepatitis-induced cirrhosis, ulcerative colitis, Crohn's disease, chronic obstructive Pulmonary diseases, asthma,idiopathic pulmonary fibrosis, cystic fibrosis, allergic rhinitis, diabetic nephropathy, diabetic cardiomyopathy, diabetic ulcers, and autosomal dominant polycystic kidney disease. A pharmaceutical composition for preventing and treating the AMPK-mediated diseases of the present invention comprises a therapeutically effective amount of the compounds of the formula (I) to (XIII) or a pharmaceutically acceptable salt or a solvate thereof as an active ingredient and a pharmaceutically acceptable excipient.

The invention provides (i) a method of treating metabolic syndrome in an animal, (ii) a method of suppressing the appetite of an animal, (iii) a method of treating obesity in an animal, (iv) a method of reducing the weight of an animal in need thereof, (v) a method of reducing a blood lipid level in an animal in need thereof, (vi) a method of treating non-alcoholic steatohepatitis in an animal, and (vii) a method of inhibiting adipogenesis. The methods comprise administering an effective amount of an active ingredient, wherein the active ingredient comprises a diketopiperazine, a prodrug of a diketopiperazine or a pharmaceutically-acceptable salt of either of them to the animal. The invention also provides a kit comprising a container holding a diketopiperazine, a prodrug of a diketopiperazine or a pharmaceutically-acceptable salt of either of them; and instructions for administration. The diketopiperazines have the formula given in the application.

A compound of Formula (I):

or a metabolite thereof, or an ester of the compound of Formula (I) or the metabolite thereof, or a pharmaceutically acceptable salt of each thereof, wherein m, n, X¹ and X² are as defined herein, is useful for treating non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH).

The invention provides various novel compositions of berberine in combination with pharmacologically active organic acids, and related methods of their use in treating various diseases or disorders. The invention further provides various novel compounds prepared from berberine and pharmacologically active organic acids and prepared from ursodeoxycholic acid and pharmacologically active organic bases, and pharmaceutical compositions thereof, and methods of their preparation and therapeutic use in treating and/or preventing various diseases or disorders. The compounds and pharmaceutical compositions of the invention can be utilized to treat various diseases or disorders, such as diabetes, diabetic complications, dyslipidemia, hyperlipidemia, obesity, metabolic syndromes, pre-diabetes, atherosclerosis, heart diseases, neurodegenerative diseases, sarcopenia, muscle atrophy, inflammation, cancer and liver diseases and conditions such as fatty liver, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, cholestatic liver diseases or graft-versus-host disease of the liver. The compounds of this invention are also useful in improving liver functions in chronic viral associated liver diseases and alcohol-related liver diseases.

The invention relates to a method of diagnosing non-alcoholic steatohepatitis (NASH) using molecular markers. The inventive method consists in detecting and quantifying, in vitro in a hepatic tissue sample, the levels of a protein which can be used as a NASH molecular marker and which is selected from apolipoprotein A1, sub-unit β of the mitochondrial ATPase, leukotriene A4 hydrolase, keratin 18, guanidine acetate N-methyltransferase, superoxide dismutase, albumin, antioxidant protein 2 (isoform 1), prohibitin 1, methionine adenosyl transferase, long-chain acyl CoA dehydrogenase, selenium binding protein, antioxidant protein 2 (isoform 2), and combinations of same. The invention further consists in comparing the results obtained with the normal values of said proteins in healthy hepatic tissue. Said method can be used to diagnose NASH and/or to assess a patient's potential risk of developing NASH.

The present invention provides pharmaceutical compositions useful as agents for the inhibition of progression of diseases associated with abnormal accumulation of liver lipids. In particular, the pharmaceutical compositions of the present invention which comprise as an active ingredient a sodium/glucose co-transporter 2 inhibitor are highly suitable as an agent for the inhibition of progression of not only common fatty liver but also non-alcholic fatty liver disease (NAFL), non-alcholic steatohepatitis (NASH), hypernutritive fatty liver, diabetic fatty liver, alcholic fatty liver disease toxic fatty liver or the like.

An anti-inflammatory and anti-fibrotic antioxidant formulation for treatment of hepatic oxidative stress and cirrhosis is disclosed. The antioxidant formulation can further include at least one of a hepatitis C virus-specific or a non-alcoholic steatohepatitis-specific formulation comprising one or more compounds to retard the progression of liver fibrosis and possibly reverse an established fibrosis. Methods of treatment or therapies for treating chronic liver disease and chronic hepatitis are also provided.

The invention relates to the treatment and reduction of fibrosis, specifically hepatic fibrosis. More specifically, embodiments of the invention provide compositions and methods useful for the treatment and inhibition of hepato-fibrotic conditions associated with Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH), employing the use of 3β-arachidylamido-7α,12α-dihydroxy-5β-cholan-24-oic acid (Aramchol) or a pharmaceutically acceptable salt thereof. In other embodiments, the treatment and inhibition of hepato-fibrotic conditions caused by contact with hepatotoxic chemical substances or by mechanical obstruction is contemplated.

The present invention relates to the discovery that acetylsalicylic acid (ASA or aspirin), salicylic acid (SA) and related salicylate esters and their pharmaceutically acceptable salts, when coadministered in effective amounts with a drug or other bioactive agent which typically (in the absence of the salicylate compound) produces significant hepatotoxicity as a secondary indication, will substantially reduce or even eliminate such hepatotoxicity. Favorable therapeutic intervention results from the use of the present invention having the effect of reducing hepatotoxicity associated with the administration of certain drugs and other bioactive agents and in certain instances of allowing the administration of higher doses of a compound which, without the coadministration, would produce hepatotoxicity which limits or even negates the therapeutic value of the compound. The invention also relates to methods of reducing the likelihood of a patient at risk for non-alcoholic fatty liver diseases (NAFLD), including non-alcoholic steatohepatitis (NASH), or treating NAFLD or NASH including primary NASH, NASH secondary to liver transplantation (NASH post-liver transplantation) or cirrhosis represent alternative aspects of the present invention.