CN-121971422-A - Application of 2-hydroxy-3-methyl valeric acid in weight and lipid reduction

Abstract

The invention discloses an application of 2-hydroxy-3-methyl valeric acid in weight and lipid reduction, belonging to the fields of biological medicine manufacturing, biological medical application and functional food development. The invention provides an application of 2-hydroxy-3-methyl valeric acid and derivatives thereof in weight loss for the first time, and the compound can inhibit the weight increase of a high-fat diet-induced obesity model mouse, reduce body fat and reduce the fat cell area of the high-fat diet-induced obesity model mouse. Compared with GLP-1 receptor weight-losing medicines, the weight-reducing effect is achieved by suppressing appetite, the compound 2-hydroxy-3-methyl valeric acid and derivatives thereof are not dependent on appetite suppression, but are used for preventing and treating obesity by accelerating fat metabolism intervention, so that the weight-reducing effect is achieved, and side effects caused by appetite intervention such as gastrointestinal discomfort, cardiovascular risk and the like are avoided. The invention provides a safe and effective new strategy for reducing weight and lipid.

Inventors

• HU JIANGNING
• CHEN XIAOCHEN

Assignees

• 大连工业大学

Dates

Publication Date

20260505

Application Date

20260310

Claims (10)

1. 1. The application of a small molecular compound 2-hydroxy-3-methyl valeric acid or acceptable derivatives thereof in preparing a medicament for treating or preventing obesity/overweight is characterized in that the efficacy component in the medicament contains 2-hydroxy-3-methyl valeric acid or acceptable derivatives thereof, so as to reduce the body fat content and/or reduce the weight of obese/overweight people, and the structure of the 2-hydroxy-3-methyl valeric acid is shown as follows: 。
2. 2. Use of the small molecule compound 2-hydroxy-3-methylpentanoic acid or a food acceptable derivative thereof for the preparation of a nutritional composition or a biomedical food for weight management, characterized in that the active ingredient of the nutritional composition or the biomedical food for use comprises 2-hydroxy-3-methylpentanoic acid or a food acceptable derivative thereof for achieving weight management comprising reducing body fat content and/or reducing body weight.
3. 3. The use according to claim 1 or 2, wherein the acceptable derivative is selected from the group consisting of a food or pharmaceutically acceptable salt, a racemate, a solvate and a carboxy terminal ester compound, wherein the food or pharmaceutically acceptable salt is an inorganic salt or an organic salt, wherein the inorganic salt is selected from the group consisting of sodium salt, calcium salt, potassium salt and magnesium salt, and wherein the organic salt is selected from the group consisting of meglumine salt, tromethamine salt, diethylamine salt, lysine salt, choline salt, arginine salt, terbutamine salt and N, N-dibenzylethylenediamine salt.
4. 4. The use according to claim 1, wherein the pharmaceutical dosage form is selected from the group consisting of tablets, capsules, elixirs, syrups, troches, inhalants, sprays, injections, films, patches, powders, granules, blocks, emulsions or suppositories.
5. 5. The use according to claim 1 or 2, wherein the pharmaceutical, nutritional composition or biomedical food comprises a pharmaceutical or food grade adjuvant comprising any one or more of solvents, propellants, solubilizers, co-solvents, emulsifiers, colorants, binders, disintegrants, fillers, lubricants, wetting agents, tonicity modifiers, stabilizers, glidants, flavoring agents, preservatives, suspending agents, coating materials, fragrances, carrier systems comprising liposomes, emulsions, nanoparticles, microcapsules, hydrogels, micelles, exosomes or chylomicron mimics.
6. 6. The use according to claim 1 or 2, wherein the medicament, nutritional composition or the biomedical food contains 2-hydroxy-3-methylpentanoic acid or a food acceptable derivative thereof, or a second functional component, for synergistic purposes, wherein the route of administration of the medicament is selected from oral, intravenous, subcutaneous, transdermal or nasal spray, preferably oral, subcutaneous injection, and wherein the nutritional composition or the biomedical food is administered orally.
7. 7. Use according to claim 1 or 2, characterized in that the 2-hydroxy-3-methylpentanoic acid or derivative thereof enhances the thermogenesis of adipose tissue, thereby reducing body fat content and/or body weight.
8. Use of 2-hydroxy-3-methylpentanoic acid in a medicament for the treatment or prevention of obesity and/or overweight in combination with a GLP-1 class of medicament, characterized in that the GLP-1 class of medicament is a GLP-1 receptor agonist and/or comprises a GLP-1 receptor agonistic activity, the GLP-1 class of medicament is selected from the group consisting of semaglutin, liraglutide, telipopeptide, dulatacin, exenatide, risinatide, abilutide or a pharmaceutically acceptable salt, prodrug, solvate or crystalline form thereof, and the 2-hydroxy-3-methylpentanoic acid and the GLP-1 class of medicament are administered in co-formulation or in combination as separate formulations.
9. 9. The use according to claim 8, wherein the combination is administered alone or simultaneously with the administration of the GLP-1 class of drugs to achieve weight loss, wherein the administration of the 2-hydroxy-3-methylpentanoic acid is continued after cessation of GLP-1 class of drugs for weight maintenance after weight loss to the desired target, or wherein the administration of the 2-hydroxy-3-methylpentanoic acid is gradually reduced or even stopped after weight maintenance.
10. 10. The use according to claim 9, wherein the increase in body weight of the subject at the end of the observation period of 2-12 weeks following cessation of GLP-1 drug administration is no more than 70% of the decrease in body weight during the GLP-1 drug treatment period relative to the body weight at the cessation of GLP-1 drug administration.

Description

Application of 2-hydroxy-3-methyl valeric acid in weight and lipid reduction Technical Field The invention belongs to the fields of biological medicine manufacturing, biological medical application and functional food development, and in particular relates to application of 2-hydroxy-3-methyl valeric acid in weight and lipid reduction. Background In recent years, with the improvement of living standard and the change of dietary structure, the occurrence rate of overweight and obesity is continuously rising worldwide, and the trend of younger is presented. Obesity not only significantly increases the risk of chronic diseases such as type 2 diabetes, fatty liver, cardiovascular diseases and the like, but also is a main factor causing preventable diseases and disability, and has become a serious public health and socioeconomic burden. Therefore, the development of a safe, effective and long-term nutritional intervention scheme is of great significance in controlling body weight and improving related metabolic disorders. Some drugs are approved for obesity management, such as orlistat, semaglutin and the like, but have certain side effect risks generally, so that the feasibility of long-term use of the drugs is limited. For example, orlistat may cause gastrointestinal discomfort, liver dysfunction, etc., GLP-1 receptor agonist polypeptides often accompany adverse effects such as nausea, diarrhea, dizziness, decreased lean body mass (mainly muscle tissue consumption), etc., and there is a risk of hypoglycemia in some people. Therefore, functional ingredients having higher safety and suitable for pharmaceutical or functional food use are increasingly demanded. Disclosure of Invention Aiming at the problem that the existing weight-reducing medicine has side effect risk, the invention provides 2-hydroxy-3-methyl valeric acid (HMVA) which is used as an active ingredient and is used for regulating organism fat metabolism disorder diseases. 2-Hydroxy-3-methylpentanoic acid (2-hydroxy-3-METHYLVALERIC ACID, HMVA) is a small molecular compound naturally occurring in a variety of fermented foods, such as certain yogurt, cheese, wine, etc., and therefore has a certain safety basis as a dietary source. HMVA as a metabolite of isoleucine in branched-chain amino acids, which has been reported to be a marker of maple diabetes by stimulating oxidative stress to damage the central nervous system of maple diabetics (Fontella FU et al., metab Brain Dis. 2002;17 (1): 47-54.). Although it has been found that the metabolic effect of glycolipid is related to the branched chain amino acid metabolite 2-hydroxy-3-methylpentanoic acid in animal liver (Trottier J, et al Nat Commun. 2022; 15;13 (1): 1343.), the effect of 2-hydroxy-3-methylpentanoic acid on weight and lipid reduction has not been explored. Moreover, biological activity studies on 2-hydroxy-3-methylpentanoic acid have been associated with anti-aging (von Saint Paul V, et al, plant cell 2011;23 (11): 4124-45.) and little research has been done on overweight and dyslipidemia. 2-Hydroxy-3-methylpentanoic acid (HMVA) having the formula C 6H12O3 and the molecular structural formula。 The present invention provides the use of 2-hydroxy-3-methylpentanoic acid or a pharmaceutically acceptable derivative thereof in the manufacture of a medicament for the treatment or prevention of obesity/overweight. The invention further provides the use of 2-hydroxy-3-methylpentanoic acid or a food acceptable derivative thereof for the preparation of a nutritional composition or a biomedical food for weight management comprising reducing body fat content and/or reducing body weight, improving body fat content and/or body weight. In an embodiment of the present invention, the nutritional composition is a composition containing one or more functional ingredients, optionally one or more of food acceptable carriers, auxiliary materials, excipients, diluents, fillers, sweeteners, flavoring agents, colorants, preservatives, stabilizers, emulsifiers, thickeners and the like, and is formulated and processed to further include a composition for supplementing nutrients needed by human body, regulating physiological functions of the human body or meeting specific nutritional requirements, wherein the nutritional composition can be a solid, semi-solid or liquid preparation, including but not limited to powder, granule, tablet, capsule, oral liquid, beverage, milk shake, meal replacement food, nutritional bar, and the nutrients include proteins, carbohydrates, fats, vitamins, minerals and dietary fibers. In an embodiment of the present invention, the biomedical food comprises one or more of proteins, carbohydrates, fats, vitamins, minerals, dietary fibers and other functional ingredients, and may further comprise food acceptable excipients, carriers, stabilizers, emulsifiers, flavoring agents. In an embodiment of the invention, the food or pharmaceutically acceptable derivative is selected from a food or pharmace