2-hydroxycitric acid composite salt as well as preparation method and application thereof

Abstract

The invention relates to the technical field of pharmaceutical preparations, in particular to 2-hydroxycitric acid composite salt as well as a preparation method and application thereof. The 2-hydroxy citric acid composite salt comprises R and 2-hydroxy citric acid M salt, wherein R is any one of L-arginine, L-lysine, L-histidine or L-carnitine, and R is any one of L-arginine, L-lysine, L-histidine and L-carnitine; m is any one of calcium, magnesium, iron or zinc. The preparation method comprises the following steps: reacting 2-hydroxycitric acid M salt with R in water, and then carrying out rotary evaporation, crystallization, filtration and drying to obtain the 2-hydroxycitric acid composite salt. The 2-hydroxycitric acid composite salt provided by the invention is a novel solid compound, is stable in property, has a weight-losing effect, can be made into various dosage forms required by consumers, and has a wide application prospect; the provided preparation process is simple and beneficial to conversion production.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical preparations, and in particular to a 2-hydroxycitric acid composite salt and a preparation method and application thereof. Background Art

[0002] With the development of social economy, people's sugar and fat intake continues to rise, coupled with the reduction of physical labor, leading to a continuous increase in obesity rates. Obesity can cause various cardiovascular and cerebrovascular diseases, and the situation is not optimistic.

[0003] Commonly used weight loss drugs include orlistat, GLP-1 receptor agonist series, lorcaserin, metformin, acarbose, phentermine-topiramate compound preparations, naltrexone-bupropion compound preparations, etc. Orlistat is a commonly used weight loss drug approved by the US FDA. It mainly inhibits the activity of gastrointestinal lipase and prevents the hydrolysis and absorption of fat in the intestine, thereby achieving the effect of weight loss and lipid reduction. However, orlistat also has certain side effects, which will affect the absorption of fat-soluble vitamins A and E. GLP-1 receptor agonists exert the effect of incretin by stimulating glucagon-like peptide-1 (GLP-1) receptors, thereby producing a hypoglycemic effect. However, GLP-1 receptor agonists often have gastrointestinal side effects, such as nausea, vomiting, constipation, diarrhea, abdominal pain, indigestion, etc., and their injection method of administration also brings inconvenience to users. Lorcaserin is a selective 5-hydroxytryptamine 2C receptor agonist that reduces food intake by regulating the appetite center. It is a psychotropic drug with many and significant side effects, including headache, dizziness, fatigue, nausea, dry mouth and constipation. Metformin acts on the liver, inhibits gluconeogenesis and glycogenolysis, and enhances the uptake and utilization of insulin by peripheral tissues (such as muscle and fat). It is generally used for the treatment of diabetes and is not suitable for weight loss in non-disease populations. Acarbose mainly inhibits the activity of α-glucosidase in the small intestine, slows down the decomposition and absorption rate of carbohydrates such as starch and disaccharides in food, thereby reducing postprandial blood sugar levels; long-term use of acarbose may have a certain effect on the liver, leading to elevated liver enzymes and yellow skin. Phentermine-topiramate compound preparation is an effective weight loss drug that achieves weight loss by suppressing appetite and enhancing satiety, but the drug also affects the body's central nervous system and cardiovascular system, causing the user to have a faster heartbeat, tension, insomnia, etc. Naltrexone-bupropion combination preparations work by inhibiting the reuptake of dopamine and norepinephrine in the synaptic cleft, activating related neurons, and suppressing appetite, especially the craving for sweets, but they are more likely to cause sleep difficulties, anxiety, and irritability.

[0004] 2-Hydroxycitric acid (HCA) can inhibit the activity of adenosine triphosphate citrate lyase (ACLY), which plays a key role in the synthesis of fatty acids, cholesterol and triglycerides. By inhibiting the activity of this enzyme, HCA can reduce the synthesis of fatty acids; the fat-reducing mechanism of L-carnitine is to transport long-chain fatty acids to mitochondria for β-oxidation, thereby promoting fat burning; however, the fat-reducing effects of both are relatively simple. Summary of the invention

[0005] In view of the above technical problems, the present invention provides a 2-hydroxycitrate complex salt and its preparation method and application. The main fat-reducing mechanism of 2-hydroxycitrate is to reduce fat synthesis, while L-carnitine increases fat oxidation; therefore, the present invention combines the two to synergistically act on fat synthesis and consumption, improve fat-reducing efficiency, and reduce the dosage of a single use, thereby reducing potential side effects.

[0006] A 2-hydroxycitric acid complex salt comprises R and 2-hydroxycitric acid M salts; wherein R is any one of L-arginine, L-lysine, L-histidine or L-carnitine; and M is any one of calcium, magnesium, iron or zinc.

[0007] For better explanation, the general formula of the 2-hydroxycitric acid complex salt is shown in general formula I: Formula I The molar ratio of the R to the 2-hydroxycitrate M salt is 1:1.

[0008] Further, when R represents L-arginine, the molar ratio of R to 2-hydroxycitrate M salt is 1:1; the 2-hydroxycitrate complex salts are: L-arginine 2-hydroxycitrate calcium salt, L-arginine 2-hydroxycitrate magnesium salt, L-arginine 2-hydroxycitrate iron salt, L-arginine 2-hydroxycitrate zinc salt. For better explanation, the structural formulas are supplemented as follows: I-1 I-2 I-3 I-4.

[0009] Further, when R represents L-lysine, the molar ratio of R to 2-hydroxycitrate M salt is 1:1; the 2-hydroxycitrate complex salts are: L-lysine 2-hydroxycitrate calcium salt, L-lysine 2-hydroxycitrate magnesium salt, L-lysine 2-hydroxycitrate iron salt, L-lysine 2-hydroxycitrate zinc salt. For better explanation, the structural formulas are supplemented as follows: I-5 I-6 I-7 I-8.

[0010] Further, when R represents L-histidine, the molar ratio of R to 2-hydroxycitrate M salt is 1:1; the 2-hydroxycitrate complex salts are: L-histidine 2-hydroxycitrate calcium salt, L-histidine 2-hydroxycitrate magnesium salt, L-histidine 2-hydroxycitrate iron salt, L-histidine 2-hydroxycitrate zinc salt. For better explanation, the structural formulas are supplemented as follows: I-9 I-10 I-11 I-12.

[0011] Further, when R represents L-carnitine, the molar ratio of R to 2-hydroxycitrate M salt is 1:1; the 2-hydroxycitrate complex salts are: L-carnitine 2-hydroxycitrate calcium salt, L-carnitine 2-hydroxycitrate magnesium salt, L-carnitine 2-hydroxycitrate iron salt, L-carnitine 2-hydroxycitrate zinc salt. For better explanation, the structural formulas are supplemented as follows: I-13 I-14 I-15 I-16.

[0012] A method for preparing a 2-hydroxycitric acid composite salt comprises the following steps: The 2-hydroxycitric acid M salt and R are reacted in water, and the 2-hydroxycitric acid composite salt is obtained by rotary evaporation, crystallization, filtration and drying.

[0013] Furthermore, the reaction temperature is 50°C-80°C, and the reaction time is 2°C-6 hours.

[0014] The 2-hydroxycitric acid complex salt provided by the present invention can be used in the preparation of food, beverage, medicine or health care product, and the active ingredient includes any one of the above-mentioned 2-hydroxycitric acid complex salts. It is known to those skilled in the art that the 2-hydroxycitric acid complex salt referred to herein includes any one or at least two 2-hydroxycitric acid complex salts covered by the general formula I, and further refers to any one or at least two 2-hydroxycitric acid complex salts in the general formulas I-1 to I-16.

[0015] Those skilled in the art will appreciate that the food, beverage, medicine or health product of the present invention may include, in addition to the active ingredients, carriers or excipients and other ingredients acceptable in the art.

[0016] Specifically, the drug described in the present invention also includes at least one pharmaceutically acceptable excipient (drug carrier). The excipient is understood by those skilled in the art, including but not limited to disintegrants, lubricants, dispersants, etc. Those skilled in the art can choose according to the actual needs of the preparation, and the present invention does not specifically limit this.

[0017] The drug described in the present invention can be prepared into various common pharmaceutical dosage forms such as tablets, capsules, pills, powders, granules, suspensions, oral solutions, etc. by conventional methods; the administration method can be oral, sublingual, etc., and can be given to animals or humans in a unit dosage form.

[0018] Suitable unit administration forms of the drug of the present invention include oral dosage forms (such as tablets, capsules, pills, powders, granules, oral solutions or suspensions), sublingual or buccal dosage forms, intravenous, subcutaneous, transdermal or intramuscular dosage forms (such as injections, powder injections, etc.); in addition, the drug can be a conventional preparation, a sustained-release preparation, a rapid-release preparation and a controlled-release preparation.

[0019] When preparing a solid pharmaceutical composition in the form of tablets or capsules, excipients that can be added to the active ingredients include diluents such as lactose, dextrin, starch, pregelatinized starch, sucrose, mannitol, microcrystalline cellulose, etc.; binders such as polyvinyl pyrrolidone, methylcellulose, hydroxypropyl methylcellulose, etc.; disintegrants such as sodium carboxymethyl starch, cross-linked carboxymethyl cellulose, low-substituted hydroxypropyl cellulose, sodium carboxymethyl cellulose, cross-linked polyvinyl pyrrolidone, etc.; lubricants such as silicon dioxide, magnesium stearate, stearate, corn starch, talc, etc., flavoring agents such as mannitol, aspartame, saccharin sodium and stevioside, etc.; in addition, surfactants such as sodium dodecyl sulfate, sodium dioctyl sulfosuccinate, sucrose esters and poloxamer, etc. can also be added. The tablets described in the present invention can be pure tablets, and the tablets can be further made into coated tablets, such as film coatings, sugar coatings, etc. By preparing a polymer matrix or using a specific polymer in a film coating, the tablets can be made into immediate release, sustained release or controlled release dosage forms. Capsules can be soft or hard capsules, without a membrane or with a membrane, so as to have immediate release, sustained release or controlled release properties.

[0020] When preparing a pharmaceutical composition in the form of pills, excipients that may be added to the active ingredients include diluents and absorbents, such as lactose, glucose, dextrin, starch, sucrose, cocoa butter, etc.; binders, such as gum arabic, tragacanth gum, gelatin, honey, etc.; disintegrants, such as methyl cellulose, ethyl cellulose, dry starch, agar powder, alginate, etc.

[0021] When preparing oral solutions or suspensions, excipients that may be added include sweeteners, such as sodium saccharin, sucrose, sodium cyclamate, aspartame and stevioside; suspending agents, such as polyvinyl pyrrolidone, microcrystalline cellulose, sucrose, hydroxypropyl methylcellulose, etc.; preservatives, such as parabens, sodium benzoate, methyl parahydroxybenzoate, propyl parahydroxybenzoate, etc.

[0022] When preparing granules, excipients that may be added include fillers, binders, colorants and flavoring agents.

[0023] As a preferred technical solution, the present invention provides a pharmaceutical preparation, which is selected from one or at least two of tablets, capsules, granules, powders, and oral liquids, and the active ingredient of the pharmaceutical preparation includes the 2-hydroxycitric acid complex salt described in any one of the above technical solutions.

[0024] A drug weight loss tablet, comprising (consisting of the following components) by weight: 500 parts of 2-hydroxycitric acid complex salt, 10 parts to 50 parts of starch, 1 part to 10 parts of talc, 10 parts to 50 parts of microcrystalline cellulose, and 0.1 parts to 3 parts of magnesium stearate.

[0025] Preferably, it comprises (consisting of the following components): 500 parts of 2-hydroxycitric acid complex salt, 20 parts to 30 parts of starch, 2 parts to 5 parts of talc, 25 parts to 35 parts of microcrystalline cellulose, and 1 part to 3 parts of magnesium stearate.

[0026] Most preferably, it comprises (consisting of the following components): 500 parts of 2-hydroxycitric acid complex salt, 20 parts of starch, 5 parts of talc, 30 parts of microcrystalline cellulose, 2 parts of magnesium stearate.

[0027] The above-mentioned drug tablets provided by the present invention can synergistically supplement 2-hydroxycitrate M salt (M is calcium, magnesium, iron or zinc) and basic amino acids or L-carnitine and multiple nutrients at the same time. It has been verified that the absorption is good and the weight loss effect is the best according to the above-mentioned ratio. The obtained drug tablets are stable, not easy to absorb moisture, and not easy to deteriorate.

[0028] A slimming beverage, comprising (consisting of the following components) by weight: 6 parts of 2-hydroxycitric acid complex salt, 1 part to 5 parts of sodium chloride, 0.1 parts to 2 parts of sodium phytate, 0.05 parts to 0.5 parts of taurine, 1 part to 10 parts of L-ascorbic acid, 20 parts to 150 parts of anhydrous glucose, 0 parts to 5 parts of spice powder, and 500 parts to 5000 parts of pure water.

[0029] Preferably, it comprises (consisting of the following components): 6 parts of 2-hydroxycitric acid complex salt, 1 part to 3 parts of sodium chloride, 0.5 parts to 1.5 parts of sodium phytate, 0.1 parts to 0.3 parts of taurine, 1 part to 5 parts of L-ascorbic acid, 50 parts to 120 parts of anhydrous glucose, 0.1 parts to 2 parts of spice powder, and 1000 parts to 3000 parts of pure water.

[0030] More preferably, it comprises (consisting of the following components): 6 parts of 2-hydroxycitric acid complex salt, 2 parts of sodium chloride, 1 part of sodium phytate, 0.2 parts of taurine, 3 parts of L-ascorbic acid, 83 parts of anhydrous glucose, 0.8 parts of spice powder, 2000 parts of pure water.

[0031] The beverage provided by the present invention can not only supplement 2-hydroxycitrate M salt (M is calcium, magnesium, iron or zinc), but also supplement alkaline amino acids or L-carnitine, so that various substances in body fluids can quickly reach a balance, and has the effect of strengthening the body while losing weight; the above formula has been verified in large quantities, not only has universal taste, but also has more balanced nutrition and outstanding stability.

[0032] The 2-hydroxycitrate complex salt of the present invention can be used to prepare health products, which may include nutritional supplements for humans or feed supplements for animals, and specifically may include supplements for supplementing L-arginine, L-lysine, L-histidine, and L-carnitine.

[0033] The 2-hydroxycitric acid composite salt provided by the present invention has the characteristics of being suitable for oral administration, stable, and not hygroscopic, and is convenient for storage and transportation, as well as for preparing solid preparations; and has stronger and more functional nutritional effects than the corresponding 2-hydroxycitric acid M (calcium, magnesium, iron, zinc) salts, especially having the effect of supplementing L-arginine, L-lysine, L-histidine, and L-carnitine, and having a better synergistic effect in weight loss.

[0034] Compared with the prior art, the beneficial effects of the present invention are as follows.

[0035] (1) The advantage of 2-hydroxycitric acid complex salt lies in its mechanism of action of directly promoting fat metabolism and relatively few side effects. Its fat-reducing effect is better than that of common weight-loss drugs such as metformin and orlistat.

[0036] (2) It is more suitable for people who want to lose weight by enhancing fat metabolism without affecting food intake.

[0037] (3) For obese people with diabetes, 2-hydroxycitric acid complex salt is a more suitable choice and does not directly affect blood sugar levels.

[0038] (4) The drug is administered orally, which is relatively simple and has a wider range of applicability. DETAILED DESCRIPTION

[0039] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative work are within the scope of protection of the present invention.

[0040] The HPLC of the following Examples 1 to 16 was measured using the following parameters: HPLC: Column: HYPERSIL C8 (5µm) 250×4.6mm; Temperature: 25℃; Mobile phase: 0.02M KH2PO4; pH: 6.0 H3PO4; Detection wavelength: 254 nm; Flow rate: 0.6 ml / min; 2-Hydroxycitric acid: Rt = 5.8 minutes; L-arginine: Rt = 6.2 minutes; L-lysine: Rt = 7.3 minutes; L-histidine: Rt = 8.1 min; L-Carnitine: Rt = 7.8 minutes.

[0041] Example 1.

[0042] This embodiment provides a method for preparing L-arginine 2-hydroxycitrate calcium salt, which specifically adopts the following steps: Dissolve 24.7 g (0.1 mol) of 2-hydroxycitrate calcium salt in water, add 17.4 g (0.1 mol) of L-arginine, react at 80°C for 3 hours, then add 0.2 g of activated carbon for decolorization for 1 hour, filter, concentrate the filtrate by rotary evaporation, crystallize with ethanol, filter, and dry to obtain the product.

[0043] The obtained L-arginine 2-hydroxycitrate calcium salt 41.5 g has good hygroscopicity resistance and a yield of 98.6%, as shown in Table 4. As shown in Table 5, it has good fluidity.

[0044] [α] D 20 = -6.8° (C=1, 2% HCl), L-arginine HPLC content 41.3%, 2-hydroxycitric acid HPLC content 49.3%, calcium content 9.4%.

[0045] Example 2.

[0046] This embodiment provides a method for preparing L-arginine 2-hydroxycitrate magnesium salt, which specifically adopts the following steps: Dissolve 23.0 g (0.1 mol) of 2-hydroxycitrate magnesium salt in water, add 17.4 g (0.1 mol) of L-arginine, react at 70°C for 4 hours, then add 0.2 g of activated carbon for decolorization for 1 hour, filter, concentrate the filtrate by rotary evaporation, crystallize with ethanol, filter, and dry to obtain the product.

[0047] The obtained L-arginine 2-hydroxycitrate magnesium salt 39.7 g, as shown in Table 4, has good hygroscopicity resistance and a yield of 98.2%. As shown in Table 5, it has good fluidity.

[0048] [α] D 20 = -7.4°(C=1, 2%HCl), L-arginine HPLC content 42.8%, 2-hydroxycitric acid HPLC content 51.3%, magnesium content 5.9%.

[0049] Example 3.

[0050] This embodiment provides a method for preparing L-arginine 2-hydroxycitrate iron salt, which specifically adopts the following steps: Dissolve 26.2 g (0.1 mol) of 2-hydroxycitrate iron salt in water, add 17.4 g (0.1 mol) of L-arginine, react at 65°C for 5 hours, then add 0.2 g of activated carbon for decolorization for 1 hour, filter, concentrate the filtrate by rotary evaporation, crystallize with ethanol, filter and dry to obtain the product.

[0051] The obtained L-arginine 2-hydroxycitrate iron salt 43.2 g has good hygroscopicity resistance and a yield of 99.1%, as shown in Table 4. As shown in Table 5, it has good fluidity.

[0052] [α] D 20 = -6.4°(C=1, 2%HCl), L-arginine HPLC content 40.0%, 2-hydroxycitric acid HPLC content 47.1%, iron content 12.9%.

[0053] Example 4.

[0054] This embodiment provides a method for preparing L-arginine 2-hydroxycitrate zinc salt, which specifically adopts the following steps: Dissolve 27.2 g (0.1 mol) of 2-hydroxycitrate zinc salt in water, add 17.4 g (0.1 mol) of L-arginine, react at 50°C for 6 hours, then add 0.2 g of activated carbon for decolorization for 1 hour, filter, concentrate the filtrate by rotary evaporation, crystallize with ethanol, filter and dry to obtain the product.

[0055] The obtained L-arginine 2-hydroxycitrate zinc salt 43.6 g has good hygroscopicity resistance and a yield of 97.8%, as shown in Table 4. As shown in Table 5, it has good fluidity.

[0056] [α] D 20 = -5.9°(C=1, 2%HCl), L-arginine HPLC content 39.0%, 2-hydroxycitric acid HPLC content 46.1%, zinc content 14.9%.

[0057] Example 5.

[0058] This embodiment provides a method for preparing L-lysine 2-hydroxycitrate calcium salt, which specifically adopts the following steps: Dissolve 24.7 g (0.1 mol) of 2-hydroxycitrate calcium salt in water, add 14.6 g (0.1 mol) of L-lysine, react at 80°C for 2 hours, then add 0.2 g of activated carbon for decolorization for 1 hour, filter, concentrate the filtrate by rotary evaporation, crystallize with ethanol, filter, and dry to obtain the product.

[0059] The obtained L-lysine 2-hydroxycitrate calcium salt 38.7 g has good hygroscopicity resistance and a yield of 98.5%, as shown in Table 4. As shown in Table 5, it has good fluidity.

[0060] [α] D 20 = -10.2° (C=1 , 2% HCl), L-lysine HPLC content 37.3%, 2-hydroxycitric acid HPLC content 52.3%, calcium content 10.4%.

[0061] Example 6.

[0062] This embodiment provides a L-lysine 2-hydroxycitrate magnesium salt and a preparation method thereof, which specifically adopts the following steps: Dissolve 23.0 g (0.1 mol) of 2-hydroxycitrate magnesium salt in water, add 14.6 g (0.1 mol) of L-lysine, react at 50°C for 6 hours, then add 0.2 g of activated carbon for decolorization for 1 hour, filter, concentrate the filtrate by rotary evaporation, crystallize with ethanol, filter, and dry to obtain the product.

[0063] The obtained L-lysine 2-hydroxycitrate magnesium salt 37.0 g has good hygroscopicity resistance and a yield of 98.4%, as shown in Table 4. As shown in Table 5, it has good fluidity.

[0064] [α] D 20 = -10.8°(C=1, 2%HCl), L-lysine HPLC content 39.0%, 2-hydroxycitric acid HPLC content 54.4%, magnesium content 6.6%.

[0065] Example 7.

[0066] This embodiment provides a method for preparing L-lysine 2-hydroxycitrate iron salt, which specifically adopts the following steps: Dissolve 26.2 g (0.1 mol) of 2-hydroxycitrate iron salt in water, add 14.6 g (0.1 mol) of L-lysine, react at 75°C for 2 hours, then add 0.2 g of activated carbon for decolorization for 1 hour, filter, concentrate the filtrate by rotary evaporation, crystallize with ethanol, filter and dry to obtain the product.

[0067] The obtained L-lysine 2-hydroxycitrate iron salt 40.0 g has good anti-hygroscopicity and a yield of 98.0%, as shown in Table 4. As shown in Table 5, it has good fluidity.

[0068] [α] D 20= -9.6°(C=1, 2%HCl), L-lysine HPLC content 35.6%, 2-hydroxycitric acid HPLC content 50.5%, iron content 13.9%.

[0069] Example 8.

[0070] This embodiment provides a method for preparing L-lysine 2-hydroxycitrate zinc salt, which specifically adopts the following steps: Dissolve 27.2 g (0.1 mol) of 2-hydroxycitrate zinc salt in water, add 14.6 g (0.1 mol) of L-lysine, react at 65°C for 5 hours, then add 0.2 g of activated carbon for decolorization for 1 hour, filter, concentrate the filtrate by rotary evaporation, crystallize with ethanol, filter, and dry to obtain the product.

[0071] The obtained L-lysine 2-hydroxycitrate zinc salt 41.4 g has good hygroscopicity resistance and a yield of 99.0%, as shown in Table 4. As shown in Table 5, it has good fluidity.

[0072] [α] D 20 = -8.9°(C=1, 2%HCl), L-lysine HPLC content 35.0%, 2-hydroxycitric acid HPLC content 49.2%, zinc content 15.8%.

[0073] Example 9.

[0074] This embodiment provides a method for preparing L-histidine 2-hydroxycitrate calcium salt, which specifically adopts the following steps: Dissolve 24.7 g (0.1 mol) of 2-hydroxycitrate calcium salt in water, add 15.5 g (0.1 mol) of L-histidine, react at 78°C for 2 hours, then add 0.2 g of activated carbon for decolorization for 1 hour, filter, concentrate the filtrate by rotary evaporation, crystallize with ethanol, filter, and dry to obtain the product.

[0075] The obtained L-histidine 2-hydroxycitrate calcium salt 39.7 g, as shown in Table 4, has good hygroscopicity resistance and a yield of 98.8%. As shown in Table 5, it has good fluidity.

[0076] [α] D 20 = -13.1° (C=1 , 2% HCl), L-histidine HPLC content 38.5%, 2-hydroxycitric acid HPLC content 51.2%, calcium content 10.3%.

[0077] Example 10.

[0078] This embodiment provides a method for preparing L-histidine 2-hydroxycitrate magnesium salt, which specifically adopts the following steps: Dissolve 23.0 g (0.1 mol) of 2-hydroxycitrate magnesium salt in water, add 15.5 g (0.1 mol) of L-histidine, react at 72°C for 3 hours, then add 0.2 g of activated carbon for decolorization for 1 hour, filter, concentrate the filtrate by rotary evaporation, crystallize with ethanol, filter, and dry to obtain the product.

[0079] The obtained L-histidine 2-hydroxycitrate magnesium salt 38.0 g has good hygroscopicity resistance and a yield of 98.7%, as shown in Table 4. As shown in Table 5, it has good fluidity.

[0080] [α] D 20 = -14.0°(C=1, 2%HCl), L-histidine HPLC content 40.1%, 2-hydroxycitric acid HPLC content 53.5%, magnesium content 6.4%.

[0081] Example 11.

[0082] This embodiment provides a method for preparing L-histidine 2-hydroxycitrate iron salt, which specifically adopts the following steps: Dissolve 26.2 g (0.1 mol) of 2-hydroxycitrate iron salt in water, add 15.5 g (0.1 mol) of L-histidine, react at 62°C for 4 hours, then add 0.2 g of activated carbon for decolorization for 1 hour, filter, concentrate the filtrate by rotary evaporation, crystallize with ethanol, filter and dry to obtain the product.

[0083] The obtained L-histidine 2-hydroxycitrate iron salt 41.1 g, as shown in Table 4, has good anti-hygroscopicity and a yield of 98.6%. As shown in Table 5, it has good fluidity.

[0084] [α] D 20 = -12.6°(C=1, 2%HCl), L-histidine HPLC content 37.1%, 2-hydroxycitric acid HPLC content 49.4%, iron content 13.5%.

[0085] Example 12.

[0086] This embodiment provides a method for preparing L-histidine 2-hydroxycitrate zinc salt, which specifically adopts the following steps: Dissolve 27.2 g (0.1 mol) of 2-hydroxycitrate zinc salt in water, add 15.5 g (0.1 mol) of L-histidine, react at 74°C for 3 hours, then add 0.2 g of activated carbon for decolorization for 1 hour, filter, concentrate the filtrate by rotary evaporation, crystallize with ethanol, filter, and dry to obtain the product.

[0087] The obtained L-histidine 2-hydroxycitrate zinc salt 41.7 g, as shown in Table 4, has good anti-hygroscopicity and a yield of 97.7%. As shown in Table 5, it has good fluidity.

[0088] [α] D 20 = -11.9°(C=1, 2%HCl), L-histidine HPLC content 36.2%, 2-hydroxycitric acid HPLC content 48.3%, zinc content 15.5%.

[0089] Example 13.

[0090] This embodiment provides a method for preparing L-carnitine 2-hydroxycitrate calcium salt, which specifically adopts the following steps: Dissolve 24.7 g (0.1 mol) of 2-hydroxycitrate calcium salt in water, add 16.1 g (0.1 mol) of L-carnitine, react at 58°C for 6 hours, then add 0.2 g of activated carbon for decolorization for 1 hour, filter, and concentrate the filtrate by rotary evaporation, crystallize with ethanol, filter, and dry to obtain the product.

[0091] The obtained L-carnitine 2-hydroxycitrate calcium salt 40.1 g has good hygroscopicity resistance and a yield of 98.3%, as shown in Table 4. As shown in Table 5, it has good fluidity.

[0092] [α] D 20 = -17.2° (C=1 , 2% HCl), L-carnitine HPLC content 39.5%, 2-hydroxycitric acid HPLC content 50.3%, calcium content 10.2%.

[0093] Example 14.

[0094] This embodiment provides a method for preparing L-carnitine 2-hydroxycitrate magnesium salt, which specifically adopts the following steps: Dissolve 23.0 g (0.1 mol) of 2-hydroxycitrate magnesium salt in water, add 16.1 g (0.1 mol) of L-carnitine, react at 66°C for 5 hours, then add 0.2 g of activated carbon for decolorization for 1 hour, filter, concentrate the filtrate by rotary evaporation, crystallize with ethanol, filter, and dry to obtain the product.

[0095] The obtained L-carnitine 2-hydroxycitrate magnesium salt 38.6 g, as shown in Table 4, has good anti-hygroscopicity and a yield of 98.7%. As shown in Table 5, it has good fluidity.

[0096] [α] D 20= -18.0°(C=1, 2%HCl), L-carnitine HPLC content 41.0%, 2-hydroxycitric acid HPLC content 52.7%, magnesium content 6.3%.

[0097] Example 15.

[0098] This embodiment provides a L-carnitine 2-hydroxycitrate iron salt and a preparation method thereof, which specifically adopts the following steps: Dissolve 26.2 g (0.1 mol) of 2-hydroxycitrate iron salt in water, add 16.1 g (0.1 mol) of L-carnitine, react at 77°C for 2 hours, then add 0.2 g of activated carbon for decolorization for 1 hour, filter, concentrate the filtrate by rotary evaporation, crystallize with ethanol, filter, and dry to obtain the product.

[0099] The obtained L-carnitine 2-hydroxycitrate iron salt 41.3 g has good hygroscopicity resistance and a yield of 97.6%, as shown in Table 4. As shown in Table 5, it has good fluidity.

[0100] [α] D 20 = -16.6°(C=1, 2%HCl), L-carnitine HPLC content 38.1%, 2-hydroxycitric acid HPLC content 48.5%, iron content 13.4%.

[0101] Example 16.

[0102] This embodiment provides a method for preparing L-carnitine 2-hydroxycitrate zinc salt, which specifically adopts the following steps: Dissolve 27.2 g (0.1 mol) of 2-hydroxycitrate zinc salt in water, add 16.1 g (0.1 mol) of L-carnitine, react at 54°C for 6 hours, then add 0.2 g of activated carbon for decolorization for 1 hour, filter, concentrate the filtrate by rotary evaporation, crystallize with ethanol, filter, and dry to obtain the product.

[0103] The obtained L-carnitine 2-hydroxycitrate zinc salt 43.0 g has good hygroscopicity resistance and a yield of 99.3%, as shown in Table 4. As shown in Table 5, it has good fluidity.

[0104] [α] D 20 = -15.9°(C=1, 2%HCl), L-carnitine HPLC content 37.2%, 2-hydroxycitric acid HPLC content 47.8%, zinc content 15.0%.

[0105] Example 17.

[0106] This embodiment provides a L-arginine 2-hydroxycitrate calcium salt weight loss tablet, comprising the following components: L-arginine 2-hydroxycitrate calcium salt 500 mg, starch 20 mg, talc 5 mg, microcrystalline cellulose 30 mg, magnesium stearate 2 mg.

[0107] Example 18.

[0108] This embodiment provides a L-lysine 2-hydroxycitrate magnesium salt weight loss tablet, comprising the following components: L-Lysine 2-hydroxycitrate magnesium salt 500 mg, starch 20 mg, talc 5 mg, microcrystalline cellulose 30 mg, magnesium stearate 2 mg.

[0109] Example 19.

[0110] This embodiment provides a L-histidine 2-hydroxycitrate iron salt weight loss tablet, comprising the following components: L-histidine 2-hydroxycitrate iron salt 500 mg, starch 20 mg, talc 5 mg, microcrystalline cellulose 30 mg, magnesium stearate 2 mg.

[0111] Example 20.

[0112] This embodiment provides a L-carnitine 2-hydroxycitrate zinc salt weight loss tablet, comprising the following components: L-Carnitine 2-hydroxycitrate zinc salt 500 mg, starch 20 mg, talc 5 mg, microcrystalline cellulose 30 mg, magnesium stearate 2 mg.

[0113] Example 21.

[0114] This embodiment provides a L-carnitine 2-hydroxycitrate calcium salt weight loss tablet, comprising the following components: L-Carnitine 2-hydroxycitrate calcium salt 500 mg, starch 20 mg, talc 5 mg, microcrystalline cellulose 30 mg, magnesium stearate 2 mg.

[0115] Example 22.

[0116] This embodiment provides a weight loss beverage, comprising the following components: 6.0g L-arginine 2-hydroxycitrate magnesium salt, 2.0g sodium chloride, 1.0g sodium phytate, 0.2g taurine, 3.0g L-ascorbic acid, 83.0g anhydrous glucose, 0.8g spice powder, and 2000.0g pure water.

[0117] Example 23.

[0118] This embodiment provides a weight loss beverage, comprising the following components: 6.0g L-lysine 2-hydroxycitrate iron salt, 3.0g sodium chloride, 2.0g sodium phytate, 0.1g taurine, 3.0g L-ascorbic acid, 83.0g anhydrous glucose, 0.8g spice powder, and 2000.0g pure water.

[0119] Example 24.

[0120] This embodiment provides a weight loss beverage, comprising the following components: 6.0g L-histidine 2-hydroxycitrate zinc salt, 2.0g sodium chloride, 1.0g sodium phytate, 0.2g taurine, 8.0g L-ascorbic acid, 83.0g anhydrous glucose, 0.5g spice powder, and 1000.0g pure water.

[0121] Example 25.

[0122] This embodiment provides a weight loss beverage, comprising the following components: 6.0g L-carnitine 2-hydroxycitrate calcium salt, 2.0g sodium chloride, 1.0g sodium phytate, 0.2g taurine, 8.0g L-ascorbic acid, 83.0g anhydrous glucose, 0.8g spice powder, 2000.0g pure water.

[0123] Comparative example 1.

[0124] This comparative example provides a method for preparing a 2-hydroxycitric acid complex salt, which is different from Example 1 to Example 16 in that R is an acidic amino acid.

[0125] Specifically, when R is glutamic acid or aspartic acid, 2-hydroxycitrate M (calcium, magnesium, iron, zinc) salt cannot react well with it to prepare a salt.

[0126] The preparation method provided in this comparative example cannot obtain a stable compound even if it is prepared into a salt, and is not conducive to the subsequent preparation of the compound as an active ingredient into a pharmaceutical preparation.

[0127] Comparative example 2.

[0128] This comparative example provides a method for preparing a 2-hydroxycitric acid complex salt, which is different from Examples 1 to 16 in that R is a neutral amino acid.

[0129] Specifically: when R is a neutral amino acid such as tryptophan, leucine, glycine, alanine, serine, threonine, methionine, valine, isoleucine, proline, tyrosine, cysteine, etc., 2-hydroxycitrate M (calcium, magnesium, iron, zinc) salt is difficult to react with it to form a salt, and can only form a mixture but cannot react to form a new compound.

[0130] The preparation method provided in this comparative example cannot obtain a stable compound even if it is prepared into a salt, and is not conducive to the subsequent preparation of the compound as an active ingredient into a pharmaceutical preparation.

[0131] Comparative example 3.

[0132] This comparative example provides a mixture tablet of 2-hydroxycitrate calcium salt and tryptophan (molar ratio 1:1), comprising the following components: 2-Hydroxycitrate calcium salt 247 mg, tryptophan 204 mg, starch 20 mg, talc 5 mg, microcrystalline cellulose 30 mg, magnesium stearate 2 mg.

[0133] Comparative example 4.

[0134] This comparative example provides a mixture tablet of 2-hydroxycitrate magnesium salt and isoleucine (molar ratio 1:1), comprising the following components: 2-Hydroxycitrate magnesium salt 230 mg, isoleucine 131 mg, starch 20 mg, talc 5 mg, microcrystalline cellulose 30 mg, magnesium stearate 2 mg.

[0135] Test example 1.

[0136] This test example provides verification of the beneficial effect (1) of the present invention: 140 healthy mice were randomly divided into a normal control group, a high-fat model group, three dose groups of L-carnitine 2-hydroxycitrate calcium 1350, 900, 450 mg / kg, three dose groups of L-carnitine 2-hydroxycitrate zinc 1350, 900, 450 mg / kg, three dose groups of metformin 1350, 900, 450 mg / kg, three dose groups of orlistat 1350, 900, 450 mg / kg, a total of 14 groups, 10 mice in each group, except for the normal control group which was fed with ordinary feed, the other five groups were fed with high-fat feed. Intragastric administration treatment began in the fifth week. One hour after administration, swimming exercise (water depth 30 cm, water temperature 25°C) was performed for half an hour for five weeks. The mice were weighed and blood was collected from orbital vein to prepare fresh serum. The levels of serum triglyceride, total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) were determined, and the differences among the groups were compared.

[0137] Table 1 Comparative test data of fat reduction effect. Group Dosage (mg / kg) Triglyceride (mmol / L) Total cholesterol (mmol / L) HDL (mmol / L) LDL (mmol / L) Weight (g) Normal control 0 0.5±0.22 2.89±0.45 2.0±0.37 0.37±0.26 31.6±3.50 High fat control 0 0.79±0.11 4.53±0.22 1.88±0.36 2.32±0.28 40.9±5.36 L-Carnitine 2-Hydroxy Calcium Citrate 1350 0.28±0.07 3.56±0.39 2.69±0.41 0.43±0.11 30.3±3.58 L-Carnitine 2-Hydroxy Calcium Citrate 900 0.31±0.12 3.43±0.49 2.75±0.57 0.40±0.08 29.0±4.20 L-Carnitine 2-Hydroxy Calcium Citrate 450 0.30±0.36 3.57±0.62 2.76±0.38 0.46±0.17 30.6±5.05 L-Carnitine 2-Hydroxycitrate Zinc 1350 0.29±0.08 3.62±0.41 2.58±0.37 0.42±0.09 30.9±3.62 L-Carnitine 2-Hydroxycitrate Zinc 900 0.30±0.15 3.38±0.46 2.72±0.55 0.41±0.07 29.8±4.24 L-Carnitine 2-Hydroxycitrate Zinc 450 0.29±0.38 3.59±0.64 2.73±0.36 0.45±0.16 31.2±5.09 Metformin 1350 0.33±0.10 4.17±0.45 3.14±0.48 0.51±0.12 35.5±4.22 Metformin 900 0.38±0.15 4.06±0.58 3.29±0.68 0.48±0.10 34.3±5.00 Metformin 450 0.36±0.44 4.21±0.74 3.31±0.46 0.55±0.21 35.9±5.97 Orlistat 1350 0.33±0.09 4.18±0.43 3.13±0.47 0.52±0.11 35.4±4.19 Orlistat 900 0.39±0.13 4.05±0.56 3.30±0.66 0.49±0.09 34.5±4.98 Orlistat 450 0.37±0.42 4.20±0.72 3.32±0.45 0.54±0.20 36.0±5.95

[0138] As shown in Table 1, the weight of mice in the high-fat model group was significantly higher than that in the normal control group (P<0.01). The weight of the L-carnitine 2-hydroxycitrate calcium, L-carnitine 2-hydroxycitrate zinc, metformin, and orlistat groups decreased significantly, but the weight loss of the metformin and orlistat groups was relatively small compared with the other two groups. There was no significant difference between L-carnitine 2-hydroxycitrate calcium and L-carnitine 2-hydroxycitrate zinc. The above conclusions show that 2-hydroxycitrate complex salt has the best weight loss (fat) effect.

[0139] Test example 2.

[0140] This test example provides a verification test of the beneficial effect (2) of the present invention: 40 healthy mice were randomly divided into 4 groups, a control group in which no L-carnitine 2-hydroxycitrate calcium salt was added to the feed, and three dosage groups with L-carnitine 2-hydroxycitrate calcium salt contents of 1350, 900, and 450 mg / kg were set up, with 10 mice in each group. They were fed with a high-fat feed and gavage treatment began in the fifth week. One hour after the administration, swimming exercise (water depth 30 cm, water temperature 25°C) was performed for half an hour for five weeks, and the changes in water intake and food intake of each mouse were measured.

[0141] Table 2 Changes in diet and drinking water of mice after taking L-carnitine 2-hydroxycitrate calcium salt.

[0142] The test results are shown in Table 2. It can be seen that under different administration conditions of L-carnitine 2-hydroxycitrate calcium salt, there was no significant change in the food and water intake of mice compared with the control group, indicating that the anti-obesity effect of L-carnitine 2-hydroxycitrate calcium salt is not caused by appetite suppression or reduced water intake.

[0143] Test example 3.

[0144] This test example provides a verification test of the beneficial effect (3) of the present invention: 40 healthy mice were randomly divided into 4 groups, and three dosage groups with L-carnitine 2-hydroxycitrate calcium salt content of 1350, 900, and 450 mg / kg were set, each group had 10 mice, and they were fed with a high-fat diet. The treatment was started by gavage in the fifth week. One hour after the administration, swimming exercise (water depth 30 cm, water temperature 25°C) was performed for half an hour. The blood sugar content was determined at 1 hour, 2 hours, 3 hours, and 4 hours after swimming, and the average value was calculated. Compared with the control group, the blood sugar content of the treatment group was not statistically different from that of the control group.

[0145] Table 3 Changes in blood glucose in mice after taking L-carnitine 2-hydroxycitrate calcium salt.

[0146] Test example 4.

[0147] This test example is a humidity comparison test of the 2-hydroxycitric acid complex salt provided in Examples 1 to 16.

[0148] The test method is to expose the sample at 25℃ and relative humidity of 60%±5% for 24 hours. The specific parameters are as follows: Equipment model: KCL-1000 constant temperature and humidity chamber; Set temperature: 25.0 ℃, set relative humidity: 65.0%; Actual temperature: 25.0 ℃, actual relative humidity: 65.0%; The test results are shown in Table 4. It can be seen from Table 4 that under the same conditions, L-carnitine has the highest hygroscopicity, L-lysine has a slight hygroscopicity, and their 2-hydroxycitric acid complex salts are non-hygroscopic and the products are very stable.

[0149] Table 4 Comparative test data of yield and humidity of 2-hydroxycitric acid complex salt. name Yield Weighing before the test Weight after 24 hours Weight gain ratio state Example 1 (L-arginine 2-hydroxycitrate calcium salt) 98.60% 12.6878 12.7157 0.22% Powder Example 2 (L-arginine 2-hydroxycitrate magnesium salt) 98.20% 12.5076 12.5276 0.16% Powder Example 3 (L-arginine 2-hydroxycitrate iron salt) 99.10% 12.6503 12.6819 0.25% Powder Example 4 (L-arginine 2-hydroxycitrate zinc salt) 97.80% 12.487 12.5112 0.19% Powder Example 5 (L-lysine 2-hydroxycitrate calcium salt) 98.50% 12.5107 12.5397 0.23% Powder Example 6 (L-lysine 2-hydroxycitrate magnesium salt) 98.40% 12.3256 12.3515 0.21% Powder Example 7 (L-lysine 2-hydroxycitrate iron salt) 98.00% 12.4357 12.4581 0.18% Powder Example 8 (L-lysine 2-hydroxycitrate zinc salt) 99.00% 12.5436 12.5674 0.19% Powder Example 9 (L-histidine 2-hydroxycitrate calcium salt) 98.80% 12.3893 12.4091 0.16% Powder Example 10 (L-histidine 2-hydroxycitrate magnesium salt) 98.70% 12.7215 12.7469 0.20% Powder Example 11 (L-histidine 2-hydroxycitrate iron salt) 98.60% 12.4233 12.4444 0.17% Powder Example 12 (L-histidine 2-hydroxycitrate zinc salt) 97.70% 12.5423 12.5686 0.21% Powder Example 13 (L-carnitine 2-hydroxycitrate calcium salt) 98.30% 12.6621 12.6849 0.18% Powder Example 14 (L-carnitine 2-hydroxycitrate magnesium salt) 98.70% 12.4343 12.4617 0.22% Powder Example 15 (L-carnitine 2-hydroxycitrate iron salt) 97.60% 12.5213 12.5451 0.19% Powder Example 16 (L-carnitine 2-hydroxycitrate zinc salt) 99.30% 12.9621 12.9945 0.25% Powder L-Arginine —— 12.5521 12.5847 0.26% Powder L-Lysine —— 12.4246 12.6234 1.60% Powder L-Histidine —— 12.7231 12.7587 0.28% Powder L-Carnitine —— 12.5656 22.6859 80.54% liquid

[0150] Test example 5.

[0151] This test example is the fluidity test results of Example 1 to Example 16.

[0152] Place the angle of repose tester horizontally on the test bench, and place the receiving dish directly below the funnel of the angle of repose tester. Measure the height h1 of the receiving dish. Place a sufficient amount of sample particles in the funnel, turn on the leak switch, and let the sample fall freely on the receiving dish. When the sample covers the receiving dish and falls from all sides, it forms a cone shape. At this time, turn off the leak switch. Measure the distance h2 from the highest point of the sample pile on the receiving dish to the bottom of the receiving dish. Repeat steps 1 to 4, and take the average value after multiple measurements (such as 6 times) as the actual measured value of the sample angle of repose.

[0153] According to the measured data, the angle of repose is calculated using the formula α=arctan(2h / d), where h is the distance from the bottom to the top of the triangular cone formed by the sample accumulation above the receiving dish (h=h2-h1), and d is the diameter of the receiving dish.

[0154] Through measurement and calculation, the repose angle α of the sample is obtained. The repose angle range (°) fluidity evaluation is: 25~30 very good, 31~35 good, 36~40 average, 41~45 qualified, 46~55 poor, 56~65 very poor, >65 difficult to flow; as shown in Table 5.

[0155] Table 5. Liquidity evaluation results.

[0156] Test example 6.

[0157] This test example compares the dissolution and solubility test results of amino acids in Examples 17 to 21 and Comparative Example 4.

[0158] Dissolution test method: Take 5 tablets prepared in Example 17-Example 21 respectively, and follow the second method of the general dissolution and release determination method of the 2015 edition of the "Chinese Pharmacopoeia", using 900 ml of 0.1% Tween 80 solution as the dissolution medium, the rotation speed is 75 rpm, and samples are taken at 10 min, 30 min, 60 min, 90 min, and 120 min respectively. Centrifuge and take the supernatant as the test solution, calculate the dissolution amount of each tablet, and calculate the average value. The results are shown in Table 6.

[0159] Table 6 Dissolution test data of Examples 17 to 21 and Comparative Example 4.

[0160] It can be seen from the data in Table 6 that the tablets prepared in Examples 17 to 21 of the present application have a higher solubility of the 2-hydroxycitric acid complex salt compound than the tablets prepared in Comparative Example 4.

[0161] This test example also provides: a solubility test using the products prepared in Example 17 and Example 21 as experimental samples, taking 0.3 g of each experimental sample (recommended dosage: 3000 mg per 1 L of water, calculated as L-arginine 2-hydroxycitrate calcium salt and L-carnitine 2-hydroxycitrate calcium salt), placing it in a Nessler colorimetric tube, adding water to dilute to 50 ml, turning it upside down 10 times at 25°C ± 2°C, and presenting a colorless, transparent, clear solution, that is, the test samples were completely dissolved, and after standing for 30 minutes, no turbidity or precipitation was generated.

[0162] The above experiments show that the product prepared by the present invention has good solubility.

[0163] Test example 7.

[0164] This experimental example compares the stability test results of the dissolution of amino acids in Examples 17 to 21 and Comparative Example 3.

[0165] Stability test method: The tablets prepared in Example 17 to Example 21 and Comparative Example 3 were placed under accelerated test conditions (temperature 40°C ± 2°C, relative humidity 75% ± 5%), and the changes in dissolution were observed at 0 month, 3 months, and 6 months. The dissolution test method was the same as that of Test Example 1, and the results are shown in Table 7.

[0166] Table 7 Dissolution test data of Example 17-Example 21 and Comparative Example 3.

[0167] From the above data, it can be seen that after each sample was placed under accelerated conditions for 6 months, the solubility of the tablets prepared in Examples 17 to 21 at each sampling point decreased slightly, with small changes; the tablets prepared in Comparative Example 3 had a relatively large change range, indicating that the 2-hydroxycitric acid complex salt solid dispersion tablets prepared by the process provided by the present invention have better stability.

[0168] Test example 8.

[0169] This test example provides a water stability test of the products of Example 2 and Example 7.

[0170] 1. Test purpose: This test uses the products prepared in Example 2 and Example 7 as test samples. Considering that the clinical recommended method is to administer the drug in drinking water, it is necessary to verify the stability of the present invention in drinking water.

[0171] 2. Test method: Take 4g of the test sample (calculated at 2 times the clinically recommended high dose concentration), place it in a 1000mL volumetric bottle, add an appropriate amount of drinking water to dissolve, dilute to the scale with drinking water, shake well, and set aside. Take samples at the end of 1h, 2h, 3h, 6h, 12h, 24h, and 36h, and test the properties of the solution and the content of the active ingredient (with 0h as 100%).

[0172] 3. Test results and analysis: The results are shown in Table 8.

[0173] As can be seen from Table 8, the samples prepared according to Example 2 and Example 7 are still colorless clear solutions after being dissolved in drinking water for 36 hours, and the content of active ingredients changes within 8.5%, indicating that the samples provided by the present invention have good stability in drinking water.

[0174] Table 8 Results of stability test in drinking water.

[0175] Test example 9.

[0176] This test example provides an accelerated stability test of the products of Example 8 and Example 13.

[0177] 1. Experimental purpose: To investigate the stability of the product obtained by the present invention.

[0178] 2. Test method: In this test, three batches of products prepared by the preparation methods in Example 8 and Example 13 were used as experimental samples.

[0179] Three batches of samples were taken and packaged as sold commercially. They were placed at a temperature of 40℃±2℃ and a relative humidity of 75%±5% for 6 months. Samples were taken at the end of the first, second, third and sixth month respectively to test the properties, active ingredient content and solubility of the samples.

[0180] 3. Test results and analysis: The results are shown in Table 9.

[0181] As shown in Table 9, after 6 months of accelerated testing, the properties and solubility of the three batches of products met the requirements, and the content of 2-hydroxycitric acid complex salt was within the range of 98.0%-100.0%.

[0182] The test results show that the product prepared by the present invention has good stability under high temperature and high humidity conditions.

[0183] Table 9 Accelerated test results.

[0184] Test example 10.

[0185] This test example provides a sensory performance test of the weight loss beverages provided in Examples 22 to 25.

[0186] The evaluation criteria for the taste and smell of the diet drinks are shown in Table 10.

[0187] Table 10 Evaluation criteria.

[0188] 200 volunteers were selected for evaluation, and the average score was used as the result. The test results are shown in Table 11.

[0189] Table 11 Sensory evaluation of beverages.

Claims

1. A 2-hydroxycitric acid composite salt, characterized in that: It comprises R and 2-hydroxycitrate M salts; wherein R is any one of L-arginine, L-lysine, L-histidine or L-carnitine; and M is any one of calcium, magnesium, iron or zinc.

2. The 2-hydroxycitrate composite salt according to claim 1, characterized in that The molar ratio of the R and the 2-hydroxycitrate M salt is 1:

1.

3. A method for preparing a 2-hydroxycitric acid composite salt as claimed in claim 1, characterized in that: The preparation method comprises the following steps: reacting 2-hydroxycitric acid M salt and R in water, and obtaining 2-hydroxycitric acid composite salt through rotary evaporation, crystallization, filtering and drying.

4. The method for preparing a 2-hydroxycitrate composite salt according to claim 3, characterized in that: The reaction temperature is 50°C-80°C, and the reaction time is 2 hours-6 hours.

5. Use of the 2-hydroxycitrate complex salt according to any one of claims 1 to 2 in the preparation of medicines.

6. Use of the 2-hydroxycitrate complex salt according to claim 5 in the preparation of medicines, characterized in that: The invention comprises 2-hydroxycitric acid complex salt and pharmaceutically acceptable auxiliary materials.

7. Use of the 2-hydroxycitrate complex salt according to claim 5 in the preparation of medicines, characterized in that: The medicine is one of tablets, capsules, pills, powders, granules, suspensions or oral solutions.

8. A pharmaceutical weight loss tablet, characterized in that: In parts by weight, it comprises: 500 parts of the 2-hydroxycitric acid complex salt as claimed in claim 1, 10 parts to 50 parts of starch, 1 part to 10 parts of talc, 10 parts to 50 parts of microcrystalline cellulose, and 0.1 parts to 3 parts of magnesium stearate.

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