WO2019218538A1 - 一种具有减肥降糖降脂作用的组合物及其制备方法和用途 - Google Patents

一种具有减肥降糖降脂作用的组合物及其制备方法和用途 Download PDF

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WO2019218538A1
WO2019218538A1 PCT/CN2018/103515 CN2018103515W WO2019218538A1 WO 2019218538 A1 WO2019218538 A1 WO 2019218538A1 CN 2018103515 W CN2018103515 W CN 2018103515W WO 2019218538 A1 WO2019218538 A1 WO 2019218538A1
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苏政权
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广东药科大学
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
    • A61K31/716—Glucans
    • A61K31/722—Chitin, chitosan
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/21—Amaranthaceae (Amaranth family), e.g. pigweed, rockwort or globe amaranth
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/33—Cactaceae (Cactus family), e.g. pricklypear or Cereus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/38—Clusiaceae, Hypericaceae or Guttiferae (Hypericum or Mangosteen family), e.g. common St. Johnswort
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/04—Anorexiants; Antiobesity agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/50—Methods involving additional extraction steps
    • A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying

Definitions

  • the invention relates to the technical field of medicine, in particular to a composition having the functions of reducing weight, reducing blood sugar and reducing fat and a preparation method thereof.
  • Diabetes is a syndrome characterized by hyperglycemia caused by insufficient insulin secretion and/or insulin resistance, and involves a variety of metabolic disorders. As people's lifestyle changes, the prevalence of diabetes is on the rise. Epidemiological surveys show that diabetes is high in developing countries. In 2005, 220 million people worldwide suffered from diabetes, and there were 40 million patients in China. There are also more people at risk of reduced glucose tolerance. About 90% are type 2 diabetes. The onset of diabetes is slow, the symptoms are concealed, the condition is complicated, and the progress of the disease is often accompanied by complications such as cardiovascular and cerebrovascular, kidney, eye and neuropathy. According to the "2011 Diabetes Market Prospects" report released by Research & Marttecs, the global diabetes drug in 2005 has reached a market size of 18.6 billion US dollars, which is estimated to have exceeded 25 billion US dollars.
  • Hyperlipidemia is a systemic disease in which blood total cholesterol (TC) and/or triglyceride (TG) is too high or high-density lipoprotein cholesterol (HDL-C) is too low.
  • Modern medicine calls it dyslipidemia. .
  • the damage to the body is occult, progressive, progressive and systemic. Its direct damage is to accelerate systemic atherosclerosis, because the vital organs of the whole body rely on arterial blood supply and oxygen supply. Once the artery is blocked by atheroma, it will lead to serious consequences. Renal failure caused by arteriosclerosis is closely related to hyperlipidemia.
  • a large number of studies have shown that hyperlipidemia is an independent and important risk factor for stroke, coronary heart disease, myocardial infarction, and sudden cardiac death. Therefore, people began to develop the lipid-regulating drugs as the focus of prevention and treatment of cardiovascular diseases.
  • hyperlipemia and diabetes For the treatment of hyperlipidemia and diabetes, the use of chemical drugs will produce different degrees of toxic and side effects, and it is easy to relapse after stopping the drug. Therefore, the treatment of hyperlipemia and diabetes is no longer using simple chemical drugs, and a large number of Natural health products have been developed, but most of these health care products only focus on a single type of patient. In fact, elderly diseases such as diabetes and hyperlipidemia usually appear in a patient.
  • Chinese Patent Application No. 201210283797.1 discloses a slimming health food product whose main raw material formula is as follows: white kidney bean extract 1% to 60%, L-malic acid 1% to 50%, L-carnitine Tartrate 1% to 65%, konjac powder 1% to 40%; also includes: excipients 1% to 95%; however, the above composition only has a weight loss effect, the effect is relatively simple; the application number is 201110421555.
  • a composition having the functions of reducing weight, reducing blood sugar and lowering fat, and is prepared from the following parts by weight of raw materials, 1-10 parts of orchid grass leaves and flowers, 1-10 parts of Polygonatum odoratum, and yam 1-10 Serving, 1-10 parts of pork broth, 1-10 parts of mulberry leaves, 1-10 parts of geranium powder.
  • the invention is a pure Chinese medicine composition which has a poor adjuvant treatment effect.
  • the present invention provides a composition comprising metformin hydrochloride and chitooligosaccharide and natural plant extract as main components, and the composition has good effects in reducing blood fat, reducing weight, lowering blood sugar and the like. Synergistic effect, long-term use has an excellent effect on reducing body weight, lowering blood sugar and blood lipids.
  • the invention has the composition of reducing weight, reducing blood sugar and lowering fat, which is prepared from the following raw materials by weight: shell fungal sugar 14-20 parts, metformin hydrochloride 1-5 parts, garcinia cambogia extract 4-10 parts, 8-12 parts of cactus extract and 12-18 parts of green scorpion extract.
  • the chitosan oligosaccharide has an average molecular weight of less than 5000 Da.
  • the method for preparing the Garcinia Cambogia extract comprises the following steps:
  • the dried Garcinia Cambogia is pulverized and passed through a 30-50 mesh sieve, and the weight of the medicinal material is 15-25 times the volume of distilled water for 1-3 hours, and the mixture is heated and refluxed for 1-3 times, each extraction time is 1-3 hours, and filtered.
  • the filtrates are combined, and the combined solution is concentrated under reduced pressure, and concentrated to 1-1.4 g of crude drug per ml.
  • the concentrate is added to a volume of 6-8 times of ethanol to dissolve, and the pectin is filtered and concentrated in vacuo to a mass concentration.
  • the concentrated liquid B is separated and purified by simulated moving bed chromatography (the simulated adsorbent for moving bed chromatography is AB-8 weakly polar macroporous adsorption resin, the water washing zone is purified water, desorbent It is 50-75% ethanol, the amount is 1-4 times of the resin volume; the resin adsorption regeneration solvent is 95% ethanol; the adsorption zone flow rate is 1-2BV/h; the water washing zone flow rate is 1-3BV/h; the desorption zone flow rate is 1- 3BV/h; regeneration zone flow rate 2-3BV/h; switching time is 600-700s; temperature control is 40°C-50°C; pressure is controlled at 0.2Mpa-0.6MPa), and hydroxy citric acid-rich components are obtained; The hydroxy citric acid-rich component is concentrated and dried to obtain the Garcinia Cambogia extract.
  • the simulated adsorbent for moving bed chromatography is AB-8 weakly polar macroporous adsorption resin
  • the water washing zone is purified water
  • the preparation method of the green scorpion extract described above comprises the following steps:
  • the preparation method of the cactus extract described therein comprises the following steps:
  • the composition having the effect of reducing weight and reducing blood sugar as described above is prepared from the following raw materials by weight: chitosan oligosaccharide 16-18 parts, metformin hydrochloride 2-4 parts, Garcinia Cambogia extract 6 -8 parts, cactus extract 9-11 parts, and green scorpion extract 14-16 parts.
  • the composition having the effect of reducing weight and reducing blood sugar as described above is prepared from the following raw materials by weight: 17 parts of chitosan oligosaccharide, 3 parts of metformin hydrochloride, 7 parts of Garcinia Cambogia extract, cactus extract 10 parts, 15 parts of the scorpion seed extract.
  • the present invention provides a method of preparing the composition comprising the steps of:
  • the health care composition can be prepared into a suitable pharmaceutical preparation for administration to a patient according to the technical knowledge in the art, and preferably, the preparation of the health care composition is an oral preparation.
  • the oral preparations include, but are not limited to, granules, oral liquids, tablets, capsules.
  • One skilled in the art can obtain the pharmaceutical preparation according to the conventional preparation method of the dosage form and the excipient selection.
  • the present invention also provides the use of the above composition for the preparation of a medicament having a slimming action.
  • the present invention also provides the use of the above composition for the preparation of a medicament having hypoglycemic action.
  • the present invention also provides the use of the above composition for the preparation of a medicament having hypolipidemic action.
  • metformin hydrochloride or a pure Chinese medicine preparation alone is relatively weak, and the inventors have surprisingly found that metformin hydrochloride is combined with chitosan oligosaccharides and extracts of natural plants to exert each other through different mechanisms of action.
  • Synergistic effect can not only exert the hypoglycemic function of metformin hydrochloride, but also metformin hydrochloride can be synergistic with shell oligosaccharide and plant extracts in reducing blood fat, losing weight and lowering blood sugar, and can significantly improve And to alleviate the symptoms caused by hyperglycemia in diabetic patients, especially the composition shows excellent and unexpected synergy in reducing blood fat, protecting cardiovascular and cerebrovascular diseases, and reducing the risk of cardiovascular and cerebrovascular diseases.
  • composition of the invention has simple formula, easy availability of raw materials, low cost, small toxic and side effects, high safety, simple preparation method, stable process and popularization and application.
  • a composition having the functions of reducing weight, reducing sugar and lowering lipid, and the raw material composition thereof is:
  • Chitosan oligosaccharide 14g metformin hydrochloride 1g, Garcinia Cambogia extract 4g, cactus extract 8g, and scorpion seed extract 12g.
  • the method for preparing the Garcinia Cambogia extract comprises the following steps:
  • the dried Garcinia Cambogia is pulverized and passed through a 30 mesh sieve, and the medicinal material is immersed in 15 volumes of distilled water for 1 hour, and heated and refluxed for 1 time, each extraction time is 1 hour, filtered, and the filtrate is combined, and the combined solution is decompressed.
  • the preparation method of the green scorpion extract described above comprises the following steps:
  • the scorpion medicinal material was pulverized and passed through a 30-mesh sieve, and the medicinal material was immersed in distilled water of 15 times volume for 0.5 hours, and heated under reflux for 1 time, each extraction time was 1 hour, and the filtrate was combined, and the combined solution was concentrated under reduced pressure.
  • the mixture was concentrated to 1 g of a crude drug per ml, and the mixture was allowed to stand for 2 hours in a 75% aqueous solution of 2% by volume of the concentrate, and the supernatant was separated, and ethanol was recovered under reduced pressure, and dried under vacuum to obtain a hazelnut extract.
  • the preparation method of the cactus extract described therein comprises the following steps:
  • Fresh cactus should be washed with water, chopped and homogenized, immersed in 10 times volume of distilled water for 1 hour, heated and refluxed for 1 hour, filtered to obtain a filtrate, and added to the residue. 10 volumes of distilled water were continuously refluxed for 1 hour, filtered to obtain a secondary filtrate, and the primary filtrate and the secondary filtrate were combined, and the combined liquid was concentrated and vacuum dried to obtain a cactus extract.
  • the preparation method of the composition comprises the following steps:
  • a composition having the functions of reducing weight, reducing sugar and lowering lipid, and the raw material composition thereof is:
  • Chitosan oligosaccharide 20g metformin hydrochloride 5g, Garcinia Cambogia extract 10g, cactus extract 12g, and scorpion seed extract 18g.
  • the method for preparing the Garcinia Cambogia extract comprises the following steps:
  • the dried garcinia cambogia is pulverized and passed through a 50 mesh sieve, and the medicinal material is immersed in distilled water of 25 times by volume for 3 hours, and heated and refluxed for 3 times, each extraction time is 3 hours, and the filtrate is combined, and the combined solution is decompressed.
  • the preparation method of the green scorpion extract described above comprises the following steps:
  • the green scorpion medicinal material was pulverized and passed through a 50 mesh sieve, and the medicinal material was immersed in distilled water of 20 times volume for 3 hours, heated and refluxed for 3 times, each extraction time was 3 hours, filtered, and the filtrate was combined, and the combined solution was concentrated under reduced pressure.
  • the mixture was concentrated to 1.2 g of a crude drug per ml, and the concentrate was added to a 3 times volume of a 75% ethanol aqueous solution for 12 hours, and the supernatant was separated, and ethanol was recovered under reduced pressure, and dried under vacuum to obtain a green scorpion extract.
  • the preparation method of the cactus extract described therein comprises the following steps:
  • Fresh cactus should be washed with water, chopped and homogenized, chopped and homogenized, soaked in distilled water of 15 times the weight of the medicinal material for 2 hours, heated and refluxed for 2 hours, filtered to obtain a filtrate, and added to the residue. 15 times of volume of distilled water was continuously refluxed for 2 hours, filtered to obtain a secondary filtrate, and the primary filtrate and the secondary filtrate were combined, and the combined liquid was concentrated and vacuum dried to obtain a cactus extract.
  • the preparation method of the composition comprises the following steps:
  • a composition having the functions of reducing weight, reducing sugar and lowering lipid, and the raw material composition thereof is:
  • Chitosan oligosaccharide 16g metformin hydrochloride 2g, Garcinia Cambogia extract 6g, cactus extract 9g, and scorpion seed extract 14g.
  • the method for preparing the Garcinia Cambogia extract comprises the following steps:
  • the dried Garcinia Cambogia is pulverized and passed through a 40 mesh sieve, and the weight of the medicinal material is soaked in 20 volumes of distilled water for 2 hours, and the mixture is heated and refluxed for 2 times, each extraction time is 2 hours, and the filtrate is combined, and the combined solution is decompressed.
  • simulated moving bed chromatography filled adsorbent is AB-8 weakly polar macroporous adsorption resin, water washing zone is purified water, desorbent is 60% ethanol, the amount is 2 times the volume of resin;
  • the resin adsorption regeneration solvent is 95% ethanol; the adsorption zone flow rate is 1.5BV/h; the water wash zone flow rate is 2BV/h; the desorption zone flow rate is 2BV/h; the regeneration zone flow rate is 2BV/h; the switching time is 600s; the temperature is controlled at 45°C; Controlled at 0.4 MPa), a component rich in hydroxycitric acid is obtained; the component rich in hydroxycitric acid is concentrated and dried to obtain an extract of Garcinia Cambogia.
  • the preparation method of the green scorpion extract described above comprises the following steps:
  • the green scorpion medicinal material was pulverized and passed through a 40 mesh sieve, and the medicinal material was immersed in distilled water of 18 times volume for 2 hours, and heated under reflux for 2 times.
  • the extraction time was 2 hours, and the filtrate was combined, and the combined solution was concentrated under reduced pressure.
  • the mixture was concentrated to 1.1 g of a crude drug per ml, and the mixture was allowed to stand for 2 hours in a 75% aqueous solution of 2% by volume of the concentrate, and the supernatant was separated, and ethanol was recovered under reduced pressure, and dried under vacuum to obtain a extract of the scorpion.
  • the preparation method of the cactus extract described therein comprises the following steps:
  • Fresh cactus should be washed with water, chopped and homogenized, soaked and homogenized, soaked in distilled water of 12 times the weight of the medicinal material for 1.5 hours, heated and refluxed for 1.5 hours, filtered to obtain a filtrate, and added to the residue. 12 volumes of distilled water were continuously refluxed for 1.5 hours, filtered to obtain a secondary filtrate, and the primary filtrate and the secondary filtrate were combined, and the combined liquid was concentrated and vacuum dried to obtain a cactus extract.
  • the preparation method of the composition comprises the following steps:
  • a composition having the functions of reducing weight, reducing sugar and lowering lipid, and the raw material composition thereof is:
  • Chitosan oligosaccharide 18g metformin hydrochloride 4g, Garcinia Cambogia extract 8g, cactus extract 11g, and scorpion seed extract 16g.
  • the method for preparing the Garcinia Cambogia extract, the cactus extract and the scutellaria extract is the same as in the third embodiment.
  • the preparation method of the composition comprises the following steps:
  • a composition having the functions of reducing weight, reducing sugar and lowering lipid, and the raw material composition thereof is:
  • Chitosan oligosaccharide 17g metformin hydrochloride 3g, Garcinia Cambogia extract 7g, cactus extract 10g, and scorpion seed extract 15g.
  • the method for preparing the Garcinia Cambogia extract, the cactus extract and the scutellaria extract is the same as in the third embodiment.
  • the preparation method of the composition comprises the following steps:
  • the test drug is provided by the inventor. Prepare a test solution of 0.4 g/mL with distilled water before use. Take 20 SPF-grade KM mice, weighing 18-22 g, half male and half female, fasting for 14 hours before the test, and administering the test drug solution of the present invention at a dose of 40 mL/Kg of maximum gastric volume, once daily for continuous observation. 7 days, record animal response, weight change and death
  • the maximum tolerated dose (NTD) of the KM mice administered with the drug of the present invention is not less than 16 g/Kg, and is calculated as 60 kg of the adult body weight, that is, not less than 230 times the clinical dose of the adult.
  • mice 4 weeks old KM mice, male and female, fed with high fat diet (high fat diet formula 1kg casein, L-cysteine 15g, maltodextrin 0.75kg, sucrose 0.35kg, cellulose 0.25kg, Soybean oil 0.15kg, lard 1.25kg). After 10 weeks of feeding, mice weighing less than 60 g were eliminated and then administered in groups. The group administration methods are shown in Table 1.
  • the high-fat diet was still administered, and the stomach was administered twice a day, and the stomach was administered at 9:00 and 21:00 for 8 weeks.
  • the body weight was weighed every 2 weeks from the second week after the administration.
  • the results showed that there was a significant difference between the experimental group 4 and the model group or the experimental group 1 from the sixth week (P ⁇ 0.05).
  • At 8 weeks there was a significant difference between the experimental group 4 and the model group or the experimental group 1 (P ⁇ 0.01).
  • the results of these tests indicate that the combination of chitosan oligosaccharide, metformin hydrochloride, garcinia cambogia extract, cactus extract and scutellaria extract has a good weight-loss effect on obese mice, thereby confirming the composition in the composition of the present invention.
  • the five substances have significant synergistic effects.
  • the experimental results are shown in Table 2.
  • the group administration method is shown in Table 3.
  • Table 3 Gastrointestinal test substances and doses of mice in each group
  • ⁇ p ⁇ 0.05, ⁇ p ⁇ 0.01, compared with predose represents the difference statistically significant statistical difference.
  • composition of the present invention (experiment 3 group) was able to significantly lower blood glucose, and was statistically significant relative to the other experimental groups (experiment 1 group, experiment 2 group), and the data showed the composition of the present invention (experiment 4 group).
  • Combined application can significantly reduce fasting blood glucose in diabetic rats.
  • mice Male and female, were randomly divided into 6 groups, 10 in each group. See Table 5 for the mode of administration.
  • the formula of high-fat diet was 1 kg of casein, 15 g of L-cysteine, 0.75 kg of maltodextrin, 0.35 kg of sucrose, and 0.25 of cellulose.
  • Kg soybean oil 0.15kg, lard 1.25kg.
  • the model mice were given 0.5 ml/g of high-fat diet in the morning and 0.2 g/kg of the test drug in the afternoon.
  • the blank control group and the model group were given distilled water control and continuously modeled. After 14 days of administration, the modeling was stopped, and then continuous administration was carried out for 7 days, blood was taken the next day, and serum triglyceride (TC) and serum cholesterol (TG) were measured.
  • TC serum triglyceride
  • TG serum cholesterol
  • composition of the present invention can significantly reduce triglyceride and serum cholesterol in blood lipids, and has obvious technical advantages compared with the experimental group 1, the experimental group 2, and the experimental group 3, and the test results are obtained. It is shown that the combination of the present invention (experiment 4 group) has a good synergistic effect on lowering blood fat for obese hyperlipidemic mice.
  • composition of the present invention (experiment 4 group) has significant progress in reducing body weight, lowering blood fat and lowering blood sugar with respect to metformin hydrochloride, chitosan oligosaccharide and plant extract alone, indicating that Metformin hydrochloride, chitosan oligosaccharides, and plant extracts in the compositions of the invention have a synergistic effect.

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Abstract

一种具有减肥降糖降脂作用的组合物及其制备方法和用途，组合物的原料为：壳寡糖、盐酸二甲双胍、藤黄果提取物、仙人掌提取物和青葙子提取物。

Description

[根据细则37.2由ISA制定的发明名称]　一种具有减肥降糖降脂作用的组合物及其制备方法和用途 技术领域
本发明涉及医药技术领域，具体涉及一种具有减肥降糖降脂作用的组合物及其制备方法。
背景技术
肥胖、高血糖、高血脂目前已经成为发达国家和发展中国家共同面临的最严重的公共健康问题之一，在中老年人上体现的尤其明显.
随着经济的发展，人们的生活水平不断提高，过度营养和高脂肪食物摄取使部分人群出现肥胖，肥胖症发生率呈逐年上升趋势。当前，肥胖的流行无论是在发达国家或者是发展中国家，均达到令人吃惊的地步。世界卫生组织已经将肥胖定义为一种疾病，而不是简单的体重过重。肥胖是体内脂肪、尤其是甘油三酯积聚过多而导致的一种状态，是一种多因素造成的慢性代谢疾病。肥胖，不仅给人们带来自身体态的烦恼，更对人类健康造成巨大威胁。研究发现，肥胖与冠心病、脑中风、脑血栓、高血压、高血脂、高血糖等疾病密切相关，危及人身健康。另外，由于环境污染、食品安全等问题日益突出，越来越多的毒素摄入到体内，再加上工作压力大和生活不规律，加速了人们皮肤的老化,如皮肤松弛，皮肤过早地出现皱纹等。
糖尿病是由胰岛素分泌不足和(或)胰岛素抵抗引起的以高血糖为主要表现，涉及多种物质代谢紊乱的综合征。随着人们生活方式的改变，糖尿病的患病率呈上升趋势，流行病学调查显示：糖尿病高发于发展中国家，2005年全球有2.2亿人患糖尿病，我国就有4000万患者。另外还有更多的人存在着糖耐受性降低的风险。约90％为2型糖尿病。糖尿病发病缓慢，症状隐匿，病情复杂，病情进展常伴心脑血管、肾、眼及神经病变等并发症。据Research&Martcets公司公布的《2011年糖尿病市场前景》报告显示，2005年全球的糖尿病药物已达到了186亿美元的市场规模，据推测目前已超过250亿美元。
高血脂症是一种全身性疾病，指血中总胆固醇(TC)和/或甘油三酯(TG)过高或高密度脂蛋白胆固醇(HDL-C)过低，现代医学称之为血脂异常。该病对身体的损害是隐匿、逐渐、进行性和全身性的。它的直接损害是加速全身动脉粥样硬化，因为全身的重要器官都要依靠动脉供血、供氧，一旦动脉被粥样斑块堵塞，就会导致严重后果。动脉硬化引起的肾功能衰竭等，都与高血脂症密切相关。大量研究资料表明，高血脂症是脑卒中、冠心病、心肌梗死、心脏猝死独立而重要的危险因素。因此，人们开始把血脂调节药的开发作为防治心血管疾病的重点。
现有的减肥的药物或保健品大多通过腹泻的方法达到目的，甚至有些还添加了麻黄素等违禁产品，服用后不仅可能对健康产生不良影响，而且可能具有较大的副作用。此外，减肥后，由于身体所含脂肪的减少，皮肤往往失去弹性、光泽度降低、发生松弛，皮肤皱纹也逐步增多。
针对高血脂、糖尿病的治疗，由于采用化学药物会产生不同程度的毒副作用，停药后易复发，因此，对于高血脂、糖尿病的治疗调理已经不再使用单纯的化学药物的方法，大量的靠天然植物发挥作用的保健品被研制出来，但这些保健品大多只注重于单一的某类患者，实际上糖尿病、高血脂等老年疾病通常在一个患者身上均会出现。
申请号为201210283797.1的中国专利，公开了一种减肥保健食品，其按重量百分比计的主要原料配方如下：白芸豆提取物1％～60％、L-苹果酸1％～50％、左旋肉碱酒石酸盐1％～65％、魔芋粉1％～40％；还包括：辅料1％～95％；然而，上述组合物仅仅具有减肥作用，作用比较单一；申请号为201110421555.X的中国专利，公开了一种具有减肥降糖降脂作用的组合物，由下列重量份数的原料制成，以任意配比的兰草叶和花1-10份，玉竹1-10份，山药1-10份，猪苓1-10份，桑叶1-10份，天花粉1-10份。该发明是纯中药组合物，其辅助治疗效果不佳。
因此，我们需要一种能够平稳的、长期使用的具有减肥、降血糖、降血脂作用的产品，即能起到降低体重、降低血糖、降低血脂的作用，又不影响人体正常的食物摄入。
发明内容
为了克服现有技术的不足，本发明提供了一种盐酸二甲双胍与壳寡糖、天然植物提取物为主要组分的组合物，这种组合物在降血脂、减肥、降血糖等方面具有良好的协同增效作用，长期服用对降低体重、降低血糖和血脂具有优异的效果。
为了实现上述目的，本发明的技术方案如下：
一种具有减肥降糖降脂作用的组合物，它是由下述重量份的原料制得：壳寡糖14-20份，盐酸二甲双胍1-5份，藤黄果提取物4-10份，仙人掌提取物8-12份，青葙子提取物12-18份。
其中，所述壳寡糖的平均分子量小于5000Da。
其中所述的藤黄果提取物的制备方法包括如下步骤：
将干燥的藤黄果粉碎后过30-50目筛，加药材重量15-25倍体积的蒸馏水浸泡1-3小时，加热回流提取1-3次，每次提取时间为1-3小时，过滤，将滤液合并，将合并液减压浓缩，浓缩至每毫升含生药1-1.4g，向浓缩液中加入其体积的6-8倍的乙醇进行溶解，过滤出果胶，真空浓缩至质量浓度为4.2g/L的浓缩液；将浓缩液B经模拟移动床色谱进行分离提纯(模拟移动床色谱填充的吸附剂为AB-8弱极性大孔吸附树脂，水洗区为纯化水，解吸剂为50-75％乙醇，其用 量为树脂体积的1-4倍；树脂吸附再生溶剂为95％乙醇；吸附区流速1-2BV/h；水洗区流速1-3BV/h；解吸区流速1-3BV/h；再生区流速2-3BV/h；切换时间为600-700s；温度控制在40℃-50℃；压力控制在0.2Mpa-0.6MPa)，得到富含羟基柠檬酸的组分；将富含羟基柠檬酸的组分浓缩、干燥，即得藤黄果提取物。
其中所述的青葙子提取物的制备方法包括如下步骤：
取青葙子药材粉碎后过30-50目筛，加药材重量15-20倍体积的蒸馏水浸泡0.5-3小时，加热回流提取1-3次，每次提取时间为1-3小时，过滤，将滤液合并，将合并液减压浓缩，浓缩至每毫升含生药1-1.2g，向浓缩液加入其体积的2-3倍的75％乙醇水溶液静置8-12小时，分离上清液，减压回收乙醇、真空干燥得到青葙子提取物。
其中所述的仙人掌提取物的制备方法包括如下步骤：
取新鲜仙人掌除刺去皮后用清水洗净，切碎、匀浆，加药材重量10-15倍体积的蒸馏水浸泡1-2小时，加热回流提取1-2小时，滤过得到一次滤液，向药渣中加入其重量10-15倍体积的蒸馏水继续回流1-2小时，滤过得到二次滤液，将一次滤液和二次滤液合并，将合并液浓缩、真空干燥，即得仙人掌提取物。
优选地，如上所述的具有减肥降糖降脂作用的组合物，它是由以下重量份的原料制得：壳寡糖16-18份，盐酸二甲双胍2-4份，藤黄果提取物6-8份，仙人掌提取物9-11份，青葙子提取物14-16份。
优选地，如上所述的具有减肥降糖降脂作用的组合物，它是由以下重量份的原料制得：壳寡糖17份，盐酸二甲双胍3份，藤黄果提取物7份，仙人掌提取物10份，青葙子提取物15份。
本发明提供了所述组合物的制备方法，包括以下步骤：
分别称取配方量的壳寡糖，盐酸二甲双胍，藤黄果提取物，仙人掌提取物和青葙子提取物，研磨，过筛，混合均匀，加入常规辅料，按照常规工艺，制成临床上可接受的剂型即得。
本领域技术人员可以根据本领域的技术知识将保健组合物制备成合适的药物制剂以便于患者服用，优选地，所述的保健组合物的制剂为口服制剂。所述的口服制剂包括但不限于颗粒剂、口服液、片剂、胶囊剂。本领域技术人员可以根据剂型的常规制备方法以及辅料选择获得所述的药物制剂。
本发明还提供上述组合物在制备具有减肥作用药物中的应用。
本发明还提供上述组合物在制备具有降血糖作用药物中的应用。
本发明还提供上述组合物在制备具有降血脂作用药物中的应用。
本发明的技术方案具有如下优点：
(1)本发明发现单独使用盐酸二甲双胍或纯中药制剂的作用相对较弱，并且发明人惊喜地发现，将盐酸二甲双胍与壳寡糖、天然植物的提取物组合，通过不同的作用机理，相互发挥协同作用，不仅能发挥盐酸二甲双胍的降血糖功能，而且盐酸二甲双胍还能与壳寡糖、植物提取物一起，在降血脂、减肥、降血糖等方面具有良好的协同增效作用，并能明显改善和缓解糖尿病患者由高血糖引发的症状，尤其是该组合物显示出优秀的、意想不到的在降血脂、保护心脑血管、降低发生心脑血管疾病导致的风险方面的协同作用。
(2)本发明所述组合物配方简单、原料易得，成本较低，而且毒副作用较小、安全性较高，同时制备方法简易，工艺稳定，可推广应用。
具体实施方式
以下通过具体实施例进一步描述本发明，但所述实施例并不以任何方式限定本发明专利保护的范围。
实施例1
一种具有减肥降糖降脂作用的组合物，其原料组成为：
壳寡糖14g，盐酸二甲双胍1g，藤黄果提取物4g，仙人掌提取物8g，青葙子提取物12g。
其中所述的藤黄果提取物的制备方法包括如下步骤：
将干燥的藤黄果粉碎后过30目筛，加药材重量15倍体积的蒸馏水浸泡1小时，加热回流提取1次，每次提取时间为1小时，过滤，将滤液合并，将合并液减压浓缩，浓缩至每毫升含生药1g，向浓缩液中加入其体积的6倍的乙醇进行溶解，过滤出果胶，真空浓缩至质量浓度为4.2g/L的浓缩液；将浓缩液B经模拟移动床色谱进行分离提纯(模拟移动床色谱填充的吸附剂为AB-8弱极性大孔吸附树脂，水洗区为纯化水，解吸剂为50％乙醇，其用量为树脂体积的1倍；树脂吸附再生溶剂为95％乙醇；吸附区流速1BV/h；水洗区流速1BV/h；解吸区流速1BV/h；再生区流速2BV/h；切换时间为600s；温度控制在40℃；压力控制在0.2MPa)，得到富含羟基柠檬酸的组分；将富含羟基柠檬酸的组分浓缩、干燥，即得藤黄果提取物。
其中所述的青葙子提取物的制备方法包括如下步骤：
取青葙子药材粉碎后过30目筛，加药材重量15倍体积的蒸馏水浸泡0.5小时，加热回流提取1次，每次提取时间为1小时，过滤，将滤液合并，将合并液减压浓缩，浓缩至每毫升含生药1g，向浓缩液加入其体积的2倍的75％乙醇水溶液静置8小时，分离上清液，减压回收乙醇、真空干燥得到青葙子提取物。
其中所述的仙人掌提取物的制备方法包括如下步骤：
取新鲜仙人掌除刺去皮后用清水洗净，切碎、匀浆，加药材重量10倍体积的蒸馏水浸泡1小时，加热回流提取1小时，滤过得到一次滤液，向药渣中加入其重量10倍体积的蒸馏水继续回流1小时，滤过得到二次滤液，将一次滤液和二次滤液合并，将合并液浓缩、真空干燥，即得仙人掌提取物。
该组合物的制备方法包括如下步骤：
分别称取配方量的壳寡糖，盐酸二甲双胍，藤黄果提取物，仙人掌提取物和青葙子提取物，研磨，过筛，混合均匀，加入常规辅料，按照常规工艺，可制得各种口服制剂，如片剂。
实施例2
一种具有减肥降糖降脂作用的组合物，其原料组成为：
壳寡糖20g，盐酸二甲双胍5g，藤黄果提取物10g，仙人掌提取物12g，青葙子提取物18g。
其中所述的藤黄果提取物的制备方法包括如下步骤：
将干燥的藤黄果粉碎后过50目筛，加药材重量25倍体积的蒸馏水浸泡3小时，加热回流提取3次，每次提取时间为3小时，过滤，将滤液合并，将合并液减压浓缩，浓缩至每毫升含生药1.4g，向浓缩液中加入其体积的8倍的乙醇进行溶解，过滤出果胶，真空浓缩至质量浓度为4.2g/L的浓缩液；将浓缩液B经模拟移动床色谱进行分离提纯(模拟移动床色谱填充的吸附剂为AB-8弱极性大孔吸附树脂，水洗区为纯化水，解吸剂为75％乙醇，其用量为树脂体积的4倍；树脂吸附再生溶剂为95％乙醇；吸附区流速2BV/h；水洗区流速3BV/h；解吸区流速3BV/h；再生区流速3BV/h；切换时间为700s；温度控制在50℃；压力控制在0.6MPa)，得到富含羟基柠檬酸的组分；将富含羟基柠檬酸的组分浓缩、干燥，即得藤黄果提取物。
其中所述的青葙子提取物的制备方法包括如下步骤：
取青葙子药材粉碎后过50目筛，加药材重量20倍体积的蒸馏水浸泡3小时，加热回流提取3次，每次提取时间为3小时，过滤，将滤液合并，将合并液减压浓缩，浓缩至每毫升含生药1.2g，向浓缩液加入其体积的3倍的75％乙醇水溶液静置12小时，分离上清液，减压回收乙醇、真空干燥得到青葙子提取物。
其中所述的仙人掌提取物的制备方法包括如下步骤：
取新鲜仙人掌除刺去皮后用清水洗净，切碎、匀浆，加药材重量15倍体积的蒸馏水浸泡2小时，加热回流提取2小时，滤过得到一次滤液，向药渣中加入其重量15倍体积的蒸馏水继续回流2小时，滤过得到二次滤液，将一次滤液和二次滤液合并，将合并液浓缩、真空干燥，即 得仙人掌提取物。
该组合物的制备方法包括如下步骤：
分别称取配方量的壳寡糖，盐酸二甲双胍，藤黄果提取物，仙人掌提取物和青葙子提取物，研磨，过筛，混合均匀，加入常规辅料，按照常规工艺，可制得各种口服制剂，如胶囊剂。
实施例3
一种具有减肥降糖降脂作用的组合物，其原料组成为：
壳寡糖16g，盐酸二甲双胍2g，藤黄果提取物6g，仙人掌提取物9g，青葙子提取物14g。
其中所述的藤黄果提取物的制备方法包括如下步骤：
将干燥的藤黄果粉碎后过40目筛，加药材重量20倍体积的蒸馏水浸泡2小时，加热回流提取2次，每次提取时间为2小时，过滤，将滤液合并，将合并液减压浓缩，浓缩至每毫升含生药1.2g，向浓缩液中加入其体积的7倍的乙醇进行溶解，过滤出果胶，真空浓缩至质量浓度为4.2g/L的浓缩液；将浓缩液B经模拟移动床色谱进行分离提纯(模拟移动床色谱填充的吸附剂为AB-8弱极性大孔吸附树脂，水洗区为纯化水，解吸剂为60％乙醇，其用量为树脂体积的2倍；树脂吸附再生溶剂为95％乙醇；吸附区流速1.5BV/h；水洗区流速2BV/h；解吸区流速2BV/h；再生区流速2BV/h；切换时间为600s；温度控制在45℃；压力控制在0.4MPa)，得到富含羟基柠檬酸的组分；将富含羟基柠檬酸的组分浓缩、干燥，即得藤黄果提取物。
其中所述的青葙子提取物的制备方法包括如下步骤：
取青葙子药材粉碎后过40目筛，加药材重量18倍体积的蒸馏水浸泡2小时，加热回流提取2次，每次提取时间为2小时，过滤，将滤液合并，将合并液减压浓缩，浓缩至每毫升含生药1.1g，向浓缩液加入其体积的2倍的75％乙醇水溶液静置10小时，分离上清液，减压回收乙醇、真空干燥得到青葙子提取物。
其中所述的仙人掌提取物的制备方法包括如下步骤：
取新鲜仙人掌除刺去皮后用清水洗净，切碎、匀浆，加药材重量12倍体积的蒸馏水浸泡1.5小时，加热回流提取1.5小时，滤过得到一次滤液，向药渣中加入其重量12倍体积的蒸馏水继续回流1.5小时，滤过得到二次滤液，将一次滤液和二次滤液合并，将合并液浓缩、真空干燥，即得仙人掌提取物。
该组合物的制备方法包括如下步骤：
分别称取配方量的壳寡糖，盐酸二甲双胍，藤黄果提取物，仙人掌提取物和青葙子提取物，研磨，过筛，混合均匀，加入常规辅料，按照常规工艺，可制得各种口服制剂，如颗粒 剂。
实施例4
一种具有减肥降糖降脂作用的组合物，其原料组成为：
壳寡糖18g，盐酸二甲双胍4g，藤黄果提取物8g，仙人掌提取物11g，青葙子提取物16g。
其中所述的藤黄果提取物、仙人掌提取物和青葙子提取物的制备方法同实施例3。
该组合物的制备方法包括如下步骤：
分别称取配方量的壳寡糖，盐酸二甲双胍，藤黄果提取物，仙人掌提取物和青葙子提取物，研磨，过筛，混合均匀，加入常规辅料，按照常规工艺，可制得各种口服制剂，如口服液。
实施例5
一种具有减肥降糖降脂作用的组合物，其原料组成为：
壳寡糖17g，盐酸二甲双胍3g，藤黄果提取物7g，仙人掌提取物10g，青葙子提取物15g。
其中所述的藤黄果提取物、仙人掌提取物和青葙子提取物的制备方法同实施例3。
该组合物的制备方法包括如下步骤：
分别称取配方量的壳寡糖，盐酸二甲双胍，藤黄果提取物，仙人掌提取物和青葙子提取物，研磨，过筛，混合均匀，加入常规辅料，按照常规工艺，可制得各种口服制剂，如胶囊剂。
实验例1急性毒性试验资料
1试验目的和方法
观察本发明的药物灌胃给予受试动物后所产生的的急性毒性反应和死亡情况。
受试药品由发明人提供。临用前用蒸馏水配成0.4g/mL的供试液。取20只SPF级KM小鼠，体重18-22g，雌雄各半，试验前禁食14小时，按最大胃容量40mL/Kg的剂量给予本发明受试药物溶液，每日给药一次，连续观察7天，记录动物的反应，体重变化及死亡情况
2试验结果
试验结果显示：小鼠经灌胃给予本发明药物后无异常反应，外观，活动，饮食，粪便均正常，体重增加。
KM种小鼠灌胃给予本发明药物的的最大耐受量(NTD)不低于16g/Kg，以成人体重60Kg计算，即不低于成人临床用药量的230倍。
实验例2本发明组合物降低体重的药效学试验研究
4周龄KM小鼠，雌雄各半,喂以高脂饲料(高脂饲料的配方为酪蛋白1kg，L-半胱氨酸15g，麦芽糊精0.75kg，蔗糖0.35kg，纤维素0.25kg，大豆油0.15kg，猪油1.25kg)。饲养10周后，淘汰体重小于60g的小鼠，然后分组给药，分组给药方式见表1。
表1各组小鼠的灌胃受试物及剂量
Figure PCTCN2018103515-appb-000001
给药期间仍喂以高脂饲料，每天灌胃两次，分别在9：00、21：00灌胃，连续8周。
从给药后第2周开始每隔2周称体重，结果显示，从第6周开始，实验4组与模型组或实验1组相比有显著性差异(P＜0.05)；另外，在第8周时，实验4组与模型组或实验1组相比具有极显著性差异(P＜0.01)，实验4组与实验2组或实验3组相比有显著性差异(P＜0.05)。这些试验结果表明壳寡糖、盐酸二甲双胍、藤黄果提取物、仙人掌提取物和青葙子提取物联合应用后对于肥胖小鼠具有很好的减肥功效，由此可以证实本发明组合物中的5种物质具有显著的协同效果。实验结果详见表2。
表2不同实验组对小鼠体重的影响(单位：g)
组别 给药第2周 给药第4周 给药第6周 给药第8周
模型对照组 71.0±8.3 73.7±6.8 75.6±7.2 77.1±8.6
实验1组 71.3±7.8 73.5±7.9 74.3±7.6 75.2±8.2
实验2组 70.4±7.2 69.3±7.4 73.7±7.2 74.2±7.6
实验3组 71.3±8.2 72.6±8.5 73.2±7.4 74.6±8.9
实验4组 69.1±3.1 67.5±6.4 66.7±7.3 *￥ 66.3±4.8 **￥￥▼△
*与模型组比较，P＜0.05；**与模型组比较，P＜0.01；
￥与实验1组组比较，P＜0.05； ￥￥与实验1组组比较，P＜0.01；
▼与实验2组组比较，P＜0.05； ▼▼与实验2组组比较，P＜0.01；
△与实验3组组比较，P＜0.05； △△与实验3组组比较，P＜0.01。
实验例3本发明组合物在降血糖方面的效果
方法：取雄性SD大鼠按照标准方法制备小剂量链佐菌素致糖尿病大鼠模型，三日后根据大鼠血糖值随机分组，分为5组，每组10只。各组连续灌胃给药8天，每日一次，空白组给予等量蒸馏水，最后一次给药后两小时取血，测定血糖和血清胰岛素。分组给药方式见表3。
表3各组小鼠的灌胃受试物及剂量
Figure PCTCN2018103515-appb-000002
表4不同实验组降血糖效果比较
Figure PCTCN2018103515-appb-000003
△p＜0.05， △△p＜0.01，表示与给药前相比具有统计学差异、显著统计学差异。
由表4可知，本发明组合物(实验3组)能够显著降低血糖，相对于其他实验组(实验1组、实验2组)具有显著统计学意义，数据显示本发明组合物(实验4组)联合应用后能显著降低糖尿病大鼠的空腹血糖。
实验例4本发明组合物在降血脂方面的效果
方法：KM小鼠，雌雄各半，随机分为6组，每组10只。分组给药方式见表5。
表5各组小鼠的灌胃受试物及剂量
Figure PCTCN2018103515-appb-000004
除了空白对照组外，其他各组动物均以高脂饲料饮食造模，高脂饲料的配方为酪蛋白1kg，L-半胱氨酸15g，麦芽糊精0.75kg，蔗糖0.35kg，纤维素0.25kg，大豆油0.15kg，猪油1.25kg。造模小鼠上午灌服高脂饲料0.5ml/g，下午各自给予受试药物0.2g/kg。空白对照组、模型组给予蒸馏水对照，连续造模。给药14天后，停止造模，然后连续给药7天，停药次日取血，测量血清甘油三酯(TC)、血清胆固醇(TG)。
表6不同实验组降血脂效果比较
Figure PCTCN2018103515-appb-000005
*p＜0.05，表示与空白组相比具有统计学差异； △p＜0.05、 △△p＜0.01表示与模型组相比具有统计学差异、显著统计学差异。
由表6可知，本发明组合物(实验4组)能够非常显著的降低血脂中的甘油三酯、血清胆固醇，相对于实验1组、实验2组、实验3组具有明显的技术优势，试验结果表明本发明组合物 (实验4组)联合应用后对于肥胖型高血脂小鼠具有很好的协同性降血脂的作用。
综合上述实验可以看到，相对于单独的盐酸二甲双胍、壳寡糖、植物提取物，本发明组合物(实验4组)在降低体重、降低血脂、降低血糖的效果上均具有显著的进步，说明本发明组合物中的盐酸二甲双胍、壳寡糖、植物提取物具有协同作用。

Claims (8)

  1. 一种具有减肥降糖降脂作用的组合物，其特征在于，它是由下述重量份的原料制得：壳寡糖14-20份，盐酸二甲双胍1-5份，藤黄果提取物4-10份，仙人掌提取物8-12份，青葙子提取物12-18份；
    其中，所述壳寡糖的平均分子量小于5000Da；
    其中所述的藤黄果提取物的制备方法包括如下步骤：
    将干燥的藤黄果粉碎后过30-50目筛，加药材重量15-25倍体积的蒸馏水浸泡1-3小时，加热回流提取1-3次，每次提取时间为1-3小时，过滤，将滤液合并，将合并液减压浓缩，浓缩至每毫升含生药1-1.4g，向浓缩液中加入其体积的6-8倍的乙醇进行溶解，过滤出果胶，真空浓缩至质量浓度为4.2g/L的浓缩液；将浓缩液B经模拟移动床色谱进行分离提纯，得到富含羟基柠檬酸的组分；将富含羟基柠檬酸的组分浓缩、干燥，即得藤黄果提取物；
    其中所述的青葙子提取物的制备方法包括如下步骤：
    取青葙子药材粉碎后过30-50目筛，加药材重量15-20倍体积的蒸馏水浸泡0.5-3小时，加热回流提取1-3次，每次提取时间为1-3小时，过滤，将滤液合并，将合并液减压浓缩，浓缩至每毫升含生药1-1.2g，向浓缩液加入其体积的2-3倍的75％乙醇水溶液静置8-12小时，分离上清液，减压回收乙醇、真空干燥得到青葙子提取物；
    其中所述的仙人掌提取物的制备方法包括如下步骤：
    取新鲜仙人掌除刺去皮后用清水洗净，切碎、匀浆，加药材重量10-15倍体积的蒸馏水浸泡1-2小时，加热回流提取1-2小时，滤过得到一次滤液，向药渣中加入其重量10-15倍体积的蒸馏水继续回流1-2小时，滤过得到二次滤液，将一次滤液和二次滤液合并，将合并液浓缩、真空干燥，即得仙人掌提取物。
  2. 根据权利要求1所述的具有减肥降糖降脂作用的组合物，其特征在于，它是由以下重量份的原料制得：壳寡糖16-18份，盐酸二甲双胍2-4份，藤黄果提取物6-8份，仙人掌提取物9-11份，青葙子提取物14-16份。
  3. 根据权利要求1所述的具有减肥降糖降脂作用的组合物，其特征在于，它是由以下重量份的原料制得：壳寡糖17份，盐酸二甲双胍3份，藤黄果提取物7份，仙人掌提取物10 份，青葙子提取物15份。
  4. 一种权利要求1-3所述的具有减肥降糖降脂作用的组合物的制备方法，其特征在于，包括以下步骤：
    分别称取配方量的壳寡糖，盐酸二甲双胍，藤黄果提取物，仙人掌提取物和青葙子提取物，研磨，过筛，混合均匀，加入常规辅料，按照常规工艺，制成临床上可接受的剂型即得。
  5. 根据权利要求4所述的制备方法制备得到的药物组合物，其特征在于，所述的药物组合物为口服制剂。
  6. 权利要求1-3任一权利要求的组合物在制备具有减肥作用药物中的应用。
  7. 权利要求1-3任一权利要求的组合物在制备具有降血糖作用药物中的应用。
  8. 权利要求1-3任一权利要求的组合物在制备具有降血脂作用药物中的应用。
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