WO2013013417A1 - Medicament useful for reducing blood sugar and body weight having the structure of stilbene compounds - Google Patents

Medicament useful for reducing blood sugar and body weight having the structure of stilbene compounds Download PDF

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WO2013013417A1
WO2013013417A1 PCT/CN2011/077765 CN2011077765W WO2013013417A1 WO 2013013417 A1 WO2013013417 A1 WO 2013013417A1 CN 2011077765 W CN2011077765 W CN 2011077765W WO 2013013417 A1 WO2013013417 A1 WO 2013013417A1
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methyl
weight
hypoglycemic
body weight
blood glucose
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PCT/CN2011/077765
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French (fr)
Chinese (zh)
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沈小玲
胡英杰
邱声祥
王璐
符林春
麦兆
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广州市允中投资发展有限公司
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Priority to CN201180002076.2A priority Critical patent/CN104470514A/en
Priority to PCT/CN2011/077765 priority patent/WO2013013417A1/en
Publication of WO2013013417A1 publication Critical patent/WO2013013417A1/en

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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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A61K31/366—Lactones having six-membered rings, e.g. delta-lactones
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid 
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/0095—Drinks; Beverages; Syrups; Compositions for reconstitution thereof, e.g. powders or tablets to be dispersed in a glass of water; Veterinary drenches
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • 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
    • A61P3/08—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
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the invention relates to a kind of blood sugar lowering and weight loss medicine, in particular to a kind of blood sugar lowering and weight loss medicine having the structure of a terpenoid compound, belonging to the technical field of medicine.
  • 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 had diabetes, and there were 40 million patients in China. More people are at risk of abnormal glucose tolerance. Diabetes is clinically classified into type 1 and type 2, with type 2 accounting for approximately 90%. The onset of diabetes is slow, the symptoms are concealed, and the condition is complicated. The progress of the disease is often accompanied by complications such as cardiovascular and cerebrovascular, kidney, eye and neuropathy. Type 1 diabetes is mostly treated with insulin, and type 2 diabetes is often treated with chemicals.
  • Sulfonylureas are the earliest oral hypoglycemic agents that are still in clinical use and are still widely used. Commonly used are glibenclamide, greepyrazine, gliclazide, gliclazide and glimepiride, etc. These drugs can stimulate the secretion and release of insulin by B-cells, so its hypoglycemic effect depends on A considerable number of functional pancreatic B-cells. In general, these drugs are safer and have a lower rate of adverse reactions, but long-term use can easily cause hypoglycemia.
  • the biguanide hypoglycemic agents are metformin, phenformin and the like. Biguanide can promote the uptake and utilization of glucose in surrounding tissues, increase the anaerobic digestion of sugar in muscle tissue, reduce the absorption of glucose in the intestine, inhibit the biosynthesis and storage of cholesterol, and reduce triglycerides and totals. The level of cholesterol.
  • the biguanide does not stimulate the pancreas to secrete insulin. It not only inhibits the absorption of glucose in the intestine, but also hinders the absorption of vitamin B12, which can cause malabsorption of nutrients and weight loss.
  • X-glucosidase inhibitors are different from the first two types of anti-diabetic drugs.
  • the hypoglycemic mechanism of X-glucosidase inhibitors is competitive inhibition in the small intestine (X-glucosidase activity, making carbon water such as starch
  • the slowing down of the hydrolysis of the compound produces glucose, delays the absorption of glucose in the intestine, and thus helps to lower the blood sugar level after the meal.
  • the side effects are mainly due to intestinal discomfort caused by carbohydrate retention and enzymatic hydrolysis in the intestine.
  • the drugs are acarbose and yuglip.
  • Insulin sensitizers such as "insulin sensitizers” of thiophene diones (TZDs)
  • TRG Troglitazone
  • RSG rosiglitazone maleate
  • ENG Engletazone
  • the early marketed troglitazone was found to have severe hepatotoxicity and even died of liver failure and has been discontinued.
  • the toxic side effects of rosiglitazone maleate (Wendiya) are relatively small, but there are still serious cardiovascular safety hazards.
  • rosiglitazone and its combination can only be considered if other hypoglycemic agents cannot be used or other hypoglycemic agents cannot achieve glycemic control goals.
  • these drugs by activating PPAR- ⁇ receptor activity, enhance insulin sensitivity, and also increase the proliferation of fat cells, leading to weight gain and even obesity, limiting the widespread use of such drugs.
  • the object of the present invention is to provide a novel blood sugar and slimming drug having a structure of a terpenoid compound containing the compound 5-0-methyl-crotonin A and a 5-0-methyl-tree bean Ester A and crotonol A, the drug is any one of 5-0-methyl- crotonin A, 5-0-methyl-culum lactone A or crotonol A
  • a pharmaceutically acceptable dosage form of any one of a tablet, a capsule, a granule, an oral solution, a sustained release preparation, a controlled release preparation, a nano preparation, and an injection prepared as a medicine or It is a health food prepared into any one of a tablet, a capsule, a granule, an oral solution, a sustained release preparation, a controlled release preparation and a nano preparation having hypoglycemic and weight loss effects, and has a significant hypoglycemic effect and a weight loss effect.
  • hypoglycemic and weight-loss drug having the structure of a terpenoid of the present invention, which comprises 5-0-methyl crotonin A having the following structural formula
  • hypoglycemic and weight-loss drugs having the structure of terpenoids of the present invention further contain a compound having the following chemical formula:
  • the invention relates to a kind of hypoglycemic and weight-loss drugs having the structure of terpenoids, which is in 5-0-methyl crotonin acid, 5-0-methyl crotonol A or crotonol A Any one of a pharmaceutically acceptable dosage form of a tablet, a capsule, a granule, an oral solution, a sustained release preparation, a controlled release preparation, a nano preparation, and an injection prepared as a blood sugar lowering and weight loss medicine as an active ingredient.
  • the invention relates to a kind of hypoglycemic and weight-loss drugs having the structure of terpenoids, which is in 5-0-methyl crotonin acid, 5-0-methyl crotonol A or crotonol A
  • terpenoids which is in 5-0-methyl crotonin acid, 5-0-methyl crotonol A or crotonol A
  • Any of the active ingredients as tablets, capsules, granules, oral liquids, sustained release preparations, controlled release having hypoglycemic and weight loss effects A health food of any one of the formulation and the nanoformulation.
  • the crotonol A according to the present invention can be extracted from the leguminous tree bean.
  • the 5-0-methyl crotonin A of the present invention can be produced by a conventional methylation method from crotonin A and dimethyl sulfate.
  • the 5-0-methyl laurel L of the present invention can be prepared by a conventional methylation method from a nutrient A and a dimethyl sulfate.
  • the present invention is achieved by the inventor's research team on the basis of the previous invention "a natural medicine for reducing blood sugar and weight loss" (CN 200810199012.6);
  • hypoglycemic and weight-loss drugs disclosed in the present invention contain anthraquinone compounds having significant hypoglycemic effects, including newly discovered terpenoids 5-0-methyl-docolic acid A and 5-0-methyl - Phytolactone A, which also includes the compound Phy Cannuone A, which has been disclosed by the inventors in the Chinese invention patent CN 200810199012.6 for chemical structure identification and target enzyme activity, and their chemistry with known hypoglycemic or weight loss drugs.
  • the structures are all different, and the present invention discloses for the first time the medicinal value of blood sugar lowering and weight loss, and discloses the main pharmacodynamic research results of blood sugar lowering and weight loss;
  • the present invention discloses for the first time the hypoglycemic and weight-loss effects of crotonol A;
  • novel hypoglycemic and weight-loss drugs having the structure of terpenoids according to the present invention can be prepared into tablets, capsules, granules, oral liquids, sustained release preparations, controlled release preparations, nano preparations, and injections. Any pharmaceutically acceptable dosage form for clinical treatment; it can also be used as a health food to serve people with diabetes and obesity, and has a broad application prospect;
  • the drug evaluation model selected for the present invention is a spontaneous obese ob/ob mouse and a spontaneous diabetes db/db mouse. These two mice were derived from genetically altered C57BL/6J mice and C57BLKS/J mice (The Jackson Laboratory), respectively. Ob/ob mice and db/db mice showed obesity, polyphagia, polydipsia, and polyuria under normal feeding. Even if the diet was controlled, obesity, blood sugar, and elevated plasma insulin levels were observed. The sugar effect and weight loss effect, the results are stable and reliable.
  • Figure 1 shows the intraperitoneal administration of 5-0-methyl crotonin A to db/db mice with body weight and fasting blood glucose. influences.
  • Figure 2 shows the effect of intraperitoneal administration of crotonol A on body weight and fasting blood glucose in db/db mice.
  • Figure 3 shows the effect of intraperitoneal administration of 5-0-methylloculinide A on body weight and fasting blood glucose in db/db mice.
  • the NMR spectrum was measured with a Bruker DRX-400 400 mega superconducting nuclear magnetic resonance spectrometer and the TMS was used as an internal standard.
  • the NMR spectrum was measured with a Bruker DRX-400 400 mega superconducting nuclear magnetic resonance spectrometer and the TMS was used as an internal standard.
  • Example 3 Effect of 5-0-methylcincosic acid A on body weight and fasting blood glucose of dM3 ⁇ 4 mice
  • Animal grouping and treatment 7-week-old male ⁇ 3 ⁇ 4 mice (Jackson Lab, USA). According to the weight, the model group, the treatment group and the positive control group were evenly divided.
  • Fasting blood glucose determination method The mice were fasted for 8 hours after the water was fasted, and the blood was cut by the tail. The blood glucose was measured by the Roche Rocco full vitality blood glucose meter.
  • Treatment group 5-0-methyl-crotonone A was dissolved in an equal volume of Tween 80 and dimethyl sulfoxide to prepare a 10 mg/mL stock solution. At the time of use, the stock solution was diluted ten times with distilled water, and intraperitoneally injected every 100 g of body weight 100 once a day until the end of the experiment at a dose of 10 mg/kg/d.
  • Rosiglitazone maleate tablets (GlaxoSmithKline Pharmaceuticals, Lot No. 09100097) was hydrolyzed and made into a suspension of 0.4 mg/mL, per 100 g body weight 100 gavage, per Once a day, until the end of the experiment, the dose was 4 mg/kg/d.
  • Model group An equal volume of mixed Tween 80 and dimethyl sulfoxide were diluted ten times with distilled water, and intraperitoneally injected every 100 g of body weight 100 once a day until the end of the experiment.
  • mice fed oral rosiglitazone maleate 4 mg/kg for 16 consecutive days showed a significant increase in body weight of 38.7%.
  • the difference in body weight gain between the 5-0-methyl-conoxone group A and the rosiglitazone maleate group was 14.8%, and the difference was significant (P ⁇ 0.01), indicating 5-0-methyl-tree Methionine A has the effect of not increasing the body weight of obese animals.
  • Animal grouping and treatment 7-week-old male ⁇ 3 ⁇ 4 mice ( Jackson Lab, USA). According to the body weight, they were evenly divided into a model group, a treatment group, and a positive control group.
  • Treatment group Phytolactone A was dissolved in an equal volume of Tween 80 and dimethyl sulfoxide to prepare a 10 mg/mL stock solution. At the time of use, the stock solution was diluted ten times with distilled water, and intraperitoneally injected every 100 g of body weight 100 once a day until the end of the experiment, at a dose of 10 mg/kg/d.
  • Model group An equal volume of mixed Tween 80 and dimethyl sulfoxide were diluted ten times with distilled water, and intraperitoneally injected every 100 g of body weight 100 once a day until the end of the experiment.
  • Weight and blood sugar value mean standard deviation
  • Example 5 Effect of 5-0-methyllocene lactone A on body weight and fasting blood glucose of db/db mice Grouping and treatment of animals: 7 weeks Male ⁇ 3 ⁇ 4 mice (Jackson Lab, USA). According to fasting blood glucose and body weight, the model group, the treatment group and the positive control group were evenly divided.
  • Treatment group 5-0-methyl laurel Lactate A was dissolved in an equal volume of Tween 80 and dimethyl sulfoxide to prepare a 10 mg/mL stock solution. At the time of use, the stock solution was diluted ten times with distilled water, and intraperitoneally injected every 100 g of body weight 100 once a day until the end of the experiment at a dose of 10 mg/kg/d.
  • Rosiglitazone maleate tablets (GlaxoSmithKline Pharmaceuticals, Lot No. 09100097) was hydrolyzed and made into a suspension of 0.4 mg/mL, per 100 g body weight 100 gavage, per Once a day, until the end of the experiment, the dose was 4 mg/kg/d.
  • Model group An equal volume of mixed Tween 80 and dimethyl sulfoxide were diluted ten times with distilled water, and intraperitoneally injected every 100 g of body weight 100 once a day until the end of the experiment.
  • Weight and blood sugar value mean standard deviation
  • Model group An equal volume of Tween 80 and dimethyl sulfoxide was diluted ten times with distilled water and intraperitoneally injected at 100 g per 10 g body weight once daily for four weeks.
  • 5-0-methyl sulphonate group Take 5-0-methyl crotonone acid A and dissolve it in an equal volume of Tween 80 and dimethyl sulfoxide to prepare a 10 mg/mL stock solution. . At the time of use, the stock solution was diluted 10 times with distilled water (1 mg/mL), and intraperitoneally injected at 100 ⁇ L per 10 g of body weight once a day for 4 weeks. The dose is 10 mg/kg/d;
  • Soyrolactone A group Take the decyl lactone A dissolved in an equal volume of Tween 80 and dimethyl sulfoxide to prepare a 10 mg/mL stock solution. At the time of use, the stock solution was diluted 10 times (1 mg/mL) with distilled water, and intraperitoneally injected with 100 ⁇ L per 10 g of body weight once a day for four weeks. The dose is 10 mg/kg/d.
  • 5-0-Methyl Bean Lactone Group A Take 5-0-methyl laurel Lactone A and dissolve it in an equal volume of Tween 80 and dimethyl sulfoxide to prepare a 10 mg/mL stock solution. . At the time of use, the stock solution was diluted 10 times with distilled water (1 mg/mL), and intraperitoneally injected at 100 ⁇ L per 10 g of body weight once a day for 4 weeks. The dose is 10 mg/kg/d.
  • Weight value average standard deviation

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Abstract

D isclosed is medicament useful for reducing blood sugar and body weight comprising 5-O-methyl Cajanonic acid A, 5-O-methyl Cajanolactone A or Cajanolactone A and having the structure of the structure of stilbene compounds. Pharmacology experiments have proved that the abovementioned compounds can reduce the fasting blood sugar and body weight, and can be used to prepare the medicament and healthcare food for treating diabetes and adiposity, especially suitable for overweight diabetic patients.

Description

具有蔵类化合物结构的降血糖和减肥药物 技术领域  Hypoglycemic and weight-loss drugs with steroid structure
本发明涉及一类降血糖和减肥药物，具体涉及一类具有蔵类化合物结构的降 血糖和减肥药物， 属于医药技术领域。  The invention relates to a kind of blood sugar lowering and weight loss medicine, in particular to a kind of blood sugar lowering and weight loss medicine having the structure of a terpenoid compound, belonging to the technical field of medicine.
背景技术 Background technique
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糖耐受性异常的 风险。 糖尿病在临床上分成 1型和 2型， 其中 2型占约 90%。 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。 1 型糖尿病多以胰岛素进行治疗， 2型糖尿病多以化学药物进行治疗。 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。常见 的抗糖尿病药物按药物来源与作用机理进行分类， 主要有胰岛素及其类似物 (主 要用于 1 型糖尿病)， 磺酰脲类， 双胍类， ex-葡萄糖苷酶抑制剂， 非磺酰脲类胰 岛素分泌促进剂， 胰岛素增敏剂 (噻唑烷二酮类)及以天然药物和中成药等类型。  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 had diabetes, and there were 40 million patients in China. More people are at risk of abnormal glucose tolerance. Diabetes is clinically classified into type 1 and type 2, with type 2 accounting for approximately 90%. The onset of diabetes is slow, the symptoms are concealed, and the condition is complicated. The progress of the disease is often accompanied by complications such as cardiovascular and cerebrovascular, kidney, eye and neuropathy. Type 1 diabetes is mostly treated with insulin, and type 2 diabetes is often treated with chemicals. According to the 2011 Diabetes Market Outlook report published by Research & Martcets, the global diabetes drug market in 2005 has reached a market size of US$18.6 billion, which is estimated to exceed US$25 billion. Common antidiabetic drugs are classified according to their source and mechanism of action, mainly insulin and its analogues (mainly used in type 1 diabetes), sulfonylureas, biguanides, ex-glucosidase inhibitors, non-sulfonylureas. Insulin-like secretion promoters, insulin sensitizers (thiazolidinediones) and natural and proprietary Chinese medicines.
磺酰脲类是临床应用最早且目前也仍在广泛使用的口服降糖药。常用的有格 列本脲， 格力吡嗪， 格列齐特， 格列喹酮和格列美脲等， 这类药物可刺激 B-细 胞分泌和释放胰岛素， 因此其降糖作用有赖于还有相当数量有功能的胰腺 B-细 胞。 总体来讲， 这类药物比较安全， 不良反应率较低， 只是长期使用容易引起低 血糖。  Sulfonylureas are the earliest oral hypoglycemic agents that are still in clinical use and are still widely used. Commonly used are glibenclamide, greepyrazine, gliclazide, gliclazide and glimepiride, etc. These drugs can stimulate the secretion and release of insulin by B-cells, so its hypoglycemic effect depends on A considerable number of functional pancreatic B-cells. In general, these drugs are safer and have a lower rate of adverse reactions, but long-term use can easily cause hypoglycemia.
双胍类降糖药有二甲双胍， 苯乙双胍等。双胍类药物可促进周围组织对葡萄 糖的摄取与利用， 增加肌肉组织中的糖的无氧酶解， 减少葡萄糖在肠道的吸收， 还可抑制胆固醇的生物合成和贮存， 降低甘油三酯和总胆固醇的水平。双胍类药 物不刺激胰腺分泌胰岛素， 它不仅抑制葡萄糖在肠道中的吸收， 还阻碍维生素 B12的吸收，可引起营养吸收不良，体重降低，适合于肥胖和伴有高血脂的病人， 但常伴着严重的毒副作用 (高达 50%)， 如乳酸酸性中毒， 甚至酮脲等， 严重地限 制了应用。 (X-葡萄糖苷酶抑制剂有别于前两类抗糖尿病药物， （X-葡萄糖苷酶抑制剂的降 糖机制为在小肠中竞争性抑制 （X-葡萄糖苷酶的活性， 使淀粉等碳水化合物水解 产生葡萄糖的速度减慢， 延缓肠道对葡萄糖的吸收， 因此有利于降低餐后的血糖 水平。其副作用主要是由于碳水化合物在肠道停留和酶解所引起的肠道不适。 目 前常用的药物是阿卡波糖和优格列波等。 The biguanide hypoglycemic agents are metformin, phenformin and the like. Biguanide can promote the uptake and utilization of glucose in surrounding tissues, increase the anaerobic digestion of sugar in muscle tissue, reduce the absorption of glucose in the intestine, inhibit the biosynthesis and storage of cholesterol, and reduce triglycerides and totals. The level of cholesterol. The biguanide does not stimulate the pancreas to secrete insulin. It not only inhibits the absorption of glucose in the intestine, but also hinders the absorption of vitamin B12, which can cause malabsorption of nutrients and weight loss. It is suitable for obesity and patients with hyperlipidemia, but often accompanied by Severe toxic side effects (up to 50%), such as lactic acidosis, even ketourea, severely limit the application. (X-glucosidase inhibitors are different from the first two types of anti-diabetic drugs. (The hypoglycemic mechanism of X-glucosidase inhibitors is competitive inhibition in the small intestine (X-glucosidase activity, making carbon water such as starch The slowing down of the hydrolysis of the compound produces glucose, delays the absorption of glucose in the intestine, and thus helps to lower the blood sugar level after the meal. The side effects are mainly due to intestinal discomfort caused by carbohydrate retention and enzymatic hydrolysis in the intestine. The drugs are acarbose and yuglip.
胰岛素增敏剂， 如噻吩烷二酮类 （TZDs) 的 "胰岛素增敏剂"， 通过改善胰 岛素抵抗状态纠正糖与脂代谢异常， 它对胰岛素的分泌没有影响。这类药物先后 上市的有曲格列酮 (Troglitazone, TRG), 马来酸罗格列酮 (Rosiglitazone, RSG; 商 品名 Avandia, 文迪雅)， 恩格列酮 (Englitazone, ENG)等。 早期上市的曲格列酮发 现具有严重的肝毒性， 甚至出现肝衰竭而死亡， 现已停止使用。 马来酸罗格列酮 (文迪雅）的毒副作用相对较小， 但仍然存在严重的心血管安全隐患， 国家药监 局 2010年卫生部、 国家食品药品监督管理局要求， 对于未使用过罗格列酮及其 复方制剂的糖尿病患者，只能在无法使用其他降糖药或使用其他降糖药无法达到 血糖控制目标的情况下， 才可考虑使用罗格列酮及其复方制剂。 另一方面， 这类 药物通过激活 PPAR-γ受体活性从而增强胰岛素敏感性的同时， 还可增加脂肪细 胞的增殖， 从而导致体重增加甚至肥胖， 限制了这类药物的广泛使用。  Insulin sensitizers, such as "insulin sensitizers" of thiophene diones (TZDs), correct for abnormal glucose and lipid metabolism by improving insulin resistance, which has no effect on insulin secretion. Such drugs have been marketed with Troglitazone (TRG), rosiglitazone maleate (RSG; trade name Avandia, Avandia), Engletazone (ENG) and so on. The early marketed troglitazone was found to have severe hepatotoxicity and even died of liver failure and has been discontinued. The toxic side effects of rosiglitazone maleate (Wendiya) are relatively small, but there are still serious cardiovascular safety hazards. The Ministry of Health and the State Food and Drug Administration requested by the State Food and Drug Administration in 2010 In patients with diabetes mellitus with rosiglitazone and its combination, rosiglitazone and its combination can only be considered if other hypoglycemic agents cannot be used or other hypoglycemic agents cannot achieve glycemic control goals. On the other hand, these drugs, by activating PPAR-γ receptor activity, enhance insulin sensitivity, and also increase the proliferation of fat cells, leading to weight gain and even obesity, limiting the widespread use of such drugs.
国内市场还可见一些有效中西药复方制剂， 如消渴丸等。但纯中药或植物药 限于其作用和机理不够确切， 临床应用面还十分有限。  The domestic market can also see some effective Chinese and Western medicine compound preparations, such as Xiaokewan. However, pure Chinese medicine or botanical medicine is limited to its role and mechanism, and its clinical application is still very limited.
研究表明， 肥胖是糖尿病的主要危险因素， 它与糖尿病的关系非常密切。肥 胖患病率高的地区糖尿病患病率也越高； 对于肥胖体型的糖尿病患者， 肥胖可以 加重胰岛素抵抗， 不利于糖尿病及其并发症的防治。 因此， 预防糖尿病必须重视 日益流行的肥胖问题。 发明内容  Studies have shown that obesity is a major risk factor for diabetes and it is closely related to diabetes. The prevalence of diabetes is higher in areas with high prevalence of obesity; for obese patients with diabetes, obesity can aggravate insulin resistance, which is not conducive to the prevention and treatment of diabetes and its complications. Therefore, prevention of diabetes must focus on the growing problem of obesity. Summary of the invention
本发明的目的是提供一类具有蔵类化合物结构的新血糖和减肥药物，该类药 物含有化合物 5-0-甲基-树豆酮酸 A， 还含有 5-0-甲基-树豆内酯 A和树豆内酯 A， 该类药物是以 5-0-甲基-树豆酮酸 A、 5-0-甲基-树豆内酯 A或树豆内酯 A 中的任一种作为药物的活性成分， 制备成药物的片剂、 胶囊、 颗粒剂、 口服液、 缓释制剂、控释制剂、纳米制剂和注射剂中任何一种药剂学上可接受的剂型， 或 是制备成具有降血糖与减肥功效的片剂、 胶囊、 颗粒剂、 口服液、 缓释制剂、 控 释制剂和纳米制剂中任何一种剂型的保健食品， 具有显著降血糖作用和减肥作 用。 The object of the present invention is to provide a novel blood sugar and slimming drug having a structure of a terpenoid compound containing the compound 5-0-methyl-crotonin A and a 5-0-methyl-tree bean Ester A and crotonol A, the drug is any one of 5-0-methyl- crotonin A, 5-0-methyl-culum lactone A or crotonol A As an active ingredient of the drug, a pharmaceutically acceptable dosage form of any one of a tablet, a capsule, a granule, an oral solution, a sustained release preparation, a controlled release preparation, a nano preparation, and an injection prepared as a medicine, or It is a health food prepared into any one of a tablet, a capsule, a granule, an oral solution, a sustained release preparation, a controlled release preparation and a nano preparation having hypoglycemic and weight loss effects, and has a significant hypoglycemic effect and a weight loss effect.
本发明的具有蔵类化合物结构的降血糖和减肥药物，含有具有如下结构式的 5-0-甲基树豆酮酸 A  The hypoglycemic and weight-loss drug having the structure of a terpenoid of the present invention, which comprises 5-0-methyl crotonin A having the following structural formula
Figure imgf000004_0001
。
Figure imgf000004_0001
.
本发明的具有蔵类化合物结构的降血糖和减肥药物还含有具有如下化学结 构式的化合物：  The hypoglycemic and weight-loss drugs having the structure of terpenoids of the present invention further contain a compound having the following chemical formula:
Figure imgf000004_0002
Figure imgf000004_0002
其中， 当 R为 Me时， 该化合物为 5-0-甲基树豆内酯 A; 当 R为 H时， 该化合物为树豆内酯 A。  Wherein, when R is Me, the compound is 5-0-methyl-lactolactone A; when R is H, the compound is cintolactone A.
本发明所述一类具有蔵类化合物结构的降血糖和减肥药物， 是以 5-0-甲基 树豆酮酸 、 5-0-甲基树豆内酯 A或树豆内酯 A中的任何一种作为活性成分， 制备成降血糖和减肥药物的片剂、胶囊、颗粒剂、 口服液、缓释制剂、控释制剂、 纳米制剂和注射剂中任何一种药剂学上可接受的剂型。  The invention relates to a kind of hypoglycemic and weight-loss drugs having the structure of terpenoids, which is in 5-0-methyl crotonin acid, 5-0-methyl crotonol A or crotonol A Any one of a pharmaceutically acceptable dosage form of a tablet, a capsule, a granule, an oral solution, a sustained release preparation, a controlled release preparation, a nano preparation, and an injection prepared as a blood sugar lowering and weight loss medicine as an active ingredient.
本发明所述一类具有蔵类化合物结构的降血糖和减肥药物， 是以 5-0-甲基 树豆酮酸 、 5-0-甲基树豆内酯 A或树豆内酯 A中的任何一种作为活性成分， 制备成具有降血糖与减肥功效的片剂、 胶囊、 颗粒剂、 口服液、 缓释制剂、 控释 制剂和纳米制剂中任何一种剂型的保健食品。 The invention relates to a kind of hypoglycemic and weight-loss drugs having the structure of terpenoids, which is in 5-0-methyl crotonin acid, 5-0-methyl crotonol A or crotonol A Any of the active ingredients as tablets, capsules, granules, oral liquids, sustained release preparations, controlled release having hypoglycemic and weight loss effects A health food of any one of the formulation and the nanoformulation.
本发明所述的树豆内酯 A可以从豆科植物树豆中提取得到。  The crotonol A according to the present invention can be extracted from the leguminous tree bean.
本发明所述的 5-0-甲基树豆酮酸 A可以由树豆酮酸 A与硫酸二甲酯按常规 甲基化方法制备。  The 5-0-methyl crotonin A of the present invention can be produced by a conventional methylation method from crotonin A and dimethyl sulfate.
本发明所述的 5-0-甲基树豆内酯 A可以由树豆内酯 A与硫酸二甲酯按常 规甲基化方法制备。  The 5-0-methyl laurel L of the present invention can be prepared by a conventional methylation method from a nutrient A and a dimethyl sulfate.
本发明相对于现有技术的有益效果在于：  The beneficial effects of the present invention over the prior art are:
( 1 ) 本发明是在前一发明 《一种具有降血糖和减肥作用的蔵类天然药物》 ( CN 200810199012.6 ) 的基础上， 通过发明人研究团队的进一步深入研究实现 的；  (1) The present invention is achieved by the inventor's research team on the basis of the previous invention "a natural medicine for reducing blood sugar and weight loss" (CN 200810199012.6);
( 2 ) 本发明公开的降血糖和减肥药物是含有具有显著降血糖作用的蔵类化 合物，包括新发现的蔵类化合物 5-0-甲基-树豆酮酸 A和 5-0-甲基-树豆内酯 A， 还包括发明人曾在中国发明专利 CN 200810199012.6 中公开过化学结构鉴定和 对靶酶活性测试的化合物树豆内酯 A， 它们与已知降血糖药物或减肥药物的化 学结构均不相同，本发明首次公开了其降血糖方面和减肥方面的药用价值， 而且 公开了其降血糖方面和减肥方面主要药效学研究结果；  (2) The hypoglycemic and weight-loss drugs disclosed in the present invention contain anthraquinone compounds having significant hypoglycemic effects, including newly discovered terpenoids 5-0-methyl-docolic acid A and 5-0-methyl - Phytolactone A, which also includes the compound Phy Cannuone A, which has been disclosed by the inventors in the Chinese invention patent CN 200810199012.6 for chemical structure identification and target enzyme activity, and their chemistry with known hypoglycemic or weight loss drugs. The structures are all different, and the present invention discloses for the first time the medicinal value of blood sugar lowering and weight loss, and discloses the main pharmacodynamic research results of blood sugar lowering and weight loss;
( 3 ) 本发明首次公开了树豆内酯 A的降血糖和减肥药效；  (3) The present invention discloses for the first time the hypoglycemic and weight-loss effects of crotonol A;
( 4 ) 本发明所述的一类具有蔵类化合物结构的新降血糖和减肥药物， 可以 制成片剂、 胶囊、 颗粒剂、 口服液、 缓释制剂、 控释制剂、 纳米制剂、 注射剂中 任何一种药学上可接受的剂型， 运用于临床治疗； 也可以制成保健食品， 服务于 糖尿病和肥胖人群， 应用前景十分广阔；  (4) The novel hypoglycemic and weight-loss drugs having the structure of terpenoids according to the present invention can be prepared into tablets, capsules, granules, oral liquids, sustained release preparations, controlled release preparations, nano preparations, and injections. Any pharmaceutically acceptable dosage form for clinical treatment; it can also be used as a health food to serve people with diabetes and obesity, and has a broad application prospect;
( 5 ) 本发明所选用的药物评价模型为自发性肥胖的 ob/ob小鼠和自发性糖 尿病的 db/db小鼠。这两种小鼠分别源自基因突变的 C57BL/6J小鼠和 C57BLKS/J 小鼠（The Jackson Laboratory )。 ob/ob小鼠和 db/db小鼠正常伺养下表现得肥胖、 多食、多饮、多尿， 即使控制饮食照样会出现肥胖、血糖和血浆胰岛素水平升高， 用于评价药物的降糖效果和和减肥效果， 所得结果稳定性可靠。 附图说明  (5) The drug evaluation model selected for the present invention is a spontaneous obese ob/ob mouse and a spontaneous diabetes db/db mouse. These two mice were derived from genetically altered C57BL/6J mice and C57BLKS/J mice (The Jackson Laboratory), respectively. Ob/ob mice and db/db mice showed obesity, polyphagia, polydipsia, and polyuria under normal feeding. Even if the diet was controlled, obesity, blood sugar, and elevated plasma insulin levels were observed. The sugar effect and weight loss effect, the results are stable and reliable. DRAWINGS
图 1为 5-0-甲基树豆酮酸 A腹腔注射给药对 db/db小鼠体重和空腹血糖的 影响。 Figure 1 shows the intraperitoneal administration of 5-0-methyl crotonin A to db/db mice with body weight and fasting blood glucose. influences.
图 2为树豆内酯 A腹腔注射给药对 db/db小鼠体重和空腹血糖的影响。 图 3为 5-0-甲基树豆内酯 A腹腔注射给药对 db/db小鼠体重和空腹血糖的 影响。 具体实施方式  Figure 2 shows the effect of intraperitoneal administration of crotonol A on body weight and fasting blood glucose in db/db mice. Figure 3 shows the effect of intraperitoneal administration of 5-0-methylloculinide A on body weight and fasting blood glucose in db/db mice. detailed description
以下通过实施例进一步说明本发明的内容，本领域技术人员能够了解本发明 具有蔵类化合物结构的新降血糖药物及其药理作用特点，但是这些实施例不得 理解为对本发明权利要求的限制。 实施例 1 5-0-甲基树豆酮酸 A的化学结构表征数据  The contents of the present invention are further illustrated by the following examples, and those skilled in the art can understand the novel hypoglycemic agents having the structure of terpenoids of the present invention and their pharmacological action characteristics, but these examples are not to be construed as limiting the claims of the present invention. Example 1 Chemical Structure Characterization Data of 5-0-Methylcincosic Acid A
核磁共振谱用 Bruker公司 DRX-400型 400兆超导核磁共振仪测定， TMS做 内标。  The NMR spectrum was measured with a Bruker DRX-400 400 mega superconducting nuclear magnetic resonance spectrometer and the TMS was used as an internal standard.
5-0-甲基树豆酮酸 A的 1H-NMR (400 Hz, 溶剂 CDC13) δ ppm: 8.040 (2H, d， J = 7.2 Hz，2'-H，6'-H)， 7.56〜7.45 (3H， m， 3'-H， 4'-H， 5'-H)， 6.522 (1H, s, 4-H), 4.909 (1H, brs, 2"-H), 4.733 (2H, s, 1"-H2), 4.022 (3H, s, OCH3)， 3.905 (3H, s， OCH3)， 3.276 (2H, d, J = 3.0 Hz, 7-H2), 1.578(3H, s, CH3), 1.563(3H， s， CH3)。 实施例 2 5-0-甲基树豆内酯 A的化学结构表征数据 1H-NMR of 5-0-methyl crotonin A (400 Hz, solvent CDC1 3 ) δ ppm: 8.040 (2H, d, J = 7.2 Hz, 2'-H, 6'-H), 7.56~ 7.45 (3H, m, 3'-H, 4'-H, 5'-H), 6.522 (1H, s, 4-H), 4.909 (1H, brs, 2"-H), 4.733 (2H, s , 1"-H 2 ), 4.022 (3H, s, OCH 3 ), 3.905 (3H, s, OCH 3 ), 3.276 (2H, d, J = 3.0 Hz, 7-H 2 ), 1.578 (3H, s , CH 3 ), 1.563 (3H, s, CH 3 ). Example 2 Chemical Structure Characterization Data of 5-0-Methylocyanolide A
核磁共振谱用 Bruker公司 DRX-400型 400兆超导核磁共振仪测定， TMS做 内标。  The NMR spectrum was measured with a Bruker DRX-400 400 mega superconducting nuclear magnetic resonance spectrometer and the TMS was used as an internal standard.
5-0-甲基树豆内酯 A的 1H-NMR (400Hz, 翻 CDC13) δ ppm: 7.864 (2H, d， J = 7.2 Hz, 2'-H， 6'-H)， 7.47〜7.41 (3H, m， 3'-H， 4'-H， 5'-H)， 6.974 (1H， s， 4-H), 6.514 (1H, s, 7-H), 5.081 (1H, brs, 2"-H), 4.024 (3H, s, OCH3)， 3.958 (3H, s， OCH3)， 3.497 (2H, d， J = 3.0 Hz, 1"-H2), 1.866(3H, s, CH3)， 1.701(3H,s, CH3)。 实施例 3 5-0-甲基树豆酮酸 A对 dM¾小鼠的体重和空腹血糖的作用 动物分组及治疗： 7周龄雄性 Λ¾小鼠 （美国 Jackson Lab )。 根据体重均 匀分为模型组、 治疗组以及阳性对照组。 空腹血糖测定方法： 小鼠禁食不禁水 8 h后剪尾取血， 用罗氏罗康全活力血 糖仪测定血糖。 1H-NMR of 5-0-methyl-runolactone A (400 Hz, turn CDC1 3 ) δ ppm: 7.864 (2H, d, J = 7.2 Hz, 2'-H, 6'-H), 7.47~7.41 (3H, m, 3'-H, 4'-H, 5'-H), 6.974 (1H, s, 4-H), 6.514 (1H, s, 7-H), 5.081 (1H, brs, 2 "-H), 4.024 (3H, s, OCH 3 ), 3.958 (3H, s, OCH 3 ), 3.497 (2H, d, J = 3.0 Hz, 1"-H 2 ), 1.866(3H, s, CH 3 ), 1.701(3H, s, CH 3 ). Example 3 Effect of 5-0-methylcincosic acid A on body weight and fasting blood glucose of dM3⁄4 mice Animal grouping and treatment: 7-week-old male Λ3⁄4 mice (Jackson Lab, USA). According to the weight, the model group, the treatment group and the positive control group were evenly divided. Fasting blood glucose determination method: The mice were fasted for 8 hours after the water was fasted, and the blood was cut by the tail. The blood glucose was measured by the Roche Rocco full vitality blood glucose meter.
( 1 ) 治疗组： 5-0-甲基-树豆酮酸 A用等体积混合的吐温 80和二甲基亚砜 溶解， 配成 10 mg/mL的储备液。 临用时将储备液用蒸馏水十倍稀释， 以每 10 g 体重 100 进行腹腔注射， 每日一次， 直到实验结束， 剂量为 10 mg/kg/d。  (1) Treatment group: 5-0-methyl-crotonone A was dissolved in an equal volume of Tween 80 and dimethyl sulfoxide to prepare a 10 mg/mL stock solution. At the time of use, the stock solution was diluted ten times with distilled water, and intraperitoneally injected every 100 g of body weight 100 once a day until the end of the experiment at a dose of 10 mg/kg/d.
(2) 阳性药组： 马来酸罗格列酮片 （葛兰素史克药业， 批号 09100097)加 水崩解后制成 0.4 mg/mL的悬液， 以每 10 g体重 100 灌胃， 每日一次， 直到 实验结束， 剂量为 4 mg/kg/d。  (2) Positive drug group: Rosiglitazone maleate tablets (GlaxoSmithKline Pharmaceuticals, Lot No. 09100097) was hydrolyzed and made into a suspension of 0.4 mg/mL, per 100 g body weight 100 gavage, per Once a day, until the end of the experiment, the dose was 4 mg/kg/d.
( 3 )模型组： 等体积混合的吐温 80和二甲基亚砜用蒸馏水十倍稀释， 以每 10 g体重 100 进行腹腔注射， 每日一次， 直到实验结束。  (3) Model group: An equal volume of mixed Tween 80 and dimethyl sulfoxide were diluted ten times with distilled water, and intraperitoneally injected every 100 g of body weight 100 once a day until the end of the experiment.
试验结果：  test results:
( 1 )与模型组相比较， 连续 16天腹腔注射 10 mg/kg/d 的 5-0-甲基-树豆酮 酸 A，对小鼠的体重没有明显的影响，两组的体重增加分别为模型组 25.7%， 5-0- 甲基-树豆酮酸 A组 23.9%。 但连续 16天口服马来酸罗格列酮 4 mg/kg的小鼠 体重显著增加了 38.7%。 5-0-甲基-树豆酮酸 A组与马来酸罗格列酮组间体重增 加值差异为 14.8%， 差异有显著性（P<0.01 )， 说明 5-0-甲基-树豆酮酸 A具有不 增加肥胖动物体重的作用。  (1) Compared with the model group, intraperitoneal injection of 10 mg-kg-kg-butyric acid A at 10 mg/kg/d for 16 consecutive days had no significant effect on the body weight of the mice. 25.7% of the model group, 23.9% of 5-0-methyl-crotonone A group. However, mice fed oral rosiglitazone maleate 4 mg/kg for 16 consecutive days showed a significant increase in body weight of 38.7%. The difference in body weight gain between the 5-0-methyl-conoxone group A and the rosiglitazone maleate group was 14.8%, and the difference was significant (P<0.01), indicating 5-0-methyl-tree Methionine A has the effect of not increasing the body weight of obese animals.
(2)与模型组相比较， 连续 16天腹腔注射 10 mg/kg/d 的 5-0-甲基-树豆酮 酸 A， 可明显降低小鼠的平均空腹血糖值， 两组血糖值分别为模型组 28.1±6.9 mmol/L, 5-0-甲基-树豆酮酸 A组 18.2±5.1 mmol/L， 组间平均空腹血糖值差异为 9.9 mmol/L, 差异有统计学意义（P<0.05 )。 阳性药马来酸罗格列酮组小鼠平均空 腹血糖值 11.2±6.4 mmol/L， 和模型组相比有显著差异 （P<0.01 )。 说明 5-0-甲 基-树豆酮酸 A有明显降低糖尿病模型动物空腹血糖值的作用。 （图 1 ) 表 1 5-0-甲基-树豆酮酸 A腹腔注射给药对 db/db小鼠体重和空腹血糖的影 响  (2) Compared with the model group, intraperitoneal injection of 10 mg-kg-kg-toluene acid A at 10 mg/kg/d for 16 consecutive days can significantly reduce the average fasting blood glucose level of the mice. For the model group, 28.1±6.9 mmol/L, and 5-0-methyl-crotonone A group 18.2±5.1 mmol/L, the mean fasting blood glucose difference between the groups was 9.9 mmol/L, the difference was statistically significant (P <0.05). The average fasting blood glucose of the positive drug rosiglitazone maleate was 11.2±6.4 mmol/L, which was significantly different from the model group (P<0.01). Description 5-0-Methyl- sulphonic acid A has a significant effect on reducing fasting blood glucose in diabetic model animals. (Fig. 1) Table 1 Effect of 5-0-methyl- sulphonic acid A intraperitoneal administration on body weight and fasting blood glucose in db/db mice
Figure imgf000007_0001
-甲基树豆酮酸 A组 7 31.8 1.0 36.4 1.2 39.4 ±1.8 23.9 23.6 ±5.6 23.5 4.1 18.2 5.1 * 马来酸罗格列酮组 6 31.8 2.5 39.6 ±2.5 44.1 2.5 38.7 25.2 5.6 15.2 ±5.9 11.2 ±6.4 体重和血糖值： 平均值士标准差
Figure imgf000007_0001
-Methyl crotonone A group 7 31.8 1.0 36.4 1.2 39.4 ±1.8 23.9 23.6 ±5.6 23.5 4.1 18.2 5.1 * Rosiglitazone maleate 6 31.8 2.5 39.6 ±2.5 44.1 2.5 38.7 25.2 5.6 15.2 ±5.9 11.2 ± 6.4 Weight and blood glucose values: Mean standard deviation
与模型组相比， <0.05 P<0.01 (t-检验）  <0.05 P<0.01 (t-test) compared to the model group
与阳性药物组相比， AP<0.05 A AP<0.01 (t-检 实施例 4 树豆内酯 A对 Λ¾小鼠的体重和空腹血糖的作用 A P<0.05 AA P<0.01 compared with the positive drug group (t-test Example 4 Effect of arganol A on body weight and fasting blood glucose in Λ3⁄4 mice
动物分组及治疗： 7周龄雄性 Λ¾小鼠 （美国 Jackson Lab )。 根据体重均 匀分为模型组、 治疗组以及阳性对照组。  Animal grouping and treatment: 7-week-old male Λ3⁄4 mice ( Jackson Lab, USA). According to the body weight, they were evenly divided into a model group, a treatment group, and a positive control group.
空腹血糖测定方法： 小鼠禁食不禁水 8 h后剪尾取血， 用罗氏罗康全活力血 糖仪测定血糖。  Fasting blood glucose determination method: The mice were fasted for 8 hours and then cut the tail to take blood. The blood glucose was measured by Roche Rocco full-vitrometer.
( 1 ) 治疗组： 树豆内酯 A用等体积混合的吐温 80和二甲基亚砜溶解， 配 成 10 mg/mL的储备液。 临用时将储备液用蒸馏水十倍稀释， 以每 10 g体重 100 进行腹腔注射， 每日一次， 直到实验结束， 剂量为 10 mg/kg/d  (1) Treatment group: Phytolactone A was dissolved in an equal volume of Tween 80 and dimethyl sulfoxide to prepare a 10 mg/mL stock solution. At the time of use, the stock solution was diluted ten times with distilled water, and intraperitoneally injected every 100 g of body weight 100 once a day until the end of the experiment, at a dose of 10 mg/kg/d.
(2) 阳性药组： 马来酸罗格列酮片 （葛兰素史克药业， 批号 09100097)加 水崩解后制成 0.4 mg/mL的悬液， 以每 10 g体重 100 灌胃， 每日一次， 直到 实验结束， 剂量为 4 mg/kg/d  (2) Positive drug group: Rosiglitazone maleate tablets (GlaxoSmithKline Pharmaceuticals, Lot No. 09100097) was hydrolyzed and made into a suspension of 0.4 mg/mL, per 100 g body weight 100 gavage, per Once a day, until the end of the experiment, the dose is 4 mg / kg / d
( 3 )模型组： 等体积混合的吐温 80和二甲基亚砜用蒸馏水十倍稀释， 以每 10 g体重 100 进行腹腔注射， 每日一次， 直到实验结束。  (3) Model group: An equal volume of mixed Tween 80 and dimethyl sulfoxide were diluted ten times with distilled water, and intraperitoneally injected every 100 g of body weight 100 once a day until the end of the experiment.
试验结果：  test results:
( 1 )与模型组相比较， 连续 16天腹腔注射 10 mg/kg/d的树豆内酯 A， 对小 鼠的体重没有明显的影响，两组的体重增加分别为模型组 25.4%，树豆内酯 A组 (1) Compared with the model group, intraperitoneal injection of 10 mg/kg/d of crotonol A for 16 consecutive days had no significant effect on the body weight of the mice. The weight gain of the two groups was 25.4% of the model group, respectively. Bean lactone group A
26.9%。 马来酸罗格列酮组的体重增加了 38.7%， 显著高于模型组和树豆内酯 A 治疗组 （P<0.05 )， 说明树豆内酯 A有不增加肥胖动物体重的作用。 26.9%. The weight of the rosiglitazone maleate group increased by 38.7%, which was significantly higher than that of the model group and the crotonide A treatment group (P<0.05), indicating that arbutolide A did not increase the body weight of obese animals.
(2)与模型组相比较， 连续 16天腹腔注射 10 mg/kg/d的树豆内酯 A， 可明 显降低小鼠的平均空腹血糖值。 两组血糖值分别为模型组 28.1±6.9 mmol/L， 树 豆内酯 A组 16.3±7.2 mmol/L。 两组数据的差异有统计学意义 （P<0.05 )。 连续 16天口服马来酸罗格列酮组小鼠平均空腹血糖值 11.2±6.4 mmol/L, 和模型组相 比有显著差异 （P<0.01 )。说明树豆内酯 A有明显降低糖尿病模型动物空腹血糖 值的作用。 （图 2) 树豆内酯 A腹腔注射给药对 db/db小鼠体重和空腹血糖的影响 (2) Compared with the model group, intraperitoneal injection of 10 mg/kg/d of crotonol A for 16 consecutive days significantly reduced the average fasting blood glucose level of the mice. The blood glucose levels of the two groups were 28.1±6.9 mmol/L in the model group and 16.3±7.2 mmol/L in the catechin group A. The difference between the two groups of data was statistically significant (P < 0.05). The average fasting blood glucose level of mice treated with oral rosiglitazone maleate for 16 consecutive days was 11.2±6.4 mmol/L, which was significantly different from the model group (P<0.01). Explain that arbutol A has a significant reduction in fasting blood glucose in diabetic model animals. The role of the value. (Fig. 2) Effect of intraperitoneal administration of saponin A on body weight and fasting blood glucose in db/db mice
Figure imgf000009_0001
Figure imgf000009_0001
体重和血糖值： 平均值士标准差  Weight and blood sugar value: mean standard deviation
与模型组相比， *P<0.05， **P<0.01 (t-:  *P<0.05, **P<0.01 (t-: compared with the model group)
与阳性药物组相比， AP<0.05 (t-检验) 实施例 5 5-0-甲基树豆内酯 A对 db/db小鼠的体重和空腹血糖的作用 动物分组及治疗： 7周龄雄性 Λ¾小鼠 （美国 Jackson Lab )。 根据空腹血 糖和体重均匀分为模型组、 治疗组以及阳性对照组。 A P<0.05 (t-test) compared with the positive drug group. Example 5 Effect of 5-0-methyllocene lactone A on body weight and fasting blood glucose of db/db mice Grouping and treatment of animals: 7 weeks Male Λ3⁄4 mice (Jackson Lab, USA). According to fasting blood glucose and body weight, the model group, the treatment group and the positive control group were evenly divided.
空腹血糖测定方法： 小鼠禁食不禁水 8 h后剪尾取血， 用罗氏罗康全活力血 糖仪测定血糖。  Fasting blood glucose determination method: The mice were fasted for 8 hours and then cut the tail to take blood. The blood glucose was measured by Roche Rocco full-vitrometer.
( 1 ) 治疗组： 5-0-甲基树豆内酯 A用等体积混合的吐温 80和二甲基亚砜 溶解， 配成 10 mg/mL的储备液。 临用时将储备液用蒸馏水十倍稀释， 以每 10 g 体重 100 进行腹腔注射， 每日一次， 直到实验结束， 剂量为 10 mg/kg/d。  (1) Treatment group: 5-0-methyl laurel Lactate A was dissolved in an equal volume of Tween 80 and dimethyl sulfoxide to prepare a 10 mg/mL stock solution. At the time of use, the stock solution was diluted ten times with distilled water, and intraperitoneally injected every 100 g of body weight 100 once a day until the end of the experiment at a dose of 10 mg/kg/d.
(2) 阳性药组： 马来酸罗格列酮片 （葛兰素史克药业， 批号 09100097)加 水崩解后制成 0.4 mg/mL的悬液， 以每 10 g体重 100 灌胃， 每日一次， 直到 实验结束， 剂量为 4 mg/kg/d。  (2) Positive drug group: Rosiglitazone maleate tablets (GlaxoSmithKline Pharmaceuticals, Lot No. 09100097) was hydrolyzed and made into a suspension of 0.4 mg/mL, per 100 g body weight 100 gavage, per Once a day, until the end of the experiment, the dose was 4 mg/kg/d.
( 3 )模型组： 等体积混合的吐温 80和二甲基亚砜用蒸馏水十倍稀释， 以每 10 g体重 100 进行腹腔注射， 每日一次， 直到实验结束。  (3) Model group: An equal volume of mixed Tween 80 and dimethyl sulfoxide were diluted ten times with distilled water, and intraperitoneally injected every 100 g of body weight 100 once a day until the end of the experiment.
试验结果：  test results:
( 1 ) 与模型组相比较， 连续 16天腹腔注射 10 mg/kg/d 的 5-0-甲基树豆内 酯 A，对小鼠的体重没有明显的影响，两组的体重增加分别为模型组 25.4%， 5-0- 甲基树豆内酯 A组 24.4%。 马来酸罗格列酮组的体重增加了 38.7%， 显著高于树 豆内酯 A治疗组 （P<0.05 )， 说明 5-0-甲基-树豆酮酸 A有不增加肥胖动物体重 的作用。 (1) Compared with the model group, intraperitoneal injection of 10 mg-methyl locustol A at 10 mg/kg/d for 16 consecutive days had no significant effect on the body weight of the mice. The model group was 25.4%, and the 5-0-methyl lenyl lactone group A was 24.4%. The weight of the rosiglitazone maleate group increased by 38.7%, significantly higher than the tree The endothelin A treatment group (P<0.05), indicating that 5-0-methyl-docolic acid A did not increase the body weight of obese animals.
(2) 与模型组相比较， 连续 16天腹腔注射 10 mg/kg/d的树豆内酯 A降低 了小鼠的平均空腹血糖值。 两组血糖值分别为模型组 28.1±6.9 mmol/L， 树豆内 酯 A组 12.8±5.1 mmol/L。 两组数据相比有非常显著差异（P<0.001 )。 连续 16天 口服马来酸罗格列酮组小鼠平均空腹血糖值 11.2±6.4 mmol/L, 和模型组相比有 显著差异 （P<0.01 )。 说明 5-0-甲基树豆内酯 A有明显降低糖尿病模型动物空腹 血糖值的作用。 （图 3 )  (2) Compared with the model group, intraperitoneal injection of 10 mg/kg/d of decanolide A for 16 consecutive days reduced the mean fasting blood glucose level of the mice. The blood glucose levels of the two groups were 28.1±6.9 mmol/L in the model group and 12.8±5.1 mmol/L in the catechin group A. There was a significant difference between the two groups (P < 0.001). The mean fasting blood glucose level of the rats in the rosiglitazone maleate group was 11.2±6.4 mmol/L for 16 consecutive days, which was significantly different from the model group (P<0.01). Description 5-0-Methyl Bean Lactone A has a significant effect on reducing fasting blood glucose levels in diabetic model animals. (image 3 )
5-0-甲基树豆内酯 A腹腔注射给药对 db/db小鼠体重和空腹血糖的影 5-0-Methyl Bean Lactone A Administration of Intraperitoneal Injection on the Weight and Fasting Blood Glucose of db/db Mice
Figure imgf000010_0001
Figure imgf000010_0001
体重和血糖值： 平均值士标准差  Weight and blood sugar value: mean standard deviation
与模型组相比， **P<0.01， ***P<0.001  Compared with the model group, **P<0.01, ***P<0.001
与阳性药物组相比， AP<0.05 (t-检验) 实施例 6 3种新型蔵类药物对 ob小鼠的体重和空腹血糖的作用 动物分组及治疗： 7周龄雄性 ob/ob小鼠 （美国 Jackson Lab), 根据体重分 为模型组、 治疗组。 Compared with the positive drug group, A P<0.05 (t-test) Example 6 Effects of three new steroids on body weight and fasting blood glucose of ob mice Animal grouping and treatment: 7-week-old male ob/ob mice (Jackson Lab, USA), divided into model group and treatment group according to body weight.
空腹血糖测定方法： 小鼠禁食不禁水 4h后剪尾取血， 用罗氏罗康全活力血 0 糖仪测定血糖。  Fasting blood glucose determination method: The mice were fasted for 4 hours and then cut off the tail to take blood. The blood sugar was measured by Roche Rokang full-vibration blood glucose meter.
( 1 ) 模型组： 等体积混合的吐温 80和二甲基亚砜用蒸馏水十倍稀释， 以每 10 g体重 100 进行腹腔注射， 每日一次， 连续四周。 (1) Model group: An equal volume of Tween 80 and dimethyl sulfoxide was diluted ten times with distilled water and intraperitoneally injected at 100 g per 10 g body weight once daily for four weeks.
(2) 治疗组：  (2) Treatment group:
5-0-甲基树豆酮酸 Α组：取 5-0-甲基树豆酮酸 A用等体积混合的吐温 80和 二甲基亚砜溶解， 配成 10 mg/mL的储备液。 临用时将储备液用蒸馏水 10倍稀 释 （1 mg/mL), 以每 10 g体重 100 μL进行腹腔注射， 每日一次， 连续给药 4周。 剂量为 10 mg/kg/d;  5-0-methyl sulphonate group: Take 5-0-methyl crotonone acid A and dissolve it in an equal volume of Tween 80 and dimethyl sulfoxide to prepare a 10 mg/mL stock solution. . At the time of use, the stock solution was diluted 10 times with distilled water (1 mg/mL), and intraperitoneally injected at 100 μL per 10 g of body weight once a day for 4 weeks. The dose is 10 mg/kg/d;
树豆内酯 A组： 取树豆内酯 A用等体积混合的吐温 80和二甲基亚砜溶解， 配成 10 mg/mL的储备液。临用时将储备液用蒸馏水 10倍稀释 （1 mg/mL), 以每 10 g体重 100 μL进行腹腔注射， 每日一次， 连续给药四周。 剂量为 10 mg/kg/d。  Soyrolactone A group: Take the decyl lactone A dissolved in an equal volume of Tween 80 and dimethyl sulfoxide to prepare a 10 mg/mL stock solution. At the time of use, the stock solution was diluted 10 times (1 mg/mL) with distilled water, and intraperitoneally injected with 100 μL per 10 g of body weight once a day for four weeks. The dose is 10 mg/kg/d.
5-0-甲基树豆内酯 A组：取 5-0-甲基树豆内酯 A用等体积混合的吐温 80和 二甲基亚砜溶解， 配成 10 mg/mL的储备液。 临用时将储备液用蒸馏水 10倍稀 释 （1 mg/mL), 以每 10 g体重 100 μL进行腹腔注射， 每日一次， 连续给药 4周。 剂量为 10 mg/kg/d。  5-0-Methyl Bean Lactone Group A: Take 5-0-methyl laurel Lactone A and dissolve it in an equal volume of Tween 80 and dimethyl sulfoxide to prepare a 10 mg/mL stock solution. . At the time of use, the stock solution was diluted 10 times with distilled water (1 mg/mL), and intraperitoneally injected at 100 μL per 10 g of body weight once a day for 4 weeks. The dose is 10 mg/kg/d.
试验结果：  test results:
( 1 ) 与模型组相比， 连续四周腹腔注射 10 mg/kg/d的 5-0-甲基树豆酮酸 A 可显著抑制小鼠的体重增长， 模型组体重增加 45.4%， 显著高于 5-0-甲基树豆内 酯 A组的 34.9%， 差异有统计学意义 （P<0.05 )， 说明此剂量下 5-0-甲基树豆酮 酸 A有明显抑制肥胖动物体重的作用， 显示出减肥作用。  (1) Compared with the model group, intraperitoneal injection of 10 mg-kg-toluene ketoacid A at 10 mg/kg/d significantly inhibited the weight gain of the mice. The weight of the model group increased by 45.4%, which was significantly higher than that of the model group. The difference was statistically significant (P<0.05) in the 5-0-methyl lenyl lactone group A (B<0.05), indicating that 5-0-methylchalonic acid A significantly inhibited the body weight of obese animals at this dose. , showing the effect of weight loss.
(2) 与模型组相比， 连续 14天腹腔注射 10 mg/kg/d的树豆内酯 A可显著 抑制小鼠的体重增长， 模型组体重增加值（45.4%)显著高于树豆内酯 A组的体 重增加值 （31.9%)， 差异有统计学意义 （P<0.01 )， 说明此剂量下树豆内酯 A有 明显抑制肥胖动物体重的作用， 显示出减肥作用。  (2) Compared with the model group, intraperitoneal injection of 10 mg/kg/d of crotonol A for 14 consecutive days significantly inhibited the weight gain of the mice. The weight gain of the model group (45.4%) was significantly higher than that of the peas. The weight gain of the ester group A (31.9%), the difference was statistically significant (P <0.01), indicating that this dose of crotonol A significantly inhibited the weight of obese animals, showing weight loss.
( 3 ) 与模型组相比， 连续四周腹腔注射 10 mg/kg/d的 5-0-甲基树豆内酯 A 可显著抑制小鼠的体重增长， 模型组体重增加值 （45.4%) 显著高于 5-0-甲基树 豆内酯 A组的体重增加值 （34.3%)， 差异有统计学意义 （P<0.05 )， 说明此剂量 下 5-0-甲基-树豆内酯 A有明显抑制肥胖动物体重的作用， 显示出减肥作用。  (3) Compared with the model group, intraperitoneal injection of 10 mg-kg-tolyl lactone A at 10 mg/kg/d for 4 consecutive weeks significantly inhibited the weight gain of the mice, and the weight gain of the model group (45.4%) was significant. The weight gain was higher than that of the 5-0-methyl lenyl lactone group A (34.3%), and the difference was statistically significant (P<0.05), indicating that 5-0-methyl-culum lactone A was present at this dose. It has a significant effect on inhibiting the weight of obese animals and shows a weight loss effect.
(4)与模型组相比， 连续四周腹腔注射 10 mg/kg/d 的 5-0-甲基树豆酮酸 A 可显著降低 ob/ob 小鼠的空腹血糖水平。 治疗结束时模型组血糖水平 19.9士 3.9mmol/L， 较治疗前 （ 18.9±4.6mmol/L) 增加 5.3%， 血糖水平基本维持不变。 而 5-0-甲基树豆酮酸 A组治疗结束时血糖水平 15.5±2.4mmol/L，较治疗前（22.2 ±5.0 mmol/L) 显著下降了 31.1%。 两组治疗前后的血糖下降值具有显著差异 (P<0.05)o 说明此剂量下 5-0-甲基树豆酮酸 A有明显降低糖尿病模型动物空腹 血糖值的作用。 (4) Compared with the model group, intraperitoneal injection of 10 mg-kg ketoacid A at 10 mg/kg/d for 4 consecutive weeks significantly reduced fasting blood glucose levels in ob/ob mice. At the end of treatment, the blood glucose level of the model group was 19.9 3.9mmol / L, compared with pre-treatment (18.9 ± 4.6mmol / L) increased by 5.3%, blood sugar levels remained basically unchanged. At the end of the 5-0-methyl crotonic acid group A, the blood glucose level was 15.5±2.4 mmol/L, which was significantly lower than that before treatment (22.2 ± 5.0 mmol/L) by 31.1%. There was a significant difference in blood glucose drop between the two groups before and after treatment (P < 0.05). This indicates that 5-0-methyl crotonin A at this dose significantly reduced the fasting blood glucose level in diabetic model animals.
(5)与模型组相比，连续四周腹腔注射 10mg/kg/d 的树豆内酯 A可显著降 低 ob/ob小鼠的空腹血糖水平。 模型组治疗前后血糖值基本维持不变， 而树豆内 酉旨 A组治疗结束时血糖水平 16.8±8.2mmol/L， 较治疗前 （21.3 ±9.0mmol/L) 显 著降低了 21.1%。 两组治疗前后的血糖下降值有显著差异 （P<0.05)。 说明此剂 量下 5-0-甲基树豆内酯 A有明显降低糖尿病模型动物空腹血糖值的作用。  (5) Compared with the model group, intraperitoneal injection of 10 mg/kg/d of ricin lactone A significantly reduced the fasting blood glucose level of ob/ob mice. The blood glucose level of the model group remained basically unchanged before and after treatment, while the blood glucose level at the end of the treatment of the group A was 16.8±8.2 mmol/L, which was significantly lower than that before treatment (21.3 ± 9.0 mmol/L) by 21.1%. There was a significant difference in blood glucose reduction between the two groups before and after treatment (P<0.05). This indicates that 5-0-methyllocene lactone A has a significant effect on reducing fasting blood glucose levels in diabetic model animals.
(6)与模型组相比，连续四周腹腔注射 10mg/kg/d 的树豆内酯 A可显著降 低 ob/ob 小鼠的空腹血糖水平。 模型组治疗前后血糖值基本维持不变， 而 5-0- 甲基树豆内酯 A组治疗结束时血糖水平 18.3±3.7 mmol/L， 较治疗前 （25.5±5.4 mmol/L)显著降低了 28.8%。 两组治疗前后的血糖下降值有显著差异（P<0.01)。 说明此剂量下 5-0-甲基树豆内酯 A有明显降低糖尿病模型动物空腹血糖值的作 用。 （表 4、 表 5)  (6) Compared with the model group, continuous intraperitoneal injection of 10 mg/kg/d of crotonol A significantly reduced the fasting blood glucose level of ob/ob mice. The blood glucose level of the model group remained basically unchanged before and after treatment, while the blood glucose level of the 5-0-methyl lenyl lactone group A was 18.3±3.7 mmol/L, which was significantly lower than that before treatment (25.5±5.4 mmol/L). 28.8%. There was a significant difference in blood glucose drop between the two groups before and after treatment (P<0.01). This indicates that 5-0-methyllocene lactone A has a significant effect on lowering the fasting blood glucose level in diabetic model animals. (Table 4, Table 5)
3种新型蔵类药物腹腔注射给药对 ob/ob小鼠体重的影响 Effects of intraperitoneal administration of three new terpenoids on body weight of ob/ob mice
Figure imgf000012_0001
Figure imgf000012_0001
体重值： 平均值士标准差  Weight value: average standard deviation
与模型组相比， <0.05， P<0.01 (t-检验）  Compared with the model group, <0.05, P<0.01 (t-test)
3种新型蔵类药物腹腔注射给药对 ob/ob小鼠空腹血糖的影响
Figure imgf000012_0002
(mmol/L) (mmol/L) 绝对值 Effects of intraperitoneal administration of three new terpenoids on fasting blood glucose in ob/ob mice
Figure imgf000012_0002
(mmol/L) (mmol/L) absolute value
相对值 (％) (mmol/L)  Relative value (%) (mmol/L)
模型组 5 18.9±4.6 19.9±3.9 1.0±3.0 5.3-0-甲基树豆酮酸 A 5 22.2±5.0 15.5±2.4 -6.9±3.3 * -31.1 树豆内酯 A 6 21.3±9.0 16.8±8.2 -4.5±3.1 -21.1-0-甲基树豆内酯 A 6 25.5±5.4 18.3±3.7 -7.2±3.8 -28.8 血糖值： 平均值士标准差  Model group 5 18.9 ± 4.6 19.9 ± 3.9 1.0 ± 3.0 5.3-0-methyl crotonone A 5 22.2 ± 5.0 15.5 ± 2.4 - 6.9 ± 3.3 * -31.1 Phytolactone A 6 21.3 ± 9.0 16.8 ± 8.2 4.5±3.1 -21.1-0-methyl lenyl lactone A 6 25.5±5.4 18.3±3.7 -7.2±3.8 -28.8 Blood glucose level: mean standard deviation
与模型组相比， <0.05， P<0.01 (t-检验）  Compared with the model group, <0.05, P<0.01 (t-test)
Figure imgf000013_0001
Figure imgf000013_0001
第 0天 第 9天 第 16天 图 1 5-0-甲基-树豆酮酸 A腹腔注射给药对 db/Wb小鼠体重和空腹血糖的影响
Figure imgf000014_0001
Day 0, Day 9 Day 16 Figure 1 Effect of 5-0-methyl-ductoic acid A administered intraperitoneally on body weight and fasting blood glucose in db/Wb mice
Figure imgf000014_0001
第 0天 第 9天 第 16天 内酯 A腹腔注射给药对 db/db小鼠体重和空腹血糖的影响 Effect of intraperitoneal administration of ester A on body weight and fasting blood glucose in db/db mice in the 16th day of day 9 on day 0
牲r鄆糊 s 郓r郓 paste s
Figure imgf000015_0001
Figure imgf000015_0001
5-0-甲基树豆内酯 A腹腔注射给药对 db/db小鼠体重和空腹血糖的影 5-0-Methyl Bean Lactone A Administration of Intraperitoneal Injection on the Weight and Fasting Blood Glucose of db/db Mice

Claims

权利要求 Rights request
1.一类具有蔵类化合物结构的降血糖和减肥药物，其特征在于含有具有如下 化学结构式的化合物 -0-甲基树豆酮酸 A: A class of hypoglycemic and weight-loss drugs having the structure of a terpenoid compound, which is characterized by containing a compound having the following chemical structural formula - 0-methyl crotonin A:
Figure imgf000016_0001
Figure imgf000016_0001
OMe 。  OMe.
2.一类具有蔵类化合物结构的降血糖和减肥药物，其特征在于还含有具有如 下化学结构式的化  2. A hypoglycemic and weight-loss drug having the structure of a terpenoid compound, characterized in that it also contains a chemical structural formula
Figure imgf000016_0002
Figure imgf000016_0002
其中， 当 R为 Me时， 该化合物为 5-0-甲基树豆内酯 A; 当 R 为 H时， 该化合物为树豆内酯 A。  Wherein, when R is Me, the compound is 5-0-methyl-lactolactone A; when R is H, the compound is cintolactone A.
3.根据权利要求 1、 2中任一项所述的一类具有蔵类化合物结构的降血糖和 减肥药物，其特征在于所述的药物是以 5-0-甲基树豆酮酸 A、 5-0-甲基树豆内酯 A或树豆内酯 A中的任何一种作为活性成分，制备成降血糖和减肥药物的片剂、 胶囊、 颗粒剂、 口服液、 缓释制剂、 控释制剂、 纳米制剂和注射剂中任何一种药 剂学上可接受的剂型。  The hypoglycemic and weight-loss drug having a steroid structure according to any one of claims 1 to 2, wherein the drug is 5-0-methyl crotonin A, A tablet, a capsule, a granule, an oral solution, a sustained-release preparation, and a preparation for lowering blood sugar and a weight-loss drug, using any one of 5-0-methyl sulphonate A or crotonol A as an active ingredient A pharmaceutically acceptable dosage form of any one of a release preparation, a nano preparation, and an injection.
4.根据权利要求 1、 2中任一项所述的一类具有蔵类化合物结构的降血糖和 减肥药物，其特征在于所述的药物是以 5-0-甲基树豆酮酸 A、 5-0-甲基树豆内酯 A或树豆内酯 A中的任何一种作为活性成分， 制备成具有降血糖与减肥功效的 片剂、 胶囊、 颗粒剂、 口服液、 缓释制剂、 控释制剂和纳米制剂中任何一种剂型 的保健食品。 The hypoglycemic and weight-loss drug having a steroid structure according to any one of claims 1 to 2, wherein the drug is 5-0-methyl crotonin A, 5-0-methyl locustactone Any one of A or a nutrient A as an active ingredient, prepared as a tablet, a capsule, a granule, an oral solution, a sustained release preparation, a controlled release preparation, and a nano preparation having hypoglycemic and weight loss effects Formulated health food.
5.根据权利要求 2所述的一类具有蔵类化合物结构的降血糖和减肥药物，其 特征在于所述的树豆内酯 A从豆科植物树豆中提取得到。  The hypoglycemic and weight-loss drug having a steroid structure according to claim 2, wherein the crotonol A is extracted from the leguminous tree bean.
PCT/CN2011/077765 2011-07-28 2011-07-28 Medicament useful for reducing blood sugar and body weight having the structure of stilbene compounds WO2013013417A1 (en)

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Cited By (3)

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Publication number Priority date Publication date Assignee Title
CN103356607A (en) * 2013-06-27 2013-10-23 广州中医药大学热带医学研究所 Application of cajanolactone A in preparation of medicine used for treating osteoporosis
CN106397207A (en) * 2016-05-13 2017-02-15 贵州医科大学 Cajanonic acid A analog, composition thereof and application thereof in drugs
WO2022011914A1 (en) * 2020-07-17 2022-01-20 广州中医药大学(广州中医药研究院) Use of cajanolactone a in preparing formulation for treating acquired obesity and concomitant diseases thereof

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CN101422450A (en) * 2008-10-09 2009-05-06 广州市允中投资发展有限公司 Cajanus cajan L. natural medicine with blood sugar reduction and weight reduction function

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CN101422450A (en) * 2008-10-09 2009-05-06 广州市允中投资发展有限公司 Cajanus cajan L. natural medicine with blood sugar reduction and weight reduction function

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103356607A (en) * 2013-06-27 2013-10-23 广州中医药大学热带医学研究所 Application of cajanolactone A in preparation of medicine used for treating osteoporosis
CN106397207A (en) * 2016-05-13 2017-02-15 贵州医科大学 Cajanonic acid A analog, composition thereof and application thereof in drugs
CN110563690A (en) * 2016-05-13 2019-12-13 贵州医科大学 Tree ketonic acid A structural analogue, composition thereof and application thereof in medicines
CN106397207B (en) * 2016-05-13 2020-12-08 贵州医科大学 Tree ketonic acid A structural analogue, composition thereof and application thereof in medicines
WO2022011914A1 (en) * 2020-07-17 2022-01-20 广州中医药大学(广州中医药研究院) Use of cajanolactone a in preparing formulation for treating acquired obesity and concomitant diseases thereof

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