WO2019218537A1 - 一种壳聚糖组合物及其制备方法 - Google Patents

一种壳聚糖组合物及其制备方法 Download PDF

Info

Publication number
WO2019218537A1
WO2019218537A1 PCT/CN2018/103509 CN2018103509W WO2019218537A1 WO 2019218537 A1 WO2019218537 A1 WO 2019218537A1 CN 2018103509 W CN2018103509 W CN 2018103509W WO 2019218537 A1 WO2019218537 A1 WO 2019218537A1
Authority
WO
WIPO (PCT)
Prior art keywords
chitosan
extract
preparation
parts
composition
Prior art date
Application number
PCT/CN2018/103509
Other languages
English (en)
French (fr)
Inventor
苏政权
Original Assignee
广东药科大学
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by 广东药科大学 filed Critical 广东药科大学
Publication of WO2019218537A1 publication Critical patent/WO2019218537A1/zh

Links

Classifications

    • 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
    • A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
    • 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
    • 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)
    • A61K36/25—Araliaceae (Ginseng family), e.g. ivy, aralia, schefflera or tetrapanax
    • A61K36/258—Panax (ginseng)
    • 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)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • 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
    • 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
    • A61K2236/30—Extraction of the material
    • A61K2236/39—Complex extraction schemes, e.g. fractionation or repeated extraction steps
    • 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
    • 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
    • A61K2236/53—Liquid-solid separation, e.g. centrifugation, sedimentation or crystallization

Definitions

  • the invention relates to the technical field of medicine, in particular to a chitosan composition and a preparation method thereof.
  • Diabetes has become an epidemic that people are paying more and more attention in recent years. According to the World Health Organization, more than 200 million people worldwide have diabetes, and this number is expected to double by 2030. According to the 2005 report of the American Diabetes Association, more than 6% of the US population has 18 million people with diabetes, of which more than 12 million have been diagnosed, and nearly six million patients do not know they have Have diabetes. According to conservative statistics, there are more than 40 million people with diabetes in China, which has surpassed India to become the country with the largest number of diabetic patients in the world. With the rapid changes in people's lifestyles, Chinese diabetes patients are increasing rapidly by 2 million to 3 million people per year. . Diabetes is the third killer of humans after cardiovascular and cancer, and more than 3 million people worldwide die each year from complications caused by diabetes or diabetes.
  • Chinese Patent Application No. 201010240555.5 discloses a slimming and lipid-lowering composition comprising 20 to 50 parts of curcumin and 50 to 80 parts of chitosan, and 10 to 30 parts may be added thereto.
  • 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 containing 1% to 65%, konjac flour 1% to 40%; further comprising: excipients 1% to 95%; Chinese Patent Application No.
  • 201210253328.5 discloses a chitosan-containing composition, the invention relates to A health care product composition having the function of regulating blood lipids or preventing hyperlipidemia, wherein the composition of the raw material is as follows: 99.5 g of chitosan and 0.5 g of vitamin C per 100 g of the product.
  • composition having a small side effect, a good therapeutic effect, and a low cost, which has the functions of reducing weight and lowering blood sugar.
  • the present invention provides a composition comprising L-carnitine tartrate and chitosan, a natural plant extract as a main component, and the composition has good effects in weight loss, blood sugar lowering, and the like. Synergistic effect, long-term use has an excellent effect on reducing body weight and lowering blood sugar.
  • a chitosan composition prepared from the following raw materials by weight:
  • chitosan 5-15 parts of chitosan, 4-10 parts of L-carnitine tartrate, 10-20 parts of kidney bean extract, and 6-12 parts of ginsenoside extract;
  • the degree of deacetylation of the chitosan is 55-85%, and the weight average molecular weight of the chitosan is 10-50 kDa;
  • the preparation method of the bean extract described therein comprises the following steps:
  • the bean After the bean is pulverized, it is sieved through 40-60 mesh, and the weight of the medicinal material is 10-15 times by volume, 60% ethanol solution is immersed for 0.5-2 hours, extracted at 40-60 ° C, extracted 1-3 times, and the extraction time is 1- After 3 hours, the filtrate was combined, and the combined liquid was concentrated under reduced pressure and dried in vacuo to obtain a bean extract;
  • the preparation method of the ginsenoside extract described above comprises the following steps:
  • Fresh ginseng is removed from the foreign body, washed with water, chopped, soaked in 6-10 volumes of 60% methanol aqueous solution for 1-2 hours, heated and refluxed for 1-3 times, each extraction time is 1-3 hours. Filtration, the filtrates are combined, the combined solution is concentrated under reduced pressure, and the concentrate is added to a volume of 1-2 times of diethyl ether for extraction twice, leaving the lower layer, and the volume of the lower layer solution is added 2-3 times the volume of saturated n-butyl The alcohol solution was extracted, concentrated under reduced pressure, and dried under vacuum to obtain a ginsenoside extract.
  • the chitosan composition as described above is prepared from the following raw materials by weight: 10 parts of chitosan, 6 parts of L-carnitine tartrate, 15 parts of kidney bean extract, and 9 parts of ginsenoside 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.
  • composition of the present invention has a certain effect on reducing body weight and inhibiting obesity, and the present invention also provides the use of the above composition in the preparation of a medicament having a slimming action.
  • composition of the present invention has a certain auxiliary therapeutic effect on lowering the blood sugar of a hyperglycemic patient, and the present invention also provides the use of the above composition in the preparation of a medicament having hypoglycemic action.
  • the present invention finds that the composition consisting of chitosan, L-carnitine tartrate, kidney bean extract and ginsenoside extract has significant weight loss and hypoglycemic effects by screening; the composition of the present invention will have different action principle components. Put together, so that they work synergistically in different ways, through the composite ratio, so that their advantages in weight loss and hypoglycemic function are fully utilized to ensure the efficacy of the product.
  • the chitosan composition of the invention has been proved to be safe and non-toxic by toxicity experiments; and the preparation method of the invention has the advantages of simple process, convenient operation, energy saving and popularization and application.
  • a chitosan composition whose raw material composition is:
  • the preparation method of the bean extract described therein comprises the following steps:
  • the beans were pulverized and passed through a 40 mesh sieve.
  • the medicinal materials were immersed in 10 times volume of 60% ethanol aqueous solution for 0.5 hour, extracted at 40 ° C, extracted once, each extraction time was 1 hour, filtered, and the filtrate was combined. Concentrated under reduced pressure and dried under vacuum to obtain a bean extract.
  • the preparation method of the ginsenoside extract described above comprises the following steps:
  • Fresh ginseng is removed from the foreign body, washed with water, chopped, soaked in 6 times volume of 60% methanol aqueous solution for 1 hour, heated and refluxed for 1 hour, each extraction time is 1 hour, filtered, the filtrate is combined, The combined liquid was concentrated under reduced pressure, and the mixture was extracted twice with a volume of diethyl ether. The lower layer was retained, and the solution was extracted twice with a saturated n-butanol solution, and concentrated under reduced pressure and dried in vacuo. Ginsenoside extract.
  • the preparation method of the composition comprises the following steps:
  • a chitosan composition whose raw material composition is:
  • the preparation method of the bean extract described therein comprises the following steps:
  • the Beans were pulverized and passed through a 60 mesh sieve.
  • the medicinal materials were immersed in a 15 times volume 60% ethanol aqueous solution for 2 hours, extracted at 60 ° C, extracted 3 times, each extraction time was 3 hours, filtered, and the filtrate was combined. Concentrated under reduced pressure and dried under vacuum to obtain a bean extract.
  • the preparation method of the ginsenoside extract described above comprises the following steps:
  • Fresh ginseng is removed from the foreign body, washed with water, chopped, soaked in 10 times volume of 60% methanol aqueous solution for 2 hours, heated and refluxed for 3 times, each extraction time is 3 hours, filtered, the filtrate is combined, The combined liquid was concentrated under reduced pressure, and the mixture was extracted twice with diethyl ether twice by volume, and the lower layer was left, and the mixture was extracted with a three-fold saturated n-butanol solution in the lower layer solution, concentrated under reduced pressure, and dried under vacuum. Ginsenoside extract.
  • the preparation method of the composition comprises the following steps:
  • a chitosan composition whose raw material composition is:
  • the preparation method of the bean extract described therein comprises the following steps:
  • the beans were pulverized and passed through a 50 mesh sieve.
  • the medicinal materials were immersed in 12 times volume of 60% ethanol aqueous solution for 1.2 hours, extracted at 50 ° C, extracted twice, each extraction time was 2 hours, filtered, and the filtrates were combined. Concentrated under reduced pressure and dried under vacuum to obtain a bean extract;
  • the preparation method of the ginsenoside extract described above comprises the following steps:
  • Fresh ginseng was removed from the foreign body, washed with water, chopped, soaked in 8 times volume of 60% methanol aqueous solution for 1.5 hours, heated and refluxed for 2 times, each extraction time was 2 hours, filtered, and the filtrate was combined. The combined liquid was concentrated under reduced pressure, and the mixture was extracted twice with 1.5 times the volume of diethyl ether. The lower layer was left, and the mixture was extracted with a 2.5-fold saturated n-butanol solution in the lower layer solution, concentrated under reduced pressure and dried in vacuo. Ginsenoside extract.
  • 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 and divided into 5 groups of 10 each.
  • 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, L-carnitine tartrate, kidney bean extract and ginsenoside extract has a good weight-loss effect on obese mice, thereby confirming that the five substances in the composition of the present invention have Significant synergy.
  • the experimental results are shown in Table 2.
  • the group administration method is shown in Table 3.
  • the composition of the present invention (experiment 4 group) can significantly lower blood sugar, and has obvious technical advantages with respect to the experimental group 1, the experimental group 2, and the experimental group 3, and the test results indicate the composition of the present invention (experiment 4) After combined application, it has a good synergistic hypoglycemic effect on fasting blood glucose in diabetic rats.
  • composition of the present invention (experiment 4 group) has significant progress in reducing body weight and lowering blood sugar with respect to chitosan alone, L-carnitine tartrate, and plant extract, indicating The chitosan, L-carnitine tartrate, and plant extracts in the compositions of the invention have a synergistic effect.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Engineering & Computer Science (AREA)
  • Hematology (AREA)
  • Biotechnology (AREA)
  • Obesity (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Mycology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Botany (AREA)
  • Medical Informatics (AREA)
  • Microbiology (AREA)
  • Child & Adolescent Psychology (AREA)
  • Emergency Medicine (AREA)
  • Endocrinology (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

一种壳聚糖组合物及其制备方法。该组合物由壳聚糖、左旋肉碱酒石酸盐、菜豆提取物和人参皂苷提取物组成，具有显著的减肥、降糖作用。该组合物安全无毒，其制备方法工艺简单，操作方便，节省能源。

Description

一种壳聚糖组合物及其制备方法 技术领域
本发明涉及医药技术领域，具体涉及一种壳聚糖组合物及其制备方法。
背景技术
由于人们生活水平的提高、营养结构的不合理以及其他一些因素，肥胖已经成为一种发病率很高的现代文明病，尤其是近年来，我国肥胖患者增长非常迅速，局部地区已达30％以上，而且青少年肥胖问题已经日益突出。肥胖，不仅影响美观，更威胁健康，会导致多种疾病的发生。
糖尿病近年来已成为人们日益关注的一种流行病。根据世界卫生组织的统计，目前全球已有超过二亿人患糖尿病，预估到2030年，这个数字还会增加一倍。根据美国糖尿病协会2005年的报导，美国人口中超过6％即有一千八百万人患有糖尿病，其中超过一千二百万人已经被确诊，另外近六百万患者还不知道他们已患有糖尿病。中国糖尿病患者据保守统计现已经超过4000万人，已超过印度成为世界上糖尿病患者最多的国家，随着人们生活方式的急剧变化，中国糖尿病患者正以每年200万-300万人的幅度急速递增。糖尿病是继心血管和癌症之后人类的第三杀手，全球每年大约有超过300万人因糖尿病或糖尿病引发的并发症而死亡。
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。由此，提供一种无毒副作用、减肥效果显著的组合物克服现有技术中存在的缺陷是业内亟待解决的问题。
针对糖尿病的治疗，虽然西药降糖机理清楚，降糖效果通常明显，对控制血糖和治疗糖尿病有肯定的作用。由于糖尿病患者需要终身服药，长期服用合成西药对人体某些器官如消化道，肝和肾的副作用也会随时间的增长而变得显著起来。许多糖尿病患者长期服用西药，逐渐对西药的降糖功能失去了作用。另外一些患者服用西药会导致低血糖的发生，还有一些患者由于肝和肾功能的缺陷，不适合选用合成药物。因此研究筛选和选用和合成药物有相同降糖功能的天然药物很自然的受到了空前的重视。
申请号为201010240555.5的中国专利，公开了一种减肥降脂组合物，该组合物由20～50份姜黄素和50～80份壳聚糖组成，在这基础上还可添加10～30份的羟基柠檬酸、L-苹果酸或酒石酸肉碱中的一种或几种。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％；申请号为201210253328.5的中国专利申请，公开了一种含有壳聚糖的组合物，该发明涉及一种具有调节血脂或预防高脂血症功能的保健品组合物，该组合物原料配方如下：每100g产品中含有壳聚糖99.5g，维生素C0.5g。
因此，研究出一种毒副作用小、治疗效果好、成本较低的具有减肥、降血糖作用的组合物具有重要意义。
发明内容
为了克服现有技术的不足，本发明提供了一种左旋肉碱酒石酸盐与壳聚糖、天然植物提取物为主要组分的组合物，这种组合物在减肥、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和降低血糖具有优异的效果。
为了实现上述目的，本发明的技术方案如下：
一种壳聚糖组合物，它是由下述重量份的原料制得：
壳聚糖5-15份，左旋肉碱酒石酸盐4-10份，菜豆提取物10-20份，人参皂苷提取物6-12份；
其中，所述壳聚糖的脱乙酰度为55-85％，所述壳聚糖中重量平均分子量是10-50kDa；
其中所述的菜豆提取物的制备方法包括如下步骤：
取菜豆粉碎后过40-60目筛，加药材重量10-15倍体积60％乙醇水溶液浸泡0.5-2小时，在40-60℃下提取，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、真空干燥，即得菜豆提取物；
其中所述的人参皂苷提取物的制备方法包括如下步骤：
取新鲜人参除异物后用清水洗净，切碎，加药材重量6-10倍体积的60％甲醇水溶液浸泡1-2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，向浓缩液加入其体积的1-2倍的乙醚萃取二次， 保留下层，向下层溶液中加入其体积的2-3倍的饱和正丁醇溶液提取，减压浓缩、真空干燥，得到人参皂苷提取物。
优选地，如上所述的壳聚糖组合物，它是由以下重量份的原料制得：壳聚糖10份，左旋肉碱酒石酸盐6份，菜豆提取物15份，人参皂苷提取物9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聚糖，左旋肉碱酒石酸盐，菜豆提取物和人参皂苷提取物，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。
申请人进行的实验证明，本发明组合物对对降低体重、抑制肥胖具有一定的效果，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。
申请人进行的实验证明，本发明组合物对降低高血糖患者的血糖具有一定的辅助治疗效果，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。
本发明的技术方案具有如下优点：
(1)本发明通过筛选发现由壳聚糖、左旋肉碱酒石酸盐、菜豆提取物和人参皂苷提取物组成的组合物具有显著的减肥、降糖作用；本发明组合物将不同作用原理的成分组合在一起，使它们以不同方式协同作用，经过复合配比，使其在减肥、降糖功能上的优势得到充分发挥，从而确保产品的功效。
(2)本发明所述的壳聚糖组合物，经毒性实验证明，安全无毒；并且本发明的制备方法工艺简单，操作方便，节省能源，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
一种壳聚糖组合物，其原料组成为：
壳聚糖5g，左旋肉碱酒石酸盐4g，菜豆提取物10g，人参皂苷提取物6g。
其中所述的菜豆提取物的制备方法包括如下步骤：
取菜豆粉碎后过40目筛，加药材重量10倍体积60％乙醇水溶液浸泡0.5小时，在40℃下提取，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、真空干燥，即得菜豆提取物。
其中所述的人参皂苷提取物的制备方法包括如下步骤：
取新鲜人参除异物后用清水洗净，切碎，加药材重量6倍体积的60％甲醇水溶液浸泡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，向浓缩液加入其体积的1倍的乙醚萃取二次，保留下层，向下层溶液中加入其体积的2倍的饱和正丁醇溶液提取，减压浓缩、真空干燥，得到人参皂苷提取物。
该组合物的制备方法包括如下步骤：
分别称取配方量的壳聚糖，左旋肉碱酒石酸盐，菜豆提取物和人参皂苷提取物，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
一种壳聚糖组合物，其原料组成为：
壳聚糖15g，左旋肉碱酒石酸盐10g，菜豆提取物20g，人参皂苷提取物12g。
其中所述的菜豆提取物的制备方法包括如下步骤：
取菜豆粉碎后过60目筛，加药材重量15倍体积60％乙醇水溶液浸泡2小时，在60℃下提取，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、真空干燥，即得菜豆提取物。
其中所述的人参皂苷提取物的制备方法包括如下步骤：
取新鲜人参除异物后用清水洗净，切碎，加药材重量10倍体积的60％甲醇水溶液浸泡2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，向浓缩液加入其体积的2倍的乙醚萃取二次，保留下层，向下层溶液中加入其体积的3倍的饱和正丁醇溶液提取，减压浓缩、真空干燥，得到人参皂苷提取物。
该组合物的制备方法包括如下步骤：
分别称取配方量的壳聚糖，左旋肉碱酒石酸盐，菜豆提取物和人参皂苷提取 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
一种壳聚糖组合物，其原料组成为：
壳聚糖10g，左旋肉碱酒石酸盐6g，菜豆提取物15g，人参皂苷提取物9g。
其中所述的菜豆提取物的制备方法包括如下步骤：
取菜豆粉碎后过50目筛，加药材重量12倍体积60％乙醇水溶液浸泡1.2小时，在50℃下提取，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、真空干燥，即得菜豆提取物；
其中所述的人参皂苷提取物的制备方法包括如下步骤：
取新鲜人参除异物后用清水洗净，切碎，加药材重量8倍体积的60％甲醇水溶液浸泡1.5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，向浓缩液加入其体积的1.5倍的乙醚萃取二次，保留下层，向下层溶液中加入其体积的2.5倍的饱和正丁醇溶液提取，减压浓缩、真空干燥，得到人参皂苷提取物。
该组合物的制备方法包括如下步骤：
分别称取配方量的壳聚糖，左旋肉碱酒石酸盐，菜豆提取物和人参皂苷提取物，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，分为5组，每组10只。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 PCTCN2018103509-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聚糖、左旋肉碱酒石酸盐、菜豆提取物和人参皂苷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 80.3±6.9 83.2±7.8 84.0±8.3 84.5±8.2
实验1组 80.3±8.0 81.8±6.8 82.4±7.2 83.1±7.9
实验2组 78.7±7.4 79.0±8.2 81.6±8.1 82.2±6.7
实验3组 79.5±8.4 80.8±7.6 81.6±6.7 82.8±8.5
实验4组 78.5±4.3 76.9±5.6 75.6±8.1* ￥ 75.1±3.4** ￥￥▼△
*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6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 PCTCN2018103509-appb-000002
表4 不同实验组降血糖效果比较
Figure PCTCN2018103509-appb-000003
Figure PCTCN2018103509-appb-000004
△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4组)能够显著降低血糖，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)联合应用后对于糖尿病大鼠的空腹血糖具有很好的协同性降血糖作用。
综合上述实验可以看到，相对于单独的壳聚糖、左旋肉碱酒石酸盐、植物提取物，本发明组合物(实验4组)在降低体重、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壳聚糖、左旋肉碱酒石酸盐、植物提取物具有协同作用。

Claims (6)

  1. 一种壳聚糖组合物，其特征在于，它是由下述重量份的原料制得：壳聚糖5-15份，左旋肉碱酒石酸盐4-10份，菜豆提取物10-20份，人参皂苷提取物6-12份；
    其中，所述壳聚糖的脱乙酰度为55-85％，所述壳聚糖中重量平均分子量是10-50kDa；
    其中所述的菜豆提取物的制备方法包括如下步骤：
    取菜豆粉碎后过40-60目筛，加药材重量10-15倍体积60％乙醇水溶液浸泡0.5-2小时，在40-60℃下提取，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、真空干燥，即得菜豆提取物；
    其中所述的人参皂苷提取物的制备方法包括如下步骤：
    取新鲜人参除异物后用清水洗净，切碎，加药材重量6-10倍体积的60％甲醇水溶液浸泡1-2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，向浓缩液加入其体积的1-2倍的乙醚萃取二次，保留下层，向下层溶液中加入其体积的2-3倍的饱和正丁醇溶液提取，减压浓缩、真空干燥，得到人参皂苷提取物。
  2. 根据权利要求1所述的壳聚糖组合物，其特征在于，它是由以下重量份的原料制得：壳聚糖10份，左旋肉碱酒石酸盐6份，菜豆提取物15份，人参皂苷提取物9份；
  3. 一种权利要求1或2所述的壳聚糖组合物的制备方法，其特征在于，包括以下步骤：
    分别称取配方量的壳聚糖，左旋肉碱酒石酸盐，菜豆提取物和人参皂苷提取物，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。
  4. 根据权利要求3所述的制备方法得到的壳聚糖组合物，其特征在于，所述的药物组合物为口服制剂。
  5. 权利要求1或2的壳聚糖组合物在制备具有减肥作用药物中的应用。
  6. 权利要求1或2的壳聚糖组合物在制备具有降血糖作用药物中的应用。
PCT/CN2018/103509 2018-05-18 2018-08-31 一种壳聚糖组合物及其制备方法 WO2019218537A1 (zh)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CN201810492383.7A CN108498563B (zh) 2018-05-18 2018-05-18 一种壳聚糖组合物及其制备方法
CN201810492383.7 2018-05-18

Publications (1)

Publication Number Publication Date
WO2019218537A1 true WO2019218537A1 (zh) 2019-11-21

Family

ID=63401083

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CN2018/103509 WO2019218537A1 (zh) 2018-05-18 2018-08-31 一种壳聚糖组合物及其制备方法

Country Status (2)

Country Link
CN (1) CN108498563B (zh)
WO (1) WO2019218537A1 (zh)

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN112931510A (zh) * 2021-02-01 2021-06-11 河北科技师范学院 一种壳聚糖及其制备方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1318317A (zh) * 2001-05-24 2001-10-24 上海华源蓝科健康产品股份有限公司 一种可减肥和降脂的保健食品
CN101112421A (zh) * 2006-07-28 2008-01-30 蔚然生物食品（上海）有限公司 一种减肥胶囊制剂
CN106689954A (zh) * 2015-11-16 2017-05-24 乌鲁木齐益广康源生物科技有限公司 一种纤瘦减肥固体饮料

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITMI20121727A1 (it) * 2012-10-12 2014-04-13 Indena Spa Formulazioni per il trattamento e la prevenzione dell'obesita'
CN103431392B (zh) * 2013-08-29 2014-12-17 青岛海百合生物技术有限公司 一种供糖尿病患者食用的复合海洋特膳食品
CN103520684B (zh) * 2013-10-21 2015-08-12 王永翠 一种降血糖的中药复合物

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1318317A (zh) * 2001-05-24 2001-10-24 上海华源蓝科健康产品股份有限公司 一种可减肥和降脂的保健食品
CN101112421A (zh) * 2006-07-28 2008-01-30 蔚然生物食品（上海）有限公司 一种减肥胶囊制剂
CN106689954A (zh) * 2015-11-16 2017-05-24 乌鲁木齐益广康源生物科技有限公司 一种纤瘦减肥固体饮料

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
WANG, DONGWEN ET AL.: "Research Progress of Diet Pills", TIANJIN PHARMAMACY, vol. 28, no. 01, 31 January 2016 (2016-01-31), pages 53 - 56 *

Also Published As

Publication number Publication date
CN108498563A (zh) 2018-09-07
CN108498563B (zh) 2020-10-23

Similar Documents

Publication Publication Date Title
CN109674958B (zh) 一种具有降尿酸功效的中药组合物及其制备方法和应用
EP3151843B1 (en) Compositions comprising cyclocarya paliurus extract and preparation method and uses thereof
US10894070B2 (en) Drug compound for the control of blood glucose, blood lipids and weight
JP2011522844A (ja) 血糖レベルを低下させる組成物及びその用途
CN112546167A (zh) 一种具有健脾利湿功能的中药组合物及其制备方法和应用
CN108434191B (zh) 一种具有减肥降脂作用的组合物及其制备方法
CN115317574A (zh) 一种用于治疗高尿酸血症的组合物及其应用
CN107569608B (zh) 一种用于降血糖的药物组合物
WO2018188546A1 (zh) 蝉花的新用途
WO2019218537A1 (zh) 一种壳聚糖组合物及其制备方法
CN107537028B (zh) 一种同时辅助降血糖及降血压的配方及其制备方法
CN108420890B (zh) 一种具有降血脂作用的组合物及其制备方法
CN107136269B (zh) 一种青钱柳苦瓜降糖茶及其制备方法
CN107266599B (zh) 金针菇多糖、提取方法及其在制备治疗功能性便秘药物方面的应用
CN107281386B (zh) 以铁皮石斛与莱菔子制备治疗高血压药物的方法及应用
JP7157253B2 (ja) 潤腸便通の漢方薬組成物、その調製方法及びその用途
WO2013056508A1 (zh) 一种调节血脂的药物组合物及其制备工艺
WO2014134833A1 (zh) 可食用组合物及其制备方法和包含该组合物的食品
CN107536016B (zh) 一种保护心脏和促进肝脏健康的营养食品
CN102225082A (zh) 一种防治糖尿病及其并发症的药物和其制备方法
WO2018188547A1 (zh) 蝉花的新用途
CN112089783B (zh) 中药组合物在制备预防或/和治疗肥胖的药物中的应用
CN110559322A (zh) 一种治疗抑郁症及预防焦虑抑郁的沙棘复合物硬胶囊及制法
KR102265793B1 (ko) 금어초 추출물을 유효성분으로 함유하는 혈당 강하용 건강기능식품 조성물
CN107753551B (zh) 一种具有降血压功能的组合物及其制备方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 18918846

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 18918846

Country of ref document: EP

Kind code of ref document: A1