WO2021213232A1 - 一种中药组合物在制备治疗或预防高血脂症的药物中的应用 - Google Patents

一种中药组合物在制备治疗或预防高血脂症的药物中的应用 Download PDF

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WO2021213232A1
WO2021213232A1 PCT/CN2021/087276 CN2021087276W WO2021213232A1 WO 2021213232 A1 WO2021213232 A1 WO 2021213232A1 CN 2021087276 W CN2021087276 W CN 2021087276W WO 2021213232 A1 WO2021213232 A1 WO 2021213232A1
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chinese medicine
traditional chinese
medicine composition
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吴铁
袁孟峰
王嘉豪
麦龙儿
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Ng Tit
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    • 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)
    • A61K36/74—Rubiaceae (Madder family)
    • A61K36/744—Gardenia
    • 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
    • A61K36/06—Fungi, e.g. yeasts
    • A61K36/07—Basidiomycota, e.g. Cryptococcus
    • A61K36/076—Poria
    • 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)
    • A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
    • 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)
    • A61K36/36—Caryophyllaceae (Pink family), e.g. babysbreath or soapwort
    • 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)
    • A61K36/53—Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/537—Salvia (sage)
    • 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)
    • A61K36/81—Solanaceae (Potato family), e.g. tobacco, nightshade, tomato, belladonna, capsicum or jimsonweed
    • A61K36/815—Lycium (desert-thorn)
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • A61K36/8998—Hordeum (barley)
    • 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)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A61K36/9064—Amomum, e.g. round cardamom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation, decoction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2236/00—Isolation or extraction methods of medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicine
    • A61K2236/30—Extraction of the material
    • A61K2236/39—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 field of medicine, in particular to the application of a traditional Chinese medicine composition in the preparation of a medicine for treating or preventing hyperlipidemia.
  • Hypertriglyceridemia refers to a heterogeneous disorder of triglyceride protein synthesis or degradation. It is an important risk factor for the occurrence of metabolic syndrome-related diseases such as coronary heart disease, hypertension, diabetes, and active control of high triglycerides is an important link in the primary prevention of metabolic syndrome-related diseases.
  • Triglyceride also known as fat, is synthesized from food fat and liver, and is a fat molecule formed by long-chain fatty acids and glycerol. It is the most important type of blood lipids in the blood. They are insoluble in water, combine with proteins to form lipoproteins, and circulate in the blood. The diglyceride interacts with the third acyl-CoA molecule to generate triglycerides, which plays a catalytic role. Triglycerides are the most abundant lipids in the human body. Most tissues can use triglyceride breakdown products to provide energy. At the same time, liver, fat and other tissues can also synthesize triglycerides and store them in adipose tissue. Triglyceride is an important indicator in blood lipid examination, and his indicator directly measures a person's health.
  • Cholesterol and triglycerides are the main components of blood lipids in plasma. Due to the significant changes in diet and lifestyle in recent years, dyslipidemia has become one of the biggest health risks for Chinese people.
  • Blood lipids is the general term for various lipids in the blood. The most important of these are cholesterol and triglycerides. Triglycerides, fats that are insoluble in water, combine with proteins to form lipoproteins and circulate in the blood. Mildly elevated triglycerides may be caused by factors such as excessive carbohydrate food intake, smoking, and obesity. Severe high triglycerides are mostly related to diabetes, liver disease, chronic nephritis, etc., and are generally secondary diseases.
  • the purpose of the present invention is to provide a new traditional Chinese medicine composition in the preparation of treatment or prevention of hyperlipidemia drugs
  • the traditional Chinese medicine composition is composed of Gardenia, Poria, Salvia, Digupi, Prince Edward It is composed of ginseng, Amomum villosum, raw malt and vegetable servings.
  • the traditional Chinese medicine composition is used in the preparation of a medicine for treating or preventing the increase of serum total cholesterol or triglyceride.
  • the application of the traditional Chinese medicine composition in the preparation of a medicine for treating or preventing elevated triglycerides is not limited.
  • the application of the traditional Chinese medicine composition in the treatment or prevention of elevated triglycerides in the treatment or prevention of elevated triglycerides; preferably, the application in the treatment or prevention of hypertriglyceridemia.
  • the application of the traditional Chinese medicine composition in the treatment or prevention of elevated triglyceride drugs to adult subjects The dosage range of the traditional Chinese medicine composition is: 5-10g/day (in Chinese medicine pills (Calculation), as an exemplary illustration, may be 5g/day, 6g/day, 7g/day, 8g/day, 9g/day, 10g/day of Chinese medicine pills of the present invention administered to adult subjects.
  • the present invention also provides a traditional Chinese medicine composition.
  • the traditional Chinese medicine composition comprises, by weight, 1.25-1.55 parts of Gardenia, 1.25-1.46 parts of Poria, 0.925-1.31 parts of Salvia miltiorrhiza, 1.1-1.37 parts of Radix Root It consists of 0.925-1.08 parts, Amomum villosum 0.55-0.68 parts, 3 parts raw malt, and 1 part Caifuzi.
  • the traditional Chinese medicine composition of the present invention is composed of 1.55 parts of Gardenia, 1.46 parts of Poria, 1.31 parts of Salvia miltiorrhiza, 1.37 parts of Radix Geophylla, 1.08 parts of Radix Ginseng, 0.68 parts of Amomum villosum, and 3 parts of raw malt by weight. It consists of 1 serving and 1 serving of Caifuzi.
  • the traditional Chinese medicine composition of the present invention is composed of 1.25 parts of Gardenia, 1.25 parts of Poria, 0.925 parts of Salvia miltiorrhiza, 1.1 parts of Radix Geophylla, 0.925 parts of Radix Ginseng, 0.55 parts of Amomum villosum, and 3.0 parts of raw malt by weight. It consists of 1.0 servings and 1.0 servings of Caifuzi.
  • the extract of the traditional Chinese medicine composition of the present invention is ethanol.
  • the present invention also provides a method for preparing a traditional Chinese medicine composition, the method comprising:
  • the prescription ratio Zhongdan participated in the extraction of gardenia with 80% ethanol for 2 times, the first time was 5 times the amount of 80% ethanol for 2 hours, the second time was 4 times the amount of 80% ethanol for 1.5 hours, filtered , The dregs are collected in a separate container for use; the two filtrates before and after are combined, and ethanol is recovered under reduced pressure to a clear ointment with a relative density of about 1.20 (70°C) for use;
  • the present invention also provides a preparation containing a traditional Chinese medicine composition.
  • the preparation is composed of a traditional Chinese medicine composition and pharmaceutical excipients.
  • the excipients include, but are not limited to, beta cyclodextrin, corn starch, and talc. , Or a combination of two or more of them.
  • the formulation includes but is not limited to pills, dripping pills, capsules or granules.
  • the preparation is preferably a pill; as one of the embodiments, the auxiliary materials of the pill are betacyclodextrin, corn starch and talc.
  • the present invention further provides a preparation method of the pill, the preparation method of the preparation includes:
  • the prescription ratio Zhongdan participated in the extraction of gardenia with 80% ethanol for 2 times, the first time was 5 times the amount of 80% ethanol for 2 hours, the second time was 4 times the amount of 80% ethanol for 1.5 hours, filtered , The dregs are collected in a separate container for use; the two filtrates before and after are combined, and ethanol is recovered under reduced pressure to a clear ointment with a relative density of about 1.20 (70°C) for use;
  • the new traditional Chinese medicine composition of the present invention has a good effect on the treatment or prevention of hyperlipidemia, especially hypertriglyceridemia, and has a good synergistic effect.
  • Figure 1 shows the body weight changes of mice fed a high-fat diet treated with Chinese medicine pills of the present invention.
  • Figure 2 shows the changes in serum total cholesterol levels of mice fed a high-fat diet treated with Chinese medicine pills of the present invention.
  • Figure 3 shows the changes in serum triglyceride levels of mice fed a high-fat diet treated with Chinese medicine pills of the present invention.
  • Figure 4 is a representative histological image (H&E, 200 times magnification) of mouse liver tissue, which shows different degrees of steatosis.
  • A 0% steatosis; B. 5-10% steatosis; C. 60% steatosis; D. 90% steatosis.
  • the present invention further illustrates the present invention through the following examples and experimental examples, and is not intended to limit its scope.
  • the prescription ratio Zhongdan participated in the extraction of gardenia with 80% ethanol for 2 times, the first time was 5 times the amount of 80% ethanol for 2 hours, the second time was 4 times the amount of 80% ethanol for 1.5 hours, filtered , The dregs are collected in a separate container for use; the two filtrates before and after are combined, and ethanol is recovered under reduced pressure to a clear ointment with a relative density of about 1.20 (70°C) for use;
  • Preparation method (1) Participate in the formulation of Zhongdan to extract gardenia with 80% ethanol for 2 times, add 5 times the amount of 80% ethanol for the first time to extract for 2 hours, and add 4 times the amount of 80% ethanol for the second time. After 1.5 hours, filter, and collect the medicine residue in another device for later use; combine the two filtrates before and after, and recover the ethanol under reduced pressure to a clear ointment with a relative density of about 1.20 (70°C) for later use;
  • the prescription ratio Zhongdan participated in the extraction of gardenia with 80% ethanol for 2 times, the first time was 5 times the amount of 80% ethanol for 2 hours, the second time was 4 times the amount of 80% ethanol for 1.5 hours, filtered , The dregs are collected in a separate container for use; the two filtrates before and after are combined, and ethanol is recovered under reduced pressure to a clear ointment with a relative density of about 1.20 (70°C) for use;
  • the prescription ratio Zhongdan participated in the extraction of gardenia with 80% ethanol for 2 times, the first time was 5 times the amount of 80% ethanol for 2 hours, the second time was 4 times the amount of 80% ethanol for 1.5 hours, filtered , The dregs are collected in a separate container for use; the two filtrates before and after are combined, and ethanol is recovered under reduced pressure to a clear ointment with a relative density of about 1.20 (70°C) for use;
  • the Chinese medicine pill of the present invention was prepared according to Example 3;
  • High-fat food (HFD Research Diets, New Brunswick, NJ; catalog number D12492), which has a fat content of 60%;
  • mice Five-week-old C57BL/6J male mice were used as animal models to simulate human metabolic abnormalities.
  • mice All mice are kept in a pathogen-free environment, with temperature (22 ⁇ 2°C), humidity (40-60%), and a light-dark cycle of 12:12 hours. All mice were fed ad libitum. After 7 days of acclimatization to the standard food environment, the mice were randomly assigned: fed a high-fat diet (HFD; Research Diets, New Brunswick, NJ; catalog number D12492) with a fat content of 60%; or its corresponding low The fat control diet (LFD; Research Diets; catalog number D12492) has a sucrose content that matches HFD, but the fat content is only 10%.
  • HFD high-fat diet
  • LFD Research Diets; catalog number D12492
  • mice were divided into different groups according to diet and intervention (Table 1). For all groups, the mice were first fed LFD or HFD for 10 weeks, and then for 8 weeks of intervention (using traditional Chinese medicine pills or water (as a placebo)).
  • Groups 3, 4, and 5 are HFD-fed mice, respectively, with different doses (low, normal or high doses) of the Chinese medicine pill of the present invention.
  • the normal dose is determined to be 46.2mg Chinese medicine pills/50g mice.
  • Traditional Chinese medicine pills are prepared in a form suspended in water and administered by oral gavage every day.
  • the high dose is set to twice the normal dose (92.4mg Chinese medicine pill/50g mouse), and the low dose is set to half the normal dose (23.1mg/50g mouse).
  • mice were weighed every week, and the dosage of Chinese medicine pills (or water) for each mouse was based on body weight. Chinese medicine pills were administered for 8 weeks.
  • the ALT/GPT Liqui-UV assay and the AST/GOT Liqui-UV assay were used to evaluate serum ALT and AST, respectively.
  • the LiquiColor triglyceride and cholesterol LiquiColor assays were used to analyze serum triglycerides and total cholesterol.
  • liver tissue specimens were fixed in 10% formalin buffer, embedded in paraffin, cut into 5 ⁇ m thick, and stained with hematoxylin and eosin.
  • the degree of steatosis was assessed by a pathologist who did not understand the experimental design and was based on the system described by Kleiner et al. (Hepatology 2005; 41:1313-21). Fat changes are expressed as the percentage of fatty degeneration cells and are classified as described previously: no steatosis ( ⁇ 5% fat change); low-grade steatosis (fat change is 5-33%); moderate steatosis (>33 -66% fat change); and severe steatosis (>66% fat change).
  • the mice fed with HFD average body weight: 44.1 ⁇ 0.5g
  • those fed with LFD average body weight
  • 29.9 ⁇ 0.6g; P ⁇ 0.001 is much heavier.
  • the average weight change of LFD-fed mice was 7.4 ⁇ 0.6g
  • the average weight change of HFD-fed mice was 22.0 ⁇ 0.5g (P ⁇ 0.001).
  • the serum total cholesterol level of HFD-fed mice (129.6 ⁇ 3.5mg/dL) was significantly higher than that of LFD-fed mice (79.1 ⁇ 8.4mg/dL; P ⁇ 0.001), and the serum glycerol of HFD-fed mice
  • mice fed by HFD to receive different doses of Chinese medicine pills (or water as a placebo control).
  • body weight, serum total cholesterol and triglycerides of the different HFD-fed mice receiving different treatments were well balanced and comparable (Table 2).
  • LFD low-fat diet
  • HFD high-fat diet
  • the average body weight of the HFD-fed control mice was 49.2 ⁇ 0.68 g, which was 14.8% heavier than the baseline (before treatment) body weight.
  • the body weight of HFD-fed mice (average increase: 5.1-12.0%) that received Chinese medicine pills also increased.
  • the weight gain of each treatment group was slightly lower than that of the HFD placebo group, but the difference in weight change was not statistically significant. No dose effect on weight change was observed in the Chinese medicine pill group (Figure 1); the experimental results show that the Chinese medicine pill of the present invention effectively reduces the weight gain effect of high-calorie diet in mice, and has corresponding effective prevention or Therapeutic effect.
  • Serum triglyceride level Serum triglyceride level
  • mice treated with traditional Chinese medicine pills had lower levels of ALT and AST, although the difference was not statistically significant, and no dose effect was observed (Table 3); ALT and AST are commonly used clinically Liver damage indicators, research results show that Chinese medicine pills effectively reduce the liver damage caused by high-calorie diet in mice, and have corresponding effective preventive or therapeutic effects.
  • ALT alanine aminotransferase
  • AST aspartate aminotransferase

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Abstract

一种治疗或预防高血脂症的中药组合物及其制备方法，以及该中药组合物在制备治疗或预防高血脂症的药物中的应用，该中药组合物由栀子1.25-1.55份、茯苓1.25-1.46份、丹参0.925-1.31份、地骨皮1.1-1.37份、太子参0.925-1.08份、砂仁0.55-0.68份、生麦芽3份、菜服子（莱菔子）1份组成。该中药组合物制成的制剂可为丸剂、滴丸、胶囊、颗粒剂。

Description

一种中药组合物在制备治疗或预防高血脂症的药物中的应用 技术领域
本发明涉及医药领域，具体涉及一种中药组合物在制备治疗或预防高血脂症的药物中的应用。
背景技术
高甘油三酯血症是指一种异族性甘油三酯蛋白合成或降解障碍。它是冠心病、高血压、糖尿病等代谢综合征相关疾病发生的重要危险因素，积极控制高甘油三酯是代谢综合征相关疾病一级预防的重要环节。
甘油三酯(Triglyceride，缩写TG)，又称脂肪，是由食物脂肪与肝脏合成的，是长链脂肪酸和甘油形成的脂肪分子。它是血液中血脂最重要的一种。它们不溶于水，与蛋白质结合成脂蛋白，在血液中循环运转。甘油二酯与第三个脂酰CoA分子作用生成甘油三酯，起催化作用。甘油三酯是人体内含量最多的脂类，大部分组织均可以利用甘油三酯分解产物供给能量，同时肝脏、脂肪等组织还可以进行甘油三酯的合成，在脂肪组织中贮存。甘油三酯是血脂检查中比较重要的一项指标，他的指标直接衡量一个人的健康状况。
胆固醇和甘油三酯是血浆中主要血脂成分，由于近年来饮食结构和生活方式的显著改变，血脂异常已经成为国人最大的一项健康隐患。
血脂是血液中各种脂类物质的总称。其中最重要的是胆固醇和甘油三酯。甘油三酯即脂肪不溶于水，与蛋白质结合成脂蛋白，在血液中循环运转。轻度甘油三酯增高，可能由于糖类食物摄入过多、吸烟、肥胖等因素引起。重度的高甘油三酯，多与糖尿病、肝病、慢性肾炎等有关，一般为继发性疾病。
现代医学治疗高脂血症的有效手段不多，西药的发对高脂血症患者 的预后进行研究较少，远期效果不甚理想。近些年来中医药对高血脂病的治疗有了长足发展，中医药采用辩证论治有针对性地治疗高脂血症。实际证明了中药能够阻止动脉粥样硬化症的形成，有利于心、脑等重要脏器和血管疾病的防治，并获得了良好的疗效。
因此，开发一种新的中药组合物用于制备治疗或预防高血脂症的药物中的应用是有必要的。
发明内容
针对以上技术现状，本发明的目的是提供一种新的中药组合物在制备治疗或预防高血脂症的药物中的应用，所述中药组合物由栀子、茯苓、丹参、地骨皮、太子参、砂仁、生麦芽和菜服子组成。
本发明中，作为实施方案之一，所述中药组合物在制备治疗或预防血清总胆固醇或甘油三酯升高的药物中的应用。
本发明中，作为实施方案之一，所述中药组合物在制备治疗或预防甘油三酯升高的药物中的应用。
本发明中，作为实施方案之一，所述中药组合物在治疗或预防甘油三酯升高的药物中的应用；优选在治疗或预防高甘油三酯血症的药物中的应用。
本发明的应用中，向成人受试者施用所述中药组合物在治疗或预防甘油三酯升高的药物中的应用所述中药组合物的剂量范围为：5～10g/天(以中药丸剂计算)，作为示例性的说明，可以为向成人受试者施用5g/每天、6g/天、7g/天、8g/天、9g/天、10g/天的本发明中药丸剂。
本发明还提供一种中药组合物，所述中药组合物、按重量计，由栀子1.25-1.55份、茯苓1.25-1.46份、丹参0.925-1.31份、地骨皮1.1-1.37份、太子参0.925-1.08份、砂仁0.55-0.68份、生麦芽3份、菜服子1份组成。
作为实施方案之一，本发明的中药组合物、按重量计，由栀子1.55份、茯苓1.46份、丹参1.31份、地骨皮1.37份、太子参1.08份、砂仁0.68份、生麦芽3份、菜服子1份组成。
作为实施方案之一，本发明的中药组合物、按重量计，由栀子1.25 份、茯苓1.25份、丹参0.925份、地骨皮1.1份、太子参0.925份、砂仁0.55份、生麦芽3.0份、菜服子1.0份组成。
作为实施方案之一，本发明中药组合物的提取物为乙醇。
本发明还提供一种中药组合物制备方法，所述方法包括：
(1)将处方配比中丹参与栀子加80％乙醇提取2次，第一次加5倍量80％乙醇提取2小时，第二次加4倍量80％乙醇提1.5小时，滤过，药渣另器收集待用；合并前后两次滤液，减压回收乙醇至相对密度约为1.20(70℃)的清膏，待用；
(2)将1/10处方量的茯苓粉碎过100目筛、筛出细粉，剩余粗粒另行待用；
(3)将处方配比中生麦芽、地骨皮、莱服子、太子参与其余处方量的茯苓及茯苓粉碎后的粗粒加7倍量水煎煮2小时，滤过，收集滤液；药渣另行收集待用；
(4)将处方配比中砂仁加8倍量的水提取挥发油2小时，收集挥发油备用；其中砂仁滤液与药渣另器收集待用；
(5)合并上述所得药渣，加5倍量水煎煮1.5小时，滤过，收集滤液；然后与步骤(3)和(4)中的滤液合并，减压浓缩至相对密度约为1.20的清膏；将所得清膏与丹参、栀子醇提清膏合并，混匀，浓缩至相对密度约为1.40的稠膏，减压干燥，粉碎成浸膏细粉即可；
(6)将浸膏细粉、砂仁挥发油及灭菌茯苓细粉混合干燥，即得。
本发明还提供一种含有中药组合物的制剂，所述制剂由中药组合物和药用辅料组成，作为实施方案之一，所述辅料包括但不限于倍他环糊精、玉米淀粉、滑石粉，或它们中的两种或两种以上组合物。
本发明中，作为实施方案之一，所述制剂为包括但不限于丸剂、滴丸、胶囊或颗粒剂。
本领域技术人员结合本领域技术常识及常规的制剂制备方法，将本发明中药组合物和包括但不限于本发明中上述辅料制备成丸剂、滴丸、胶囊或颗粒剂。
作为实施方案之一，所述制剂优选为丸剂；作为实施方案之一，所 述丸剂的辅料为倍他环糊精、玉米淀粉和滑石粉。
本发明进一步提供一种所述丸剂的制备方法，所述制剂的制备方法包括：
(1)将处方配比中丹参与栀子加80％乙醇提取2次，第一次加5倍量80％乙醇提取2小时，第二次加4倍量80％乙醇提1.5小时，滤过，药渣另器收集待用；合并前后两次滤液，减压回收乙醇至相对密度约为1.20(70℃)的清膏，待用；
(2)将处方中1/10处方量的茯苓粉碎过100目筛、筛出细粉，剩余粗粒另行待用；
(3)将处方配比中生麦芽、地骨皮、莱服子、太子参与其余处方量的茯苓及茯苓粉碎后的粗粒加7倍量水煎煮2小时，滤过，收集滤液；药渣另器收集待用；
(4)将处方配比中砂仁加8倍量的水提取挥发油2小时，收集挥发油，用倍他环糊精包合，得砂仁挥发油倍他环糊精包合物备用；砂仁滤液与药渣分别收集待用；
(5)合并上述所得药渣，加5倍量水煎煮1.5小时，滤过，收集滤液；然后与步骤(3)和(4)所得滤液合并，减压浓缩至相对密度约为1.20(70℃)的清膏；将所得清膏与丹参、栀子醇提清膏合并，混匀，浓缩至相对密度约为1.40(70℃)的稠膏，减压干燥，粉碎成浸膏细粉即可；
(6)将浸膏细粉、砂仁挥发油倍他环糊精包合物及灭菌茯苓细粉，用蜜水(炼蜜:水＝1：3)制丸，干燥，用玉米淀粉和滑石粉包衣，即得。
本发明新的中药组合物对治疗或预防高血脂症，特别高甘油三酯血症具有很好效果，具有很好的协同效应。
附图说明
图1示出了用本发明中药丸剂处理的高脂饮食饲喂小鼠的体重变化。
图2示出了用本发明中药丸剂处理的高脂饮食饲喂小鼠的血清总胆固醇水平变化。
图3示出了用本发明中药丸剂处理的高脂饮食饲喂小鼠的血清甘油三酯水平变化。
图4是小鼠肝组织的代表性组织学图像(H&E，200倍放大率)，其示出了不同程度的脂肪变性。A.0％脂肪变性；B.5-10％脂肪变性；C.60％脂肪变性；D.90％脂肪变性。
具体实施方式
本发明通过以下实施例和实验例对本发明进行进一步的说明，并非用于限制其范围。
中药组合物的制备
实施例1
1)中药组合物配方(以重量份计)：
Figure PCTCN2021087276-appb-000001
2)制备方法：
(1)将处方配比中丹参与栀子加80％乙醇提取2次，第一次加5倍量80％乙醇提取2小时，第二次加4倍量80％乙醇提1.5小时，滤过，药渣另器收集待用；合并前后两次滤液，减压回收乙醇至相对密度约为1.20(70℃)的清膏，待用；
(2)将1/10处方量的茯苓粉碎过100目筛、筛出细粉，剩余粗粒另行待用；
(3)将处方配比中生麦芽、地骨皮、莱服子、太子参与其余处方量的茯苓及茯苓粉碎后的粗粒加7倍量水煎煮2小时，滤过，收集滤液；药渣另行收集待用；
(4)将处方配比中砂仁加8倍量的水提取挥发油2小时，收集挥发油备用；其中砂仁滤液与药渣另器收集待用；
(5)合并上述所得药渣，加5倍量水煎煮1.5小时，滤过，收集滤液；然后与步骤(3)和(4)中的滤液合并，减压浓缩至相对密度约为1.20的清膏；将所得清膏与丹参、栀子醇提清膏合并，混匀，浓缩至相对密度约为1.40的稠膏，减压干燥，粉碎成浸膏细粉即可；
(6)将浸膏细粉、砂仁挥发油及灭菌茯苓细粉混合干燥，即得。
实施例2
1)中药组合物配方(以重量份计)
Figure PCTCN2021087276-appb-000002
2)制备方法：(1)将处方配比中丹参与栀子加80％乙醇提取2次，第一次加5倍量80％乙醇提取2小时，第二次加4倍量80％乙醇提1.5小时，滤过，药渣另器收集待用；合并前后两次滤液，减压回收乙醇至相对密度约为1.20(70℃)的清膏，待用；
(2)将1/10处方量的茯苓粉碎过100目筛、筛出细粉，剩余粗粒另行待用；
(3)将处方配比中生麦芽、地骨皮、莱服子、太子参与其余处方量的茯苓及茯苓粉碎后的粗粒加7倍量水煎煮2小时，滤过，收集滤液；药渣另行收集待用；
(4)将处方配比中砂仁加8倍量的水提取挥发油2小时，收集挥发油备用；其中砂仁滤液与药渣另器收集待用；
(5)合并上述所得药渣，加5倍量水煎煮1.5小时，滤过，收集滤液；然后与步骤(3)和(4)中的滤液合并，减压浓缩至相对密度约为1.20的清膏；将所得清膏与丹参、栀子醇提清膏合并，混匀，浓缩至相对密度约为1.40的稠膏，减压干燥，粉碎成浸膏细粉即可；
(6)将浸膏细粉、砂仁挥发油及灭菌茯苓细粉混合干燥，即得。
中药组合物丸剂的制备
实施例3
1)中药组合物配方(以重量份计)
Figure PCTCN2021087276-appb-000003
2)辅料
倍他环糊精  0.04
玉米淀粉    3％(以总混物的量为基础)
滑石粉    0.8％(以总混物的量为基础)
3)制备方法
(1)将处方配比中丹参与栀子加80％乙醇提取2次，第一次加5倍量80％乙醇提取2小时，第二次加4倍量80％乙醇提1.5小时，滤过，药渣另器收集待用；合并前后两次滤液，减压回收乙醇至相对密度约为1.20(70℃)的清膏，待用；
(2)将处方中1/10处方量的茯苓粉碎过100目筛、筛出细粉，剩余粗粒另行待用；
(3)将处方配比中生麦芽、地骨皮、莱服子、太子参与其余处方量的茯苓及茯苓粉碎后的粗粒加7倍量水煎煮2小时，滤过，收集滤液；药渣另器收集待用；
(4)将处方配比中砂仁加8倍量的水提取挥发油2小时，收集挥发油，用倍他环糊精包合，得砂仁挥发油倍他环糊精包合物备用；砂仁滤液与药渣分别收集待用；
(5)合并上述所得药渣，加5倍量水煎煮1.5小时，滤过，收集滤液；然后与步骤(3)和(4)所得滤液合并，减压浓缩至相对密度约为1.20(70℃)的清膏；将所得清膏与丹参、栀子醇提清膏合并，混匀，浓缩至相对密度约为1.40(70℃)的稠膏，减压干燥，粉碎成浸膏细粉即可；
(6)将浸膏细粉、砂仁挥发油倍他环糊精包合物及灭菌茯苓细粉，用蜜水(炼蜜:水＝1：3)制丸，干燥，制成1000g，用玉米淀粉和滑石粉包衣，即得。
实施例4
1)中药组合物
Figure PCTCN2021087276-appb-000004
Figure PCTCN2021087276-appb-000005
2)辅料(以重量份计)
倍他环糊精  0.04
玉米淀粉    3％(以总混物的量为基础)
滑石粉      0.8％(以总混物的量为基础)
3)制备方法
(1)将处方配比中丹参与栀子加80％乙醇提取2次，第一次加5倍量80％乙醇提取2小时，第二次加4倍量80％乙醇提1.5小时，滤过，药渣另器收集待用；合并前后两次滤液，减压回收乙醇至相对密度约为1.20(70℃)的清膏，待用；
(2)将处方中1/10处方量的茯苓粉碎过100目筛、筛出细粉，剩余粗粒另行待用；
(3)将处方配比中生麦芽、地骨皮、莱服子、太子参与其余处方量的茯苓及茯苓粉碎后的粗粒加7倍量水煎煮2小时，滤过，收集滤液；药渣另器收集待用；
(4)将处方配比中砂仁加8倍量的水提取挥发油2小时，收集挥发油，用倍他环糊精包合，得砂仁挥发油倍他环糊精包合物备用；砂仁滤液与药渣分别收集待用；
(5)合并上述所得药渣，加5倍量水煎煮1.5小时，滤过，收集滤液；然后与步骤(3)和(4)所得滤液合并，减压浓缩至相对密度约为1.20(70℃)的清膏；将所得清膏与丹参、栀子醇提清膏合并，混匀，浓缩至相对密度约为1.40(70℃)的稠膏，减压干燥，粉碎成浸膏细粉即可；
(6)将浸膏细粉、砂仁挥发油倍他环糊精包合物及灭菌茯苓细粉，用蜜水(炼蜜:水＝1：3)制丸，干燥，制成1000g，用玉米淀粉和滑石粉包衣，即得。
试验例1
样品和试剂
本发明中药丸剂，按实施例3制备；
高脂食物：(HFD Research Diets，New Brunswick，NJ；商品目录号D12492)，其脂肪含量为60％；
低脂对照饮食(LFD；Research Diets；商品目录号D12492),脂肪含量仅为10％。
动物模型和研究设计
使用五周龄的C57BL/6J雄性小鼠作为动物模型来模拟人类代谢异常。
所有小鼠都被饲养在无病原体的环境中，温度(22±2℃)，湿度(40-60％)，以及12:12小时的明暗循环。自由喂养(ad libitum)所有小鼠。经过7天的标准食物环境适应后，将小鼠随机分配：饲喂高脂饮食(HFD；Research Diets，New Brunswick，NJ；商品目录号D12492)，其脂肪含量为60％；或其相应的低脂对照饮食(LFD；Research Diets；商品目录号D12492)，其蔗糖含量与HFD相匹配，但脂肪含量仅为10％。
根据饮食和干预将小鼠分为不同的组(表1)。对于所有组，首先给小鼠饲喂LFD或HFD 10周，然后进行8周的干预期(用中药丸剂或水(作为安慰剂))。
表1.不同组小鼠的饮食和处理方案
Figure PCTCN2021087276-appb-000006
Figure PCTCN2021087276-appb-000007
*剂量定义：正常＝46.2mg/50g小鼠；低剂量＝正常剂量的一半(23.1mg/50g小鼠)；高剂量＝正常剂量的二倍(92.4mg/50g小鼠)。
每组由10只小鼠组成。第1组由LFD-饲喂的小鼠(n＝10)组成，其用作低脂正常对照。第2组是用HFD-饲喂的小鼠(n＝10)的模型对照。第3、4和5组是HFD-饲喂的小鼠，分别用不同剂量(低、正常或高剂量)的本发明中药丸剂给药。
确定正常剂量为46.2mg中药丸剂/50g小鼠。中药丸剂制备为悬浮于水中的形式，每天通过口服灌胃给药。高剂量设定为正常剂量的两倍(92.4mg中药丸剂/50g小鼠)，低剂量设定为正常剂量的一半(23.1mg/50g小鼠)。作为安慰剂，给无干预的对照小鼠施用相当于中药丸剂体积的水。
每周对小鼠称重，每只小鼠的中药丸剂(或水)的剂量基于体重。中药丸剂给药8周。
在基线时，(在中药丸剂处理/安慰剂之前)，从尾静脉收集50μL血液。在实验结束时(干预8周后)处死小鼠，并收集血液和肝组织进行分析。所有动物实验均按照香港大学教学与研究活体动物使用委员会的实验动物使用指南进行。
生化分析
分别使用ALT/GPT Liqui-UV测定法和AST/GOT Liqui-UV测定法(均来自Stanbio Laboratory，Boerne，TX)评估血清ALT和AST。分别使用LiquiColor甘油三酯和胆固醇LiquiColor测定法(均来自Stanbio Laboratory)分析血清甘油三酯和总胆固醇。
组织学分析
将肝组织标本固定在10％福尔马林缓冲液中，包埋在石蜡中，切成 5μm厚，并用苏木精和曙红染色。脂肪变性的程度由病理学家评估，其不了解实验设计，并根据Kleiner等人(Hepatology 2005；41:1313-21)描述的系统。脂肪变化表示为脂肪变性细胞的百分比，并按照先前的描述进行分类：无脂肪变性(<5％脂肪变化)；低度脂肪变性(脂肪变化为5-33％)；中度脂肪变性(>33-66％的脂肪变化)；和严重脂肪变性(>66％的脂肪变化)。
使用SPSS 25.0(SPSS，芝加哥，伊利诺伊州)进行统计分析。连续变量表示为平均值±平均值标准误差(SEM)，并使用学生t检验或单向ANOVA检验进行分析。使用卡方检验或Fisher精确检验对分类变量进行了分析。P<0.05被认为具有统计学意义。
实验结果
基线特征
在饲喂不同饮食之前，被分配为LFD和HFD的小鼠具有相当的体重(分别为22.5±0.3g和22.1±0.1g；P＝0.331)。在干预的第0周(基线)(即，差异饮食10周后和中药丸剂给药之前)，饲喂HFD的小鼠(平均体重：44.1±0.5g)比饲喂LFD的小鼠(平均体重：29.9±0.6g；P<0.001)重得多。在饮食10周后，LFD饲喂的小鼠平均体重变化为7.4±0.6g，而HFD饲喂的小鼠平均体重变化为22.0±0.5g(P<0.001)。
HFD饲喂的小鼠的血清总胆固醇水平(129.6±3.5mg/dL)明显高于LFD饲喂的小鼠(79.1±8.4mg/dL；P<0.001)，HFD饲喂的小鼠的血清甘油三酯水平(76.0±6.1mg/dL)比LFD饲喂的小鼠(41.4±3.8mg/L；P＝0.052)更高。
然后指定由HFD饲喂的小鼠接受不同剂量的中药丸剂(或以水作为安慰剂对照)。在基线时(中药丸剂处理开始)，接受不同处理的不同HFD饲喂小鼠组间的体重、血清总胆固醇和甘油三酯平衡良好且具有可比性(表2)。
表2.不同组小鼠的基线特征
Figure PCTCN2021087276-appb-000008
LFD：低脂饮食；HFD：高脂饮食
本发明中药丸剂对高脂饮食诱导的脂肪肝小鼠的影响
平均体重
在实验结束时，HFD饲喂的对照小鼠(第2组)的平均体重为49.2±0.68g，比基线(处理前)体重重14.8％体重。在处理结束时，HFD饲喂的对照小鼠的体重增加明显大于LFD饲喂的对照小鼠(第1组)，后者的平均体重增加了3.3％(P＝0.041)。接受中药丸剂的HFD饲喂小鼠(平均增加：5.1-12.0％)的体重也有所增加。各个处理组的体重增加略低于HFD安慰剂组，但体重变化的差异无统计学意义。在中药丸剂组中均未观察到对体重变化的剂量效应(图1)；该实验结果表明，本发明中药丸剂有效降低了高热量饮食导致小鼠的体重增加作用，具有相应的有效的预防或治疗作用。
总胆固醇水平
在LFD饲喂的对照小鼠中，处理结束时总胆固醇水平进一步增加了16.9％(与基线相比)，而HFD饲喂的安慰剂小鼠在处理结束时总胆固醇增加了57.7％(P＝0.073)。对于用中药丸剂处理的小鼠(图2)，低、正常和高剂量中药丸剂处理结束时总胆固醇水平的平均增加分别为 39.4％，14.6％和7.9％。P值(与安慰剂相比)分别为0.388、0.075和0.049。总体而言，通过比较安慰剂组和中药丸剂的三个剂量组，可以观察到血清总胆固醇的剂量效应(P＝0.043)；该研究结果表明，中药丸剂有效降低了高热量饮食导致小鼠血清胆固醇增加作用，具有相应的有效的预防或治疗作用。
血清甘油三酸酯水平
与基线相比，LFD饲喂的小鼠的血清甘油三酯水平到实验结束时进一步增加了6.5％。用LFD饲喂的小鼠的血清甘油三酯的平均增加量显著小于HFD饲喂的安慰剂对照小鼠的甘油三酯(与基线相比增加了35.0％；P＝0.022)。在用中药丸剂处理的所有小鼠中，处理结束时血清甘油三酯均降低。低剂量、正常剂量和高剂量中药丸剂处理的小鼠中甘油三酯平均减少为4.2％、11.2％和18.6％(与安慰剂组相比，所有P<0.05；图3)。中药丸剂处理的小鼠观察到血清甘油三酯水平呈剂量依赖性降低(P＝0.006)；(该实验结果表明，中药丸剂有效降低了高热量饮食导致小鼠血清甘油三酯增加作用，具有相应的有效的预防或治疗作用。
血清ALT和AST
在处理期结束时，LFD饲喂的对照小鼠的血清ALT和AST平均值为17.6±7.8U/L和69.3±5.9U/L，分别低于HFD饲喂的安慰剂小鼠(ALT：55.8±11.0U/L；P＝0.013和AST：128.3±23.1U/L；P＝0.035)。与安慰剂组相比，接受中药丸剂处理的小鼠的ALT和AST含量较低，尽管差异在统计学上无统计学意义，并且未观察到剂量效应(表3)；ALT和AST是临床常用肝损伤指标，研究结果表明中药丸剂有效降低了高热量饮食导致小鼠肝损伤作用，具有相应的有效的预防或治疗作用。
表3.实验结束时不同组小鼠的肝脏酶水平
Figure PCTCN2021087276-appb-000009
*相对于对照组P＜0.05(第2组)
ALT：丙氨酸氨基转移酶；AST：天冬氨酸氨基转移酶
肝脏脂肪变性程度
表4实验结束时肝脏的肝脏脂肪变性程度
Figure PCTCN2021087276-appb-000010
无脂肪变性(脂肪变化细胞＜5％)；低度脂肪变性(脂肪变化细胞5-33％)；中度脂肪变性(脂肪变化细胞＞33-66％)；严重脂肪变性(脂肪变化细胞＞66％)
实验结束时，所有LFD饲喂的对照小鼠的脂肪变化均小于5％(无脂肪变性)，而HFD饲喂的10安慰剂只小鼠中有9只(90％)患有严重的脂肪变性(其余小鼠患有中度脂肪变性)。总体而言，在用中药丸剂处理的30只小鼠中，有15只(50％)患有严重的脂肪变性，而7只(23.3％)无脂 肪变性或低度脂肪变性。中药丸剂处理的具有严重脂肪变性的小鼠比例显著低于未处理的HFD饲喂的安慰剂小鼠(P＝0.025)。代表性的组织学结果见图4；该实验结果表明，中药丸剂有效降低了高热量饮食导致小鼠肝内脂肪蓄积(即脂肪肝)的作用，具有相应的有效的预防或治疗作用。

Claims (13)

  1. 一种中药组合物在制备治疗或预防高血脂症的药物中的应用，所述中药组合物由栀子、茯苓、丹参、地骨皮、太子参、砂仁、生麦芽和菜服子组成。
  2. 根据权利要求1所述的应用，其特征在于，所述中药组合物在制备治疗或预防血清总胆固醇或甘油三酯升高的药物中的应用。
  3. 根据权利要求2所述的应用，其特征在于，所述中药组合物在制备治疗或预防甘油三酯升高的药物中的应用；优选在制备治疗或预防高甘油三酯血症的药物中的应用。
  4. 根据权利要求2所述的应用，其特征在于，所述中药组合物在治疗或预防甘油三酯升高的药物中的应用。
  5. 根据权利要求1所述的应用，其特征在于，所述中药组合物的剂量为：5～10g/天。
  6. 一种用于权利要求1应用的中药组合物，其特征在于，所述中药组合物、按重量计，由栀子1.25-1.55份、茯苓1.25-1.46份、丹参0.925-1.31份、地骨皮1.1-1.37份、太子参0.925-1.08份、砂仁0.55-0.68份、生麦芽3份、菜服子1份组成。
  7. 根据权利要求6所述的中药组合物，其特征在于，所述中药组合物、按重量计，由栀子1.55份、茯苓1.46份、丹参1.31份、地骨皮1.37份、太子参1.08份、砂仁0.68份、生麦芽3份、菜服子1份组成。
  8. 根据权利要求6所述的中药组合物，其特征在于，所述中药组合物、按重量计，由栀子1.25份、茯苓1.25份、丹参0.925份、地骨皮1.1份、太子参0.925份、砂仁0.55份、生麦芽3.0份、菜服子1.0份组成。
  9. 权利要求6～8任一所述中药组合物制备方法，其特征在于，所述方法包括：
    (1)将处方配比中丹参与栀子加80％乙醇提取2次，第一次加5倍量80％乙醇提取2小时，第二次加4倍量80％乙醇提1.5小时，滤过，药渣另器收集待用；合并前后两次滤液，减压回收乙醇至相对密度约为 1.20(70℃)的清膏，待用；
    (2)将1/10处方量的茯苓粉碎过100目筛，筛出细粉，剩余粗粒另行待用；
    (3)将处方配比中生麦芽、地骨皮、莱服子、太子参与其余处方量的茯苓及茯苓粉碎后的粗粒加7倍量水煎煮2小时，滤过，收集滤液；药渣另行收集待用；
    (4)将处方配比中砂仁加8倍量的水提取挥发油2小时，收集挥发油备用；其中砂仁滤液与药渣另器收集待用；
    (5)合并上述所得药渣，加5倍量水煎煮1.5小时，滤过，收集滤液；然后与步骤(3)和(4)中的滤液合并，减压浓缩至相对密度约为1.20的清膏；将所得清膏与丹参、栀子醇提清膏合并，混匀，浓缩至相对密度约为1.40的稠膏，减压干燥，粉碎成浸膏细粉即可；
    (6)将浸膏细粉、砂仁挥发油及灭菌茯苓细粉混合干燥，即得。
  10. 含有权利要求6～8任一所述中药组合物或根据权利要求9所述方法制备的中药组合物的制剂，其特征在于，所述制剂由中药组合物和药用辅料组成，其中所述辅料为倍他环糊精、玉米淀粉、滑石粉，或它们中的两种或两种以上组合物。
  11. 根据权利要求10所述的制剂，其特征在于，所述制剂为丸剂、滴丸、胶囊、颗粒剂。
  12. 根据权利要求11所述的制剂，其特征在于，所述制剂为丸剂。
  13. 根据权利要求12所述丸剂的制备方法，其特征在于，所述制备方法包括：
    (1)将处方配比中丹参与栀子加80％乙醇提取2次，第一次加5倍量80％乙醇提取2小时，第二次加4倍量80％乙醇提1.5小时，滤过，药渣另器收集待用；合并前后两次滤液，减压回收乙醇至相对密度约为1.20(70℃)的清膏，待用；
    (2)将1/10处方量的茯苓粉碎分别得细粉、粗粒待用过100目筛、筛出细粉，剩余粗粒另行待用；
    (3)将处方配比中生麦芽、地骨皮、莱服子、太子参与其余处方量 的茯苓及茯苓粉碎后的粗粒加7倍量水煎煮2小时，滤过，收集滤液；药渣另行收集待用；
    (4)将处方配比中砂仁加8倍量的水提取挥发油2小时，收集挥发油，用倍他环糊精包合，得砂仁挥发油倍他环糊精包合物备用；砂仁滤液与药渣另器收集待用；
    (5)合并上述所得药渣，加5倍量水煎煮1.5小时，滤过，收集滤液；然后与步骤(3)和(4)中的滤液合并，减压浓缩至相对密度约为1.20的清膏；将所得清膏与丹参、栀子醇提清膏合并，混匀，浓缩至相对密度约为1.40的稠膏，减压干燥，粉碎成浸膏细粉即可；
    (6)将浸膏细粉、砂仁挥发油倍他环糊精包合物及灭菌茯苓细粉，用蜜水(炼蜜:水＝1：3)制丸，干燥，用玉米淀粉和滑石粉包衣，即得。
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