A traditional Chinese medicine composition and its preparation method and use

Abstract

The present invention discloses a Chinese medicine composition for preventing and treating coronary heart disease and angina pectoris and a preparation method thereof, belonging to the field of Chinese medicine preparations. The Chinese medicine composition is prepared from 17 Chinese medicinal herbs: astragalus, codonopsis, rhodiola, poria, ophiopogon, schisandra, rehmannia root, polygonatum, epimedium, kudzu root, angelica, salvia miltiorrhiza, honeysuckle, kelp, kelp, oyster, and immature bitter orange. The composition of the present invention is well-matched and synergistic, and has the effects of invigorating qi and activating blood circulation, resolving phlegm and unblocking meridians. It is suitable for treating chest pain caused by qi and yin deficiency, phlegm and blood stasis, coronary heart disease, and angina pectoris, as well as pharmacodynamic tests. Pharmacodynamic tests show that the Chinese medicine composition of the present invention can significantly prolong the hypoxia tolerance time of mice, has a certain antagonistic effect on acute myocardial ischemia caused by vasopressin in rats, has a significant reducing effect on ST segment elevation caused by coronary artery ligation in rats, can significantly reduce the range of myocardial infarction caused by coronary artery ligation, and has a reducing effect on hyperlipidemia in rats fed a high-fat diet.

Description

Technical Field

[0001] The invention belongs to the field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating coronary heart disease and angina pectoris and a preparation method thereof. Background Art

[0002] Coronary heart disease (CHD), also known as coronary heart disease (CHD), is a heart disease caused by atherosclerotic changes in the coronary arteries, which lead to narrowing or occlusion of the coronary artery lumen, resulting in ischemia, hypoxia, and even necrosis of the corresponding arteries. The World Health Organization classifies CHD into five major clinical categories: asymptomatic myocardial ischemia (latent coronary heart disease), angina pectoris, myocardial infarction, ischemic heart failure (ischemic heart disease), and sudden death.

[0003] Angina pectoris, a type of coronary artery disease, refers to an acute myocardial hypoxia syndrome caused by an imbalance between cardiac oxygen demand and supply. Angina pectoris is most common in people over 40 years old. Clinical symptoms of angina pectoris include a feeling of pressure and fullness behind the sternum, accompanied by noticeable pain, lasting three to five minutes. The pain often radiates to the left arm, shoulder, jaw, throat, and back, and can also radiate to the right arm. Sometimes, the pain accumulates in these areas without affecting the retrosternal area. Exertional angina occurs when exertion, emotional excitement, cold weather, or a large meal increase cardiac oxygen demand, and is relieved by rest and the use of nitroglycerin. Sometimes, angina pectoris is atypical, presenting with shortness of breath, fainting, weakness, and belching, particularly in the elderly. Angina pectoris is categorized as stable or unstable angina based on the frequency and severity of attacks.

[0004] Modern Chinese medicine considers coronary heart disease and angina pectoris to fall under the categories of "chest pain" and "heart pain." The Golden Chamber Synopsis defines the etiology and pathogenesis of these conditions as "weak yang and stringy yin," a syndrome characterized by underlying deficiency and superficial excess. The superficial excess is primarily characterized by blood stasis and turbid phlegm, while the underlying deficiency is characterized by deficiency of qi, blood, yin, and yang. With the increasing severity of my country's aging population, the incidence of coronary heart disease and angina pectoris is increasing year by year, with a trend toward younger patients. Their treatment is drawing increasing attention from medical professionals, and the development of therapeutic drugs for these conditions is of great practical significance.

[0005] Currently, four main types of Western medications are widely used in clinical practice to treat angina pectoris caused by coronary heart disease: ① aspirin; ② nitrates, such as nitroglycerin, nitroglycerin, nitroglycerin, and isosorbide mononitrate (Imodium); ③ beta-blockers, such as metoprolol, propranolol, and bisoprolol fumarate; and ④ statins, such as atorvastatin. While these medications offer relatively satisfactory efficacy, long-term use can lead to poor tolerance, drug resistance, and severe adverse reactions. For example, long-term aspirin use can cause adverse reactions such as gastrointestinal bleeding, while statins can cause liver damage. Surgical treatment, on the other hand, presents numerous contraindications, a high postoperative recurrence rate, and considerable cost, making it difficult for the average patient to accept. Traditional Chinese medicine, while slower to take effect than Western medicine, offers distinct advantages by addressing both the underlying cause and the underlying symptoms, providing significant and long-lasting efficacy, and fewer adverse reactions.

[0006] CN1287835C discloses a pharmaceutical composition for treating coronary heart disease and angina pectoris and a preparation method thereof. The Chinese medicinal composition is prepared from 13 herbs, namely, astragalus, codonopsis, ophiopogon, polygonum multiflorum, epimedium, kudzu root, angelica, salvia miltiorrhiza, honeysuckle thorn, seaweed, kelp, oyster, and immature bitter orange, and is treated by different physical or chemical methods according to the different physical and chemical properties of the effective components of each Chinese medicinal ingredient to obtain an effective preparation. The preparation has a significant clinical effect in treating coronary heart disease and angina pectoris.

[0007] CN101780212B discloses a pharmaceutical composition and preparation method for preventing and treating coronary heart disease and angina pectoris. The product, now approved for production, is "Xintong Oral Liquid." This product is made from 13 herbs: Astragalus, Codonopsis, Radix Ophiopogonis, Polygonum Multiflorum, Epimedium, Radix Puerariae, Radix Angelicae Sinensis, Salvia Miltiorrhiza, Spina Gleditsiae, Sargassum, Kelp, Oyster, and Fructus Aurantii Immaturus. These herbs are treated with different physical or chemical methods based on the different physicochemical properties of each herbal active ingredient. The formula is unique and clinically indicated for treating chest pain, qi deficiency, phlegm and blood stasis syndromes, heartache, palpitations, chest tightness and shortness of breath, restlessness and fatigue, and a deep, stringy, slippery, and intermittent pulse; these symptoms are also present in patients with coronary heart disease and angina pectoris. In recent years, Xintong Oral Liquid has gained widespread recognition among doctors and patients for its proven efficacy.

[0008] The Polygonum multiflorum in the formula is the dried root of Polygonum multiflorum Thunb., a plant of the Polygonaceae family. Polygonum multiflorum and processed Polygonum multiflorum are included in the 2020 edition of the Chinese Pharmacopoeia. Polygonum multiflorum has the effects of detoxification, eliminating carbuncle, and moistening the intestines and promoting bowel movements, and has always been highly praised by ancient and modern doctors and dietetics. As a commonly used Chinese medicine, Polygonum multiflorum and its formula preparations are increasingly used in the treatment and prevention of diseases, and people's understanding of the safety of Polygonum multiflorum is also becoming more and more in-depth. However, in recent years, there have been increasing reports at home and abroad on adverse reactions to Polygonum multiflorum and its preparations, especially liver toxicity, which has attracted much attention from all walks of life to the safety of such Chinese herbal medicines and Chinese patent medicines. Summary of the Invention

[0009] In view of the deficiency of the existing Xintong preparation that long-term use of Polygonum multiflorum may pose a risk of liver toxicity, the present invention provides a traditional Chinese medicine composition for preventing and treating angina pectoris caused by coronary heart disease, which can retain the main functions and definite clinical efficacy of Xintong oral liquid without using Polygonum multiflorum medicinal materials, thereby avoiding the possible risk of liver toxicity.

[0010] A traditional Chinese medicine composition is prepared from the following components: astragalus root, codonopsis pilosula, rhodiola rosea, tuckahoe, ophiopogon japonicus, schisandra chinensis, rehmannia root, epimedium, kudzu root, angelica sinensis, salvia miltiorrhiza, honeysuckle thorn, seaweed, kelp, oyster, immature bitter orange, and polygonatum.

[0011] Preferably, the Chinese medicine composition comprises the following components in parts by weight:

[0012] 260-350 parts by weight of Astragalus root 120-200 parts by weight of Codonopsis pilosula 100-150 parts by weight of Rhodiola rosea

[0013] 120-200 parts by weight of Poria cocos, 80-140 parts by weight of Ophiopogon japonicus, 100-150 parts by weight of Schisandra chinensis

[0014] 220-300 parts by weight of Rehmannia root, 60-120 parts by weight of Epimedium, 200-280 parts by weight of Pueraria root

[0015] 60-120 parts by weight of Chinese Angelica sinensis, 140-200 parts by weight of Salvia miltiorrhiza, 60-120 parts by weight of Gleditsia sinensis

[0016] 120-180 parts by weight of seaweed 120-180 parts by weight of kelp 120-180 parts by weight of oyster 120-180 parts by weight

[0017] 40-100 parts by weight of Fructus Aurantii Immaturus and 200-280 parts by weight of Rhizoma Polygonati Sinensis.

[0018] Preferably, the Chinese medicine composition comprises the following components in parts by weight:

[0019] 280-320 parts by weight of Astragalus root 140-180 parts by weight of Codonopsis pilosula 120-140 parts by weight of Rhodiola rosea

[0020] 140-180 parts by weight of Poria cocos 100-120 parts by weight of Ophiopogon japonicus 120-140 parts by weight of Schisandra chinensis

[0021] 240-280 parts by weight of Rehmannia root, 80-100 parts by weight of Epimedium, 220-260 parts by weight of Pueraria root

[0022] 80-100 parts by weight of Chinese Angelica sinensis, 150-180 parts by weight of Salvia miltiorrhiza, 80-100 parts by weight of Gleditsia sinensis

[0023] 140-160 parts by weight of seaweed 140-160 parts by weight of kelp 140-160 parts by weight of oyster 140-160 parts by weight

[0024] 60-90 parts by weight of Fructus Aurantii Immaturus and 220-260 parts by weight of Rhizoma Polygonati Sinensis.

[0025] In a preferred embodiment, the traditional Chinese medicine composition comprises the following components in parts by weight:

[0026] 300 weight parts of Astragalus root, 160 weight parts of Codonopsis pilosula, 130 weight parts of Rhodiola rosea

[0027] 160 parts by weight of Poria cocos 110 parts by weight of Radix Ophiopogonis 130 parts by weight of Schisandra chinensis

[0028] 260 parts by weight of Rehmannia root, 90 parts by weight of Epimedium, 250 parts by weight of Pueraria root

[0029] 90 parts by weight of Chinese Angelica sinensis, 170 parts by weight of Salvia miltiorrhiza, 90 parts by weight of Gleditsia sinensis

[0030] 150 parts by weight of seaweed 150 parts by weight of kelp 150 parts by weight of oyster

[0031] 80 parts by weight of Fructus Aurantii Immaturus and 240 parts by weight of Rhizoma Polygonati Sinensis.

[0032] According to Traditional Chinese Medicine (TCM), the pathogenesis of coronary heart disease lies in the intertwining of phlegm and blood stasis, which obstructs the chest yang and heart meridians, leading to coronary heart disease. This condition falls under the TCM categories of "chest pain," "heart pain," and "true heart pain." Atherosclerosis and elevated blood lipids are considered manifestations of "phlegm," while myocardial ischemia and altered hemorheology are considered manifestations of "stasis." The "Golden Chamber Essentials: Chest Bi, Heart Pain, Shortness of Breath, Pulse Symptoms and Treatments" states that chest pain is primarily manifested by chest qi congestion, heart pain, and shortness of breath. The key pathological finding is extreme deficiency of chest yang qi. Therefore, clinically, it often presents as both underlying deficiency and superficial excess. The underlying deficiency is primarily characterized by deficiency of zang-qi, while the superficial excess is often characterized by blood stasis and phlegm obstruction. This condition often arises from the gradual decline of visceral function in middle-aged and elderly people, damage to the spleen and stomach caused by the consumption of rich, sweet foods, or internal trauma caused by the seven emotions, leading to qi stagnation, blood stasis, and the accumulation of turbid phlegm. This obstruction leads to pain and blockage of the meridians.

[0033] Based on this, astragalus, codonopsis, rhodiola, poria, ophiopogon, schisandra, rehmannia root, polygonatum, epimedium, kudzu root, angelica, salvia miltiorrhiza, soapberry thorn, seaweed, kelp, oyster and immature bitter orange are selected to make a formula with the effects of invigorating qi and promoting blood circulation, resolving phlegm and unblocking meridians. In the formula, Astragalus is the main drug, which is sweet, warm and pure Yang in nature. It can replenish various deficiencies, benefit the vital energy and strengthen the spleen and stomach. The spleen is the source of biochemical metabolism, and the lungs are the main body of Qi. Deficiency of spleen and lung Qi will lead to symptoms such as poor appetite, loose stools, shortness of breath and fatigue. Therefore, Astragalus is mainly used to replenish spleen and lung Qi or sinking of middle Qi. Codonopsis strengthens the spleen and lungs, nourishes blood and produces body fluid, and is used for fatigue of limbs caused by insufficient middle Qi. Rhodiola has the effects of replenishing Qi, activating blood circulation, unblocking meridians and relieving asthma. It is mostly used for symptoms such as Qi deficiency and blood stasis, chest pain, heart pain, hemiplegia caused by stroke, fatigue and asthma. The two are combined with Astragalus to enhance the function of replenishing Qi and have the effect of removing blood stasis. Insufficient kidney Yang and loss of heart warmth can also lead to insufficient heart Yang. , it is unable to stimulate and forms stasis; Rehmannia root can nourish yin and blood, and "Compendium of Materia Medica" says: "It nourishes kidney water, fills bone marrow, benefits blood vessels, and replenishes true yin"; Polygonatum sibiricum has the effects of replenishing qi and nourishing yin, strengthening the spleen, moistening the lungs, and benefiting the kidneys. Schisandra chinensis has the functions of astringency, replenishing qi and promoting fluid, replenishing the kidneys and calming the mind. It can not only replenish the heart and kidneys, but also calm the mind and tranquilize the nerves. It can treat yin and blood deficiency, malnutrition of the heart and mind, or heart-kidney disharmony, restlessness, palpitations, insomnia and dreaminess; Salvia miltiorrhiza can remove blood and nourish blood and is used for a variety of diseases caused by blood stasis or poor blood circulation; Angelica sinensis can not only replenish blood and promote blood circulation but also relieve pain. It is used with Astragalus membranaceus to enhance the effect of nourishing the heart and blood and relieving pain. Ophiopogon nourishes yin and produces body fluid, which is used to clear the heart, relieve restlessness and calm the mind; Pueraria root and Epimedium replenish kidney yang to relieve heart fire, and can assist Astragalus in its yang-raising effect; Poria is good at draining away water and dampness, so that dampness has nowhere to accumulate and phlegm has no reason to form, and it can treat dizziness and palpitations caused by phlegm and fluid; Seaweed, kelp, oyster and Citrus aurantium are used to resolve phlegm, soften hard masses and promote qi; Soapberry thorn activates blood circulation to assist Angelica sinensis and Salvia miltiorrhiza in their blood circulation and yin-nourishing effects; the above eight herbs, including Ophiopogon, are all used as adjuvants.

[0034] This prescription is warming in nature, with the primary goal of warming and promoting the flow of Yang Qi. Therefore, it aims to invigorate Qi, nourish Yin, soften and disperse Qi stagnation, thereby promoting the smooth flow of Qi and blood and relieving pain. The above-mentioned herbs are combined with remarkable efficacy, achieving the miraculous effects of invigorating Qi and nourishing Yin, softening and resolving phlegm, removing blood stasis and unblocking meridians, and relieving acute pain.

[0035] Another object of the present invention is to provide a method for preparing the composition, wherein the Chinese medicinal components are extracted with alcohol or water and then added with pharmaceutically acceptable excipients to prepare a clinically acceptable dosage form.

[0036] The preparation method of the Chinese medicine composition comprises the following steps:

[0037] 1) Weigh 17 medicinal materials, including astragalus, codonopsis, rhodiola, poria, ophiopogon, schisandra, rehmannia root, epimedium, kudzu root, angelica, salvia miltiorrhiza, honey locust thorn, seaweed, kelp, oyster, immature bitter orange, and polygonatum, wherein ophiopogon, epimedium, and immature bitter orange are cleaned, codonopsis, seaweed, and kelp are cleaned and cut into sections, rhodiola, poria, rehmannia root, polygonatum, kudzu root, and oyster are cleaned and cut into pieces, astragalus, angelica, and salvia miltiorrhiza are cleaned and sliced, and schisandra and honey locust thorn are cleaned and crushed into coarse powder for later use;

[0038] 2) Weigh the prescribed amount of Pueraria root, Salvia miltiorrhiza, and Schisandra chinensis, add 4-12 times the amount of 40%-80% ethanol, reflux and extract 1-3 times, each time for 0.5-3 hours, filter, collect the filtrate and the residue, and set aside;

[0039] 3) adding the remaining thirteen medicinal pieces including the astragalus root to the residue obtained in step 2), adding 4-12 times the amount of water and decocting 1-3 times, filtering, and concentrating the filtrate under reduced pressure to an extract with a relative density of 1.15-1.25 at 60° C.;

[0040] 4) combining the filtrate obtained in step 2) with the extract obtained in step 3), adding ethanol to a concentration of 40% to 80% alcohol, refrigerating for 24 to 48 hours, recovering the ethanol, and concentrating to an extract having a relative density of 1.1 to 1.5 at 60° C., and adding pharmaceutically acceptable excipients through conventional processes to prepare a clinically acceptable dosage form.

[0041] Preferably, the pharmaceutically acceptable excipients include one or more of flavoring agents, diluents, lubricants, disintegrants, dispersants, thickeners, preservatives, and colorants.

[0042] The pharmaceutically acceptable excipients include, but are not limited to, lactose, starch, dextrin, powdered sugar, magnesium stearate, maltose, lemonade, tartaric acid, sodium hydroxide, aspartame, stevioside, cyclamate, protein sugar, acesulfame potassium, aspartame, sucralose, α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, etc.

[0043] Preferably, in step 2), 7 times the amount of ethanol is added for alcohol extraction, and reflux extraction is performed twice, each time for 2 hours.

[0044] Preferably, in step 3), 9 times the amount of water is added and boiled twice.

[0045] Preferably, in step 4), ethanol is added to make the alcohol content 60%, and the mixture is refrigerated for 36 hours.

[0046] When the dosage form is a granule, the extract is dried or not, and a pharmaceutically acceptable excipient is added, and the granule is obtained by dry or wet granulation.

[0047] Preferably, the excipients include but are not limited to starch, dextrin, powdered sugar, lactose, magnesium stearate, maltodextrin, citric acid, tartaric acid, sodium bicarbonate, aspartame, stevioside, cyclamate and protein sugar.

[0048] In one embodiment, the extract is vacuum dried, and appropriate amounts of lactose and magnesium stearate are added to the dry powder, mixed, and then dry granulated to obtain granules.

[0049] In another embodiment, the extract is added with appropriate amounts of powdered sugar and starch, mixed evenly, made into a soft material with 80% ethanol, granulated and dried to obtain granules.

[0050] In another embodiment, the extract is spray-dried, and appropriate amounts of lactose, maltodextrin, magnesium stearate, and aspartame are added to the dry powder, mixed, and dry granulated to obtain granules.

[0051] When the dosage form is an oral liquid preparation, the extract is added with activated carbon and heated to keep warm, filtered, precipitated and recovered ethanol is concentrated to an appropriate amount, filtered, precipitated, an appropriate amount of excipient is added, stirred to dissolve, the pH is adjusted to 6-8, water is added to the total amount of preparation, stirred evenly, filtered, potted, and sterilized to obtain the oral liquid preparation.

[0052] In one embodiment, the extract is added with activated carbon at a mass fraction of 0.01-1%, heated and kept warm, filtered, and condensed for 24-168 hours. An appropriate amount of sucrose or aspartame is added and stirred to dissolve. The pH is adjusted to 6-8. Water is added to the total amount of the preparation, stirred, filtered, potted, and sterilized to obtain an oral liquid preparation.

[0053] In another embodiment, the obtained extract is added with activated carbon at a mass fraction of 0.01-1%, heated and kept warm, filtered, and condensed for 24-168 hours. The pH is adjusted to 6.5-8.0, and the inclusion material is added and stirred for inclusion, filtered, and water is added to the total amount of the preparation. After filtering until the clarity is qualified, the extract is filled and sterilized to obtain an oral liquid preparation.

[0054] Preferably, the inclusion material is any one of cyclodextrin or its derivatives; more preferably α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, and even more preferably β-cyclodextrin.

[0055] The Chinese medicine composition is used in preparing medicines for treating coronary heart disease and angina pectoris.

[0056] Coronary heart disease angina pectoris is a common clinical disease and a frequently-occurring disease in the elderly. Its main pathogenesis is qi deficiency and blood stasis. Modern medicine believes that lipid metabolism is disordered, and high blood fat is the main factor that induces coronary artery atherosclerosis. Platelet aggregation is higher than that of normal people, which forms thrombus, causes lumen stenosis, causes imbalance between oxygen supply and demand, and causes the main cause of temporary myocardial ischemia and hypoxia. Experimental results show that Chinese medicine composition of the present invention not only has obvious antiplatelet aggregation effect, but also has the effect of reducing blood fat and anti-atherosclerosis, and can significantly prolong the survival time of hypoxic cells, which is consistent with the prolongation of the beating time of myocardial cells under the condition of hypoxia of the invention liquid. In a word, this experiment is that the invention Chinese medicine composition has the effect of invigorating qi and tonifying the kidney, softening and dispersing hard masses, promoting blood circulation and removing blood stasis, and treating both the symptoms and the root cause, and provides reliable experimental basis for the clinical prevention and treatment of coronary heart disease angina pectoris.

[0057] In order to verify the efficacy of the drug in preventing and treating coronary heart disease and angina pectoris, the inventors have carried out a large number of pharmacodynamic tests and studies. It should be noted that the drugs selected for the pharmacodynamic tests of the drugs of the present invention are drugs obtained by the representative formulas and preparation methods of the present invention. Due to space limitations, the tests and results involved in the drugs obtained by other formulas and preparation methods included in the present invention are not listed here in full.

[0058] Experimental Example 1 Effects of drugs on the hypoxia tolerance of mice

[0059] 1. Materials

[0060] 1.1 Experimental animals and feed

[0061] Fifty healthy female KM mice, weighing (20 ± 2) g, were provided by Lunan Pharmaceutical Co., Ltd. (Experimental Animal License No.: SYXK(Lu)20180008). Before the experiment, the mice were acclimatized in a clean animal laboratory for 1 week at room temperature of 20–25°C, relative humidity of 40%–60%, and natural light, with free access to food and water.

[0062] 1.2 Instruments, reagents and drugs

[0063] AG285 electronic analytical balance (Mettler-Toledo, Switzerland), soda lime (Hubei Zhongwei Calcium Industry Co., Ltd.); the test drug was the granule sample prepared according to the formula and process under Example 1, and the positive control drug was Xintong Granules (Batch No.: 20058001, produced by Lunan Houpu Pharmaceutical Co., Ltd.).

[0064] 2 Methods

[0065] 2.1 Grouping and modeling

[0066] According to the normobaric hypoxia tolerance test method, 50 healthy KM mice were randomly divided into five groups: model control, positive control, high-dose, medium-dose, and low-dose groups, with 10 mice in each group. All groups were administered intragastrically. The dose conversion coefficients for different animals in the appendix of the "Guidelines for Clinical Research of New Chinese Medicines" were used for dose conversion. The positive control group was administered 3.06 g / kg of Xintong Granules by oral gavage. The high-dose, medium-dose, and low-dose groups were administered 6.12 g / kg (2 times the human equivalent dose), 3.06 g / kg (human equivalent dose), and 1.53 g / kg (0.5 times the human equivalent dose) of the test drug by oral gavage, respectively. The model control group was administered an equal volume of normal saline by oral gavage once daily for 7 consecutive days.

[0067] 2.2 Detection indicators and methods

[0068] Eight hours after administration on the 7th day, 50 mice were placed in wide-mouth bottles containing soda lime (15 g). The bottle caps were tightly closed and the survival time of the mice was recorded with a stopwatch.

[0069]

[0070] 2.3 Statistical analysis

[0071] SPSS 19.0 statistical software was used for analysis, and the experimental data were expressed as “mean ± standard deviation”. ". One-way analysis of variance was used to compare multiple groups, and P < 0.05 indicated statistically significant differences.

[0072] 3 Results

[0073] Compared with the model control group, the survival time of mice in the positive control group and the high, medium, and low dose groups was significantly prolonged, with the differences being statistically significant (P < 0.05). The medium dose group had an effect comparable to that of the positive control, indicating that the Chinese herbal composition of the present invention can effectively improve the hypoxia tolerance of mice. The test results are shown in Table 1.

[0074] Table 1 Effects of hypoxia tolerance on survival time of mice ( n=10)

[0075]

[0076] Note: Compared with the model control group, P < 0.05 is indicated by "*".

[0077] Experimental Example 2 Effects of ADP-induced Platelet Aggregation in Rats

[0078] 1. Materials

[0079] 1.1 Experimental animals and feed

[0080] Sixty SPF Sprague-Dawley rats, half male and half female, weighing (200 ± 20) g, were provided by Lunan Pharmaceutical Group Co., Ltd., Laboratory Animal License No. SYXK(Lu)20180008. Before the experiment, the rats were acclimatized for one week in a clean animal laboratory, separated by sex, at room temperature of 20–25°C, relative humidity of 40%–60%, under natural light, and with free access to food and water.

[0081] 1.2 Instruments, reagents and drugs

[0082] AG285 electronic analytical balance (Mettler-Toledo, Switzerland), fully automatic platelet aggregometer NKK-3 (Hitachi, Japan); adenosine diphosphate ADP (Sigma, USA), high-fat feed (Beijing Huafukang Biotechnology Co., Ltd.), vitamin D3 (Suzhou Sixth Pharmaceutical Institute), posterior pituitary hormone (Nanjing Xinbai Pharmaceutical Co., Ltd.), urethane (Shandong Qilu Xinghua Pharmaceutical Co., Ltd.), sodium citrate (Jiangsu Hengrui Medicine Co., Ltd.); the test drug was the granule sample prepared according to the formula and process under Example 1, and the positive control drug was Xintong Granules (Batch No.: 20058001, produced by Lunan Houpu Pharmaceutical Co., Ltd.).

[0083] 2 Methods

[0084] 2.1 Grouping and modeling

[0085] Sixty SPF Sprague-Dawley rats were randomly divided into six groups: a normal control group, a model control group, a positive control group, a high-dose experimental group, a medium-dose experimental group, and a low-dose experimental group, with 10 rats in each group, half male and half female. Except for the normal control group, the rats in the other five groups received a single intraperitoneal injection of vitamin D3.6 million IU / kg at the beginning of modeling and were fed a high-fat diet for 12 consecutive weeks (high-fat diet ratio: 3% cholesterol, 0.5% sodium cholate, 0.2% propylthiouracil, 5% white sugar, 10% lard, 81.3% basal feed). For the final three days, rats in each model group received three daily intraperitoneal injections of 30 U / kg of vasopressin. The rats in the normal control group were fed a normal diet.

[0086] 2.2 Administration

[0087] At the same time as modeling, each group was gavaged with the drug from the beginning of the experiment. The dose conversion was performed according to the dose conversion coefficients for different animals in the appendix of the "Guidelines for Clinical Research of New Chinese Medicines". The positive control group was gavaged with 2.12 g / kg of Xintong Granules, and the high-dose group, medium-dose group and low-dose group were gavaged with the test drug 4.24 g / kg (2 times the human equivalent dose), 2.12 g / kg (human equivalent dose) and 1.06 g / kg (0.5 times the human equivalent dose) respectively. The normal control group and model control group were given an equal volume of normal saline by gavage, once a day, for 12 consecutive weeks.

[0088] 2.3 Detection indicators and methods

[0089] Platelet aggregation was determined using a turbidimetric method. Rats were fasted for 12 hours before testing and anesthetized intraperitoneally with 20% urethane (1 g / kg). Blood was collected from the inferior vena cava (5 ml). 2 mL of blood was added to a "maximum platelet aggregation rate (MPAR)" centrifuge tube containing 38 g / L sodium citrate (prepared at a blood-to-anticoagulant ratio of 9:1). The tube was centrifuged at 200 g for 8 minutes to separate the upper platelet-rich plasma (PRP). The remaining blood was centrifuged again at 2200 g for 10 minutes to separate the upper platelet-poor plasma (PPP). PPP was adjusted to zero, and 300 μL of PRP was added to a turbidimetric tube. The tube was incubated at 37°C for 5 minutes. 15 μL of 300 μmol / L ADP, a platelet aggregation inducer, was added, and the tube was placed in an automated platelet aggregometer for aggregation for different times. The maximum platelet aggregation rate and the platelet aggregation rate at different time points (1, 3, and 5 minutes) were recorded.

[0090] 2.4 Statistical analysis

[0091] SPSS 19.0 statistical software was used for analysis, and the experimental data were expressed as “mean ± standard deviation”. ". One-way analysis of variance was used to compare multiple groups, and P < 0.05 indicated statistically significant differences.

[0092] 3 Results

[0093] Compared with the normal control group, the platelet aggregation rates and maximum platelet aggregation rates of the model control group rats were significantly increased at 1 minute, 2 minutes, and 5 minutes, with statistically significant differences (P < 0.05). Compared with the model control group rats, the platelet aggregation rates and maximum platelet aggregation rates of the positive control group and the high, medium, and low dose groups were significantly decreased at 1 minute, 2 minutes, and 5 minutes, with statistically significant differences (P < 0.05). These results indicate that the Chinese herbal composition of the present invention can significantly inhibit ADP-induced platelet aggregation, thereby exerting a therapeutic effect on rats with coronary heart disease. The results are shown in Table 2.

[0094] Table 2 Effects of ADP on platelet aggregation in rats ( n=10)

[0095]

[0096]

[0097] Note: Compared with the normal control group, P < 0.05 is indicated by "△"; compared with the model control group, P < 0.05 is indicated by "*".

[0098] Experimental Example 3 Effects on Whole Blood Viscosity and Plasma Viscosity in Rats

[0099] 1. Materials

[0100] 1.1 Experimental animals and feeds were the same as those in Experimental Example 2.

[0101] 1.2 Instruments, reagents and drugs

[0102] AG285 electronic analytical balance (Mettler-Toledo, Switzerland), fully automatic platelet aggregometer NKK-3 (Hitachi, Japan); adenosine diphosphate ADP (Sigma, USA), high-fat feed (Beijing Huafukang Biotechnology Co., Ltd.), vitamin D3 (Suzhou Sixth Pharmaceutical Institute), posterior pituitary hormone (Nanjing Xinbai Pharmaceutical Co., Ltd.), urethane (Shandong Qilu Xinghua Pharmaceutical Co., Ltd.), sodium citrate (Jiangsu Hengrui Medicine Co., Ltd.); the test drug was the granule sample prepared according to the formula and process under Example 1, and the positive control drug was Xintong Granules (Batch No.: 20058001, produced by Lunan Houpu Pharmaceutical Co., Ltd.).

[0103] 2 Methods

[0104] 2.1 Grouping and modeling methods are the same as those in Experimental Example 2.

[0105] 2.2 The administration method was the same as that in Experimental Example 2.

[0106] 2.3 Detection indicators and methods

[0107] Before the test, rats were fasted for 12 hours and anesthetized with 20% urethane (1 g / kg) intraperitoneally. Blood was collected from the abdominal aorta and heparin sodium 20 kU·L -1 Anticoagulation. Rat whole blood viscosity was measured using a cone-plate rotational viscometer. 0.8 mL of heparin-anticoagulated whole blood was added to the sample cell of the viscometer. The whole blood viscosity was measured at 37°C at shear rates of 200, 100, 50, and 1 / s. The erythrocyte aggregation index (EAI) was calculated as EAI = η1 / η. 100 , where η1 is the shear rate 1s -1 Whole blood viscosity under 100 is the shear rate 100s -1 Take 2 mL of heparinized blood, centrifuge at 3000 g for 15 min, and take 0.8 mL of plasma to measure the plasma viscosity at 37°C.

[0108] 2.4 Statistical analysis

[0109] SPSS 19.0 statistical software was used for analysis, and the experimental data were expressed as “mean ± standard deviation”. ". One-way analysis of variance was used to compare multiple groups, and P < 0.05 indicated statistically significant differences.

[0110] 3 Results

[0111] Compared with the normal control group, the rats in the model control group had a higher shear rate at 200, 100, 50 and 1s -1 Whole blood viscosity and shear rate under 50s -1 Compared with the model control group, the plasma viscosity of the rats in the positive control group and the high, medium and low dose groups increased significantly at 200, 100, 50 and 1s -1 Whole blood viscosity and shear rate under 50s -1 The plasma viscosity was significantly reduced under the condition of 40 mg / kg / day (P < 0.05). The above results show that the Chinese medicine composition of the present invention can significantly improve blood viscosity, thereby exerting a therapeutic effect on rats with coronary heart disease. The results are shown in Table 3.

[0112] Table 3 Effects on whole blood viscosity and plasma viscosity of rats ( n=10)

[0113]

[0114] Note: Compared with the normal control group, P < 0.05 is indicated by "△"; compared with the model control group, P < 0.05 is indicated by "*".

[0115] Experimental Example 4 Effects on Hyperlipidemia in Rats

[0116] 1. Materials

[0117] Fifty SPF Sprague-Dawley rats, half male and half female, weighing (200 ± 20) g, were provided by Lunan Pharmaceutical Group Co., Ltd., Laboratory Animal License No. SYXK(Lu)20180008. Before the experiment, the rats were acclimatized in a clean animal laboratory for one week, separated by sex, at room temperature of 20–25°C, relative humidity of 40%–60%, under natural light, and with free access to food and water.

[0118] High-fat feed (Beijing Huafukang Biotechnology Co., Ltd.), the test drug is the oral liquid preparation sample prepared according to the formula and process under Example 2, and the positive control drug is Xintong Oral Liquid (Batch No.: 10920014, produced by Lunan Houpu Pharmaceutical Co., Ltd.).

[0119] 2 Methods

[0120] 2.1 Grouping and Dosing

[0121] The above rats were randomly divided into 6 groups, namely blank control group, model control group, positive control group, experimental high-dose group, experimental medium-dose group and experimental low-dose group.

[0122] After grouping, except for the blank control group, the mice were fed a high-fat diet and given drugs by gavage. The model control group and the blank group were given the same volume of normal saline by gavage, the positive control group was given 6 ml / kg of Xintong oral solution by gavage, the high-dose group was given 12 ml / kg of the oral solution prepared in Example 2 by gavage, the medium-dose group was given 6 ml / kg of the oral solution prepared in Example 2 by gavage, and the low-dose group was given 3 ml / kg of the oral solution prepared in Example 2 by gavage, once a day for 14 consecutive days.

[0123] 2.2 Detection

[0124] On the 14th day, the subjects were fasted for 12 hours and anesthetized with sodium pentobarbital. Blood was collected from the abdominal aorta. Serum total cholesterol (CH) and high-density lipoprotein (HDL-C) were determined by enzymatic method, and triglyceride (TG) content was determined by acetylacetone colorimetric method.

[0125] 2.3 Statistical analysis

[0126] SPSS 19.0 statistical software was used for analysis, and the experimental data were expressed as “mean ± standard deviation”. ". One-way analysis of variance was used to compare multiple groups, and P < 0.05 indicated statistically significant differences.

[0127] 3 Results

[0128] The high-dose, medium-dose, and low-dose groups of the present invention, as well as the positive control group, were able to reduce CH and TG values ​​in rats with hyperlipidemia (P < 0.01). The high-dose, medium-dose, and positive control groups of the present invention also increased HDL-C values ​​(P < 0.01). The results are shown in Table 4.

[0129] Table 4 Effect of the present invention on serum CH, TG and HDL-C values ​​in experimental hyperlipidemic rats (X ± SD)

[0130]

[0131] Note: Compared with the normal control group, P < 0.05 is indicated by "△"; compared with the model control group, P < 0.05 is indicated by "*".

[0132] The present composition primarily contains 17 medicinal herbs, including Astragalus, Codonopsis, Rhodiola, Schisandra, and Rehmannia. Pharmacodynamic studies have shown that the present composition significantly prolongs the hypoxia tolerance of mice, significantly reduces platelet aggregation in rats, improves blood viscosity, and lowers CH and TG values ​​in rats with hyperlipidemia, demonstrating its therapeutic effect on rats with coronary heart disease. DETAILED DESCRIPTION

[0133] The technical solutions of the present invention are further illustrated below through specific examples. However, those skilled in the art should be aware that the examples do not limit the present invention in any way.

[0134] Example 1 Preparation of granules

[0135]

[0136]

[0137] 1) Weigh 17 medicinal materials, including astragalus, codonopsis, rhodiola, poria, ophiopogon, schisandra, rehmannia root, epimedium, kudzu root, angelica, salvia miltiorrhiza, honey locust thorn, seaweed, kelp, oyster, immature bitter orange, and polygonatum, wherein ophiopogon, epimedium, and immature bitter orange are cleaned, codonopsis, seaweed, and kelp are cleaned and cut into sections, rhodiola, poria, rehmannia root, polygonatum, kudzu root, and oyster are cleaned and cut into pieces, astragalus, angelica, and salvia miltiorrhiza are cleaned and sliced, and schisandra and honey locust thorn are cleaned and crushed into coarse powder for later use;

[0138] 2) Extract Puerariae Radix, Salviae Miltiorrhizae, and Schisandrae Chinensis Chinensis by alcohol extraction with 6 times the volume of 60% ethanol, reflux extraction twice for 1 hour each time, combine the ethanol solutions, filter, and collect the filtrate and the residue;

[0139] 3) adding the residue obtained in step 2) to thirteen medicinal slices including Astragalus membranaceus, adding 6 times the amount of water, decocting twice, each time for 1.5 hours, combining the decoctions, filtering, and concentrating the filtrate under reduced pressure to an extract with a relative density of 1.20; combining the filtrates obtained in step 1) and adding ethanol to a concentration of 70% alcohol, refrigerating for 24 hours, filtering, recovering the ethanol from the filtrate, and concentrating it to an extract with a relative density of 1.3 (60° C.);

[0140] 4) Add appropriate amount of dextrin and aspartame to the extract, mix well, wet-clean with 80% ethanol, and dry at 80°C to obtain granules.

[0141] Example 2 Preparation of Oral Liquid Preparation

[0142]

[0143] 1) Weigh 17 medicinal materials, including astragalus, codonopsis, rhodiola, poria, ophiopogon, schisandra, rehmannia root, epimedium, kudzu root, angelica, salvia miltiorrhiza, honey locust thorn, seaweed, kelp, oyster, immature bitter orange, and polygonatum, wherein ophiopogon, epimedium, and immature bitter orange are cleaned, codonopsis, seaweed, and kelp are cleaned and cut into sections, rhodiola, poria, rehmannia root, polygonatum, kudzu root, and oyster are cleaned and cut into pieces, astragalus, angelica, and salvia miltiorrhiza are cleaned and sliced, and schisandra and honey locust thorn are cleaned and crushed into coarse powder for later use;

[0144] 2) Extract Puerariae Radix, Salvia miltiorrhizae, and Schisandrae Chinensis Chinensis using alcohol extraction method with 6 times the volume of 60% ethanol and reflux extraction for 3 times, each time for 2 hours. Combine the ethanol solutions, filter, and collect the filtrate and the residue.

[0145] 3) adding the residue obtained in step 2) to thirteen medicinal slices including Astragalus membranaceus, adding 8 times the amount of water, decocting twice, each time for 1.5 hours, combining the decoctions, filtering, and concentrating the filtrate under reduced pressure to an extract with a relative density of 1.20; combining the filtrates obtained in step 1) and adding ethanol to an alcohol content of 60%, refrigerating for 48 hours, filtering, recovering the ethanol from the filtrate, and concentrating to a relative density of 1.1 (60° C.);

[0146] 4) Add 0.1% by weight activated carbon to the liquid obtained in step 3), heat to 80°C for 1 hour, filter, cool the filtrate for 48 hours, adjust the pH to 6-8, add 3% by weight β-cyclodextrin, incubate at 40°C for 60 minutes, filter, and adjust the volume to the total volume with purified water. Stir well, filter, seal, and sterilize to obtain an oral liquid preparation.

[0147] Example 3 Preparation of granules

[0148]

[0149] 1) Weigh 17 medicinal materials, including astragalus, codonopsis, rhodiola, poria, ophiopogon, schisandra, rehmannia root, epimedium, kudzu root, angelica, salvia miltiorrhiza, honey locust thorn, seaweed, kelp, oyster, immature bitter orange, and polygonatum, wherein ophiopogon, epimedium, and immature bitter orange are cleaned, codonopsis, seaweed, and kelp are cleaned and cut into sections, rhodiola, poria, rehmannia root, polygonatum, kudzu root, and oyster are cleaned and cut into pieces, astragalus, angelica, and salvia miltiorrhiza are cleaned and sliced, and schisandra and honey locust thorn are cleaned and crushed into coarse powder for later use;

[0150] 2) Extract Puerariae Radix, Salviae Miltiorrhizae, and Schisandrae Chinensis Chinensis by alcohol extraction with 7-fold volume of 60% ethanol, reflux extraction twice for 1 hour each time, combine the ethanol solutions, filter, and collect the filtrate and the residue;

[0151] 3) adding the residue obtained in step 2) to thirteen medicinal slices including Astragalus membranaceus, adding 10 times the amount of water, decocting twice, each time for 1 hour, combining the decoctions, filtering, and concentrating the filtrate under reduced pressure to an extract having a relative density of 1.1 (at 60° C.); combining the filtrates obtained in step 1) and adding ethanol to a concentration of 60% alcohol, refrigerating for 36 hours, filtering, recovering the ethanol from the filtrate, and concentrating it to an extract having a relative density of 1.4 (at 60° C.);

[0152] 4) The extract is spray-dried, and appropriate amounts of lactose and magnesium stearate (0.3% of the dry granules) are added, mixed, dry-granulated, and packaged to obtain the product.

[0153] Example 4 Preparation of granules

[0154]

[0155] 1) Weigh 17 medicinal materials, including astragalus, codonopsis, rhodiola, poria, ophiopogon, schisandra, rehmannia root, epimedium, kudzu root, angelica, salvia miltiorrhiza, honey locust thorn, seaweed, kelp, oyster, immature bitter orange, and polygonatum, wherein ophiopogon, epimedium, and immature bitter orange are cleaned, codonopsis, seaweed, and kelp are cleaned and cut into sections, rhodiola, poria, rehmannia root, polygonatum, kudzu root, and oyster are cleaned and cut into pieces, astragalus, angelica, and salvia miltiorrhiza are cleaned and sliced, and schisandra and honey locust thorn are cleaned and crushed into coarse powder for later use;

[0156] 2) Extract Puerariae Radix, Salvia miltiorrhizae, and Schisandrae Chinensis Chinensis using alcohol extraction method with 5 times the volume of 70% ethanol and reflux extraction for 3 times, each time for 1 hour. Combine the ethanol solutions, filter, and collect the filtrate and the residue.

[0157] 3) adding the residue obtained in step 2) to thirteen medicinal slices including Astragalus membranaceus, adding 7 times the amount of water, decocting twice, each time for 2 hours, combining the decoctions, filtering, and concentrating the filtrate under reduced pressure to an extract having a relative density of 1.2 (at 60° C.); combining the filtrates obtained in step 1) and adding ethanol to an alcohol content of 75%, refrigerating for 48 hours, filtering, recovering the ethanol from the filtrate, and concentrating it to an extract having a relative density of 1.4 (at 60° C.);

[0158] 4) The extract is spray-dried, and a small amount of lactose and an appropriate amount of magnesium stearate (0.2% of the weight of the dry granules) are added to the dry powder, mixed evenly, dry granulated, and packaged.

[0159] Example 5 Preparation of Oral Liquid Preparation

[0160]

[0161] 1) Weigh 17 medicinal materials, including astragalus, codonopsis, rhodiola, poria, ophiopogon, schisandra, rehmannia root, epimedium, kudzu root, angelica, salvia miltiorrhiza, honey locust thorn, seaweed, kelp, oyster, immature bitter orange, and polygonatum, wherein ophiopogon, epimedium, and immature bitter orange are cleaned, codonopsis, seaweed, and kelp are cleaned and cut into sections, rhodiola, poria, rehmannia root, polygonatum, kudzu root, and oyster are cleaned and cut into pieces, astragalus, angelica, and salvia miltiorrhiza are cleaned and sliced, and schisandra and honey locust thorn are cleaned and crushed into coarse powder for later use;

[0162] 2) Extract Puerariae Radix, Salviae Miltiorrhizae, and Schisandrae Chinensis Chinensis by alcohol extraction with 5 times the volume of 70% ethanol, reflux extraction twice for 1 hour each time, combine the ethanol solutions, filter, and collect the filtrate and the residue;

[0163] 3) adding the residue obtained in step 2) to thirteen medicinal slices including Astragalus membranaceus, adding 8 times the amount of water, decocting twice, each time for 1.5 hours, combining the decoctions, filtering, and concentrating the filtrate under reduced pressure to an extract with a relative density of 1.3; combining the filtrates obtained in step 1) and adding ethanol to an alcohol content of 60%, refrigerating for 48 hours, filtering, recovering the ethanol from the filtrate, and concentrating to a relative density of 1.2 (60° C.);

[0164] 4) Add 0.2% by mass activated carbon to the liquid obtained in step 3), heat to 80°C for 1 hour, filter, and cool the filtrate for 48 hours. Add 5% by mass sucrose, stir well, adjust the pH to 6-8, add purified water to the total volume, stir well, filter, fill, and sterilize to obtain an oral liquid preparation.

[0165] Example 6 Preparation of Tablets

[0166]

[0167]

[0168] 1) Weigh 17 medicinal materials, including astragalus, codonopsis, rhodiola, poria, ophiopogon, schisandra, rehmannia root, epimedium, kudzu root, angelica, salvia miltiorrhiza, honey locust thorn, seaweed, kelp, oyster, immature bitter orange, and polygonatum, wherein ophiopogon, epimedium, and immature bitter orange are cleaned, codonopsis, seaweed, and kelp are cleaned and cut into sections, rhodiola, poria, rehmannia root, polygonatum, kudzu root, and oyster are cleaned and cut into pieces, astragalus, angelica, and salvia miltiorrhiza are cleaned and sliced, and schisandra and honey locust thorn are cleaned and crushed into coarse powder for later use;

[0169] 2) Extract Puerariae Radix, Salvia miltiorrhizae, and Schisandrae Chinensis Chinensis using alcohol extraction method with 8 times the volume of 40% ethanol and reflux extraction for 3 times, each time for 2 hours. Combine the ethanol solutions, filter, and collect the filtrate and the residue.

[0170] 3) adding the residue obtained in step 2) to thirteen medicinal slices including Astragalus membranaceus, adding 4 times the amount of water, decocting three times, each time for 1 hour, combining the decoctions, filtering, and concentrating the filtrate under reduced pressure to an extract having a relative density of 1.3 (at 60° C.); combining the filtrates obtained in step 1) and adding 95% ethanol to a 75% alcohol content, refrigerating for 48 hours, filtering, recovering the ethanol from the filtrate, and concentrating it to an extract having a relative density of 1.5 (at 60° C.);

[0171] 4) The extract is vacuum-dried, and appropriate amounts of sucrose and starch are added, mixed, and an appropriate amount of 80% ethanol is added to prepare a soft material, granulate, and tablet.

[0172] Example 7 Preparation of Capsules

[0173]

[0174] 1) Weigh 17 medicinal materials, including astragalus, codonopsis, rhodiola, poria, ophiopogon, schisandra, rehmannia root, epimedium, kudzu root, angelica, salvia miltiorrhiza, honey locust thorn, seaweed, kelp, oyster, immature bitter orange, and polygonatum, wherein ophiopogon, epimedium, and immature bitter orange are cleaned, codonopsis, seaweed, and kelp are cleaned and cut into sections, rhodiola, poria, rehmannia root, polygonatum, kudzu root, and oyster are cleaned and cut into pieces, astragalus, angelica, and salvia miltiorrhiza are cleaned and sliced, and schisandra and honey locust thorn are cleaned and crushed into coarse powder for later use;

[0175] 2) Extract Puerariae Radix, Salviae Miltiorrhizae, and Schisandrae Chinensis Chinensis by alcohol extraction with 4 times the volume of 80% ethanol, reflux extraction twice for 2 hours each time, combine the ethanol solutions, filter, and collect the filtrate and the residue;

[0176] 3) adding the residue obtained in step 2) to thirteen medicinal slices including Astragalus membranaceus, adding 9 times the amount of water, decocting twice, each time for 1.5 hours, combining the decoctions, filtering, and concentrating the filtrate under reduced pressure to an extract having a relative density of 1.1 (at 60° C.); combining the filtrates obtained in step 1) and adding 95% ethanol to a concentration of 45% alcohol, refrigerating for 48 hours, filtering, recovering the ethanol from the filtrate, and concentrating it to an extract having a relative density of 1.2 (at 60° C.);

[0177] 4) The extract is vacuum dried, and the dry powder is added with an appropriate amount of starch and stevia, mixed evenly, and an appropriate amount of 60% ethanol is added to prepare a soft material, and granules are prepared and filled into capsule shells.

[0178] Example 8 Preparation of Oral Liquid Preparation

[0179]

[0180] 1) Weigh 17 medicinal materials, including astragalus, codonopsis, rhodiola, poria, ophiopogon, schisandra, rehmannia root, epimedium, kudzu root, angelica, salvia miltiorrhiza, honey locust thorn, seaweed, kelp, oyster, immature bitter orange, and polygonatum, wherein ophiopogon, epimedium, and immature bitter orange are cleaned, codonopsis, seaweed, and kelp are cleaned and cut into sections, rhodiola, poria, rehmannia root, polygonatum, kudzu root, and oyster are cleaned and cut into pieces, astragalus, angelica, and salvia miltiorrhiza are cleaned and sliced, and schisandra and honey locust thorn are cleaned and crushed into coarse powder for later use;

[0181] 2) Extract Puerariae Radix, Salviae Miltiorrhizae, and Schisandrae Chinensis Chinensis by alcohol extraction with 8 times the volume of 60% ethanol, reflux extraction twice for 3 hours each time, combine the ethanol solutions, filter, and collect the filtrate and the residue;

[0182] 3) adding the residue obtained in step 2) to thirteen medicinal slices including Astragalus membranaceus, adding 10 times the amount of water, decocting twice, each time for 1 hour, combining the decoctions, filtering, and concentrating the filtrate under reduced pressure to an extract with a relative density of 1.2; combining the filtrates obtained in step 1) and adding ethanol to a concentration of 60% alcohol content, refrigerating for 48 hours, filtering, recovering ethanol from the filtrate, and concentrating to a relative density of 1.1 (60° C.);

[0183] 4) adding 0.1% by weight activated carbon to the liquid obtained in step 3), heating to 80°C for 1 hour, filtering, and cooling the filtrate for 48 hours. Adding 5% by weight aspartame, stirring well, adjusting the pH to 6-8, adding purified water to the total volume, stirring well, filtering, filling, and sterilizing to obtain an oral liquid preparation.

[0184] Example 9 Preparation of Pills

[0185]

[0186] 1) Weigh 17 medicinal materials, including astragalus, codonopsis, rhodiola, poria, ophiopogon, schisandra, rehmannia root, epimedium, kudzu root, angelica, salvia miltiorrhiza, honey locust thorn, seaweed, kelp, oyster, immature bitter orange, and polygonatum, wherein ophiopogon, epimedium, and immature bitter orange are cleaned, codonopsis, seaweed, and kelp are cleaned and cut into sections, rhodiola, poria, rehmannia root, polygonatum, kudzu root, and oyster are cleaned and cut into pieces, astragalus, angelica, and salvia miltiorrhiza are cleaned and sliced, and schisandra and honey locust thorn are cleaned and crushed into coarse powder for later use;

[0187] 2) Extract Puerariae Radix, Salviae Miltiorrhizae, and Schisandrae Chinensis Chinensis by alcohol extraction with 7-fold volume of 60% ethanol, reflux extraction twice for 1.5 h each time, combine the ethanol solutions, filter, and collect the filtrate and the residue;

[0188] 3) adding the residue obtained in step 2) to thirteen medicinal slices including Astragalus membranaceus, adding 7 times the amount of water, decocting twice, each time for 1.5 hours, combining the decoctions, filtering, and concentrating the filtrate under reduced pressure to an extract with a relative density of 1.20; combining the filtrates obtained in step 1) and adding ethanol to a concentration of 70% alcohol, refrigerating for 36 hours, filtering, recovering the ethanol from the filtrate, and concentrating to an extract with a relative density of 1.4 (60° C.);

[0189] 4) The extract is spray-dried, and the dry powder is added with an appropriate amount of dextrin and mixed evenly, formed into pills, and dried.

[0190] Example 10 Preparation of syrup

[0191]

[0192] 1) Weigh 17 medicinal materials, including astragalus, codonopsis, rhodiola, poria, ophiopogon, schisandra, rehmannia root, epimedium, kudzu root, angelica, salvia miltiorrhiza, honey locust thorn, seaweed, kelp, oyster, immature bitter orange, and polygonatum, wherein ophiopogon, epimedium, and immature bitter orange are cleaned, codonopsis, seaweed, and kelp are cleaned and cut into sections, rhodiola, poria, rehmannia root, polygonatum, kudzu root, and oyster are cleaned and cut into pieces, astragalus, angelica, and salvia miltiorrhiza are cleaned and sliced, and schisandra and honey locust thorn are cleaned and crushed into coarse powder for later use;

[0193] 2) Extract Puerariae Radix, Salviae Miltiorrhizae, and Schisandrae Chinensis Chinensis by alcohol extraction with 6 times the volume of 60% ethanol, reflux extraction twice for 1 hour each time, combine the ethanol solutions, filter, and collect the filtrate and the residue;

[0194] 3) adding the residue obtained in step 2) to thirteen medicinal slices including Astragalus membranaceus, adding 6 times the amount of water, decocting twice, each time for 1.5 hours, combining the decoctions, filtering, and concentrating the filtrate under reduced pressure to an extract with a relative density of 1.10; combining the filtrates obtained in step 1) and adding ethanol to an alcohol content of 80%, refrigerating for 48 hours, filtering, recovering the ethanol from the filtrate, and concentrating it to an extract with a relative density of 1.3 (60° C.);

[0195] 4) Add monosaccharide syrup to the extract, mix well, and divide into portions to obtain the product.

Claims

1. A Chinese medicine composition, characterized in that Made from the following Chinese medicinal ingredients: 300 weight parts of Astragalus root, 160 weight parts of Codonopsis pilosula, 130 weight parts of Rhodiola rosea 160 parts by weight of Poria cocos 110 parts by weight of Radix Ophiopogonis 130 parts by weight of Schisandra chinensis 260 parts by weight of Rehmannia root, 90 parts by weight of Epimedium, 250 parts by weight of Pueraria root 90 parts by weight of Chinese Angelica sinensis, 170 parts by weight of Salvia miltiorrhiza, 90 parts by weight of Gleditsia sinensis 150 parts by weight of seaweed 150 parts by weight of kelp 150 parts by weight of oyster 80 parts by weight of Fructus Aurantii Immaturus and 240 parts by weight of Rhizoma Polygonati Sinensis.

2. The method for preparing the Chinese medicine composition according to claim 1, wherein: The steps include: 1) Weigh 17 medicinal materials, including astragalus, codonopsis, rhodiola, poria, ophiopogon, schisandra, rehmannia root, epimedium, kudzu root, angelica, salvia miltiorrhiza, honey locust thorn, seaweed, kelp, oyster, immature bitter orange, and polygonatum, wherein ophiopogon, epimedium, and immature bitter orange are cleaned, codonopsis, seaweed, and kelp are cleaned and cut into sections, rhodiola, poria, rehmannia root, polygonatum, kudzu root, and oyster are cleaned and cut into pieces, astragalus, angelica, and salvia miltiorrhiza are cleaned and sliced, and schisandra and honey locust thorn are cleaned and crushed into coarse powder for later use; 2) Weigh the prescribed amount of Pueraria root, Salvia miltiorrhiza, and Schisandra chinensis, add 4-12 times the amount of 40%-80% ethanol, and reflux extract 1-3 times, each time for 0.5-3 hours. Filter, collect the filtrate and the residue, and set aside. 3) Add the remaining thirteen medicinal pieces including the astragalus root to the residue obtained in step 2), add 4-12 times the amount of water, and boil for 1-3 times, filter, and concentrate the filtrate under reduced pressure to an extract having a relative density of 1.15-1.25 at 60°C; 4) The filtrate obtained in step 2) is combined with the extract obtained in step 3), and ethanol is added to increase the alcohol content to 40%-80%. The extract is refrigerated for 24-48 hours, the ethanol is recovered, and the extract is concentrated to an extract having a relative density of 1.1-1.5 at 60°C. Pharmaceutically acceptable excipients are added through conventional processes to prepare a clinically acceptable dosage form.

3. The preparation method according to claim 2, characterized in that Step 2) Add 7 times the amount of 60% ethanol for alcohol extraction, and reflux extraction twice, each time for 2 hours.

4. The preparation method according to claim 3, characterized in that Step 3) Add 9 times the amount of water and boil twice.

5. The preparation method according to claim 3, characterized in that Step 4) Add ethanol to make the alcohol content 60%, and refrigerate for 36 hours.

6. The preparation method according to any one of claims 2 to 5, characterized in that The pharmaceutically acceptable excipients include one or more of flavoring agents, diluents, lubricants, disintegrants, dispersants, thickeners, preservatives, and colorants.

7. The preparation method according to any one of claims 2 to 5, characterized in that The clinically acceptable dosage form is one of tablets, pills, granules, capsules and syrups.

8. Use of the Chinese medicine composition according to any one of claims 1 to 7 in the preparation of medicines for treating coronary heart disease and angina pectoris.

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