CN116942771B - Traditional Chinese medicine composition for treating coronary heart disease and application thereof - Google Patents
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Abstract
The invention provides a traditional Chinese medicine composition for treating coronary heart disease, which comprises the following medicine formula in parts by weight: 8-12 parts of semen trichosanthis, 8-12 parts of coix seed, 5-7 parts of hemerocallis, 5-7 parts of water river sword, 5-7 parts of ailanthus altissima swingle, 2-4 parts of Japanese cayratia herb, 2-4 parts of pinellia tuber, 2-4 parts of radix sophorae falvescentis and 1-2 parts of liquorice. The preparation method comprises the following steps: decocting all the prescription medicines with water twice, wherein the first time is to be decocted with 10-12 times of water for 2-3 hours, the second time is to be decocted with 8-10 times of water for 1-3 hours, the decoctions are combined, filtered, and the filtrate is concentrated to thick paste with the relative density of 1.20-1.25. The patient treated by the traditional Chinese medicine composition has obviously reduced angina pectoris attack frequency, obviously reduced attack duration, small side effect, obvious improvement of blood lipid index, more than 90% of effective rate after clinical treatment and obvious effect.
Description
Technical Field
The invention relates to the field of traditional Chinese medicine compositions, in particular to a traditional Chinese medicine composition for treating coronary heart disease and application thereof.
Background
Coronary heart disease is a heart disease that occurs due to myocardial ischemia, hypoxia or necrosis caused by lumen stenosis or occlusion due to atherosclerosis of coronary arteries, and is therefore also called ischemic heart disease. Clinical research and study of modern medicine show that myocardial tissue hypoxia and ischemia caused by coronary insufficiency is a direct cause of the disease, and simultaneously, factors such as emotional agitation, physical labor, coldness, satiation and the like in daily life can induce the disease. The Chinese medicinal composition can show various clinical symptoms such as chest distress and chest pain, palpitation, shortness of breath and the like during the attack, and has great harm to the health of patients.
At present, western medicine is mainly used for clinical treatment such as anticoagulation, lipid reduction, coronary expansion and the like, and clinical symptoms of patients can be relieved in a short time, but the long-term treatment effect is poor, and adverse reactions of various medicines are easily caused after long-term administration, so that the clinical treatment effect is influenced, and the prognosis of the patients is not improved.
In recent years, with the deep research of traditional Chinese medicines, the method for treating coronary heart disease in traditional Chinese medicine is actively explored clinically. Coronary heart disease and angina pectoris belong to the categories of 'true heart pain', 'chest stuffiness and pain', and the like, and deficiency of qi and blood and heart vessel stasis are main causes of pathopoiesia, so the treatment should follow the principles of tonifying middle-jiao and Qi, activating blood and dissolving stasis.
Numerous formulations have been disclosed in the prior art, for example: CN109602866a discloses a traditional Chinese medicine composition for treating coronary heart disease, a preparation method and application thereof, wherein the active components of the traditional Chinese medicine composition are prepared from the following raw materials in parts by weight: 30-50 parts of sandalwood, 30-50 parts of safflower, 50-70 parts of szechuan lovage rhizome, 50-70 parts of Chinese angelica, 40-60 parts of tabasheer, 40-60 parts of grassleaf sweelflag rhizome, 10-20 parts of borneol and 30-50 parts of liquoric root.
CN114887024a discloses a traditional Chinese medicine composition for treating coronary heart disease, which is prepared from the following traditional Chinese medicine raw materials: 30-40 parts of astragalus membranaceus, 20-30 parts of poria with hostwood, 20-30 parts of bighead atractylodes rhizome, 15-25 parts of cassia twig, 10-20 parts of ginger, 20-30 parts of achyranthes root, 10-20 parts of fructus aurantii, 10-20 parts of dried orange peel, 20-30 parts of red paeony root, 10-20 parts of ligusticum wallichii, 5-15 parts of peach seed, 5-15 parts of safflower, 20-30 parts of ginseng, 20-30 parts of grifola, 20-30 parts of semen lepidii, 5-10 parts of radix trichosanthis, 20-30 parts of perilla seed, 10-20 parts of semen brassicae and 20-30 parts of radix peucedani.
The above formula has advantages and disadvantages, so that the development of a novel traditional Chinese medicine composition for treating coronary heart disease and a preparation method and application thereof have important significance.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a traditional Chinese medicine composition formula for treating coronary heart disease, and a preparation method and application thereof. The traditional Chinese medicine composition provided by the invention has the advantages of simple preparation method, unique formula, synergistic effect between the formulas, and remarkable effect, and the effective rate of the traditional Chinese medicine composition after clinical treatment can reach more than 90%.
The technical scheme of the invention is as follows:
a traditional Chinese medicine composition for treating coronary heart disease comprises semen trichosanthis and pinellia ternate, and the medicine formula comprises the following components in parts by weight: 8-12 parts of semen trichosanthis, 8-12 parts of coix seed, 5-7 parts of hemerocallis, 5-7 parts of water river sword, 5-7 parts of ailanthus altissima swingle, 2-4 parts of Japanese cayratia herb, 2-4 parts of pinellia tuber, 2-4 parts of radix sophorae falvescentis and 1-2 parts of liquorice.
The preferred pharmaceutical formulation in example 1 is as follows in parts by weight: 10 parts of semen trichosanthis, 10 parts of coix seed, 6 parts of hemerocallis root, 6 parts of water river sword, 6 parts of ailanthus altissima, 3 parts of Japanese cayratia herb, 3 parts of pinellia tuber, 3 parts of radix seu herba Chuangensis and 2 parts of liquorice.
The preferred pharmaceutical formulation in example 5 is as follows in parts by weight: 12 parts of semen trichosanthis, 12 parts of coix seed, 7 parts of hemerocallis root, 7 parts of water river sword, 7 parts of ailanthus altissima, 4 parts of cayratia japonica, 4 parts of pinellia ternate, 4 parts of radix sophorae flavescentis and 2 parts of liquorice.
The preparation method comprises the following steps: decocting all the prescription medicines with water twice, wherein the first time is to be decocted with 10-12 times of water for 2-3 hours, the second time is to be decocted with 8-10 times of water for 1-3 hours, the decoctions are combined, filtered, and the filtrate is concentrated to thick paste with the relative density of 1.20-1.25.
Further, the traditional Chinese medicine composition is prepared into one of tablets, granules, dripping pills, capsules and oral liquid according to the conventional technology in the field.
The invention also provides application of the traditional Chinese medicine composition in preparing medicines for treating coronary heart disease.
Further, the application of the traditional Chinese medicine composition in preparing the medicines for reducing the levels of CK, CK-MB and LDH in rat serum and prolonging the hypoxia tolerance time of mice is provided.
The formula of the invention has the following compatibility principle:
root of Hemerocallis: cool in nature, sweet in flavor and toxic. Enter spleen meridian, liver meridian and bladder meridian. Has effects of clearing heat, promoting diuresis, cooling blood, stopping bleeding, removing toxic substance, and relieving swelling.
Shui He sword: cold nature, slightly bitter and astringent taste. Enter meridian and are temporary deficiency. Has effects of cooling blood, stopping bleeding, promoting urination, and treating stranguria.
Herba Eichhorniae, bitter, astringent, cool, etc. Enter stomach, large intestine and small intestine meridians. Has the effects of stopping Li, stopping bleeding, clearing heat and eliminating dampness, etc. Can be used for treating hematochezia, leukorrhagia, turbid urine, hematuria, and metrorrhagia.
Root-penetrating vine: bitter, pungent and flat; liver and heart channel returning; has the effects of detumescence and acesodyne, relaxing tendons and activating collaterals, dispelling wind-dampness, etc., and can be used for treating wet arthralgia, limb numbness, lumbar muscle strain, ischialgia, multiple carbuncle swelling, etc.
Cayratia japonica: whole grass of Ampelopsis grossedentata belonging to Vitaceae. Cold nature, bitter and sour. It enters heart meridian, liver meridian and stomach meridian. Has effects of clearing heat, detoxicating, promoting diuresis and detumescence. Belongs to the category of heat-clearing and dampness-drying herbs. Antiviral, anti-inflammatory, antipyretic; antibacterial; has anticoagulant and immunity regulating effects.
Semen Trichosanthis, sweet and cold. Enter lung, stomach and large intestine meridians. Lung moistening, phlegm resolving, intestine smoothing and constipation relieving. Semen Trichosanthis is rich in oil, sterol, triterpene, saponin, protein and amino acids, and has effects in moistening lung, resolving phlegm, loosening bowel, and relieving constipation, and can be used for treating acute mastitis, pulmonary abscess, cough due to lung heat, yellow and thick phlegm, constipation, etc. Modern pharmacological researches also show that semen trichosanthis has various pharmacological effects such as anti-inflammatory and anti-tumor effects.
Pinellia ternate: the Chinese medicinal composition has the effects of removing dampness and resolving phlegm, calming the adverse-rising energy, relieving vomiting, relieving stuffiness and resolving masses and the like, has the characteristics of pungent taste, warm nature, spleen, stomach and lung channel, has the effects of drying dampness and resolving phlegm, calming the adverse-rising energy, relieving stuffiness and resolving masses and the like, and has pharmacological activities of relieving cough and asthma, eliminating phlegm, relieving cough and the like, and contains various chemical components such as volatile oils, organic acids, alkaloids, amino acids, flavonoids, saccharides, various trace elements and the like.
Semen Coicis: the Chinese medicinal composition has the effects of invigorating spleen, stomach and lung meridian, promoting diuresis, strengthening spleen, relaxing tendons, removing arthralgia, clearing heat, expelling pus, removing toxic substances, and resolving hard mass, and is mainly used for treating edema, beriberi, dribbling urine, diarrhea, rheumatalgia, spasm of tendons and vessels, flat wart and the like. Modern pharmacological researches show that the triglyceride component in coix seed has an anti-tumor effect, and in recent years, the coix seed is continuously and deeply researched at home and abroad, so that the coix seed has the effects of easing pain, resisting inflammation, reducing blood pressure, improving glycolipid metabolism, regulating intestinal flora, whitening and the like.
Licorice root: it has sweet and neutral nature and taste, and can restore heart, lung, spleen and stomach channels, has effects of invigorating spleen and replenishing qi, moistening lung and relieving cough, relieving pain, harmonizing various medicines, and relieving drug property, and can be used for treating spleen and stomach weakness, deficiency of middle-jiao, cough and asthma, carbuncle, toxic swelling, food and drug poisoning.
The formula of the invention is a formula for clearing heat, resolving dampness, clearing blood and cooling blood according to the principle of dialectical treatment of traditional Chinese medicine. In the recipe, semen trichosanthis has the effects of clearing heat and resolving phlegm, promoting qi circulation and resolving masses, coix seed has the effects of promoting diuresis and strengthening spleen, relaxing tendons and removing arthralgia, clearing heat and expelling pus, and removing toxin and resolving masses, and both are sweet in nature, can enter the two meridians of lung and stomach, and mainly has the effects of clearing heat and resolving phlegm and eliminating dampness; is taken as a monarch drug; the hemerocallis root has the effects of clearing heat and promoting diuresis, cooling blood and stopping bleeding, and detoxifying and relieving swelling; herba Eichhorniae has effects of relieving Li, stopping bleeding, clearing heat and eliminating dampness, and can be used for treating hematochezia, leukorrhagia, turbid urine, hematuria, metrorrhagia, etc. Shui He Sword is cold in nature and slightly bitter and astringent in taste. Has effects of cooling blood, stopping bleeding, promoting urination and treating stranguria; the three are synergistic and are used as ministerial drugs, so that the effect of clearing heat and eliminating dampness of the monarch drugs is enhanced, and the defect of the monarch drugs in cooling blood and stopping bleeding is overcome. Pinellia tuber has the effects of eliminating dampness and phlegm, lowering adverse qi, relieving vomiting, relieving stuffiness and resolving masses; the radix sophorae tonkinensis has the effects of relieving swelling and pain, relaxing tendons and activating collaterals, dispelling wind and dampness, clearing heat and detoxicating, promoting diuresis and relieving swelling, and the liquorice harmonizes the medicines, so that the medicines are used together as the auxiliary materials and the auxiliary materials, and the effects of clearing heat and detoxicating, reducing phlegm and eliminating dampness in the whole formula are enhanced. The recipe combines the medicines, has the functions of clearing heat, eliminating dampness, cooling blood and stopping bleeding, and has the functions of eliminating turbid dampness, eliminating phlegm and heat, regulating qi and promoting blood stasis.
Compared with the prior art, the invention has the advantages that:
1. clinical use effects prove that the frequency of angina pectoris attacks is obviously reduced, the duration of attacks is obviously reduced, side effects are small, blood fat indexes are obviously improved, the effective rate after clinical treatment can reach more than 90%, and the effect is obvious.
2. The pharmacological experiment result shows that the traditional Chinese medicine composition has a better treatment effect on experimental rat coronary heart disease, and can obviously reduce the serum CK, CK-MB and LDH levels of rats; rat coronary artery and cardiomyocyte histopathology picture display: the coronary artery vascular wall is uniform in morphology, endothelial cells are orderly arranged, inflammatory cell infiltration is avoided, surrounding myocardial cells are orderly arranged, the myocardial cells are full, cytoplasm is uniformly colored, the myocardial interstitium is free of edema, the hypoxia tolerance time of a mouse can be remarkably prolonged, and the anti-hypoxia effect is obvious.
3. The toxicity test of repeated administration of the traditional Chinese medicine composition for 3 months and the toxicity test of single administration by oral administration of rats show that the traditional Chinese medicine composition has high safety and no toxic or side effect.
4. Compared with the formulation of the comparative example, the invention has a plurality of unique additive components, and the addition of the medicaments and the formulation of other medicaments generate synergistic effect, thereby having better curative effect.
In a word, the traditional Chinese medicine composition provided by the invention is simple in preparation method and definite in action and effect.
The detailed structure of the present invention is further described below with reference to the accompanying drawings and detailed description.
Drawings
FIG. 1 is a photograph of rat coronary artery and myocardial cell histopathology (HE, ×200), wherein: a blank control group, a model control group, a comparative example 1 group, a comparative example 2 group, an example 1 group, and an F compound danxin tablet group. The blank control group has uniform coronary artery vascular wall morphology, ordered endothelial cell arrangement, no inflammatory cell infiltration, ordered peripheral myocardial cell arrangement, full myocardial cell, uniform cytoplasmic staining, no pathological changes such as edema of cardiac interstitial, the model control group has swollen and disordered arrangement of coronary endothelial cells, partial endomembrane shedding, denaturation and necrosis of peripheral myocardial cells accompanied by inflammatory cell infiltration, the comparative example 1 group has uniform coronary artery vascular wall morphology, ordered endothelial cell arrangement, slight edema of peripheral tissues and inflammatory cell infiltration, the comparative example 2 group has uniform coronary vascular wall morphology, ordered endothelial cell arrangement, no inflammatory cell infiltration, ordered peripheral myocardial cell arrangement, full myocardial cells, uniform cytoplasmic staining, no edema of cardiac interstitial, the example 1 group has uniform coronary vascular wall morphology, ordered endothelial cell arrangement, full myocardial cell, uniform cytoplasmic staining, no edema of cardiac interstitial, the compound salvia miltiorrhiza group has uniform coronary artery vascular wall morphology, ordered endothelial cell arrangement, no inflammatory cell infiltration, ordered peripheral myocardial cell arrangement, full myocardial cell staining, uniform myocardial interstitial staining, and no edema of cardiac interstitial.
Detailed Description
Example 1
A Chinese medicinal composition for treating coronary heart disease comprises the following components: the weight portions are as follows: 10 parts of semen trichosanthis, 10 parts of coix seed, 6 parts of hemerocallis root, 6 parts of water river sword, 6 parts of ailanthus altissima, 3 parts of Japanese cayratia herb, 3 parts of pinellia tuber, 3 parts of radix seu herba Chuangensis and 2 parts of liquorice.
The preparation method comprises the following steps: decocting all the raw materials in water twice, wherein the first time is 2 hours by adding 10 times of water, the second time is 1 hour by adding 8 times of water, mixing decoctions, filtering, and concentrating the filtrate to thick paste with the relative density of 1.20-1.25 (60 ℃); mixing Mel and water, stirring, adding sorbic acid 1g, and concentrating to obtain soft extract with relative density not lower than 1.35 (20deg.C).
Example 2 toxicity test of the oral administration of the Chinese medicinal composition of example 1 to rats
The purpose is as follows: the study is carried out according to the national GLP specification, and the acute toxicity reaction and death condition of SD rats after twice oral administration of the traditional Chinese medicine composition of the example 1 within 24 hours are observed, so that reference materials are provided for repeated administration toxicity tests.
Experimental materials
Test substance (test substance): traditional Chinese medicine composition of example 1 (Gu Yitang (Hunan) health science, inc.), clinical proposed dose: clinical proposed dose: 92.5g decoction pieces per day, the clinical intended use route: orally taken, 1 bag at a time, 3 times a day, and clinically taken as a treatment course: 1 month
Reagent: isoflurane (21121101, shenzhen Ruiword life technologies Co., ltd.), specification: 100 mL/bottle of experimental animal: SPF-class SD rats 40, male and female halves, body weight range at dosing: 180.3-205.9 g. (Hunan Laike Jingda laboratory animal Co., ltd., NO. 430727221101954557)
The test method comprises the following steps: 40 SPF-grade SD rats qualified in quarantine are selected, and the weight of the SPF-grade SD rats is 180.3-205.9 g, and the SPF-grade SD rats are bred in 475mmX1350 mm×200mm cages, wherein 5 SPF-grade SD rats are bred in each cage. Raising according to the environmental condition requirements of international (GB 14125-2010) SPF grade experimental animals, quarantining animals and adapting to the environment for 5 days. The body weight was randomly divided into 2 groups according to sex, a blank group and example 1 group (218 g crude drug/kg), each group being 20. The animals were fasted before the experiment without water inhibition for more than 12 hours, then were orally administered with pure water and the traditional Chinese medicine composition of example 1 respectively at 20mL/kg, and were administered 2 times a day, and the poisoning performance and characteristics, the toxic reaction occurrence and recovery time, the death condition, etc. of each group of animals were closely observed and recorded within 4 hours after administration, then were observed 2 times a day, once each in the morning and afternoon, and continuously observed for 14 days. Animals were weighed on day 4, day 7, day 10 and day 14 before and after the administration, respectively, and weight changes and death were recorded.
Test results: 1) Influence on general activity status, animal poisoning symptoms and death conditions: within 0-4 hours after oral gastric lavage administration, the behavior activity, the mental state and the diet of rats in the blank control group and the example 1 group are not obviously abnormal, and no related toxic reaction and animal death are observed. The rats in the blank group and the rats in the example 1 group showed no obvious abnormality in voluntary activity, mental state and diet, no related toxic reaction and no death of animals, which were observed continuously for 14 days after administration. 2) Influence on body weight: animals were weighed on day 4, day 7, day 10 and day 14 after dosing, and animals in group 1 were not statistically different from the contemporaneous placebo group in weight gain and were within normal gain range, indicating that oral administration of the traditional Chinese medicine composition of example 1 by SD rats had no significant effect on weight gain in rats. 3) Visual observations were generally dissected for SD rats at the end of the trial: no obvious abnormalities were seen on the surface and the section of each organ.
Conclusion: under the test conditions, the traditional Chinese medicine composition of the example 1 is orally infused into rats, the administration volume is 20mL/kg, the administration is carried out 2 times on the same day, the cumulative dose is 218g crude drug/kg, which is equivalent to 165 times of the dose of the adult clinical intended kg body weight (1.321 g crude drug/kg daily dose for adults), and the animals do not see related toxic reaction and death.
6. Results and analysis
6.1 effects on general activity status: within 0-4 hours after the end of intragastric administration, neither the placebo nor the SD rats of example 1 showed significant abnormalities in voluntary activity, mental state, and eating. The behavior activity, the mental state and the eating condition of the SD rats with the blank control group and the snakegourd heart nourishing paste are not obviously abnormal after the administration and are continuously observed for 14 days.
6.2 symptoms of poisoning and death in animals: no animal death was seen throughout the trial.
6.3 body weight: animals were weighed on day 4, day 7, day 10 and day 14 after dosing, and animals in group 1 showed no statistically significant differences in weight and weight gain within normal growth range compared to the contemporaneous placebo group, indicating that oral administration of the traditional Chinese medicinal composition of example 1 by SD rats had no significant effect on weight gain in rats, see tables 1, 2 and 3 in detail.
6.4 general anatomic examination results: after the test is finished, all test animals are killed by isoflurane anesthesia, and the animals are subjected to general anatomic examination, and the surface and section color, shape, size, texture and the like of each organ (lung, liver, kidney, spleen, heart, brain, skin and the like) are observed visually, so that the examination results show that no obvious abnormal condition is found on the surface and section of each organ.
7. Conclusion and evaluation
Under the test conditions, the traditional Chinese medicine composition of the example 1 is orally infused into rats, the administration volume is 20mL/kg, the administration is carried out 2 times on the same day, the cumulative dose is 218g crude drug/kg, which is equivalent to 165 times of the dose of the adult clinical intended kg body weight (1.321 g crude drug/kg daily dose for adults), and the animals do not see related toxic reaction and death.
Table 1 effect of the traditional Chinese medicine composition of example 1 on SD rat body weight (n=20,)
table 2 effect of the traditional Chinese medicinal composition of example 1 on female SD rat body weight (n=10,)
table 3 effect of the traditional Chinese medicinal composition of example 1 on body weight of male SD rats (n=10,)
example 2 toxicity test of the oral administration of the Chinese medicinal composition of example 1 by rats for 3 months
1. Purpose of investigation
The study adopts SD rats to orally administer the traditional Chinese medicine composition liquid medicine of the example 1 in different doses, the administration is carried out for 3 months (13 weeks), and the clinical adverse reaction possibly caused by the test object is predicted from the toxicity test result of the rats through 2 weeks of stopping administration and the recovery period, including the nature, degree, dose-response relation, time-response relation, reversibility and the like of the adverse reaction; judging the toxic target organ or target tissue to which the test substance is repeatedly administered; presuming a safe dose range for initial and repeat doses of the first clinical trial; prompting an index to be monitored in a clinical test; provides reference for monitoring and rescuing measures, clinical tests and clinical medication of toxic reaction in clinical tests.
2 Experimental materials
Test substance (test substance): the traditional Chinese medicine composition of example 1 (Gu Yitang (Hunan) health science and technology Co., ltd.) contains: 1g of extract corresponds to 4.47g of crude drug, and the clinical dosage is as follows: clinical proposed dose: 92.5g decoction pieces per day, the clinical intended use route: orally taken, 1 bag at a time, 3 times a day, and clinically taken as a treatment course: for 1 month, experimental animals: 80 SPF-class SD rats, each half male and female, have a body weight of 176.9-220.7 g and supply units: hunan Slaikuda laboratory animal Co., ltd, no.430727221102010738
3 test method
80 qualified SD rats are selected, the male and female rats are half, the weight is 176.9-220.7 g,475 multiplied by 350 multiplied by 200mm 3 Raising in cages, wherein 5 cages are used for each cage. Raising according to the environmental condition requirements of international (GB 14125-2010) SPF grade experimental animals, quarantining the experimental animals and raising the experimental animals in an environment-adaptive manner for 5 days. The animals were randomly divided into 4 groups according to sex weight, each group was 20 experimental animals, and the control group, the low, medium and high dose group (20.45, 40.90, 81.80g crude drug/kg) of example 1 were selected. The administration was performed by gavage in a volume of 15mL/kg for 3 months (13 weeks). The end of dosing (weekend 13) and end of recovery (weekend 15) were each planned to dissect 40 rats, male and female halves. The inspection items include: general clinical observations; body weight and food intake were measured; hematology, blood biochemistry, coagulation and organ coefficient measurement; histopathological examination.
Test results: during the test period, all experimental animals are euthanized according to the plan, and no experimental animal is abnormally dead during the test process.
General clinical observations: during the observation period, the dose groups of example 1 were compared with the contemporaneous blank control group, and no abnormal reaction related to drug toxicity was observed in the appearance signs, behavior activities, secretions of each cavity and the general condition of the experimental animals.
Weight of: compared with the blank control group at the same time, the dose groups in the example 1 have no obvious effect on the weight of rats.
Food intake: compared with the blank control group at the same time, the average feeding amount of rats is not obviously affected by each dose group in the embodiment 1.
Hematology examination: compared with the blank control group at the same time, the hematology index of each dosage group of the example 1 is not changed in a toxicological significance, and the result shows that the example 1 has no obvious effect on the hematology index of rats.
Biochemical examination of blood: compared with the blank control group at the same time, the blood biochemical indexes of each dosage group of the example 1 have no toxicologically significant change, and the result shows that the example 1 has no obvious effect on the blood biochemical indexes of rats.
Coagulation examination: compared with the blank control group at the same time, the coagulation index of each dosage group of the example 1 has no toxicologically significant change, and the result shows that the example 1 has no obvious effect on the coagulation index of rats.
Organ coefficients: compared with the blank control group at the same time, the organ coefficients of each dosage group of the example 1 have no obvious abnormality, and the result shows that the example 1 has no obvious influence on the organ coefficient index of rats.
General anatomy: no obvious change was observed in visual inspection of the surface, size, texture, etc. of the viscera of the experimental animals dissected in the low, medium, and high dose groups of the end-of-dose and recovery period blank control group and example 1.
Pathological examination: example 1 dissected at the end of dosing, recovery period the high dose group of experimental animals showed no significant differences compared to the contemporaneous placebo group and no toxicologically significant pathological changes were found.
Conclusion: under the test conditions, SD rats were orally administrated for example 13 months, and no significant drug-related toxicity response dose (NOAEL) was found to be 81.80g crude drug/kg (corresponding to 62 times the clinical proposed dose for 70kg adult, 9.8 times the equivalent dose).
Table 4 effect of example 1 on experimental animal body weight (g,)
table 5 the effect of example 1 on the average feed intake of experimental animals (g/day,)
TABLE 6 influence of example 1 on hematology of experimental animalsn＝10)
Note that: in comparison with the blank group, * P<0.05。
TABLE 7 influence of example 1 on the biochemical index of blood of experimental animalsn＝10)
Note that: in comparison with the blank group, * P<0.05， ** P<0.01。
table 8 implementationEXAMPLE 1 Effect on coagulation of Experimental animalsn＝10)
TABLE 9 influence of example 1 on organ coefficients of laboratory animalsg/g,n＝10)/>
Example 3: pharmacodynamic study data for the formulation of example 1
1. Effect of the formulation of example 1 on coronary heart disease model rats
1 purpose of test
The test is to replicate a coronary heart disease rat model, and administer different doses of the traditional Chinese medicine composition liquid medicine of the example 1 and the traditional Chinese medicine composition liquid medicine of the comparative example 2 to the rat model by lavage, observe the influence of the traditional Chinese medicine composition of the example 1 and the traditional Chinese medicine composition of the comparative example 2 on the coronary heart disease rat model, and provide pharmacological basis for clinical application.
Wherein the formulation of comparative example 1: the weight portions are as follows: 10 parts of semen trichosanthis, 10 parts of coix seed, and 6 parts of hemerocallis root. The preparation method is the same as in example 1.
Formulation of comparative example 2: 10 parts of semen trichosanthis, 10 parts of semen coicis, 6 parts of hemerocallis root, 3 parts of cayratia japonica, 3 parts of pinellia ternate and 2 parts of liquorice. The preparation method is the same as in example 1.
2.1 test materials
Test substance (test substance): the Chinese medicinal compositions (Gu Yitang (Hunan) of health science and technology Co., ltd.) of example 1 and comparative example 2, 1g of the extract contained crude drug 4.47g of crude drug, the paste, the clinical dose to be used: 92.5g decoction pieces/day; the clinical approach is as follows: the clinical approach is as follows: orally taken, 1 bag at a time, 3 times a day, and clinically taken as a treatment course: for 1 month, positive control, name: compound red sage root tablet, specification: 0.32 g of 200 tablets, production unit: guangzhou Baiyunshan and Xuang XUN Chinese medicine Co., ltd
Experimental animals: SPF-grade SD male rats, 80, used weight range: 176.1-238.4g; (Hunan Laike Jingda laboratory animal Co., ltd.)
Test method
Modeling and administration
80 qualified SD rats are selected, males are randomly selected, 10 rats are selected as blank control groups, the rest rats are fed with high-fat feed, the continuous 6 weeks are carried out, the interval 24h after 6 weeks is carried out, 30 (10) IU/kg of pituitary posterior elements are injected intraperitoneally, the continuous 3 times are carried out, and the success of the preparation of a rat Coronary Heart Disease (CHD) model is determined by taking the downward shift of an electrocardiogram ST segment and the change of T waves as the standard. The successful rats were randomly divided into model control groups, example 1 group and comparative example 2 group, compound red sage root tablet group, 10 each. The drug group was infused with the corresponding doses of drug at 10mL/kg, and the blank control group and the model control group were infused with the equal volumes of purified water at 1 time a day for 4 weeks.
3.1 design of dosage of test and control
The clinical planned dose of the traditional Chinese medicine compositions of the example 1 and the comparative example 2 is 92.5g decoction pieces per day, according to Wei Wei, the pharmaceutical experimental methodology, fourth edition, the conversion table of the body surface area of equivalent doses among animal species, the equivalent dose of rats is adult drug amount×0.018×5=8.325 g crude drug per kg, and the equivalent dose of compound salvia miltiorrhiza tablet=adult drug amount×0.018×5=0.260 g per kg.
Table 10 dose schedule for each group
Preparing the medicine:
the Chinese medicinal compositions of example 1 and comparative example 2: weighing 5.7g of each of the fluid extracts of the traditional Chinese medicine compositions of the example 1 and the comparative example 2, adding pure water, stirring and mixing uniformly until the volume reaches 30mL (0.19 g extract/mL), and stirring uniformly before use for 1 time a day.
Compound red sage root tablet group: taking 10 granules (3.2 g) of compound red sage root tablet, adding pure water, stirring and uniformly mixing until 123mL (0.026 g/mL) is obtained, and stirring uniformly before use for 1 time a day.
4.4 detection index
General observations: after molding, the appearance signs, behavior activities, secretions, excretions, dietary conditions and the like of each group of experimental animals are closely observed and recorded after administration. If the experimental animal is found to die or dying, the experimental animal should be observed in a timely manner. The body weight of the experimental animal was weighed weekly.
Fasted for more than 12 hours after the last administration, the abdominal aorta is sampled and tested for Lactate Dehydrogenase (LDH), phosphocreatine kinase (CK) and creatine kinase isozyme (CK-MB), and the thoracic aorta and the heart are taken for histopathological examination.
4.5 results calculation and statistics
Data statistics, test data, using SPSS16.0 softwareThe comparison between the groups is firstly performed by normal and variance alignment, the variance alignment is checked by adopting a single-factor analysis of variance when the variance is uniform and the normal is met, the Nonparaametric T is checked when the variance is not met, the Tamhane's T2 is checked when the variance is not uniform and the Kruskal-Wallis is checked if the variance is not met, and the Mann-Whitney is used for comparison analysis. P (P)<0.05 represents a statistically significant, P<0.01 indicates that the difference examined is of very significant significance.
5. Experimental results
5.1 Effect on serum CK, CK-MB and LDH levels in rats with coronary heart disease models
Compared with the blank control group, the serum CK, CK-MB and LDH levels of the rats in the model control group are obviously increased (P < 0.01); compared with the model control group, the serum CK, CK-MB and LDH levels of rats in the group of comparative example 1, the group of comparative example 2, the group of example 1 and the compound salvia tablet group are obviously reduced (P <0.05 or P < 0.01). LDH, CK, CK-MB is an enzymatic index related to myocardial injury, and can be released into blood when myocardial cells are damaged, so that the serum level is increased. The results show that the groups of comparative example 1, comparative example 2 and example 1 have obvious therapeutic effect on coronary heart disease model rats. The results are shown in Table 11.
Table 11 influence of groups on the biochemical index of rats with coronary heart disease modeln＝10)
Note that: in comparison to the blank control, "×" indicates P <0.01, in comparison to the model control, "Δ" indicates P <0.05, "Δ" indicates P <0.01, and "#" indicates P <0.05 in comparison to comparative example 1; comparison with comparative example 2 "" means P <0.05
5.4 histopathological observations of coronary artery and myocardial cells in the coronary heart disease model rat
The rat coronary artery vessel wall of the blank control group has uniform morphology, ordered endothelial cell arrangement, no inflammatory cell infiltration, complete peripheral myocardial cell arrangement, full myocardial cell, uniform cytoplasmic staining, no edema of the myocardial interstitium and other pathological changes; model control group animal coronary artery endothelial cells are swollen and arranged in disorder, partial endomembrane is shed, and peripheral myocardial cells are denatured and necrotized and are accompanied by inflammatory cell infiltration; compared with the model control group, each administration group has obvious treatment effect, wherein the treatment effect of the embodiment 1 group is the best, and the blank control group, the embodiment 1 group, the compound red sage root tablet group, the comparative example 2 group, the comparative example 1 group and the model control group are sequentially arranged. The pathological picture is shown in figure 1.
Experimental results: effects on coronary heart disease model rats: the serum CK, CK-MB and LDH levels of rats in the groups of example 1 and comparative example 2 are significantly increased (P < 0.01) compared with the blank control group; the serum CK, CK-MB and LDH levels of rats in the groups of the example 1, the comparative example 2 and the compound red sage root tablet group are obviously reduced (P <0.05 or P < 0.01) compared with the model control group; example 1 has more remarkable effect (P < 0.05) compared with comparative example 1 and comparative example 2, and comparative example 2 has better effect compared with comparative example 1 without remarkable difference (P > 0.05); the results of the histopathological examination showed that: the groups of example 1 and comparative example 2 have significant repair effects on coronary artery and myocardial cells of rats with coronary heart disease and the effect of example 1 is most significant.
6. Conclusion(s)
The experimental results show that: under the test condition, the groups of the example 1, the comparative example 1 and the comparative example 2 can obviously reduce the levels of CK, CK-MB and LDH (P <0.05 or P < 0.01) in serum of a rat with the coronary heart disease model, improve the coronary artery and myocardial cytopathy degree of the rat with the model, and have obvious therapeutic effect on the rat with the coronary heart disease model. Example 1 has a more remarkable effect (P < 0.05) than comparative examples 1 and 2.
2. Hypoxia tolerance test
1. Purpose of investigation
In the experiment, the traditional Chinese medicine composition liquid medicines of the example 1 and the comparative example 2 are administrated to rats through gastric lavage, the anti-hypoxia effect of the traditional Chinese medicine composition liquid medicines of the example 1 and the comparative example 2 on mice is observed, and an experimental basis is provided for clinical application.
Wherein the formulation of comparative example 1: the weight portions are as follows: 10 parts of semen trichosanthis, 10 parts of coix seed, and 6 parts of hemerocallis root. The preparation method is the same as in example 1.
Formulation of comparative example 2: the weight portions are as follows: the formula comprises the following components: 10 parts of semen trichosanthis, 10 parts of semen coicis, 6 parts of hemerocallis root, 3 parts of cayratia japonica, 3 parts of pinellia ternate and 2 parts of liquorice. The preparation method is the same as in example 1.
2.1 test materials
Test substance (test substance): the Chinese medicinal compositions (Gu Yitang (Hunan) of health science and technology Co., ltd.) of example 1 and comparative example 2, 1g of the extract contained crude drug 4.47g of crude drug, the paste, the clinical dose to be used: 92.5g decoction pieces/day; the clinical approach is as follows: orally taken, 1 bag at a time, 3 times a day, and clinically taken as a treatment course: positive control drug 1 month, name: compound red sage root tablet, specification: 0.32 g of 200 tablets, production unit: guangzhou Baiyunshan and Xuang XUN Chinese medicine Co., ltd
Experimental animals: SPF-grade ICR mice were used in 60 halves, with a weight range: 20.1-24.2 g; (Hunan Laike Jingda laboratory animal Co., ltd.)
Sodium lime as main reagent, manufacturer: shanghai five-four chemical reagent Co., ltd
4 test method
4.1 grouping and administration
50 ICR mice qualified for quarantine are selected, and each half of the mice is randomly divided into 5 groups according to sex weight, wherein the groups are respectively a blank control group, a snakegourd fruit heart nourishing paste low, medium and high dose group and a compound red sage root tablet group, and each group comprises 10 mice. After grouping, each group of mice is respectively infused with corresponding medicines according to 20mL/kg, and the blank control group is infused with equal volume of pure water for 1 time/day, and the administration is carried out for 7 days continuously. Immediately after the last 60min of dosing, each group of mice was placed into a 250mL sealed bottleneck (1/bottle) containing 10g of soda lime, and the mice were observed and recorded for hypoxia-resistant survival time.
4.2 dose setting
The clinical planned dose of example 1 and comparative example 2 was 92.5g crude drug/day, and according to Wei Wei, the fourth edition, the table of equivalent dose body surface area between animal species was converted into mouse clinical equivalent dose=adult dose×0.0026× 50= 12.025g crude drug/kg. Equivalent dose of compound red sage root tablet = adult dose x 0.0026 x 50 = 0.374g/kg, see table 12 for details.
Table 12 design table for each dose
4.3 preparation method of medicine:
compound red sage root tablet group: taking 5 granules (1.6 g) of compound red sage root tablet, adding pure water, stirring and uniformly mixing until 85mL (0.019 g/mL) is obtained, and stirring uniformly before use for 1 time a day. The Chinese medicinal compositions of example 1 and comparative example 2: 2.6g of each of the fluid extracts of the Chinese medicinal compositions of example 1 and comparative examples 1 and 2 was weighed, and mixed with pure water to 20mL (0.13 g extract/mL) with stirring, 1 time a day, and stirred well before use.
4.4 detection index
General observations: after molding, the appearance signs, behavior activities, secretions, excretions, dietary conditions and the like of each group of experimental animals are closely observed and recorded after administration. If the experimental animal is found to die or dying, the experimental animal should be observed in a timely manner.
Detecting the index: immediately after the last 60min of dosing, each group of mice was placed into a 250mL sealed bottleneck (1/bottle) containing 10g of soda lime, and the mice were observed and recorded for hypoxia-resistant survival time.
5 test results
Compared with the blank control group, the mice in the example 1 have significantly prolonged hypoxia tolerance time (P < 0.01), the example 1 has a certain hypoxia tolerance effect compared with the comparison examples 1 and 2, the example 1 has more obvious effect (P < 0.05) compared with the comparison examples 1 and 2, and the comparison example 2 has better effect compared with the comparison example 1 but has no obvious difference (P > 0.05). See Table 13 for details.
TABLE 13 influence of groups on the hypoxia tolerance time of micen＝10)
Note that: in comparison to the blank group, "x" means P <0.05, "x" means P <0.01; comparison of "#" with comparative example 1 indicates P <0.05; comparison with comparative example 2 "" means P <0.05
6. Conclusion(s)
Under the test conditions, the group of the example 1 can prolong the hypoxia tolerance time of the mice to a significant extent. The traditional Chinese medicine composition of the embodiment 1 has obvious anti-hypoxia effect.
EXAMPLE 4 clinical Studies
Clinical analysis data of the Chinese medicinal composition of example 1 of the present invention
122 patients with coronary heart disease are selected for observation according to the selection criteria, and are divided into an example 1 and a control group according to a random method, wherein 40 patients with male patients in the example 1, 21 patients with female patients with ages of 43-75 years, and average ages (60.15 +/-2.13) years; the disease course is 2 months to 9 years, and the average (5.25+/-1.13) years. In the control group, 42 male patients and 19 female patients were aged 44-77 years, the average age (61.28 + -2.27) years, the course of the disease was 3 months-10 years, and the average age (5.16+ -1.17) years. The two groups were not significantly different in terms of age and course of disease, and were not statistically different (P > 0.5).
Diagnosis standard Western medicine diagnosis is based on the diagnosis standard of coronary heart disease in ischemic heart disease naming and diagnosis standard made by International Association of heart society and clinical naming standardization of world health organization; the diagnosis of traditional Chinese medicine is based on the diagnosis standard of chest stuffiness and pains in the traditional Chinese medicine diagnosis curative effect standard.
Inclusion criteria 1) meets the diagnostic criteria of the traditional Chinese and western medicine; 2) Age 40-80 years old;
exclusion criteria 1) those who received anticoagulation treatment within 1 month; 2) Combining myocardial infarction and other heart diseases; 3) Chest pain due to non-cardiac causes; 4) Receiving percutaneous coronary intervention; 5) Patients with severe mental diseases or unconsciousness and incapacitation of being matched with treatment; 6) Patients with malignant tumors; 7) Combining liver and kidney dysfunction and serious diseases of important tissues and organs; 8) Allergic or other contraindications to the medication of the study; 9) Positive pregnant or lactating female patients.
Treatment method Western medicine control group is given metoprolol succinate once daily, and 47.5mg each time is taken orally; the traditional Chinese medicine composition in the example 1 is administered 1 bag at a time, 13g of the traditional Chinese medicine composition is administered in each bag (each bag corresponds to 30.83g of decoction pieces), 3 times a day, and 2 groups of patients are continuously treated for 1 month.
Efficacy criteria 1) efficacy of disease: the effect is shown: the clinical symptoms basically disappear, the angina pectoris attack frequency is reduced by more than or equal to 70 percent, and the electrocardiogram is basically recovered to be normal; the method is effective: the clinical symptoms are improved, the angina pectoris attack frequency is reduced by more than or equal to 50 percent, the original flat T wave of the electrocardiographic examination becomes upright, and the ST segment is raised by more than 0.05mv; invalidation: the above standard or exacerbation is not achieved after treatment. Total effective rate= (significant effect + effective)/total number of treatment cases x 100% 2) electrocardiogram efficacy: the medicine is prepared by referring to the national traditional Chinese medicine and western medicine combination treatment of coronary heart disease, angina pectoris and arrhythmia seat talk in 1979, and has obvious effect: the electrocardiogram is approximately recovered to be normal; the method is effective: the S-T section rises by more than 0.05mv but does not reach the normal level, the main lead is inverted to lighten the T wave or is changed from flat to upright, and the conduction block is improved; invalidation: the electrocardiogram is unchanged. Total effective rate = (effective + effective)/total number of treatment cases x 100%
The observation index 1) observes the angina pectoris attack before and after the treatment of 2 groups of patients; 2) The blood lipid index (TC, TG, LDL-C) changes before and after treatment; 3) Adverse reactions (nausea, vomiting, headache, dizziness, abdominal discomfort, facial flushing). Statistical methods: the study adopts SPSS22.0 statistical software to carry out arrangement and analysis, the t test is used for comparing metering data, and the x is used for comparing counting data 2 Checking; p (P)<0.05 indicates a statistical significance.
Results
The disease efficacy of group 2 patients is compared to Table 14.
Table 14 comparative efficacy of disease in group 2 patients [ example (%), number of people outside brackets, percentage in brackets ]
| Group of | Number of examples | Has obvious effect | Effective and effective | Invalidation of | Total effective rate/% |
| Control group | 61 | 12(19.67) | 38(62.30) | 11(18.03) | 50(81.97) |
| Example 1 | 61 | 23(37.70) | 36(59.02) | 2(3.28) | 59(96.72)* |
Note that: compared with the control group, "x" indicates P <0.05
Electrocardiogram curative effect comparison of 2 groups of patients is shown in table 15
Table 15 Electrocardiogram efficacy of group 2 patients comparative [ example (%), number of people outside brackets, percentage inside brackets ]
| Group of | Number of examples | Has obvious effect | Effective and effective | Invalidation of | Total effective rate/% |
| Control group | 61 | 18(29.51) | 30(49.18) | 13(21.31) | 48(78.69) |
| Example 1 | 61 | 28(45.90) | 30(49.18) | 3(4.92) | 58(95.08)* |
Note that: compared with the control group, "x" indicates P <0.05
The comparison of angina pectoris attacks before and after treatment for group 2 patients is shown in Table 16
Table 16 comparison of the frequency and duration of angina attacks before and after treatment (x.+ -. S) for group 2 patients
Note that: compared to the pre-treatment group, "x" indicates P <0.05; compared with the control group after treatment, "#" indicates P <0.05
Comparison of blood lipid level changes before and after treatment of group 2 patients
Table 17 group 2 comparison of changes in TC, TG, LDL-c levels before and after treatment (x.+ -. S, mmol/L)
| Group of | Time | TC | TG | LDL-c |
| Control group | Before treatment | 6.45±1.41 | 2.47±0.67 | 3.95±0.78 |
| (61 example) | After treatment | 5.53±0.93* | 1.73±0.45* | 2.65±0.60* |
| Observation group | Before treatment | 6.41±1.33 | 2.50±0.64 | 3.93±0.81 |
| (61 example) | After treatment | 4.62±0.71*# | 1.21±0.28#* | 1.64±0.34*# |
Note that: compared to the pre-treatment group, "x" indicates P <0.05; compared with the control group after treatment, "#" indicates P <0.05
Adverse reaction occurrence comparison of group 2 patients
Table 18 comparative adverse reaction occurrence of group 2 patients [ example (%)
| Group of | Number of examples | Nausea and vomiting | Headache and dizziness | Abdominal discomfort | Facial flushing | Yield/% |
| Control group | 61 | 3(4.92) | 2(3.28) | 2(3.28) | 1(1.64) | 8(13.12) |
| Example 1 | 61 | 0(0.0) | 0(0.0) | 0(0.0) | 1(1.64) | 1(1.64)* |
Note that: compared with the control group, "x" indicates P <0.05
The treatment effect and the electrocardiogram effect of the group 1 are obviously better than those of the control group, the treatment frequency of angina pectoris is reduced, the duration is shortened (P < 0.05) and the blood lipid index is improved compared with those of the control group, the treatment effect of the group 1 is more obvious (P < 0.05) than that of the control group, and the treatment effect of the group 1 is less than that of the control group (P < 0.05). The embodiment 1 has better curative effect on coronary heart disease, can effectively reduce the blood lipid level of patients, relieve atherosclerosis, alleviate clinical symptoms, and has smaller adverse reaction and higher safety.
Example 5
A Chinese medicinal composition for treating coronary heart disease comprises the following components: the weight portions are as follows: 12 parts of semen trichosanthis, 12 parts of coix seed, 7 parts of hemerocallis root, 7 parts of water river sword, 7 parts of ailanthus altissima, 4 parts of cayratia japonica, 4 parts of pinellia ternate, 4 parts of radix sophorae flavescentis and 2 parts of liquorice.
The preparation method is similar to that of example 1 in terms of therapeutic effect, and is not described here.
The foregoing is a specific embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art should be able to apply equivalents and modifications to the technical solution and the concept thereof within the scope of the present invention as defined in the appended claims.
Claims (7)
1. A traditional Chinese medicine composition for treating coronary heart disease comprises semen trichosanthis and pinellia ternate and is characterized in that the medicine formula comprises the following components in parts by weight: 8-12 parts of semen trichosanthis, 8-12 parts of coix seed, 5-7 parts of hemerocallis, 5-7 parts of water river sword, 5-7 parts of ailanthus altissima swingle, 2-4 parts of Japanese cayratia herb, 2-4 parts of pinellia tuber, 2-4 parts of radix sophorae falvescentis and 1-2 parts of liquorice.
2. The traditional Chinese medicine composition for treating coronary heart disease according to claim 1, wherein the medicine formula comprises the following components in parts by weight: 10 parts of semen trichosanthis, 10 parts of coix seed, 6 parts of hemerocallis root, 6 parts of water river sword, 6 parts of ailanthus altissima, 3 parts of Japanese cayratia herb, 3 parts of pinellia tuber, 3 parts of radix seu herba Chuangensis and 2 parts of liquorice.
3. The traditional Chinese medicine composition for treating coronary heart disease according to claim 1, wherein the medicine formula comprises the following components in parts by weight: 12 parts of semen trichosanthis, 12 parts of coix seed, 7 parts of hemerocallis root, 7 parts of water river sword, 7 parts of ailanthus altissima, 4 parts of cayratia japonica, 4 parts of pinellia ternate, 4 parts of radix sophorae flavescentis and 2 parts of liquorice.
4. The Chinese medicinal composition for treating coronary heart disease according to any one of claims 1 to 3, which is characterized by comprising the following preparation method: decocting all the prescription medicines with water twice, wherein the first time is to be decocted with 10-12 times of water for 2-3 hours, the second time is to be decocted with 8-10 times of water for 1-3 hours, the decoctions are combined, filtered, and the filtrate is concentrated to thick paste with the relative density of 1.20-1.25.
5. The Chinese medicinal composition for treating coronary heart disease according to any one of claims 1-3, wherein the Chinese medicinal composition is formulated into one of a tablet, a granule, a drop pill, a capsule and an oral liquid according to conventional techniques in the art.
6. Use of a Chinese medicinal composition according to any one of claims 1-3 for the preparation of a medicament for the treatment of coronary heart disease.
7. The use of claim 6, wherein the use of the Chinese medicinal composition in the preparation of a medicament for reducing serum CK, CK-MB, LDH levels in rats and prolonging hypoxia tolerance time in mice is provided.
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| CN103656007A (en) * | 2013-11-29 | 2014-03-26 | 刘艺 | Traditional Chinese medicine formula for treating coronary heart disease |
| CN106581462A (en) * | 2015-10-15 | 2017-04-26 | 吴志锋 | Traditional Chinese medicine composition for treating coronary heart disease |
| CN105148206A (en) * | 2015-10-22 | 2015-12-16 | 周佰芹 | Traditional Chinese medicine for treating coronary heart disease |
| CN106421702A (en) * | 2016-11-01 | 2017-02-22 | 张志明 | Traditional Chinese medicine composite for treating coronary heart disease |
| CN106924471A (en) * | 2017-03-29 | 2017-07-07 | 辽宁中医药大学附属医院 | A kind of Chinese medicine preparation for causing the turbid coronary heart disease of insufficiency of the spleen phlegm by atherosclerosis for treating |
| CN109954093A (en) * | 2017-12-22 | 2019-07-02 | 天津春福河生物科技有限公司 | A kind of prescription for treating coronary heart disease |
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