CN117643605A - Traditional Chinese medicine composition for treating coronary heart disease with syndrome of qi deficiency and blood stasis - Google Patents
Traditional Chinese medicine composition for treating coronary heart disease with syndrome of qi deficiency and blood stasis Download PDFInfo
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Abstract
The invention discloses a traditional Chinese medicine composition I and a traditional Chinese medicine composition II for treating coronary heart disease due to qi deficiency and blood stasis, and medical applications thereof. The traditional Chinese medicine composition I comprises the following raw materials: 400-700 parts of astragalus membranaceus, 500-800 parts of ginkgo leaves, 50-250 parts of red sage root and 150-350 parts of earthworm; the traditional Chinese medicine composition II comprises 50-120 parts by weight of astragalus extract, 10-30 parts by weight of ginkgo leaf extract, 10-35 parts by weight of red sage root extract and 25-60 parts by weight of earthworm extract.
Description
Cross Reference to Related Applications
The present patent application claims the priority of chinese invention patent application No. CN202311258131.5 filed at 2023, 9 and 27, the entire contents of which are incorporated herein by reference.
Technical Field
The invention belongs to the field of traditional Chinese medicines and medicine, and in particular relates to a traditional Chinese medicine composition for treating coronary heart disease due to qi deficiency and blood stasis.
Background
Coronary atherosclerotic heart disease (coronary heart disease) refers to heart disease caused by stenosis or blockage of blood vessels due to coronary atherosclerosis or by ischemia or necrosis of the heart muscle due to functional changes (spasms) in the coronary arteries.
The traditional Chinese medicine has certain advantages in treating coronary heart disease, and generally takes qi-tonifying and blood-activating as therapeutic principles. The Chinese patent application with publication No. CN103393934A (11 months and 20 days of publication No. 2013) discloses a medicine for treating coronary heart disease, which consists of 30-50g of rhizoma corydalis, 25-45g of nutgrass galingale rhizome, 35-45g of astragalus root, 20-40g of tulip, 25-45g of kudzuvine root, 30-50g of cattail pollen, 25-35g of red sage root, 25-35g of red paeony root, 20-40g of rhizoma alismatis, 15-25g of earthworm, 25-35g of snakegourd fruit, 25-35g of basil and the like. Also, as in chinese patent application publication No. CN111437350a (24 days of 7 months of 2020), a Chinese medicinal preparation for treating cardiovascular and cerebrovascular diseases is disclosed, which comprises radix Ginseng, radix astragali, radix Salviae Miltiorrhizae, pheretima, hirudo, radix Angelicae sinensis, rhizoma corydalis, radix Paeoniae alba, fructus Phyllanthi, rhizoma Chuanxiong, pollen Typhae, semen Persicae, rhizoma Gastrodiae, folium Ginkgo, fructus crataegi, radix Puerariae, semen Cassiae, and Mel.
The traditional Chinese medicine composition has complex prescription, more than ten kinds of medicines and more than ten kinds of medicines; not only increases the burden of patients, but also is inconvenient for preparation.
Disclosure of Invention
In order to overcome the defects of the prior art, the invention provides a traditional Chinese medicine composition for treating coronary heart disease due to qi deficiency and blood stasis. The traditional Chinese medicine composition has simple formula and definite curative effect.
In order to achieve the aim of the invention, the invention adopts the following technical scheme:
a traditional Chinese medicine composition I for treating coronary heart disease with qi deficiency and blood stasis comprises the following traditional Chinese medicinal materials in parts by weight:
400-700 parts of astragalus membranaceus, 500-800 parts of ginkgo leaves, 50-250 parts of red sage root and 150-350 parts of earthworm.
Preferably, the traditional Chinese medicine composition I comprises the following traditional Chinese medicinal materials in parts by weight:
450-650 parts of astragalus root, 500-700 parts of ginkgo leaf, 100-250 parts of red sage root and 200-350 parts of earthworm.
More preferably, the raw materials of the traditional Chinese medicine composition I comprise the following traditional Chinese medicinal materials in parts by weight:
500-600 parts of astragalus root, 500-600 parts of ginkgo leaf, 150-250 parts of red sage root and 250-350 parts of earthworm.
As a preferred embodiment, the invention provides a traditional Chinese medicine composition I for treating coronary heart disease due to qi deficiency and blood stasis, which is prepared from astragalus, ginkgo, red sage root and earthworm, wherein the weight parts of the raw materials are as defined above.
The invention also provides a traditional Chinese medicine composition II for treating coronary heart disease with the syndrome of qi deficiency and blood stasis, which comprises the following raw materials in parts by weight:
50-120 parts of astragalus extract, 10-30 parts of ginkgo leaf extract, 10-35 parts of red sage root extract and 25-60 parts of earthworm extract;
wherein the astragalus extract is prepared by the following method:
decocting radix astragali in water for three times, each time with 5-10 times of water, each time for 1-2 hr; filtering while the mixture is hot, combining the filtrates, and concentrating the filtrate until each 1ml of the filtrate is equivalent to 1-2g of astragalus; adding ethanol to make ethanol content 75%, refrigerating for 12 hr, collecting supernatant, filtering, recovering ethanol from filtrate, concentrating until no ethanol smell exists, adding dextrin to make extract relative density 1.03-1.05 (40deg.C), and spray drying to obtain radix astragali extract;
the ginkgo leaf extract is prepared by the following method:
reflux extracting folium Ginkgo with 65% ethanol twice, each time with 4-5 times of 65% ethanol, each time for 1-2 hr, filtering while hot, and mixing filtrates; adjusting pH to 7.5-8.0 with 40% sodium hydroxide solution, standing for 12 hr, filtering, adjusting pH to 5.0-6.0 with 10% hydrochloric acid solution, recovering ethanol until no ethanol smell, adding purified water according to the proportion of 5ml purified water per 1g folium Ginkgo, stirring, adjusting pH to 4.0-4.5 with 10% hydrochloric acid, centrifuging, filtering, purifying the filtrate with macroporous adsorbent resin column, washing with water, eluting with 20% ethanol, collecting eluate, recovering ethanol under reduced pressure, concentrating to thick paste, and drying to obtain folium Ginkgo extract;
the red sage root extract is prepared by the following method:
reflux-extracting Saviae Miltiorrhizae radix with 70% ethanol for three times, each time with 3-6 times of 70% ethanol, each time for 1-2 hr; filtering while the mixture is hot, and combining the filtrates; recovering ethanol from the filtrate until no ethanol smell is present, adding dextrin to obtain extract with relative density of 1.05-1.07 (40deg.C), and spray drying to obtain Saviae Miltiorrhizae radix extract;
the earthworm extract is prepared by the following method:
decocting Lumbricus with 5-10 times of water for 1-2 hr, filtering, and mixing filtrates; concentrating the filtrate under reduced pressure to relative density of 1.10-1.20 (35-40deg.C), vacuum drying, adding corn starch 13-15% of Lumbricus weight, preferably 14% when the extract is viscous, mixing, drying, pulverizing, and sieving with 80 mesh sieve to obtain Lumbricus extract.
Preferably, in the preparation of the ginkgo leaf extract, the macroporous resin is HPD450, and the weight ratio of the resin to the ginkgo leaf is 0.5-2:1, preferably 1:1.
Preferably, in the preparation of the ginkgo leaf extract, the weight ratio of the volume of the washing water to the macroporous resin is 1-2ml to 1g, more preferably 1ml to 1g.
Also preferably, in the preparation of the ginkgo leaf extract, the weight ratio of 20% ethanol to macroporous resin is 1-3ml to 1g, more preferably 1.5-2ml to 1g.
Preferably, the traditional Chinese medicine composition II comprises the following raw materials in parts by weight:
60-100 parts of astragalus extract, 10-25 parts of ginkgo leaf extract, 15-35 parts of red sage extract and 30-60 parts of earthworm extract.
More preferably, the traditional Chinese medicine composition II comprises the following raw materials in parts by weight:
70-90 parts of astragalus extract, 10-20 parts of ginkgo leaf extract, 20-35 parts of red sage root extract and 40-60 parts of earthworm extract.
As a preferred embodiment, the invention provides a traditional Chinese medicine composition II for treating coronary heart disease due to qi deficiency and blood stasis, which is prepared from the following raw materials in parts by weight as defined before, wherein the raw materials comprise the astragalus extract, the ginkgo leaf extract, the red sage extract and the earthworm extract.
The invention also aims at providing a medicament which comprises the traditional Chinese medicine composition I or the traditional Chinese medicine composition II and also comprises or does not comprise pharmaceutically acceptable auxiliary materials.
The medicine is any clinically acceptable preparation, preferably an oral preparation.
Preferably, the oral preparation is selected from one or more of decoction, powder, capsule, tablet, honeyed pill, water pill, concentrated pill, paste pill, wax pill, granule, oral liquid and dripping pill, more preferably granule, tablet and/or capsule, and most preferably granule and/or capsule.
The invention also provides a preparation method of the medicine, which comprises the steps of preparing all traditional Chinese medicinal materials or raw materials according to the parts by weight, and preparing clinically acceptable preparations according to a conventional method in the field with or without adding pharmaceutically acceptable auxiliary materials.
Pharmaceutically acceptable excipients of the present invention include, but are not limited to: (1) Diluents such as starch, powdered sugar, dextrin, lactose, pregelatinized starch, microcrystalline cellulose, inorganic calcium salts (e.g., calcium sulfate, dibasic calcium phosphate, pharmaceutically acceptable calcium carbonate, etc.), mannitol, vegetable oils, polyethylene glycols, etc.; (2) Binders such as distilled water, ethanol, starch slurry, sodium carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, and ethyl cellulose, hydroxypropyl methylcellulose, and the like; (3) Disintegrants such as dry starch, sodium carboxymethyl starch, low-substituted hydroxypropylcellulose, crosslinked polyvinylpyrrolidone, crosslinked sodium carboxymethyl cellulose, etc.; (4) Lubricants such as magnesium stearate, silica gel micropowder, talc, hydrogenated vegetable oils, polyethylene glycols, magnesium lauryl sulfate, etc.
As a preferred embodiment, the invention provides a preparation method of granules for coronary heart disease with qi deficiency and blood stasis, which comprises the following operations:
preparing astragalus root, ginkgo leaf, red sage root and earthworm according to the traditional Chinese medicine composition I; decocting with water for 1-3 times, each time with 5-10 times of water, each time for 1-2 hr; filtering while the mixture is hot, and combining the filtrates; concentrating the filtrate to relative density of 1.05-1.10 (60deg.C), adding part of dextrin, mixing, spray drying, adding the rest dextrin, mixing, and dry granulating; wherein the total weight of the dextrin is 30% -50% of the total weight of the medicinal materials.
Preferably, astragalus root, ginkgo leaf, red sage root and earthworm are decocted with water twice, and water which is 10 times of the total weight of the medicinal materials is added for the first time, and the decoction is carried out for 1 hour; adding water 8 times of the total weight of the medicinal materials for the second time, and decocting for 1 hour.
As a preferred embodiment, the invention provides a preparation method of a capsule for treating coronary heart disease with qi deficiency and blood stasis, which comprises the following steps:
preparing the astragalus extract, the ginkgo leaf extract, the red sage extract and the earthworm extract according to the traditional Chinese medicine composition II; adding pharmaceutically acceptable adjuvants, mixing, granulating by dry method, and making into capsule.
Preferably, the pharmaceutically acceptable auxiliary materials are microcrystalline cellulose and magnesium stearate.
In addition, the invention also aims to provide the application of the traditional Chinese medicine composition I, the traditional Chinese medicine composition II, the medicine, the granules and the capsule in preparing medicines for treating coronary heart disease due to qi deficiency and blood stasis.
In the specification, "parts by weight" of each Chinese medicinal material refers to the ratio relationship of the dosage of each Chinese medicinal material, rather than the actual mass unit. The unit weight part may be any mass, for example, 1 part by weight may be 1g, 500g or 1kg, and may even be 15g, 30g, etc., according to actual circumstances.
In the specification, unless specified otherwise, the concentration of the ethanol is the volume percentage concentration, and the concentration of the ethanol is 95-100% of the volume percentage concentration. In addition to the ethanol solution, other solutions, such as 40% sodium hydroxide solution and 10% hydrochloric acid solution, are all in mass percent concentration.
In the present specification, the term "purified water" refers to water obtained by treatment such as distillation and deionization.
In the present specification, the "crude drug" or "crude drug" may be used interchangeably, and refer to the total weight (mass) of the medicinal materials that are added when the extract or clinically acceptable preparation is prepared from the Chinese medicinal materials.
Drawings
The invention is further described below with reference to the accompanying drawings.
Fig. 1: photomicrographs of study example 4 after HE staining of the heart sections of rats in the blank group; wherein, the left side A is a photograph enlarged by 20 times, and the right side B is a photograph enlarged by 200 times.
Fig. 2: photomicrographs of model control group rat heart sections of study example 4 after HE staining; wherein, the left side A is a photograph enlarged by 20 times, and the right side B is a photograph enlarged by 200 times.
Fig. 3: microphotographs of positive drug control group rats of study example 4 after HE staining of heart sections; wherein, the left side A is a photograph enlarged by 20 times, and the right side B is a photograph enlarged by 200 times.
Fig. 4: photomicrographs of study example 4 after HE staining of heart sections of rats in the experimental high dose group; wherein, the left side A is a photograph enlarged by 20 times, and the right side B is a photograph enlarged by 200 times.
Fig. 5: photomicrographs of the dose group rat heart sections after HE staining in the trial of study example 4; wherein, the left side A is a photograph enlarged by 20 times, and the right side B is a photograph enlarged by 200 times.
Fig. 6: photomicrographs of study example 4 following HE staining of heart sections of rats in the experimental low dose group; wherein, the left side A is a photograph enlarged by 20 times, and the right side B is a photograph enlarged by 200 times.
Detailed Description
The invention is described below with reference to specific examples. It will be appreciated by those skilled in the art that these examples are for illustration of the invention only and are not intended to limit the scope of the invention in any way.
The experimental methods in the following examples are conventional methods unless otherwise specified. The raw materials and reagent materials used in the examples below are all commercially available products unless otherwise specified. Wherein, the purchasing conditions of partial reagents and medicinal materials are as follows:
radix astragali: dried root of astragalus mongholicus Astragalus membranaceus (fishe.) bge. Purchased from the company of Shennonggu, bo, china, usta.
Root of red-rooted salvia: rhizome of Salvia Miltiorrhiza Salvia miltiorrhiza bge of Labiatae. Purchased from the company of Shennonggu, bo, china, usta.
Earthworm: dried body of limnodrilus Pheretima aspergillum (e.perrier) of the earthworm family animal. Purchased from Anhui Heniantang traditional Chinese medicine decoction pieces limited.
Ginkgo leaf: dried leaves of Ginkgo Ginkgo biloba L. Purchased from the company of Shennonggu, bo, china, usta.
Example 1Traditional Chinese medicine composition I for qi deficiency and blood stasis type coronary heart disease
The composition of the traditional Chinese medicine composition i in this example is (1 part by weight=1g):
700 parts of astragalus root, 800 parts of ginkgo leaf, 50 parts of red sage root and 150 parts of earthworm.
Example 2Traditional Chinese medicine composition I for qi deficiency and blood stasis type coronary heart disease
The composition of the traditional Chinese medicine composition i in this example is (1 part by weight=1g):
450 parts of astragalus root, 700 parts of ginkgo leaf, 100 parts of red sage root and 200 parts of earthworm.
Example 3Traditional Chinese medicine composition I for qi deficiency and blood stasis type coronary heart disease
The composition of the traditional Chinese medicine composition i in this example is (1 part by weight=1g):
600 parts of astragalus root, 500 parts of ginkgo leaf, 150 parts of red sage root and 350 parts of earthworm.
Example 4Traditional Chinese medicine composition I for qi deficiency and blood stasis type coronary heart disease
The composition of the traditional Chinese medicine composition i in this example is (1 part by weight=1g):
500 parts of astragalus membranaceus, 600 parts of ginkgo leaves, 250 parts of red sage root and 250 parts of earthworm.
Example 5Traditional Chinese medicine composition I for qi deficiency and blood stasis type coronary heart disease
The composition of the traditional Chinese medicine composition i in this example is (1 part by weight=1g):
550 parts of astragalus membranaceus, 550 parts of ginkgo leaves, 200 parts of red sage root and 300 parts of earthworm.
Example 6Granule for treating coronary heart disease with qi deficiency and blood stasis
Taking the traditional Chinese medicine composition described in the embodiment 5; decocting in water for 2 times, adding water 10 times the total weight of the medicinal materials for the first time, decocting for 1 hr, and filtering; adding 8 times of water for decocting for 1 hour, filtering, mixing filtrates, concentrating the filtrate to relative density of 1.05-1.10 (60 deg.C), adding 5% dextrin, mixing, and spray drying to obtain spray-dried powder. Adding dextrin, mixing, granulating by dry method, making into 1000g, and packaging with 2g per bag.
Example 7Preparation of the extract
1. Preparation of astragalus extract
Decocting radix astragali in water for three times, adding water with the weight being 8 times that of radix astragali for the first time, soaking for 30 minutes, and decocting for 1.5 hours; adding water with the weight being 6 times of that of the astragalus, and decocting for 1.5 hours; adding water 5 times of total weight of radix astragali for the third time, decocting for 1.5 hr, filtering while hot, and mixing filtrates; concentrating the filtrate to 1-2g (relative density: 1.14-1.23 (40deg.C)) of radix astragali, adding ethanol to make alcohol content 75%, refrigerating for 12 hr, collecting supernatant, and filtering; recovering ethanol from the filtrate, concentrating until no ethanol smell is present, adding dextrin about 10% of total weight of radix astragali to obtain extract with relative density of 1.03-1.05 (40deg.C), and spray drying to obtain radix astragali extract;
2. preparation of ginkgo leaf extract
Reflux-extracting folium Ginkgo with 65% ethanol twice; adding 65% ethanol 5 times of the weight of folium Ginkgo for the first time, soaking for 2 hr, and reflux extracting for 2 hr; adding 65% ethanol 4 times of the weight of folium Ginkgo for reflux extraction for 1.5 hr; filtering while the mixture is hot, and combining the filtrates; adjusting pH to 7.5-8.0 with 40% sodium hydroxide solution, standing for 12 hr, filtering, adjusting pH to 5.0-6.0 with 10% hydrochloric acid solution, recovering ethanol until no ethanol smell, diluting with purified water (5 ml purified water for every 1g folium Ginkgo), stirring, adjusting pH to 4.0-4.5 with 10% hydrochloric acid, centrifuging, filtering, passing the filtrate through HPD450 macroporous adsorbent resin column (resin to folium Ginkgo weight ratio of 1:1), washing with water at a ratio of 1ml water per 1g macroporous resin, eluting with 20% ethanol (1.5 ml 20% ethanol per 1g macroporous resin), collecting eluate, recovering ethanol under reduced pressure, concentrating to soft extract, and drying to obtain folium Ginkgo extract;
3. preparation of red sage root extract
Reflux-extracting Saviae Miltiorrhizae radix with 70% ethanol for three times, adding 70% ethanol 6 times the weight of Saviae Miltiorrhizae radix for the first time, soaking for 30 min, and reflux-extracting for 1.5 hr; adding 70% ethanol 4 times the weight of Saviae Miltiorrhizae radix, and reflux extracting for 1.5 hr; adding 70% ethanol 4 times the weight of Saviae Miltiorrhizae radix for reflux extraction for 1 hr. Filtering while the extract is hot, mixing the filtrates, recovering ethanol under reduced pressure at 60deg.C until no ethanol smell is generated, adding dextrin accounting for 8% of total weight of Saviae Miltiorrhizae radix to obtain extract with relative density of 1.05-1.07 (40deg.C), and spray drying to obtain Saviae Miltiorrhizae radix extract;
4. preparation of Lumbricus extract
Decocting Lumbricus with water twice, adding water 10 times the weight of Lumbricus for the first time, soaking for 20 min, decocting for 2 hr, and filtering; adding water with the weight being 8 times of that of the earthworm for the second time, decocting for 1 hour, filtering, and combining the filtrates; concentrating the filtrate under reduced pressure to relative density of 1.10-1.20 (35-40deg.C), vacuum drying at 70deg.C, adding corn starch about 14% of Lumbricus weight when the extract is thick, mixing, drying, pulverizing, and sieving with 80 mesh sieve to obtain Lumbricus extract.
Example 8A Chinese medicinal composition II for treating coronary heart disease due to qi deficiency and blood stasis
The composition of the traditional Chinese medicine composition II in this example is (1 part by weight=1g):
80 parts of astragalus extract, 17 parts of ginkgo leaf extract, 25 parts of red sage root extract and 50 parts of earthworm extract;
wherein each extract was prepared as described in example 7.
Example 9Traditional Chinese medicine composition II for qi deficiency and blood stasis type coronary heart disease
The composition of the traditional Chinese medicine composition II in this example is (1 part by weight=1g):
90 parts of astragalus extract, 10 parts of ginkgo leaf extract, 20 parts of red sage root extract and 60 parts of earthworm extract;
wherein each extract was prepared as described in example 7.
Example 10Traditional Chinese medicine composition II for qi deficiency and blood stasis type coronary heart disease
The composition of the traditional Chinese medicine composition II in this example is (1 part by weight=1g):
70 parts of astragalus extract, 20 parts of ginkgo leaf extract, 35 parts of red sage root extract and 40 parts of earthworm extract;
wherein each extract was prepared as described in example 7.
Example 11Traditional Chinese medicine composition II for qi deficiency and blood stasis type coronary heart disease
The composition of the traditional Chinese medicine composition II in this example is (1 part by weight=1g):
120 parts of astragalus extract, 25 parts of ginkgo leaf extract, 15 parts of red sage root extract and 30 parts of earthworm extract;
wherein each extract was prepared as described in example 7.
Example 12Traditional Chinese medicine composition II for qi deficiency and blood stasis type coronary heart disease
The composition of the traditional Chinese medicine composition II in this example is (1 part by weight=1g):
50 parts of astragalus extract, 30 parts of ginkgo leaf extract, 10 parts of red sage root extract and 25 parts of earthworm extract;
wherein each extract was prepared as described in example 7.
Example 13Capsule for treating coronary heart disease due to qi deficiency and blood stasis
Taking the traditional Chinese medicine composition II described in the embodiment 8; adding 176g microcrystalline cellulose and 2g magnesium stearate, mixing, granulating by dry method to obtain 350g granule, encapsulating, making into 1000 granule, 0.35 g/granule,
and (5) packaging by aluminum plastic, and adding a composite film bag.
Comparative example 1A Chinese medicinal composition
The traditional Chinese medicine composition of the comparative example comprises the following raw materials (1 part by weight=1g):
120 parts of astragalus, 10 parts of ginkgo leaf, 20 parts of red sage root and 3 parts of earthworm.
A spray-dried powder was prepared as in example 6.
Comparative example 2A Chinese medicinal composition
The traditional Chinese medicine composition of the comparative example comprises the following raw materials (1 part by weight=1g):
120 parts by weight of astragalus membranaceus, 10 parts by weight of ginkgo leaf, 20 parts by weight of salvia miltiorrhiza, 15 parts by weight of pseudo-ginseng, 6 parts by weight of angelica sinensis, 5 parts by weight of radix paeoniae rubra, 3 parts by weight of peach seed, 3 parts by weight of ligusticum wallichii, 3 parts by weight of safflower, 3 parts by weight of earthworm, 3 parts by weight of ginseng, 3 parts by weight of American ginseng, 3 parts by weight of radix pseudostellariae and 3 parts by weight of rhodiola rosea
The extract was prepared according to the method for preparing the Chinese medicinal composition of effect example 1 "(4) in patent application CN 105012388A, at a concentration of 1.54g crude drug/ml.
Study example 1The influence of the Chinese medicinal composition on the coagulation time of rats (capillary glass tube method)
SPF-class SD rats 112, male and female halves, body weight 230g-250g, purchased from Liaoning long Biotechnology, inc., animal use license number: SYXK (black) 2018-007, animal production license number: SCXK (Liao) 2020-0001. Randomly dividing into 14 groups of 8 male and female halves. The blank control group, the positive medicine control group, the test 1-10 groups and the comparison 1-2 groups are respectively. Each group was given the following drugs by gavage:
blank control group: distilled water, 10ml/kg;
positive drug control group: capsule for activating heart meridian (product batch number: B2207569, shijia Kagaku Co., ltd.) content of 0.140g/kg body weight at a time, a dose volume of 10ml/kg body weight;
test 1-5 groups: the Chinese medicinal compositions of examples 1-5 were spray-dried powder prepared in example 6, 1.755g crude drug/kg body weight each time, and the administration volume was 10ml/kg body weight;
test 6-10 groups: the Chinese medicinal composition of examples 8-12, each time 0.378g/kg body weight, was administered in a volume of 10ml/kg body weight;
comparison group 1: the traditional Chinese medicine composition of comparative example 1 is spray-dried powder prepared in example 6, and the dosage volume of the spray-dried powder is 10ml/kg body weight, wherein 1.755g crude drug/kg body weight is taken each time;
comparison group 2: the concentration of the traditional Chinese medicine composition prepared in comparative example 2 is 1.54g crude drug/ml, and the administration volume is 10ml/kg body weight.
Each group was dosed 1 time per day for 10 consecutive days.
After the last administration for 1h, the rat orbit was bled, the capillary glass tube (produced by Huaxi medical university instrument factory) was broken every 15s until blood streaks appear, and the time from when the blood fills the capillary glass tube to the appearance of blood streaks, i.e. the clotting time, was recorded.
Statistical analysis was performed using IBM SPSS25.0 software, all data expressed as mean ± standard deviation (±s), the comparisons between groups were in accordance with normal distribution and the variance was uniform using one-way analysis of variance (ANOVA), with P <0.05 as the difference being statistically significant.
The results are shown in Table 1.
TABLE 1 Effect of the Chinese medicinal composition of the invention on coagulation time of rats
| Group of | Number of animals | Medicament | Coagulation time(s) |
| Blank control group | 8 | Distilled water | 47.63±14.99 |
| Positive control group | 8 | Capsule content for dredging heart meridian | 65.00±9.09 *# |
| Test 1 group | 8 | Example 1 a | 69.28±6.44 ** |
| Test 2 groups | 8 | Example 2 a | 69.34±9.02 ** |
| Test 3 groups | 8 | Example 3 a | 70.41±8.17 ** |
| Test 4 groups | 8 | Example 4 a | 70.88±7.26 ** |
| Test 5 groups | 8 | Example 5 a | 71.36±5.90 ** |
| Test 6 groups | 8 | Example 8 | 73.25±6.07 ** |
| Test 7 groups | 8 | Example 9 | 72.77±5.96 ** |
| Test 8 groups | 8 | Example 10 | 72.56±7.64 ** |
| Test 9 groups | 8 | Example 11 | 71.89±8.21 ** |
| Test 10 groups | 8 | Example 12 | 71.92±7.33 ** |
| Comparative group 1 | 8 | Traditional Chinese medicine composition of comparative example 1 | 60.74±10.15 *## |
| Comparative group 2 | 8 | Traditional Chinese medicine composition of comparative example 2 | 66.55±8.82 **# |
a: the spray-dried powder prepared by the method of the example 6 by taking the traditional Chinese medicine composition of the example as a raw material;
note that: compared to the blank control group,: p <0.05,: p is less than 0.01; in comparison with the group of test 6, # ：P＜0.05， ## ：P＜0.01。
the data in Table 1 show that each of the Chinese medicinal compositions of the present invention can significantly prolong the clotting time of rats (P < 0.01), and has a significantly different effect (P <0.05, P < 0.01) than the comparison group and the positive control group. The above table data also shows that the traditional Chinese medicine composition II of example 8 has the strongest effect of prolonging clotting time of rats.
Study example 2Effects of the Chinese medicinal composition on rat thrombosis
SPF-grade SD rats 40, male and female halves, body weight 230g-250g, purchased from Liaoning long Biotechnology Co., ltd., animal use license number: SYXK (black) 2018-007, animal production license number: SCXK (Liao) 2020-0001. Randomly dividing into 5 groups of 8 male and female halves. The blank control group, the positive control group, the test group and the comparison 1-2 group respectively. Each group was given the following drugs by gavage:
blank control group: distilled water, 10ml/kg;
positive control group: capsule for activating heart meridian (product batch number: B2207569, shijia Kagaku Co., ltd.) content of 0.140g/kg body weight at a time, a dose volume of 10ml/kg body weight;
test group: the Chinese medicinal composition of example 8 was administered at a dose of 0.378g/kg body weight, with a volume of 10ml/kg body weight;
comparison group 1: the traditional Chinese medicine composition of comparative example 1 is spray-dried powder prepared in example 6, and the dosage volume of the spray-dried powder is 10ml/kg body weight, wherein 1.755g crude drug/kg body weight is taken each time;
comparison group 2: the concentration of the traditional Chinese medicine composition prepared in comparative example 2 is 1.54g crude drug/ml, and the administration volume is 10ml/kg body weight.
Each group was dosed 1 time per day for 10 consecutive days.
After the last administration for 1h, the abdominal cavity was anesthetized by injecting chloral hydrate (product lot: 20201215, tianjin chemical reagent factory), separating the right common carotid artery and the left external jugular vein, placing a 6 cm long No. four surgical line in the middle section of the three-section polyethylene tube, and filling the polyethylene tube cavity with heparin (lot: FS208A, sainofil pharmaceutical Co., ltd.) physiological saline (12.5U/ml). After one end of the tube is inserted into the left external jugular vein, the other end of the tube is inserted into the right common carotid artery, and the arterial clamp is opened, so that blood flows through the polyethylene tube from the right common carotid artery and returns to the left external jugular vein. After 20 minutes of open blood flow, blood flow was interrupted, the silk threads were rapidly removed and weighed, and the total weight minus the silk thread weight was the wet weight of the thrombus. The inhibition ratio was calculated according to the following formula:
inhibition rate= (thrombus weight of blank control group-thrombus weight of administration group)/thrombus weight of blank control group x 100%.
Statistical analysis was performed using IBM SPSS25.0 software, all data expressed as mean ± standard deviation (±s), the comparisons between groups were in accordance with normal distribution and the variance was uniform using one-way analysis of variance (ANOVA), with P <0.05 as the difference being statistically significant.
The results are shown in Table 2.
TABLE 2 Effect of the Chinese medicinal composition of the invention on rat thrombosis
| Group of | Number of animals | Dosage (g/kg) | Weight of thrombus | Thrombus inhibition Rate (%) |
| Blank control group | 8 | - | 52.68±6.45 | - |
| Positive control group | 8 | 0.140 | 51.29±15.06 | 2.6 |
| Test group | 8 | 0.378 | 47.04±17.07 | 10.7 |
| Comparative group 1 | 8 | 1.755 (crude drug) | 50.67±16.54 | 3.8 |
| Comparative group 2 | 8 | 15.4 (crude drug) | 49.31±6.24 | 6.4 |
The data in table 2 show that there was a decrease in thrombus weight for the positive control, test and each control, but the difference was not significant, compared to the blank; however, the test group had the least weight of thrombus, which indicates that the Chinese medicinal composition of example 8 of the present invention has a stronger effect on inhibiting thrombus than the other groups.
Study example 3Influence of the composition of the present invention on blood stasis model (anticoagulation)
SPF-grade SD rats 60, male and female halves, body weight 230g-250g, purchased from Liaoning long Biotechnology Co., ltd., animal use license number: SYXK (black) 2018-007, animal production license number: SCXK (Liao) 2020-0001. The random number is divided into 6 groups of 10 animals each, and the male and female parts are half. The blank control group, the model control group, the positive control group, the test group and the comparison 1-2 group respectively. Each group was given the following drugs by gavage:
blank and model controls: distilled water, 10ml/kg;
positive control group: capsule for activating heart meridian (product batch number: B2207569, shijia Kagaku Co., ltd.) content of 0.140g/kg body weight each time, a dose volume of 10ml/kg;
test group: the Chinese medicinal composition of example 8 was administered at a dose of 0.378g/kg body weight, with a dose volume of 10ml/kg;
comparison group 1: the traditional Chinese medicine composition of comparative example 1 is spray-dried powder prepared in example 6, and the dosage volume is 10ml/kg, and the crude drug is 1.755 g/kg each time;
comparison group 2: the concentration of the traditional Chinese medicine composition prepared in comparative example 2 is 1.54g crude drug/ml, and the administration volume is 10ml/kg body weight.
And (3) model preparation: the rats of each group except the blank group were subcutaneously injected with isoprenaline injection (62302142, kansui patent medicine Co., ltd.) (100 mg/kg), the blank group was injected with an equal amount of physiological saline, and continuous injection was carried out for 3 days, and the rats except the blank group were measured for electrocardiogram, and the ST segment arch back elevation was presented to indicate that the molding was successful.
During molding, each group was administered by gavage 1 time a day for 15 consecutive days.
After the end of the last administration, rats were anesthetized by intraperitoneal injection with 0.3ml/100g of 10% chloral hydrate solution, and blood was collected from the abdominal aorta using heparin sodium blood collection tubes (product lot number: 20210420, medical product factory in Wu county, shandong) and blood collection needles. The haemorheology index was directly detected within 4 hours after abdominal aortic blood collection using an LB-2A full-automatic haemorheology analyzer (Tang Yu medical instruments science and technology development limited, tianjin).
Statistical analysis was performed using IBM SPSS25.0 software, all data expressed as mean ± standard deviation (±s), the comparisons between groups were in accordance with normal distribution and the variance was uniform using one-way analysis of variance (ANOVA), with P <0.05 as the difference being statistically significant.
The results are shown in Table 3 and Table 4
TABLE 3 Effect of the Chinese medicinal composition of the invention on Whole blood viscosity and Whole blood reduction viscosity of rats
Note that: in contrast to the blank group, ## ：P<0.01; in comparison with the model control group, ** ：P<0.01， * ：P<0.05。
TABLE 4 Effect of the Chinese medicinal composition of the invention on rat plasma viscosity and erythrocyte function
Note that: in contrast to the blank group, ## ：P<0.01; in comparison with the model control group, ** ：P<0.01。
the data in tables 3 and 4 show that the whole blood viscosity, the whole blood reduction viscosity, the plasma viscosity, and the hematocrit, the metacentric index, the rigidity index, and the aggregation index of the rats in the model control group were all significantly increased (P < 0.01) compared to the blank control group, showing that the modeling was successful. The comparison model control groups of the rats in the test group, such as the whole blood viscosity, the whole blood reduction viscosity, the plasma viscosity and the like, are obviously reduced (P <0.01, P < 0.05), which indicates that the traditional Chinese medicine composition has obvious anticoagulation effect, and the effect is obviously stronger than that of each control group.
Study example 4Therapeutic effects of the inventive composition on IOS-induced myocardial infarction rats
SPF-class SD rats 84, male and female halves, body weights 230g-250g, purchased from Liaoning long Biotechnology, inc., animal use license number: SYXK (black) 2018-007, animal production license number: SCXK (Liao) 2020-0001. The male and female halves are randomly divided into 6 groups of 14. The control group is a blank control group, a model control group, a positive control group, a test high-dose group, a test medium-dose group and a test low-dose group respectively.
Preparation of animal model: after purchase of SD rats, the rats were acclimatized for 7 days, followed by a random grouping of 14 animals per group, and after the end of the acclimation period, 300mg/ml of ISO solution was prepared. The blank group was not treated at all, and the remaining 5 groups were subcutaneously injected at a dose of 100mg/kg for three consecutive days at intervals of 24 hours or more.
After the molding, each group starts to be irrigated with corresponding drugs, 3 groups of high, medium and low tests are respectively irrigated with the content of the capsule prepared in the example 13 of the traditional Chinese medicine composition of the example 8, and the administration doses are respectively 0.756g/kg body weight, 0.378g/kg body weight and 0.189g/kg body weight; the positive control group was given a capsule for smoothing heart and collaterals of 0.140g/kg body weight by lavage. The administration volume was 10ml/kg body weight. The blank control and the model control were given the same volume of distilled water. The administration was continued for 14 days 1 time per day.
After the last administration, rats were anesthetized by intraperitoneal injection with a 10% aqueous chloral (product lot number: 20201215, tianjin's Methao chemical reagent Co., ltd.) solution of 0.3ml/100g body weight, (1) were collected from the abdominal aorta with a disposable vacuum blood collection tube (product lot number: 21097004, hebei Xinle medical instruments and technologies Co., ltd.) and a blood collection needle. After blood collection, the mixture was centrifuged at about 4000 Xg for 10min at low temperature, and the supernatant was carefully aspirated by a pipette and dispensed into 2ml centrifuge tubes and stored at-80℃for further use. The rat heart injury was detected using Chemray240 full-automatic biochemical apparatus (Shenzhen Lei Du life technologies Co., ltd.). (2) The heart was rapidly removed, washed with normal saline, removed from the heart, blotted with filter paper, fixed in 10% neutral formalin (lot number 20220805, beijing Yili Fine chemical Co., ltd.), and HE stained to observe the pathological changes of heart tissue.
Statistical analysis was performed using IBM SPSS25.0 software, all data expressed as mean ± standard deviation (±s), the comparisons between groups were in accordance with normal distribution and the variance was uniform using one-way analysis of variance (ANOVA), with P <0.05 as the difference being statistically significant.
(1) The results of the cardiac injury measurements are shown in Table 5.
TABLE 5 Effect of the compositions of the invention on rat serum myocardial infarction injury markers
Note that: in comparison with the model control group, ## P<0.01, compared with the blank control group, ** P<0.01，*P<0.05。
the results in Table 5 show that the CK, CKMB, LDH values of the rats in the model control group are all significantly higher (P < 0.01) than those in the blank control group, showing successful modeling. Compared with a model control group, the CK, CKMB, LDH value of rats in each test group is obviously reduced (P is less than 0.01 and P is less than 0.05), which indicates that the traditional Chinese medicine composition has obvious anticoagulation effect, compared with a positive control group, a high-dose group shows better treatment effect, CKBB and LDH levels are obviously different (P is less than 0.01 and P is less than 0.05), and a medium-low-dose group also shows better treatment effect compared with the positive control group, but the difference is not obvious (P is more than 0.05).
(2) Effects on cardiac pathology
The microphotographs of heart sections of the rats of each group after HE staining are shown in FIGS. 1 to 6.
FIG. 1 shows that heart tissue of a rat in a blank group has clear endocardial, myocardium and epicardium structures, and no obvious abnormality is seen in heart walls and heart chambers; the myocardial fiber is uniformly colored, the cell demarcation is clear, the shape of the cells is consistent, the transverse lines of the myocardial cells are clear, the bright and dark phases are separated, and the interstitium is not abnormal; no significant inflammatory changes were seen.
FIG. 2 shows that heart tissue of the model control rats can be seen as small area myocardial cell necrosis, nuclear fragmentation (indicated by arrow 1), connective tissue hyperplasia, with small lymphocyte infiltration (indicated by arrow 2); irregular vacuoles are seen in small numbers of cardiomyocyte cytoplasm.
FIG. 3 shows that heart tissue of rats in the positive drug control group was seen to have small areas of myocardial cell necrosis, nuclear fragmentation (indicated by arrow 1), connective tissue hyperplasia, and small amounts of lymphocyte infiltration (indicated by arrow 2).
FIG. 4 shows that heart tissue from the high dose group of rats is examined for a small amount of lymphocyte infiltration (indicated by arrow 1) at the epicardium; the interstitium is seen as a large amount of vascular congestion (indicated by arrow 2); the myocardial fiber is evenly colored, the cell demarcation is clear, the shape of the cells is consistent, the transverse lines of the myocardial cells are clear, the bright and dark phases are alternate, and the interstitium is not abnormal.
FIG. 5 shows that heart tissue from rats in the dose group in the trial was seen to have a small amount of myocardial cells necrotic, lysed, with a small amount of lymphocyte infiltration (indicated by arrow 1) at the epicardium; interstitial small amounts of vascular congestion (indicated by arrow 2).
Figure 6 shows that heart tissue from the low dose group of rats tested showed small areas of myocardial cell necrosis, nuclear fragmentation (indicated by arrow 1), connective tissue hyperplasia, with small amounts of lymphocyte infiltration (indicated by arrow 2).
The test result proves that the test model is successful; compared with the model control group, the positive control group and the high, medium and low dose administration groups have the improvement effect on myocardial cells, wherein the high dose group has the best effect, and myocardial fibers are uniformly colored, and cells are clearly delimited and have consistent shape.
Study example 5Safety study
Acute toxicity test: the maximum dose method is adopted, the rat is administrated by lavage, 1.4525g/ml of the capsule content of the example 13, the maximum administration volume of the rat by lavage is 20ml/kg of body weight, the rat is administrated by lavage for 1 time in one day, and the toxic reaction and death of the animal are continuously observed in 14 days.
As a result, the maximum dose of the capsule of example 13 was 29.05g/kg body weight, which corresponds to 153.7 times the clinically intended dose. All rats were in good general status, smooth and bright hair, normal activities and diets, fecal formation, and no death of animals from the day of administration to the end of observation. Weight was abnormal during the individual periods, but weight tended to increase, indicating that the capsule of example 13 did not affect the growth of the test animals after intragastric administration. On the day of the end of the test, no changes of volume, color, texture and the like of animal organs are observed by naked eyes, and important organs such as brain, heart, liver, spleen, lung, kidney and the like are not found to bleed, engorge, ooze, ulcer, perforation, inflammation and hydrops of thoracic cavity, abdominal cavity and pericardial cavity.
Toxicity study for 3 months: according to the guidelines of drug repeated administration toxicity test technology issued by the national food and drug administration in 2014, 5 months, rats are continuously filled with three doses of 10 times, 30 times and 60 times of the clinical dosage of the capsule of example 13 and distilled water for 3 months respectively. As a result, rats of each administration group were active and the hair was smooth, and were not changed in difference or abnormality; the average feeding amount and average weight of rats in each dosage group in the administration period and the recovery period are different from those in the contemporaneous control group to a certain extent, but only exist at individual detection time points, have no regular and trend changes, lack a dosage response relationship, and preliminarily judge that the difference has no toxicological significance; compared with the contemporaneous control group, the hematology and blood biochemical indexes of each group of animals have abnormal changes of individual indexes, but have no dose-response correlation, and the analysis can be transient response; comparing the urine routine index with the contemporaneous control group, no abnormal change of dose-response correlation is seen; all organ coefficients between groups at the end of administration and the end of recovery period have no abnormal changes in physiological significance, and all microscopic tissue organs have no pathological changes in quantitative toxicity, and have no delayed toxic reaction. Under the experimental conditions, no definite toxic target organ and no definite toxic reaction were found at the dose of 11.34g/kg/d (about 60 times the clinical dose) when the capsule of example 13 was administered by repeated gavage for three months in rats.
Claims (10)
1. A traditional Chinese medicine composition I for treating coronary heart disease with qi deficiency and blood stasis comprises the following traditional Chinese medicinal materials in parts by weight:
400-700 parts of astragalus membranaceus, 500-800 parts of ginkgo leaves, 50-250 parts of red sage root and 150-350 parts of earthworm.
2. The traditional Chinese medicine composition I according to claim 1, wherein the raw materials of the traditional Chinese medicine composition I comprise the following traditional Chinese medicinal materials in parts by weight:
450-650 parts of astragalus root, 500-700 parts of ginkgo leaf, 100-250 parts of red sage root and 200-350 parts of earthworm;
preferably, the traditional Chinese medicine composition I comprises the following traditional Chinese medicinal materials in parts by weight:
500-600 parts of astragalus root, 500-600 parts of ginkgo leaf, 150-250 parts of red sage root and 250-350 parts of earthworm.
3. A traditional Chinese medicine composition II for treating coronary heart disease with qi deficiency and blood stasis comprises the following raw materials in parts by weight:
50-120 parts of astragalus extract, 10-30 parts of ginkgo leaf extract, 10-35 parts of red sage root extract and 25-60 parts of earthworm extract.
4. The traditional Chinese medicine composition II according to claim 3, wherein the traditional Chinese medicine composition II comprises the following raw materials in parts by weight:
60-100 parts of astragalus extract, 10-25 parts of ginkgo leaf extract, 15-35 parts of red sage extract and 30-60 parts of earthworm extract;
preferably, the traditional Chinese medicine composition II comprises the following raw materials in parts by weight:
70-90 parts of astragalus extract, 10-20 parts of ginkgo leaf extract, 20-35 parts of red sage root extract and 40-60 parts of earthworm extract.
5. The traditional Chinese medicine composition II according to claim 3 or 4, wherein the astragalus extract is prepared by the following method:
decocting radix astragali in water for three times, each time with 5-10 times of water, each time for 1-2 hr; filtering while the mixture is hot, combining the filtrates, and concentrating the filtrate until each 1ml of the filtrate is equivalent to 1-2g of astragalus; adding ethanol to make ethanol content 75%, refrigerating for 12 hr, collecting supernatant, filtering, recovering ethanol from filtrate, concentrating until no ethanol smell exists, adding dextrin to make extract relative density 1.03-1.05 (40deg.C), and spray drying to obtain radix astragali extract;
the ginkgo leaf extract is prepared by the following method:
reflux extracting folium Ginkgo with 65% ethanol twice, each time with 4-5 times of 65% ethanol, each time for 1-2 hr, filtering while hot, and mixing filtrates; adjusting pH to 7.5-8.0 with 40% sodium hydroxide solution, standing for 12 hr, filtering, adjusting pH to 5.0-6.0 with 10% hydrochloric acid solution, recovering ethanol until no ethanol smell, adding purified water according to the proportion of 5ml purified water per 1g folium Ginkgo, stirring, adjusting pH to 4.0-4.5 with 10% hydrochloric acid, centrifuging, filtering, purifying the filtrate with macroporous adsorbent resin column, washing with water, eluting with 20% ethanol, collecting eluate, recovering ethanol under reduced pressure, concentrating to thick paste, and drying to obtain folium Ginkgo extract;
the red sage root extract is prepared by the following method:
reflux-extracting Saviae Miltiorrhizae radix with 70% ethanol for three times, each time with 3-6 times of 70% ethanol, each time for 1-2 hr; filtering while the mixture is hot, and combining the filtrates; recovering ethanol from the filtrate until no ethanol smell is present, adding dextrin to obtain extract with relative density of 1.05-1.07 (40deg.C), and spray drying to obtain Saviae Miltiorrhizae radix extract;
the earthworm extract is prepared by the following method:
decocting Lumbricus with 5-10 times of water for 1-2 hr, filtering, and mixing filtrates; concentrating the filtrate under reduced pressure to relative density of 1.10-1.20 (35-40deg.C), vacuum drying, adding corn starch 13% -15%, preferably 14% of Lumbricus when the extract is viscous, mixing, drying, pulverizing, and sieving with 80 mesh sieve to obtain Lumbricus extract;
preferably, in the preparation of the ginkgo leaf extract, the macroporous resin is HPD450, and the weight ratio of the resin to the ginkgo leaf is 0.5-2:1, preferably 1:1;
preferably, in the preparation of the ginkgo leaf extract, the weight ratio of the volume of the washing water to the macroporous resin is 1-2ml to 1g, more preferably 1ml to 1g;
also preferably, in the preparation of the ginkgo leaf extract, the weight ratio of 20% ethanol to macroporous resin is 1-3ml to 1g, more preferably 1.5-2ml to 1g.
6. A medicament comprising the traditional Chinese medicine composition I according to claim 1 or 2 or the traditional Chinese medicine composition II according to any one of claims 3 to 5, and optionally pharmaceutically acceptable auxiliary materials;
the medicine is any clinically acceptable preparation, preferably an oral preparation;
preferably, the oral preparation is selected from one or more of decoction, powder, capsule, tablet, honeyed pill, water pill, concentrated pill, paste pill, wax pill, granule, oral liquid and dripping pill, more preferably granule, tablet and/or capsule, and most preferably granule and/or capsule.
7. The preparation method of the medicine as claimed in claim 6, comprising preparing each traditional Chinese medicine or raw material according to the weight parts, and preparing clinically acceptable preparations according to the conventional method in the field with or without adding pharmaceutically acceptable auxiliary materials.
8. A preparation method of granules for coronary heart disease with qi deficiency and blood stasis comprises the following operations:
the preparation of a Chinese medicinal composition I according to claim 1 or 2, comprising astragalus root, ginkgo leaf, red sage root and earthworm; decocting with water for 1-3 times, each time with 5-10 times of water, each time for 1-2 hr; filtering while the mixture is hot, and combining the filtrates; concentrating the filtrate to relative density of 1.05-1.10 (60deg.C), adding part of dextrin, mixing, spray drying, adding the rest dextrin, mixing, and dry granulating; wherein the total weight of the dextrin is 30% -50% of the total weight of the medicinal materials;
preferably, astragalus root, ginkgo leaf, red sage root and earthworm are decocted with water twice, and water which is 10 times of the total weight of the medicinal materials is added for the first time, and the decoction is carried out for 1 hour; adding water 8 times of the total weight of the medicinal materials for the second time, and decocting for 1 hour.
9. A preparation method of a capsule for treating coronary heart disease with qi deficiency and blood stasis comprises the following steps:
preparing the astragalus extract, ginkgo leaf extract, red sage extract and earthworm extract according to the Chinese medicinal composition II of any one of claims 3 to 5; adding pharmaceutically acceptable adjuvants, mixing, granulating by dry method, and making into capsule;
preferably, the pharmaceutically acceptable auxiliary materials are microcrystalline cellulose and magnesium stearate.
10. Use of a traditional Chinese medicine composition i according to claim 1 or 2, a traditional Chinese medicine composition ii according to any one of claims 3 to 5, a medicament according to claim 6, a granule prepared according to the preparation method of claim 8 or a capsule prepared according to the preparation method of claim 9 in the preparation of a medicament for treating coronary heart disease due to qi deficiency and blood stasis.
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| CN202311258131 | 2023-09-27 | ||
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