Traditional Chinese medicine compound composition for treating cardiovascular and cerebrovascular diseases as well as preparation method and application thereof

Abstract

The invention discloses a traditional Chinese medicine compound composition for treating cardiovascular and cerebrovascular diseases and a preparation method and application thereof. The traditional Chinese medicine compound composition consists of American ginseng, pseudo-ginseng, astragalus membranaceus, kudzu vine root, hawthorn, ligusticum wallichii and salvia miltiorrhiza. The traditional Chinese medicine compound composition is prepared by adopting a modern preparation technology, extracting and separating according to effective chemical components of different medicines to obtain various medicine effective components such as saponins, polysaccharides, flavonoids, alkaloids, phenolic acids and the like, and then fermenting and degrading through probiotics. The traditional Chinese medicine compound composition disclosed by the invention has the effects of tonifying vitality, promoting blood circulation to remove blood stasis, dredging channels and collaterals, restoring consciousness and inducing resuscitation, and is used for treating and preventing coronary heart disease, arteriosclerosis, fatigue, limb numbness, ischemic cerebral apoplexy and cerebral hemorrhage sequelae caused by deficiency of qi and blood as well as anticoagulation and thrombus prevention after heart stent treatment; the medicine is small in dosage, and can be easily absorbed and utilized by the body to exert the medicine effect through fermentation.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine and health product preparations. Specifically, a traditional Chinese medicine compound composition for preventing and / or treating cardiovascular and cerebrovascular diseases such as arteriosclerosis, coronary heart disease, and ischemic stroke, and its preparation method and application are disclosed. Background Art

[0002] Cardiovascular and cerebrovascular diseases are a general term for heart blood vessel and cerebrovascular diseases, generally referring to ischemic or hemorrhagic diseases that occur in the heart, brain, and whole body tissues caused by hyperlipidemia, blood viscosity, atherosclerosis, hypertension, etc. Cardiovascular and cerebrovascular diseases not only have a serious impact on the quality of life of patients, but may also cause serious complications such as heart failure and multiple organ failure, further threatening the life safety of patients.

[0003] Currently, the drugs used to treat cardiovascular and cerebrovascular diseases mainly follow the treatment principles of promoting blood circulation to remove blood stasis and dredging meridians. Through further understanding of cardiovascular and cerebrovascular diseases, we realize that: blood carries qi and operates in the vessels, and qi pushes blood to reach all parts of the body. Therefore, the key to treating cardiovascular and cerebrovascular diseases is to supplement qi and nourish blood, and solve the problems of deficiency of yin and yang and internal stasis of blood stasis by supplementing qi and promoting blood circulation, so as to truly solve cardiovascular and cerebrovascular diseases from the root cause. Patent CN101020028A discloses a traditional Chinese medicine for treating cardiovascular and cerebrovascular diseases. Although it has the effects of supplementing qi, nourishing blood, promoting blood circulation to remove blood stasis, and dilating blood vessels, it has a large number of components, contains precious and rare medicinal materials, has a high cost, and the treatment effect on cardiovascular and cerebrovascular diseases needs to be further improved. Summary of the Invention

[0004] The purpose of the present invention is to overcome the above-mentioned defects and deficiencies in the prior art, and provide a traditional Chinese medicine compound composition, which can not only supplement primordial qi, promote qi and blood circulation, but also promote blood circulation to remove blood stasis and dredge meridians, so that qi and blood are abundant, thereby promoting the heart to be strong. It not only has simple components and low cost, but also significantly improves the treatment effect on cardiovascular and cerebrovascular diseases.

[0005] The second purpose of the present invention is to provide a preparation method of the traditional Chinese medicine compound composition.

[0006] The third purpose of the present invention is to provide the application of the traditional Chinese medicine compound composition.

[0007] The above purposes of the present invention are achieved by the following technical solutions: A traditional Chinese medicine compound composition is prepared from the following traditional Chinese medicine components in the following weight ratios: American ginseng: notoginseng: astragalus membranaceus: kudzu root: hawthorn: ligusticum wallichii: salvia miltiorrhiza = (0.5 - 2):(0.5 - 2):(1 - 3):(1 - 4):(1 - 3):(0.5 - 2):(1 - 3).

[0008] In the traditional Chinese medicine compound composition of the present invention: American ginseng is the dried root of Panax quinquefolius L., which is sweet, slightly bitter, and cool in nature, and has the effects of replenishing qi and nourishing yin, clearing heat and promoting fluid production. Its main functions include enhancing immunity and relieving fatigue. It mainly contains effective components such as ginsenosides and polysaccharides. American ginseng Astragalus membranaceus (Fisch.) Bge. or Astragalus membranaceus (Bge.) Hsiao is the dried root of the leguminous plant Astragalus membranaceus (Fisch.) Bge. or Astragalus membranaceus (Bge.) Hsiao, which is sweet in taste and warm in nature, and has the effects of replenishing qi and raising yang, strengthening the exterior and consolidating the superficial resistance, inducing diuresis and alleviating edema, and promoting granulation and detoxicating. It mainly acts on the nutrient qi and defensive qi, especially on tonifying the defensive qi, that is, the deficiency of the body surface. It mainly contains astragalosides and astragalus polysaccharides.

[0009] Astragalus membranaceus (Fisch.) Bge. or Astragalus membranaceus (Bge.) Hsiao is the dried root of the leguminous plant Astragalus membranaceus (Fisch.) Bge. or Astragalus membranaceus (Bge.) Hsiao, which is sweet in taste and warm in nature, and has the effects of replenishing qi and raising yang, strengthening the exterior and consolidating the superficial resistance, inducing diuresis and alleviating edema, and promoting granulation and detoxicating. It mainly acts on the nutrient qi and defensive qi, especially on tonifying the defensive qi, that is, the deficiency of the body surface. It mainly contains astragalosides and astragalus polysaccharides. Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.)Hsiao or Astragalus membranaceus (Fisch.) Bge. is the dried root of the leguminous plant Astragalus membranaceus (Fisch.) Bge. or Astragalus membranaceus (Bge.) Hsiao, which is sweet in taste and warm in nature, and has the effects of replenishing qi and raising yang, strengthening the exterior and consolidating the superficial resistance, inducing diuresis and alleviating edema, and promoting granulation and detoxicating. It mainly acts on the nutrient qi and defensive qi, especially on tonifying the defensive qi, that is, the deficiency of the body surface. It mainly contains astragalosides and astragalus polysaccharides. Astragalus membranaceus (Fisch.)Bge. is the dried root of the leguminous plant Astragalus membranaceus (Fisch.) Bge. or Astragalus membranaceus (Bge.) Hsiao, which is sweet in taste and warm in nature, and has the effects of replenishing qi and raising yang, strengthening the exterior and consolidating the superficial resistance, inducing diuresis and alleviating edema, and promoting granulation and detoxicating. It mainly acts on the nutrient qi and defensive qi, especially on tonifying the defensive qi, that is, the deficiency of the body surface. It mainly contains astragalosides and astragalus polysaccharides.

[0010] Kudzu root is the dried root of Pueraria lobata (Willd.) Ohwi, which is sweet, pungent, and cool in nature, and has the functions of relieving muscle spasms and fever, promoting fluid production and quenching thirst, promoting eruption, raising yang and stopping diarrhea, dredging channels and collaterals, and relieving alcohol toxicity. Kudzu root can dilate microvessels, improve microcirculation, and help prevent and treat peripheral vascular diseases. The contained puerarin flavonoids and polysaccharides are all its effective components. Kudzu root (Willd.) Ohwi is the dried root of Pueraria lobata (Willd.) Ohwi, which is sweet, pungent, and cool in nature, and has the functions of relieving muscle spasms and fever, promoting fluid production and quenching thirst, promoting eruption, raising yang and stopping diarrhea, dredging channels and collaterals, and relieving alcohol toxicity. Kudzu root can dilate microvessels, improve microcirculation, and help prevent and treat peripheral vascular diseases. The contained puerarin flavonoids and polysaccharides are all its effective components.

[0011] Hawthorn is the dried ripe fruit of Crataegus pinnatifida Bge. var. major N. E. Br. or Crataegus pinnatifida Bge., which is sour, sweet, and slightly warm in nature, and has the effects of promoting digestion and strengthening the stomach, promoting qi circulation and removing stasis, and reducing turbidity and lipid. Hawthorn can act on vascular smooth muscle, dilate blood vessels, lower blood pressure, and reduce the burden on the heart. It mainly contains flavonoids and phenolic acids. Hawthorn fruit Bge. var. major N. E. Br. or Crataegus pinnatifida Bge. is the dried ripe fruit of Crataegus pinnatifida Bge. var. major N. E. Br. or Crataegus pinnatifida Bge., which is sour, sweet, and slightly warm in nature, and has the effects of promoting digestion and strengthening the stomach, promoting qi circulation and removing stasis, and reducing turbidity and lipid. Hawthorn can act on vascular smooth muscle, dilate blood vessels, lower blood pressure, and reduce the burden on the heart. It mainly contains flavonoids and phenolic acids. Hawthorn fruit Bge. is the dried ripe fruit of Crataegus pinnatifida Bge. var. major N. E. Br. or Crataegus pinnatifida Bge., which is sour, sweet, and slightly warm in nature, and has the effects of promoting digestion and strengthening the stomach, promoting qi circulation and removing stasis, and reducing turbidity and lipid. Hawthorn can act on vascular smooth muscle, dilate blood vessels, lower blood pressure, and reduce the burden on the heart. It mainly contains flavonoids and phenolic acids.

[0012] Chuanxiong is the dried rhizome of Ligusticum chuanxiong Hort., which is pungent and warm in nature, and has the functions of promoting blood circulation and qi movement, dispelling wind and relieving pain. It is mainly used for chest pain and hypochondriac pain, and plays an important role in the prevention and treatment of cardiovascular and cerebrovascular diseases. It can guide drugs to ascend into the brain. It mainly contains chuanxiong alkaloids and flavonoids. Sichuan lovage rhizome Hort. is the dried rhizome of Ligusticum chuanxiong Hort., which is pungent and warm in nature, and has the functions of promoting blood circulation and qi movement, dispelling wind and relieving pain. It is mainly used for chest pain and hypochondriac pain, and plays an important role in the prevention and treatment of cardiovascular and cerebrovascular diseases. It can guide drugs to ascend into the brain. It mainly contains chuanxiong alkaloids and flavonoids.

[0013] Salvia miltiorrhiza is the dried root and rhizome of Salvia miltiorrhiza Bge., which is bitter and slightly cold in nature, and has the effects of promoting blood circulation to remove stasis, dredging channels and relieving pain, clearing the heart and relieving vexation, cooling blood and dissipating carbuncles. Salvia miltiorrhiza has a significant effect on inhibiting platelet aggregation and promoting vascular repair. The contained salvianolic acids and flavonoids are all its effective components. Danshen root Bge. is the dried root and rhizome of Salvia miltiorrhiza Bge., which is bitter and slightly cold in nature, and has the effects of promoting blood circulation to remove stasis, dredging channels and relieving pain, clearing the heart and relieving vexation, cooling blood and dissipating carbuncles. Salvia miltiorrhiza has a significant effect on inhibiting platelet aggregation and promoting vascular repair. The contained salvianolic acids and flavonoids are all its effective components.

[0014] "Plain Questions: On the Harmony between Man and Nature" clearly states: "When the vital qi is stored internally, pathogens cannot cause harm." This fully demonstrates the important role of vital qi in defending against pathogens and maintaining a healthy state. When the vital qi is insufficient, pathogens are likely to invade the human body, leading to various diseases. In the case of cardiovascular and cerebrovascular diseases, their pathogenesis is closely related to insufficient vital qi.

[0015] It is recorded in "Synopsis of the Golden Chamber": "Blood stasis is inside while obstruction is outside" and "When phlegm and blood stasis are in the epigastric region, there will be palpitations", which profoundly reveals the important pathogenic role of blood stasis in cardiovascular and cerebrovascular diseases. However, currently, most traditional Chinese medicines for treating cardiovascular and cerebrovascular diseases in clinical practice mainly follow the therapeutic principles of promoting blood circulation to remove blood stasis and dredging the channels and collaterals.

[0016] Through a systematic review of traditional Chinese medical literature, the present invention realizes that: Blood depends on the promotion of qi to flow in the vessels, and qi reaches all parts of the body through the transportation of blood, that is, the so-called "when qi moves, blood moves". Therefore, the key to treating cardiovascular and cerebrovascular diseases lies in supplementing qi and nourishing blood. Only by supplementing qi and promoting blood circulation can the problems of deficiency of yin and yang and internal retention of blood stasis be effectively solved, and cardiovascular and cerebrovascular diseases can be fundamentally prevented and treated.

[0017] Therefore, the present invention relates to a traditional Chinese medicine composition, comprising American ginseng, notoginseng, astragalus membranaceus, kudzu root, hawthorn, ligusticum wallichii, and salvia miltiorrhiza. This traditional Chinese medicine composition includes two major categories: traditional Chinese medicines for supplementing qi and traditional Chinese medicines for promoting blood circulation. Among them, the traditional Chinese medicines for supplementing qi are American ginseng and astragalus membranaceus, which indirectly support the health of the cardiovascular and cerebrovascular systems by enhancing immunity and improving heart and lung functions; while the traditional Chinese medicines for promoting blood circulation are notoginseng, kudzu root, hawthorn, ligusticum wallichii, and salvia miltiorrhiza, which directly act on the cardiovascular and cerebrovascular systems, promote blood circulation, inhibit platelet aggregation, dilate blood vessels, reduce inflammation and oxidative damage, thereby preventing and treating cardiovascular and cerebrovascular diseases. The two categories of traditional Chinese medicines have a complementary synergistic effect. The traditional Chinese medicines for supplementing qi provide a stable physical basis for the traditional Chinese medicines for promoting blood circulation and enhance their curative effects; while the traditional Chinese medicines for promoting blood circulation further enhance the effects of the traditional Chinese medicines for supplementing qi by improving blood circulation and blood vessel functions. The synergistic effect of this combination can comprehensively prevent and treat cardiovascular and cerebrovascular diseases, improve the quality of life, and extend lifespan.

[0018] Furthermore, the traditional Chinese medicine compound composition is prepared from the following traditional Chinese medicine components in the following weight ratios: American ginseng: notoginseng: astragalus membranaceus: kudzu root: hawthorn: ligusticum wallichii: salvia miltiorrhiza = (1 - 2):(1 - 2):(1 - 2):(1 - 3):(1 - 3):(1 - 2):(1 - 3).

[0019] Preferably, the traditional Chinese medicine compound composition is prepared from the following traditional Chinese medicine components in the following weight ratios: American ginseng: notoginseng: astragalus membranaceus: kudzu root: hawthorn: ligusticum wallichii: salvia miltiorrhiza = 1:1:1.25:1.875:1.625:1:1.625. For example: 80 g of American ginseng, 80 g of notoginseng, 100 g of astragalus membranaceus, 150 g of kudzu root, 130 g of hawthorn, 80 g of ligusticum wallichii, and 130 g of salvia miltiorrhiza.

[0020] The present invention also provides a preparation method of the traditional Chinese medicine compound composition described in any one of the above, specifically including the following steps: S1. Mix and pulverize American ginseng and pseudo-ginseng into fine powder, or soak American ginseng and pseudo-ginseng in 8-10 times the amount of water for 1-4 hours, then heat and extract for 1.5-3 hours each time, extract 2-3 times, filter, and concentrate to obtain a water extract; S2. Soak astragalus membranaceus, kudzu root, and salvia miltiorrhiza in 8-10 times the amount of water for 1-4 hours, then heat and extract for 1.5-3 hours each time, extract 2-3 times, filter, and concentrate to obtain a water extract, or concentrate the water extract to a thick extract, dry under reduced pressure, and pulverize to obtain a water extract powder; S3. Add hawthorn and chuanxiong rhizome to 6-9 times the amount of 60-80% ethanol, heat and reflux for 2-3.5 hours each time, extract 2-3 times, filter, combine the extracts, recover ethanol to obtain an alcohol extract, or dry the alcohol extract under reduced pressure and pulverize to obtain an alcohol extract powder; S4. Mix the fine powder of American ginseng and pseudo-ginseng, the water extract powder of astragalus membranaceus, kudzu root, and salvia miltiorrhiza, and the alcohol extract powder of hawthorn and chuanxiong rhizome obtained in steps S1-S3 uniformly to obtain a mixed powder; or mix the water extracts of American ginseng and pseudo-ginseng, astragalus membranaceus, kudzu root, and salvia miltiorrhiza, and the alcohol extracts of hawthorn and chuanxiong rhizome obtained in steps S1-S3 uniformly to obtain a mixed liquid.

[0021] The traditional Chinese medicine compound composition of the present invention combines tonifying qi traditional Chinese medicine and activating blood circulation traditional Chinese medicine through scientific compatibility, combines modern extraction and preparation technologies, extracts and separates the effective chemical components of American ginseng, pseudo-ginseng, astragalus membranaceus, kudzu root, hawthorn, chuanxiong rhizome, and salvia miltiorrhiza to obtain various effective drug components such as saponins, polysaccharides, flavonoids, alkaloids, and phenolic acids. The refined extracts can be directly made into suitable preparations.

[0022] Further, the fine powder in step S1 is 80-100 mesh.

[0023] Further, the ethanol in step S3 is 70% ethanol.

[0024] Further, the present invention also innovatively provides a preparation method for fermenting the composition to form a preparation that is more easily absorbed and exerts its efficacy. The principle is as follows: Patients with cardiovascular and cerebrovascular diseases, hypertension, coronary heart disease, heart failure, etc. will all be accompanied by the occurrence of qi deficiency syndrome. The intestinal flora of patients is mostly disordered, the digestive enzymes are insufficient, and the digestive and absorption abilities are weakened. At present, the traditional Chinese medicine compositions for treating qi and blood weakness mainly contain ginseng, American ginseng, and astragalus membranaceus. However, most of the effective components of such drugs are macromolecular substances such as saponins and polysaccharides, with low bioavailability and low intestinal absorption, which will lead to an extended treatment cycle and the treatment obstacle of "being unable to receive tonics due to weakness".

[0025] Probiotics are a type of microorganisms beneficial to the host and are widely present in the human intestinal tract and reproductive system, playing an important role in the digestion and absorption of food and drugs. Using probiotics to transform components such as saponins, polysaccharides, flavonoid glycosides, alkaloids, and phenolic acids in traditional Chinese medicine can promote the transformation of active ingredients into smaller molecular substances that are more easily absorbed by the human body, and even produce new substances with stronger activity, achieving a rapid effect of replenishing qi and activating blood circulation.

[0026] Specifically, the method is to add probiotics to the extract obtained by mixing the water extract of American ginseng and notoginseng in step S4, the water extract of astragalus membranaceus, kudzu root, and salvia miltiorrhiza, and the alcohol extract of hawthorn and ligusticum wallichii, ferment for 1 - 3 days to obtain a fermentation broth, and then concentrate it to obtain the product. Each extract of the compound composition of the present invention is further fermented and degraded by probiotics such as lactobacillus and bifidobacterium, converting macromolecular saponins into sapogenins or smaller molecular secondary saponins, polysaccharides being cleaved into smaller molecular sugar chains, and glycosides such as flavonoids, alkaloids, and phenolic acids being degraded into small molecules, which is beneficial for the drug to be absorbed by the body and better exerts the effects of replenishing primordial qi, promoting blood circulation to remove stasis, dredging meridians, and clearing the orifices of the mind.

[0027] Furthermore, the probiotics are common strains including the genus Lactobacillus and the genus Bifidobacterium, preferably Lactobacillus plantarum.

[0028] Furthermore, the method is to add lactobacillus or bifidobacterium powder to sterile physiological saline to prepare a bacterial suspension of 1 - 2 mg / mL (preferably 1 mg / mL), add the bacterial suspension to the mixed extract of step S4 at 1% of the volume of the mixed solution, ferment at a temperature of 36 - 37 °C (preferably 36 °C) for 36 - 48 hours (preferably 48 hours) for fermentation culture, and after completion, concentrate to obtain a fermented concentrate; vacuum dry or spray dry the fermented concentrate, and add pharmaceutically suitable excipients to prepare a directly usable traditional Chinese medicine preparation.

[0029] Tests show that the traditional Chinese medicine compound composition of the present invention has the effects of replenishing primordial qi, promoting blood circulation to remove stasis, dredging meridians, and clearing the orifices of the mind, and is used for the treatment and prevention of coronary heart disease, arteriosclerosis, fatigue, limb numbness, ischemic stroke, sequelae of cerebral hemorrhage, and anticoagulation and thrombus prevention after cardiac stent treatment caused by qi and blood deficiency. Its dosage is small, and fermentation makes it more easily absorbed and utilized by the body to exert its medicinal effects.

[0030] Therefore, the present invention also provides the application of any of the above - mentioned traditional Chinese medicine compound compositions in the preparation of drugs for preventing and / or treating cardiovascular and cerebrovascular diseases.

[0031] Furthermore, the cardiovascular and cerebrovascular diseases include coronary heart disease, arteriosclerosis, fatigue, limb numbness, ischemic stroke, sequelae of cerebral hemorrhage, or anticoagulation and thrombus prevention after cardiac stent treatment caused by qi and blood deficiency.

[0032] Furthermore, the pharmaceutical preparation includes, but is not limited to, water pills, granules, tablets, capsules, etc.

[0033] The present invention also provides a drug for preventing and / or treating cardiovascular and cerebrovascular diseases, containing any one of the above-mentioned traditional Chinese medicine compound compositions.

[0034] Furthermore, the drug also includes pharmaceutically acceptable excipients.

[0035] For example: Mix the fine powders of American ginseng and notoginseng obtained by the above extraction, the water extract powders of astragalus, kudzu root, and salvia miltiorrhiza, and the alcohol extract powders of hawthorn and ligusticum wallichii evenly, and add pharmaceutically suitable excipients to make a directly usable traditional Chinese medicine preparation. Vacuum dry or spray dry the above fermentation concentrate, and add pharmaceutically suitable excipients to make a directly usable traditional Chinese medicine preparation.

[0036] Compared with the prior art, the present invention has the following beneficial effects: The present invention provides a traditional Chinese medicine compound composition for treating cardiovascular and cerebrovascular diseases. The traditional Chinese medicine compound composition is composed of American ginseng, notoginseng, astragalus, kudzu root, hawthorn, ligusticum wallichii, and salvia miltiorrhiza. The traditional Chinese medicine compound composition is prepared by using modern preparation techniques, extracting and separating according to the effective chemical components of different medicinal flavors to obtain various drug effective components such as saponins, polysaccharides, flavonoids, alkaloids, phenolic acids, etc., or further prepared by fermenting and degrading with probiotics. The traditional Chinese medicine compound composition of the present invention has the effects of tonifying primordial qi, promoting blood circulation to remove blood stasis, dredging meridians, and resuscitating the mind. It is used for treating and preventing coronary heart disease, arteriosclerosis, fatigue, limb numbness, ischemic stroke, sequelae of cerebral hemorrhage, and anticoagulation and thrombus prevention after cardiac stent treatment caused by qi and blood deficiency. Its dosage is small, and fermentation makes it easier to be absorbed and utilized by the body to exert its medicinal effects; the traditional Chinese medicine compound composition of the present invention not only has simple components and low cost, but also significantly improves the treatment effect on cardiovascular and cerebrovascular diseases. Detailed implementation manners

[0037] The following specific examples are used to further illustrate the present invention, but the examples do not limit the present invention in any form. Unless otherwise specified, the reagents, methods, and equipment used in the present invention are conventional reagents, methods, and equipment in the technical field.

[0038] Unless otherwise specified, the reagents and materials used in the following examples are all commercially available. Example 1

[0039] A traditional Chinese medicine compound composition for treating cardiovascular and cerebrovascular diseases and its preparation method

[0040] The described traditional Chinese medicine compound composition is composed of American ginseng 40 kg, notoginseng 40 kg, astragalus membranaceus 50 kg, kudzu root 75 kg, hawthorn 65 kg, chuanxiong rhizome 40 kg, and salvia miltiorrhiza 65 kg with the following proportion of medicinal flavors.

[0041] The preparation method of the above traditional Chinese medicine compound composition is as follows: (1) Mix and pulverize American ginseng and notoginseng into fine powder of 80 - 100 meshes, 80 kg, and set aside.

[0042] (2) Soak astragalus membranaceus, kudzu root, and salvia miltiorrhiza in 8 - 10 times the amount of water for 1 - 4 hours, then heat for extraction, 1.5 - 3 hours each time, extract 2 - 3 times, filter, concentrate, obtain the water extract, concentrate to thick extract, dry under reduced pressure, pulverize, and obtain 47.2 kg of water extract powder with a yield of 24.8%, and set aside.

[0043] (3) Add hawthorn and chuanxiong rhizome to 6 - 9 times the amount of 70% ethanol, heat under reflux for extraction, 2 - 3.5 hours each time, extract 2 - 3 times, filter, combine the extracts, recover ethanol, obtain the ethanol extract solution, dry under reduced pressure, pulverize, and obtain 17.5 kg of ethanol extract powder with a yield of 16.7%, and set aside.

[0044] (4) Mix 80 kg of the mixed fine powder of American ginseng and notoginseng obtained by extraction, 47.2 kg of the water extract powder of astragalus membranaceus, kudzu root, and salvia miltiorrhiza, and 17.5 kg of the ethanol extract powder of hawthorn and chuanxiong rhizome, and mix evenly to obtain a total of 144.7 kg.

[0045] (5) Take 20 kg of the mixed powder, add microcrystalline cellulose and 75% ethanol to moisten and make soft materials, mold into water pills, then cover the surface, dry, coat with carbonized rush pith, and polish to make water pill preparations.

[0046] (6) Take 20 kg of the mixed powder, add microcrystalline cellulose and 75% ethanol to moisten and make granules, dry, press into tablets or load into capsules after drying to make tablet preparations or capsule preparations. Example 2

[0047] The traditional Chinese medicine compound composition is composed of American ginseng 20 kg, notoginseng 20 kg, astragalus membranaceus 25 kg, kudzu root 37.5 kg, hawthorn 32.5 kg, chuanxiong rhizome 20 kg, and salvia miltiorrhiza 32.5 kg with the following proportion of medicinal flavors.

[0048] The preparation method of the above traditional Chinese medicine compound composition is as follows: (1) Crush American ginseng and notoginseng into coarse granules, soak in 8 - 10 times the amount of water for 1 - 4 hours, then heat for extraction, 1.5 - 3 hours each time, extract 2 - 3 times, filter, concentrate, dry under reduced pressure, pulverize, and obtain 10.6 kg of water extract powder with a yield of 26.4%, and set aside.

[0049] (2) Take 23.6 kg of the water extract powder prepared from Astragalus membranaceus, Pueraria lobata, and Salvia miltiorrhiza as in Example 1 and set aside.

[0050] (3) Take 8.75 kg of the ethanol extract powder prepared from Crataegus pinnatifida and Ligusticum chuanxiong as in Example 1 and set aside.

[0051] (4) Mix 10.6 kg of the mixed water extract powder of American ginseng and Panax notoginseng, 23.6 kg of the water extract powder of Astragalus membranaceus, Pueraria lobata, and Salvia miltiorrhiza, and 8.75 kg of the ethanol extract powder of Crataegus pinnatifida and Ligusticum chuanxiong, and mix them evenly to obtain a total of 42.9 kg.

[0052] (5) Take 10 kg of the mixed powder, add microcrystalline cellulose and 75% ethanol to moisten and make soft materials, plasticize them into water pills, then cover the surface, dry, coat with carbonized Juncus effusus L. clothes, and polish to make water pill preparations.

[0053] (6) Take 10 kg of the mixed powder, add microcrystalline cellulose and 75% ethanol to moisten and make granules, dry, compress into tablets or load them into capsules after drying to make tablet preparations or capsule preparations.

[0054] (7) Take 10 kg of the mixed powder, add dextrin and 75% ethanol to moisten and make granules, dry, and package to make granule preparations. Example 3

[0055] The traditional Chinese medicine compound composition consists of 20 kg of American ginseng, 20 kg of Panax notoginseng, 25 kg of Astragalus membranaceus, 37.5 kg of Pueraria lobata, 32.5 kg of Crataegus pinnatifida, 20 kg of Ligusticum chuanxiong, and 32.5 kg of Salvia miltiorrhiza in the following medicinal ingredient ratios.

[0056] The preparation method of the above traditional Chinese medicine compound composition is as follows: (1) Crush American ginseng and Panax notoginseng into coarse particles, soak them in 8 - 10 times the amount of water for 1 - 4 hours, then heat and extract for 1.5 - 3 hours each time, extract 2 - 3 times, filter, and concentrate to obtain a water extract solution, and set it aside.

[0057] (2) Soak Astragalus membranaceus, Pueraria lobata, and Salvia miltiorrhiza in 8 - 10 times the amount of water for 1 - 4 hours, then heat and extract for 1.5 - 3 hours each time, extract 2 - 3 times, filter, and concentrate to obtain a water extract solution, and set it aside.

[0058] (3) Add 6 - 9 times the amount of 70% ethanol to Crataegus pinnatifida and Ligusticum chuanxiong, heat and reflux for extraction for 2 - 3.5 hours each time, extract 2 - 3 times, filter, combine the extraction solutions, recover ethanol, and obtain an ethanol extract solution, and set it aside.

[0059] (4) Mix the water extract solutions of American ginseng and Panax notoginseng, the water extract solutions of Astragalus membranaceus, Pueraria lobata, and Salvia miltiorrhiza, and the ethanol extract solution of Crataegus pinnatifida and Ligusticum chuanxiong obtained by extraction evenly according to the prescription ratio, cool to 36°C, and set it aside.

[0060] (5) Add Lactobacillus plantarum into sterile physiological saline to prepare a bacterial suspension of 1 mg / mL. Add the bacterial suspension into the mixture in step (4). The volume of the bacterial suspension is 1 - 3% of the volume of the mixture, and then carry out fermentation culture at a fermentation temperature of 36°C for 36 - 48 hours. Concentrate to obtain a fermented concentrate for standby.

[0061] (6) Carry out vacuum drying or spray drying and pulverization on the fermented concentrate in the above step (5) to obtain 41.5 kg of dry powder.

[0062] (5) Take 10 kg of the mixed powder, add microcrystalline cellulose and 75% ethanol to moisten and make soft materials, then plasticize into water pills, and then cover the surface, dry, coat with carbonized rush pith, and polish to make water pill preparations.

[0063] (6) Take 10 kg of the mixed powder, add microcrystalline cellulose and 75% ethanol to moisten and make granules, dry, compress into tablets or load into capsules after drying to make tablet preparations or capsule preparations.

[0064] (7) Take 10 kg of the mixed powder, add dextrin, etc. and 75% ethanol to moisten and make granules, dry, and package to make granule preparations.

[0065] The traditional Chinese medicine compound composition and its preparations of the present invention have the effects of tonifying primordial qi, promoting blood circulation to remove blood stasis, dredging meridians, and rescuing the consciousness from coma, and have the use for treating and preventing cardiovascular and cerebrovascular diseases. The cardiovascular and cerebrovascular diseases include treating and preventing coronary heart disease, arteriosclerosis, fatigue, limb numbness, ischemic stroke, sequelae of cerebral hemorrhage, and anticoagulation and thrombus prevention after cardiac stent treatment caused by qi and blood deficiency.

[0066] Experimental Example 1 Protective effects of different drug administration groups on myocardial injury in a rat model of coronary heart disease Animals: 90 male SD rats, with a body weight of 220 - 250 g.

[0067] Drugs: The water pill preparation of Example 1, the granule preparation of Example 2, the granule preparation of Example 3, positive drug: Dioscoreae bulbiferae saponins tablet, control group: prepare tablets according to the method in the specific implementation manner of CN101020028A.

[0068] Method: Randomly divide into groups, with 10 rats in each group, namely blank group, model group, low-dose drug administration group, high-dose drug administration group, and positive drug group. Except for the blank group, the modeling rats were given a high-fat and high-methionine diet (87.3% basal diet, 0.5% sodium cholate, 0.2% propylthiouracil, 2% cholesterol, 3% methionine, 10% lard) for 6 weeks, and at the same time, 30 g / kg of pituitary posterior lobe hormone was intraperitoneally injected every 2 weeks, once a day for 3 consecutive days. Modeling was considered successful when the ST segment elevation > 0.1 mV and the T wave was tall in the electrocardiogram 30 minutes after injection.

[0069] Administration method: After confirming the successful establishment of the model, intragastric administration was started and continued for 14 days. The blank group and the model group were given corresponding volumes of normal saline. The daily intragastric administration doses were as follows: low-dose group: 1.89 g / Kg, high-dose group: 3.78 g / Kg, positive drug group: 3.78 g / Kg, control group: 1.89 g / Kg (low dose), 3.78 g / Kg (high dose). After the last administration, 4 mL of rat tail vein blood was collected, centrifuged for 15 min (radius 3 cm, rotation speed 3000 r / min), and the supernatant was extracted. The levels of cardiac troponin (cTn) I and creatine kinase isoenzyme (CK-MB) in each group were detected. The experimental results are shown in Table 1.

[0070]

[0071] Results: According to the experimental data of the myocardial injury protection experiment of different drug treatment groups on the coronary heart disease rat model in Table 1 above, the traditional Chinese medicine compound composition prepared in the examples of the present invention can significantly reduce the levels of cardiac troponin (cTn) I and creatine kinase isoenzyme (CK-MB) in the coronary heart disease model rats. It shows that the traditional Chinese medicine compound composition of the present invention can reduce the contents of the main substances reflecting myocardial cell injury, namely cardiac troponin and creatine kinase isoenzyme, so as to achieve the effect of reducing myocardial injury in coronary heart disease rats. Among the administration groups of the traditional Chinese medicine compound composition with different dosage forms, preparation methods and different compatibility of medicinal materials, the effects are better than those of the positive drug group and the control group (low-dose and high-dose groups). Among them, the effect of the high dose of Example 3 is the most significant, indicating that different drug combinations and ratios have obvious differences. In particular, the traditional Chinese medicine compound composition of the present invention can be further improved in treatment effect after being fermented by probiotics.

[0072] Experimental conclusion: The traditional Chinese medicine compound composition of the present invention can improve the myocardial injury caused by coronary heart disease.

[0073] Test Example 2 Effects of Different Drug Treatment Groups on Hemorheology and Hemodynamics of Atherosclerotic Rats Animals: 140 male SD rats, weighing 180 - 220 g.

[0074] Drugs: Pills of Example 1, granules of Example 2, granules of Example 3, positive drug: Di'ao Xinxuekang, control group (same as Test Example 1).

[0075] Method: Random grouping, with 10 rats in each group, namely the blank group, the model group, the low-dose administration group, the high-dose administration group, and the positive drug group. Except for the blank group, the remaining groups were fed a high-fat diet continuously for 10 weeks. After 1 week of feeding, 600,000 U / kg of vitamin D3 solution was intraperitoneally injected (once). Under an optical microscope, atherosclerotic plaques were formed on the aortic tissue of the rats, and the blood vessel wall and intima were significantly thickened, indicating that the AS rat model was successfully constructed.

[0076] Administration method: After confirming the successful establishment of the model, intragastric administration was started and continued for 4 weeks. The blank group and the model group were given the corresponding volume of normal saline. The daily intragastric administration doses were as follows: the low-dose group was 1.89 g / Kg, the high-dose group was 3.78 g / Kg, the positive drug group was 3.78 g / Kg, and the control group was 1.89 g / Kg (low dose) and 3.78 g / Kg (high dose). After the last administration of the rats, the rats were anesthetized with 3% sodium pentobarbital, the right common carotid artery was separated, and a catheter was inserted into the left ventricle. The maximum rate of rise of ventricular pressure (lv+dp / dtmax) and the time to peak ventricular pressure (t - dp / dtmax) of the rats in each group were monitored through the MS4000U-1C biological signal recording system. The experimental results are shown in Table 2. Subsequently, the abdominal aortic blood of the rats was collected and placed in a test tube containing sodium heparin, and the whole blood viscosity (low shear, medium shear, high shear), plasma viscosity, hematocrit, and platelet adhesion rate were measured. The experimental results are shown in Table 3.

[0077]

[0078]

[0079] Results: According to Tables 2 and 3 above, it can be seen from the experimental data on the effects of different drug administration groups on hemorheology and hemodynamics of atherosclerotic rats that the traditional Chinese medicine compound composition prepared in the examples of the present invention can shorten the time to peak ventricular pressure (t-dp / dtmax / ms) and increase the maximum rate of rise of ventricular pressure (lv+dp / dtmax (mmHg / s)); in addition, it can also reduce the whole blood viscosity (low shear, medium shear, high shear), plasma viscosity, and platelet adhesion rate of rats, and there is also an obvious downward trend in hematocrit. Among them, the high-dose group of Example 3, that is, the administration group prepared by fermentation, showed a significant decrease in hematocrit, indicating that the effect on hematocrit was significant after fermentation. The detection results of each example group were significantly better than those of the control group (low dose and high dose groups), and the low-dose group and high-dose group of Example 3 were particularly significant.

[0080] It is shown that the traditional Chinese medicine compound composition of the present invention can promote blood circulation to remove blood stasis, dredge meridians and collaterals by reducing blood viscosity, hematocrit and platelet adhesion rate, and play a role in treating and preventing atherosclerosis. Among the administration groups of the traditional Chinese medicine compound composition with different dosage forms, preparation methods and different compatibility of medicinal materials, the effects are slightly different, and the effect of Example 3 is the most significant, indicating that the traditional Chinese medicine compound composition of the present invention can further improve the treatment effect after being fermented by probiotics.

[0081] Experimental conclusion: The traditional Chinese medicine compound composition of the present invention has the functions of promoting blood circulation to remove blood stasis and dredging meridians and collaterals, and can significantly improve atherosclerosis.

[0082] Test Example 3 Protective effects of different drug administration groups on rats with ischemic stroke Animals: 180 male SD rats, weighing 220 - 250 g.

[0083] Drugs: Pills of Example 1, granules of Example 2, granules of Example 3, positive drug: Dioscoreae bulbiferae Rhizoma extract tablets, control group (same as Test Example 1).

[0084] Methods: Random grouping, 20 rats in each group, namely sham operation group, model group, low-dose administration group, high-dose administration group, and positive drug group. After anesthetizing the rats, fix the rats on a thermostatic electric heating plate at 37°C. Bluntly separate the neck muscles, successively expose the left common carotid artery, external carotid artery and internal carotid artery, ligate the common carotid artery and external carotid artery. Clamp the internal carotid artery, make a small incision at the distal end of the common carotid artery, insert a nylon wire with a diameter of 0.26 mm along the common carotid artery into the internal carotid artery to block the blood flow of the middle cerebral artery. After 2 h of ischemia, restore blood supply, ligate the internal carotid artery and close the surgical field, and intramuscularly inject penicillin to prevent infection. The sham operation group only separates the blood vessels without performing ischemia-reperfusion operation.

[0085] Administration method: After confirming the success of modeling, start gavage administration for 4 consecutive weeks. The model group and the sham operation group are given corresponding volumes of normal saline. The daily gavage administration doses are respectively: low-dose group 1.89 g / Kg, high-dose group: 3.78 g / Kg, positive drug group: 3.78 g / Kg, control group: 1.89 g / Kg (low dose), 3.78 g / Kg (high dose). After the last administration of the rats, anesthetize the rats with 3% sodium pentobarbital, take blood from the carotid artery of the rats, place it in a test tube containing sodium heparin, and perform hemorheology detection. The experimental results are shown in Table 4.

[0086]

[0087] Results: As can be seen from the test data in Table 4 above, the traditional Chinese medicine compound composition prepared in the embodiments of the present invention can reduce the blood viscosity of rats and has a significant inhibitory effect on platelet aggregation. Compared with the model group, each embodiment group can prolong the TT time, and the PT time of each embodiment group is prolonged, showing significant differences ( P <0.01), significantly superior to the control groups (low-dose and high-dose groups).

[0088] It shows that the traditional Chinese medicine compound composition of the present invention can reduce blood viscosity, inhibit platelet aggregation, activate blood circulation to remove stasis, dredge meridians and collaterals, and has the effects of treating ischemic stroke and preventing thrombosis. Among the administration groups of the traditional Chinese medicine compound composition with different dosage forms, preparation methods and different compatibility of medicinal materials, the effects are slightly different. Among them, the high dose of Example 3 has the most significant effect, indicating that the traditional Chinese medicine compound composition of the present invention can further improve the treatment effect after being fermented by probiotics.

[0089] Experimental conclusion: The traditional Chinese medicine compound composition of the present invention has the functions of activating blood circulation to remove stasis and dredging meridians and collaterals, and can be used for the treatment and prevention of ischemic stroke, sequelae of cerebral hemorrhage and anticoagulation and thrombosis prevention after cardiac stent treatment.

[0090] Test Example 4 Observation on the Medication of Patients with Limb Numbness after Stroke

[0091] Inclusion criteria: (1) Meeting the diagnostic criteria of traditional Chinese and Western medicine; (2) Confirmed by MRI or CT diagnosis; (3) The course of disease is more than 1 month; (4) Stable vital signs and able to communicate normally; (5) The patient or family member gives informed consent and signs the informed consent form.

[0092] Efficacy criteria: (1) Cure: Symptoms and signs basically disappear, muscle strength reaches grade 4, speech is clear, limb numbness basically disappears, social function is basically restored, and life can be self-care or able to work again. (2) Marked effect: Symptoms and signs are significantly improved, muscle strength is increased by 2 grades on the original basis, limb numbness is reduced, limb mobility is increased, and social function is significantly restored, but the fine motor activities of life are slightly poor. (3) Effective: Symptoms and signs are partially improved, muscle strength is increased by 1 grade on the original basis, limb numbness is slightly reduced, limb movement has a certain improvement, and social function is restored to some extent. (4) Ineffective: Can perform simple limb activities, and symptoms and signs are not significantly improved.

[0093] Administration method: (1) Drugs: Water pills of the traditional Chinese medicine compound composition prepared in Example 1, granules of the traditional Chinese medicine compound composition prepared in Example 2, granules of the traditional Chinese medicine compound composition prepared by fermentation in Example 3, and the original powder tablets made of the traditional Chinese medicine compound composition in the control group (the same as Test Example 1). (2) Administration dose: Each administration dose of the groups of Examples 1, 2, and 3 is 3 g / time; the control group takes tablets of the same dose of 3 g / time. (3) Medication method: Once in the morning and once in the evening, orally for 21 - 28 days continuously, and take with warm water.

[0094] Observe and record the improvement of symptoms. The results are shown in Table 5.

[0095]

[0096] Among them, there were 2 ineffective patients after treatment in Example 1, and the total effective rate was 93.3%; in Example 2, all were processed by extraction and then used as medicine, which was equivalent to a higher content of the active ingredients in the composition. After treatment, there was 1 ineffective patient, and the total effective rate reached 96.7%; in Example 3, all were processed by extraction and then prepared by probiotic fermentation, which was equivalent to a higher content of the active ingredients in the composition and was more easily absorbed by the intestine after fermentation to exert the medicinal effect. After treatment, the effects of all patients were obvious and the cure rate was higher; while for the composition of the comparative example, because it contained precious and rare medicinal materials, it was not only expensive but also had a large dosage, and the compliance of patients was not ideal. There were 4 ineffective patients, and the total effective rate was 83.3%, which was significantly lower than the pharmaceutical composition of the present invention.

[0097] The pharmaceutical composition of the present invention has definite curative effects, a simple prescription and relatively low cost, and can be used by a large number of patients. Most of the patients with ineffective application are the elderly with long-term chronic underlying diseases, and other therapeutic drugs are taken simultaneously during the medication period, making it difficult to exclude the interference of other drugs. After using the composition of the present invention, the limb movement has improved, but the effect is not obvious. The curative effects of the convalescent and young and middle-aged patients are significant, mostly showing marked effects, and a few are effective.

[0098] In addition, the outstanding feature of the present invention is that the effect is better after fermentation. Especially for elderly patients with cardiovascular and cerebrovascular diseases, most of them have weakened gastrointestinal digestion and absorption functions, and the absorption effect of drugs is also affected. It is observed that patients are more likely to accept the granule of the pharmaceutical composition of the present invention after fermentation, which is not greasy, easy to absorb and has a fast onset.

[0099] Conclusion: The effective rate for patients with limb numbness after stroke is as high as over 93.3%. The traditional Chinese medicine compound composition of the present invention can significantly relieve the clinical symptoms of stroke patients, improve the daily living ability and the effect of limb motor function.

[0100] It should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than a limitation on the protection scope of the present invention. Any simple modification or equivalent replacement made by those of ordinary skill in the art to the technical solution of the present invention shall not depart from the essence and scope of the technical solution of the present invention.

Claims

1. A traditional Chinese medicine compound composition, characterized in that, It is prepared from the following traditional Chinese medicine components in the following weight ratios: American ginseng: Notoginseng: Astragalus membranaceus: Pueraria lobata: Hawthorn: Ligusticum chuanxiong: Salvia miltiorrhiza = (0.5 - 2):(0.5 - 2):(1 - 3):(1 - 4):(1 - 3):(0.5 - 2):(1 - 3).

2. The traditional Chinese medicine compound composition according to claim 1, wherein It is prepared from the following traditional Chinese medicine components in the following weight ratios: American ginseng: Notoginseng: Astragalus membranaceus: Pueraria lobata: Hawthorn: Ligusticum chuanxiong: Salvia miltiorrhiza = (1 - 2):(1 - 2):(1 - 2):(1 - 3):(1 - 3):(1 - 2):(1 - 3).

3. The preparation method of the traditional Chinese medicine compound composition according to claim 1 or 2, characterized in that, It includes the following steps: S1. Mix and pulverize American ginseng and notoginseng into fine powder, or soak American ginseng and notoginseng in 8 - 10 times the amount of water for 1 - 4 hours, then heat and extract for 1.5 - 3 hours each time, extract 2 - 3 times, filter, and concentrate to obtain a water extract solution; S2. Soak Astragalus membranaceus, Pueraria lobata, and Salvia miltiorrhiza in 8 - 10 times the amount of water for 1 - 4 hours, then heat and extract for 1.5 - 3 hours each time, extract 2 - 3 times, filter, and concentrate to obtain a water extract solution, or concentrate the water extract solution to a thick extract, dry it under reduced pressure, and pulverize to obtain a water extract powder; S3. Add 6 - 9 times the amount of 60 - 80% ethanol to hawthorn and Ligusticum chuanxiong, heat and reflux for extraction for 2 - 3.5 hours each time, extract 2 - 3 times, filter, combine the extraction solutions, recover ethanol to obtain an alcohol extract solution, or dry the alcohol extract solution under reduced pressure and pulverize to obtain an alcohol extract powder; S4. Mix the fine powder of American ginseng and notoginseng obtained in steps S1 - S3, the water extract powder of Astragalus membranaceus, Pueraria lobata, and Salvia miltiorrhiza, and the alcohol extract powder of hawthorn and Ligusticum chuanxiong evenly to obtain a mixed powder; or mix the water extract solutions of American ginseng and notoginseng, Astragalus membranaceus, Pueraria lobata, and Salvia miltiorrhiza, and the alcohol extract solution of hawthorn and Ligusticum chuanxiong obtained in steps S1 - S3 evenly to obtain a mixed solution.

4. The preparation method according to claim 3, wherein The said step also includes adding probiotics to the extraction solution after mixing the water extract solutions of American ginseng and notoginseng, Astragalus membranaceus, Pueraria lobata, and Salvia miltiorrhiza, and the alcohol extract solutions of hawthorn and Ligusticum chuanxiong in step S4, fermenting for 1 - 3 days to obtain a fermentation solution, and concentrating to obtain the product.

5. The preparation method according to claim 3, characterized in that, The fine powder described in step S1 is 80 - 100 mesh.

6. Use of the traditional Chinese medicine compound composition according to claim 1 or 2 in the preparation of a pharmaceutical preparation for preventing and / or treating cardiovascular and cerebrovascular diseases.

7. The application according to claim 6, wherein The said cardiovascular and cerebrovascular diseases include coronary heart disease due to qi and blood deficiency, arteriosclerosis, fatigue, limb numbness, ischemic stroke, sequelae of cerebral hemorrhage, or anticoagulation and thrombus prevention after cardiac stent treatment.

8. The application according to claim 6, characterized in that The said pharmaceutical preparation includes water pills, granules, tablets, or capsules.

9. A drug for preventing and / or treating cardiovascular and cerebrovascular diseases, characterized in that, It contains the traditional Chinese medicine compound composition according to claim 1 or 2.

10. The drug according to claim 9, characterized in that, It also includes pharmaceutically acceptable excipients.

Images