Traditional Chinese medicine composition for preventing and treating cardiovascular and cerebrovascular diseases

Abstract

The invention provides a traditional Chinese medicine composition for preventing and treating cardiovascular and cerebrovascular diseases, which is based on differentiation treatment of cold and heat properties of medicinal materials and is integrated with a modern preparation technology to improve the efficacy. Cold medicinal materials are subjected to superfine grinding and subcritical CO2 blasting pretreatment, and multi-enzyme step-by-step fermentation and a dynamic water extraction technology are combined, so that dissolution of active ingredients is enhanced; warm medicinal materials are subjected to gradient ethanol extraction assisted by microwave-ultrasonic synergistic effect, so that the enrichment efficiency of thermosensitive components is optimized; the neutral medicinal materials are separated by adopting an acid-base adaptive separation method, and polysaccharide and flavonoid substances are selectively retained. The components are constructed into an inner-layer, middle-layer and outer-layer structure, so that the bioavailability and the multi-target synergistic effect can be remarkably improved, and the composition has a good effect in preventing and treating cardiovascular and cerebrovascular diseases.

Description

Technical Field

[0001] The present invention belongs to the field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for preventing and treating cardiovascular and cerebrovascular diseases. Background Art

[0002] Panax notoginseng is an important traditional Chinese medicine, with significant pharmacological effects and traditional uses. Its main pharmacological effects include hemostasis, promoting blood circulation to remove blood stasis, anti-inflammatory, anti-tumor, reducing blood lipid, reducing blood sugar, anti-aging, etc. The main active ingredients of Panax notoginseng are saponin compounds, such as ginsenoside Rb1, Rb2 and notoginsenoside R1, and these ingredients show significant curative effects in cardiovascular diseases, blood system diseases and immune regulation, etc.

[0003] Hawthorn is a traditional Chinese medicine with rich pharmacological properties and traditional uses. Its main effects include promoting digestion and resolving food stagnation, promoting qi circulation and dispersing stasis, promoting blood circulation to remove blood stasis, reducing blood lipid, reducing blood pressure, antioxidant, antibacterial, anti-inflammatory, etc. Hawthorn contains various chemical components, such as crataegolic acid, flavonoid compounds, triterpenic acids, vitamin C, etc., and these components endow hawthorn with a wide range of pharmacological effects.

[0004] Salvia miltiorrhiza is a traditional Chinese medicine with a long history, and its pharmacological properties and traditional uses are very extensive. According to the "Shennong Ben Cao Jing" record, Salvia miltiorrhiza is bitter and slightly cold, and has the effects of promoting blood circulation to remove blood stasis, cooling blood and dissipating carbuncles, clearing the heart and relieving restlessness, etc., and is mainly used for treating symptoms such as pathogenic factors in the heart and abdomen, irregular menstruation, abdominal pain due to postpartum stasis, chest impediment and heart pain, etc.

[0005] Atractylodes lancea has a wide range of applications in traditional Chinese medicine, and its pharmacological effects cover multiple aspects such as anti-inflammatory, antioxidant, anti-ulcer, anti-tumor, liver protection, reducing blood sugar, etc. Modern research further reveals its application potential in digestive system diseases, immune system regulation, anti-tumor, etc.

[0006] Lycium barbarum L. is a traditional Chinese medicine with a long medicinal history. Its nature and flavor are sweet and flat, and it belongs to the liver and kidney meridians. Its main effects are nourishing the liver and kidney, benefiting essence and improving eyesight, moistening the lungs and relieving cough, etc. In traditional medicine, Lycium barbarum L. is often used to treat symptoms such as liver and kidney yin deficiency, soreness and weakness of the waist and knees, dizziness and vertigo, consumptive fatigue cough, thirst, spermatorrhea, impotence, etc.

[0007] Epimedium is a traditional Chinese medicine, with pungent, sweet and warm medicinal properties, and belongs to the liver and kidney meridians. Its main effects are tonifying the kidney and strengthening yang, strengthening muscles and bones, dispelling wind and dampness. Its traditional uses include treating symptoms such as impotence, spermatorrhea, flaccidity of muscles and bones, rheumatic arthralgia, numbness and contracture, etc.

[0008] Licorice (scientific name: Glycyrrhiza uralensis Fisch.) is a perennial herbaceous plant of the genus Glycyrrhiza in the Leguminosae family. Its roots and rhizomes are the main medicinal parts. Licorice is sweet and neutral in nature. It enters the heart, lung, spleen, stomach, and kidney meridians. It has multiple functions such as tonifying the spleen and replenishing qi, clearing away heat and detoxifying, moistening the lungs and relieving cough, relieving acute pain, and harmonizing various medicines. Its application prospects in modern medicine are broad, but individual differences and contraindications still need to be paid attention to.

[0009] Chuanxiong contains a variety of active ingredients such as volatile oils, alkaloids, phenolic compounds, lactones and ferulic acid, which have the effects of promoting blood circulation and qi, dispelling wind and relieving pain, and have multiple pharmacological effects such as sedation, anti-inflammatory, antioxidant, anti-platelet aggregation, anti-tumor, anti-aging, anti-depression, etc. For example, ligustrazine can inhibit platelet aggregation and improve microcirculation.

[0010] Astragalus is sweet and slightly warm in nature, and belongs to the lung and spleen meridians. It has the effects of replenishing qi and strengthening the exterior, promoting diuresis and reducing swelling, improving immunity, resisting fatigue, and anti-aging. Its main active ingredients include astragaloside IV, astragaloside polysaccharides, saponins, and various amino acids and trace elements. These ingredients give Astragalus a wide range of pharmacological activities. Modern pharmacological studies have shown that Astragalus has a variety of biological activities such as strengthening the heart, lowering blood pressure, protecting the liver, antiviral, anti-inflammatory, and antioxidant.

[0011] Euryale ferox Salisb. is a Chinese medicinal material that can be used as both medicine and food. Euryale ferox Salisb. is sweet, astringent, and flat in nature. It enters the spleen and kidney meridians and has the effects of tonifying the kidney and consolidating essence, strengthening the spleen and stopping diarrhea, and removing dampness and stopping leukorrhea. Modern research shows that Euryale ferox Salisb. contains a variety of chemical components, including polyphenols, flavonoids, sterols, etc., and has multiple pharmacological effects such as antioxidant, antibacterial, anti-inflammatory, hypoglycemic, and hypolipidemic. Its extract also shows certain anti-tumor, anti-fatigue, and cardiovascular disease improvement effects.

[0012] Pueraria root is a traditional Chinese medicine with a long history, and its pharmacological properties and traditional uses are very rich. Pueraria root is cool in nature, sweet and spicy in taste, and mainly enters the spleen, stomach, and lung meridians. It has the effects of relieving muscle and reducing fever, promoting body fluid and quenching thirst, clearing rashes, and raising yang and stopping diarrhea. It is often used to treat exogenous fever, headache, thirst, thirst, measles that does not break out, heat dysentery, and neck pain caused by hypertension. Modern research shows that Pueraria root contains rich isoflavone compounds (such as puerarin, soybean aglycone, etc.), which have multiple biological activities such as vasodilation, lowering blood sugar, lowering blood lipids, anti-oxidation, and anti-inflammatory, and have significant therapeutic effects on cardiovascular diseases, diabetes, hypertension, etc. In addition, Pueraria root is also used to improve brain blood circulation, regulate endocrine, resist fatigue, and enhance immunity.

[0013] Angelica sinensis (scientific name: Angelica sinensis) is the dried root of the plant Angelica sinensis in the Umbelliferae family. It has a long medicinal history and is known as the "sacred medicine in blood". It is warm in nature, sweet and pungent in taste, and belongs to the liver, heart, and spleen meridians. Its main effects include enriching blood and promoting blood circulation, regulating menstruation and relieving pain, and moistening the intestines and promoting defecation, etc.

[0014] Crocus sativus L. (scientific name), also known as saffron and crocus, is the stigma of a perennial herbaceous plant in the Iridaceae family and has important pharmacological properties and traditional uses. Crocus sativus has a significant effect of promoting blood circulation and removing blood stasis, can promote blood circulation, improve blood flow, and reduce blood coagulation, and is suitable for treating amenorrhea, dysmenorrhea, retention of lochia after childbirth, traumatic injuries and other symptoms.

[0015] In recent years, the research on traditional Chinese medicine compound preparations has mostly focused on the extraction and purification of single medicinal material components or the overall efficacy evaluation of simple compounds, and insufficient attention has been paid to the classification and synergistic action mechanism under the guidance of the theory of the properties and channels tropism of traditional Chinese medicine. The traditional process often adopts the mode of mixed extraction or unified treatment, ignoring the influence of the differences in the cold, heat, warm, and cool properties of medicinal materials on the dissolution and stability of active ingredients. For example, heat-sensitive components are mostly contained in cold and cool medicinal materials, and high-temperature treatment is likely to cause oxidation and inactivation; while the active ingredients of warm and hot medicinal materials often require specific polar solvent gradient release. Existing technologies such as the conventional water extraction and alcohol precipitation method or the homogenization and pulverization process can achieve basic extraction, but it is difficult to take into account the maximum retention and targeted release requirements of different medicinal property components. Research shows that if the compatibility of cold and heat medicinal properties in the compound is not optimized specifically in the process, it may lead to antagonism or degradation between components, thus weakening the overall efficacy.

[0016] On the other hand, although modern traditional Chinese medicine preparation technologies have introduced means such as microencapsulation and nano-embedding, they are mostly limited to the sustained release or stability improvement of single components, and the research on the multi-level and multi-target synergistic delivery mechanism of compound preparations is insufficient. The traditional preparation process often simply mixes each component, resulting in the synchronous release of different medicinal property components in the body and unable to simulate the sequential action law of "sovereign, ministerial, assistant, and guide" in traditional Chinese medicine theory. Some research points out that the low bioavailability of compound preparations is often related to the disorder of the component release sequence. Therefore, developing a hierarchical delivery system based on the classification of medicinal properties is an important direction to break through the bottleneck of the modernization of traditional Chinese medicine compound preparations. Summary of the Invention

[0017] The present invention discloses a traditional Chinese medicine composition for preventing and treating cardiovascular and cerebrovascular diseases to solve any of the above and potential problems in the prior art. To solve the above technical problems, the preparation method of the present invention is as follows:

[0018] 10 - 20 parts of American ginseng, 15 - 25 parts of notoginseng, 12 - 18 parts of salvia miltiorrhiza, 20 - 28 parts of pueraria lobata, 8 - 15 parts of epimedium; 25 - 35 parts of astragalus membranaceus, 18 - 26 parts of ligusticum wallichii, 15 - 25 parts of atractylodes lancea, 10 - 18 parts of angelica sinensis; 30 - 36 parts of hawthorn, 25 - 35 parts of wolfberry, 5 - 10 parts of crocus sativus, 25 - 30 parts of euryale ferox, 15 - 22 parts of liquorice.

[0019] Take American ginseng, notoginseng, salvia miltiorrhiza, pueraria lobata, and epimedium as the cold - natured medicinal material treatment group. Use the ultra - fine powder low - temperature cold breaking - wall technology to obtain crushed particles. First, introduce 30 MPa of sub - critical CO2 and maintain for 5 minutes, then quickly release the pressure to atmospheric pressure. Immediately input into a solution containing 0.3% cellulase, 0.1% pectinase, 0.05% neutral protease at a material - liquid ratio of 1:15, at 45°C, pH 5.0, and ferment for 2 h. Then add sodium hydroxide to adjust to pH 6.0, at 50°C, and continue to ferment for 1 h. Subsequently, perform dynamic water extraction at 50°C twice, 20 minutes each time. Add 60% ethanol to precipitate impurities and then concentrate to a density of 1.2 g / ml to obtain the extraction solution of the cold - natured group;

[0020] Take 25 - 35 parts of astragalus membranaceus, 18 - 26 parts of ligusticum wallichii, 15 - 25 parts of atractylodes lancea, and 10 - 18 parts of angelica sinensis as the warm - natured medicinal material treatment group. Coarsely crush to 80 mesh at - 30°C, and use gradient ethanol extraction. The ethanol in the extraction solution is recovered by vacuum distillation. Then the extraction solution is purified by a 10 kDa ultrafiltration membrane and concentrated to a density of 1.2 g / ml to obtain the extraction solution of the warm - natured group;

[0021] Take 30 - 36 parts of hawthorn, 25 - 35 parts of wolfberry, 5 - 10 parts of crocus sativus, 25 - 30 parts of euryale ferox, and 15 - 22 parts of liquorice as the mild - neutral medicinal material treatment group; Hawthorn is dried by hot air at 60°C and then separately crushed to 200 mesh, and extracted with a sodium dihydrogen phosphate solution at pH 6.5 at a material - liquid ratio of 1:12 at 80°C for 30 minutes. Other components are impregnated with 70% ethanol at a material - liquid ratio of 1:8 at 50°C for 48 hours. Then, the ethanol is recovered by vacuum distillation, and the extraction solution is concentrated to a density of 1.2 g / ml to obtain the extraction solution of the mild - neutral group;

[0022] Layer - by - layer embed the extraction solution of the mild - neutral group, the extraction solution of the cold - natured group, and the extraction solution of the warm - natured group according to the inner - middle - outer structure to obtain Chinese medicine composition particles with a particle size of 400 μm.

[0023] The specific ultra - fine powder low - temperature cold breaking - wall technology is to pre - cool the cold - natured medicinal material treatment group to - 40°C with liquid nitrogen and then crush it to 500 mesh under nitrogen protection using an ultra - fine pulverizer.

[0024] The gradient ethanol extraction of the warm-natured medicinal materials includes: first, reflux extraction is carried out at 70°C for 60 minutes with 50% ethanol at a material-liquid ratio of 1:10, and at the same time, the microwave pulse mode is adopted, with 5 seconds on and 3 seconds off. Then, extraction is carried out for 30 minutes with 30% ethanol at a material-liquid ratio of 1:8 combined with 40 kHz ultrasonic assistance to obtain the extract.

[0025] The extract of the cold-cool group further includes adding 2% β-glucan solution and homogenizing at 15000 rpm for 5 minutes; the extract of the warm-natured group further includes adding 1% beeswax and ultrasonic dispersing at 40°C with 40 kHz for 10 minutes; in the extract of the mild-neutral group, hawthorn liquid and other neutral medicinal material extracts are mixed according to a ratio of 2:1, and 0.5% pectin is added and stirred at 50°C for 30 minutes.

[0026] The specific process of layered embedding is as follows: taking the mixed extract of the mild-neutral group as the liquid core, dropping it into an edible-grade solidifying liquid containing 5% calcium lactate through a dropper with a 0.8 mm aperture at a rate of 60 drops / min for 25 minutes to form the inner liquid-core pellets; then spraying the extract of the cold-cool group onto the surface of the inner pellets in a fluidized bed at 42°C with an atomization pressure of 0.2 MPa at a rate of 6 g / min to form a sustained-release intermediate layer. After the coating weight gain reaches 30%, drying is carried out with circulating hot air at 45°C for 1.5 hours; the extract of the warm-natured group is sprayed in a fluidized bed at 36°C with an atomization pressure of 0.25 MPa at a rate of 9 g / min to form an enteric-coated outer layer. After the coating weight gain reaches 50%, curing is carried out at 38°C for 3 hours; a soluble dietary fiber binder is used between the layers and sprayed at a rate of 0.3 ml / 100 g to enhance the binding force, and then dried in a ventilated manner at 40°C for 30 minutes to obtain the traditional Chinese medicine composition particles with a particle size of 1.3 - 1.7 mm.

[0027] The advantages and beneficial effects of the present invention are as follows:

[0028] 1. The traditional Chinese medicine composition synergistically improves the hemorheological properties, reduces blood viscosity and blood lipid levels through components such as American ginseng, notoginseng, and salvia miltiorrhiza; the active substances such as pueraria lobata, chuanxiong rhizome, and astragalus membranaceus bidirectionally regulate blood pressure and dilate vascular smooth muscle; hawthorn, epimedium, and saffron are rich in antioxidant components, enhancing vascular elasticity and inhibiting arteriosclerosis; the compatibility of angelica sinensis, atractylodes lancea, and euryale ferox can inhibit abnormal platelet aggregation and reduce the risk of thrombus formation; wolfberry, licorice, and ginkgo biloba regulate immune response and metabolic balance, forming a multi-target intervention mechanism, and comprehensively achieving the effects of protecting the cardiovascular and cerebrovascular systems, preventing thrombosis, and maintaining the body's homeostasis.

[0029] 2. Cold-natured medicinal materials such as American ginseng and notoginseng, warm-natured medicinal materials such as astragalus membranaceus and ligusticum wallichii, and mild-neutral medicinal materials such as hawthorn and wolfberry are classified and processed separately, giving full play to the compatibility principle of "cold, heat, warmth, and coolness" in traditional Chinese medicine theory. For the cold-natured group of medicinal materials, the liquid nitrogen cryogenic and subcritical CO2 cell wall breaking technology is used. It can not only protect heat-sensitive components such as ginsenosides and puerarin flavonoids from being damaged, but also release liposoluble and macromolecular active substances through ultrafine grinding and compound enzymatic hydrolysis in a targeted manner. Compared with traditional high-temperature decoction or single-solvent extraction, the component dissolution rate is increased, and the oxidation and degradation of components such as tanshinone are avoided. For the warm-natured group of medicinal materials, through gradient ethanol and dual-frequency electromagnetic coupling, and dynamic extraction of microwave and ultrasonic waves, polar-difference components such as astragalus polysaccharides and ligustrazine are accurately captured. Among them, the microwave pulse mode can reduce the loss of volatile oils. For the neutral group of medicinal materials, aiming at the component characteristics such as hawthorn organic acids and wolfberry polysaccharides, pH buffer solution and low-temperature ethanol are used for step-by-step treatment. It not only maintains the stability of glycyrrhizic acid and crocin, but also realizes the synchronous dissolution of multiple components through pH regulation. Its extraction uniformity is optimized compared with the traditional water extraction and alcohol precipitation process.

[0030] 3. Through different extraction processes of classification and grouping, the limitation of mutual antagonism between cold and heat components in traditional compound prescriptions can be broken through, and the bioavailability can be improved. In addition, the combination of subcritical CO2 cell wall breaking and electromagnetic field pre-activation technology enhances the cell wall permeability while activating the endogenous converting enzymes in the medicinal materials, promoting the conversion of tanshinone IIA into danshensu with higher water solubility. This treatment solves problems such as component interference and poor stability in compound preparations.

[0031] 4. A three-layer inclusion is used to construct a three-level core-shell structure to precisely control the absorption and interaction of cold, warm, and neutral components. The outer warm component is released initially in the stomach, playing the role of warming and dredging the meridians to enhance the gastrointestinal absorption function; the middle cold layer is then slowly released, using the activated blood circulation to improve the targeted delivery efficiency of heat-clearing components; the inner neutral core is finally released in the intestine, playing a dual role of regulating the medicinal properties and promoting nutrient absorption. This design conforms to the sequential treatment theory of traditional Chinese medicine of "warming and dredging first, then clearing heat, and finally regulating harmony". The outer warm components first improve the body's absorption state, the middle cold medicinal effects take effect precisely in the best physiological environment, and the inner neutral components finally maintain the medicinal effect balance. It not only avoids direct conflict between cold and heat medicinal properties, but also maximizes the slow-release efficacy of components through the gradual opening of the absorption channels, while reducing the risk of gastrointestinal irritation.

[0032] 5. Compared with the conventional traditional Chinese medicine compound process, the present invention uses different inner, middle, and outer three-layer structures to avoid the mutual exclusion and pH incompatibility problems of cold and heat components, increasing the coexistence stability of tanshinone and angelica volatile oil; secondly, such a drug structure can precisely match the treatment logic of first regulating the environment, then suppressing inflammation and finally repairing, improving the clinical efficacy compared with single slow-release technology, and having good effects in the prevention and treatment of cardiovascular and cerebrovascular diseases. Specific implementation method

[0033] The present invention will be further described in detail below in conjunction with embodiments.

[0034] Embodiment 1

[0035] 15 parts of American ginseng, 20 parts of notoginseng, 15 parts of salvia miltiorrhiza, 24 parts of kudzu root, and 12 parts of epimedium are used as the cold-natured medicinal material treatment group;

[0036] 30 parts of astragalus membranaceus, 22 parts of ligusticum wallichii, 20 parts of atractylodes lancea, and 14 parts of angelica sinensis are used as the warm-natured medicinal material treatment group;

[0037] 33 parts of hawthorn, 30 parts of wolfberry, 8 parts of saffron, 28 parts of euryale ferox, and 18 parts of liquorice are used as the mild-neutral medicinal material treatment group;

[0038] The cold-natured group of medicinal materials is treated by the ultra-fine powder low-temperature cold-breaking wall technology. It is pre-cooled to -40°C with liquid nitrogen, and then pulverized to 500 meshes by an ultra-fine pulverizer under nitrogen protection to obtain pulverized particles. First, 30 MPa of subcritical CO2 is introduced and maintained for 5 minutes, and then the pressure is quickly released to atmospheric pressure. Immediately, it is put into a solution containing 0.3% cellulase, 0.1% pectinase, 0.05% neutral protease at a material-liquid ratio of 1:15, at 45°C, pH 5.0, and fermented for 2 h. Then, sodium hydroxide is added to adjust the pH to 6.0, at 50°C, and fermentation continues for 1 h. Subsequently, dynamic water extraction is carried out twice at 50°C for 20 minutes each time. After adding 60% ethanol to precipitate impurities, it is concentrated to a density of 1.2 g / ml;

[0039] The warm-natured group of medicinal materials is coarsely pulverized to 80 meshes at -30°C and extracted by gradient ethanol. First, 50% ethanol is used for reflux extraction at a material-liquid ratio of 1:10 at 70°C for 60 minutes, and at the same time, the microwave pulse mode of 5 s on and 3 s off is adopted. Then, 30% ethanol is used for ultrasonic-assisted extraction at a material-liquid ratio of 1:8 in combination with 40 kHz for 30 minutes to obtain the extract. The ethanol in the extract is recovered by vacuum distillation. Then, the extract is purified by a 10 kDa ultrafiltration membrane and concentrated to a density of 1.2 g / ml;

[0040] The hawthorn in the mild-neutral group is dried by hot air at 60°C and then separately pulverized to 200 meshes, and extracted at a material-liquid ratio of 1:12 with a sodium dihydrogen phosphate solution at pH 6.5 at 80°C for 30 minutes. The other components are impregnated with 70% ethanol at a material-liquid ratio of 1:8 at 50°C for 48 hours. Then, the ethanol is recovered by vacuum distillation, and the extract is concentrated to a density of 1.2 g / ml;

[0041] 2% β-glucan solution is added to the cold-natured group extract, and homogenized at 15000 rpm for 5 min; 1% beeswax is added to the warm-natured group extract, and ultrasonically dispersed at 40°C at 40 kHz for 10 min; neutral group mixture: hawthorn liquid: other neutral medicinal material extracts are mixed in a ratio of 2:1, and 0.5% pectin is added and stirred at 50°C for 30 min;

[0042] The above-mentioned extracted liquids of the cold group, the warm group, and the mild neutral group were embedded in layers according to the inner, middle, and outer structure. The mixed extracted liquid of the mild neutral group was used as the liquid core, and through a 0.8 mm aperture dropper, it was dropped into an edible solidifying liquid containing 5% calcium lactate at a rate of 60 drops / min for 25 min to form the inner-layer liquid-core pellets. Then, the concentrated liquid of the cold group was sprayed onto the surface of the inner-layer pellets in a fluidized bed at 42 °C with an atomization pressure of 0.2 MPa at a rate of 6 g / min to form a sustained-release intermediate layer. After the coating weight gain reached 30%, it was dried with circulating hot air at 45 °C for 1.5 hours. The concentrated liquid of the warm group was sprayed in a fluidized bed at 36 °C with an atomization pressure of 0.25 MPa at a rate of 9 g / min to form an enteric-coated outer layer. After the coating weight gain reached 50%, it was cured at 38 °C for 3 hours. A soluble dietary fiber binder was used between the layers and sprayed at a rate of 0.3 ml / 100 g to enhance the binding force, and then dried in a ventilated manner at 40 °C for 30 min to obtain Chinese medicine composition granules with a particle size of 1.5 - 1.7 mm.

[0043] Example 2

[0044] 20 parts of American ginseng, 15 parts of notoginseng, 18 parts of salvia miltiorrhiza, and 20 parts of kudzu root were used as the treatment group of cold-natured medicinal materials;

[0045] 35 parts of astragalus membranaceus, 18 parts of ligusticum wallichii, 25 parts of atractylodes lancea, and 18 parts of angelica sinensis were used as the treatment group of warm-natured medicinal materials;

[0046] 30 parts of hawthorn, 35 parts of wolfberry, 5 parts of saffron, 30 parts of euryale ferox, and 15 parts of liquorice were used as the treatment group of mild neutral medicinal materials;

[0047] The medicinal materials of the cold group were processed by the ultra-fine powder low-temperature cold-breaking technology. They were pre-cooled to -40 °C with liquid nitrogen and then pulverized to 500 meshes by an ultra-fine pulverizer under nitrogen protection to obtain pulverized microparticles. First, 30 MPa subcritical CO2 was introduced and maintained for 5 minutes, then the pressure was quickly released to atmospheric pressure. Immediately, the material-liquid ratio of 1:15 was used to add 0.3% cellulase, 0.1% pectinase, 0.05% neutral protease, at 45 °C, pH 5.0, and fermented for 2 h. Then, sodium hydroxide was added to adjust the pH to 6.0, at 50 °C, and fermentation continued for 1 h. Subsequently, dynamic water extraction was carried out twice at 50 °C for 20 minutes each time. After adding 60% ethanol to precipitate impurities, it was concentrated to a density of 1.2 g / ml;

[0048] The medicinal materials of the warm group were coarsely pulverized to 80 meshes at -30 °C and extracted by gradient ethanol. First, 50% ethanol was used for reflux extraction at a material-liquid ratio of 1:10 at 70 °C for 60 minutes, and at the same time, the microwave pulse mode of 5 s on and 3 s off was used. Then, 30% ethanol was used for ultrasonic-assisted extraction at a material-liquid ratio of 1:8 combined with 40 kHz for 30 minutes to obtain the extract. The ethanol in the extract was recovered by vacuum distillation, and then the extract was purified by a 10 kDa ultrafiltration membrane and concentrated to a density of 1.2 g / ml;

[0049] The hawthorn in the mild neutral group was dried by hot air at 60°C and then crushed separately to 200 mesh, extracted with sodium dihydrogen phosphate solution at pH 6.5 at a solid-liquid ratio of 1:12 at 80°C for 30 minutes. The other components were impregnated with 70% ethanol at a solid-liquid ratio of 1:8 at 50°C for 48 hours, then the ethanol was recovered by reduced pressure distillation, and the extract was concentrated to a density of 1.2 g / ml.

[0050] The extract of the cold group was added with 2% β-glucan solution and homogenized at 15000 rpm for 5 min; the extract of the warm group was added with 1% beeswax and ultrasonically dispersed at 40 kHz for 10 min at 40°C; the mixed solution of the neutral group: hawthorn solution: extract of other neutral Chinese medicinal materials was mixed in a ratio of 2:1, and 0.5% pectin was added and stirred at 50°C for 30 min.

[0051] The above-mentioned mixed extracts of the cold group, warm group, and mild neutral group were embedded in layers according to the inner, middle, and outer structure. The mixed extract of the mild neutral group was used as the liquid core, and was dropped into the food-grade solidifying solution containing calcium lactate with a mass fraction of 5% at a rate of 60 drops / min through a dropper with a pore diameter of 0.8 mm and solidified for 25 min to form the inner layer liquid-core pellets. Then, the concentrated solution of the cold group was sprayed onto the surface of the inner layer pellets in a fluidized bed at 42°C at an atomization pressure of 0.2 MPa at a rate of 6 g / min to form a sustained-release intermediate layer. After the coating weight gain was 30%, it was dried with circulating hot air at 45°C for 1.5 hours; the concentrated solution of the warm group was sprayed in a fluidized bed at 36°C at an atomization pressure of 0.25 MPa at a rate of 9 g / min to form an enteric-coated outer layer. After the coating weight gain was 50%, it was cured at 38°C for 3 hours; a soluble dietary fiber binder was used between the layers and sprayed at a rate of 0.3 ml / 100 g to enhance the binding force, and dried in a ventilated manner at 40°C for 30 min to obtain Chinese medicinal composition granules with a particle size of 1.3 - 1.5 mm.

[0052] Example 3

[0053] 10 parts of American ginseng, 25 parts of notoginseng, 12 parts of salvia miltiorrhiza, 28 parts of pueraria lobata, and 15 parts of epimedium were used as the treatment group of cold-natured Chinese medicinal materials;

[0054] 25 parts of astragalus membranaceus, 26 parts of ligusticum wallichii, 15 parts of atractylodes lancea, and 10 parts of angelica sinensis were used as the treatment group of warm-natured Chinese medicinal materials;

[0055] 36 parts of hawthorn, 25 parts of wolfberry, 10 parts of saffron, 25 parts of euryale ferox, and 22 parts of licorice were used as the treatment group of mild neutral Chinese medicinal materials;

[0056] The medicinal materials in the cold group are processed using the ultra-fine powder low-temperature cold wall-breaking technology. They are pre-cooled to -40°C with liquid nitrogen and then pulverized to 500 mesh under nitrogen protection using an ultra-fine pulverizer to obtain pulverized particles. First, 30 MPa of subcritical CO2 is introduced and maintained for 5 minutes, then the pressure is quickly released to atmospheric pressure. Immediately, it is put into a solution containing 0.3% cellulase, 0.1% pectinase, 0.05% neutral protease at a material-liquid ratio of 1:15, at 45°C and pH 5.0, and fermented for 2 hours. Then, sodium hydroxide is added to adjust the pH to 6.0, and fermentation continues at 50°C for 1 hour. Subsequently, dynamic water extraction is carried out twice at 50°C for 20 minutes each time. After adding 60% ethanol to precipitate impurities, it is concentrated to a density of 1.2 g / ml;

[0057] The medicinal materials in the warm group are coarsely pulverized to 80 mesh at -30°C and then extracted using gradient ethanol. First, 50% ethanol is used for reflux extraction at a material-liquid ratio of 1:10 at 70°C for 60 minutes, and at the same time, the microwave pulse mode is 5 s on and 3 s off. Then, 30% ethanol is used for ultrasonic-assisted extraction at a material-liquid ratio of 1:8 combined with 40 kHz for 30 minutes to obtain the extract. The ethanol in the extract is recovered by vacuum distillation, and then the extract is purified through a 10 kDa ultrafiltration membrane and concentrated to a density of 1.2 g / ml;

[0058] The hawthorn in the mild neutral group is dried by hot air at 60°C and then separately pulverized to 200 mesh. It is extracted at a material-liquid ratio of 1:12 with a sodium dihydrogen phosphate solution at pH 6.5 at 80°C for 30 minutes. The other components are impregnated with 70% ethanol at a material-liquid ratio of 1:8 at 50°C for 48 hours. Then, the ethanol is recovered by vacuum distillation, and the extract is concentrated to a density of 1.2 g / ml;

[0059] 2% β-glucan solution is added to the extract of the cold group, and homogenized at 15000 rpm for 5 min; 1% beeswax is added to the extract of the warm group, and ultrasonically dispersed at 40°C and 40 kHz for 10 min; the neutral group mixture: hawthorn liquid: extract of other neutral medicinal materials is mixed at a ratio of 2:1, and 0.5% pectin is added and stirred at 50°C for 30 min;

[0060] The above-mentioned extracted liquids of the cold group, the warm group, and the mild neutral group are embedded in layers according to the inner, middle, and outer structures. The mixed extracted liquid of the mild neutral group is used as the liquid core. Through a dropper with a pore diameter of 0.8 mm, it is dropped into an edible solidifying liquid containing 5% calcium lactate at a rate of 60 drops / min for 25 min to form inner-layer liquid-core pellets. Then, the concentrated liquid of the cold group is sprayed onto the surface of the inner-layer pellets in a fluidized bed at 42 °C with an atomization pressure of 0.2 MPa at a rate of 6 g / min to form a sustained-release intermediate layer. After the coating weight gain reaches 30%, it is dried with circulating hot air at 45 °C for 1.5 hours. The concentrated liquid of the warm group is sprayed in a fluidized bed at 36 °C with an atomization pressure of 0.25 MPa at a rate of 9 g / min to form an enteric-coated outer layer. After the coating weight gain reaches 50%, it is cured at 38 °C for 3 hours. A soluble dietary fiber binder is used between the layers and sprayed at a rate of 0.3 ml / 100 g to enhance the binding force, and then dried in a ventilated manner at 40 °C for 30 min to obtain Chinese medicine composition particles with a particle size of 1.4 - 1.6 mm.

[0061] Comparative Example 1

[0062] The difference between this comparative example and Example 1 is that in this comparative example, the Chinese medicinal materials are not grouped, and the ultrafine powder low-temperature cold breaking technology and mixed enzyme extraction are directly used to concentrate and prepare the Chinese medicine composition. The process is as follows:

[0063] Take 15 parts of American ginseng, 20 parts of notoginseng, 15 parts of salvia miltiorrhiza, 24 parts of kudzu root, 12 parts of epimedium, 30 parts of astragalus membranaceus, 22 parts of chuanxiong rhizome, 20 parts of atractylodes lancea, 14 parts of angelica sinensis, 33 parts of hawthorn, 30 parts of wolfberry, 8 parts of saffron, 28 parts of euryale ferox, and 18 parts of licorice root, and perform ultrafine powder low-temperature cold breaking treatment. After precooling to -40 °C with liquid nitrogen, use an ultrafine pulverizer to pulverize to 500 meshes under nitrogen protection to obtain pulverized particles. First, introduce 30 MPa of subcritical CO2 and maintain for 5 minutes, then quickly release the pressure to atmospheric pressure. Immediately, put it into a solution containing 0.3% cellulase, 0.1% pectinase, 0.05% neutral protease at a solid-liquid ratio of 1:15, at 45 °C, pH 5.0, and ferment for 2 h. Then add sodium hydroxide to adjust to pH 6.0, 50 °C, and continue to ferment for 1 h. Subsequently, perform dynamic water extraction at 50 °C twice for 20 minutes each time. Add 60% ethanol to precipitate impurities and then concentrate to a density of 1.2 g / ml; concentrate to a density of 1.36 at 38 °C and -0.095 MPa, add 0.8% of sodium carboxymethyl starch, mix at a rotation speed of 20 rpm for 30 min, add it to a wet granulator to prepare uniform wet particles with a particle size of 1.5 mm, and perform drying. Set the inlet air temperature at 60 °C, the wind speed at 1.5 m 3 / min, and dry until the water content of the particles ≤ 5%, then the Chinese medicine particles are obtained.

[0064] Comparative Example 2

[0065] The difference between this comparative example and Example 1 is that in this comparative example, the Chinese medicinal materials are not grouped, and the ultrafine powder low-temperature cold wall-breaking technology and gradient ethanol extraction are directly used to concentrate and prepare the Chinese medicine composition. The process is as follows: Take 15 parts of American ginseng, 20 parts of Panax notoginseng, 15 parts of Salvia miltiorrhiza, 24 parts of Pueraria lobata, 12 parts of Epimedium brevicornu, 30 parts of Astragalus membranaceus, 22 parts of Ligusticum chuanxiong, 20 parts of Atractylodes lancea, 14 parts of Angelica sinensis, 33 parts of Hawthorn, 30 parts of Lycium barbarum, 8 parts of Crocus sativus, 28 parts of Euryale ferox, and 18 parts of Glycyrrhiza uralensis. Perform ultrafine powder low-temperature cold wall-breaking treatment. Pre-cool to -40°C with liquid nitrogen, and use an ultrafine pulverizer to pulverize to 500 meshes under nitrogen protection to obtain pulverized particles. Then, perform gradient ethanol extraction. First, reflux and extract at 70°C for 60 minutes with 50% ethanol at a material-liquid ratio of 1:10, and at the same time, use the microwave pulse mode of 5s on and 3s off. Then, use 30% ethanol at a material-liquid ratio of 1:8 and combine with 40kHz ultrasonic wave to assist extraction for 30 minutes to obtain the extract. The ethanol in the extract is recovered by vacuum distillation. Then, the extract is purified by a 10kDa ultrafiltration membrane and concentrated to a density of 1.2g / ml; add 0.8% sodium carboxymethyl starch, mix at 20rpm for 30min, add it to a wet granulator to prepare uniform wet granules with a particle size of 1.5mm, and perform drying. Set the inlet air temperature at 60°C and the wind speed at 1.5m 3 / min, and dry until the water content of the granules ≤ 5%, then the Chinese medicine granules are obtained.

[0066] Comparative Example 3

[0067] The difference between this comparative example and Example 1 is that its preparation process is as follows: Group A Chinese medicinal materials: Take 15 parts of American ginseng, 20 parts of Panax notoginseng, 15 parts of Salvia miltiorrhiza, 24 parts of Pueraria lobata, 12 parts of Epimedium brevicornu, 22 parts of Ligusticum chuanxiong, 20 parts of Atractylodes lancea, and 8 parts of Crocus sativus. Perform ultrafine powder low-temperature cold wall-breaking treatment. Pre-cool to -40°C with liquid nitrogen, and use an ultrafine pulverizer to pulverize to 500 meshes under nitrogen protection to obtain pulverized particles. First, introduce 30MPa subcritical CO2 and maintain for 5 minutes, then quickly release the pressure to normal pressure. Use an ultrafine pulverizer to pulverize to 500 meshes under nitrogen protection to obtain pulverized particles. First, introduce 30MPa subcritical CO2 and maintain for 5 minutes, then quickly release the pressure to normal pressure. Immediately input at a material-liquid ratio of 1:15 containing 0.3% cellulase, 0.1% pectinase, 0.05% neutral protease, at 45°C, pH5.0, and ferment for 2h. Then, add sodium hydroxide to adjust to pH6.0, at 50°C, and continue to ferment for 1h. Subsequently, perform dynamic water extraction at 50°C twice, each time for 20 minutes. Add 60% ethanol to precipitate impurities and then concentrate to a density of 1.2g / ml;

[0068] Group B medicinal materials: Take 24 parts of Pueraria lobata, 30 parts of Astragalus membranaceus, 14 parts of Angelica sinensis, 33 parts of Hawthorn, 30 parts of Lycium barbarum, 28 parts of Euryale ferox, and 18 parts of Glycyrrhiza uralensis. Coarsely crush them to 80 meshes at -30°C, and extract them with gradient ethanol. First, reflux and extract with 50% ethanol at a solid-liquid ratio of 1:10 at 70°C for 60 minutes, and at the same time, use the microwave pulse mode of 5s on and 3s off. Then, extract with 30% ethanol at a solid-liquid ratio of 1:8 combined with 40kHz ultrasonic assistance for 30 minutes to obtain the extract. The ethanol in the extract is recovered by vacuum distillation. Then, the extract is purified by a 10kDa ultrafiltration membrane and concentrated to a density of 1.2g / ml;

[0069] Add 2% β-glucan solution to the concentrated solution of Group A and homogenize at 15000rpm for 5min; add 1% beeswax to the concentrated solution of Group B and disperse it ultrasonically at 40°C and 40kHz for 10min;

[0070] For the above-mentioned mixed concentrated solution of Group A and concentrated solution of Group B, according to the internal and external structure, take the mixed solution of Group A as the liquid core, and drip it into the food-grade solidifying solution containing calcium lactate with a mass fraction of 5% at a rate of 60 drops / min through a 0.8mm orifice dropper to solidify for 25min to form the inner liquid-core pellets; then, spray the mixed solution of Group B onto the surface of the pellets in a fluidized bed at 42°C with an atomization pressure of 0.2MPa at a rate of 6g / min to form the outer layer. After the coating weight gain is 50%, dry it with circulating hot air at 45°C for 1.5 hours and ventilate and dry it at 40°C for 30min to obtain the traditional Chinese medicine composition particles with a particle size of 1.0 - 1.2mm; thus obtained.

[0071] Comparative Example 4

[0072] The difference between this comparative example and Example 1 is that the specific process of this comparative example is: 15 parts of American ginseng, 20 parts of Panax notoginseng, 15 parts of Salvia miltiorrhiza, 24 parts of Pueraria lobata, and 12 parts of Epimedium brevicornum are used as the cold-natured medicinal material treatment group;

[0073] 30 parts of Astragalus membranaceus, 22 parts of Ligusticum chuanxiong, 20 parts of Atractylodes lancea, and 14 parts of Angelica sinensis are used as the warm-natured medicinal material treatment group;

[0074] 33 parts of Hawthorn, 30 parts of Lycium barbarum, 8 parts of Crocus sativus, 28 parts of Euryale ferox, and 18 parts of Glycyrrhiza uralensis are used as the mild-neutral medicinal material treatment group;

[0075] The medicinal materials in the cold group are processed by the ultra-fine powder low-temperature cold-breaking wall technology. They are pre-cooled to -40°C with liquid nitrogen and then pulverized to 500 meshes by an ultra-fine pulverizer under nitrogen protection to obtain pulverized particles. First, 30 MPa of subcritical CO2 is introduced and maintained for 5 minutes, then the pressure is quickly released to atmospheric pressure. Immediately, the material-liquid ratio of 1:15 is used to add a solution containing 0.3% cellulase, 0.1% pectinase, 0.05% neutral protease, at 45°C and pH 5.0, and fermented for 2 hours. Then sodium hydroxide is added to adjust the pH to 6.0, and continue to ferment at 50°C for 1 hour. Subsequently, dynamic water extraction is carried out twice at 50°C for 20 minutes each time. After adding 60% ethanol to precipitate impurities, it is concentrated to a density of 1.2 g / ml;

[0076] The medicinal materials in the warm group are roughly pulverized to 80 meshes at -30°C and extracted by gradient ethanol. First, 50% ethanol is used for reflux extraction at a material-liquid ratio of 1:10 at 70°C for 60 minutes, and at the same time, the microwave pulse mode is 5 s on and 3 s off. Then, 30% ethanol is used for ultrasonic-assisted extraction at a material-liquid ratio of 1:8 combined with 40 kHz for 30 minutes to obtain the extract. The ethanol in the extract is recovered by vacuum distillation, and then the extract is purified by a 10 kDa ultrafiltration membrane and concentrated to a density of 1.2 g / ml;

[0077] In the mild neutral group, hawthorn is dried by hot air at 60°C and then pulverized separately to 200 meshes. It is extracted with a sodium dihydrogen phosphate solution at pH 6.5 at a material-liquid ratio of 1:12 at 80°C for 30 minutes. Other components are impregnated with 70% ethanol at a material-liquid ratio of 1:8 at 50°C for 48 hours. Then, ethanol is recovered by vacuum distillation, and the extract is concentrated to a density of 1.2 g / ml;

[0078] The concentrated solutions of the above cold group, warm group, and mild neutral group are subjected to layered embedding treatment: The concentrated solution of the neutral group is used as the liquid core, and through a 0.8 mm aperture dropper, it is dropped into an edible-grade solidifying solution containing 5% calcium lactate at a rate of 60 drops / min for 25 minutes to form the inner liquid-core pellets; Then, the concentrated solution of the cold group is sprayed onto the surface of the inner pellets in a fluidized bed at 42°C with an atomization pressure of 0.2 MPa at a rate of 6 g / min to form a sustained-release intermediate layer. After the coating weight gain is 30%, it is dried by circulating hot air at 45°C for 1.5 hours; The concentrated solution of the warm group is sprayed in a fluidized bed at 36°C with an atomization pressure of 0.25 MPa at a rate of 9 g / min to form an enteric-coated outer layer. After the coating weight gain is 50%, it is cured at 38°C for 3 hours; Soluble dietary fiber binder is used between layers and sprayed at a rate of 0.3 ml / 100 g to enhance the binding force, and dried by ventilation at 40°C for 30 minutes to obtain Chinese medicine composition particles with a particle size of 1.5 - 1.6 mm.

[0079] Comparative Example 5

[0080] The difference between this comparative example and Example 1 is that the specific process of this comparative example is:

[0081] 15 parts of American ginseng, 20 parts of notoginseng, 15 parts of salvia miltiorrhiza, 24 parts of kudzu root, and 12 parts of epimedium are used as the cold-natured medicinal material treatment group;

[0082] 30 parts of astragalus membranaceus, 22 parts of chuanxiong rhizome, 20 parts of atractylodes lancea, and 14 parts of angelica sinensis are used as the warm-natured medicinal material treatment group;

[0083] 33 parts of hawthorn, 30 parts of wolfberry, 8 parts of saffron, 28 parts of euryale ferox, and 18 parts of licorice are used as the mild-neutral medicinal material treatment group;

[0084] The cold-natured group of medicinal materials is processed by the ultrafine powder low-temperature cold-breaking wall technology. It is pre-cooled to -40°C with liquid nitrogen and then pulverized to 500 meshes by an ultrafine pulverizer under nitrogen protection to obtain pulverized particles. First, 30 MPa of subcritical CO2 is introduced and maintained for 5 minutes, then the pressure is quickly released to atmospheric pressure. Immediately, it is put into a solution containing 0.3% cellulase, 0.1% pectinase, 0.05% neutral protease at a material-liquid ratio of 1:15, at 45°C, pH 5.0, and fermented for 2 h. Then sodium hydroxide is added to adjust to pH 6.0, at 50°C, and fermentation continues for 1 h. Subsequently, dynamic water extraction is carried out twice at 50°C for 20 minutes each time. After adding 60% ethanol to precipitate impurities, it is concentrated to a density of 1.2 g / ml;

[0085] The warm-natured group of medicinal materials is coarsely pulverized to 80 meshes at -30°C and extracted by gradient ethanol. First, 50% ethanol is used for reflux extraction at a material-liquid ratio of 1:10 at 70°C for 60 minutes, and at the same time, the microwave pulse mode is 5 s on and 3 s off. Then, 30% ethanol is used for ultrasonic-assisted extraction at a material-liquid ratio of 1:8 in combination with 40 kHz for 30 minutes to obtain the extract. The ethanol in the extract is recovered by vacuum distillation, and then the extract is purified by a 10 kDa ultrafiltration membrane and concentrated to a density of 1.2 g / ml;

[0086] In the mild-neutral group, the hawthorn is dried by hot air at 60°C and then separately pulverized to 200 meshes. It is extracted with a sodium dihydrogen phosphate solution at pH 6.5 at a material-liquid ratio of 1:12 at 80°C for 30 minutes. The other components are impregnated with 70% ethanol at a material-liquid ratio of 1:8 at 50°C for 48 hours. Then, the ethanol is recovered by vacuum distillation, and the extract is concentrated to a density of 1.2 g / ml;

[0087] The extract of the cold-natured group, the extract of the warm-natured group, and the mixed solution of the neutral group are respectively added with 2% β-glucan solution and homogenized at 15000 rpm for 5 min;

[0088] The above-mentioned extracted liquid of the cold group, the extracted liquid of the warm group, and the extracted liquid of the mild neutral group are embedded in layers according to the inner, middle, and outer structure. The mixed extracted liquid of the mild neutral group is used as the liquid core. Through a dropper with a pore diameter of 0.8 mm, it is dropped into an edible solidifying liquid containing 5% calcium lactate at a rate of 60 drops / min for 25 min to form inner-layer liquid-core pellets; then the concentrated liquid of the cold group is sprayed onto the surface of the inner-layer pellets in a fluidized bed at 42 °C with an atomization pressure of 0.2 MPa at a rate of 6 g / min to form a sustained-release intermediate layer. After the coating weight gain reaches 30%, it is dried with circulating hot air at 45 °C for 1.5 hours; the concentrated liquid of the warm group is sprayed in a fluidized bed at 36 °C with an atomization pressure of 0.25 MPa at a rate of 9 g / min to form an enteric-coated outer layer. After the coating weight gain reaches 50%, it is cured at 38 °C for 3 hours; a soluble dietary fiber binder is used between the layers and sprayed at a rate of 0.3 ml / 100 g to enhance the binding force, and then dried in a ventilated manner at 40 °C for 30 min to obtain traditional Chinese medicine composition granules with a particle size of 1.3 - 1.5 mm.

[0089] Comparative Example 6

[0090] The difference between this comparative example and Example 1 lies in that the specific process of this comparative example is as follows:

[0091] 15 parts of American ginseng, 20 parts of notoginseng, 15 parts of salvia miltiorrhiza, 24 parts of kudzu root, and 12 parts of epimedium are used as the treatment group of cold-natured medicinal materials;

[0092] 30 parts of astragalus membranaceus, 22 parts of ligusticum wallichii, 20 parts of atractylodes lancea, and 14 parts of angelica sinensis are used as the treatment group of warm-natured medicinal materials;

[0093] 33 parts of hawthorn, 30 parts of wolfberry, 8 parts of saffron, 28 parts of euryale ferox, and 18 parts of liquorice are used as the treatment group of mild neutral medicinal materials;

[0094] The cold-natured medicinal materials are processed by an ultra-fine powder low-temperature cold-breakthrough technology. They are pre-cooled to -40 °C with liquid nitrogen and then pulverized to 500 meshes by an ultra-fine pulverizer under nitrogen protection to obtain pulverized microparticles. First, 30 MPa of subcritical CO2 is introduced and maintained for 5 minutes, then the pressure is quickly released to atmospheric pressure. Immediately, the material-liquid ratio of 1:15 is put into a solution containing 0.3% cellulase, 0.1% pectinase, 0.05% neutral protease, at 45 °C, pH 5.0, and fermented for 2 h. Then sodium hydroxide is added to adjust the pH to 6.0, at 50 °C, and continue to ferment for 1 h. Subsequently, dynamic water extraction is carried out twice at 50 °C for 20 minutes each time. After adding 60% ethanol to precipitate impurities, it is concentrated to a density of 1.2 g / ml;

[0095] The medicinal materials in the warm-heat group were coarsely pulverized to 80 meshes at -30°C, and extracted with gradient ethanol. First, 50% ethanol was used for reflux extraction at a material-liquid ratio of 1:10 at 70°C for 60 minutes, and at the same time, the microwave pulse mode was adopted with 5 s on and 3 s off. Then, 30% ethanol was used for ultrasonic-assisted extraction at a material-liquid ratio of 1:8 combined with 40 kHz for 30 minutes to obtain the extract. The ethanol in the extract was recovered by vacuum distillation, and then the extract was purified by a 10 kDa ultrafiltration membrane and concentrated to a density of 1.2 g / ml;

[0096] The hawthorn in the mild-neutral group was dried by hot air at 60°C and then separately pulverized to 200 meshes, and extracted with a sodium dihydrogen phosphate solution at pH 6.5 at a material-liquid ratio of 1:12 at 80°C for 30 minutes. The other components were impregnated with 70% ethanol at a material-liquid ratio of 1:8 at 50°C for 48 hours, and then the ethanol was recovered by vacuum distillation, and the extract was concentrated to a density of 1.2 g / ml;

[0097] 2% β-glucan solution was added to the extract of the cold-cool group, and homogenized at 15000 rpm for 5 min; 1% beeswax was added to the extract of the warm-heat group, and ultrasonically dispersed at 40°C and 40 kHz for 10 min; the mixture of the neutral group: hawthorn liquid: extract of other neutral medicinal materials was mixed at a ratio of 2:1, and 0.5% pectin was added and stirred at 50°C for 30 min;

[0098] The above-mentioned mixed extracts of the cold-cool group, warm-heat group, and mild-neutral group were homogenized at 15000 rpm for 20 min, 0.8% sodium carboxymethyl starch was added, and mixed at a rotation speed of 20 rpm for 30 min. Then it was added to a wet granulator to prepare uniform wet granules with a particle size of 1.5 mm, and dried. The inlet air temperature was set at 60°C, and the air velocity was 1.5 m 3 / min, and dried until the water content of the granules ≤ 5%, then the traditional Chinese medicine granules were obtained.

[0099] Experiment 1: Effect of the medicinal effect test on the hemorheology of model rats

[0100] I. Experimental animals: SD rats, half male and half female, with a body weight of 240 - 260 g.

[0101] II. Experimental drugs: The treatment group was the traditional Chinese medicine composition of the present invention. The traditional Chinese medicine granules prepared in Examples 1 - 3 and Comparative Examples 1 - 6 were administered at a drug dosage of 1.5 g / kg; the blank group and the model group were given the same volume of normal saline; the positive control group (Ginkgo biloba tablets) was ground into powder and formulated into a solution with a concentration of 0.2 g / ml with purified water, and the administration dosage was 1.5 g / kg.

[0102] III. Test method: SD rats were freely fed for 1 week and randomly divided into 12 groups, with half males and half females, 10 rats in each group, namely the blank group, the model group, the positive group, the groups of Example 1-3, and the groups of Comparative Example 1-6. High-fat formula: Disperse edible oil with hot water to contain 18%, and then sequentially add 10% cholesterol, 0.2% propylthiouracil, 5% sodium cholate, and 50% Tween-80 based on the mass of water, stir, and heat the water to 100 mL and stir evenly to obtain. The rats in each group were allowed to eat and drink freely. Except for the rats in the blank group, the rats in other groups were fed the high-fat formula every morning for 3 weeks. After 3 weeks of intragastric administration, the rats were fasted for 12 h without water deprivation, blood was taken from the fundus venous plexus, plasma was separated, and the levels of total cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein were measured by ELISA method. The results are shown in Table 1.

[0103] Table 1

[0104]

[0105]

[0106] Experiment 3: Effect of traditional Chinese medicine composition on myocardial ischemia in rats induced by Pituitrin

[0107] (1) Preparation of diabetic model mice

[0108] Select 120 Wistar rats with a body weight of 250 ± 15 g. After 1 week of adaptive feeding, randomly select 10 rats as normal controls, and the remaining 110 rats are injected with Pituitrin through the sublingual vein at a dose of 1.5 IU / kg to cause coronary artery constriction, resulting in myocardial ischemia and hypoxia, and at the same time causing systemic small blood vessel constriction, increasing the cardiac afterload, and further aggravating myocardial ischemia and hypoxia, indicating that a rat myocardial ischemia model is successfully established.

[0109] (2) Grouping and administration

[0110] Randomly group the rats with myocardial ischemia model, 10 rats in each group. Among them, 1 group is the model control group, 1 group is the positive drug group (the dose of Ginaton tablets is 1.5 g / kg), and the remaining 9 groups are the groups of Example 1-3 and Comparative Example 1-6 of the present invention. The dose is 1.5 g / kg; the rats in each group are continuously intragastrically administered for 7 days according to the administration dose of each group, and the normal control group and the Pituitrin ischemia group are given the same volume of sodium chloride injection.

[0111] (3) Determination

[0112] Seven days later, blood is taken from the abdominal aorta of the rats by intubation, a part of the plasma is separated to obtain serum, and the contents of GSH-Px, SOD, and MDA in the serum are measured. The measurement results are shown in Table 2.

[0113] Table 2

[0114]

[0115]

Claims

1. A traditional Chinese medicine composition for preventing and treating cardiovascular and cerebrovascular diseases, characterized in that: Comprising: 10 - 20 parts of American ginseng, 15 - 25 parts of notoginseng, 12 - 18 parts of salvia miltiorrhiza, 20 - 28 parts of kudzu root, 8 - 15 parts of epimedium; 25 - 35 parts of astragalus membranaceus, 18 - 26 parts of chuanxiong rhizome, 15 - 25 parts of atractylodes lancea, 10 - 18 parts of angelica sinensis; 30 - 36 parts of hawthorn, 25 - 35 parts of wolfberry, 5 - 10 parts of crocus sativus, 25 - 30 parts of euryale ferox, 15 - 22 parts of licorice root.

2. A preparation method of a traditional Chinese medicine composition for preventing and treating cardiovascular and cerebrovascular diseases, characterized in that: Taking American ginseng, notoginseng, salvia miltiorrhiza, kudzu root, and epimedium as the cold - natured medicinal material treatment group, using the ultra - fine powder low - temperature cold - breaking technology to obtain pulverized particles. First, introduce 30 MPa sub - critical CO2 and maintain for 5 minutes, then quickly release the pressure to atmospheric pressure. Immediately, add the material - liquid ratio of 1:15 and contain 0.3% cellulase, 0.1% pectinase, 0.05% neutral protease, at 45 °C, pH 5.0, ferment for 2 h, then add sodium hydroxide to adjust to pH 6.0, at 50 °C, continue to ferment for 1 h. Subsequently, perform dynamic water extraction at 50 °C twice, each time for 20 minutes, add 60% ethanol to precipitate impurities and then concentrate to a density of 1.2 g / ml to obtain the cold - natured group extraction solution; Taking 25 - 35 parts of astragalus membranaceus, 18 - 26 parts of chuanxiong rhizome, 15 - 25 parts of atractylodes lancea, 10 - 18 parts of angelica sinensis as the warm - natured medicinal material treatment group, coarsely pulverize to 80 meshes at - 30 °C, adopt gradient ethanol extraction, recover the ethanol in the extraction solution by vacuum distillation, and then purify the extraction solution through a 10 kDa ultrafiltration membrane and concentrate to a density of 1.2 g / ml to obtain the warm - natured group extraction solution; Taking 30 - 36 parts of hawthorn, 25 - 35 parts of wolfberry, 5 - 10 parts of crocus sativus, 25 - 30 parts of euryale ferox, 15 - 22 parts of licorice root as the mild - neutral medicinal material treatment group; after drying hawthorn at 60 °C by hot air and then separately pulverizing to 200 meshes, extract at 80 °C for 30 minutes with a sodium dihydrogen phosphate solution at pH 6.5 according to a material - liquid ratio of 1:

12. Other components are impregnated at 50 °C for 48 hours with a 70% ethanol material - liquid ratio of 1:8, then recover ethanol by vacuum distillation, and concentrate the extraction solution to a density of 1.2 g / ml to obtain the mild - neutral group extraction solution; Layering and embedding the mild - neutral group extraction solution, the cold - natured group extraction solution, and the warm - natured group extraction solution according to the inner - middle - outer structure to obtain traditional Chinese medicine composition particles with a particle size of 400 μm.

3. The preparation method of a traditional Chinese medicine composition for preventing and treating cardiovascular and cerebrovascular diseases according to claim 2, characterized in that: The ultra - fine powder low - temperature cold - breaking technology is specifically that the cold - natured medicinal material treatment group is pre - cooled to - 40 °C by liquid nitrogen and then pulverized to 500 meshes by an ultra - fine pulverizer under nitrogen protection.

4. The preparation method of a traditional Chinese medicine composition for preventing and treating cardiovascular and cerebrovascular diseases according to claim 2, characterized in that: The gradient ethanol extraction of the warm - natured medicinal materials includes: first, reflux and extract at 70 °C for 60 minutes with 50% ethanol according to a material - liquid ratio of 1:10, and at the same time adopt a microwave pulse mode of 5 s on and 3 s off, then extract with 30% ethanol at a material - liquid ratio of 1:8 combined with 40 kHz ultrasonic assistance for 30 minutes to obtain the extraction solution.

5. The preparation method of a traditional Chinese medicine composition for preventing and treating cardiovascular and cerebrovascular diseases according to claim 2, characterized in that: The extraction solution of the cold group further includes adding 2% β-glucan solution and homogenizing at 15,000 rpm for 5 min; the extraction solution of the warm group further includes adding 1% beeswax and ultrasonically dispersing at 40 kHz for 10 min at 40°C; in the extraction solution of the mild neutral group, hawthorn liquid and other neutral medicinal material extraction solutions are mixed in a ratio of 2:1, and 0.5% pectin is added and stirred at 50°C for 30 min.

6. The preparation method of a traditional Chinese medicine composition for preventing and treating cardiovascular and cerebrovascular diseases according to claim 2, wherein: The layered embedding specifically is: taking the mixed extraction solution of the mild neutral group as the liquid core, dripping it into the food-grade solidifying solution containing 5% calcium lactate through a 0.8 mm aperture dropper at a rate of 60 drops / min to solidify for 25 min to form the inner liquid core pellets; then spraying the extraction solution of the cold group onto the surface of the inner pellets in a fluidized bed at 42°C with an atomization pressure of 0.2 MPa at a rate of 6 g / min to form a sustained-release intermediate layer, drying with hot air circulated at 45°C for 1.5 hours after the coating weight gain reaches 30%; spraying the extraction solution of the warm group in a fluidized bed at 36°C with an atomization pressure of 0.25 MPa at a rate of 9 g / min to form an enteric-coated outer layer, curing at 38°C for 3 hours after the coating weight gain reaches 50%; using a soluble dietary fiber binder between the layers and spraying it at a rate of 0.3 ml / 100 g to enhance the binding force, drying in ventilation at 40°C for 30 min to obtain the traditional Chinese medicine composition granules.

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