Traditional Chinese medicine composition for treating cardiovascular and cerebrovascular diseases

Abstract

The invention provides a traditional Chinese medicine composition for treating cardiovascular and cerebrovascular diseases. The traditional Chinese medicine composition is prepared from rhodiola rosea, crocus sativus, codonopsis pilosula, poria cocos, American ginseng, hawthorn, the root of kudzu vine, longan, liquorice, astragalus membranaceus, the fruit of Chinese wolfberry, peach kernels, spina date seeds, eucommia male flowers and radix paeoniae alba. The traditional Chinese medicine composition which has the effects of promoting blood circulation to remove blood stasis, reinforcing qi and nourishing yin, clearing away heat and toxic materials, reducing phlegm and dredging collaterals and the like is obtained by performing different extraction processes and optimization treatment on traditional Chinese medicines such as crocus sativus and the like so as to improve cardiovascular and cerebrovascular functions and prevent and treat cardiovascular diseases.

Description

Technical Field

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

[0002] The number of patients with cardiovascular and cerebrovascular diseases is huge, and the market demand is huge. With the arrival of an aging society and the rising incidence of chronic diseases, the market prospects of traditional Chinese medicine cardiovascular disease preparations are broad. Rhodiola rosea has the effects of invigorating qi and relieving asthma, unblocking meridians and activating blood circulation, and is suitable for symptoms of qi deficiency, fatigue, shortness of breath, fatigue, and blood stasis, especially for those with hot constitution. It can improve blood circulation, reduce blood viscosity, and prevent thrombosis. Saffron has the effects of promoting blood circulation and removing blood stasis, dredge menstruation and relieve pain, and is suitable for cardiovascular diseases such as coronary heart disease and angina pectoris. It can reduce blood viscosity, resist thrombosis, and improve myocardial ischemia. Codonopsis pilosula has the effects of tonifying the middle and replenishing qi, strengthening the spleen and benefiting the lungs, and is suitable for symptoms such as qi and blood deficiency, palpitations and fatigue. It can enhance immunity and improve heart function. Poria has the effects of promoting water and dampness, strengthening the spleen and calming the mind, and is suitable for symptoms such as spleen deficiency and dampness, palpitations and insomnia. It can regulate blood lipids and prevent atherosclerosis. American ginseng has the effects of nourishing qi and yin, promoting fluid and quenching thirst, and is suitable for symptoms such as palpitations, insomnia, and fatigue. It can improve immunity and antioxidant capacity, and prevent and treat cardiovascular and cerebrovascular diseases. Hawthorn has the effects of digestion, stomach, blood circulation and blood stasis, and is suitable for cardiovascular diseases such as coronary heart disease and hypertension. It can lower blood pressure and improve cholesterol levels. Pueraria root has the effects of dispelling cold, promoting fluid and quenching thirst, and is suitable for cardiovascular diseases such as coronary heart disease and angina pectoris. It can dilate coronary arteries, lower blood pressure, and improve myocardial ischemia. Longan has the effects of nourishing blood and calming the nerves, and is suitable for symptoms such as insufficient heart blood, palpitations and insomnia. It can improve heart function and strengthen physical fitness. Licorice has the effects of harmonizing medicinal properties, relieving pain, and is suitable for symptoms such as palpitations, chest pain, and heartache. It can protect myocardial cells and resist platelet aggregation. Astragalus has the effects of nourishing qi and strengthening the exterior, astringing sores and promoting muscle growth, and is suitable for symptoms such as qi deficiency and fatigue, palpitations and fatigue. It can regulate blood pressure and blood lipid levels and prevent cardiovascular diseases. Lycium barbarum has the effects of nourishing the liver and kidney, improving the eyesight, and is suitable for symptoms such as liver and kidney yin deficiency, soreness of the waist and knees. It can improve blood circulation and enhance immunity. Peach kernel has the effects of promoting blood circulation and removing blood stasis, moistening the intestines and relieving constipation, and is suitable for cardiovascular diseases such as coronary heart disease and angina pectoris. It can improve blood circulation and prevent thrombosis. Ziziphus jujuba seed has the effect of nourishing the heart and calming the mind, and is suitable for symptoms such as palpitations, insomnia, and restlessness. It can improve heart function and enhance sleep quality. Eucommia male flower has the effects of nourishing the liver and kidney, strengthening tendons and bones, and is suitable for symptoms such as liver and kidney deficiency, soreness of the waist and knees. It can improve blood circulation and enhance physical fitness. White peony root has the effects of nourishing blood and softening the liver, relieving acute pain, and is suitable for symptoms such as liver depression and qi stagnation, chest and flank pain. It can regulate blood lipids and improve heart function. The existing technology has achieved certain results in the traditional Chinese medicine method for treating cardiovascular and cerebrovascular diseases. For formulas with more medicinal flavors, it is necessary to ensure the extraction of key drugs to ensure its efficacy in improving cardiovascular and cerebrovascular diseases.

[0003] Follow the principle of "monarch, minister, assistant and messenger", take Rhodiola rosea and Crocus as the core, supplemented with other qi-invigorating medicinal materials to enhance metabolism, supplemented with blood circulation and blood stasis-removing ingredients, so that the medicine is harmonized. Among them, for the varieties of different Chinese medicines, different extraction methods can be used to avoid the interference of different polar components, such as the precipitation of saponins and polysaccharides. Extracting water-soluble components first and then processing fat-soluble components can reduce solvent cross-contamination. Among them, high-temperature extraction of water-soluble Chinese medicine components during the extraction process will cause the loss of components that are not resistant to high temperatures, and the pH stable values ​​are different between different water-soluble effective ingredients, so how to retain the effective ingredients to the greatest extent on the basis of ensuring the extraction rate and reduce the degradation of the effective ingredients is the focus of the present invention. For light and heat sensitive components, low temperature, light-avoiding and other processing processes are also required to achieve more efficient targeted extraction, and improving the selectivity and process economy of the components is the research focus of the present invention. Summary of the invention

[0004] The present invention discloses a Chinese medicine composition for treating cardiovascular and cerebrovascular diseases to solve the above and any potential problems in the prior art. In order to solve the above technical problems, the preparation method of the present invention is:

[0005] A Chinese medicine composition for treating cardiovascular and cerebrovascular diseases, characterized in that the preparation method comprises:

[0006] 15-20 parts of Rhodiola rosea, 10-15 parts of Astragalus membranaceus, and 12-16 parts of Pueraria root are subjected to high temperature water extraction, filtered, and concentrated under reduced pressure at 60°C and vacuum degree -0.08MPa to a relative density of 1.15;

[0007] The high-temperature water extraction comprises: adding the above-mentioned pueraria root and rhodiola rosea crushed to 40 mesh, adding 10 times of water, 100°C, high temperature and rapid dissolution of glycoside components for 0.5h, and adding 0.1% by mass of citric acid to adjust the pH to 5.0 to inhibit the oxidation of puerarin; then adding astragalus crushed to 40 mesh, maintaining high temperature and adding 0.05% by mass of sodium bicarbonate to adjust the pH to 6.5, and continuing to extract at 100°C for 1.5h; then adding 2 times of water to cool to 85°C, adding 0.2% β-cyclodextrin for embedding treatment, and simultaneously starting a dynamic countercurrent circulation flow rate of 1.5L / min to form a co-solubilized colloid with flavonoids and polysaccharides to avoid precipitation loss;

[0008] 6-10 parts of hawthorn and 6-10 parts of peach kernels were crushed to 80 mesh and subjected to supercritical CO 2 Extraction: CO 2 The pressure is 25 MPa, the temperature is 45°C, the entrainer is 5% ethanol, and the extraction time is 2 h to obtain the extract;

[0009] 8-14 parts of American ginseng, 5-8 parts of Eucommia ulmoides male flowers, and 8-15 parts of Codonopsis pilosula are subjected to low temperature alcohol extraction to obtain an extract;

[0010] 10-15 parts of saffron and 5-8 parts of spiny jujube seeds are subjected to low-temperature dynamic percolation to obtain a percolation liquid;

[0011] The supercritical CO 2 The extract is obtained, the low-temperature alcohol extraction extract and the percolate are mixed, and the ethanol is recovered by rotary evaporation at 50°C, and concentrated until there is no ethanol;

[0012] 5-9 parts of Poria cocos, 3-6 parts of longan, 5-10 parts of white peony root, 5-8 parts of wolfberry, 3-7 parts of liquorice. Enzymatic hydrolysis assisted water extraction: After mixing the medicinal materials, add 5 times of water, add 0.5% cellulase, stir evenly, enzymolyze at 50℃ for 1h, then add 8 times of water and extract at 80℃ for 1h. 60℃, vacuum degree -0.08MPa, reduce pressure and concentrate to a relative density of 1.15;

[0013] The above concentrated products are mixed to obtain the product.

[0014] Among them, low-temperature alcohol extraction of American ginseng, male flowers of Eucommia ulmoides and Codonopsis pilosula also includes: the first stage of subcritical pretreatment: 5-8 portions of male flowers of Eucommia ulmoides crushed to 40 mesh are separately put into a subcritical reactor, extracted at 0.8MPa pressure, 55°C, 65% ethanol, containing 0.1% citric acid, for 10 minutes to quickly release chlorogenic acid, and then the pressure is released to normal pressure and quickly cooled to 30°C;

[0015] The second stage of microwave-ultrasound synergy: continue to add 8-14 parts of American ginseng crushed to 40 mesh and 8-15 parts of Codonopsis pilosula, adjust the ethanol concentration to 70%, first use microwave 400W / 30s to break through the cell wall, then switch to ultrasound 40kHz / 300W oscillation for 20 minutes, and microwave-ultrasound cycle 3 times;

[0016] The third stage is low-temperature reverse filtration: After the extract is rapidly cooled at -20°C, it is filtered through a 0.1μm ceramic membrane to separate the saponin / polysaccharide complex. The filtrate can be recycled and used in the initial extraction stage of Eucommia male flowers.

[0017] Among them, the low-temperature dynamic percolation treatment of saffron and sour jujube kernel includes: after the medicinal materials are crushed to 60 mesh, the percolation column is filled in the order of sour jujube kernel at the bottom and saffron at the top, and a 0.2mm aperture stainless steel sieve is pre-laid at the bottom, the sour jujube kernel layer accounts for 30% of the height, and the saffron layer accounts for 60%; a 3V / cm DC pulse electric field is applied to the sour jujube kernel layer, the frequency is 50Hz, and the duty cycle is 1:1 to promote the migration of saponin A ions. The saffron layer uses a UV shielding glass column and is covered with a nitrogen protective layer to block photooxidation; a three-stage countercurrent is used. The system uses 50% ethanol containing 0.05% ascorbic acid to percolate from the Ziziphus jujuba seed layer upwards at a flow rate of 1 mL / min and 25°C in the first stage, and 50% ethanol containing 0.1% β-cyclodextrin to percolate from the saffron layer downwards at a flow rate of 3 mL / min and 20°C in the second stage. The final mixed solution is filtered through a 0.45 μm membrane and then recycled. The Ziziphus jujuba seed layer is first percolated for 0.5 h, and after the dissolution rate of saponin A reaches 80%, the percolation of the saffron layer is started for 3 h, and the total time is shortened to 3.5 h.

[0018] The advantages and beneficial effects of the present invention are:

[0019] 1. The present invention provides a Chinese medicine composition for treating cardiovascular and cerebrovascular diseases, which is extracted by high-temperature water, supercritical CO, and extracts from different Chinese medicines, including rhodiola rosea, saffron, codonopsis pilosula, tuckahoe, American ginseng, hawthorn, kudzu root, longan, licorice, astragalus, wolfberry, peach kernel, spiny jujube kernel, eucommia male flower, white peony root, and saffron. 2 The extraction methods of low-temperature dynamic percolation and enzymatic hydrolysis-assisted water extraction obtain a Chinese medicine composition which has the effects of promoting blood circulation and removing blood stasis, invigorating qi and nourishing yin, clearing away heat and detoxifying, resolving phlegm and dredging collaterals, thereby improving cardiovascular and cerebrovascular functions and preventing and treating cardiovascular diseases.

[0020] 2. Salidroside in Rhodiola rosea, puerarin in Pueraria root, and astragaloside IV in Astragalus are all water-soluble glycosides, which can be fully dissolved at high temperatures and have the effects of promoting blood circulation and removing blood stasis, anti-oxidation, and improving microcirculation. However, directly mixing them and extracting them at high temperatures will lead to the loss of components that are not resistant to high temperatures, and puerarin stable in acidic conditions will conflict with astragalus polysaccharides stable in neutral pH, which will reduce the content of effective ingredients.

[0021] 3. Therefore, by precisely matching the timing control with the physical and chemical conditions, the pH conflict between puerarin and astragalus polysaccharide was avoided by step-by-step feeding. The thermal degradation rate of salidroside was reduced by 40% after embedding. The gradient temperature control made the puerarin extraction rate 10-20% higher than that of traditional extraction. The countercurrent circulation process reduced the total solvent usage by 25% and shortened the concentration time by more than 30%. The water-soluble glycoside components obtained by high-temperature extraction were greatly increased, and the effects of promoting blood circulation, anti-oxidation, and improving microcirculation were better.

[0022] 4. Ursolic acid in hawthorn and amygdalin in peach kernel are fat-soluble components. Supercritical extraction can efficiently extract the fat-soluble components and avoid the hydrolysis of amygdalin to produce toxic hydrogen cyanide caused by traditional decoction.

[0023] 5. American ginseng saponins (Rb1, Rg1), Codonopsis polysaccharides, and Eucommia chlorogenic acid have higher solubility in ethanol. Low-temperature ultrasound can reduce the degradation of heat-sensitive components (such as chlorogenic acid). Low-temperature alcohol extraction can enrich saponins and phenolic acid components in a targeted manner and improve antioxidant activity. Low-temperature alcohol extraction of American ginseng, Eucommia male flowers, and Codonopsis pilosula will result in a degradation rate of chlorogenic acid in Eucommia male flowers of >15%. Therefore, the degradation rate of chlorogenic acid can be reduced to <3% after subcritical pretreatment of Eucommia male flowers alone, and citric acid can inhibit oxidative browning; microwave-ultrasound alternation increases the extraction rate of American ginseng saponin Rb1 and the yield of Codonopsis polysaccharides. Afterwards, membrane separation is used to block the hydrogen bond between saponins and polysaccharides to avoid precipitation losses; this switch from subcritical to normal pressure can reduce ethanol consumption by more than 35%, and reverse filtration and reuse can achieve closed-loop extraction, forming a breakthrough advantage in component targeting, system compatibility, and industrialization cost.

[0024] 6. Crocin in crocin is sensitive to light and heat, and its activity can be retained by low-temperature and light-proof treatment. Jujube seed saponin A has a high solubility in ethanol. It is necessary to retain the light and heat sensitive components to the maximum extent possible to avoid oxidative losses. Compared with products on the market, the activity retention rate of normal high-temperature decoction is increased by more than 30%. In the low-temperature dynamic percolation process of saffron and jujube seeds, it is necessary to solve the problem of competitive dissolution and interaction of components during mixed percolation through sequential layered loading + electric field-countercurrent synergistic extraction. The layered loading avoids the competitive dissolution of crocin and jujube seed saponin, and β-cyclodextrin encapsulation reduces the photodegradation rate of crocin to less than 5%;

[0025] 7. The electric field assisted extraction rate of jujube seed saponin A was greatly improved, and the countercurrent system reduced the amount of ethanol by 40%. Nitrogen protection plus ascorbic acid can make the 6-hour oxidation loss rate of safranin less than 2%, which is much lower than the conventional dynamic percolation loss rate. This process achieves efficient targeted extraction of two types of photosensitive and electroactive components through spatial separation and time sequence regulation, which is more selective and economical.

[0026] 8. Enzyme-assisted extraction of tuckahoe and wolfberry polysaccharides increased the extraction rate by 40%. Enzyme-assisted water extraction can enhance the immunomodulatory function of the composition. Tuckahoe polysaccharides and wolfberry polysaccharides are wrapped by cell walls. Cellulase hydrolyzes the cell walls to increase the dissolution rate. Glycyrrhizic acid in licorice is more stable under weak acidity. After enzymolysis, the pH is adjusted to 5.5. This process can improve the extraction efficiency of polysaccharide components and reduce the damage of glycyrrhizic acid to high temperature. DETAILED DESCRIPTION

[0027] The present invention is further described in detail below in conjunction with the examples. The Chinese medicines used in the following examples and comparative examples were all purchased from Bozhou Tengwang Pharmaceutical Co., Ltd.

[0028] Example 1

[0029] 18 parts of Rhodiola rosea and 14 parts of Pueraria root were subjected to high-temperature water extraction, crushed to 40 mesh, added with 10 times of water, 100°C, and the glycoside components were quickly dissolved at high temperature for 0.5h, and 0.1% by mass of citric acid was added to adjust the pH to 5.0 to inhibit the oxidation of puerarin; then 12 parts of Astragalus membranaceus crushed to 40 mesh were added, the high temperature was maintained, and 0.05% by mass of sodium bicarbonate was added to adjust the pH to 6.5, and the extraction was continued at 100°C for 1.5h; then 2 times of water was added to cool to 85°C, 0.2% β-cyclodextrin was added for embedding treatment, and the dynamic countercurrent circulation flow rate of 1.5L / min was simultaneously started to form a co-solubilized colloid with flavonoids and polysaccharides to avoid precipitation loss; filtered, and concentrated under reduced pressure at 60°C and vacuum degree -0.08MPa to a relative density of 1.15;

[0030] 8 parts of hawthorn and 8 parts of peach kernel were crushed to 80 mesh and subjected to supercritical CO 2 Extraction: CO 2 The pressure is 25 MPa, the temperature is 45°C, the entrainer is 5% ethanol, and the extraction time is 2 h to obtain the extract;

[0031] 11 parts of American ginseng, 6 parts of male flowers of Eucommia ulmoides and 12 parts of Codonopsis pilosula were subjected to low-temperature alcohol extraction. The first stage was subcritical pretreatment: the male flowers of Eucommia ulmoides crushed to 40 mesh were put into a subcritical reactor alone, extracted for 10 minutes at 0.8 MPa pressure, 55°C, and 65% ethanol containing 0.1% citric acid, and the chlorogenic acid was quickly released. The pressure was then released to normal pressure and quickly cooled to 30°C. The second stage was microwave-ultrasound synergy: American ginseng and Codonopsis pilosula crushed to 40 mesh were continued to be added, and the ethanol concentration was adjusted to 70%. The cell wall was first penetrated by microwave 400W / 30s, and then switched to ultrasound 40kHz / 300W for 20 minutes, and the microwave-ultrasound cycle was repeated 3 times. The third stage was low-temperature reverse filtration: the extract was rapidly cooled at -20°C, filtered through a 0.1μm ceramic membrane, and the saponin / polysaccharide complex was separated. The filtrate could be recycled and used in the initial extraction stage of male flowers of Eucommia ulmoides to obtain an extract.

[0032] 12 parts of saffron and 6 parts of sour jujube kernel were subjected to low-temperature dynamic percolation treatment: after the medicinal materials were crushed to 60 mesh, the percolation column was filled in the order of sour jujube kernel at the bottom and saffron at the top, and a 0.2mm pore size stainless steel sieve was pre-laid at the bottom. The sour jujube kernel layer accounted for 30% of the height, and the saffron layer accounted for 60%; a 3V / cm DC pulse electric field with a frequency of 50Hz and a duty cycle of 1:1 was applied to the sour jujube kernel layer to promote the migration of saponin A ions. The saffron layer used a UV shielding glass column and was covered with a nitrogen protective layer to block photooxidation; a three-stage countercurrent system was used , the first stage is to use 50% ethanol containing 0.05% ascorbic acid to percolate from the Ziziphus jujuba layer upwards, with a flow rate of 1mL / min, 25°C, the second stage is to use 50% ethanol containing 0.1% β-cyclodextrin to percolate from the Crocus saffron layer downwards, with a flow rate of 3mL / min, 20°C, and the final mixed solution is filtered through a 0.45μm membrane and then recycled; the Ziziphus jujuba layer is first run for 0.5h of electric field percolation, and after the dissolution rate of saponin A reaches 80%, the percolation of the Crocus saffron layer is started for 3h, and the total time is shortened to 3.5h to obtain the percolate;

[0033] The supercritical CO 2 The extract is obtained, the low-temperature alcohol extraction extract and the percolate are mixed, and the ethanol is recovered by rotary evaporation at 50°C, and concentrated until there is no ethanol;

[0034] 7 parts of Poria cocos, 5 parts of longan, 8 parts of white peony root, 7 parts of wolfberry, 5 parts of liquorice enzymatic hydrolysis assisted water extraction: after mixing the medicinal materials, add 5 times of water, add 0.5% cellulase, stir evenly, enzymatic hydrolysis at 50℃ for 1h, then add 8 times of water and extract at 80℃ for 1h. 60℃, vacuum degree -0.08MPa, reduce pressure and concentrate to relative density 1.15;

[0035] The above concentrated products are mixed to obtain the product.

[0036] Example 2

[0037] 20 parts of Rhodiola rosea and 12 parts of Pueraria root were subjected to high-temperature water extraction, crushed to 40 mesh, added with 10 times of water, 100°C, and the glycoside components were quickly dissolved at high temperature for 0.5h, and 0.1% mass fraction of citric acid was added to adjust the pH to 5.0 to inhibit the oxidation of puerarin; then 15 parts of Astragalus membranaceus crushed to 40 mesh were added, the high temperature was maintained, and 0.05% mass fraction of sodium bicarbonate was added to adjust the pH to 6.5, and the extraction was continued at 100°C for 1.5h; then 2 times of water was added to cool to 85°C, 0.2% β-cyclodextrin was added for embedding treatment, and the dynamic countercurrent circulation flow rate of 1.5L / min was simultaneously started to form a co-solubilized colloid with flavonoids and polysaccharides to avoid precipitation loss; filtered, and concentrated under reduced pressure at 60°C and vacuum degree -0.08MPa to a relative density of 1.15;

[0038] 6 parts of hawthorn and 10 parts of peach kernel were crushed to 80 mesh and subjected to supercritical CO 2 Extraction: CO2 The pressure is 25 MPa, the temperature is 45°C, the entrainer is 5% ethanol, and the extraction time is 2 h to obtain the extract;

[0039] 14 parts of American ginseng, 5 parts of male flowers of Eucommia ulmoides and 15 parts of Codonopsis pilosula were subjected to low-temperature alcohol extraction. The first stage was subcritical pretreatment: the male flowers of Eucommia ulmoides crushed to 40 mesh were put into a subcritical reactor alone, extracted for 10 minutes at 0.8 MPa pressure, 55°C, and 65% ethanol containing 0.1% citric acid, and the chlorogenic acid was quickly released. The pressure was then released to normal pressure and quickly cooled to 30°C. The second stage was microwave-ultrasound synergy: American ginseng and Codonopsis pilosula crushed to 40 mesh were continued to be added, and the ethanol concentration was adjusted to 70%. The cell wall was first penetrated by microwave 400W / 30s, and then switched to ultrasound 40kHz / 300W for 20 minutes, and the microwave-ultrasound cycle was repeated 3 times. The third stage was low-temperature reverse filtration: the extract was rapidly cooled at -20°C, filtered through a 0.1μm ceramic membrane, and the saponin / polysaccharide complex was separated. The filtrate could be recycled and used in the initial extraction stage of male flowers of Eucommia ulmoides to obtain an extract.

[0040] 15 parts of saffron and 8 parts of sour jujube kernel were subjected to low-temperature dynamic percolation treatment: after the medicinal materials were crushed to 60 mesh, the percolation column was filled in the order of sour jujube kernel at the bottom and saffron at the top, and a 0.2mm pore size stainless steel sieve was pre-laid at the bottom. The sour jujube kernel layer accounted for 30% of the height, and the saffron layer accounted for 60%; a 3V / cm DC pulse electric field with a frequency of 50Hz and a duty cycle of 1:1 was applied to the sour jujube kernel layer to promote the migration of saponin A ions. The saffron layer used a UV shielding glass column and was covered with a nitrogen protective layer to block photooxidation; a three-stage countercurrent system was used , the first stage is to use 50% ethanol containing 0.05% ascorbic acid to percolate from the Ziziphus jujuba layer upwards, with a flow rate of 1mL / min, 25°C, the second stage is to use 50% ethanol containing 0.1% β-cyclodextrin to percolate from the Crocus saffron layer downwards, with a flow rate of 3mL / min, 20°C, and the final mixed solution is filtered through a 0.45μm membrane and then recycled; the Ziziphus jujuba layer is first run for 0.5h of electric field percolation, and after the dissolution rate of saponin A reaches 80%, the percolation of the Crocus saffron layer is started for 3h, and the total time is shortened to 3.5h to obtain the percolate;

[0041] The supercritical CO 2 The extract is obtained, the low-temperature alcohol extraction extract and the percolate are mixed, the ethanol is recovered by rotary evaporation at 50°C, and the mixture is concentrated until there is no ethanol;

[0042] 5 parts of Poria cocos, 6 parts of longan, 5 parts of white peony root, 8 parts of wolfberry, and 3 parts of liquorice were extracted by enzymatic hydrolysis: 5 times water was added after mixing the medicinal materials, 0.5% cellulase was added, stirred evenly, and enzymatic hydrolysis was performed at 50℃ for 1h, and then 8 times water was added to extract at 80℃ for 1h. 60℃, vacuum degree -0.08MPa, reduced pressure concentration to relative density 1.15;

[0043] The above concentrated products are mixed to obtain the product.

[0044] Example 3

[0045] 15 parts of Rhodiola rosea and 16 parts of Pueraria root were subjected to high-temperature water extraction, crushed to 40 mesh, added with 10 times of water, 100°C, and the glycoside components were quickly dissolved at high temperature for 0.5h, and 0.1% by mass of citric acid was added to adjust the pH to 5.0 to inhibit the oxidation of puerarin; then 10 parts of Astragalus membranaceus crushed to 40 mesh were added, the high temperature was maintained, and 0.05% by mass of sodium bicarbonate was added to adjust the pH to 6.5, and the extraction was continued at 100°C for 1.5h; then 2 times of water was added to cool to 85°C, 0.2% β-cyclodextrin was added for embedding treatment, and the dynamic countercurrent circulation flow rate of 1.5L / min was simultaneously started to form a co-solubilized colloid with flavonoids and polysaccharides to avoid precipitation loss; filtered, and concentrated under reduced pressure at 60°C and vacuum degree -0.08MPa to a relative density of 1.15;

[0046] 10 parts of hawthorn and 6 parts of peach kernel were crushed to 80 mesh and subjected to supercritical CO 2 Extraction: CO 2 The pressure is 25 MPa, the temperature is 45°C, the entrainer is 5% ethanol, and the extraction time is 2 h to obtain the extract;

[0047] 8 parts of American ginseng, 8 parts of male flowers of Eucommia ulmoides and 8 parts of Codonopsis pilosula were subjected to low-temperature alcohol extraction. The first stage was subcritical pretreatment: the male flowers of Eucommia ulmoides crushed to 40 mesh were put into a subcritical reactor alone, extracted for 10 minutes at 0.8 MPa pressure, 55°C, and 65% ethanol containing 0.1% citric acid, and the chlorogenic acid was quickly released. The pressure was then released to normal pressure and quickly cooled to 30°C. The second stage was microwave-ultrasound synergy: American ginseng and Codonopsis pilosula crushed to 40 mesh were continued to be added, and the ethanol concentration was adjusted to 70%. The cell wall was first penetrated by microwave 400W / 30s, and then switched to ultrasound 40kHz / 300W for 20 minutes, and the microwave-ultrasound cycle was repeated 3 times. The third stage was low-temperature reverse filtration: the extract was rapidly cooled at -20°C, and then filtered through a 0.1μm ceramic membrane to separate the saponin / polysaccharide complex. The filtrate could be recycled and used in the initial extraction stage of male flowers of Eucommia ulmoides to obtain an extract.

[0048] 10 parts of saffron and 5 parts of sour jujube kernel were subjected to low-temperature dynamic percolation treatment: after the medicinal materials were crushed to 60 mesh, the percolation column was filled in the order of sour jujube kernel at the bottom and saffron at the top, and a 0.2mm pore size stainless steel sieve was pre-laid at the bottom. The sour jujube kernel layer accounted for 30% of the height, and the saffron layer accounted for 60%; a 3V / cm DC pulse electric field with a frequency of 50Hz and a duty cycle of 1:1 was applied to the sour jujube kernel layer to promote the migration of saponin A ions. The saffron layer used a UV shielding glass column and was covered with a nitrogen protective layer to block photooxidation; a three-stage countercurrent system was used , the first stage is to use 50% ethanol containing 0.05% ascorbic acid to percolate from the Ziziphus jujuba layer upwards, with a flow rate of 1mL / min, 25°C, the second stage is to use 50% ethanol containing 0.1% β-cyclodextrin to percolate from the Crocus saffron layer downwards, with a flow rate of 3mL / min, 20°C, and the final mixed solution is filtered through a 0.45μm membrane and then recycled; the Ziziphus jujuba layer is first run for 0.5h of electric field percolation, and after the dissolution rate of saponin A reaches 80%, the percolation of the Crocus saffron layer is started for 3h, and the total time is shortened to 3.5h to obtain the percolate;

[0049] The supercritical CO 2 The extract is obtained, the low-temperature alcohol extraction extract and the percolate are mixed, the ethanol is recovered by rotary evaporation at 50°C, and the mixture is concentrated until there is no ethanol;

[0050] 9 parts of Poria cocos, 3 parts of longan, 10 parts of white peony root, 5 parts of wolfberry, 7 parts of liquorice enzymatic hydrolysis assisted water extraction: after mixing the medicinal materials, add 5 times of water, add 0.5% cellulase, stir evenly, enzymatic hydrolysis at 50℃ for 1h, then add 8 times of water and extract at 80℃ for 1h. 60℃, vacuum degree -0.08MPa, reduce pressure and concentrate to relative density 1.15;

[0051] The above concentrated products are mixed to obtain the product.

[0052] Comparative Example 1

[0053] The difference between this comparative example and Example 1 is that the process adopted in this comparative example is as follows:

[0054] Low temperature alcohol extraction of 20 parts of Rhodiola rosea, 12 parts of Pueraria root and 15 parts of Astragalus membranaceus: crush the medicinal materials to 40 mesh, add 8 times the amount of 70% ethanol, perform ultrasonic assisted extraction at 60℃ for 3 times, each time for 30 minutes, and combine the extracts;

[0055] 6 parts of hawthorn and 10 parts of peach kernel were crushed to 80 mesh and subjected to supercritical CO 2 Extraction: CO 2 The pressure is 25 MPa, the temperature is 45°C, the entrainer is 5% ethanol, and the extraction time is 2 h to obtain the extract;

[0056] 11 parts of American ginseng, 6 parts of Eucommia male flowers, and 12 parts of Codonopsis pilosula were subjected to low-temperature alcohol extraction: the medicinal materials were crushed to 40 mesh, 8 times the amount of 70% ethanol was added, and ultrasonic-assisted extraction was performed at 60°C for 3 times, each time for 30 minutes, and the extracts were combined;

[0057] Low-temperature dynamic percolation of 12 parts of saffron and 6 parts of spiny jujube kernel: After the medicinal materials are crushed to 60 mesh, add 5 times the amount of 50% ethanol and perform dynamic percolation at 25°C with a flow rate of 2mL / min, and collect the percolation liquid; mix the supercritical CO2 extract and the percolation liquid, and recover the ethanol by rotary evaporation at 50°C, and concentrate until there is no ethanol taste;

[0058] 7 parts of Poria cocos, 5 parts of longan, 8 parts of white peony root, 7 parts of wolfberry, 5 parts of liquorice enzymatic hydrolysis assisted water extraction: after mixing the medicinal materials, add 5 times of water, add 0.5% cellulase, stir evenly, enzymatic hydrolysis at 50℃ for 1h, then add 8 times of water and extract at 80℃ for 1h. 60℃, vacuum degree -0.08MPa, reduce pressure and concentrate to relative density 1.15;

[0059] The above concentrated products are mixed to obtain the product.

[0060] Comparative Example 2

[0061] The difference between this comparative example and Example 1 is that the extraction process of Rhodiola rosea, Pueraria lobata and Astragalus membranaceus in this comparative example is as follows: 20 parts of Rhodiola rosea, 12 parts of Pueraria lobata and 15 parts of Astragalus membranaceus are crushed to 40 mesh and low-temperature alcohol extraction is performed, 8 times the amount of 70% ethanol is added, and ultrasonic-assisted extraction is performed at 60°C for 3 times, each time for 30 minutes, and the extracts are combined; the rest is the same as Example 1.

[0062] Comparative Example 3

[0063] The difference between this comparative example and Example 1 is that the extraction process of American ginseng, Eucommia ulmoides male flower and Codonopsis pilosula in this comparative example is as follows: the medicinal materials are crushed to 40 mesh, 8 times the amount of 70% ethanol is added, and ultrasonic-assisted extraction is performed at 60°C for 3 times, each time for 30 minutes, and the extracts are combined; the rest is the same as Example 1.

[0064] Comparative Example 4

[0065] The difference between this comparative example and Example 1 is that in this comparative example, American ginseng, Eucommia male flower and Codonopsis pilosula do not undergo a subcritical pretreatment process for Eucommia male flower, and the specific extraction process is as follows: the first stage of ultrasonic treatment: add American ginseng, Codonopsis pilosula and Eucommia male flower crushed to 40 mesh, the ethanol concentration is 70%, first penetrate the cell wall with microwave 400W / 30s, then switch to ultrasonic 40kHz / 300W oscillation for 20 minutes, and microwave-ultrasound cycle 3 times; the second stage of low-temperature reverse filtration: after the extract is rapidly cooled at -20°C, it is filtered through a 0.1μm ceramic membrane to separate the saponin / polysaccharide complex, and the filtrate can be recycled for the initial extraction stage of Eucommia male flower to obtain an extract; the rest is the same as Example 1.

[0066] Comparative Example 5

[0067] The difference between this comparative example and Example 1 is that in this comparative example, the extraction process of American ginseng, male flowers of Eucommia ulmoides and Codonopsis pilosula is as follows: the first stage of subcritical pretreatment: the male flowers of Eucommia ulmoides crushed to 40 mesh are put into a subcritical reactor alone, and extracted for 10 minutes at 0.8 MPa pressure, 55°C, 65% ethanol, containing 0.1% citric acid, to quickly release chlorogenic acid, and then the pressure is released to normal pressure and quickly cooled to 30°C; the second stage of microwave-ultrasound synergy: continue to add American ginseng and Codonopsis pilosula crushed to 40 mesh, adjust the ethanol concentration to 70%, first penetrate the cell wall with microwave 400W / 30s, then switch to ultrasound 40kHz / 300W oscillation for 20 minutes, and microwave-ultrasound cycle 3 times; then filter through a 0.1μm ceramic membrane to separate the saponin / polysaccharide complex, and the filtrate can be recycled for the initial extraction stage of male flowers of Eucommia ulmoides to obtain an extract; the rest is the same as Example 1.

[0068] Comparative Example 6

[0069] The difference between this comparative example and Example 1 is that the low-temperature dynamic percolation of saffron and Chinese jujube kernel is as follows: 12 parts of saffron and 6 parts of Chinese jujube kernel are subjected to low-temperature dynamic percolation: after the medicinal materials are crushed to 60 mesh, 5 times the amount of 50% ethanol is added for dynamic percolation at 25°C, with a flow rate of 2mL / min, and the percolation liquid is collected; the supercritical CO2 extract and the percolation liquid are mixed, and the ethanol is recovered by rotary evaporation at 50°C, and concentrated to have no ethanol taste; the rest is the same as Example 1.

[0070] Comparative Example 7

[0071] The difference between this comparative example and Example 1 is that the low-temperature dynamic percolation of saffron and spinach kernels is not subjected to stratification treatment. The specific process is as follows: 12 parts of saffron and 6 parts of spinach kernels are crushed to 60 meshes, and then the spinach kernels are pressed at the bottom, mixed and filled into a percolation column, a 0.2 mm pore size stainless steel screen is pre-laid at the bottom, and a 3V / cm DC pulse electric field is applied at a frequency of 50 Hz; a three-stage countercurrent system is adopted, and 50% ethanol containing 0.05% ascorbic acid is used in the first stage to pass from the spinach kernel layer to the spinach kernel layer. The upper percolation was carried out at a flow rate of 1 mL / min and 25°C. The secondary percolation was carried out with 50% ethanol containing 0.1% β-cyclodextrin. The percolation was carried out downward from the saffron layer at a flow rate of 3 mL / min and 20°C. The final mixed solution was filtered through a 0.45 μm membrane and then recycled. The Ziziphus jujuba seed layer was first percolated for 0.5 h. After the dissolution rate of saponin A reached 80%, the percolation of the saffron layer was started for 3 h. The total time was shortened to 3.5 h to obtain a percolate solution. The rest was the same as in Example 1.

[0072] Experiment 1: Effect of drug efficacy test on blood rheology in model rats

[0073] 1. Experimental animals: SD rats, half male and half female, weighing 240-260 g, purchased from Jiangsu Huachuang Xinnuo Pharmaceutical Technology Co., Ltd.

[0074] 2. Experimental drugs: The treatment group was the Chinese medicine composition of the present invention. The granules prepared in Examples 1-3 and Comparative Examples 1-7 were respectively prepared with purified water to form a solution with a concentration of 0.2 g / m1, and administered at a dose of 2.0 g / kg; the blank group and the model group were given the same volume of normal saline; the positive control group (Ginaduo tablets) was ground into powder and prepared with purified water to form a solution with a concentration of 0.2 g / m1, and the dosage was 2.0 g / kg.

[0075] 3. Experimental method: SD rats were fed freely for 1 week and randomly divided into 13 groups, half male and half female, 8 rats in each group, namely blank group, model group, positive group, Example 1-3 group, Comparative Example 1-7 group, high-fat formula: edible oil was dispersed with hot water to contain 18%, 10% cholesterol, 0.2% propylthiouracil, 5% sodium cholate, 50% Tween-80 were added in turn, stirred, heated water to 100mL and stirred evenly. Each group of rats was fed with a free diet. Except for the blank group rats, the other groups of rats were fed with a high-fat formula every morning for 3 weeks. After 3 weeks of oral administration, fasting but not water for 12h, blood was collected from the venous plexus of the fundus, plasma was separated, and the levels of total cholesterol, triglycerides, low-density lipoprotein, and high-density lipoprotein were determined by ELISA. The whole blood high shear viscosity (nH), whole blood low shear viscosity (nL), plasma viscosity (np), and hematocrit (HCT) of rats were measured using a fully automatic blood rheology detector. The results are shown in Tables 1-2.

[0076] Table 1

[0077]

[0078] Table 2

[0079]

[0080]

Claims

1. A Chinese medicine composition for treating cardiovascular and cerebrovascular diseases, characterized in that: Including Rhodiola rosea, saffron, Codonopsis pilosula, Poria cocos, American ginseng, hawthorn, Pueraria lobata, longan, licorice, astragalus, wolfberry, peach kernel, spiny jujube kernel, Eucommia ulmoides flower, and white peony root.

2. A Chinese medicine composition for treating cardiovascular and cerebrovascular diseases according to claim 1, characterized in that: The preparation method comprises: 15-20 parts of Rhodiola rosea, 10-15 parts of Astragalus membranaceus, and 12-16 parts of Pueraria root are subjected to high temperature water extraction, filtered, and concentrated under reduced pressure at 60°C and vacuum degree -0.08MPa to a relative density of 1.15; The high-temperature water extraction comprises: adding the above-mentioned pueraria root and rhodiola rosea crushed to 40 mesh, adding 10 times of water, 100° C., high-temperature rapid dissolution of glycoside components for 0.5 h, and adding 0.1% by mass of citric acid to adjust the pH to 5.0 to inhibit puerarin oxidation; then adding astragalus crushed to 40 mesh, maintaining high temperature and adding 0.05% by mass of sodium bicarbonate to adjust the pH to 6.5, and continuing to extract at 100° C. for 1.5 h; then adding 2 times of water to cool to 85° C., adding 0.2% β-cyclodextrin for embedding treatment, and simultaneously starting a dynamic countercurrent circulation flow rate of 1.5 L / min to form a co-solubilized colloid with flavonoids and polysaccharides to avoid precipitation loss; 6-10 parts of hawthorn and 6-10 parts of peach kernels are crushed to 80 meshes for supercritical CO2 extraction: CO2 pressure 25MPa, temperature 45°C, entrainer 5% ethanol, extraction time 2h to obtain an extract; 8-14 parts of American ginseng, 5-8 parts of Eucommia ulmoides male flowers, and 8-15 parts of Codonopsis pilosula are subjected to low temperature alcohol extraction to obtain an extract; 10-15 parts of saffron and 5-8 parts of spiny jujube kernels are subjected to low-temperature dynamic percolation to obtain a percolation liquid; The supercritical CO2 is used to obtain an extract, the low-temperature alcohol extraction extract and the percolate are mixed, and the ethanol is recovered by rotary evaporation at 50°C, and concentrated to a state without ethanol; 5-9 parts of Poria cocos, 3-6 parts of longan, 5-10 parts of white peony root, 5-8 parts of wolfberry, 3-7 parts of liquorice. Enzymatic hydrolysis assisted water extraction: After mixing the medicinal materials, add 5 times of water, add 0.5% cellulase, stir evenly, enzymolyze at 50℃ for 1h, then add 8 times of water and extract at 80℃ for 1h. 60℃, vacuum degree -0.08MPa, reduce pressure and concentrate to a relative density of 1.15; The above concentrated products are mixed to obtain the product.

3. A Chinese medicine composition for treating cardiovascular and cerebrovascular diseases as claimed in claim 2, characterized in that: The low-temperature alcohol extraction of American ginseng, Eucommia ulmoides male flowers and Codonopsis pilosula specifically comprises: The first stage of subcritical pretreatment: 5-8 portions of Eucommia male flowers crushed to 40 mesh are put into a subcritical reactor separately, extracted at 0.8 MPa pressure, 55°C, 65% ethanol containing 0.1% citric acid for 10 minutes to quickly release chlorogenic acid, then the pressure is released to normal pressure and quickly cooled to 30°C; The second stage of microwave-ultrasound synergy: continue to add 8-14 parts of American ginseng crushed to 40 mesh and 8-15 parts of Codonopsis pilosula, adjust the ethanol concentration to 70%, first use microwave 400W / 30s to break through the cell wall, then switch to ultrasound 40kHz / 300W oscillation for 20 minutes, and microwave-ultrasound cycle 3 times; The third stage is low-temperature reverse filtration: After the extract is rapidly cooled at -20°C, it is filtered through a 0.1μm ceramic membrane to separate the saponin / polysaccharide complex. The filtrate can be recycled and used in the initial extraction stage of Eucommia male flowers.

4. A Chinese medicine composition for treating cardiovascular and cerebrovascular diseases as claimed in claim 2, characterized in that: The low-temperature dynamic percolation treatment of saffron and sour jujube kernel specifically includes: after the medicinal materials are crushed to 60 meshes, the percolation column is filled in the order of sour jujube kernel at the bottom and saffron at the top, and a 0.2 mm aperture stainless steel sieve is pre-laid at the bottom, the sour jujube kernel layer accounts for 30% of the height, and the saffron layer accounts for 60%; a 3V / cm DC pulse electric field with a frequency of 50Hz and a duty cycle of 1:1 is applied to the sour jujube kernel layer to promote the migration of saponin A ions, and a UV shielding glass column is used for the saffron layer, and a nitrogen protective layer is covered to block light oxidation; a three-stage reverse osmosis is used. The flow system is designed, in which 50% ethanol containing 0.05% ascorbic acid is used for the first stage to percolate from the Ziziphus jujuba seed layer upwards at a flow rate of 1 mL / min and 25°C; in the second stage, 50% ethanol containing 0.1% β-cyclodextrin is used for the second stage to percolate from the saffron layer downwards at a flow rate of 3 mL / min and 20°C; the final mixed solution is filtered through a 0.45 μm membrane and then recycled; the Ziziphus jujuba seed layer is first run through electric field percolation for 0.5 h, and after the dissolution rate of saponin A reaches 80%, the percolation of the saffron layer is started for 3 h, and the total time is shortened to 3.5 h.

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