CN108403882B - Salvia miltiorrhiza composition for treating coronary heart disease and preparation method thereof - Google Patents

Salvia miltiorrhiza composition for treating coronary heart disease and preparation method thereof Download PDF

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CN108403882B
CN108403882B CN201810380744.9A CN201810380744A CN108403882B CN 108403882 B CN108403882 B CN 108403882B CN 201810380744 A CN201810380744 A CN 201810380744A CN 108403882 B CN108403882 B CN 108403882B
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extract
extracting
concentrating
salvia miltiorrhiza
ethanol
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曾德成
刘然
张永嵩
巫涛
王芹
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Sichuan Guangda Pharmaceutical Co ltd
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Abstract

The invention belongs to the field of traditional Chinese medicines, and provides a traditional Chinese medicine composition containing salvia miltiorrhiza and a preparation method thereof, wherein the traditional Chinese medicine composition specifically comprises the following components in parts by weight: 800 portions of salvia miltiorrhiza bunge, 300 portions of scandent schefflera stem and leaf and 5 to 20 portions of grassleaf sweelflag rhizome, the invention extracts and purifies the components in the composition, adds cyclodextrin to ensure the solubility of fat-soluble ingredients, adds proper auxiliary materials to prepare the corresponding preparation, further limits the active ingredients of the preparation and is beneficial to the quality control of the medicine. The components of the composition provided by the invention are synergistic to play a role, so that the effect of treating coronary heart disease is greatly improved.

Description

Salvia miltiorrhiza composition for treating coronary heart disease and preparation method thereof
Technical Field
The invention relates to a traditional Chinese medicine composition and a preparation method thereof, in particular to a salvia miltiorrhiza composition for treating coronary heart disease and a preparation method thereof.
Background
Coronary atherosclerotic heart disease (CHD), abbreviated coronary heart disease, refers to a pathological change of the heart caused by myocardial ischemia, hypoxia or necrosis due to stenosis or complete occlusion of arterial vessel lumen caused by atherosclerosis of coronary artery. Coronary heart disease is the most common type of organ lesion caused by atherosclerosis, and is a common disease and frequently encountered disease which seriously harm human health at present. There are data showing that the prevalence of coronary heart disease increases 1-fold for every 10 years of age from 40 years old, that coronary atherosclerosis develops more rapidly in men 50 years old and in women 60 years old, and that the risk of myocardial infarction increases with age. The incidence of diseases in developed countries is high, the incidence of diseases is in a trend of youth in recent years, the incidence of diseases in China also rises year by year, and the disease is one of the main diseases threatening the health of human beings at present.
Coronary heart disease angina pectoris is a heart disease caused by myocardial ischemia and anoxia caused by blood vessel obstruction or/and coronary artery functional change (spasm) caused by coronary atherosclerosis, is one of common types of coronary heart disease, and seriously threatens public health globally.
With the development of modern science and technology, people have made some progress on the diagnosis and prevention of coronary heart disease, for example, in the aspect of examination, the application, biochemical examination and cardiac function determination method of dynamic electrocardiogram, echocardiography, coronary angiography and electron beam CT machine is also continuously improved from the conventional electrocardiogram and load electrocardiogram examination, thereby providing a good means for early diagnosis; the prevention and treatment aspects comprise the establishment of CCV, the establishment of coronary artery bypass surgery and the like; in the aspect of drug treatment, on the basis of coronary artery dilation, the application of calcium ion antagonists, beta-receptor blockers and thrombolytic drugs appears, and a plurality of means are provided for treating coronary heart disease.
However, clinical practice shows that pure western medicine treatment only treats the symptoms and the root causes, and particularly the side effects of the medicine cause the patients to be difficult to accept and take the medicine for a long time. With the improvement of economic level, modern human beings do not simply require the curative effect of the medicine, the safety requirement on the medicine is increasingly strong, and natural nuisanceless traditional Chinese medicine treatment is generally desired, so that a good opportunity is provided for the development of the traditional Chinese medicine. In the field of traditional Chinese medicine, coronary heart disease angina belongs to the category of chest stuffiness, pain in chest, even chest pain involving the back and inability to lie on a bed, is a disease with main symptoms of chest stuffiness, such as suffocation and hypopnea, in a mild case, pain such as stabbing, such as burning and twisting in a severe case, and pain in heart, pain in back and pain in back in a severe case.
Salvia miltiorrhiza is a labiate plant and has the effects of activating blood circulation to dissipate blood stasis, stimulating menstrual flow to relieve pain, clearing away heart-fire and relieving restlessness, cooling blood and eliminating carbuncle. It is commonly indicated for chest stuffiness and pain, abdominal pain, hypochondriac pain, mass, pain due to heat arthralgia, restlessness, insomnia, irregular menstruation, dysmenorrhea, amenorrhea, sore with swelling and pain. The medicine has obvious curative effect on treating cardiovascular and cerebrovascular diseases, especially coronary heart disease, and has the main active components of tanshinone and salvianolic acid, which can increase coronary blood flow, promote collateral circulation and improve myocardial microcirculation without increasing ventricular function and myocardial oxygen consumption and increase coronary blood flow. In recent years, people have increased the research of treating coronary heart disease with salvia miltiorrhiza, have achieved certain achievements, there are many varieties used in clinic, oral medicines include compound salvia miltiorrhiza tablet, compound salvia miltiorrhiza drop pill, etc., its main ingredients are salvia miltiorrhiza, notoginseng and borneol, wherein the compound salvia miltiorrhiza drop pill is used in clinic because of its good curative effect and rapid and extensive action.
Besides, a plurality of Chinese medicinal compositions which are compounded with the salvia miltiorrhiza for treating the coronary heart disease are also prepared. Patent CN100556445C discloses a Chinese medicinal composition with effects of regulating qi-flowing, relieving chest stuffiness, eliminating turbid pathogen, resolving stagnation, removing blood stasis and dredging collaterals, which is prepared from radix Salviae Miltiorrhizae, fructus Trichosanthis, radix Curcumae and rhizoma Acori Tatarinowii, and can be used for patients with coronary heart disease and angina pectoris.
Patent application CN105212504A discloses that the combination of radix Salviae Miltiorrhizae, flos Carthami, rhizoma Chuanxiong, radix Paeoniae Rubra, and lignum Dalbergiae Odoriferae has effects of promoting blood circulation, removing blood stasis, dredging collaterals, and relieving pain, and can be used for treating coronary heart disease.
However, the effective components in the above patent compositions are not clear, which is not good for the quality control of the medicine.
Tianjin Tianshili pharmaceutical Co Ltd applies for a series of Chinese medicinal compositions for treating coronary heart disease with Saviae Miltiorrhizae radix as core, such as a composition for treating coronary heart disease prepared from Saviae Miltiorrhizae radix, Notoginseng radix, rosewood oil or storax in patent CN 1778344B; the patent CN1778334B discloses a Chinese medicinal dripping pill prepared from radix Salviae Miltiorrhizae, rhizoma Chuanxiong and Borneolum Syntheticum, which has the curative effect of treating coronary heart disease and angina pectoris. However, the two patents are prepared by using an ultrafiltration process, the process is complex, and the manufacturing cost is greatly increased.
Disclosure of Invention
Based on the defects of the prior art, the invention provides the salvia miltiorrhiza composition, which is a traditional Chinese medicine composition for treating coronary heart disease, and the traditional Chinese medicine composition has reasonable components, clear components, obvious effect and low side effect, and fully exerts the synergistic effect of the salvia miltiorrhiza, the scandent schefflera stem and leaf and the grassleaf sweelflag rhizome by reasonably proportioning the salvia miltiorrhiza, the scandent schefflera stem and leaf and the grassleaf sweelflag rhizome, and limits the content of active ingredients in the composition.
The invention provides a salvia miltiorrhiza composition for treating coronary heart disease, which comprises 800 parts of salvia miltiorrhiza by weight, 300 parts of scandent schefflera root by weight and 5-20 parts of grassleaf sweelflag rhizome by weight.
Further, the composition comprises, by weight, 700 parts of salvia miltiorrhiza bunge, 200 parts of scandent schefflera stem and leaf and 10-15 parts of acorus gramineus.
Furthermore, the composition comprises 650 parts of salvia miltiorrhiza, 180 parts of scandent schefflera root and 12 parts of grassleaf sweelflag rhizome by weight.
Still further, the composition further comprises 50 parts by weight of cortex albiziae.
The invention also provides a traditional Chinese medicine preparation containing the salvia miltiorrhiza composition, which consists of the salvia miltiorrhiza composition and pharmaceutically acceptable auxiliary materials.
Further, tanshinone II in the preparationA0.10-0.50 percent of mass percent, 3.0-5.0 percent of salvianolic acid B, 0.20-0.40 percent of total saponin and 0.02-0.05 percent of volatile oil.
Further, tanshinone II in the preparationA0.20-0.40 percent of mass percent, 3.5-4.0 percent of salvianolic acid B, 0.25-0.35 percent of total saponin and 0.03-0.04 percent of volatile oil.
Further, the pharmaceutically acceptable excipients include hydroxypropyl-beta-cyclodextrin.
Further, the traditional Chinese medicine preparation comprises granules, tablets, capsules and pills.
The invention further provides a preparation method of the salvia miltiorrhiza composition preparation, which comprises the following steps:
(1) extracting the salvia miltiorrhiza: drying and pulverizing Saviae Miltiorrhizae radix, soaking in ethanol, extracting with a flash extractor, concentrating, passing the concentrated solution through HPD100 macroporous resin column, sequentially washing with water and ethanol, collecting eluate, concentrating, adding hydroxypropyl-beta-cyclodextrin, grinding, and drying to obtain Saviae Miltiorrhizae radix extract clathrate;
(2) extraction of scandent schefflera root: drying and crushing scandent schefflera stem and leaf, performing ultrasonic assisted extraction by using ethanol, performing reflux extraction by using a Soxhlet extractor, concentrating and drying filtrate to obtain a scandent schefflera stem and leaf extract, diluting the extract by adding water, sequentially extracting the diluted extract by using petroleum ether, dichloromethane, ethyl acetate and n-butyl alcohol, concentrating the n-butyl alcohol extract, performing gradient elution by using dichloromethane-methanol 100: 0-0: 100, respectively collecting fractions, combining and concentrating similar components by TLC identification to obtain a scandent schefflera stem and leaf extract;
(3) extracting the grassleaf sweelflag rhizome: pulverizing rhizoma Acori Graminei, and supercritical CO2Extracting to obtain rhizoma Acori Graminei volatile oil liquid, adding hydroxypropyl-beta-cyclodextrin, and grinding to obtain rhizoma Acori Graminei volatile oil clathrate;
(4) extracting cortex albiziae: defatting cortex Albizziae with petroleum ether, reflux-extracting with ethanol, concentrating the filtrate, drying to obtain cortex Albizziae extract, dissolving the extract, sequentially extracting with petroleum ether, dichloromethane, ethyl acetate and n-butanol, concentrating the n-butanol extractive solution, eluting with alumina column, eluting with ethanol, concentrating the eluate, and drying to obtain cortex Albizziae extract. (5) Pulverizing Saviae Miltiorrhizae radix extract clathrate, radix Schefflerae Arboricolae fraction extract and rhizoma Acori Graminei volatile oil clathrate, mixing, adding appropriate adjuvant, and preparing according to conventional method of Chinese medicinal preparation; or pulverizing Saviae Miltiorrhizae radix extract clathrate, radix Schefflerae Arboricolae fraction extract, rhizoma Acori Graminei volatile oil clathrate and cortex Albizziae extract, mixing, adding appropriate adjuvant, and making into desired dosage form by conventional method.
Further, the preparation method of the salvia miltiorrhiza composition preparation comprises the following steps:
(1) extracting the salvia miltiorrhiza: drying and crushing the salvia miltiorrhiza, soaking the salvia miltiorrhiza in 10-15 times of 70-80% ethanol for 10-30min, extracting the salvia miltiorrhiza for 3-10min at room temperature by using a flash extractor, standing the extract for 5-20min after extraction, extracting the extract twice, combining the filtrates, concentrating, passing the concentrated solution through an HPD100 macroporous resin column, sequentially washing the concentrated solution by using 2-3 times of column water, 25% ethanol, 50% ethanol, 75% ethanol and 100% ethanol, eluting at the flow rate of 2-3 times of column volume per hour, collecting the eluent, concentrating, adding hydroxypropyl-beta-cyclodextrin, fully grinding and drying to obtain the salvia miltiorrhiza extract clathrate compound.
(2) Extraction of scandent schefflera root: drying and crushing scandent schefflera stem and leaf, adding 8-12 times of 70-80% ethanol, performing ultrasonic assisted extraction for 50-60min, performing reflux extraction for 3-4h at 50-60 ℃, extracting for 2-3 times, centrifuging for 10-20min at 4000r/min of 3500-.
(3) Extracting the grassleaf sweelflag rhizome: pulverizing rhizoma Acori Graminei, and supercritical CO2Extracting at constant temperature and pressure for 1.5-3 hr at flow rate of 2-3L/h and extraction pressure of 5.0-7.0MPa and extraction temperature of 40-50 deg.C to obtain rhizoma Acori Graminei volatile oil liquid, adding hydroxypropyl-beta-cyclodextrin, and grinding to obtain rhizoma Acori Graminei volatile oil clathrate.
(4) Extracting cortex albiziae: extracting cortex Albizziae with 5-10 times of petroleum ether, refluxing at 60-70 deg.C, heating for defatting, adding 8-12 times of 70-80% ethanol, reflux extracting at 50-60 deg.C, concentrating and drying the filtrate to obtain cortex Albizziae extract, dissolving the extract, sequentially extracting with 10-20 times of petroleum ether, dichloromethane, ethyl acetate and n-butanol, concentrating n-butanol extractive solution, eluting with alumina column, eluting with 55-65% ethanol, concentrating and drying the eluate to obtain cortex Albizziae extract.
(5) Pulverizing Saviae Miltiorrhizae radix extract clathrate, radix Schefflerae Arboricolae extract and rhizoma Acori Graminei volatile oil clathrate, mixing, adding appropriate adjuvant, and preparing according to conventional method of Chinese medicinal preparation; or pulverizing Saviae Miltiorrhizae radix extract clathrate, radix Schefflerae Arboricolae fraction extract, rhizoma Acori Graminei volatile oil clathrate and cortex Albizziae extract, mixing, adding appropriate adjuvant, and making into desired dosage form by conventional method.
Furthermore, in the preparation method, the weight ratio of the salvia miltiorrhiza bunge and the hydroxypropyl-beta-cyclodextrin in the step (1) is 100: 2-5.
Furthermore, in the preparation method, the weight ratio of the rhizoma acori graminei and the hydroxypropyl-beta-cyclodextrin in the step (3) is 100: 2-5.
The invention also provides the application of the salvia miltiorrhiza composition in preparing a medicine for treating coronary heart disease.
Preferably, the salvia miltiorrhiza composition is applied to the preparation of a medicament for treating angina caused by coronary heart disease.
The invention has the beneficial effects that:
(1) in the salvia miltiorrhiza composition provided by the invention, salvia miltiorrhiza has the effects of activating blood and removing stasis, and stimulating menstrual flow and relieving pain; the scandent schefflera root has the effects of dispelling wind, relieving pain, activating blood and reducing swelling; rhizoma Acori Graminei has the effects of inducing resuscitation, eliminating phlegm, refreshing mind and improving intelligence. The components are mutually synergistic to play a role, so that the composition has the effect of remarkably treating coronary heart disease, particularly angina pectoris, and the cortex albiziae has the effects of promoting blood circulation, removing blood stasis, resolving stagnation, relieving pain and the like, so that the effect of the composition in treating coronary heart disease is further enhanced.
(2) The invention can treat tanshinone II as active component in the preparationAThe contents of the salvianolic acid B, the total saponins and the volatile oil are clearly limited, the safety of clinical medication is ensured, and the product quality is easy to control.
(3) The process of the invention extracts, separates and purifies the active ingredients to prepare the tanshinone II in the traditional Chinese medicine preparationAThe purity of the salvianolic acid B, the total saponin and the volatile oil is higher, the functions of the salvianolic acid B, the total saponin and the volatile oil are facilitated, especially, the triterpenoid saponin taking oleanolic acid as a main component and the volatile oil mainly taking beta-asarone have good effect of expanding arterial blood vessels, the four active components have the mutual synergistic effect, and the curative effect of the composition for treating coronary heart disease is obviously improved.
(4) The invention has simple extraction process, and the hydroxypropyl-beta-cyclodextrin is added to respectively carry out inclusion on the salvia miltiorrhiza extract and the grassleaf sweelflag rhizome essential oil, thereby increasing the solubility of the medicine which is difficult to dissolve in water, simultaneously improving the slow release effect of the medicine and greatly increasing the exertion of the medicine effect of the effective components.
Detailed Description
EXAMPLE 1 Salvia miltiorrhiza composition and preparation thereof
According to the weight portion, the traditional Chinese medicine composition is composed of 650 portions of salvia miltiorrhiza, 180 portions of scandent schefflera root and 12 portions of grassleaf sweelflag rhizome.
The preparation method of the compound salvia miltiorrhiza granules comprises the following steps:
(1) extracting the salvia miltiorrhiza: drying and crushing salvia miltiorrhiza, soaking the salvia miltiorrhiza in 12 times of 75% ethanol for 20min, extracting the salvia miltiorrhiza in a flash extractor for 5min at room temperature, standing the salvia miltiorrhiza for 10min after extraction, extracting the salvia miltiorrhiza twice, combining the filtrates, concentrating the combined filtrates, passing the concentrated solution through an HPD100 macroporous resin column, sequentially washing the concentrated solution with 2 times of column water, 25% ethanol, 50% ethanol, 75% ethanol and 100% ethanol at an elution flow rate of 3 times of column volume per hour, collecting the eluent, concentrating the eluent, adding 19.5 parts of hydroxypropyl-beta-cyclodextrin, fully grinding and drying the mixture to obtain a salvia miltiorrhiza extract clathrate compound;
(2) extraction of scandent schefflera root: drying and crushing scandent schefflera stem and leaf, adding 10 times of 75% ethanol, performing ultrasonic assisted extraction for 55min, performing reflux extraction for 3.5h at 55 ℃, extracting for 2 times, centrifuging for 10min at 4000r/min, combining filtrates, concentrating and drying to obtain a scandent schefflera stem and leaf extract, diluting the extract with water, sequentially extracting with 10 times of petroleum ether, dichloromethane, ethyl acetate and n-butyl alcohol, concentrating the n-butyl alcohol extract, passing through a silica gel (200-mesh and 300-mesh) column, performing gradient elution with dichloromethane-methanol of 100:0, 100:25, 100:50, 100:100, 50:100, 25:100 and 0:100, respectively collecting fractions, performing TLC identification, combining the components, determining and concentrating the part with the highest total saponin content to obtain a scandent schefflera stem fraction extract;
(3) extracting the grassleaf sweelflag rhizome: pulverizing rhizoma Acori Graminei, and supercritical CO2Extracting at constant temperature and constant pressure for 2h at flow rate of 2.5L/h and extraction pressure of 6.0MPa and extraction temperature of 45 deg.C to obtain rhizoma Acori Graminei volatile oil liquid, adding 0.36 parts of hydroxypropyl-beta-cyclodextrin, and grinding to obtain rhizoma Acori Graminei volatile oil clathrate;
(4) pulverizing Saviae Miltiorrhizae radix extract clathrate, radix Schefflerae Arboricolae fraction extract and rhizoma Acori Graminei volatile oil clathrate, mixing, adding appropriate adjuvant, and making into granule by conventional method.
EXAMPLE 2 Salvia miltiorrhiza compositions and their preparation
The traditional Chinese medicine composition comprises, by weight, 600 parts of salvia miltiorrhiza, 200 parts of scandent schefflera root and 15 parts of grassleaf sweelflag rhizome.
The preparation method of the compound salvia tablet comprises the following steps:
(1) extracting the salvia miltiorrhiza: drying and crushing salvia miltiorrhiza, soaking the salvia miltiorrhiza in 10 times of 80% ethanol for 30min, extracting the salvia miltiorrhiza in a flash extractor at room temperature for 3min, standing the salvia miltiorrhiza for 20min after extraction, extracting the salvia miltiorrhiza twice, combining the filtrates, concentrating the filtrate, passing the concentrated solution through an HPD100 macroporous resin column, sequentially washing the concentrated solution with 3 times of column water, 25% ethanol, 50% ethanol, 75% ethanol and 100% ethanol at an elution flow rate of 2 times of column volume per hour, collecting the eluate, concentrating the eluate, adding 30 parts of hydroxypropyl-beta-cyclodextrin, fully grinding and drying the mixture to obtain a salvia miltiorrhiza extract clathrate compound;
(2) extraction of scandent schefflera root: drying and crushing scandent schefflera stem and leaf, adding 8 times of 70% ethanol, performing ultrasonic assisted extraction for 50min, performing reflux extraction at 50 ℃ for 4h, extracting for 2 times, centrifuging for 10min at 4000r/min, merging filtrate, concentrating and drying to obtain a scandent schefflera stem and leaf extract, diluting the extract with water, sequentially extracting with 20 times of petroleum ether, dichloromethane, ethyl acetate and n-butyl alcohol, concentrating the n-butyl alcohol extract, passing through a silica gel (200-300 meshes) column, performing gradient elution with dichloromethane-methanol of 100:0, 100:25, 100:50, 100:100, 50:100, 25:100 and 0:100, respectively collecting fractions, performing TLC identification, merging the components, determining and concentrating the part with the highest total saponin content to obtain a scandent schefflera stem fraction extract;
(3) extracting the grassleaf sweelflag rhizome: pulverizing rhizoma Acori Graminei, and supercritical CO2Extracting at constant temperature and constant pressure for 3h at flow rate of 2L/h, extraction pressure of 5.0MPa and extraction temperature of 40 deg.C to obtain rhizoma Acori Graminei volatile oil liquid, adding 0.75 part of hydroxypropyl-beta-cyclodextrin, and grinding to obtain rhizoma Acori Graminei volatile oil clathrate;
(4) pulverizing Saviae Miltiorrhizae radix extract clathrate, radix Schefflerae Arboricolae fraction extract and rhizoma Acori Graminei volatile oil clathrate, mixing, adding appropriate adjuvant, and tabletting.
EXAMPLE 3 Salvia miltiorrhiza compositions and their preparation
According to the weight portion, the traditional Chinese medicine composition is composed of 500 portions of salvia miltiorrhiza, 150 portions of scandent schefflera root and 5 portions of grassleaf sweelflag rhizome.
The preparation method of the compound salvia miltiorrhiza capsule comprises the following steps:
(1) extracting the salvia miltiorrhiza: drying and crushing salvia miltiorrhiza, soaking the salvia miltiorrhiza in 15 times of 75% ethanol for 25min, extracting the salvia miltiorrhiza in a flash extractor for 8min at room temperature, standing the extract for 5min, extracting the extract twice, combining the filtrates, concentrating the filtrate, passing the concentrated solution through an HPD100 macroporous resin column, sequentially washing the concentrated solution with 2 times of column water, 25% ethanol, 50% ethanol, 75% ethanol and 100% ethanol at an elution flow rate of 2 times of column volume per hour, collecting the eluate, concentrating the eluate, adding 10 parts of hydroxypropyl-beta-cyclodextrin, fully grinding and drying the eluate to obtain a salvia miltiorrhiza extract clathrate compound;
(2) extraction of scandent schefflera root: drying and crushing scandent schefflera stem and leaf, adding 10 times of 80% ethanol, carrying out ultrasonic assisted extraction for 60min, carrying out reflux extraction for 4h at 55 ℃, extracting for 3 times, centrifuging for 20min at 3500r/min, combining filtrates, concentrating and drying to obtain a scandent schefflera stem and leaf extract, diluting the extract with water, sequentially extracting with 12 times of petroleum ether, dichloromethane, ethyl acetate and n-butyl alcohol, concentrating the n-butyl alcohol extract, passing through a silica gel (200-300 meshes) column, carrying out gradient elution on dichloromethane-methanol (100: 0, 100:25, 100:50, 100:100, 50:100, 25:100 and 0: 100), respectively collecting fractions, carrying out TLC identification, combining the components, determining and concentrating the part with the highest total saponin content to obtain a scandent schefflera stem fraction extract;
(3) extracting the grassleaf sweelflag rhizome: pulverizing rhizoma Acori Graminei, and supercritical CO2Extracting at constant temperature and constant pressure for 1.5h at flow rate of 3L/h, extraction pressure of 6.0MPa and extraction temperature of 45 deg.C to obtain rhizoma Acori Graminei volatile oil liquid, adding 0.25 part of hydroxypropyl-beta-cyclodextrin, and grinding to obtain rhizoma Acori Graminei volatile oil clathrate;
(4) pulverizing Saviae Miltiorrhizae radix extract clathrate, radix Schefflerae Arboricolae fraction extract and rhizoma Acori Graminei volatile oil clathrate, mixing, adding appropriate adjuvant, granulating, and encapsulating.
EXAMPLE 4 Salvia miltiorrhiza compositions and their preparation
According to the weight portion, the traditional Chinese medicine composition is composed of 700 portions of salvia miltiorrhiza, 300 portions of scandent schefflera root and 20 portions of grassleaf sweelflag rhizome.
The preparation method of the compound salvia miltiorrhiza granules comprises the following steps:
(1) extracting the salvia miltiorrhiza: drying and crushing salvia miltiorrhiza, soaking the salvia miltiorrhiza in 12 times of 70% ethanol for 10min, extracting the salvia miltiorrhiza in a flash extractor for 10min at room temperature, standing the extract for 15min, extracting the extract twice, combining the filtrates, concentrating the filtrate, passing the concentrated solution through an HPD100 macroporous resin column, sequentially washing the concentrated solution with 2.5 times of column water, 25% ethanol, 50% ethanol, 75% ethanol and 100% ethanol at the elution flow rate of 3 times of column volume per hour, collecting the eluate, concentrating the eluate, adding 28 parts of hydroxypropyl-beta-cyclodextrin, fully grinding and drying the mixture to obtain a salvia miltiorrhiza extract clathrate compound;
(2) extraction of scandent schefflera root: drying and crushing scandent schefflera stem and leaf, adding 75% ethanol with the volume being 12 times that of the crushed scandent schefflera stem and leaf, carrying out ultrasonic assisted extraction for 60min, carrying out reflux extraction for 3h at the temperature of 60 ℃, extracting for 2 times, centrifuging for 20min at 3500r/min, merging filtrate, concentrating and drying to obtain a scandent schefflera stem and leaf extract, adding water to dilute the extract, then sequentially extracting with petroleum ether, dichloromethane, ethyl acetate and n-butyl alcohol with the volume being 15 times that of the extract, concentrating the n-butyl alcohol extract, passing through a silica gel (200-300 meshes) column, carrying out gradient elution on dichloromethane-methanol with the concentration ratio of 100:0, 100:25, 100: 50:100, 25:100 and 0:100, respectively collecting fractions, merging the components through TLC identification, determining and concentrating;
(3) extracting the grassleaf sweelflag rhizome: pulverizing rhizoma Acori Graminei, and supercritical CO2Extracting at constant temperature and constant pressure for 2.5 hr at flow rate of 2.5L/h and extraction pressure of 7.0MPa and extraction temperature of 50 deg.C to obtain rhizoma Acori Graminei volatile oil liquid, adding 0.4 part of hydroxypropyl-beta-cyclodextrin, and grinding to obtain rhizoma Acori Graminei volatile oil clathrate;
(4) pulverizing Saviae Miltiorrhizae radix extract clathrate, radix Schefflerae Arboricolae fraction extract and rhizoma Acori Graminei volatile oil clathrate, mixing, adding appropriate adjuvant, and granulating with fluidized bed to obtain granule.
EXAMPLE 5 Salvia miltiorrhiza compositions and their preparation
The traditional Chinese medicine composition comprises 800 parts of salvia miltiorrhiza, 120 parts of scandent schefflera root and 10 parts of grassleaf sweelflag rhizome by weight.
The preparation method of the compound salvia tablet comprises the following steps:
(1) extracting the salvia miltiorrhiza: drying and crushing salvia miltiorrhiza, soaking the salvia miltiorrhiza in 15 times of 75% ethanol for 15min, extracting the salvia miltiorrhiza in a flash extractor for 10min at room temperature, standing the salvia miltiorrhiza for 15min after extraction, extracting the salvia miltiorrhiza twice, combining the filtrates, concentrating the combined filtrates, passing the concentrated solution through an HPD100 macroporous resin column, sequentially washing the concentrated solution with 3 times of column water, 25% ethanol, 50% ethanol, 75% ethanol and 100% ethanol at an elution flow rate of 3 times of column volume per hour, collecting the eluent, concentrating the eluent, adding 30 parts of hydroxypropyl-beta-cyclodextrin, fully grinding and drying the mixture to obtain a salvia miltiorrhiza extract clathrate compound;
(2) extraction of scandent schefflera root: drying and crushing scandent schefflera stem and leaf, adding 10 times of 75% ethanol, performing ultrasonic assisted extraction for 60min, performing reflux extraction for 3h at 60 ℃, extracting for 2 times, centrifuging for 20min at 3500r/min, combining filtrates, concentrating and drying to obtain a scandent schefflera stem and leaf extract, diluting the extract with water, sequentially extracting with 10 times of petroleum ether, dichloromethane, ethyl acetate and n-butyl alcohol, concentrating the n-butyl alcohol extract, passing through a silica gel (200-300 meshes) column, performing gradient elution with dichloromethane-methanol of 100:0, 100:25, 100:50, 100:100, 50:100, 25:100 and 0:100, respectively collecting fractions, performing TLC identification, combining the components, determining and concentrating the part with the highest total saponin content to obtain a scandent schefflera stem fraction extract;
(3) extracting the grassleaf sweelflag rhizome: pulverizing rhizoma Acori Graminei, and supercritical CO2Extracting at constant temperature and constant pressure for 2.5h at flow rate of 2.5L/h and extraction pressure of 6.0MPa and extraction temperature of 45 deg.C to obtain rhizoma Acori Graminei volatile oil liquid, adding 0.5 part of hydroxypropyl-beta-cyclodextrin, and grinding to obtain rhizoma Acori Graminei volatile oil clathrate;
(4) pulverizing Saviae Miltiorrhizae radix extract clathrate, radix Schefflerae Arboricolae fraction extract and rhizoma Acori Graminei volatile oil clathrate, mixing, and making into tablet according to conventional prescription of Chinese medicinal tablet.
EXAMPLE 6 Salvia miltiorrhiza compositions and their preparation
According to the weight portion, the traditional Chinese medicine composition is composed of 650 portions of salvia miltiorrhiza, 180 portions of scandent schefflera root, 12 portions of grassleaf sweelflag rhizome and 50 portions of silktree albizzia bark.
The preparation method of the compound salvia miltiorrhiza granules comprises the following steps:
(1) extracting the salvia miltiorrhiza: drying and crushing salvia miltiorrhiza, soaking the salvia miltiorrhiza in 12 times of 75% ethanol for 20min, extracting the salvia miltiorrhiza in a flash extractor for 5min at room temperature, standing the salvia miltiorrhiza for 10min after extraction, extracting the salvia miltiorrhiza twice, combining the filtrates, concentrating the combined filtrates, passing the concentrated solution through an HPD100 macroporous resin column, sequentially washing the concentrated solution with 2 times of column water, 25% ethanol, 50% ethanol, 75% ethanol and 100% ethanol at an elution flow rate of 3 times of column volume per hour, collecting the eluent, concentrating the eluent, adding 19.5 parts of hydroxypropyl-beta-cyclodextrin, fully grinding and drying the mixture to obtain a salvia miltiorrhiza extract clathrate compound;
(2) extraction of scandent schefflera root: drying and crushing scandent schefflera stem and leaf, adding 10 times of 75% ethanol, performing ultrasonic assisted extraction for 55min, performing reflux extraction for 3.5h at 55 ℃, extracting for 2 times, centrifuging for 10min at 4000r/min, combining filtrates, concentrating and drying to obtain a scandent schefflera stem and leaf extract, diluting the extract with water, sequentially extracting with 10 times of petroleum ether, dichloromethane, ethyl acetate and n-butyl alcohol, concentrating the n-butyl alcohol extract, passing through a silica gel (200-mesh and 300-mesh) column, performing gradient elution with dichloromethane-methanol of 100:0, 100:25, 100:50, 100:100, 50:100, 25:100 and 0:100, respectively collecting fractions, performing TLC identification, combining the components, determining and concentrating the part with the highest total saponin content to obtain a scandent schefflera stem fraction extract;
(3) extracting the grassleaf sweelflag rhizome: pulverizing rhizoma Acori Graminei, and supercritical CO2Extracting at constant temperature and constant pressure for 2h at flow rate of 2.5L/h and extraction pressure of 6.0MPa and extraction temperature of 45 deg.C to obtain rhizoma Acori Graminei volatile oil liquid, adding 0.36 parts of hydroxypropyl-beta-cyclodextrin, and grinding to obtain rhizoma Acori Graminei volatile oil clathrate;
(4) extracting cortex albiziae: performing reflux heating degreasing on the albizzia julibrissin by using petroleum ether of 8 times, performing reflux heating degreasing at 65 ℃, adding 75% ethanol of 10 times, performing reflux extraction at 55 ℃, concentrating and drying filtrate to obtain an albizzia julibrissin extract, sequentially extracting the extract by using petroleum ether, dichloromethane, ethyl acetate and n-butyl alcohol of 15 times of volume after dissolving the extract, concentrating an n-butyl alcohol extract, eluting by using an alumina column, eluting by using 60% ethanol, concentrating and drying an eluent to obtain an albizzia julibrissin extract;
(5) pulverizing Saviae Miltiorrhizae radix extract clathrate, radix Schefflerae Arboricolae fraction extract, rhizoma Acori Graminei volatile oil clathrate and cortex Albizziae extract, mixing, adding appropriate adjuvant, and making into granule by conventional method.
Comparative example 1 salvia miltiorrhiza composition without scandent schefflera root and preparation thereof
According to the weight portion, the medicine is composed of 650 portions of salvia miltiorrhiza and 12 portions of acorus gramineus.
The preparation method of the compound salvia miltiorrhiza preparation comprises the following steps:
(1) extracting the salvia miltiorrhiza: drying and crushing salvia miltiorrhiza, soaking the salvia miltiorrhiza in 12 times of 75% ethanol for 20min, extracting the salvia miltiorrhiza in a flash extractor for 5min at room temperature, standing the salvia miltiorrhiza for 10min after extraction, extracting the salvia miltiorrhiza twice, combining the filtrates, concentrating the combined filtrates, passing the concentrated solution through an HPD100 macroporous resin column, sequentially washing the concentrated solution with 2 times of column water, 25% ethanol, 50% ethanol, 75% ethanol and 100% ethanol at an elution flow rate of 3 times of column volume per hour, collecting the eluent, concentrating the eluent, adding 19.5 parts of hydroxypropyl-beta-cyclodextrin, fully grinding and drying the mixture to obtain a salvia miltiorrhiza extract clathrate compound;
(2) extracting the grassleaf sweelflag rhizome: pulverizing rhizoma Acori Graminei, and supercritical CO2Extracting at constant temperature and constant pressure for 2h at flow rate of 2.5L/h and extraction pressure of 6.0MPa and extraction temperature of 45 deg.C to obtain rhizoma Acori Graminei volatile oil liquid, adding 0.36 parts of hydroxypropyl-beta-cyclodextrin, and grinding to obtain rhizoma Acori Graminei volatile oil clathrate;
(3) pulverizing Saviae Miltiorrhizae radix extract clathrate and rhizoma Acori Graminei volatile oil clathrate, mixing, adding appropriate adjuvant, and making into granule by conventional method.
Comparative example 2 Salvia miltiorrhiza composition without Acorus gramineus soland and preparation thereof
According to the weight portion, the traditional Chinese medicine composition is composed of 650 portions of salvia miltiorrhiza and 180 portions of scandent schefflera root.
The preparation method of the compound salvia miltiorrhiza granules comprises the following steps:
(1) extracting the salvia miltiorrhiza: drying and crushing salvia miltiorrhiza, soaking the salvia miltiorrhiza in 12 times of 75% ethanol for 20min, extracting the salvia miltiorrhiza in a flash extractor for 5min at room temperature, standing the salvia miltiorrhiza for 10min after extraction, extracting the salvia miltiorrhiza twice, combining the filtrates, concentrating the combined filtrates, passing the concentrated solution through an HPD100 macroporous resin column, sequentially washing the concentrated solution with 2 times of column water, 25% ethanol, 50% ethanol, 75% ethanol and 100% ethanol at an elution flow rate of 3 times of column volume per hour, collecting the eluent, concentrating the eluent, adding 19.5 parts of hydroxypropyl-beta-cyclodextrin, fully grinding and drying the mixture to obtain a salvia miltiorrhiza extract clathrate compound;
(2) extraction of scandent schefflera root: drying and crushing scandent schefflera stem and leaf, adding 10 times of 75% ethanol, performing ultrasonic assisted extraction for 55min, performing reflux extraction for 3.5h at 55 ℃, extracting for 2 times, centrifuging for 10min at 4000r/min, combining filtrates, concentrating and drying to obtain a scandent schefflera stem and leaf extract, diluting the extract with water, sequentially extracting with 10 times of petroleum ether, dichloromethane, ethyl acetate and n-butyl alcohol, concentrating the n-butyl alcohol extract, passing through a silica gel (200-mesh and 300-mesh) column, performing gradient elution with dichloromethane-methanol of 100:0, 100:25, 100:50, 100:100, 50:100, 25:100 and 0:100, respectively collecting fractions, performing TLC identification, combining the components, determining and concentrating the part with the highest total saponin content to obtain a scandent schefflera stem fraction extract;
(3) pulverizing Saviae Miltiorrhizae radix extract clathrate and radix Schefflerae Arboricolae fraction extract, mixing, adding appropriate adjuvant, and making into granule by conventional method.
Comparative example 3 Salvia miltiorrhiza composition prepared without hydroxypropyl-beta-cyclodextrin and preparation thereof
According to the weight portion, the traditional Chinese medicine composition is composed of 650 portions of salvia miltiorrhiza, 180 portions of scandent schefflera root and 12 portions of grassleaf sweelflag rhizome.
The preparation method of the compound salvia miltiorrhiza granules comprises the following steps:
(1) extracting the salvia miltiorrhiza: drying and crushing the salvia miltiorrhiza, soaking the salvia miltiorrhiza in 12 times of 75% ethanol for 20min, extracting the salvia miltiorrhiza in a flash extractor for 5min at room temperature, standing the salvia miltiorrhiza for 10min after extraction, extracting the salvia miltiorrhiza twice, combining the filtrates, concentrating the filtrate, passing the concentrated solution through an HPD100 macroporous resin column, sequentially washing the salvia miltiorrhiza with 2 times of column body water, 25% ethanol, 50% ethanol, 75% ethanol and 100% ethanol at an elution flow rate of 3 times of column volume per hour, collecting the eluent, concentrating the eluent, and drying the eluent to obtain salvia miltiorrhiza extract;
(2) extraction of scandent schefflera root: drying and crushing scandent schefflera stem and leaf, adding 10 times of 75% ethanol, performing ultrasonic assisted extraction for 55min, performing reflux extraction for 3.5h at 55 ℃, extracting for 2 times, centrifuging for 10min at 4000r/min, combining filtrates, concentrating and drying to obtain a scandent schefflera stem and leaf extract, diluting the extract with water, sequentially extracting with 10 times of petroleum ether, dichloromethane, ethyl acetate and n-butyl alcohol, concentrating the n-butyl alcohol extract, passing through a silica gel (200-mesh and 300-mesh) column, performing gradient elution with dichloromethane-methanol of 100:0, 100:25, 100:50, 100:100, 50:100, 25:100 and 0:100, respectively collecting fractions, performing TLC identification, combining the components, determining and concentrating the part with the highest total saponin content to obtain a scandent schefflera stem fraction extract;
(3) extracting the grassleaf sweelflag rhizome: pulverizing rhizoma Acori Graminei, and supercritical CO2Extracting at constant temperature and constant pressure for 2 hr at flow rate of 2.5L/hr and extraction pressure of 6.0MPa and extraction temperature of 45 deg.C to obtain rhizoma Acori Graminei volatile oil liquid and rhizoma Acori Graminei volatile oil liquid;
(4) pulverizing Saviae Miltiorrhizae radix extract and scandent schefflera stem and leaf extract, mixing, spraying rhizoma Acori Graminei volatile oil, adding appropriate adjuvant, and making into granule by conventional method.
Comparative example 4 Salvia miltiorrhiza composition with unreasonable component content and preparation thereof
According to the weight portion, the traditional Chinese medicine composition is composed of 400 portions of salvia miltiorrhiza, 100 portions of scandent schefflera root and 30 portions of grassleaf sweelflag rhizome.
The preparation method of the compound salvia miltiorrhiza granules comprises the following steps:
(1) extracting the salvia miltiorrhiza: drying and crushing salvia miltiorrhiza, soaking the salvia miltiorrhiza in 12 times of 75% ethanol for 20min, extracting the salvia miltiorrhiza in a flash extractor for 5min at room temperature, standing the salvia miltiorrhiza for 10min after extraction, extracting the salvia miltiorrhiza twice, combining the filtrates, concentrating the combined filtrates, passing the concentrated solution through an HPD100 macroporous resin column, sequentially washing the concentrated solution with 2 times of column water, 25% ethanol, 50% ethanol, 75% ethanol and 100% ethanol at an elution flow rate of 3 times of column volume per hour, collecting the eluent, concentrating the eluent, adding 19.5 parts of hydroxypropyl-beta-cyclodextrin, fully grinding and drying the mixture to obtain a salvia miltiorrhiza extract clathrate compound;
(2) extraction of scandent schefflera root: drying and crushing scandent schefflera stem and leaf, adding 10 times of 75% ethanol, performing ultrasonic assisted extraction for 55min, performing reflux extraction for 3.5h at 55 ℃, extracting for 2 times, centrifuging for 10min at 4000r/min, combining filtrates, concentrating and drying to obtain a scandent schefflera stem and leaf extract, diluting the extract with water, sequentially extracting with 10 times of petroleum ether, dichloromethane, ethyl acetate and n-butyl alcohol, concentrating the n-butyl alcohol extract, passing through a silica gel (200-mesh and 300-mesh) column, performing gradient elution with dichloromethane-methanol of 100:0, 100:25, 100:50, 100:100, 50:100, 25:100 and 0:100, respectively collecting fractions, performing TLC identification, combining the components, determining and concentrating the part with the highest total saponin content to obtain a scandent schefflera stem fraction extract;
(3) extracting the grassleaf sweelflag rhizome: pulverizing rhizoma Acori Graminei, and supercritical CO2Extracting at constant temperature and constant pressure for 2h at flow rate of 2.5L/h and extraction pressure of 6.0MPa and extraction temperature of 45 deg.C to obtain rhizoma Acori Graminei volatile oil liquid, adding 0.36 parts of hydroxypropyl-beta-cyclodextrin, and grinding to obtain rhizoma Acori Graminei volatile oil clathrate;
(4) pulverizing Saviae Miltiorrhizae radix extract clathrate, radix Schefflerae Arboricolae fraction extract and rhizoma Acori Graminei volatile oil clathrate, mixing, adding appropriate adjuvant, and making into granule by conventional method.
EXAMPLE 6 pharmacodynamic Studies of Salvia miltiorrhiza composition
6.1 therapeutic action of Salvia miltiorrhiza composition on myocardial ischemia in rats
6.1.1 grouping and administration mode
One week after adaptive feeding of rats, the rats are immediately divided into 10 groups, each group comprises 5 animals with half male and female, and the groups are respectively blank group, model group, example 1 group, example 2 group, example 6 group, comparative examples 1-4 group, and commercially available compound radix salviae miltiorrhizae dripping pill group, the daily dose is 0.18g/kg, the compound radix salviae miltiorrhizae dripping pill group is converted into daily dose (3 pills/kg) of the rats, and 4U sublingual intravenous injection of hypophysin (3U/ml) is given to each sublingual vein to hypophysin, so as to cause acute myocardial ischemia model.
6.1.2 myocardial ischemia model
And (3) irrigating distilled water into the blank group and the model group, respectively irrigating the medicines into the administration group for 7 days, after the medicine is administered for 1h on the 7 th day, carrying out intraperitoneal injection of 10% chloral hydrate for anesthesia, fixing the medicine on an operating table in a supine position, carrying out sublingual intravenous injection of hypophysin (3U/ml) according to 4U per kilogram of body weight to cause an acute myocardial ischemia model, after 20min of modeling, taking blood from the abdominal aorta, placing the blood in a coagulation-promoting vacuum blood collection tube, centrifuging the blood for 10min at 4 ℃ and 3500r/min, and separating the serum and centrifuging the blood to obtain serum. The content of Creatine Kinase (CK) and Lactate Dehydrogenase (LDH) in serum is detected by a biochemical method.
6.1.3 results of the experiment
TABLE 1 results of anti-myocardial ischemia drug effect
Group of N Dosage form CK(U/L) LDH(U/L)
Blank group 5 - 1296.37±147.32a 702.33±78.51a
Model set 5 - 3217.22±156.41b 1546.78±101.30b
Example 1 5 0.18g/kg 1754.21±112.21c 894.25±54.33c
Example 2 5 0.18g/kg 1875.14±143.52c 954.12±96.30c
Example 6 5 0.18g/kg 1731.31±134.21c 880.35±58.36c
Comparative example 1 5 0.18g/kg 2514.67±175.65d 1314.22±54.21d
Comparative example 2 5 0.18g/kg 2344.14±153.20d 1296.45±68.54d
Comparative example 3 5 0.18g/kg 2314.55±110.01d 1302.54±78.31d
Comparative example 4 5 0.18g/kg 2001.30±98.54e 1143.02±104.38e
Compound red sage dripping pill 5 3 pills/kg 2115.67±145.32e 1042.1±121.11e
Note: the representations in the same column have significant differences.
As can be seen from Table 1, the model group and the blank group have significant differences, indicating that the molding was successful. Compared with comparative examples 1-4 and the compound salvia dropping pills sold in the market, the CK and LDH values of examples 1, 2 and 6 have significant differences, and the CK and LDH values of rats with myocardial ischemia can be significantly reduced, so that the salvia composition provided by the invention has a better effect of treating myocardial ischemia. The absence of any one component or the adjustment of the ratio between the components in the composition will affect the efficacy of the composition.
6.2 Effect of Salvia miltiorrhiza compositions on myocardial infarction Range of rats
6.2.1 grouping and administration
Wistar rats were randomly divided into 9 groups, and 8ml of 0.9% physiological saline, examples 1, 2, and 6, comparative examples 1 to 4, and a commercially available compound Danshen drop pill group were administered to the model group. The daily dose is 0.18g/kg, the daily dose (3 pills/kg) of compound Danshen dripping pills is converted into rat, and the administration is performed by gastric lavage.
6.2.2 establishment of rat myocardial infarction model
The animals were fixed in the supine position by intraperitoneal injection and anesthesia (45 mg/kg). Trachea cannula, making 2cm longitudinal incision on left side of sternum, cutting 3 rd and 4 th costal cartilage on side near sternum, opening thoracic cavity, and connecting with artificial respirator (approximate air volume 2ml/100g, 50 times/min). Cutting pericardium, exposing heart, threading root of left anterior branch of coronary artery for ligation, recording standard II-lead electrocardiogram, stabilizing for 10min, ligating left anterior descending branch of coronary artery, and closing thoracic cavity. Sucking out animal laryngeal secretion by using a syringe so as to enable the animal to recover spontaneous respiration. The coronary artery was ligated for 15min and then administered by intragastric administration. After 4 hours, the heart was harvested and 5 slices below the ligature were stained with nitronium chloride gene azote blue (N-BT) to calculate the percentage of the area of the infarcted area of the myocardium to the area of the ventricle and heart.
6.2.3 results of the experiment
TABLE 2 Effect of Salvia miltiorrhiza compositions on the extent of experimental myocardial infarction in rats
Figure BDA0001641056890000131
Note: the representations in the same column have significant differences.
As can be seen from table 2, compared with the model group, the myocardial infarction areas of the groups of medicaments after treatment are all significantly reduced, the best effect is achieved in example 6, and the myocardial infarction areas are significantly lower than those of the salvia miltiorrhiza composition provided in comparative examples 1 to 4 and the commercially available compound salvia miltiorrhiza dropping pills, which indicates that the components of the salvia miltiorrhiza composition provided by the invention act synergistically, the range of myocardial infarction is significantly reduced, and the effect on treating coronary heart disease is significant.
6.3 protective action of Salvia miltiorrhiza composition on reperfusion injury of isolated heart of SD rat
6.3.1 Experimental groups and modes of administration
SD rats were divided into 10 groups. Blank group: continuously perfusing with oxygen-containing K-H liquid for 120 min; model group: perfusing with oxygen-containing K-H liquid for 15min, stopping perfusing for 25min, and recovering oxygen-containing K-H liquid perfusing for 60 min; examples 1, 2 and 6, comparative examples 1 to 4 were administered at 0.18g/kg and the commercially available compound Danshen dripping pill group was administered at 3 pills/kg, the administration methods were: when the perfusion is recovered, different perfusion liquids containing medicines are used for perfusion, and the whole reperfusion process is continued.
6.3.2 Experimental methods
After the abdominal cavity of a rat is anesthetized, the chest is opened quickly, the heart is lifted lightly, tissues around the superior vena cava, the inferior vena cava, the pulmonary artery, the aorta and the heart are cut off, the heart and a section of aorta are taken out quickly, the length of the root of the aorta is kept about 0.5-1cm, and a cardiac cannula is prepared. Immediately transferring to 4 deg.C oxygen-containing K-H solution (K-H solution component (g/L): NaCl 6.9g, KCl 0.35g, CaCl20.28g of anhydrous MgSO4 0.14g、KH2PO4 0.16g、NaHCO32.09g and Glu 2.08g, pH 7.4) and gently squeezing the heart to drain the residual blood in the ventricle, cleaning the residual blood in the heart, hanging on a Langendorff perfusion device, and connecting the ascending aorta of the heart to a perfusion cannula and ligating and fixing the ascending aorta of the heart by cotton threads. Immediately perfusing with oxygen-containing K-H solution at constant temperature (37 + -0.5) ° C; the pressure is 70mm Hg and the flow rate (11.5 +/-0.5) ml/min. A small opening was cut in the left atrial sidewall and a small latex sac was inserted into the left ventricle through the atrioventricular orifice. The latex water bag and the connected conduit are filled with ultrapure water, and the other end of the conduit is connected with the pressure transducer through the tee joint, so that large and small bubbles inside the conduit are thoroughly removed. The water quantity of the water sac in the ventricle is adjusted by finely adjusting the water injector so as to keep the final diastolic pressure of the ventricle within the range of 4-6 mmHg. The left room pressure was stabilized for 30min before testing. Recording the coronary flow of the heart every minute with a graduated cylinder; the pressure transducer signal is input into the multichannel recording system through the bridge amplifier for real-time signal acquisition and processing.
Each group recorded the coronary flow (CBF), left ventricular diastolic pressure (LVEDP), and maximum rate of rise of left ventricular pressure (+ dp/dt) every 10min from the 10 th min before discontinuation and after reperfusionmax) And maximum rate of decrease of left indoor pressure-dp/dtmax)，n＝8。
6.3.3 results of the experiment
TABLE 3 Effect of Salvia miltiorrhiza compositions on hemodynamics of rat isolated heart reperfusion for 60min
Figure BDA0001641056890000141
Note: the representations in the same column have significant differences.
As shown in Table 3, CBF, LVEDP, + dp/dt were observed in the model group at 60min after ischemia-reperfusion compared with the control groupmax、 -dp/dtmaxAll have significant differences, which indicates that the model of the reperfusion injury model is successfully molded. Compared with a model group, all indexes of each administration group are obviously improved, wherein the effect of reducing the rat isolated heart ischemia reperfusion injury by the salvia miltiorrhiza composition provided by the example 6 is optimal, and the decrease of coronary flow, the rise of left ventricular diastolic pressure, the decrease of the maximum rising rate of left ventricular pressure and the decrease of the maximum falling rate of left ventricular pressure caused by ischemia reperfusion can be inhibited. The salvia miltiorrhiza composition provided by the invention is prompted to obviously improve coronary blood flow, improve isolated cardiac aorta diastolic function and systolic function of damaged cardiac muscle, and protect cardiac ischemia reperfusion injury. The three components of the salvia miltiorrhiza composition provided by the invention are absent, and the optimal treatment effect is achieved through reasonable proportioning.
EXAMPLE 7 clinical therapeutic Effect of Salvia miltiorrhiza compositions
7.1 design of the test:
by adopting a multi-center, random, double-blind and double-simulation test method, male and female patients with the age of 45-70 years are selected, cases which accord with the diagnosis and differentiation standard of coronary heart disease and angina pectoris are taken as observation objects, and the clinical efficacy of the salvia miltiorrhiza composition for treating the coronary heart disease and angina pectoris is evaluated.
Treatment and administration: subjects received 4 weeks of drug treatment after being randomly assigned to either the test or control groups. The treatment groups respectively take the salvia miltiorrhiza composition granules of the embodiments 1 and 6 orally, 3 times a day, 1 bag each time, and the granules are taken before meals; control groups 1-4 were orally administered with the Saviae Miltiorrhizae radix composition granules of comparative examples 1-4 respectively 3 times daily, 1 packet each time, before meal. And the positive control group takes the compound red sage root dripping pills sold on the market 3 times a day, 10 pills each time and before meals.
7.2 evaluation index:
the effect is shown: the principal symptoms such as angina pectoris disappear or reach the significant standard, the electrocardiogram returns to the normal electrocardiogram or reaches the approximately normal electrocardiogram (namely the electrocardiogram in the normal range);
the method has the following advantages: the major symptoms such as angina pectoris and the like are relieved or reach the effective standard, and the electrocardiogram improvement reaches the effective standard;
and (4) invalidation: the principal symptoms of angina pectoris, etc. are not improved, and the electrocardiogram is basically the same as before treatment.
When the effect of the principal symptoms such as angina pectoris is inconsistent with the effect of electrocardiogram, the result of low effect should be used as the comprehensive effect.
7.3 Combined therapeutic effects
TABLE 4 comparison of the comprehensive therapeutic effects of the Salvia miltiorrhiza compositions
Figure BDA0001641056890000151
Figure BDA0001641056890000161
Note: the representations in the same column have significant differences.
As can be seen from the above table, the salvia miltiorrhiza composition provided by the invention can effectively improve the symptoms of angina pectoris of patients with coronary heart disease, and is obviously superior to comparative examples 1-4 and commercially available compound salvia miltiorrhiza dropping pills.
7.4 Effect of Salvia miltiorrhiza composition on nitroglycerin use
TABLE 5 Effect of Salvia miltiorrhiza compositions on nitroglycerin use
Figure BDA0001641056890000162
Note: the rate of decrease is (number of persons who did not require nitroglycerin after treatment-number of persons who did not require nitroglycerin before treatment)/number of cases who required nitroglycerin before treatment × 100%
The representations in the same column have significant differences.
As can be seen from the table above, the use of nitroglycerin by patients and the toxic and side effects of the medicine can be reduced by using the salvia miltiorrhiza composition provided by the invention.
7.5 evaluation of safety
Before and after treatment, general vital signs (body temperature, respiration, pulse, blood pressure), blood, urine, feces convention (+ occult blood) and liver (ALT, AST), renal function (BUN, Cr) and electrocardiogram examination are carried out, and adverse reactions, especially digestive tract reaction, which may occur in the whole medication process are observed. The number of people with abnormalities after 4 weeks was recorded and the results are shown in Table 6.
TABLE 6 influence of Salvia miltiorrhiza Bunge composition on safety evaluation index of angina pectoris patients
Figure BDA0001641056890000163
Figure BDA0001641056890000171
As can be seen from Table 6, the Salvia miltiorrhiza Bunge composition provided by the invention has no adverse effect on patients with coronary heart disease and angina pectoris, and has no gastrointestinal adverse reaction.
The above detailed description is specific to one possible embodiment of the present invention, and the embodiment is not intended to limit the scope of the present invention, and all equivalent implementations or modifications without departing from the scope of the present invention should be included in the technical scope of the present invention.

Claims (9)

1. The salvia miltiorrhiza composition for treating coronary heart disease is characterized by comprising the following traditional Chinese medicine components in parts by weight: 800 portions of salvia miltiorrhiza bunge, 300 portions of scandent schefflera stem and leaf and 5 to 20 portions of grassleaf sweelflag rhizome;
the preparation method of the composition preparation comprises the following steps:
(1) extracting the salvia miltiorrhiza: drying and pulverizing Saviae Miltiorrhizae radix, soaking in ethanol, extracting with a flash extractor, concentrating, passing the concentrated solution through HPD100 macroporous resin column, sequentially washing with water and ethanol, collecting eluate, concentrating, adding hydroxypropyl-beta-cyclodextrin, grinding, and drying to obtain Saviae Miltiorrhizae radix extract clathrate;
(2) extraction of scandent schefflera root: drying and crushing scandent schefflera stem and leaf, performing ultrasonic assisted extraction by using ethanol, performing reflux extraction by using a Soxhlet extractor, concentrating and drying filtrate to obtain a scandent schefflera stem and leaf extract, diluting the extract by adding water, sequentially extracting the diluted extract by using petroleum ether, dichloromethane, ethyl acetate and n-butyl alcohol, concentrating the n-butyl alcohol extract, performing gradient elution by using dichloromethane-methanol 100: 0-0: 100, respectively collecting fractions, combining and concentrating similar components by TLC identification to obtain a scandent schefflera stem and leaf extract;
(3) extracting the grassleaf sweelflag rhizome: pulverizing rhizoma Acori Graminei, and supercritical CO2Extracting to obtain rhizoma Acori Graminei volatile oil liquid, adding hydroxypropyl-beta-cyclodextrin to perform inclusion to obtain rhizoma Acori Graminei volatile oil inclusion compound;
(4) pulverizing Saviae Miltiorrhizae radix extract clathrate, radix Schefflerae Arboricolae fraction extract and rhizoma Acori Graminei volatile oil clathrate, mixing, adding appropriate adjuvant, and making into desired dosage form by conventional method.
2. The salvia miltiorrhiza composition for treating coronary heart disease according to claim 1, wherein the composition is prepared from the following traditional Chinese medicine components in parts by weight: 600-700 parts of salvia miltiorrhiza bunge, 200 parts of scandent schefflera root and 10-15 parts of grassleaf sweelflag rhizome.
3. The salvia miltiorrhiza composition for treating coronary heart disease according to claim 2, wherein the composition is prepared from the following traditional Chinese medicine components in parts by weight: 650 parts of salvia miltiorrhiza, 180 parts of scandent schefflera root and 12 parts of grassleaf sweelflag rhizome.
4. The salvia miltiorrhiza composition for treating coronary heart disease is characterized by comprising the following components in parts by weight: 800 portions of salvia miltiorrhiza bunge, 300 portions of scandent schefflera root, 5 to 20 portions of grassleaf sweelflag rhizome and 50 portions of cortex albiziae; the preparation method of the composition preparation comprises the following steps:
(1) extracting the salvia miltiorrhiza: drying and pulverizing Saviae Miltiorrhizae radix, soaking in ethanol, extracting with a flash extractor, concentrating, passing the concentrated solution through HPD100 macroporous resin column, sequentially washing with water and ethanol, collecting eluate, concentrating, adding hydroxypropyl-beta-cyclodextrin, grinding, and drying to obtain Saviae Miltiorrhizae radix extract clathrate;
(2) extraction of scandent schefflera root: drying and crushing scandent schefflera stem and leaf, performing ultrasonic assisted extraction by using ethanol, performing reflux extraction by using a Soxhlet extractor, concentrating and drying filtrate to obtain a scandent schefflera stem and leaf extract, diluting the extract by adding water, sequentially extracting the diluted extract by using petroleum ether, dichloromethane, ethyl acetate and n-butyl alcohol, concentrating the n-butyl alcohol extract, performing gradient elution by using dichloromethane-methanol 100: 0-0: 100, respectively collecting fractions, combining and concentrating similar components by TLC identification to obtain a scandent schefflera stem and leaf extract;
(3) extracting the grassleaf sweelflag rhizome: pulverizing rhizoma Acori Graminei, and supercritical CO2Extracting to obtain rhizoma Acori Graminei volatile oil liquid, adding hydroxypropyl-beta-cyclodextrin to perform inclusion to obtain rhizoma Acori Graminei volatile oil inclusion compound;
(4) extracting cortex albiziae: defatting cortex Albizziae with petroleum ether, reflux-extracting with ethanol, concentrating the filtrate, drying to obtain cortex Albizziae extract, dissolving the extract, sequentially extracting with petroleum ether, dichloromethane, ethyl acetate and n-butanol, concentrating the n-butanol extractive solution, eluting with alumina column, eluting with ethanol, concentrating the eluate, and drying to obtain cortex Albizziae extract;
(5) pulverizing Saviae Miltiorrhizae radix extract clathrate, radix Schefflerae Arboricolae fraction extract, rhizoma Acori Graminei volatile oil clathrate and cortex Albizziae extract, mixing, adding appropriate adjuvant, and making into desired dosage form by conventional method.
5. A Chinese medicinal preparation containing a Saviae Miltiorrhizae radix composition, which comprises the composition of any one of claims 1-4 and pharmaceutically acceptable adjuvants.
6. The traditional Chinese medicine preparation as claimed in claim 5, wherein the preparation comprises tanshinone 0.10-0.50 wt%, salvianolic acid B3-5 wt%, total saponin 0.20-0.40 wt%, and volatile oil 0.02-0.05 wt%.
7. The Chinese medicinal preparation of claim 6, wherein the Chinese medicinal preparation is in the form of granule, tablet, capsule or pill.
8. A method of preparing a formulation of a composition as claimed in any one of claims 5 to 7, comprising the steps of:
(1) extracting the salvia miltiorrhiza: drying and pulverizing Saviae Miltiorrhizae radix, soaking in ethanol, extracting with a flash extractor, concentrating, passing the concentrated solution through HPD100 macroporous resin column, sequentially washing with water and ethanol, collecting eluate, concentrating, adding hydroxypropyl-beta-cyclodextrin, grinding, and drying to obtain Saviae Miltiorrhizae radix extract clathrate;
(2) extraction of scandent schefflera root: drying and crushing scandent schefflera stem and leaf, performing ultrasonic assisted extraction by using ethanol, performing reflux extraction by using a Soxhlet extractor, concentrating and drying filtrate to obtain a scandent schefflera stem and leaf extract, diluting the extract by adding water, sequentially extracting the diluted extract by using petroleum ether, dichloromethane, ethyl acetate and n-butyl alcohol, concentrating the n-butyl alcohol extract, performing gradient elution by using dichloromethane-methanol 100: 0-0: 100, respectively collecting fractions, combining and concentrating similar components by TLC identification to obtain a scandent schefflera stem and leaf extract;
(3) extracting the grassleaf sweelflag rhizome: pulverizing rhizoma Acori Graminei, and supercritical CO2Extracting to obtain rhizoma Acori Graminei volatile oil liquid, adding hydroxypropyl-beta-cyclodextrin to perform inclusion to obtain rhizoma Acori Graminei volatile oil inclusion compound;
(4) extracting cortex albiziae: defatting cortex Albizziae with petroleum ether, reflux-extracting with ethanol, concentrating the filtrate, drying to obtain cortex Albizziae extract, dissolving the extract, sequentially extracting with petroleum ether, dichloromethane, ethyl acetate and n-butanol, concentrating the n-butanol extractive solution, eluting with alumina column, eluting with ethanol, concentrating the eluate, and drying to obtain cortex Albizziae extract;
(5) pulverizing Saviae Miltiorrhizae radix extract clathrate, radix Schefflerae Arboricolae fraction extract and rhizoma Acori Graminei volatile oil clathrate, mixing, adding appropriate adjuvant, and preparing according to conventional method of Chinese medicinal preparation; or pulverizing Saviae Miltiorrhizae radix extract clathrate, radix Schefflerae Arboricolae fraction extract, rhizoma Acori Graminei volatile oil clathrate and cortex Albizziae extract, mixing, adding appropriate adjuvant, and making into desired dosage form by conventional method.
9. Use of a composition according to any one of claims 1 to 4 for the manufacture of a medicament for the treatment of coronary heart disease.
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