CN102228596A - Pharmaceutical composition and preparation and applications thereof in treating coronary heart disease and angina pectoris - Google Patents
Pharmaceutical composition and preparation and applications thereof in treating coronary heart disease and angina pectoris Download PDFInfo
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Abstract
The invention discloses a pharmaceutical composition and preparation and applications thereof in treating coronary heart disease and angina pectoris. The pharmaceutical composition comprises the following raw medicines in parts by weight: 15-21 parts of kudzu root, 15-21 parts of yam and 15-21 parts of ginkgo leaf. The pharmaceutical composition is prepared by the following steps of: pretreating the raw medicines, crushing, extracting by reflux with 50-70% ethanol, filtering, combining the ethanol extraction solutions, concentrating at 55-65 DEG C until the relative density is 1.15-1.17, cooling and drying to obtain the pharmaceutical composition in a dry powder state. The pharmaceutical composition and pharmaceutically acceptable auxiliary materials can be prepared into granules, capsules, pills, dripping pills, powder, soluble granules and tablets. The pharmaceutical composition preparation in any dosage form is applied to treatment of coronary heart disease and angina pectoris. The pharmaceutical composition disclosed by the invention has reasonable compatibility and high utilization rate of active ingredients, has an obvious effect on acute myocardial ischemia, has an obvious inhibiting effect on thrombosis of the arteriovenous shut, enhances the hypoxia tolerance ability of a body, promotes the restoration of cardiac functions, is safe, and has low toxicity. Proven by clinical tests, the pharmaceutical composition has obvious therapeutic effects on coronary heart disease and angina pectoris.
Description
Technical field
The invention belongs to Chinese medicine preparation and preparing technical field thereof, be specifically related to a kind of pharmaceutical composition and preparation thereof and in treatment coronary heart disease, angina pectoris, use with it.
Background technology
Coronary heart disease, angina pectoris, deficiency myocardial blood supply are the common clinical diseases of middle-aged and elderly people, are with sclerosis coronarius, the narrow heart disease that causes poor blood circulation, cardiac blood supply deficiency and then cause myocardial ischemia-anoxemia to cause of occurring.Along with people living condition's continuous improvement, the development of health service, people's average life rises appreciably.But constitute tripartite surface analysis demonstration from sick kind of prevalence, sickness rate and inpatient: the quantity of cardiovascular disease increases absolute and relatively, and has become the principal disease that causes the human mortality.
The tradition traditional Chinese medical science there is no the name of disease of " coronary heart disease, angina pectoris ", and is from record and the description of traditional Chinese medical science ancient books to diseases such as " cardiopalmus ", " angina pectoris ", " thoracic obstruction ", very similar to modern coronary heart disease, angina pectoris, deficiency myocardial blood supply.Therefore, it is generally acknowledged that angina pectoris belongs to the category of " thoracic obstruction ", " pained " in the traditional Chinese medical science.The traditional Chinese medical science thinks, this disease is many because of person in middle and old age's function degradation, and Sorghum vulgare Pers. savoury impairing the spleen and stomach, or the stagnation of QI due to the internal injury caused by excess of seven emotions, blood stasis, expectorant give birth in turbid, makes venation obstructed, the heart are become homeless and supported and fall ill.Since stop in the blood stasis, stagnation of heart-blood, not general rule ambition twinge, and fix and do not move; Stasis of blood blood pertaining to YIN, also belong to the moon night, and People of the same tastes and habits like to be together then goes into Night Watch very; Stagnation of heart-blood, heart arteries and veins lose supports then palpitation and uneasiness, insomnia unhappiness; Darkish complexion is not magnificent, dimly red tongue or ecchymosis is arranged, and is resembling of stagnation of heart-blood.Therefore, though cause of coronary heart disease mechanism and the deficiency of vital energy, yang deficiency, expectorant is turbid, cold coagulation, the stagnation of QI are relevant, but but because of factors such as cold coagulation, accumulation of heat, stagnation of phlegm, the stagnation of QI, deficiency of vital energy hyperamization arteries and veins stasis all, causing blood stasis not stagnate looses, heart arteries and veins is obstructed, so pain is as stinging as twisting and pain in fixed position, so the relation of coronary heart disease, angina pectoris and blood stasis is more direct.To sum up, coronary heart disease, anginal main diseases position be at the heart, and pathogenesis mainly is due to the blood stasis stagnating heart meridian, therefore, and should be in treatment based on blood circulation promoting and blood stasis dispelling.
Though it is various in style to be used for the treatment of this sick Chinese patent medicine at present, but nothing more than focusing on heart Yuan capsule, heart nourishing sheet, the reinforcing the heart gas of setting upright mind calming and growing the heart-yin oral liquid, Rhizoma Zingiberis Recens liquid etc., or focus on storax pill for treating coronary heart disease, Heart pill of Musk, heart treasured of aromatic herbs activating YANG etc., or focus on the FUFANG DANSHEN PIAN of blood circulation promoting and blood stasis dispelling and drop pill, SUXIAO JIUXIN WAN, XINKESHU PIAN, BUCHANG NAOXINTONG, SHANHAI PILL, golden damp coronary disease glue is assisted etc.Except that above three class medicines, also have some from Chinese herbal medicine, to extract the preparation of active ingredient, as Semen Ginkgo Tian Bao, Flavonihippophae, DIAOXINXUE KANG etc.Above medicine all only is confined to set upright single indications such as mind calming, aromatic herbs activating YANG or blood circulation promoting and blood stasis dispelling, whole symptom that can't all-out confrontation coronary heart disease.
Summary of the invention
The present invention is in order to overcome the prior art deficiency, and first purpose of the present invention is to provide a kind of pharmaceutical composition; Second purpose is to provide this preparation of pharmaceutical compositions method; The 3rd purpose is to provide a kind of drug combination preparation of being made by pharmaceutical composition; The 4th purpose is the application of this drug combination preparation in treatment coronary heart disease, angina pectoris.
First purpose of the present invention is achieved in that the former medicated bag of described pharmaceutical composition draws together 15 ~ 21 parts of (parts by weight) Radix Puerariaes, 15 ~ 21 parts of Rhizoma Dioscoreae Nipponicae, 15 ~ 21 parts of Folium Ginkgos.
As optimal technical scheme, the former medicine of described pharmaceutical composition also comprises 8 ~ 14 parts of (parts by weight) Radix Ilicis Pubescentiss.
The former medicine of described pharmaceutical composition also comprises 8 ~ 14 parts of (parts by weight) Radix Ilicis Pubescentiss, 8 ~ 14 parts of Herba Viscis.
The former medicine of described pharmaceutical composition also comprises 8 ~ 14 parts of (parts by weight) Radix Ilicis Pubescentiss, 8 ~ 14 parts of Herba Viscis, 8 ~ 14 parts of Rhizoma Chuanxiongs.
The former medicine of described pharmaceutical composition also comprises 8 ~ 14 parts of (parts by weight) Radix Ilicis Pubescentiss, Herba Visci 8-14 part, 8 ~ 14 parts of Rhizoma Chuanxiongs, 8 ~ 14 parts of Rhizoma Corydalis.
Radix Puerariae, sweet in the mouth, suffering, cool in nature are returned the taste warp, have the tool expelling pathogenic factors from muscles for reducing heat, promoting the production of body fluid to quench thirst, relieving spasm to stop pain, the yang invigorating effect of invigorating blood circulation, the Radix Puerariae nature and flavor are sweet hot cool, return lung taste warp, and the energy sending up the lucid YANG has blood circulation-promoting functions again.Recent studies finds that Radix Puerariae has coronary artery dilator, reduces myocardial oxygen consumption, increases brain and coronary blood flow, improves effects such as heart and brain blood circulation, therefore, from the modern Chinese medicine theory, has tangible function of promoting blood circulation to disperse blood clots.Pharmacological evaluation finds that also Radix Puerariae total flavones has the effect of blood flow increasing to cerebral circulation and arteria coronaria circulation, puerarin is allevating angina pectoris obviously, daiazi in the Radix Puerariae and big legumin have the anti-acetylcholine effect, can prevent the experimental arrhythmia of rat, big legumin is the main effective ingredient of spasmolytic, and the acute myocardial ischemia that pituitrin is caused has protective effect; Therefore, usually be used for clinically coronary heart disease, angina pectoris, cerebral thrombosis, headache, dizziness, neck pain etc. treatment of diseases.As puerarin injection, yufeng ningxin tablets, yufeng ningxin pian (single Radix Puerariae) etc. all is the medicine commonly used that is used for coronary heart disease, so be monarch drug with the Radix Puerariae.
Rhizoma Dioscoreae Nipponicae, property is flat, sweet in the mouth, hardship is returned liver, lung meridian, has promoting blood circulation to remove obstruction in the collateral, muscles and tendons relaxing to alleviate pain, the merit of expelling wind and removing dampness.The Rhizoma Dioscoreae Nipponicae dispelling wind and removing obstruction in the collateral is apt to away the meridians blood vessels, and its property is walked and do not kept sharp blood vessels, blood stasis dispelling blood, logical muscles and bones, interior then logical blood vessels all over the body, then logical outward muscles and bones all over the body, therefore, both can be used for treating the obstruction of qi in the chest and cardialgia due to the stagnation of blood stasis, blockage of the cardiac vessels can be used for the obstructed rheumatalgia of muscle arteries and veins again, the muscles and bones numbness.Modern clinical practice is found, the dioscin that Rhizoma Dioscoreae Nipponicae contains multiple steroid saponin compositions such as (dioscin), it also is the Main Ingredients and Appearance of DIAOXINXUE KANG, can increase cardiac contractile force, improve blood supply of cardiac muscle, coronary blood flow increasing, reduce plasma cholesterol, alleviate the deposition of lipoids at aorta vessel and important organ, the effect of tool arteriosclerosis, the coronary heart disease that stagnation of blood stasis heart arteries and veins is caused has therapeutical effect preferably, be equal to usefulness with Radix Puerariae, not only for coronary heart disease, and can be used for because cerebral infarction diseases such as hemiplegia.Folium Ginkgo, nature and flavor are sweet, bitter, puckery, and flat, GUIXIN, lung meridian have blood circulation promoting and blood stasis dispelling, the merit of removing obstruction in the collateral to relieve pain.Modern pharmacology confirms that also the flavone and the lactone that contain in the Folium Ginkgo have coronary artery dilator, and coronary flow is increased, and energy antiplatelet aggregation and reduction plasma viscosity, thereby improves the circulatory function of cardiovascular and cerebrovascular vessel.It all is blood circulation promoting and blood stasis dispelling, TONGMAI SHULUO basically that the function of the multiple gingko leaf preparation of clinical practice now cures mainly, be used for coronary blood supply insufficiency, angina pectoris, myocardial infarction, cerebral thrombosis, cerebral vasospasm due to arteriosclerosis and the hypertension etc., and the bad caused disease of arteries blood supply.Therefore in pharmaceutical composition of the present invention with Rhizoma Dioscoreae Nipponicae and Folium Ginkgo as ministerial drug.
Radix Ilicis Pubescentis, bitter in the mouth, puckery, cold in nature, GUIXIN, liver, lung meridian have blood circulation and channel invigorating, reducing swelling and alleviating pain, antipyretic and antidote functions is the common drug of blood circulation promoting and blood stasis dispelling.Normal and the Rhizoma Chuanxiong of Radix Ilicis Pubescentis share, and both can strengthen function of promoting blood circulation to disperse blood clots, can pin down the hot property of Rhizoma Chuanxiong again, is used for the treatment of diseases such as blood stasis chest pain and hemiplegia.Pharmacological research discovery Radix Ilicis Pubescentis and flavonoid glycosides energy blood vessel dilating thereof, microcirculation improvement, be used for coronary heart disease, angina pectoris, make coronary flow significantly increase the myocardial ischemia that pituitrin is caused certain antagonism is arranged, share with monarch drug Radix Puerariae, ministerial drug Folium Ginkgo etc., can play synergistic therapeutical effect.Rhizoma Chuanxiong, acrid in the mouth, warm in nature.GUIXIN, liver, gallbladder meridian have blood-activating and qi-promoting, the wind-expelling pain-stopping effect.Rhizoma Chuanxiong is good at row and is scattered strongly fragrantly, and merit is arrogated to oneself current blood vessels, and its gas fragrance is walked to scurry, and has again can rise the effect that can fall, can invigorate blood circulation, again can circulation of qi promoting, and especially be longer than and invigorate blood circulation, so be called as " the gas medicine in the blood ".Rhizoma Corydalis, acrid in the mouth, hardship, warm in nature.Return liver, spleen channel, have and invigorate blood circulation, circulation of qi promoting, analgesic effect.Rhizoma Corydalis is a blood-activating and qi-promoting analgesic key medicine, and its merit can be gone into blood system with blood circulation promoting and blood stasis dispelling, can go into edema caused by disorder of QI again and loose stagnate with circulation of qi promoting, and is distinguished with pain relieving effectiveness especially, which kind of pain no matter, but all compatibility is used, control caused by energy stagnation and blood stasis obstruction of qi in the chest and cardialgia, normal and Rhizoma Chuanxiong is equal to usefulness.Herba Visci, bitter in the mouth, property is flat, and GUIXIN, liver, kidney channel have wind-damp dispelling, invigorating the liver and kidney, bone and muscle strengthening, the effect of the meridian dredging, it is empty with losing of invigorating the liver and kidney to use Herba Visci, congenital abundance, the cloudy blood of the heart is supplemented nutrition, and does not have the worry of sufferer certainly.Modern study finds that Herba Visci has coronary artery dilator, and coronary blood flow increasing improves the myocardial ischemia effect.Coronary heart disease is had the obvious treatment effect, also usually be used for the clinical treatment of coronary heart disease in recent years.Therefore, can cooperate with Radix Ilicis Pubescentis, Rhizoma Chuanxiong, Herba Visci, Rhizoma Corydalis adjuvant drug as we.
The all medicines in comprehensive full side, this product has blood circulation promoting and blood stasis dispelling, and it is active to promote blood circulation, regulating QI to relieve pain, the Shujin that dispels the wind, the merit of promoting blood circulation, all medicines are made a concerted effort, and have played blood circulation promoting and blood stasis dispelling, and it is active to promote blood circulation, and the effect of the meridian and relieving pain that relaxes is just in time with the pathogenesis stagnation of blood stasis passages through which vital energy circulates basically identical of this product.
The present invention's second purpose is achieved in that described preparation method may further comprise the steps:
A, former medicine is purified respectively and pulverization process;
B, the former medicine of Chinese medicine after will handling take by weighing by formula proportion, and fully mixing adds 2 ~ 5 times of amounts (weight ratio), 50 ~ 70% ethanol, reflux, extract, 2 times, and each 2 hours, the filtrate merging with 2 extractions obtained alcohol extract;
C, to B step gained alcohol extract decompression recycling ethanol, and under 55 ~ 65 ℃, be evaporated to relative density 1.15 ~ 1.17, after cooling, the drying dry powder attitude pharmaceutical composition.
55 ~ 65% the ethanol that can preferably add 3 ~ 4 times of amounts in the described B step; The concentrating under reduced pressure temperature is 60 ℃ in the described C step.
The present invention's the 3rd purpose is achieved in that described pharmaceutical preparation is for by pharmaceutical composition and granule, capsule, the honey pill agent made of acceptable medical accessory pharmaceutically, drop pill, powder, electuary and tablet.
The present invention's the 4th purpose is achieved in that the application of any one forms of pharmaceutical compositions preparation in treatment coronary heart disease, angina pectoris.
Pharmaceutical composition of the present invention and preparation compatibility thereof are reasonable, and disease is taken into account comprehensively, and blood circulation promoting and blood stasis dispelling is gathered in the medication combined use of multi-flavor altogether, and it is active to promote blood circulation, regulating QI to relieve pain, the Shujin that dispels the wind, the merit of promoting blood circulation.And preparation technology is easy, medicine effective ingredient-use efficient height.Animal experiment shows that the present invention has tangible effect to acute myocardial ischemia, and to the significant inhibitory effect that is formed with of artery and vein bypass thrombosis, the hypoxia-bearing capability of enhancing body promotes cardiac function to recover, and safety, toxicity are little.The clinical trial proof has the effect of blood circulation promoting and blood stasis dispelling, removing obstruction in the collateral to relieve pain, and to diseases such as coronary heart disease, angina pectoriss, especially the coronary heart disease of blood stasis pattern of syndrome, angina pectoris have the obvious treatment effect.
The specific embodiment
Below enforcement of the present invention is further described, but never in any form the present invention is limited, any conversion based on training centre of the present invention is done all falls into protection scope of the present invention.
The former medicated bag of pharmaceutical composition of the present invention is drawn together 15 ~ 21 parts of (parts by weight) Radix Puerariaes, 15 ~ 21 parts of Rhizoma Dioscoreae Nipponicae, 15 ~ 21 parts of Folium Ginkgos.
As preferred implementation:
The former medicine of described pharmaceutical composition also comprises 8 ~ 14 parts of (parts by weight) Radix Ilicis Pubescentiss.
The former medicine of described pharmaceutical composition also comprises 8 ~ 14 parts of (parts by weight) Radix Ilicis Pubescentiss, 8 ~ 14 parts of Herba Viscis.
The former medicine of described pharmaceutical composition also comprises 8 ~ 14 parts of (parts by weight) Radix Ilicis Pubescentiss, 8 ~ 14 parts of Herba Viscis, 8 ~ 14 parts of Rhizoma Chuanxiongs.
The former medicine of described pharmaceutical composition also comprises 8 ~ 14 parts of (parts by weight) Radix Ilicis Pubescentiss, Herba Visci 8-14 part, 8 ~ 14 parts of Rhizoma Chuanxiongs, 8 ~ 14 parts of Rhizoma Corydalis.
Above-mentioned any one preparation of drug combination method may further comprise the steps:
A, former medicine is purified respectively and pulverization process;
B, the former medicine of Chinese medicine after will handling take by weighing by formula proportion, and fully mixing adds 2 ~ 5 times of amounts (weight ratio), 50 ~ 70% ethanol, reflux, extract, 2 times, and each 2 hours, the filtrate merging with 2 extractions obtained alcohol extract;
C, to B step gained alcohol extract decompression recycling ethanol, and under 55 ℃ ~ 65 ℃, be evaporated to relative density 1.15 ~ 1.17, after cooling, the drying dry powder attitude pharmaceutical composition.
55 ~ 65% the ethanol that adds 3 ~ 4 times of amounts in the described B step; The concentrating under reduced pressure temperature is 60 ℃ in the described C step.
Described pharmaceutical preparation is for by pharmaceutical composition and pharmaceutically oral, injection of granule, capsule, honey pill agent, drop pill, powder, electuary, tablet, freeze-dried powder and the injection etc. made of acceptable medical accessory and percutaneous drug administration preparation.
Described medical accessory includes but not limited to excipient, correctives, disintegrating agent, antiseptic, binding agent, absorbent, wetting agent, coating materials class.Above-mentioned medical accessory includes but not limited to Different concentrations of alcohol, sucrose, dextrin, starch, amylum pregelatinisatum, carboxymethyl starch, microcrystalline Cellulose, methylcellulose, hydroxy methocel, hydroxypropyl emthylcellulose, hydroxypropyl cellulose, Polyethylene Glycol, acrylic resin, polyvinylpyrrolidone, micropowder silica gel, gas-producing disintegrant, Aspartane, Mel, lactose, stevioside, protein sugar, xylitol, high fructose, cyclamate and other (inorganic calciums, aluminum, magnesium salt) etc.
Application in application, the especially angina pectoris of blood stasis pattern of syndrome of described any one forms of pharmaceutical compositions preparation in treatment coronary heart disease, angina pectoris.
Embodiment 1
15 parts of former medicine (parts by weight) Radix Puerariaes, 21 parts of Rhizoma Dioscoreae Nipponicae, Folium Ginkgo are carried out respectively for 21 parts being ground into coarse powder after the pretreatment, medicated powder is pressed the formula proportion mixing, add 3 times of amounts (weight ratio), 50% ethanol, reflux, extract, 2 times, each 2 hours, to merge behind 2 extracting liquid filterings, alcohol extract is evaporated to relative density 1.15 ~ 1.17 under 55 ℃, get dry powder attitude pharmaceutical composition after cooling, the drying.
Embodiment 2
21 parts of former medicine (parts by weight) Radix Puerariaes, 15 parts of Rhizoma Dioscoreae Nipponicae, Folium Ginkgo are carried out respectively for 15 parts being ground into coarse powder after the pretreatment, medicated powder is pressed the formula proportion mixing, add 4 times of amounts (weight ratio), 70% ethanol, reflux, extract, 2 times, each 2 hours, to merge behind 2 extracting liquid filterings, alcohol extract is evaporated to relative density 1.15 ~ 1.17 under 65 ℃, get dry powder attitude pharmaceutical composition after cooling, the drying.
Embodiment 3
21 parts of former medicine (parts by weight) Radix Puerariaes, 15 parts of Rhizoma Dioscoreae Nipponicae, 15 parts of Folium Ginkgos, Radix Ilicis Pubescentis are carried out respectively for 14 parts being ground into coarse powder after the pretreatment, medicated powder is pressed the formula proportion mixing, add 3 times of amounts (weight ratio), 70% ethanol, reflux, extract, 2 times, each 2 hours, to merge behind 2 extracting liquid filterings, alcohol extract is evaporated to relative density 1.15 ~ 1.17 under 65 ℃, get dry powder attitude pharmaceutical composition after cooling, the drying.
Embodiment 4
19 parts of former medicine (parts by weight) Radix Puerariaes, 19 parts of Rhizoma Dioscoreae Nipponicae, 19 parts of Folium Ginkgos, 10 parts of Radix Ilicis Pubescentiss, Herba Visci are carried out respectively for 8 parts being ground into coarse powder after the pretreatment, medicated powder is pressed the formula proportion mixing, add 2 times of amounts (weight ratio), 65% ethanol, reflux, extract, 2 times, each 2 hours, to merge behind 2 extracting liquid filterings, alcohol extract is evaporated to relative density 1.15 ~ 1.17 under 60 ℃, get dry powder attitude pharmaceutical composition after cooling, the drying.
Embodiment 5
17 parts of former medicine (parts by weight) Radix Puerariaes, 21 parts of Rhizoma Dioscoreae Nipponicae, 21 parts of Folium Ginkgos, 10 parts of Radix Ilicis Pubescentiss, 11 parts of Herba Viscis, Rhizoma Chuanxiong are carried out respectively for 8 parts being ground into coarse powder after the pretreatment, medicated powder is pressed the formula proportion mixing, add 5 times of amounts (weight ratio), 60% ethanol, reflux, extract, 2 times, each 2 hours, to merge behind 2 extracting liquid filterings, alcohol extract is evaporated to relative density 1.15 ~ 1.17 under 55 ℃, get dry powder attitude pharmaceutical composition after cooling, the drying.
Embodiment 6
20 parts of former medicine (parts by weight) Radix Puerariaes, 17 parts of Rhizoma Dioscoreae Nipponicae, 18 parts of Folium Ginkgos, 12 parts of Radix Ilicis Pubescentiss, 14 parts of Herba Viscis, 13 parts of Rhizoma Chuanxiongs, Rhizoma Corydalis are carried out respectively for 8 parts being ground into coarse powder after the pretreatment, medicated powder is pressed the formula proportion mixing, add 4 times of amounts (weight ratio), 50% ethanol, reflux, extract, 2 times, each 2 hours, to merge behind 2 extracting liquid filterings, alcohol extract is evaporated to relative density 1.15 ~ 1.17 under 55 ℃, get dry powder attitude pharmaceutical composition after cooling, the drying.
Embodiment 7
21 parts of former medicine (parts by weight) Radix Puerariaes, 21 parts of Rhizoma Dioscoreae Nipponicae, 20 parts of Folium Ginkgos, 10 parts of Radix Ilicis Pubescentiss, 14 parts of Herba Viscis, 14 parts of Rhizoma Chuanxiongs, Rhizoma Corydalis are carried out respectively for 14 parts being ground into coarse powder after the pretreatment, medicated powder is pressed the formula proportion mixing, add 5 times of amounts (weight ratio), 60% ethanol, reflux, extract, 2 times, each 2 hours, to merge behind 2 extracting liquid filterings, alcohol extract is evaporated to relative density 1.15 ~ 1.17 under 65 ℃, get dry powder attitude pharmaceutical composition after cooling, the drying.
Embodiment 8
15 parts of former medicine (parts by weight) Radix Puerariaes, 15 parts of Rhizoma Dioscoreae Nipponicae, 21 parts of Folium Ginkgos, 8 parts of Radix Ilicis Pubescentiss, 8 parts of Herba Viscis, 8 parts of Rhizoma Chuanxiongs, Rhizoma Corydalis are carried out respectively for 12 parts being ground into coarse powder after the pretreatment, medicated powder is pressed the formula proportion mixing, add 5 times of amounts (weight ratio), 55% ethanol, reflux, extract, 2 times, each 2 hours, to merge behind 2 extracting liquid filterings, alcohol extract is evaporated to relative density 1.15 ~ 1.17 under 60 ℃, get dry powder attitude pharmaceutical composition after cooling, the drying.
Embodiment 9
In the dry-powder medicament compositions routinely dosage add excipient dextrin and correctives Aspartane, and with 70-80% ethanol as wetting agent, mixing, through granulate, dry, granulate, make granule.
Embodiment 10
In the dry-powder medicament compositions routinely dosage add Mel and mix thoroughly, make honey pill agent by technology.
Application in application, the especially angina pectoris of blood stasis pattern of syndrome of above-mentioned any one dosage form in treatment coronary heart disease, angina pectoris disease.
Pharmaceutical preparation pharmacodynamics test situation of the present invention:
1, to cause the test of the mice of acute myocardial ischemia with pituitrin:
By the body weight dosage mice is divided into 1.0g/kg group, 2.0g/kg group and 4.0g/kg group, the result shows: test group mice serum SOD vigor is obviously than model control group mice rising (P＜0.01), Content of MDA obviously reduces (P＜0.05 or P＜0.01) than the model control group mice, sees Table 1
The influence of table 1 pair SOD in serum, MDA (
± S)
Annotate: compare with model control group:
※P＜0.05,
※ ※P＜0.01.
By the body weight dosage mice is divided into 1.0g/kg group, 2.0g/kg group and 4.0g/kg group, the result shows: test group mouse cardiac muscle SOD vigor is obviously than model control group mice rising (P＜0.05 or P＜0.01), cardiac muscle MDA content obviously reduces (P＜0.01) than the model control group mice, sees Table 2
The influence of table 2 pair SOD of heart tissue, MDA (
± S)
Annotate: compare with model control group:
※P＜0.05,
※ ※P＜0.01.
By the body weight dosage mice is divided into 1.0g/kg group, 2.0g/kg group and 4.0g/kg group, the result shows: test group mice serum LDH, CK vigor all obviously reduce (P＜0.05 or P＜0.01) than the model control group mice, see Table 3
The influence of table 3 pair serum CK, LDH (
± S)
Annotate: compare with model control group
※P＜0.05,
※ ※P＜0.01.
2, to the thrombotic influence test of rat artery and vein bypass:
By the body weight dosage rat is divided into 0.8g/kg group, 1.6g/kg group and 3.2g/kg group, the result shows: the rats in test groups thrombus weight obviously than model control group rat light (P＜0.01), sees Table 4
The table 4 pair thrombotic influence of rat artery and vein bypass (
± S)
Annotate: compare with model control group
*P＜0.05
*P＜0.01.
3, thrombotic influence test shows to rats in vitro:
By the body weight dosage rat is divided into 0.8g/kg group, 1.6g/kg group and 3.2g/kg group, the result shows: rats in test groups wet weight of thrombus, dry weight are all obviously shone group rat light (P＜0.01) to model, show its significant inhibitory effect that is formed with, see Table 5 the rats in vitro thrombosis
The thrombotic influence of table 5 pair rats in vitro (
± S)
Annotate: compare with model control group
*P＜0.05
*P＜0.01.
4, the influence test to hypoxia-bearing capability under the mice normal pressure shows:
By the body weight dosage mice is divided into 1.0g/kg group, 2.0g/kg group and 4.0g/kg group, the result shows: the test group mice time-to-live obviously prolongs (P＜0.05 or P＜0.01) than the model control group rat, sees Table 6
The influence of hypoxia-bearing capability under the table 6 pair mice normality (
± S)
Annotate: compare with model control group
*P＜0.05
*P＜0.01.
The influence of hypoxia-bearing capability test during 5, to the high oxygen consumption of mouse cardiac muscle:
By the body weight dosage mice is divided into 0.8g/kg group, 1.6g/kg group and 3.2g/kg group, the result shows: the test group mice time-to-live obviously prolongs (P＜0.05 or P＜0.01) than the model control group mice, sees Table 7
The influence of hypoxia-bearing capability during the high oxygen consumption of table 7 pair mouse cardiac muscle (
± S)
Annotate: compare with model control group
*P＜0.05
*P＜0.01.
6, to dog cardiac function and hemodynamic influence test
5 of test group are set, dog only are divided into small dose group (0.5g/kg), middle dosage group (1.0g/kg) and heavy dose of group (2.0g/kg), 1 of 1 of positive drug group (diltiazem is by body weight administration 5mg/kg) and blank group is set simultaneously by the body weight dosage.
Arteriotony, heart rate and Electrocardiographic influence to dog:
During 30 minutes, 45 minutes, 60 minutes, 90 minutes, 120 minutes time points, the blood pressure of dog all reduces (P＜0.05 or P＜0.01) than blank group Canis familiaris L. to the positive drug group after administration, and heart rate is all than blank group Canis familiaris L. slow down (P＜0.05 or P＜0.01).
Test group is corresponding time point after administration, and heart rate of dog and blood pressure all do not have significant change (P〉0.05) than blank group Canis familiaris L..
To the coronary flow of dog and the influence of arteria coronaria resistance:
During 30 minutes, 45 minutes, 60 minutes, 90 minutes, 120 minutes time points, the coronary flow of dog all obviously increases (P＜0.01) than blank group Canis familiaris L. to the positive drug group after administration, and coronary resistance reduces (P＜0.01) than blank group Canis familiaris L..
Test group is corresponding time point after administration, and the coronary flow of dog all obviously increases (P＜0.05 or P＜0.01) than blank group Canis familiaris L., and coronary resistance all obviously reduces (P＜0.05 or P＜0.01) than blank group Canis familiaris L..
Influence to the left ventricle of dog, the maximum climbing speed of left indoor pressure:
During 30 minutes, 45 minutes, 60 minutes, 90 minutes, 120 minutes time points, the left ventricle of dog, the maximum climbing speed of left indoor pressure all reduce (P＜0.05 or P＜0.01) than blank group Canis familiaris L. to the positive drug group after administration.
Test group is corresponding time point after administration, and the left ventricle of dog, the maximum climbing speed of left indoor pressure all do not have significant change (P〉0.05) than blank group Canis familiaris L..
To the cardiac output of dog, the influence of heartbeat output:
After positive drug group and the test group administration, each time point does not all have significant change (P〉0.05) than blank group Canis familiaris L. after the cardiac output of dog, the administration of heartbeat output.
The exponential influence of cardiac index, heartbeat to dog:
The positive drug group is after administration during 30 minutes, 45 minutes, 60 minutes, 90 minutes, 120 minutes time points, the cardiac index of dog does not all have significant change (P〉0.05) than blank group Canis familiaris L., and the heartbeat index all reduces (P＜0.05 or P＜0.01) than blank group Canis familiaris L..
The 2.0g/kg of test group group, after administration 60 minutes, cardiac index reduced (P＜0.05) than blank group Canis familiaris L., the no significant change of other times point (P〉0.05); 1.0g/kg group, after the administration 45 minutes, cardiac index reduced (P＜0.05) than blank group Canis familiaris L., the no significant change of other times point (P〉0.05); The heartbeat index of each time point after the administration of three granule test group does not all have significant change (P〉0.05) than blank group Canis familiaris L..
To the left chamber work done of dog, the influence of oxygen consumption index:
During 15 minutes, 30 minutes, 45 minutes, 60 minutes, 90 minutes, 120 minutes time points, left chamber work done of dog and oxygen consumption index all reduce (P＜0.05 or P＜0.01) than blank group Canis familiaris L. to the positive drug group after administration.
Test group is corresponding time point after administration, and the left chamber work done of dog does not all have significant change (P〉0.05) than blank group Canis familiaris L.; 2.0g/kg the oxygen consumption index of 30 minutes, 45 minutes time points all reduces (P＜0.05 or P＜0.01) than blank group Canis familiaris L. after the group administration, 0.5g/kg, 1.0g/kg group each time point behind medicine, the dog oxygen consumption index does not all have significant change (P〉0.05) than blank group Canis familiaris L..
Influence to the total peripheral resistance of dog:
30 minutes, 45 minutes time points after the administration of positive drug group, the total peripheral resistance of dog all reduce (P＜0.05) than blank group Canis familiaris L..
The 1.0g/kg of test group and 2.0g/kg group, 30 minutes, 45 minutes time points after the administration, the total peripheral resistance of dog all reduce (P＜0.05) than blank group Canis familiaris L.; 0.5g/kg group, each time point after administration, the total peripheral resistance of dog all do not have significant change (P〉0.05) than blank group Canis familiaris L..
Pharmaceutical preparation toxicity test of the present invention:
1, acute toxicity test:
Carry out the maximum dosage-feeding of mouse stomach administration measures with pharmaceutical composition of the present invention, the maximum dosage-feeding of mouse stomach administration is 64.0g/kg/ day, amount to crude drug amount 410.24g/kg/ day, 280.7 times (clinical adult 70kg, consumption 16.0g extract dry powder/day) of the clinical consumption that is equivalent to be grown up.
The result shows: each is organized, and mice general state in 7 days is good, and hair color is smooth, body weight gain, and diet and movable no abnormality seen, the overt toxicity reaction is not found in none death, illustrates that this poison of drug is very little.See Table 8 and table 9.
Table 8 respectively organize the mice body weight change (
± S, n=10)
| Natural law (d) | Matched group (♂) | Matched group (♀) | Administration group (♂) | Administration group (♀) |
| 0 | 19.81±1.04 | 19.75±1.00 | 20.35±1.02 | 20.38±0.97 |
| 1 | 20.88±1.41 | 20.52±1.23 | 21.06±1.25 | 21.27±1.32 |
| 2 | 21.71±1.41 | 21.09±1.30 | 21.67±1.46 | 22.31±1.23 |
| 3 | 22.61±1.54 | 22.10±1.48 | 22.38±1.31 | 23.17±1.22 |
| 4 | 23.88±1.56 | 22.91±1.64 | 23.20±1.29 | 23.92±1.07 |
| 5 | 24.56±1.40 | 23.44±1.70 | 23.86±1.39 | 24.42±1.12 |
| 6 | 24.99±1.26 | 24.09±1.57 | 24.56±1.18 | 24.97±1.15 |
| 7 | 25.77±1.27 | 24.74±1.39 | 25.17±1.20 | 25.63±1.23 |
Table 9 is respectively organized the mice food-intake and is changed (g/ only, n=10)
| Natural law (d) | Matched group (♂) | Matched group (♀) | Administration group (♂) | Administration group (♀) |
| 0 | 6.7 | 5.0 | 6.6 | 5.6 |
| 1 | 6.9 | 4.8 | 5.6 | 5.6 |
| 2 | 5.9 | 4.3 | 5.8 | 4.9 |
| 3 | 6.0 | 3.9 | 6.0 | 5.4 |
| 4 | 6.1 | 4.0 | 6.3 | 5.0 |
| 5 | 5.5 | 4.0 | 5.6 | 4.8 |
| 6 | 6.0 | 4.4 | 5.4 | 5.0 |
| 7 | 5.2 | 5.0 | 5.9 | 4.8 |
2, long term toxicity test:
With pharmaceutical composition of the present invention rat has been carried out six months long term toxicity test.Adopt three dosage: low dose of (4.0g/kg is equivalent to 17.5 times of clinical application), middle dosage (8.0g/kg is equivalent to 35 times of clinical application), heavy dose of (16.0g/kg is equivalent to 70 times of clinical application).
The result shows, test group does not all have obvious influence to the general situation of rat, body weight, hematological indices, ten biochemical indicators and main organs coefficient; Each internal organs naked eyes and mirror are observed down, also do not have obvious pathological change.Show that this medicine does not have the overt toxicity reaction, its nontoxic amounts of reactants is 16.0g/kg/day.
Pharmaceutical preparation clinical trial of the present invention:
II clinical trial phase result: adopt multi-center randomized double and with the method for positive drug parallel control, 220 routine experimenter's clinical test results tentatively show through 4 tame national drug clinical trial bases, pharmaceutical composition of the present invention has blood circulation promoting and blood stasis dispelling preferably to coronary heart disease, angina pectoris (syndrome of blood stasis), the effect of removing obstruction in the collateral to relieve pain, can improve the use of anginal seizure frequency, persistent period, pain degree and nitroglycerine tablets effectively, simultaneously can improve myocardial ischemia and syndrome of blood stasis syndrome, not see obvious toxic and side effects.II clinical trial phase result has tentatively shown the safety and the effectiveness of treatment by Chinese herbs coronary heart disease of the present invention, angina pectoris (syndrome of blood stasis), recommends to continue clinical research.
III clinical trial phase result: adopt multi-center randomized double and with the method for positive drug parallel control, 412 routine experimenter's clinical test results further confirm through 5 tame national drug clinical trial bases, pharmaceutical composition of the present invention has blood circulation promoting and blood stasis dispelling preferably to angina pectoris (syndrome of blood stasis), the effect of removing obstruction in the collateral to relieve pain, can effectively improve the seizure frequency of stable angina of effort, persistent period, the use of pain degree and nitroglycerine tablets, can improve myocardial ischemia and syndrome of blood stasis syndrome, may occur the property a crossed transaminase in the medication process and raise, the untoward reaction of gastrointestinal reaction and xerostomia.III clinical trial phase result has further confirmed the safety and the effectiveness of treatment by Chinese herbs coronary heart disease of the present invention, angina pectoris (syndrome of blood stasis).
Claims (9)
1. pharmaceutical composition, it is characterized in that: the former medicated bag of described pharmaceutical composition is drawn together 15 ~ 21 parts of (parts by weight) Radix Puerariaes, 15 ~ 21 parts of Rhizoma Dioscoreae Nipponicae, 15 ~ 21 parts of Folium Ginkgos.
2. pharmaceutical composition according to claim 1 is characterized in that: the former medicine of described pharmaceutical composition also comprises 8 ~ 14 parts of (parts by weight) Radix Ilicis Pubescentiss.
3. pharmaceutical composition according to claim 1 is characterized in that: the former medicine of described pharmaceutical composition also comprises 8 ~ 14 parts of (parts by weight) Radix Ilicis Pubescentiss, 8 ~ 14 parts of Herba Viscis.
4. pharmaceutical composition according to claim 1 is characterized in that: the former medicine of described pharmaceutical composition also comprises 8 ~ 14 parts of (parts by weight) Radix Ilicis Pubescentiss, 8 ~ 14 parts of Herba Viscis, 8 ~ 14 parts of Rhizoma Chuanxiongs.
5. pharmaceutical composition according to claim 1 is characterized in that: the former medicine of described pharmaceutical composition also comprises 8 ~ 14 parts of (parts by weight) Radix Ilicis Pubescentiss, Herba Visci 8-14 part, 8 ~ 14 parts of Rhizoma Chuanxiongs, 8 ~ 14 parts of Rhizoma Corydalis.
6. any one preparation of drug combination method of claim 1 ~ 5 is characterized in that: may further comprise the steps:
A, former medicine is purified respectively and pulverization process;
B, the former medicine of Chinese medicine after will handling take by weighing by formula proportion, and fully mixing adds 2 ~ 5 times of amounts (weight ratio), 50 ~ 70% ethanol, reflux, extract, 2 times, and each 2 hours, the filtrate merging with 2 extractions obtained alcohol extract;
C, to B step gained alcohol extract decompression recycling ethanol, and under 55 ~ 65 ℃, be evaporated to relative density 1.15 ~ 1.17, after cooling, the drying dry powder attitude pharmaceutical composition.
7. preparation of drug combination method according to claim 5 is characterized in that: 55 ~ 65% the ethanol that adds 3 ~ 4 times of amounts in the described B step; The concentrating under reduced pressure temperature is 60 ℃ in the described C step.
8. by the drug combination preparation of any one preparation of pharmaceutical compositions of claim 1 ~ 5, it is characterized in that: described pharmaceutical preparation is for by pharmaceutical composition and granule, capsule, honey pill agent, drop pill, powder, electuary, tablet, lyophilized injectable powder and the injection made of acceptable medical accessory pharmaceutically.
9. the application of any one forms of pharmaceutical compositions preparation in treatment coronary heart disease, angina pectoris for preparing by claim 8.
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| CN103316286A (en) * | 2013-05-23 | 2013-09-25 | 太仓市胜舟生物技术有限公司 | Application of medicine in treatment stent post-operation angiogenesis promoting medicines |
| CN109602795A (en) * | 2018-12-25 | 2019-04-12 | 北京鑫开元医药科技有限公司 | A kind of pharmaceutical composition and its extracting method, pharmaceutical preparation, purposes |
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| CN1356113A (en) * | 2000-11-28 | 2002-07-03 | 袁曙光 | Process for preparing Chinese medicine to treat cardiovascular and cerebrovascular diseases |
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| Title |
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| 杨锁成: "复方丹参降浊丸最佳制备工艺优选", 《中国实验方剂学杂志》 * |
| 王昌利: "复方龙脉宁滴丸质量标准研究", 《中成药》 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103316286A (en) * | 2013-05-23 | 2013-09-25 | 太仓市胜舟生物技术有限公司 | Application of medicine in treatment stent post-operation angiogenesis promoting medicines |
| CN109602795A (en) * | 2018-12-25 | 2019-04-12 | 北京鑫开元医药科技有限公司 | A kind of pharmaceutical composition and its extracting method, pharmaceutical preparation, purposes |
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