CN106420694A - Pharmaceutical composition for preventing and treating cardiovascular diseases - Google Patents
Pharmaceutical composition for preventing and treating cardiovascular diseases Download PDFInfo
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- CN106420694A CN106420694A CN201610861993.0A CN201610861993A CN106420694A CN 106420694 A CN106420694 A CN 106420694A CN 201610861993 A CN201610861993 A CN 201610861993A CN 106420694 A CN106420694 A CN 106420694A
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- acid
- pharmaceutical composition
- salvianolic acid
- salvianolic
- cardiovascular disease
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- A61K31/192—Carboxylic acids, e.g. valproic acid having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid
-
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Abstract
The invention relates to a pharmaceutical composition for preventing and treating cardiovascular diseases. The pharmaceutical composition is prepared from the following components in percentage by weight: 25-35% of tanshinol, 15-25% of hydroxysafflor yellow A, 0.4-1.5% of p-coumaric acid, 3.0-4.2% of salvianolic acid D, 5.0-8.0% of rosmarinic acid, 1.3-2.5% of alkannic acid, 13-20% of salvianolic acid B and 15-25% of salvianolic acid A. The pharmaceutical composition provided by the invention can reduce whole blood viscosity, improve a coagulation function and inhibit the increase in fibrinogen, so that a relatively good effect of preventing and treating myocardial ischemia is achieved.
Description
Technical field
The invention belongs to pharmaceutical technology field, and in particular to a kind of pharmaceutical composition of prevention and cure of cardiovascular disease.
Background technology
Cardiovascular disease incidence rate, disability rate height, are the first causes of death of China resident.With prolonging for the average life span
The long, affluence of material conditions and the change of life culture mode, cardiovascular risk factors persistent levels increase, and cardiovascular diseasess bear
Load day by day increases, it has also become great public health problem.Chinese urban and rural residents cardiovascular diseasess illness rate is in rising trend, dead
Rate remains high, and the whole nation there are about 3,500,000 people every year and die from cardiovascular diseasess.At present, estimate that there is cardiovascular patient 2.9 hundred million in the whole nation,
Wherein hypertension 2.7 hundred million, apoplexy at least 7,000,000, myocardial infarction 2,500,000, heart failure 4,500,000, pulmonary heart disease 500
Ten thousand, rheumatic heart disease 2,500,000, congenital heart disease 2,000,000.1 people is had to suffer from cardiovascular diseasess in being grown up per 5.Cardiovascular and cerebrovascular vessel disease
Disease becomes one of principal element of threat human health.
But for cardiovascular disease incidence mechanism complexity, the medicine of clinically common treatment cardiovascular disease has nitric acid
Glycerol, calcium ion channel blockor, but these medicine long-term takings, can produce the untoward reaction such as dizziness, palpitating speed.Western medicine
Single target treatment gradually shows limitation.Such as primary fatal disease coronary heart disease in cardiovascular disease, at present with single target
The effect of point western medicine is not obvious, and the mortality rate of coronary heart disease is still without reduction.While Western medicine is often with substantial amounts of side effect.
With going deep into for research, compound medicine, particularly with the compound medicine of native compound composition exploitation, can be made by Multiple components
For multiple target spots, while a plurality of pathological change approach of control, plays synergism, so as to suppress the progress of disease comprehensively,
With significant advantage in the prevention and treatment of complex disease.It would therefore be highly desirable to develop that clinical efficacy is notable, untoward reaction is less,
The good new anti-cardiovascular drugses of simple production process, quality stability, this provides for the animals and plants for making full use of China's abundant
Source is enriched, and the pressure for alleviating social medical expense is also significant.
Danshensu, from labiate Radix Salviae Miltiorrhizae Salvia miltiorrhiza Bge and the root of Salvia przewalskii.Should
Compound is phenol aromatic acid compound, brownish-yellow powder or yellow powder.Its pharmacological action is：Suppression platelet aggregation and
Anticoagulation, anti-inflammation and enhancing human body immunity effect, atherosclerosiss and effect for reducing blood fat.It is used for promoting blood circulationization
The stasis of blood, regulating QI to relieve pain, feel oppressed for breast, angina pectoriss.
S-A Hydroxysafflor yellow A (hydroxysafflor yellow A) derives from feverfew Flos Carthami
Carthamustinctorius L dries flower.The compound has single chalcone glycoside structure, is that Flos Carthami is topmost effectively
Water soluble ingredient, can suppress platelet aggregation and the release of platelet activating factor induction, and suppression platelet in contestable ground swashs
The combination of the factor living and platelet receptor, so as to play the pharmacological action of blood circulation promoting and blood stasis dispelling.
P-coumaric acid (p-Coumaric acid), chemical name is 4- hydroxycinnamic acid, to be widely present in natural plant
Central, it is one of effective ingredient of Herba Hedyotidis Diffusae, Herba lygodii, Folium Eucommiae.P-coumaric acid has prevention of cardiovascular disease, resists
Oxidation, anti-cancer, the biological activity beneficial to human body such as anti-inflammation and function of gallbladder promoting.
Salvianolic acid D, dries root and rhizome from labiate Radix Salviae Miltiorrhizae Salvia miltiorrhiza Bunge.
Which has the pharmacological action that antioxidation, protection brain tissue cell damaged, protected cardio-cerebrovascular.
Rosmarinic acid, is isolated a kind of water from labiate Herba Rosmarini Officinalis Rosmarinus officinalis
The natural phenolic acid class compound of dissolubility, distribution is relatively broad, is primarily present in Labiatae, Boraginaceae, Cucurbitaceae, Tiliaceae, umbrella
In the various plants such as shape section, especially with content highest in Chun Xing section and comfrey.Which has stronger anti-inflammatory activity, while fan
Repeatedly fragrant acid also has antibacterial, antiviral, antineoplastic activity.
Alkannic acid, from the root of Labiatae S.Przewalskii Maxim Salvia przewalskii Maxim, with extensive pharmacology
Function：Improve renal function, prevention and cure of cardiovascular disease, antioxidation, ischemia resisting damage, liver protection, fibrosis, preventing and treating neurotoxicity,
The pharmacological actions such as anticoagulant.
Salvianolic acid B, extracts from the root and rhizome of labiate Radix Salviae Miltiorrhizae Salvia miltiorrhiza Bge and obtains.Medicine
Pharmacological research shows, salvianolic acid B has to the protective effect of myocardial ischemia reperfusion injury, to heart microvascular endothelial cell
Delayed Protection, to atherosclerotic preventive and therapeutic effect.
Salvianolic acid A, is present in the root of labiate Radix Salviae Miltiorrhizae Salvia miltiorrhiza Bge.Twist suitable for the heart
Pain and acute myocardial infarction, the sequela for treating cerebral thrombosiss is also effective.In addition can be additionally used in treating rhomboembolia type
The disease such as vasculitiss, scleroderma, embolism of central retinal artery, nerve deafness, white thiophene Cotard and erythema nodosum.
By retrieving the domestic and international Searches of Patent Literature, do not report with regard to danshensu, hydroxyl Flos Carthami yellow in prior art
Element, P-coumaric acid, salvianolic acid D, rosmarinic acid, alkannic acid, salvianolic acid B, the relevant report of the pharmaceutical composition of salvianolic acid A.
Content of the invention
In order to solve above-mentioned technical problem, the invention provides a kind of pharmaceutical composition of prevention and cure of cardiovascular disease, this Shen
Inventor please is studied by lot of experiments and persistent exploration, is finally obtained determined curative effect, the little drug regimen of toxic and side effects
Thing.The pharmaceutical composition can reduce rat whole blood viscosity, improve coagulation function, the rising of suppression Fibrinogen, to cardiac muscle
Ischemia plays preferable preventive and therapeutic action.
The present invention is achieved by the following technical solutions：A kind of pharmaceutical composition of prevention and cure of cardiovascular disease, the medicine
Compositions are made up of the component of following weight percentage ratio：Danshensu 25～35%, S-A Hydroxysafflor yellow A 15～25%,
P-coumaric acid 0.4～1.5%, salvianolic acid D 3.0～4.2%, rosmarinic acid 5.0～8.0%, alkannic acid 1.3～2.5%, red phenol
Sour B13～20%, salvianolic acid A 15%～25%.
Used as the preferred of the present invention, described pharmaceutical composition is made up of the component of following weight percentage ratio：Danshensu 27
～33%, S-A Hydroxysafflor yellow A 17～23%, P-coumaric acid 0.6～1.2%, salvianolic acid D 3.2～4.0%, rosmarinic acid
6.0～7.0%, alkannic acid 1.6～2.2%, salvianolic acid B 15～18%, salvianolic acid A 18%～22%.
Used as the optimal preferred of the present invention, described pharmaceutical composition is made up of the component of following weight percentage ratio：Radix Salviae Miltiorrhizae
Element 30.4%, S-A Hydroxysafflor yellow A 19.8%, P-coumaric acid 0.9%, salvianolic acid D 3.6%, rosmarinic acid 6.5%, Radix Arnebiae (Radix Lithospermi)
Acid 1.9%, salvianolic acid B 16.9%, salvianolic acid A 20%.
As present invention further optimization, the dosage form of described pharmaceutical composition is injection, lyophilized powder, capsule,
Granule, tablet, drop pill, oral solutionses, pill, soft capsule.
The adjuvant used by the Chinese medicine injection can be, water for injection, ethanol, glycerol, Propylene Glycol, Polyethylene Glycol-
200th, -300, -400, -600, benzyl alcohol etc..
The adjuvant used by the lyophilized powder can be, Lactose, Mannitol, sorbitol, glucose, trehalose, dextrose
Acid anhydride etc..
The adjuvant used by the capsule can be, starch, dalcium biphosphate, starch slurry, syrup, water, ethanol, micropowder
Silica gel, carboxymethyl starch sodium etc..
The adjuvant that the granule is used can be starch, Lactose, dextrin, Icing Sugar, sucrose, Mannitol, Microcrystalline Cellulose,
Glucose.
The tablet using adjuvant can be, starch, dextrin, calcium phosphate, Microcrystalline Cellulose, carboxymethyl starch sodium, hard
Fatty acid magnesium etc..
The adjuvant used by the drop pill can be that polyethylene glycols, stearic acid, sodium stearate, poloxamer, list are hard
Fat acid glyceride etc..
The adjuvant that the oral solutionses are used can be Mel, citric acid, poly yamanashi esters, sodium benzoate, sorbic acid etc..
The adjuvant that the pill is used can be water, Mel, syrup, sodium carboxymethyl cellulose, hydroxypropyl methyl cellulose
Deng.
Purposes of the pharmaceutical composition of the present invention in the medicine for preparing prevention and cure of cardiovascular disease.
The adjuvant that the soft capsule is used can be vegetable oil, PEG400, Cera Flava, glycerol, gelatin, water etc..
The beneficial effect of pharmaceutical composition of the present invention：
(1), the prescription of pharmaceutical composition of the present invention is preferred
The prescription of pharmaceutical composition of the present invention, selects danshensu and two medicine phases of S-A Hydroxysafflor yellow A to join, can both suppress blood
Platelet is assembled, and contestable ground suppresses the combination of platelet activating factor and platelet receptor so that pharmaceutical composition has
Function of promoting blood circulation to disperse blood clots；P-coumaric acid and salvianolic acid D component is equipped with, protection brain tissue cell damage can be played, can be to cardiac muscle
Ischemia plays preferable preventive and therapeutic action；Selected with rosmarinic acid, Radix Arnebiae (Radix Lithospermi) acid constituents again so that prescription has ischemia resisting damage
Injure the effect of antiinflammatory；Salvianolic acid A and B component are finally equipped with, and two medicines are used cooperatively, and can play Synergistic so that medicine
Compositionss have protective effect first to myocardial ischemia reperfusion injury, can make above-mentioned effective ingredient again preferably by blood brain
Barrier, increases distribution and metabolism of the effective ingredient in brain, to strengthen the therapeutic effect of pharmaceutical composition.
(2), the beneficial effect of pharmaceutical composition of the present invention
The pharmaceutical composition of the present invention has the advantage that pharmacological effect effect is obvious, safety is good.And medicine group of the present invention
Each crude drug abundance of compound, inexpensive, have no toxic and side effects, preparation process is simple, can be made into injection, lyophilized powder, glue
Wafer, granule, tablet, drop pill, oral solutionses, pill, soft capsule.Pharmaceutical composition of the present invention can improve 5 and cut
Whole blood viscosity, Blood Coagulation PT, APTT under variability, and the rising of Fibrinogen can be significantly inhibited.These data are also said
Bright, the stronger function of resisting myocardial ischemia of pharmaceutical composition of the present invention.
Pharmaceutical composition of the present invention is it has surprisingly been found that ALT (alanine aminotransferase), the AST of model group significantly can be lowered
(aspartic transaminase), TBIL (total bilirubin), LDH (serum lactate dehydrogenase (SLD)), the indices of CREA (serum creatinine),
Illustrate that pharmaceutical composition of the present invention has protective effect to lesions of liver and kidney.
Description of the drawings
5s after Fig. 1-each experimental group administration-1The improvement situation of whole blood viscosity under shear rate；
30s after Fig. 2-each experimental group administration-1The improvement situation of whole blood viscosity under shear rate；
50s after Fig. 3-each experimental group administration-1The improvement situation of whole blood viscosity under shear rate；
150s after Fig. 4-each experimental group administration-1The improvement situation of whole blood viscosity under shear rate；
200s after Fig. 5-each experimental group administration-1The improvement situation of whole blood viscosity under shear rate；
The improvement situation of APTT after Fig. 6-each experimental group administration；
The improvement situation of PT after Fig. 7-each experimental group administration；
The improvement situation of Fbg after Fig. 8-each experimental group administration；
The improvement situation of alanine aminotransferase (ALT) after Fig. 9-administration；
The improvement situation of aspartic transaminase (AST) after Figure 10-administration；
The improvement situation of total bilirubin (TBIL) after Figure 11-administration；
The improvement situation of serum lactate dehydrogenase (SLD) (LDH) after Figure 12-administration；
The improvement situation of serum creatinine (CREA) after Figure 13-administration.
Specific embodiment
The present invention is further illustrated with reference to embodiments, but the present invention is not limited only to these embodiments, not
On the premise of departing from present inventive concept, any improvement that is made is within the scope of the present invention.1 present invention of embodiment
The pharmacodynamic experiment of pharmaceutical composition
1.1 test materials and instrument
1.1.1 laboratory animal：
Male SD rat 24, body weight 240-260g, SPF level, supplied by Guangdong Medical Lab Animal Center, the quality certification
Number：SCXK- (Guangdong) 2013-0002.
1.1.2 experimental drug and reagent：
S-A Hydroxysafflor yellow A (lot number：11637-201207), purchased from Nat'l Pharmaceutical ＆ Biological Products Control Institute, purity is
92.5%；Salvianolic acid A (lot number：151017), rosmarinic acid (lot number：150210), danshensu (lot number：151106), alkannic acid
(lot number：151004), salvianolic acid B (lot number：121521), salvianolic acid D (lot number：142998), P-coumaric acid (lot number：
150927), purchased from Shanghai Yuan Mu bio tech ltd, purity is all higher than 98% through HPLC detection；0.1% hydrochloric acid adrenal gland
Plain injection (Shanghai Hefeng Pharmaceutical Co., Ltd., lot number：130301), with normal saline dilution to 0.4mg/ml；0.9% chlorination
Sodium injection two citric acid monohydrate trisodiums；Chloral hydrate (chloral hydrate).
1.1.3 experimental apparatus：
Ultimate 3000DGLC high performance liquid chromatograph (Dionex company of the U.S., the double ternary pumps of DGP-3600SD,
SRD-3600 degasser, WPS-3000SL automatic sampler, TCC3000-RS column oven, DAD detector, Chromeleon7.2
Data processing software)；Chromatographic column：Elite Hypersil ODS2 (4.6 × 250mm, 5 μm, S.N.E2618699).Vortex shakes
Swing device：Scientific Industries Vortex-Genie 2；100000/electronic balance：sartorius
BP211D；Ultra cold storage freezer：Haier BCD-568W；Refrigerated centrifuger：Eppendorf 5430R、TD5A-WS、TDL-5M；Beijing
Puli gives birth to LBY-NJ4 platelet aggregation instrument；Sysmex CA-510 full-automatic blood coagulation analyzer；Beijing Puli life LBY-N6B is complete certainly
Dynamic self-cleaning blood rheological instrument；The full-automatic Dynamic Erythrocyte Sediment Rate tester of Beijing Puli life LBY-XC40 carries out erythrocyte sedimentation rate detection.
1.1.4 experimental situation：Raise in Guangdong Province through the approval of Life Science College animal welfare committee of Zhongshan University
Mountain university ocean and Chinese medicine laboratory SPF level Animal House, credit number：SCXK- (Guangdong) 2009-0020.20 DEG C of room temperature of observation-
23 DEG C, relative humidity 50%-65%, pellet, start experiment experimentation after laboratory animal shakes down one week
In take appropriate method to mitigate the injury to animal.Pharmacodynamics index detection is commented in Guangzhou Institute of Pharmaceutical Industry's medicine non-clinical
Valency research center animal medicine portion, Zhongshan University of Guangdong Province ocean and Chinese medicine laboratory are carried out.
1.2 experimental technique
1.2.1 the preparation of pharmaceutical composition sample of the present invention：
Precision weighs danshensu, S-A Hydroxysafflor yellow A, P-coumaric acid, salvianolic acid D, rosmarinic acid, alkannic acid, red phenol
Sour B, appropriate salvianolic acid A, plus normal saline make every 1ml 1.17mg containing danshensu, S-A Hydroxysafflor yellow A 0.76mg, to perfume (or spice)
Bean acid 0.033mg, salvianolic acid D 0.14mg, rosmarinic acid 0.25mg, alkannic acid 0.075mg, salvianolic acid B 0.65mg, salvianolic acid A
The solution of 0.77mg, obtains final product.
1.2.2 the structure of stasis syndrome rat model：
Experiment packet and administration：Rat is randomly divided into 3 groups, respectively normal group, acute blood-stasis model group, medicine of the present invention
Compositionss group 3ml/kg/d.Laboratory animal starts administration after adapting to one week in feeding environment, administering mode is intramuscular injection, empty
White matched group and model group intramuscular injection same volume normal saline, are administered once a day, successive administration 10d.
1.2.3 rat acute blood stasis model is set up：
30min after last dose, the equal subcutaneous injection adrenalin hydrochloride 0.8mg/kg of remaining each group rat in addition to normal group,
Normal rats subcutaneous injection normal saline, after crossing 2h, in addition to normal group, remaining each group rat is all immersed in 0-4 DEG C of frozen water
Subcutaneous injection equivalent adrenalin hydrochloride 0.8mg/kg again is carried out after cold stimulation 5min, 2h, after place postpones fasting 12h, each group is entered
Row administration, 10% chloral hydrate 0.35ml/100g intraperitoneal injection of anesthesia after 1h, ventral aorta is taken a blood sample, sodium citrate 1:9 anticoagulants,
Blood sample treatments and detection are all carried out according to standard operating procedure, and it is related with coagulation function that taken blood is completely used for hemorheology
Pharmacodynamics index is detected.
1.2.4 rat blood pharmacodynamics index is detected：
Take 1.5ml anticoagulated blood and be put into TDL-5M refrigerated centrifuger and be centrifuged (3820r/m, 2000g, 15min, 20 DEG C)
Blood plasma is obtained, a part of blood plasma is put into Sysmex CA-510 full-automatic blood coagulation analyzer and carries out activated partial thromboplastin time
(APTT), prothrombin time (PT) and Fibrinogen (Fbg) item detection；Take 0.9ml anticoagulated blood and be put into Beijing Puli
Raw LBY-N6B Full-automatic self-cleaning blood rheological instrument carries out whole blood viscosity (WBV, 5s-1、30s-1、50s-1、150s-1、200s-1) etc.
The detection of index.
1.2.5 data processing method：
Gained measurement data is all represented with means standard deviation, one factor analysis of variance is used using SPSS18.0 version
(ANOVA) and T inspection method carry out data analysiss, P value thinks there is significant difference less than 0.05 and P value less than 0.01.
1.3 experimental result：
1.3.1 the impact to whole blood viscosity index
It is the macroscopic view embodiment of high blood coagulation state that whole blood viscosity is raised, it is considered to be the weight of most cardiovascular and cerebrovascular diseases
Want one of risk factor.Experimental result (see accompanying drawing 1-5) shows：Model group whole blood viscosity is in 5s-1、30s-1、50s-1、150s-1、
200s-1(P is significantly raised under shear rate<0.05)；Pharmaceutical composition of the present invention all has to whole blood viscosity under 5 shear rates and necessarily changes
Kind effect.
1.3.2 the impact to Blood Coagulation
PT, APTT are respectively the pharmacodynamics index for characterizing exogenous and intrinsic coagulation system, are commonly used to monitor thrombolytic drug
Clinical efficacy.Experimental result (see accompanying drawing 6,7) shows：PT, APTT of model group all significantly reduces (P<0.01).Medicine of the present invention
Compositions have certain improvement result to PT, APTT.
1.3.3 the impact to Fibrinogen index
The increasing of Fibrinogen is common in angina pectoriss, acute myocardial infarction, cerebral infarction and waits indefinitely disease, is clinical to commonly use blood coagulation
One of four test ratings.Experimental result (see accompanying drawing 8) shows：Model group Fibrinogen significantly raises (fibrin original shape
The time of fibroblast cells significantly shortens) (P<0.01).Pharmaceutical composition of the present invention can all significantly inhibit the liter of Fibrinogen
Height (P<0.05).
1.3.4 the impact to lesions of liver and kidney index of correlation
Alanine aminotransferase (ALT), aspartic transaminase (AST), total bilirubin (TBIL) are commonly used to indicate liver
Or whether biliary tract there is exception, be inflamed when liver, necrosis, the infringement such as poisoning when, these three indexs are all raised.Serum lactic
Dehydrogenase (LDH) is one of important enzyme system of sugared anerobic glycolysises and glyconeogenesis, is widely present in tissue, can auxiliary diagnosis
The diseases such as heart infarction, hepatopathy.Serum creatinine (CREA) increases that to see various nephropathy, acute or chronic renal failure, severe congested
Heart failure, myocarditiss, muscle injury, gigantism, acromegaly etc..
Experimental result (see accompanying drawing 9-13) shows：After modeling, ALT, AST, TBIL, LDH, CREA of model group all significantly rise
Height (P<0.01), prompting rat liver and kidney sustain damage.Pharmaceutical composition of the present invention can suppress the exception of this several index
Raise, illustrate pharmaceutical composition of the present invention with having protective effect to lesions of liver and kidney.
The toxicity test of the pharmaceutical composition of the present invention of embodiment 2
Healthy mice 20, body weight is in 18～24g, and using the solution for preparing in the present embodiment, tail vein injection is administered, gives
Pharmaceutical quantities are 10ml/Kg, to observation post administration, none animal dead situation in 7d.
Rat long term toxicity test selects health, body weight 70～110g Wistar rat 40, using the embodiment of the present invention
The medicinal composition solution for preparing in 1, tail vein injection is administered, and dosage is 8ml/Kg/d, weekly measurement rat weight 1
Secondary, dosage is adjusted according to weight, and the survey of routine blood test, blood parameters after successive administration 90d, is done to most of rat extracting blood
Fixed, and put to death and take main organs and carry out histopathologic examination.After being discontinued 2 weeks, remaining rat is put to death, taking main organs carries out disease
Reason histological examination, judges the delayed toxicity of medicine.As a result show, after 3 months, experimental rat general status are good, and growth is sent out
Educate normally, body weight growth rate, the acropetal coefficient of rat, blood biochemical index, major organs are included on the heart, liver,spleen,kidney, kidney
Gland, brain, thymus, testis, ovary, stomach, intestinal etc. are showed no exception.This also illustrates that pharmaceutical composition safety of the present invention is good.
The preparation of the pharmaceutical composition Chinese medicine of the present invention of embodiment 3
Take danshensu 30.4g, S-A Hydroxysafflor yellow A 19.8g, P-coumaric acid 0.9g, salvianolic acid D 3.6g, rosmarinic acid
6.5g, alkannic acid 1.9g, salvianolic acid B 16.9g, salvianolic acid A 20g, above-mentioned raw materials medicine is carried out mix homogeneously, and by above-mentioned original
Material medicine is added in 1000ml distilled water, carries out dissolving dispersion, then respectively glycerol 10g, Propylene Glycol 5g, be stirred, mixing is equal
After even, filter, embedding, sterilizing, subpackage 1000, obtain final product.
The preparation of the pharmaceutical composition freeze dried powder of the present invention of embodiment 4
Take danshensu 31g, S-A Hydroxysafflor yellow A 18g, P-coumaric acid 1.0g, salvianolic acid D 3.3g, rosmarinic acid
6.2g, alkannic acid 1.7g, salvianolic acid B 16.0g, salvianolic acid A 21g, Mannitol 21g, glucose 10g, distilled water 1000ml, will
After said components are mixed, freeze-dried, subpackage 1000, obtain final product.The preparation of the medicament composition capsule agent of the present invention of embodiment 5
Take danshensu 33g, S-A Hydroxysafflor yellow A 17g, P-coumaric acid 1.2g, salvianolic acid D 3.2g, rosmarinic acid 7.0g,
Alkannic acid 2.2g, salvianolic acid B 15g, salvianolic acid A 22g, after said medicine component is mixed, add appropriate starch, phosphoric acid hydrogen
Calcium, granulation, encapsulated, make hard capsule.
The preparation of the medicament composition granule agent of the present invention of embodiment 5
Take danshensu 27g, S-A Hydroxysafflor yellow A 23g, P-coumaric acid 0.6g, salvianolic acid D 4.0g, rosmarinic acid 6.0g,
Alkannic acid 1.6g, salvianolic acid B 18g, salvianolic acid A 18g, said medicine is uniformly mixed, and adds appropriate dextrin, sucrose,
Mix, granulation, dry, make granule.
The preparation of the medicinal composition tablets of the present invention of embodiment 6
Take danshensu 35g, S-A Hydroxysafflor yellow A 25g, P-coumaric acid 1.5g, salvianolic acid D 3.0g, rosmarinic acid 8.0g,
Alkannic acid 1.3g, salvianolic acid B 20g, salvianolic acid A 15g, said medicine is uniformly mixed, and adds appropriate microcrystalline cellulose
Element, magnesium stearate, mixing, granulation, tabletted.
The preparation of the medicament composition dropping pills agent of the present invention of embodiment 7
Take danshensu 25g, S-A Hydroxysafflor yellow A 15g, P-coumaric acid 0.4g, salvianolic acid D 4.2g, rosmarinic acid 5.0g,
Alkannic acid 2.5g, salvianolic acid B 13g, salvianolic acid A 25g, said medicine is uniformly mixed, add PEG4000,
PEG6000 after heated and stirred is uniform, is carried out dripping, makes drop pill as substrate.The pharmaceutical composition mouth of the present invention of embodiment 8
Take the preparation of liquid
Take danshensu 30g, S-A Hydroxysafflor yellow A 20g, P-coumaric acid 0.9g, salvianolic acid D 3.6g, rosmarinic acid 6.5g,
Alkannic acid 1.9g, salvianolic acid B 16g, salvianolic acid A 20g, said medicine is uniformly mixed, and adds Mel, citric acid, Pyrusussuriensiss
Sour potassium, after stirring, makes oral solutionses.
The preparation of the pharmaceutical composition pill of the present invention of embodiment 9
Take danshensu 30g, S-A Hydroxysafflor yellow A 20g, P-coumaric acid 1.0g, salvianolic acid D 3.6g, rosmarinic acid 6.5g,
Alkannic acid 1.9g, salvianolic acid B 16g, salvianolic acid A 20g, said medicine is uniformly mixed, and adds hydroxypropyl methyl fiber
Element, then with 70% ethanol as binding agent, pill, after being dried, pelletization.
The preparation of the medicinal composition soft capsule of the present invention of embodiment 10
Take danshensu 31g, S-A Hydroxysafflor yellow A 18g, P-coumaric acid 0.8g, salvianolic acid D 3.4g, rosmarinic acid 6.8g,
Alkannic acid 2.1g, salvianolic acid B 18g, salvianolic acid A 17g, said medicine is uniformly mixed, and adds PEG400, sweet
Oil, obtains cyst fluid, then by after the heating melting of glycerol, gelatin and water, finally adds potassium sorbate after stirring evenly, even through colloid mill mill,
After making rubber, cyst fluid will be continued to employ and suppressed with rubber, be pressed into soft capsule.
Claims (5)
1. a kind of pharmaceutical composition of prevention and cure of cardiovascular disease, it is characterised in that described pharmaceutical composition be by following weight hundred
The component of ratio is divided to make：Danshensu 25～35%, S-A Hydroxysafflor yellow A 15～25%, P-coumaric acid 0.4～1.5%, pellet
Phenolic acid D 3.0～4.2%, rosmarinic acid 5.0～8.0%, alkannic acid 1.3～2.5%, salvianolic acid B 13～20%, salvianolic acid A
15%～25%.
2. the pharmaceutical composition of prevention and cure of cardiovascular disease as claimed in claim 1, it is characterised in that described pharmaceutical composition be by
The component of following weight percentage ratio is made：Danshensu 27～33%, S-A Hydroxysafflor yellow A 17～23%, P-coumaric acid 0.6～
1.2%th, salvianolic acid D 3.2～4.0%, rosmarinic acid 6.0～7.0%, alkannic acid 1.6～2.2%, salvianolic acid B 15～18%,
Salvianolic acid A 18%～22%.
3. the pharmaceutical composition of prevention and cure of cardiovascular disease as claimed in claim 2, it is characterised in that described pharmaceutical composition be by
The component of following weight percentage ratio is made：Danshensu 30.4%, S-A Hydroxysafflor yellow A 19.8%, P-coumaric acid 0.9%, pellet
Phenolic acid D 3.6%, rosmarinic acid 6.5%, alkannic acid 1.9%, salvianolic acid B 16.9%, salvianolic acid A 20%.
4. as arbitrary described pharmaceutical composition in claims 1 to 3, it is characterised in that the dosage form of described pharmaceutical composition is：Note
Penetrate agent, lyophilized powder, capsule, granule, tablet, drop pill, oral solutionses, pill, soft capsule.
5. as purposes of arbitrary described pharmaceutical composition in prevention and cure of cardiovascular disease medicine is prepared in claims 1 to 3,
The cardiovascular disease includes but is not limited to coronary heart diseases and angina pectoris, myocardial infarction, atherosclerosiss, the blood stasis type lung heart
The diseases such as disease, ischemic encephalopathy, cerebral thrombosiss.
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