CN102068440B - Drug composition for treating cardio-cerebrovascular diseases and preparation method - Google Patents
Drug composition for treating cardio-cerebrovascular diseases and preparation method Download PDFInfo
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Abstract
The invention provides a drug composition for treating cardio-cerebrovascular diseases and a preparation method. The drug composition is jointly formed by such active ingredients as 2-10 parts by weight of salvianolic acid B, 0.1-0.5 part by weight of tanshinone IIA, 0.1-0.5 part by weight of ferulic acid, 0.4-2 parts by weight of ligustilide and 2-10 parts by weight of puerarin and the auxiliary added ingredients acceptable in the drugs. Tests show that the drug composition can obviously reduce brain tissue hemorrhagic necrosis caused by brain ischemia reperfusion injury and alleviate injuries of nerve cells and nerve fibers.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition of treating cardiovascular and cerebrovascular disease, particularly a kind of pharmaceutical composition of forming by the effective ingredient of natural drug, and preparation method thereof.
Background technology
Cardiovascular and cerebrovascular disease is a kind of common and multiple sexually transmitted disease (STD), and the sickness rate with mid-aged population is high especially, the healthy and quality of life of serious harm middle-aged and elderly people.Traditional single medicinal material and compound medicine thereof have prevention and therapeutical effect preferably to cardiovascular and cerebrovascular disease; Has stasis-dispelling and pain-killing like Radix Salviae Miltiorrhizae; Promoting blood circulation to restore menstrual flow, the effect of the relieving restlessness that clears away heart-fire often is used to the prevention and the treatment of cardiovascular and cerebrovascular disease; Its aqueous soluble active constituent is for comprising multiple salvianolic acid composition (Du Guanhua etc.: preclinical medicine and clinical, 2000 such as salvianolic acid A, salvianolic acid B, salvianolic acid C; (5): 10), content of danshinolic acid B the highest (content is about 4% in the Radix Salviae Miltiorrhizae) wherein.Salvianolic acid and main component thereof mainly show as the protective effect of cardiovascular and cerebrovascular vessel: (1) has protective effect to the brain injury that cerebral ischemia re-pouring causes; Can reduce MDA content in the cerebral tissue, the memory dysfunction that cerebral ischemia re-pouring is caused improves significantly.(2) myocardial cell injury and the arrhythmia that myocardial ischemia-reperfusion are caused have significant protective effect, in body thrombosis the dose-dependent inhibition effect are arranged to experimental, and the platelet aggregation that multiple factor is caused all has significant inhibitory effect.The fat-soluble effective ingredient of Radix Salviae Miltiorrhizae is for comprising multiple TANSHINONES compositions such as Tanshinone I, tanshinone, Tanshinone II B, cryptotanshinone, and is wherein the highest with tanshinone content.The research proof TANSHINONES of pharmacological evaluation and clinical observation has definite curative effect to cardiovascular and cerebrovascular disease, and main effect has: (1) suppresses vascular smooth muscle cell proliferation, and (2) suppress vascellum endometrial hyperplasia; (3) improve coronary artery, (4) alleviate myocardial ischemia reperfusion injury, and (5) prevent myocardial hypertrophy; (6) control arrhythmia; (7) alleviate the cerebral hypoxia ischemia damage, (Tan Weihua etc.: Guiyang College of Traditional Chinese Medicine's journal, 2007 such as (8) control cerebral ischemia reperfusion injury; 29 (3): 52-54).
Rhizoma Chuanxiong has blood-activating and qi-promoting, the effect of wind-expelling pain-stopping, and main effective ingredient is compositions such as Rhizoma Chuanxiong volatile oil, phenolic acids.The bibliographical information Rhizoma Chuanxiong volatile oil has microcirculation improvement, and the effect of cerebral blood flow increasing amount can make the blood capillary spasmolytic, increases the open number of blood capillary, accelerates VPV, makes accumulative erythrocyte depolymerization etc.The Rhizoma Chuanxiong volatile oil main component comprises ligustilide, butylphthalide, butylidene phthalide etc., and wherein ligustilide content is the highest, in Rhizoma Chuanxiong medical material and the Rhizoma Chuanxiong oil content of ligustilide be about 1.5% respectively, 20-50%.Liposoluble ingredient also is an active component important in the Rhizoma Chuanxiong, has antithrombotic, blood fat reducing, prevents and treats pharmacologically actives such as coronary heart disease; Wherein ferulic acid has atherosclerosis, antiplatelet aggregation, antioxidation; Anti-inflammation isoreactivity (Zhang Ling etc.: modern Chinese medicine research and practice; 2009,23 (4): 41), the main representative composition of Rhizoma Chuanxiong phenolic acid is ferulic acid, feruloyl quinic acid, chlorogenic acid, caffeic acid etc.
Radix Puerariae has expelling pathogenic factors from muscles for reducing heat; Promote the production of body fluid; Rash, the effect of yang invigorating antidiarrheal, kudzu vine root comprises flavones ingredients such as puerarin, daiazi, daidzein, 3 '-hydroxyl puerarin, 3 '-methoxy puerarin; The vasospasm that hyperkalemia and norepinephrine are caused has tangible relexation, can significantly resist repeatability cerebral ischemia brain water content, Ca
2+And MDA content raises inhibition Ca
2+The reduction of-ATPase and superoxide dismutase activity, has protective effect to cerebral ischemia at the breathing persistent period behind the significant prolongation mice broken end.Puerarin has effects such as blood fat reducing, protection cardiac muscle, microcirculation improvement, antioxidation.Yufeng ningxin tablets, yufeng ningxin pian that records of Pharmacopoeia of the People's Republic of China version in 2010 is the medicine of single Radix Puerariae raw material through being processed into, and has relieving spasm to stop pain, strengthens the effect of brain and arteria coronaria blood flow; In addition, puerarin injection is the common drug of treatment cardiovascular and cerebrovascular disease.Radix Puerariae that records of Pharmacopoeia of the People's Republic of China version in 2010 is divided into two kinds of Herba Gelsemii Elegantis and Pachyrhizua angulatus; Wherein puerarin (greater than 2.4%) and total yellow content are very high in the Herba Gelsemii Elegantis; Puerarin in the Pachyrhizua angulatus (greater than 0.3%) and total yellow content are lower, so the first-selected Herba Gelsemii Elegantis of general extraction puerarin and flavones ingredient feeds intake.
With above-mentioned Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, Radix Puerariae is " preparation of promoting blood circulation " (TONGMAI CHONGJI and TONGMAI KOUFUYE) of feedstock production; Record in the 4th and the 20 in the Sanitation Ministry medicine standard Chinese traditional patent formulation preparation; Widely-used in clinical, the main pharmacodynamics effect has: (1) antithrombotic, (2) coronary artery dilator, resisting myocardial ischemia; (3) spasmolytic, microcirculation improvement, (4) anti-cerebral ischemia, anoxia etc.The prescription of preparation of promoting blood circulation is: Radix Salviae Miltiorrhizae 500g, Rhizoma Chuanxiong 500g, Radix Puerariae 500g, more than three flavor medical materials, the decocte with water secondary, 1.5 hours for the first time, 1 hour for the second time, filter while hot, merging filtrate is processed electuary or oral liquid by conventional method.
Publication number CN1839931A Chinese patent has been reported a kind of pharmaceutical composition of treating cardiovascular and cerebrovascular disease; Form by Radix Salviae Miltiorrhizae total phenolic acids, Rhizoma Chuanxiong volatile oil and Radix Puerariae total flavones; It extracts raw material and is respectively Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong and Radix Puerariae; Wherein, Radix Salviae Miltiorrhizae and Radix Puerariae adopt respectively that water is carried, macroporous absorption tree fingering is separated and obtained salvianolic acid extract and Radix Puerariae flavone extract, and Rhizoma Chuanxiong employing supercritical carbon dioxide extraction obtains the Rhizoma Chuanxiong volatile oil extract.
Test shows, the composition of the said medicine part that still comes with some shortcomings has respectively not only influenced giving full play to of the useful curative effect of medicine, has also caused the waste of medicinal raw material.
Summary of the invention
To above-mentioned situation, the present invention at first provides more than one to state compound mode to be the basis, can to help the pharmaceutical composition of the treatment cardiovascular and cerebrovascular disease that curative effect of medication gives full play to, and this preparation of drug combination method further is provided on this basis.
The present invention treats the pharmaceutical composition of cardiovascular and cerebrovascular disease, is effective ingredient with salvianolic acid B, tanshinone, ferulic acid, ligustilide, puerarin, forms jointly with the auxiliary adding ingredient of acceptable in the medicine.The weight of said effective ingredient consists of: 2～10 parts of salvianolic acid Bs, 0.1～0.5 part of tanshinone, 0.1～0.5 part of ferulic acid, 0.4～2 part of ligustilide, 2～10 parts of puerarins.
In the above-mentioned pharmaceutical composition, the preferred weight of said effective ingredient composition is: 6 parts of salvianolic acid Bs, 0.4 part of tanshinone, 0.2 part of ferulic acid, 1 part of ligustilide, 5 parts of puerarins.
In the composition of pharmaceutical composition; Said effective ingredient salvianolic acid B, tanshinone, ferulic acid, ligustilide, puerarin; Can also can extract or prepare for available from the composition of the single pure article form of commercially available corresponding commodity by the method for at present existing bibliographical information.For example, at present to existing report of the full chemosynthesis mode of ferulic acid and/or use; By suitable natural medicinal raw material extract compositions such as salvianolic acid B, tanshinone, ferulic acid, ligustilide, puerarin the also existing at present report of method and/use, and the latter's extracting mode usually can be more easy and commonly used.For example, said effective ingredient salvianolic acid B allows to adopt the salvianolic acid extract replacement from the medicinal raw material Radix Salviae Miltiorrhizae that contains said amount; The effective ingredient tanshinone allows to adopt the tanshinone extract replacement from the medicinal raw material Radix Salviae Miltiorrhizae that contains said amount; The effective ingredient ferulic acid allows to adopt the Rhizoma Chuanxiong phenolic acid extract replacement from the medicinal raw material Rhizoma Chuanxiong that contains said amount; The effective ingredient ligustilide allows to adopt the Rhizoma Chuanxiong volatile oil extract replacement from the medicinal raw material Rhizoma Chuanxiong that contains said amount; The effective ingredient puerarin allows to adopt the Radix Puerariae flavone extract replacement from the medicinal raw material Radix Puerariae that contains said amount.Here said replacement in practical application, can only be directed against the replacement of one or more effective ingredient wherein according to practical situation, also can be the replacement to whole effective ingredient.
Further; When employing is replaced with raw extract by crude drug; To used extract except that the said effective ingredient of the single respective pure form that can adopt present known correlation method to carry out to obtain behind the purification; Also allow to be employed in when containing said effective ingredient, also contain same constituents that mainly is present in its extract and/or other composition or the impurity that drug action has no adverse effect to the present composition.As, in the salvianolic acid extract, except that salvianolic acid B, also allow to contain just like other compositions such as salvianolic acid A, Radix Salviae Miltiorrhizae acid C; In tanshinone extract, except that tanshinone, also allow to contain just like other compositions such as Tanshinone I, Tanshinone II B, cryptotanshinones; In the Rhizoma Chuanxiong phenolic acid extract, except that ferulic acid, also allow to contain just like other compositions such as feruloyl quinic acid, caffeic acid, alkaloids; In the Rhizoma Chuanxiong volatile oil extract, except that ligustilide, also allow to contain just like phthalide-type compositions such as cnidium lactone, butyphthalide and fatty oils other composition that becomes to grade; In the Radix Puerariae flavone extract except that puerarin, also allow to contain just like daidzin, 3 '-hydroxyl puerarin, 3 '-other compositions such as methoxy puerarin.Test shows; In aforementioned pharmaceutical compositions of the present invention; Salvianolic acid B, tanshinone, ferulic acid, ligustilide, the puerarin effective ingredient of employing to contain said proportional quantities; Or the corresponding salvianolic acid extract, tanshinone extract, Rhizoma Chuanxiong phenolic acid extract, Rhizoma Chuanxiong volatile oil extract, the Radix Puerariae flavone extract that also have said other composition are simultaneously replaced; Generally tangible interference or adverse effect can not arranged, can have same effect the drug action of said effective ingredient.
The pharmaceutical composition that the present invention is above-mentioned is preferably with said effective ingredient, with the conventional corresponding oral drug preparation of assisting adding ingredient to be prepared from of acceptable in the oral drugs.For example; With can received disintegrating agent in oral formulations, after auxiliary interpolation compositions commonly used such as excipient, lubricant, binding agent, filler mix; Handle the oral drugs of solid preparation forms such as the slow releasing agent of the tablet of processing, pill, granule, capsule or appropriate format, controlled release agent by corresponding common process method; Or mix with commonly used surfactants such as solubilizing agent, emulsifying agent, wetting agent, foaming or defoamer, diluent, antiseptic, stabilizing agent, correctives, thickening agent etc.; Handle by corresponding common process method, be made for the oral drugs of liquid preparation forms such as water preparation, syrup.
Wherein, filler can comprise like starch commonly used, dextrin, Icing Sugar, pregelatinized Starch, lactose, glucose, microcrystalline Cellulose, calcium carbonate, calcium sulfate, calcium bicarbonate etc.;
Adhesive can comprise like hypromellose commonly used, polyvidone, starch slurry, dextrin slurry, syrup, rubber cement, sodium alginate, Polyethylene Glycol, Resina persicae, arabic gum etc.;
Disintegrating agent can comprise like cross-linking sodium carboxymethyl cellulose commonly used, polyvinylpolypyrrolidone, carboxymethyl starch sodium, hydroxypropyl starch, low-substituted hydroxypropyl cellulose citric acid, tartaric acid, anhydride, sodium bicarbonate, sodium carbonate etc.;
The lubricating value agent can comprise like magnesium stearate (sodium) commonly used, Pulvis Talci, micropowder silica gel, liquid paraffin, Polyethylene Glycol etc.;
Substrate in the soft capsule can comprise like vegetable oil (like salad oil, Oleum Ricini, hydrogenated soybean wet goods), Polyethylene Glycol (like PEG 300, PEG 400, PEG 6000 etc.) commonly used; And antioxidants such as sodium sulfite commonly used, sodium sulfite, sodium pyrosulfite, sodium thiosulfate, ascorbic acid, cysteine, butylated hydroxyarisol, two fourth cresols, vitamin E;
Blocker in the oral sustained-release preparation can comprise like Cera Flava commonly used; Brazil wax; Hydrogenated vegetable oil; Stearyl alcohol; Glyceryl monostearate; The cellulose acetate phthalate ester; L-or S-acrylic resin; The hypromellose phthalate ester; Hydroxypropyl Methyl Cellulose Phthalate; Methylcellulose; Sodium carboxymethyl cellulose; Hypromellose; Polyvidone; Carbopol; Sodium alginate; Chitosan; Ethyl cellulose; Polymethacrylates; Non-toxic polyvinyl chloride; Polyethylene; Ethylene-vinyl acetate copolymer; Silicone rubber; And like thickening agent commonly used such as gelatin, polyvidone, sodium carboxymethyl cellulose, polyvinyl alcohol, dextran;
And used in case of necessity cyclodextrin clathrate; The stabilizing agent that surfactant etc. are commonly used, and/or as the available pH value regulator of physiology used always such as citric acid, fumaric acid, glutamic acid, L-aspartic acid, lactic acid, lactobionic acid, galactobionic acid Galactonic acid, glucuronic acid, ascorbic acid, hydrochloric acid, acetic acid etc.These conventional auxiliary adding ingredients that use can be selected to use according to different preparations and/or needs.
As above-mentioned, in preparation during pharmaceutical composition of the present invention, said effective ingredient can adopt the corresponding extract replacement of the salvianolic acid B that contains said proportional quantities, tanshinone, ferulic acid, ligustilide, puerarin.Said these extracts can adopt following manner to extract and obtain.For example:
Tanshinone extract in the said effective ingredient adopts one of following manner to prepare:
Method 1: with supercritical carbon dioxide circulation reflux type the Radix Salviae Miltiorrhizae after pulverizing is extracted the back and separate, obtain the effective ingredient tanshinone extract;
Method 2: after with the alcoholic solution of volume content >=80% Radix Salviae Miltiorrhizae after pulverizing being extracted, extracting solution is removed ethanol, and deposition is filtered, and obtains the effective ingredient tanshinone extract;
Method 3: the alcoholic solution with volume content >=80% extracts the Radix Salviae Miltiorrhizae after pulverizing, and extracting solution is removed ethanol, concentrates, and drying obtains the effective ingredient tanshinone extract.
Salvianolic acid extract in the said effective ingredient adopts one of following manner to prepare:
Method 1: behind medicinal raw material Radix Salviae Miltiorrhizae extraction tanshinone extract, residue extracts through the ethanol-water mixed solvent of water or volume content≤80%, reclaims solvent, concentrates, and drying obtains effective ingredient salvianolic acid extract;
Method 2: after extracting tanshinone extract by the medicinal raw material Radix Salviae Miltiorrhizae, residue extracts through the ethanol-water mixed solvent of water or volume content≤80%, the water extract or remove ethanol after extracting solution; After macroporous resin column absorption and water washing remove impurity; The use alcohol volume content is alcohol-water mixed liquid eluting of 40～80%, collects eluent and also removes ethanol, concentrates; Drying obtains effective ingredient salvianolic acid extract.
Rhizoma Chuanxiong volatile oil extract in the said effective ingredient adopts one of following manner to prepare:
Method 1: after with supercritical carbon dioxide circulation reflux type the Rhizoma Chuanxiong after pulverizing being extracted, separate, obtain effective ingredient Rhizoma Chuanxiong volatile oil extract;
Method 2: get Rhizoma Chuanxiong; Pulverize, use lower boiling organic solvent extraction, after separation is removed and extracted organic solvent; Obtain effective ingredient Rhizoma Chuanxiong volatile oil extract, said extraction solvent is at least a in petroleum ether, gasoline, No. 6 solvent naphthas, normal hexane and the cyclohexane extraction;
Method 3: get Rhizoma Chuanxiong, extract with the alcoholic solution of volume content >=80%, extracting solution is removed ethanol, concentrates, and drying obtains effective ingredient Rhizoma Chuanxiong volatile oil extract.
Rhizoma Chuanxiong phenolic acid extract in the said effective ingredient adopts one of following manner to prepare:
Method 1: behind medicinal raw material Rhizoma Chuanxiong extraction Rhizoma Chuanxiong volatile oil extract, residue extracts with the ethanol-water mixed solvent of water or volume content≤80%, reclaims solvent, concentrates, and drying obtains effective ingredient Rhizoma Chuanxiong phenolic acid extract;
Method 2: after extracting the Rhizoma Chuanxiong volatile oil extract by the medicinal raw material Rhizoma Chuanxiong, residue extracts with the ethanol-water mixed solvent of water or volume content≤80%, the water extract or remove ethanol after extracting solution; After macroporous resin column absorption and water washing remove impurity; The use alcohol volume content is alcohol-water mixed liquid eluting of 30～70%, collects eluent and also removes ethanol, concentrates; Drying obtains effective ingredient Rhizoma Chuanxiong phenolic acid extract.
Radix Puerariae flavone extract in the said effective ingredient adopts one of following manner to prepare:
Method 1: Radix Puerariae is pulverized, and decocting boils after-filtration, and filtrating is after macroporous resin column absorption and water washing remove impurity; The use alcohol volume content is alcohol-water mixed liquid eluting of 60～80%, collects eluent and also removes ethanol, concentrates; Drying obtains the Radix Puerariae flavone extract of effective ingredient;
Method 2: Radix Puerariae is pulverized, and the ethanol-water mixed solvent of water or volume content≤80% extracts, and reclaims solvent, concentrates, and drying obtains the Radix Puerariae flavone extract of effective ingredient.
Said extracted prepares in the process used macroporous resin in the said above-mentioned said macroporous resin column, generally can select the resin of present the most widely used HPD-100 or D101 model.
Unique curative effect advantage of traditional Chinese compound medicine is embodied in the collaborative integration of multicomponent, many target spots in its compound recipe.The above-mentioned pharmaceutical composition of the present invention is to use Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, Radix Puerariae main effective ingredient salvianolic acid B, tanshinone, ferulic acid, ligustilide, puerarin separately to be effective ingredient; Though overcome fully and adopted similar or similar medicinal raw material at present but because the loss or the defective of having lost the similar medicine of one or more effective ingredient wherein fully; Messenger drug can be given full play to it separately and collaborative beneficial effect with the various effective ingredient in the raw material; Significantly improved curative effect; Also improve the utilization rate of medicinal raw material greatly, reduced the waste of medicinal raw material.
Below again foregoing of the present invention is done further to specify through the specific embodiment of embodiment.But should this be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following instance.Do not breaking away under the above-mentioned technological thought situation of the present invention, various replacements or change according to ordinary skill knowledge and customary means are made all should comprise within the scope of the invention.
The specific embodiment
Embodiment 1
Take by weighing commodity salvianolic acid B 60g, ferulic acid 2g, the puerarin 50g of commercial single pure article composition form respectively, tanshinone 4g, ligustilide 10g and pharmaceutic adjuvant are in right amount as raw material.Salvianolic acid B, ferulic acid and puerarin add tanshinone, ligustilide and pharmaceutic adjuvant after adding medicinal PEG400 dissolving again, and mixing is subsequent use.Got it filled with gelatin, G & W in 3: 1.2: 3 by volume, process the capsule material after, above-mentioned subsequent use medicinal liquid and capsule material are pressed into soft capsule on the soft capsule press, every heavy 0.5g is capsule medicine of the present invention.
Embodiment 2
With same salvianolic acid B 20g, Tanshinone I I A 1g, ferulic acid 5g, puerarin 20g, micronization joins in the PEG-6000 fused solution respectively; Add ligustilide 20g again; Stirring and evenly mixing is processed 1000 drop pill in the drop pill machine, be drop pill medicine of the present invention.
Embodiment 3
Take by weighing same salvianolic acid B 100g, ferulic acid 1g, puerarin 100g, tanshinone 5g and ligustilide 4g respectively, add medicinal right amount of auxiliary materials, by the conventional method tabletting, process 1000, the bag film-coat is tablet medicine of the present invention.
Embodiment 4
Get it filled with the coarse powder 100kg of raw material Radix Salviae Miltiorrhizae, adopt supercritical fluid CO
2Circulation counter-current extraction, separation, extracting pressure 35MPa, 50 ℃ of extraction temperature, entrainer is 95% ethanol, and 4 hours extraction time, separator is resolved pressure 10Mpa, and 30 ℃ of resolution temperatures obtain containing the tanshinone extract of effective composition.Radix Salviae Miltiorrhizae decoction dregs after the extraction adds 8 times in water, 6 times and 6 times more respectively, extracts 3 times in 70 ℃ of dynamic agitation warm macerating, filters; Filtrating is through 150 liter HPD-100 macroporous resins (Cangzhou, Hebei precious grace chemical industry company limited is produced) adsorption column is housed, with 300 liter water washing remove impurity, and reuse 450 liter 50%v/v ethanol elutions; Collect ethanol elution, decompression recycling ethanol is concentrated into thick paste; In 65 ℃ of drying under reduced pressure, obtain the salvianolic acid extract.
Get it filled with the coarse powder 100kg of raw material Rhizoma Chuanxiong, supercritical fluid CO
2The circulation counter-current extraction with separate extracting pressure 40MPa, 60 ℃ of extraction temperature, extractant CO
21000 kilograms of consumptions/time, 5 hours extraction time, separator is resolved pressure 10Mpa, and 50 ℃ of resolution temperatures obtain the Rhizoma Chuanxiong volatile oil extract.Its Rhizoma Chuanxiong medicinal residues add 12,10 times in water more respectively, and reflux, extract, 2 times is filtered; Filtrating is through 120 liter HPD-100 macroporous resin adsorption posts are housed, with 200 liter water washing remove impurity, and reuse 350 liter 50%v/v ethanol elutions; Collect ethanol elution, decompression recycling ethanol concentrates; Drying under reduced pressure obtains the Rhizoma Chuanxiong phenolic acid extract.
Get it filled with the coarse powder 100kg of raw material Radix Puerariae (Herba Gelsemii Elegantis), add 10,8,6 times in water respectively, decoct 3 times, filter; Filtrating is regulated pH value to 4～5, through 200 liter D141 macroporous resins (Zhonglan Chenguang Chemical Inst's production) adsorption column is housed, with 300 liter water washing remove impurity; Reuse 500 liter 70%v/v ethanol elutions are collected ethanol elution, decompression recycling ethanol; Be concentrated into thick paste, drying obtains the Radix Puerariae flavone extract.
Take by weighing above-mentioned salvianolic acid extract, the Rhizoma Chuanxiong phenolic acid extract that contains ferulic acid 3g, the Radix Puerariae flavone extract that contains puerarin 60g that contains salvianolic acid B 50g, the tanshinone extract that contains Tanshinone I I A 3g respectively; With the Rhizoma Chuanxiong volatile oil extract that contains ligustilide 4g; Add medicinal right amount of auxiliary materials,, process 3000 by the conventional method tabletting; The bag film-coat is tablet medicine of the present invention.
Embodiment 5
Get it filled with the coarse powder 100kg of raw material Radix Salviae Miltiorrhizae, with the alcohol reflux of volume content 95% 2 times, extracting solution reclaims ethanol, concentrates, and drying obtains containing the extract of effective composition TANSHINONES.The alcohol reflux of the Radix Salviae Miltiorrhizae decoction dregs reuse volume content 60% behind above-mentioned ethanol extraction, the reclaim under reduced pressure solvent concentrates, and drying obtains containing the extract of effective composition salvianolic acid.
Get it filled with the coarse powder 100kg of raw material Rhizoma Chuanxiong, with the alcohol reflux of volume content 95% 3 times, extracting solution reclaims ethanol, concentrates, and drying obtains containing the extract of effective composition Rhizoma Chuanxiong volatile oil.The alcohol reflux of the Rhizoma Chuanxiong medicinal residues reuse volume content 70% behind this ethanol extraction, the reclaim under reduced pressure solvent concentrates, and drying obtains containing the extract of effective composition Rhizoma Chuanxiong phenolic acid.
Get it filled with the coarse powder 100kg of raw material Radix Puerariae, with the alcohol reflux of volume content 70% 3 times, reclaim solvent, concentrate, drying obtains containing the extract of effective composition Radix Puerariae flavone.
Take by weighing above-mentioned salvianolic acid extract 100g (in salvianolic acid B), Rhizoma Chuanxiong phenolic acid extract 5g (in ferulic acid), Radix Puerariae flavone extract 20g (in puerarin), tanshinone extract 5g (in tanshinone) and Rhizoma Chuanxiong volatile oil extract 10g (in ligustilide) respectively; Add medicinal right amount of auxiliary materials; Process 5000 of capsules by conventional method, be capsule medicine of the present invention.
Embodiment 6
With medicinal raw material Radix Salviae Miltiorrhizae coarse powder 100kg, with the alcohol reflux of volume content 90% 3 times, extracting solution is removed ethanol, staticly settles, filters, and obtains containing the extract of effective composition TANSHINONES, and filtrated stock is subsequent use.The alcohol reflux of above-mentioned Radix Salviae Miltiorrhizae decoction dregs reuse volume content 50% behind ethanol extraction 2 times, extracting solution is removed ethanol, merges with subsequent use TANSHINONES filtrated stock; After absorption of D101 macroporous resin column and water washing remove impurity; The use volume content is 70% ethanol elution, collects eluent and also removes ethanol, concentrates; Drying obtains containing the extract of effective composition salvianolic acid.
With medicinal raw material Rhizoma Chuanxiong coarse powder 100kg,, separate and remove the extract that solvent obtains containing effective composition Rhizoma Chuanxiong volatile oil with petroleum ether or No. 6 solvent naphtha reflux, extract, 3 times; Above-mentioned Rhizoma Chuanxiong medicinal residues behind petroleum ether or Pinusolvent-extracted oil No. 6 extraction are again with water reflux, extract, 3 times; The water extract is after absorption of D101 macroporous resin column and water washing remove impurity; The use volume content is 60% ethanol elution, collects eluent and also removes ethanol, concentrates; Drying obtains containing the extract of effective composition Rhizoma Chuanxiong phenolic acid.
Medicinal raw material Radix Puerariae coarse powder 100kg with water boiling and extraction 2 times, is filtered, and the water extract is after absorption of HPD-100 macroporous resin column and water washing remove impurity; The use volume content is 70% ethanol elution, collects eluent and also removes ethanol, concentrates; Drying obtains containing the extract of effective composition Radix Puerariae flavone.
Take by weighing above-mentioned salvianolic acid extract 20g (in salvianolic acid B), Rhizoma Chuanxiong phenolic acid extract 1g (in ferulic acid), Radix Puerariae flavone extract 100g (in puerarin), tanshinone extract 1g (in tanshinone) respectively; Micronization; Join in the PEG-6000 fused solution, add Rhizoma Chuanxiong volatile oil extract 20g (in ligustilide) again, stirring and evenly mixing; In the drop pill machine, process 5000 drop pill, be drops medicine of the present invention.
With salvianolic acid B, tanshinone, ferulic acid, ligustilide, puerarin serve as the pharmaceutical composition of the present invention processed of main effectively medicinal ingredient as the following experiment that trial drug carries out, can show the beneficial effect that pharmaceutical composition of the present invention has.
Test 1 pair of endotheliocyte and the protective effect of oxygen supply again of neuron anoxia
1, experimental technique: referring to E Zheng chief editor's " tissue culture and molecular biosciences cytologic technology ", Beijing: Beijing Publishing House, in December, 1994,438 pages.
(1) mtt assay is measured the endotheliocyte survival rate
Fine and close cell monolayer behind drug effect, with ice-cold PBS solution washing 2 times, adding 0.5mg/ml MTT solution 100 μ l; 37 ℃ were mixed 4 hours; Residual liquid is removed in suction, adds acidify isopropyl alcohol chromophoric solution 100 μ l, and inherent wavelength 595nm place surveyed the absorbance A value with ELIASA in 30 minutes.The viewing test medicine is to the influence of cultured cell existence.
(2) mtt assay is measured neuron survival rate
Behind the cell culture 10 days, add 0.5% MTT 10 μ l to every hole and continue to cultivate 4 hours, inhale and abandon culture fluid, add dimethyl sulfoxine (DMSO) 200 μ l/ holes, treat that the granule dissolving is placed on the ELIASA, the absorbance A value in each hole of detection at wavelength 570nm place.The viewing test medicine is to cultivating the influence of neuron existence.
(3) cultured cell anoxia/is again given thin oxygen model
The normal cultured base is used 95%N
2And 5%CO
2After the mist balance 30 minutes, obtain the anoxia culture medium.Cell is put into the anoxia storehouse and (is continued to feed 95%N with the anoxia culture medium rearmounted culture plate that suspends
2And 5%CO
2Mist is anaerobic environment for this reason), 37 ℃ hatch 2 hours (anoxia time) after, change normal culture medium immediately, hatch 4 hours (oxygen supply again) again.With unprocessed cell as contrast.
(4) medicine gives method
Trial drug is mixed with the concentration of 10ug/ml with culture medium, and medicine is with the preparation of anoxia culture medium between anaerobic phase, and medicine is prepared with ordinary culture medium during the oxygen supply again.
2, experimental result
(1) to the protective effect of oxygen supply damage in 4 hours again in 2 hours of endotheliocyte anoxia
New born bovine brain micro blood vessel endothelium cell is through anoxia 2 hours oxygen supply after 4 hours again; Produce the tangible phenomena of mortality; MTT detects and shows, anoxia oxygen supply (H/R) group cell absorbance more obviously reduces, and the cell of protecting through trial drug all demonstrates very significant protection effect; Compare P＜0.01 with matched group, as shown in table 1.In addition, can also be clear that by table 1: pharmaceutical composition of the present invention was with weight proportion 6: 0.4: 0.2: the protective effect of oxygen supply (H/R) is best again to the endotheliocyte anoxia for 1: 5 ratio compatibility.
(2) to cultivating the protective effect of oxygen supply damage in 4 hours again in 2 hours of neuron anoxia
The neonate rat brain neuron is through anoxia 2 hours oxygen supply after 4 hours again; Produce the tangible phenomena of mortality; MTT detects and shows, anoxia oxygen supply (H/R) group cell absorbance more obviously reduces, and the cell of protecting through trial drug all demonstrates very significant protection effect; Compare P＜0.01 with matched group, as shown in table 2.In addition, can also be clear that by table 2: pharmaceutical composition of the present invention was with 6: 0.4: 0.2: the protective effect of oxygen supply (H/R) is best again to the neuron anoxia for 1: 5 ratio compatibility.
Table 1 pharmaceutical composition of the present invention is to the protective effect of oxygen supply (H/R) again of endotheliocyte anoxia
X ± s, n=6, compare with matched group:
*P＜0.01.
* represent salvianolic acid B: tanshinone: ferulic acid: ligustilide: puerarin (pure article weight proportion).
Table 2 pharmaceutical composition of the present invention is to the protective effect of oxygen supply (H/R) again of neuron anoxia
X ± s, n=6, compare with matched group:
*P＜0.05.
* represent salvianolic acid B: tanshinone: ferulic acid: ligustilide: the weight proportion of puerarin.
The influence of 2 pairs of mice hypoxia-bearing capabilities of experiment
1, experimental animal: 90 of ICR mices are divided into 9 groups at random.
2, experimental technique:
Get 90 of mices; Body weight is 18-22g; Be divided into 9 groups at random; Every group 10, male and female half and half are respectively as trial drug group of the present invention (salvianolic acid B: tanshinone: ferulic acid: ligustilide: high and low dose group puerarin), breviscapine group and model group (giving the normal saline of equivalent).In the experiment preceding 6 days, every day gastric infusion once, with variable concentrations isometric(al) administration 0.1ml/10g body weight.After the last administration in the 7th day 30 minutes, mice is placed the airtight wide mouthed bottle of the 60ml that the 25g sodica calx is housed, the death time of record mice.
3, dosage setting: the mice low dosage is 50mg/kg, and high dose is 100mg/kg.
4, solvent control: normal saline is pressed 0.1ml/10g and is irritated stomach.
5, route of administration: gastric infusion.
6, administration number of times: 1 time/day, all administration is 7.
7, observation index and observing time: observe the time that mice survives under anaerobic environment.Experimental result is seen table 3.
The influence of table 3 pair mice hypoxia-bearing capability
☆ representes salvianolic acid B: tanshinone: ferulic acid: ligustilide: the weight proportion of puerarin.Compare with model group,
*P＜0.05,
*P＜0.01
8, conclusion: trial drug-salvianolic acid B of the present invention: tanshinone: ferulic acid: ligustilide: puerarin (2: 0.5: 0.5: 0.4: 2,10: 0.1: 0.1: 2: 10,6: 0.4: 0.2: 1: 5) but the equal time-to-live of significant prolongation mice under anaerobic condition of low dose group and high dose group; Compared highly significant difference (P＜0.01) with model group, as shown in table 4.Show with salvianolic acid B, tanshinone, ferulic acid, ligustilide, puerarin and to form trial drug of the present invention as effective medicinal ingredient, but the time-to-live of significant prolongation mice under anaerobic condition.In addition; Can also be clear that by table 4; Under the condition of same dose; Trial drug 6: 0.4: 0.2: 1: 5 group drug activity is superior to 2: 0.5: 0.5: 0.4: 2 and 10: 0.1: 0.1: 2: 10 groups, explain that salvianolic acid B, tanshinone, ferulic acid, ligustilide, puerarin were by 6: 0.4: 0.2 in the pharmaceutical composition of the present invention: 1: 5 proportioning is excellent.
Test the therapeutical effect of 3 pairs of bolt collimation method focal brain ischemia-reperfusion injury in rats models
1, experimental animal: 264 of SD rats are divided into 11 groups at random.
2, test method: referring to Xu Jiang equality " Chinese combination of Chinese and Western medicine first aid journal, 2003; 10 (1): 31.
Irritate stomach respectively by group and receive reagent thing or solvent control, give 7 days continuously, underwent surgery as follows in 2 hours after the last administration.
With 10% chloral hydrate 3ml/kg intraperitoneal injection of anesthesia, the neck median incision separates and ligation right carotid proximal part, external carotid artery and bifurcated artery thereof with rat.Separate the right side internal carotid artery, separate wing jaw tremulous pulse downwards along internal carotid artery, this branch of root ligation.Be equipped with line, far-end placement bulldog clamp at the internal carotid artery near-end, common carotid artery crotch otch inserts the 4-0 nylon wire, and its degree of depth is 17～20mm, and the bolt line gets into internal carotid artery, goes into cranium to anterior cerebral artery, all blood flows sources of blocking-up middle cerebral artery.Remove bulldog clamp, tighten line fully, stay the long the end of a thread of 1cm outward, skin suture.Ischemia is perfusion again after 2 hours, need not anaesthetize and cut skin once more, lifts institute's the end of a thread that stays to resistance is arranged time prompting nylon wire head end gently to the common carotid artery incision, makes blood flow logical again.Sham operated rats is except that plug wire not, and all the other steps are the same.
After the survival Mus pours into 24 again, observe rat behavior and change, carry out behavior scoring.The five-grade marking system standards of grading with reference to Zea Longa: 0 minute, normal, impassivity damage symptom; 1 minute, can not full extension offside fore paw; 2 minutes, turn-take laterally; 3 minutes, topple over to offside; 4 minutes, can not spontaneously walk loss of consciousness.Broken end is got the experimental mouse brain fast then, and a part is the left and right cerebral hemisphere weight in wet base of weighing respectively, puts in 160 ℃ of baking boxs and claims dry weight after 24 hours, calculates brain water content by following formula: brain water content (%)=(weight in wet base-dry weight)/weight in wet base * 100%; Another part downcuts the crown brain sheet of thick about 2mm on the anterior commissure plane, place 2%TTC solution at once, hatches 30 minutes for 37 ℃.Infarct presents white, and non-infarct presents redness.Digital camera is taken record, measures brain sheet cumulative volume and infarct volume with Medbrain 2.0 softwares, and calculates the percentage ratio (%) that infarct accounts for whole cerebral tissue; Another part is made tectology and is observed: cerebral tissue after fixing, the crown brain that cuts, conventional dehydration, the FFPE film-making, HE dyeing, light microscopic is checked.
3, trial drug and dosage setting:
Trial drug I: with salvianolic acid B, tanshinone, ferulic acid, ligustilide and puerarin is effective ingredient, and its weight ratio is 6: 0.4: 0.2: 1: 5.The rat dosage is 100.8mg/kg.
Trial drug II: with the salvianolic acid extract among the embodiment 4, tanshinone extract, Rhizoma Chuanxiong phenolic acid extract, Rhizoma Chuanxiong volatile oil extract and Radix Puerariae flavone extract is effective ingredient, and wherein the weight ratio of salvianolic acid B, tanshinone, ferulic acid, ligustilide, puerarin is 6: 0.4: 0.2: 1: 5.The rat dosage is 100.8mg/kg (in the weight of salvianolic acid B, tanshinone, ferulic acid, ligustilide and puerarin).
Trial drug III: with the salvianolic acid extract among the embodiment 5, tanshinone extract, Rhizoma Chuanxiong phenolic acid extract, Rhizoma Chuanxiong volatile oil extract and Radix Puerariae flavone extract is effective ingredient, and wherein the weight ratio of salvianolic acid B, tanshinone, ferulic acid, ligustilide, puerarin is 6: 0.4: 0.2: 1: 5.The rat dosage is 100.8mg/kg (in the weight of salvianolic acid B, tanshinone, ferulic acid, ligustilide and puerarin).
Trial drug IV: with salvianolic acid B, ligustilide and puerarin is effective ingredient, and its weight ratio is 6: 1: 5.The rat dosage is 96mg/kg.
Trial drug V: with the salvianolic acid extract among the embodiment 4, Rhizoma Chuanxiong volatile oil extract and Radix Puerariae flavone extract is effective ingredient, and wherein the weight ratio of salvianolic acid B, ligustilide, puerarin is 6: 1: 5.The rat dosage is 96mg/kg (in the weight of salvianolic acid B, ligustilide and puerarin).
Trial drug VI: with the salvianolic acid extract among the embodiment 5, Rhizoma Chuanxiong volatile oil extract and Radix Puerariae flavone extract is effective ingredient, and wherein the weight ratio of salvianolic acid B, ligustilide, puerarin is 6: 1: 5.The rat dosage is 96mg/kg (in the weight of salvianolic acid B, ligustilide and puerarin).
Trial drug VII: with the salvianolic acid extract among the embodiment 6, tanshinone extract, Rhizoma Chuanxiong phenolic acid extract, Rhizoma Chuanxiong volatile oil extract and Radix Puerariae flavone extract is effective ingredient, and wherein the weight ratio of salvianolic acid B, tanshinone, ferulic acid, ligustilide, puerarin is 6: 0.4: 0.2: 1: 5.The rat dosage is 100.8mg/kg (in the weight of salvianolic acid B, tanshinone, ferulic acid, ligustilide and puerarin).
Trial drug VIII: with the salvianolic acid extract among the embodiment 6, Rhizoma Chuanxiong volatile oil extract and Radix Puerariae flavone extract is effective ingredient, and wherein the weight ratio of salvianolic acid B, ligustilide, puerarin is 6: 1: 5.The rat dosage is 96mg/kg (in the weight of salvianolic acid B, ligustilide and puerarin).
4, medicine preparation: use the 4%Tween-80 mixing, the reuse pure water is mixed with desired concn, presses the 1ml/100g gastric infusion.
5, the pure water of solvent control: 4%Tween 80 is pressed 1ml/100g and is irritated stomach.
6, route of administration: gastric infusion.
7, administration number of times: all successive administration is 7, every day 1 time.
8, observation index and observing time: observe the variation of rat behavior, cerebral infarct volume, tectology.Observing time is for poured into 24 hours again.
9, result of the test: see table 4.
(1) to the influence of behavior: all no abnormal behavior of sham operated rats rat, neural behavior scoring is 0; The nerve injury symptom that the solvent control group rat occurs can not full extension, the offside fore paw is turn-taked laterally or topple over to offside, behavior scoring is 1.75 ± 0.58; Trial drug I～VIII group all can significantly reduce the rat nerves behavior scoring, with solvent control group highly significant difference (P＜0.01) arranged relatively.
Table 4 pair rat ischemia poured into the influence of 24 hours neurological's scoring, cerebral hemisphere water content and cerebral infarct volume in 2 hours again
Compare with sham operated rats,
##P＜0.01; Compare with solvent control group,
*P＜0.05,
*P＜0.01.
In the table: " trial drug V " is the medicine of CN1839931A patent documentation;
" trial drug II " is the pharmaceutical composition of the present invention of the foregoing description 4.
(2) to the influence of brain water content: solvent control group ischemia-reperfusion one side (right hemisphere) brain water content highly significant is higher than the group of doing evil through another person.Trial drug I～VIII group brain water content all significantly is lower than solvent control group.
(3) to the influence of cerebral infarct volume: the sham operated rats cerebral tissue does not have infraction, and solvent control group ischemia side cerebral tissue has the infraction phenomenon, and the percentage ratio that infarct accounts for whole brain tissue is 30.4 ± 6.5%.Trial drug I～VI group all can significantly be dwindled ischemia side cerebral tissue infarct volume, compared highly significant difference (P＜0.01) with solvent control group; And trial drug I, II, III, VII group are respectively with IV, V, VI, relatively there were significant differences (P＜0.05) for the VIII group.
(4) to the influence of tectology: sham operated rats both sides cerebral tissue is normal, and it is all normal that solvent control group, trial drug I～VIII organize non-ischemia side cerebral tissue.For ischemia side brain hemisphere: cerebral tissue hemorrhagic necrosis and the serious edema of cerebral tissue, focal necrosis appear in solvent control group, and trial drug I～VIII group all can be dwindled the hemorrhagic necrosis kitchen range; And the hemorrhagic necrosis kitchen range of trial drug IV, V, VI, VIII group is significantly less than I, II, III, VII group.
(5) result of trial drug I～III, VII group is also clear shows;, can not produce the drug action of pharmaceutical composition of the present invention and to disturb or adverse effect as the active drug composition with salvianolic acid extract, the tanshinone extract that contains significant proportion amount tanshinone that contains significant proportion amount salvianolic acid B, the Rhizoma Chuanxiong phenolic acid extract that contains significant proportion amount ferulic acid, the Radix Puerariae flavone extract that contains the Rhizoma Chuanxiong volatile oil extract of significant proportion amount ligustilide and contain significant proportion amount puerarin.
(6) trial drug I/IV group, II/V group, III/VI group and the comparative analysis as a result of VII/VIII group show; Tanshinone I I A, ferulic acid in the pharmaceutical composition of the present invention and contain significant proportion amount Tanshinone I I A tanshinone extract, contain the Rhizoma Chuanxiong phenolic acid extract of significant proportion amount ferulic acid; Drug action to said pharmaceutical composition has crucial influence, has synergistic function with salvianolic acid B, ligustilide and puerarin compatible combination.
Table 4 experimental result shows: shown by trial drug I/IV group, II/V group, III/VI group and the comparative analysis as a result of VII/VIII group; Tanshinone I I A, ferulic acid in the pharmaceutical composition of the present invention and contain same proportional quantities Tanshinone I I A tanshinone extract, contain the Rhizoma Chuanxiong phenolic acid extract of same proportional quantities ferulic acid; Drug action to said pharmaceutical composition has crucial influence, has synergistic function with salvianolic acid B, ligustilide and puerarin compatible combination.And; Effective ingredient salvianolic acid B in the pharmaceutical composition can replace with the salvianolic acid extract that is obtained by the medicinal raw material Radix Salviae Miltiorrhizae; Tanshinone can replace with the tanshinone extract that is obtained by the medicinal raw material Radix Salviae Miltiorrhizae; Ferulic acid can replace with the Rhizoma Chuanxiong phenolic acid extract that is obtained by the medicinal raw material Rhizoma Chuanxiong, and ligustilide can replace with the Rhizoma Chuanxiong volatile oil extract that is obtained by the medicinal raw material Rhizoma Chuanxiong, and puerarin can replace with the Radix Puerariae flavone extract that is obtained by the medicinal raw material Radix Puerariae.
Above-mentioned experimental result fully shows; With salvianolic acid B, Tanshinone I I A, ferulic acid, ligustilide and puerarin as effective medicinal ingredient; Form trial drug of the present invention, can obviously dwindle the cerebral tissue hemorrhagic necrosis kitchen range that cerebral ischemia reperfusion injury causes, the damage that alleviates neurocyte and nerve fiber.
Claims (14)
1. treat the pharmaceutical composition of cardiovascular and cerebrovascular disease; It is characterized in that with salvianolic acid B, tanshinone, ferulic acid, ligustilide, puerarin be effective ingredient, form jointly that the weight of said effective ingredient consists of: 2～10 parts of salvianolic acid Bs with the auxiliary adding ingredient of acceptable in the medicine; 0.1～0.5 part of tanshinone; 0.1～0.5 part of ferulic acid, 0.4～2 part of ligustilide, 2～10 parts of puerarins.
2. pharmaceutical composition as claimed in claim 1 is characterized in that the weight of said effective ingredient consists of: 6 parts of salvianolic acid Bs, 0.4 part of Tanshinone I I A, 0.2 part of ferulic acid, 1 part of ligustilide, 5 parts of puerarins.
3. treat the pharmaceutical composition of cardiovascular and cerebrovascular disease; It is characterized in that with salvianolic acid extract, tanshinone, ferulic acid, ligustilide, puerarin from the medicinal raw material Radix Salviae Miltiorrhizae be effective ingredient, form jointly that the weight of said effective ingredient consists of: the salvianolic acid extract that contains 2～10 parts of salvianolic acid Bs with the auxiliary adding ingredient of acceptable in the medicine; 0.1～0.5 part of tanshinone; 0.1～0.5 part of ferulic acid, 0.4～2 part of ligustilide, 2～10 parts of puerarins.
4. treat the pharmaceutical composition of cardiovascular and cerebrovascular disease; It is characterized in that with salvianolic acid B, the tanshinone extract from the medicinal raw material Radix Salviae Miltiorrhizae, ferulic acid, ligustilide, puerarin be effective ingredient, form jointly that the weight of said effective ingredient consists of: 2～10 parts of salvianolic acid Bs with the auxiliary adding ingredient of acceptable in the medicine; The tanshinone extract that contains 0.1～0.5 part of Tanshinone I I A; 0.1～0.5 part of ferulic acid, 0.4～2 part of ligustilide, 2～10 parts of puerarins.
5. treat the pharmaceutical composition of cardiovascular and cerebrovascular disease; It is characterized in that with salvianolic acid B, tanshinone, the Rhizoma Chuanxiong phenolic acid extract from the medicinal raw material Rhizoma Chuanxiong, ligustilide, puerarin be effective ingredient, form jointly that the weight of said effective ingredient consists of: 2～10 parts of salvianolic acid Bs with the auxiliary adding ingredient of acceptable in the medicine; 0.1～0.5 part of tanshinone; The Rhizoma Chuanxiong phenolic acid extract that contains 0.1～0.5 part of ferulic acid, 0.4～2 part of ligustilide, 2～10 parts of puerarins.
6. treat the pharmaceutical composition of cardiovascular and cerebrovascular disease; It is characterized in that with salvianolic acid B, Tanshinone I I A, ferulic acid, from Rhizoma Chuanxiong volatile oil extract, the puerarin of medicinal raw material Rhizoma Chuanxiong be effective ingredient, form jointly that the weight of said effective ingredient consists of: 2～10 parts of salvianolic acid Bs with the auxiliary adding ingredient of acceptable in the medicine; 0.1～0.5 part of tanshinone; 0.1～0.5 part of ferulic acid contains the Rhizoma Chuanxiong volatile oil extract of 0.4～2 part of ligustilide, 2～10 parts of puerarins.
7. treat the pharmaceutical composition of cardiovascular and cerebrovascular disease; It is characterized in that with salvianolic acid B, Tanshinone I I A, ferulic acid, ligustilide, from the Radix Puerariae flavone extract of medicinal raw material Radix Puerariae be effective ingredient, form jointly that the weight of said effective ingredient consists of: 2～10 parts of salvianolic acid Bs with the auxiliary adding ingredient of acceptable in the medicine; TANSHINONES HA0.1～0.5 part; 0.1～0.5 part of ferulic acid, 0.4～2 part of ligustilide contains the Radix Puerariae flavone extract of 2～10 parts of puerarins.
8. like the described pharmaceutical composition of one of claim 1 to 7, it is characterized in that being oral formulations.
9. the method for preparing the pharmaceutical composition of one of claim 1 to 8 said treatment cardiovascular and cerebrovascular disease; After it is characterized in that obtaining said effective ingredient by medicinal raw material Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong and Radix Puerariae respectively, be prepared from the auxiliary adding ingredient of acceptable in said ratio and the medicine.
10. like the preparation of drug combination method of the said treatment cardiovascular and cerebrovascular disease of claim 4, it is characterized in that the tanshinone extract in the said effective ingredient adopts one of following manner to prepare:
Method 1: with supercritical carbon dioxide circulation reflux type the Radix Salviae Miltiorrhizae after pulverizing is extracted the back and separate, obtain the effective ingredient tanshinone extract;
Method 2: after with the alcoholic solution of volume content >=80% Radix Salviae Miltiorrhizae after pulverizing being extracted, extracting solution is removed ethanol, and deposition is filtered, and obtains the effective ingredient tanshinone extract;
Method 3: the alcoholic solution with volume content >=80% extracts the Radix Salviae Miltiorrhizae after pulverizing, and extracting solution is removed ethanol, concentrates, and drying obtains the effective ingredient tanshinone extract.
11., it is characterized in that the salvianolic acid extract in the said effective ingredient adopts one of following manner to prepare like the preparation of drug combination method of the said said treatment cardiovascular and cerebrovascular disease of claim 3:
Method 1: behind medicinal raw material Radix Salviae Miltiorrhizae extraction tanshinone extract, residue extracts through the ethanol-water mixed solvent of water or volume content≤80%, reclaims solvent, concentrates, and drying obtains effective ingredient salvianolic acid extract;
Method 2: after extracting tanshinone extract by the medicinal raw material Radix Salviae Miltiorrhizae, residue extracts through the ethanol-water mixed solvent of water or volume content≤80%, the water extract or remove ethanol after extracting solution; After macroporous resin column absorption and water washing remove impurity; The use alcohol volume content is alcohol-water mixed liquid eluting of 40～80%, collects eluent and also removes ethanol, concentrates; Drying obtains effective ingredient salvianolic acid extract.
12., it is characterized in that the Rhizoma Chuanxiong volatile oil extract in the said effective ingredient adopts one of following manner to prepare like the preparation of drug combination method of the said treatment cardiovascular and cerebrovascular disease of claim 6:
Method 1: after with supercritical carbon dioxide circulation reflux type the Rhizoma Chuanxiong after pulverizing being extracted, separate, obtain effective ingredient Rhizoma Chuanxiong volatile oil extract;
Method 2: get Rhizoma Chuanxiong; Pulverize, use lower boiling organic solvent extraction, after separation is removed and extracted organic solvent; Obtain effective ingredient Rhizoma Chuanxiong volatile oil extract, said extraction solvent is at least a in petroleum ether, gasoline, No. 6 solvent naphthas, normal hexane and the cyclohexane extraction;
Method 3: get Rhizoma Chuanxiong, extract with the alcoholic solution of volume content >=80%, extracting solution is removed ethanol, concentrates, and drying obtains effective ingredient Rhizoma Chuanxiong volatile oil extract.
13., it is characterized in that the Rhizoma Chuanxiong phenolic acid extract in the said effective ingredient adopts one of following manner to prepare like the preparation of drug combination method of the said treatment cardiovascular and cerebrovascular disease of claim 5:
Method 1: behind medicinal raw material Rhizoma Chuanxiong extraction Rhizoma Chuanxiong volatile oil extract, residue extracts with the ethanol-water mixed solvent of water or volume content≤80%, reclaims solvent, concentrates, and drying obtains effective ingredient Rhizoma Chuanxiong phenolic acid extract;
Method 2: after extracting the Rhizoma Chuanxiong volatile oil extract by the medicinal raw material Rhizoma Chuanxiong, residue extracts with the ethanol-water mixed solvent of water or volume content≤80%, the water extract or remove ethanol after extracting solution; After macroporous resin column absorption and water washing remove impurity; The use alcohol volume content is alcohol-water mixed liquid eluting of 30～70%, collects eluent and also removes ethanol, concentrates; Drying obtains effective ingredient Rhizoma Chuanxiong phenolic acid extract.
14., it is characterized in that the Radix Puerariae flavone extract in the said effective ingredient adopts one of following manner to prepare like the preparation of drug combination method of the said treatment cardiovascular and cerebrovascular disease of claim 7:
Method 1: Radix Puerariae is pulverized, and decocting boils after-filtration, and filtrating is after macroporous resin column absorption and water washing remove impurity; The use alcohol volume content is alcohol-water mixed liquid eluting of 60～80%, collects eluent and also removes ethanol, concentrates; Drying obtains the Radix Puerariae flavone extract of effective ingredient;
Method 2: Radix Puerariae is pulverized, and the ethanol-water mixed solvent of water or volume content≤80% extracts, and reclaims solvent, concentrates, and drying obtains the Radix Puerariae flavone extract of effective ingredient.
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| CN103585159A (en) * | 2013-12-02 | 2014-02-19 | 四川省中医药科学院 | Composition with hypoglycemic effect, and preparation and drug thereof |
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| CN113499333A (en) * | 2021-08-30 | 2021-10-15 | 北京中医药大学 | Application of caffeic acid in preparing medicine for improving myocardial hypertrophy |
| CN114469934B (en) * | 2022-02-11 | 2023-08-25 | 津药达仁堂集团股份有限公司第六中药厂 | Composition and pharmaceutical preparation thereof |
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