CN103372053A - Medicinal composition for treating cardiovascular and cerebrovascular diseases and preparation method of medicament - Google Patents
Medicinal composition for treating cardiovascular and cerebrovascular diseases and preparation method of medicament Download PDFInfo
- Publication number
- CN103372053A CN103372053A CN 201210118717 CN201210118717A CN103372053A CN 103372053 A CN103372053 A CN 103372053A CN 201210118717 CN201210118717 CN 201210118717 CN 201210118717 A CN201210118717 A CN 201210118717A CN 103372053 A CN103372053 A CN 103372053A
- Authority
- CN
- China
- Prior art keywords
- extract
- salviae miltiorrhizae
- radix ginseng
- radix salviae
- solution
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Abstract
The invention discloses a medicinal composition for treating cardiovascular and cerebrovascular diseases and a preparation method of the medicament. The medicament is prepared from a ginseng extract, a red-rooted salvia root extract and a hemlock parsley extract according to a certain weight proportion, wherein the ginseng extract, the red-rooted salvia root and the hemlock parsley extract can be obtained by commercial way or extracted from medicinal materials. The medicament can be prepared to form an arbitrary pharmaceutically acceptable preparation, preferably pills. The medicament has effects of tonifying qi and activating blood circulation, can be used for treating cardiovascular and cerebrovascular diseases, in particular treating acute and early recovery phase of cerebral thrombosis, cerebral ischemia, cerebral infarction and other ischemic cerebrovascular diseases.
Description
Technical field
The present invention relates to a kind of pharmaceutical composition that is used for the treatment of cardiovascular and cerebrovascular disease and preparation method thereof, be used in particular for treating ischemic encephalopathy, belong to the field of Chinese medicines.
Background technology
Cerebral ischemia claims again Ischemic Stroke, cerebral infarction, and the traditional Chinese medical science belongs to the category of apoplexy, is that a class is because cerebral blood flow is supplied the disease that obstacle causes ischemia, anoxia, causes the necrosis of brain limitation or cerebral malacia.Ischemic brain injury comprises ischemic stage primary injury and flush phase secondary injury again, and the initiating link in its pathological process is ischemia, and the hemoperfusion that recovers cerebral tissue is its treatment basis, but it is then inevitable to pour into secondary injury again.Ischemic cerebrovascular is very harmful.Data shows in 57 countries, have 40 countries that the mortality rate of ischemic cerebrovascular has been listed in front 3, wherein ranks first in Japan and China.In developed country, the acute ischemic cerebral apoplexy mortality rate surpasses Several Kinds of Malignancy, is the 2nd large cause of disease that causes death, and also is to cause the long-term handicapped common disease of adult.Except the strike to patient and family, also caused heavy financial burden.Die from apoplexy (apoplexy) person domestic every year 1600000 crowd is arranged, and new cases 1,500,000 people are arranged, total number of patients surpasses 5,000,000 people, wherein the sickness rate of cerebral infarction is far above hemorrhagic cerebral apoplexy, account for the 70%-80% of apoplexy sum, and along with the process of aged tendency of population, the cerebral infarction sickness rate rises year by year.Therefore, research cerebral ischemia and reperfusion damage mechanism, the medicine of research and development control cerebral ischemia and reperfusion damage, reduce mortality rate and the disability rate of ischemic cerebrovascular, study a kind of cardiovascular and cerebrovascular disease for the treatment of, and be used in particular for treating the medicine of ischemic encephalopathy, be current be an important topic of sanitary work and scientific research.
At present Chinese medicine only has the only a few single preparations of ephedrine and by the compound preparation of two active regions in the medicine for the treatment of apoplexy, for example patent retrieval to application number be 200310103833, Radix Salviae Miltiorrhizae+Rhizoma Chuanxiong of 200710127787, application number is Radix Ginseng+Rhizoma Chuanxiong of 200410065378, application number is 200510021321, Radix Ginseng+Radix Salviae Miltiorrhizae of 200410074598, but on the link that most pathology that have at ischemic cerebrovascular improve dynamics not and the unclear weak tendency of effect composition, cause being difficult to use separately in clinical in the ischemic cerebrovascular acute stage, have certain limitation.
The present invention forms a Chinese medicine by Radix Ginseng extract, Radix Salviae Miltiorrhizae extract and Rhizoma Chuanxiong extract and newly fills a prescription, dosage form is ejection preparation, preferred lyophilized injectable powder, belong to Yiqi Huoxue Recipe, both can be used for suffering from acute stroke and recovered early stage, can be used for again stroke in convalescent stage, Western medicine mechanism of action and the single defective of target spot have been overcome, avoided the inadequate and unclear inferior position of action component of Chinese medicine effect dynamics, given full play to multi-level, the multipath of Chinese medicine, the Action advantage of many target spots, be existing in, Western medicine is incomparable.And compare with general formulation, injection has unique dosage form advantage, and it is reliable rapidly to show as effect, not affected by pH, enzyme, food etc., without first pass effect, is suitable for rescuing the usefulness of critical illness.And morbidity is anxious, the state of an illness is critical because cerebral infarction has, change the characteristics such as fast, therefore utilizes the advantage of injection to carry out in time the patient, rationally, effectively treat, and can obtain better therapeutic effect.And the new prescription composition of the three flavor medicines that the present invention relates to is clear, and mechanism of action is clear and definite, and quality safety is controlled, is that existing Chinese medicine can not be compared.
Summary of the invention
The purpose of this invention is to provide a kind of new pharmaceutical composition, said composition has the effect of benefiting QI for activating blood circulation, be used for the treatment of cardiovascular and cerebrovascular disease, especially for treatment and prevention cerebral ischemia and cerebral ischemia reperfusion injury, be applicable to suffering from acute stroke, recover early stage blood stasis due to qi deficiency disease, disease is seen hemiplegia, crooked mouth and tongue, aphasia, refreshing tired weak.
Another object of the present invention provides the preparation method of aforementioned pharmaceutical compositions.
The present invention is achieved by the following technical solutions:
Pharmaceutical composition of the present invention is to be formed by Radix Ginseng extract, Radix Salviae Miltiorrhizae extract, Rhizoma Chuanxiong extract prescription, specifically, is made by the crude drug of following weight portion: Radix Ginseng extract 1-200 part, Radix Salviae Miltiorrhizae extract 1-300 part, Rhizoma Chuanxiong extract 1-200 part.
Be preferably: Radix Ginseng extract 1-100 part, Radix Salviae Miltiorrhizae extract 1-60 part, Rhizoma Chuanxiong extract 1-60 part.
More preferably: Radix Ginseng extract 3-80 part, Radix Salviae Miltiorrhizae extract 5-55 part, Rhizoma Chuanxiong extract 3-50 part.
Continue to be preferably: Radix Ginseng extract 5-70 part, Radix Salviae Miltiorrhizae extract 6-50 part, Rhizoma Chuanxiong extract 4-45 part.
More preferably: Radix Ginseng extract 10-60 part, Radix Salviae Miltiorrhizae extract 7-40 part, Rhizoma Chuanxiong extract 5-40 part.
The Radix Ginseng extract that this paper mentions can be Radix Ginseng total saponins; Radix Salviae Miltiorrhizae extract can be Radix Salviae Miltiorrhizae total phenolic acids; Rhizoma Chuanxiong extract can be ligustrazine or ligustrazine hydrochloride or ligustrazine phosphate or its pharmaceutical salts;
Make pharmaceutical composition of the present invention can also for:
Radix Ginseng total saponins 20-50 part, Radix Salviae Miltiorrhizae total phenolic acids 10-30 part, ligustrazine or ligustrazine hydrochloride or ligustrazine phosphate or its pharmaceutical salts 8-30 part.
Specifically can be:
80 parts of 48 parts of Radix Ginseng total saponinss, 200 parts of Radix Salviae Miltiorrhizae total phenolic acidss, ligustrazine or ligustrazine hydrochloride or ligustrazine phosphate or its pharmaceutical salts.
40 parts of 48 parts of Radix Ginseng total saponinss, 50 parts of Radix Salviae Miltiorrhizae total phenolic acidss, ligustrazine or ligustrazine hydrochloride or ligustrazine phosphate or its pharmaceutical salts.
20 parts of 48 parts of Radix Ginseng total saponinss, 25 parts of Radix Salviae Miltiorrhizae total phenolic acidss, ligustrazine or ligustrazine hydrochloride or ligustrazine phosphate or its pharmaceutical salts.
Above-described Radix Ginseng extract or Radix Ginseng total saponins, Radix Salviae Miltiorrhizae extract or Radix Salviae Miltiorrhizae total phenolic acids, Rhizoma Chuanxiong extract are to prepare by the following method:
Radix Ginseng total saponins is like this preparation: the people participates in the alcohol reflux of variable concentrations, merge extractive liquid,, concentrating under reduced pressure Recycled ethanol, upper macroporous resin column absorption, washing resin is used ethanol elution, collect ethanol elution, Recycled ethanol adds the suitable quantity of water dissolving, filter, filtrate adds organic solvent extraction, collects extract, dehydration, reclaim organic solvent, drying under reduced pressure, and get final product;
Radix Salviae Miltiorrhizae total phenolic acids is like this preparation: Radix Salviae Miltiorrhizae powder is broken into coarse powder, the acid adding aqueous solution soaking, and percolation extracts, collect percolate, filter, macroporous resin column absorption on the filtrate, use respectively alcoholic solution, the ethanol elution of aqueous acid, acidify, collect eluent, Recycled ethanol, suitably concentrated, and adjust pH is to acidity, organic solvent extraction, collect extract, organic solvent is reclaimed in dehydration, drying under reduced pressure, and get final product;
Rhizoma Chuanxiong extract is like this preparation: gets Rhizoma Chuanxiong power and is broken into coarse powder, and the water saturated organic solvent extraction of acid adding, merge extractive liquid,, the reclaim under reduced pressure organic solvent, residue adds dissolve with ethanol, decompression recycling ethanol, drying under reduced pressure, and get final product.
Be preferably:
Radix Ginseng total saponins is like this preparation: the people participates in 6-12 and doubly measures the 50-95% alcohol reflux 1-4 time, each 1-3 hour, merge extractive liquid,, concentrating under reduced pressure Recycled ethanol, upper macroporous resin column absorption, 10-50% alcoholic solution washing resin with alkalization, and be washed till neutrality with purified water, and use the 50-95% ethanol elution, collect ethanol elution, Recycled ethanol, add the suitable quantity of water dissolving, ultrafiltrate is collected in ultrafiltration, add n-butanol extraction 1-7 time, collect n-butyl alcohol liquid, n-butyl alcohol is reclaimed in dehydration, drying under reduced pressure, and get final product; Wherein, the 10-50% alcoholic solution of alkalization refers to the 10-50% alcoholic solution of 0.5% sodium bicarbonate; Dehydration refers to dewater with anhydrous magnesium sulfate.
Radix Salviae Miltiorrhizae total phenolic acids is like this preparation: Radix Salviae Miltiorrhizae powder is broken into coarse powder, adds 2-6 and doubly measures aqueous acid immersion 2-6 hour, and the aqueous acid percolation extracts, collect 10-20 and doubly measure percolate, filter, macroporous resin column absorption on the filtrate, use respectively 10-50% alcoholic solution, the 50-95% ethanol elution of aqueous acid, acidify, collect eluent, Recycled ethanol, suitably concentrated, and adjust pH adds ethyl acetate extraction 1-7 time to 1-2, collect acetic acid ethyl fluid, ethyl acetate is reclaimed in dehydration, drying under reduced pressure, and get final product; Wherein, aqueous acid refers to the 0.01mol/L hydrochloric acid solution; Dehydration refers to dewater with anhydrous magnesium sulfate.
Rhizoma Chuanxiong extract is like this preparation: get Rhizoma Chuanxiong power and be broken into coarse powder, add the water saturated ethyl acetate backflow of pH=3.0 acid and extract each 1-3 hour 1-4 time, merge extractive liquid,, the reclaim under reduced pressure ethyl acetate, residue adds the 50-95% dissolve with ethanol, decompression recycling ethanol, drying under reduced pressure, and get final product.
Wherein, the Radix Ginseng mentioned of this paper can also be Folium Ginseng or Stem and leaf of Radix Ginseng or Leptoradix Ginseng or remove Lu Rencan or Herba Herminii or Radix Ginseng or Radix Ginseng Rubra or Radix Ginseng processed product; Radix Salviae Miltiorrhizae can also be Radix Salviae Miltiorrhizae, Salvia przewalskii Maxim., Salvia miltiorrhiza Bge or Radix Salviae Miltiorrhizae processed product; Rhizoma Chuanxiong can also be that wine Rhizoma Chuanxiong (parched), Rhizoma Zingiberis Recens are processed Rhizoma Chuanxiong, vinegar Rhizoma Chuanxiong (processed), steeping in wine parched with bran Rhizoma Chuanxiong.
Radix Ginseng total saponins accounts for more than 65% of Radix Ginseng extract total solids content; Radix Salviae Miltiorrhizae total phenolic acids accounts for more than 75% of Radix Salviae Miltiorrhizae extract total solids content; Ferulic acid is that the phenol of representative and phthalide-type sum that ligustilide is representative account for more than 50% of Rhizoma Chuanxiong extract total solids content.
Radix Ginseng extract, Radix Salviae Miltiorrhizae extract, Rhizoma Chuanxiong extract, Radix Ginseng total saponins, Radix Salviae Miltiorrhizae total phenolic acids, ligustrazine or ligustrazine hydrochloride or ligustrazine phosphate or its pharmaceutical salts can also be by commercially available direct acquisitions.
The active component of medicine of the present invention can directly be used as medicine take or add on the pharmaceutics acceptable adjuvant routinely technique be prepared into required preparation.As making the oral drugs of the solid preparation forms such as tablet commonly used (dispersible tablet, effervescent tablet, oral cavity disintegration tablet, buccal tablet, chewable tablet, effervescent tablet), capsule (hard capsule, soft capsule), granule, pill (drop pill), powder, also can make the oral drugs of the liquid preparation forms such as syrup, oral liquid; Can also make the external used medicine of the external preparation forms such as unguentum, gel, ointment, cataplasma, emplastrum, liniment, lotion, liniment.Therefore, except effective ingredient, can also contain pharmaceutically acceptable adjuvant in this pharmaceutical composition.
Adjuvant described here can be different according to different preparations, such as diluent commonly used in the solid preparations such as tablet, capsule, granule, disintegrating agent, excipient, binding agent, lubricant, surfactant, filler etc.; The surfactant of in the liquid preparation forms such as syrup, oral liquid, commonly using, diluent, antiseptic, stabilizing agent, correctives, thickening agent, fluidizer etc.; The medicinal oleaginous base of in the external preparation forms such as gel, ointment, commonly using, aqueous matrix, antiseptic, antioxidant, wetting agent, Percutaneous absorption enhancer, surfactant etc.
Its adjuvant commonly used such as starch, lactose, dextrin, Icing Sugar, microcrystalline Cellulose, mannitol, xylitol, Polyethylene Glycol, calcium sulfate, calcium hydrogen phosphate, calcium carbonate, modified starch, sorbitol, polyvidon, Heavy Magnesium Carbonate, sodium carboxymethyl cellulose, hydroxypropyl methylcellulose, methylcellulose, ethyl cellulose, carboxymethylstach sodium, hydroxypropyl cellulose, PVP K30, betacyclodextrin, kaolin, pregelatinized Starch, magnesium stearate, Pulvis Talci, micropowder silica gel, stevioside, betanin, aspartame, glycyrrhizin, saccharin sodium, citric acid, sodium bicarbonate, sodium carbonate, carrageenan, agar, gelatin, sodium alginate, xanthan gum, guar gum, tragcanth, arabic gum, locust bean gum, POLY-karaya, stearic acid, glyceryl monostearate, polyacrylamide, cross linked sodium polyacrylate, polyvinyl alcohol, carbomer, sorbic acid, potassium sorbate, ethyl hydroxybenzoate, benzyl alcohol, nipalgin, thimerosal, dimethyl sulfoxide, azone, triethanolamine, sodium hydroxide, glycerol, propylene glycol, BHT, BHA, sodium lauryl sulphate, Tweens, spans etc.
For the above-mentioned preparation of mentioning, pharmaceutical composition of the present invention is that technique prepares injection, injectable sterile powder, Injectable sterile block, concentrated solution for injection routinely.
Wherein, injectable sterile powder is like this preparation:
Method one: get Rhizoma Chuanxiong extract and add an amount of water for injection dissolving, get solution A; Get Radix Salviae Miltiorrhizae extract and add the dissolving of an amount of water for injection, and adjust pH is to 6-7, stirring and dissolving gets solution B; Keep stirring, solution A is added in the solution B, and adjust pH gets solution C to 6-7; Gets Radix Ginseng extract and an amount of mannitol injects the dissolving of blunging, mixes with solution C, stir, and adjust pH is to 6-7, inject water to quantitative, activated carbon adsorption, filtration, filtering with microporous membrane, packing, lyophilization, and get final product.
Method two: get Radix Ginseng extract, Radix Salviae Miltiorrhizae extract, Rhizoma Chuanxiong extract and add an amount of water for injection dissolving, add mannitol, stir evenly, the sodium hydroxide solution adjust pH of 1mol/L is to 6-7, inject water to quantitatively, microporous filter membrane filters, fine straining, packing, lyophilization, and get final product.
Injection is like this preparation:
Get Radix Ginseng extract, Radix Salviae Miltiorrhizae extract, Rhizoma Chuanxiong extract and add an amount of water for injection dissolving, add or do not add adjuvant, stir evenly, adjust pH injects water to quantitatively, and microporous filter membrane filters, fine straining, and packing, sterilization, and get final product.
The Injectable sterile block is like this preparation:
Get Radix Ginseng extract, Radix Salviae Miltiorrhizae extract, Rhizoma Chuanxiong extract and add an amount of water for injection dissolving, add or do not add adjuvant, stir evenly, adjust pH injects water to quantitatively, and microporous filter membrane filters, fine straining, and packing, lyophilization, and get final product.
Concentrated solution for injection is like this preparation:
Get Radix Ginseng extract, Radix Salviae Miltiorrhizae extract, Rhizoma Chuanxiong extract and add an amount of water for injection dissolving, add or do not add adjuvant, stir evenly, technique prepares concentrated solution for injection routinely.
Drug mechanism of the present invention and compatibility of drugs principle of the present invention are as follows:
Prescription of the present invention with the Qi-tonifying drug Radix Ginseng as monarch drug, wherein Radix Ginseng strongly invigorating primordial QI, invigorating the spleen to benefit the lung, the Fructus Alpiniae Oxyphyllae of promoting the production of body fluid, calm the nerves, the gas of kind spleen reinforcing lung.The strong fortune of temper, lung qi a surname is smooth, and then expectorant is turbid can reach the purpose of strengthening vital QI to eliminate pathogenic factors from disappearing, the medicine that effects a permanent cure for apoplexy.Radix Salviae Miltiorrhizae is ministerial drug, and stasis-dispelling and pain-killing, promoting blood circulation to restore menstrual flow, the relieving restlessness that clears away heart-fire are the key medicine of blood circulation promoting and blood stasis dispelling, are widely used in various blood stasis diseases.Rhizoma Chuanxiong is adjuvant drug, promoting QI circulation for relieving depression, dispeiling pathogenic wind and removing dampness, promoting blood circulation and stopping pain.Ancient Chinese medicine doctor thinks that it is apt to control apoplexy, is " the gas medicine in the blood ", " controlling the wind panacea ".Radix Salviae Miltiorrhizae and ginseng compatibility, for the pathogenesis blood stasis due to qi deficiency of apoplexy, QI invigorating and blood circulation promoting and blood stasis dispelling are worked along both lines, and complement each other.Rhizoma Chuanxiong is not only gone up thorough brains and is controlled wind, and simultaneously conducting blood to flow downwards enters again blood system, the descending sea of blood that reaches, and function of promoting blood circulation to disperse blood clots is extensive, and the suitable various diseases of stagnation of blood stasis have played the effect of getting twice the result with half the effort to the inrigorating qi and promoting blood circulation function of Radix Ginseng and Radix Salviae Miltiorrhizae.Three medicine compatibilities, benefiting QI for activating blood circulation, eliminating blood stasis and smoothing collaterals brings out the best in each other.
Radix Ginseng extract: be the total saponins of root through being processed into of Araliaceae Radix Ginseng Panax ginseng C.A.Mey..Radix Ginseng has that strongly invigorating primordial QI, multiple arteries and veins take off admittedly, invigorating the spleen to benefit the lung, the effect of promoting the production of body fluid, calming the nerves.Can effectively alleviate the neurological functional deficit of patients with acute cerebral infarction in the Radix Ginseng as main preparation take ginsenoside Rg1, Re, improve its daily life active ability, improve Quality of Life, to the Internal Carotid System patients with acute ischemic cerebral stroke, can improve lighter patient's short-term prognosis and heavier patient's long-term prognosis, therapeutic effect is obvious.
Radix Salviae Miltiorrhizae extract: get for the root and rhizome of labiate Radix Salviae Miltiorrhizae Salvia Miltiorrhiza Bge. extracts.Radix Salviae Miltiorrhizae has stasis-dispelling and pain-killing, promoting blood circulation to restore menstrual flow, the effect of the relieving restlessness that clears away heart-fire.Radix Salviae Miltiorrhizae total phenolic acids effective site by anticoagulant, antithrombotic, removing free radical, improve microcirculation and anticoagulant, inhibition excitatory amino acid, remove oxygen-derived free radicals, antagonism Ca
2+Effect, the unconventionality expression of removing the nitric oxide synthase gene due to oxygen-derived free radicals, the downward modulation cerebral ischemia, inhibited apoptosis, neuroprotective cell etc., have obvious treating cerebral ischemia.
Rhizoma Chuanxiong extract: get for samphire Rhizoma Chuanxiong Ligusticum chuanxiong Hort. rhizome extracts.Rhizoma Chuanxiong has the effect of blood-activating and qi-promoting, wind-expelling pain-stopping.Ligustrazine is used for the treatment of ischemic cerebrovascular clinically; obtain good therapeutic effect; its mechanism of action is blood vessel dilating, improves microcirculation, blood circulation promoting and blood stasis dispelling, antithrombotic, blood viscosity lowering, anticoagulant, inhibition calcium overload, alleviates free radical and vascular endothelial cell damage, neuroprotective, alleviates the ischemic injuries of cortical neurogenic cell etc., and reperfusion injury has protective effect to cerebral hypoxia ischemia.
The present invention selects Radix Ginseng extract, Radix Salviae Miltiorrhizae extract and Rhizoma Chuanxiong extract compatibility, both can be used for suffering from acute stroke, can be used for again apoplexy and recover early stage, Western medicine mechanism of action and the single defective of target spot have been overcome, avoided the inadequate and unclear inferior position of action component of Chinese medicine effect dynamics, given full play to multi-level, the multipath of Chinese medicine, the Action advantage of many target spots, be existing in, Western medicine is incomparable.
Medicine of the present invention has the effect of benefiting QI for activating blood circulation; be applicable to suffering from acute stroke, recover early stage blood stasis due to qi deficiency disease; disease is seen hemiplegia; crooked mouth and tongue; dysphasia, refreshing tired weak, be used for the treatment of the ischemic cerebrovascular such as cerebral blood supply insufficiency, cerebral thrombosis, cerebral infarction; protection cerebral ischemia (comprise ischemic stage primary injury and flush phase secondary injury again, be used in particular for pouring into again secondary injury).
Medicine of the present invention has antiplatelet aggregation, blood viscosity lowering, anticoagulant, thrombolytic, inhibition thrombosis, blood fat reducing, improves microcirculation, increases blood flow and the pharmacological actions such as flow velocity, blood vessel dilating.
Pharmaceutical composition of the present invention also can be applicable to other cardiovascular and cerebrovascular diseases, for example, myocardial ischemia, myocardial ischemia reperfusion injury, angina pectoris, hypertension, pours into arrhythmia, acute myocardial infarction, thromboangiitis obliterans etc. again.
Pharmaceutical composition of the present invention also can be used for other ischemic diseasess, for example, and intestinal ischemia, hepatic ischemia, ischemia of lung etc.
Pharmaceutical composition of the present invention also can be applied to according to its mechanism of action the treatment of other diseases, for example, heart failure, chronic pulmonary heart disease, fetal in utero poor growth, chronic hepatitis B, pregnancy induced hypertension syndrome, diabetic neuropathy, adult respiratory distress syndrome, bronchopneumonia, chronic obstructive pneumonia etc.
The safety of Chinese medicine is a hot issue during drug safety is estimated always, existing Chinese medicine kind exists much that composition is indefinite, quality is uncontrollable, batch between the quality homogeneity is bad, safety is stable not problem.Because the existing Chinese medicine that contains Radix Ginseng or Radix Salviae Miltiorrhizae or Rhizoma Chuanxiong is to adopt traditional water alcohol technique to make mostly, composition is indefinite, unstable because of one-tenth split poles such as salvianolic acid Bs again, when adding precipitate with ethanol because a large amount of separating out of carbohydrate content and wrapped and adsorb, the rate of transform that causes extracting these determined curative effect compositions in the purge process is quite low, and traditional water decoction-alcohol sedimentation technique is to resin, tannin, protein, oxalates, the removal of the harmful substances such as macromole endogenous material is extremely limited, be difficult to these harmful components are thoroughly removed, salvianolic acid B is extremely unstable in liquid preparation in addition, this is so that the amount of these effective ingredient is difficult to control in finished product, the stability of the quality of the pharmaceutical preparations, controllability, effectiveness, batch between the quality homogeneity particularly safety be difficult to be guaranteed, brought very large hidden danger to clinical application.
Ejection preparation of the present invention adopts modern extraction and purification process to replace traditional handicraft, the development definite ingredients, quality controllable, stable, criticize between the quality homogeneity good, be the reliable Chinese medicine of application safety, curative effect.
The specific embodiment
The specific embodiment of form is described in further detail foregoing of the present invention by the following examples.But this should be interpreted as that the scope of the above-mentioned theme of the present invention only limits to following embodiment.All technology that realizes based on foregoing of the present invention all belong to scope of the present invention.
Embodiment 1
Radix Ginseng total saponins 35g Radix Salviae Miltiorrhizae total phenolic acids 20g ligustrazine hydrochloride 20g
Get ligustrazine hydrochloride and add an amount of water for injection dissolving, get solution A; Get Radix Salviae Miltiorrhizae total phenolic acids and add the dissolving of an amount of water for injection, and adjust pH is to 6-7, stirring and dissolving gets solution B; Keep stirring, solution A is added in the solution B, and adjust pH gets solution C to 6-7; Gets Radix Ginseng total saponins and an amount of mannitol injects the dissolving of blunging, mixes with solution C, stir, and adjust pH is to 6-7, inject water to quantitative, activated carbon adsorption, filtration, filtering with microporous membrane, packing, lyophilization namely gets injectable sterile powder.
Embodiment 2
Radix Ginseng total saponins 50g Radix Salviae Miltiorrhizae total phenolic acids 10g ligustrazine 8g
Get ligustrazine and add an amount of water for injection dissolving, get solution A; Get Radix Salviae Miltiorrhizae total phenolic acids and add the dissolving of an amount of water for injection, and adjust pH is to 6-7, stirring and dissolving gets solution B; Keep stirring, solution A is added in the solution B, and adjust pH gets solution C to 6-7; Gets Radix Ginseng total saponins and an amount of mannitol injects the dissolving of blunging, mixes with solution C, stir, and adjust pH is to 6-7, inject water to quantitative, activated carbon adsorption, filtration, filtering with microporous membrane, packing, lyophilization namely gets injectable sterile powder.
Embodiment 3
Radix Ginseng total saponins 20g Radix Salviae Miltiorrhizae total phenolic acids 30g ligustrazine phosphate 30g
Get ligustrazine phosphate and add an amount of water for injection dissolving, get solution A; Get Radix Salviae Miltiorrhizae total phenolic acids and add the dissolving of an amount of water for injection, and adjust pH is to 6-7, stirring and dissolving gets solution B; Keep stirring, solution A is added in the solution B, and adjust pH gets solution C to 6-7; Gets Radix Ginseng total saponins and an amount of mannitol injects the dissolving of blunging, mixes with solution C, stir, and adjust pH is to 6-7, inject water to quantitative, activated carbon adsorption, filtration, filtering with microporous membrane, packing, lyophilization namely gets injectable sterile powder.
Embodiment 4
Radix Ginseng total saponins 48g Radix Salviae Miltiorrhizae total phenolic acids 25g ligustrazine hydrochloride 20g
Get ligustrazine hydrochloride and add an amount of water for injection dissolving, get solution A; Get Radix Salviae Miltiorrhizae total phenolic acids and add the dissolving of an amount of water for injection, and adjust pH is to 6-7, stirring and dissolving gets solution B; Keep stirring, solution A is added in the solution B, and adjust pH gets solution C to 6-7; Gets Radix Ginseng total saponins and an amount of mannitol injects the dissolving of blunging, mixes with solution C, stir, and adjust pH is to 6-7, inject water to quantitative, activated carbon adsorption, filtration, filtering with microporous membrane, packing, lyophilization namely gets injectable sterile powder.
Embodiment 5
Radix Ginseng extract 10g Radix Salviae Miltiorrhizae extract 40g Rhizoma Chuanxiong extract 40g
Get Rhizoma Chuanxiong extract and add an amount of water for injection dissolving, get solution A; Get Radix Salviae Miltiorrhizae extract and add the dissolving of an amount of water for injection, and adjust pH is to 6-7, stirring and dissolving gets solution B; Keep stirring, solution A is added in the solution B, and adjust pH gets solution C to 6-7; Gets Radix Ginseng extract and an amount of mannitol injects the dissolving of blunging, mixes with solution C, stir, and adjust pH is to 6-7, inject water to quantitative, activated carbon adsorption, filtration, filtering with microporous membrane, packing, lyophilization namely gets injectable sterile powder.
Embodiment 6
Radix Ginseng extract 60g Radix Salviae Miltiorrhizae extract 7g Rhizoma Chuanxiong extract 5g
Get Rhizoma Chuanxiong extract and add an amount of water for injection dissolving, get solution A; Get Radix Salviae Miltiorrhizae extract and add the dissolving of an amount of water for injection, and adjust pH is to 6-7, stirring and dissolving gets solution B; Keep stirring, solution A is added in the solution B, and adjust pH gets solution C to 6-7; Gets Radix Ginseng extract and an amount of mannitol injects the dissolving of blunging, mixes with solution C, stir, and adjust pH is to 6-7, inject water to quantitative, activated carbon adsorption, filtration, filtering with microporous membrane, packing, lyophilization namely gets injectable sterile powder.
Embodiment 7
Radix Ginseng extract 3g Radix Salviae Miltiorrhizae extract 50g Rhizoma Chuanxiong extract 50g
Get Radix Ginseng extract, Radix Salviae Miltiorrhizae extract, Rhizoma Chuanxiong extract and add an amount of water for injection dissolving, add mannitol, stir evenly, the sodium hydroxide solution adjust pH of 1mol/L is to 6-7, inject water to quantitatively, microporous filter membrane filters, fine straining, packing, lyophilization namely gets injectable sterile powder.
Embodiment 8
Radix Ginseng total saponins 48g Radix Salviae Miltiorrhizae total phenolic acids 50g ligustrazine hydrochloride 40g
Get ligustrazine hydrochloride and add an amount of water for injection dissolving, get solution A; Get Radix Salviae Miltiorrhizae total phenolic acids and add the dissolving of an amount of water for injection, and adjust pH is to 6-7, stirring and dissolving gets solution B; Keep stirring, solution A is added in the solution B, and adjust pH gets solution C to 6-7; Gets Radix Ginseng total saponins and an amount of mannitol injects the dissolving of blunging, mixes with solution C, stir, and adjust pH is to 6-7, inject water to quantitative, activated carbon adsorption, filtration, filtering with microporous membrane, packing, lyophilization namely gets injectable sterile powder.
Embodiment 9
Radix Ginseng extract 80g Radix Salviae Miltiorrhizae extract 5g Rhizoma Chuanxiong extract 3g
Get Radix Ginseng extract, Radix Salviae Miltiorrhizae extract, Rhizoma Chuanxiong extract and add an amount of water for injection dissolving, add mannitol, stir evenly, the sodium hydroxide solution adjust pH of 1mol/L is to 6-7, inject water to quantitatively, microporous filter membrane filters, fine straining, packing, lyophilization namely gets injectable sterile powder.
Embodiment 10
Radix Ginseng extract 1g Radix Salviae Miltiorrhizae extract 60g Rhizoma Chuanxiong extract 60g
Get Rhizoma Chuanxiong extract and add an amount of water for injection dissolving, get solution A; Get Radix Salviae Miltiorrhizae extract and add the dissolving of an amount of water for injection, and adjust pH is to 6-7, stirring and dissolving gets solution B; Keep stirring, solution A is added in the solution B, and adjust pH gets solution C to 6-7; Gets Radix Ginseng extract and an amount of mannitol injects the dissolving of blunging, mixes with solution C, stir, and adjust pH is to 6-7, inject water to quantitative, activated carbon adsorption, filtration, filtering with microporous membrane, packing, lyophilization namely gets injectable sterile powder.
Embodiment 11
Radix Ginseng extract 100g Radix Salviae Miltiorrhizae extract 1g Rhizoma Chuanxiong extract 1g
Get Rhizoma Chuanxiong extract and add an amount of water for injection dissolving, get solution A; Get Radix Salviae Miltiorrhizae extract and add the dissolving of an amount of water for injection, and adjust pH is to 6-7, stirring and dissolving gets solution B; Keep stirring, solution A is added in the solution B, and adjust pH gets solution C to 6-7; Gets Radix Ginseng extract and an amount of mannitol injects the dissolving of blunging, mixes with solution C, stir, and adjust pH is to 6-7, inject water to quantitative, activated carbon adsorption, filtration, filtering with microporous membrane, packing, lyophilization namely gets injectable sterile powder.
Embodiment 12
Radix Ginseng extract 200g Radix Salviae Miltiorrhizae extract 1g Rhizoma Chuanxiong extract 1g
Get Rhizoma Chuanxiong extract and add an amount of water for injection dissolving, get solution A; Get Radix Salviae Miltiorrhizae extract and add the dissolving of an amount of water for injection, and adjust pH is to 6-7, stirring and dissolving gets solution B; Keep stirring, solution A is added in the solution B, and adjust pH gets solution C to 6-7; Gets Radix Ginseng extract and an amount of mannitol injects the dissolving of blunging, mixes with solution C, stir, and adjust pH is to 6-7, inject water to quantitative, activated carbon adsorption, filtration, filtering with microporous membrane, packing, lyophilization namely gets injectable sterile powder.
Embodiment 13
Radix Ginseng extract 1g Radix Salviae Miltiorrhizae extract 300g Rhizoma Chuanxiong extract 200g
Get Rhizoma Chuanxiong extract and add an amount of water for injection dissolving, get solution A; Get Radix Salviae Miltiorrhizae extract and add the dissolving of an amount of water for injection, and adjust pH is to 6-7, stirring and dissolving gets solution B; Keep stirring, solution A is added in the solution B, and adjust pH gets solution C to 6-7; Gets Radix Ginseng extract and an amount of mannitol injects the dissolving of blunging, mixes with solution C, stir, and adjust pH is to 6-7, inject water to quantitative, activated carbon adsorption, filtration, filtering with microporous membrane, packing, lyophilization namely gets injectable sterile powder.
Embodiment 14
Radix Ginseng total saponins 58g Radix Salviae Miltiorrhizae total phenolic acids 28g Rhizoma Chuanxiong extract 18g
Get Rhizoma Chuanxiong extract and add an amount of water for injection dissolving, get solution A; Get Radix Salviae Miltiorrhizae total phenolic acids and add the dissolving of an amount of water for injection, and adjust pH is to 6-7, stirring and dissolving gets solution B; Keep stirring, solution A is added in the solution B, and adjust pH gets solution C to 6-7; Gets Radix Ginseng total saponins and an amount of mannitol injects the dissolving of blunging, mixes with solution C, stir, and adjust pH is to 6-7, inject water to quantitative, activated carbon adsorption, filtration, filtering with microporous membrane, packing, lyophilization namely gets injectable sterile powder.
Embodiment 15
Radix Ginseng total saponins 50g Radix Salviae Miltiorrhizae extract 15g ligustrazine 16g
Get ligustrazine and add an amount of water for injection dissolving, get solution A; Get Radix Salviae Miltiorrhizae extract and add the dissolving of an amount of water for injection, and adjust pH is to 6-7, stirring and dissolving gets solution B; Keep stirring, solution A is added in the solution B, and adjust pH gets solution C to 6-7; Gets Radix Ginseng total saponins and an amount of mannitol injects the dissolving of blunging, mixes with solution C, stir, and adjust pH is to 6-7, inject water to quantitative, activated carbon adsorption, filtration, filtering with microporous membrane, packing, lyophilization namely gets injectable sterile powder.
Embodiment 16
Radix Ginseng extract 59g Radix Salviae Miltiorrhizae total phenolic acids 27g ligustrazine hydrochloride 10g
Get Radix Ginseng extract, Radix Salviae Miltiorrhizae total phenolic acids and add an amount of water for injection dissolving, add ligustrazine hydrochloride, it is an amount of to add mannitol, and the sodium hydroxide solution of 1mol/L is regulated pH to 6-7, it is an amount of to inject water, filtering with microporous membrane, fine straining, packing, lyophilization namely gets injectable sterile powder.
Embodiment 17
Radix Ginseng extract 5g Radix Salviae Miltiorrhizae extract 55g Rhizoma Chuanxiong extract 3g
Get Radix Ginseng extract, Radix Salviae Miltiorrhizae extract and add an amount of water for injection dissolving, add Rhizoma Chuanxiong extract, it is an amount of to add mannitol, and the sodium hydroxide solution of 1mol/L is regulated pH to 6-7, it is an amount of to inject water, filtering with microporous membrane, fine straining, packing, lyophilization namely gets the Injectable sterile block.
Embodiment 18
Radix Ginseng extract 90g Radix Salviae Miltiorrhizae extract 3g Rhizoma Chuanxiong extract 50g
Get Radix Ginseng extract, Radix Salviae Miltiorrhizae extract, Rhizoma Chuanxiong extract and add an amount of water for injection dissolving, add or do not add adjuvant, stir evenly, adjust pH injects water to quantitatively, and microporous filter membrane filters, fine straining, and packing, sterilization namely gets injection.
Embodiment 19
Radix Ginseng total saponins 48g Radix Salviae Miltiorrhizae total phenolic acids 25g ligustrazine hydrochloride 20g
Get ligustrazine hydrochloride and add an amount of water for injection dissolving, get solution A; Get Radix Salviae Miltiorrhizae total phenolic acids and add the dissolving of an amount of water for injection, and adjust pH is to 6-7, stirring and dissolving gets solution B; Keep stirring, solution A is added in the solution B, and adjust pH gets solution C to 6-7; Gets Radix Ginseng total saponins and an amount of mannitol injects the dissolving of blunging, mixes with solution C, stir, and adjust pH is to 6-7, inject water to quantitative, activated carbon adsorption, filtration, filtering with microporous membrane, packing, lyophilization namely gets injectable sterile powder.
Embodiment 20
Radix Ginseng extract 10g Radix Salviae Miltiorrhizae extract 10g Rhizoma Chuanxiong extract 40g
Get Radix Ginseng extract, Radix Salviae Miltiorrhizae extract, Rhizoma Chuanxiong extract and add an amount of water for injection dissolving, add an amount of mannitol, stir evenly, technique prepares concentrated solution for injection routinely.
Embodiment 21
Radix Ginseng extract 70g Radix Salviae Miltiorrhizae extract 8g Rhizoma Chuanxiong extract 8g
Get Radix Ginseng extract, Radix Salviae Miltiorrhizae extract, Rhizoma Chuanxiong extract and add an amount of water for injection dissolving, stir evenly, technique prepares concentrated solution for injection routinely.
Embodiment 22
Radix Ginseng total saponins 90g Radix Salviae Miltiorrhizae total phenolic acids 40g Rhizoma Chuanxiong extract 40g
Get Radix Ginseng total saponins, Radix Salviae Miltiorrhizae total phenolic acids, Rhizoma Chuanxiong extract and add an amount of water for injection dissolving, it is an amount of to add mannitol, stirs evenly, and adjust pH injects water to quantitatively, and microporous filter membrane filters, fine straining, and packing, lyophilization namely gets the Injectable sterile block.
Embodiment 23
Radix Ginseng extract 95g Radix Salviae Miltiorrhizae extract 55g ligustrazine 10g
Get ligustrazine and add an amount of water for injection dissolving, get solution A; Get Radix Salviae Miltiorrhizae extract and add the dissolving of an amount of water for injection, and adjust pH is to 6-7, stirring and dissolving gets solution B; Keep stirring, solution A is added in the solution B, and adjust pH gets solution C to 6-7; Gets Radix Ginseng extract and an amount of mannitol injects the dissolving of blunging, mixes with solution C, stir, and adjust pH is to 6-7, inject water to quantitative, activated carbon adsorption, filtration, filtering with microporous membrane, packing, lyophilization, and get final product.
The Radix Ginseng extract of mentioning in the above embodiment of the present invention (Radix Ginseng total saponins), Radix Salviae Miltiorrhizae extract (Radix Salviae Miltiorrhizae total phenolic acids), Rhizoma Chuanxiong extract (ligustrazine or ligustrazine hydrochloride or ligustrazine phosphate or its pharmaceutical salts) can or include but not limited to by commercially available acquisition adopt the preparation method of the present invention's three kinds of extracts mentioned above to obtain, and also can be to obtain by additive method.
Further set forth the beneficial effect of pharmaceutical composition of the present invention by following experiment:
Experimental example 1: medicine antagonism Mouse Whole Brain ischemia of the present invention and ischemical reperfusion injury pharmacodynamics test
Set up chmice acute global brain ischemia and ischemia-reperfusion injury model, take mouse survival time, brain water content as reference, investigate respectively pharmaceutical composition of the present invention to mice acute phase of cerebral ischemia, the early stage therapeutical effect of recovery.The result is as follows:
Table 1 antagonism Mouse Whole Brain ischemia and ischemical reperfusion injury pharmacodynamics test (
N=10)
*P＜0.05 vs M **P＜0.01vs M
As shown in Table 1, compare with model group, pharmaceutical composition of the present invention all can obviously prolong the mean survival time (P＜0.05) of mice; All can obviously suppress the brain water content increase (P＜0.05) that the CIR damage causes.Wherein the compositions of " Radix Ginseng extract 20-50 part, Radix Salviae Miltiorrhizae extract 10-30 part, Rhizoma Chuanxiong extract 8-30 part " is obvious with the composition effect of " Radix Ginseng extract 10-60 part, Radix Salviae Miltiorrhizae extract 7-40 part, Rhizoma Chuanxiong extract 5-40 part ", and is best with the composition effect of " Radix Ginseng extract 20-50 part, Radix Salviae Miltiorrhizae total phenolic acids 10-30 part, ligustrazine or ligustrazine hydrochloride or ligustrazine phosphate or its pharmaceutical salts 8-30 part ".
Experimental example 2: medicine of the present invention and any two medicine compatibilities, single medicine prescription are relatively
(1) antagonism Mouse Whole Brain ischemia (acute stage) and ischemical reperfusion injury (recovering early stage) pharmacodynamics test
Set up chmice acute global brain ischemia and ischemia-reperfusion injury model (recovering early stage), with the mouse survival time, brain water content, malonaldehyde in the cerebral tissue (MDA) content, superoxide dismutase (SOD), the indexs such as lactic acid dehydrogenase (LDH) and glutathion peroxidase (GSH-Px) are active are changed to reference, investigate respectively people's Danshen injection (R), Danshen root injection (S), Rhizoma Chuanxiong injection (L), Radix Ginseng Danshen root injection (RS), Radix Ginseng Rhizoma Chuanxiong injection (RL), red sage and chuanxiong rhizome injection (SL), in 7 kinds of medicines of medicine Radix Ginseng red sage and chuanxiong rhizome injection of the present invention (RSL) to the mice acute phase of cerebral ischemia, recover early stage therapeutical effect.The result is as follows:
1, on the impact of acute brain damage following complete mouse survival time:
Table 2 on the impact of acute brain damage following complete male mice death toll and mean survival time (
N=12)
*P＜0.05vs M，
#P＜0.05vs R，
&P＜0.05vs RL
As shown in table 2, for male mice, after bilateral common carotid arteries merged the vagus nerve ligation, model group, Ginseng Injection group, Radix Salviae Miltiorrhizae Injection group, Radix Ginseng ligustrazine injection group mice were most of dead in 2h.The mice of Radix Ginseng Radix Salviae Miltiorrhizae Injection group 58% is dead in 2h, and 42% is dead in 6h.The mice of ligustrazine injection group, Radix Ginseng red-rooted-salvia-root chuanxiong-rhizome azine injecta group 8% is dead in 2h, and 92% death in 6h.The mice of red-rooted-salvia-root chuanxiong-rhizome azine injecta group 16% is dead in 2h, and 84% death in 6h.Compare with model group, the mice mean survival time of ligustrazine injection group, red-rooted-salvia-root chuanxiong-rhizome azine injecta group, Radix Ginseng red-rooted-salvia-root chuanxiong-rhizome azine injecta group obviously prolongs (P＜0.05).Compare with Ginseng Injection group or Radix Ginseng ligustrazine injection, the ability that the Radix Ginseng red-rooted-salvia-root chuanxiong-rhizome azine injecta prolongs the mouse survival time obviously strengthens (P＜0.05).
Table 3 on the impact of acute brain damage following complete female mice death toll and mean survival time (
N=12)
*P＜0.05vs M，
#P＜0.05vs S，
@P＜0.05vs RS，
&P＜0.05vs SL
As shown in table 3, for female mice, model group, Danshen root injection group, Rhizoma Chuanxiong injection group, red sage and chuanxiong rhizome injection group, most of dead in the Radix Ginseng Danshen root injection group mice 2h.The mice of people's Danshen injection group 50% is dead in 2h, and 25% is dead in 6h, and 25% is dead in 12h.The mice of Radix Ginseng Rhizoma Chuanxiong injection group 25% is dead in 2h, and 50% is dead in 6h, and 25% is dead in 12h.The mice of Radix Ginseng red sage and chuanxiong rhizome injection group 16% is dead in 2h, and 42% is dead in 6h, and 42% is dead in 12h.Compare with model group, Radix Ginseng Rhizoma Chuanxiong injection group, Radix Ginseng red sage and chuanxiong rhizome injection group mice mean survival time obviously prolong (P＜0.05).Compare with Danshen root injection, Radix Ginseng Danshen root injection and red sage and chuanxiong rhizome injection, the ability that Radix Ginseng red sage and chuanxiong rhizome injection prolongs the mice mean survival time obviously strengthens (P＜0.05).
2, on the impact of mice after global cerebral ischemia-reperfusion brain water content:
Set up Mouse Whole Brain ischemia-reperfusion injury model (CIR)
Table 4 on the impact of male CIR mouse brain water content (
N=10)
*P＜0.05vs M，
#P＜0.05vs S
As shown in table 4, for male mice, CIR model group brain water content obviously raises.Compare with the CIR model group, 7 kinds of medicines all can obviously suppress the brain water content increase (P＜0.05) that the CIR damage causes.In addition, compare with the Radix Salviae Miltiorrhizae group, Radix Ginseng red sage and chuanxiong rhizome group reduces the effect more obvious (P＜0.05) that brain water content increases.
Table 5 on the impact of female CIR mouse brain water content (
N=10)
*P＜0.05vs M
As shown in table 5, for female mice, CIR model group brain water content also obviously increases.Compare with the CIR model group, only Radix Ginseng group, Rhizoma Chuanxiong group, Radix Ginseng Rhizoma Chuanxiong group, red sage and chuanxiong rhizome group and Radix Ginseng red sage and chuanxiong rhizome group can obviously suppress the brain water content increase (P＜0.05) that the CIR damage causes.
3, to mice after global cerebral ischemia-reperfusion cerebral tissue MDA content, the impact of SOD activity, LDH and GSH-Px activity:
Table 6 pair CIR mouse brain is organized MDA content, the impact of SOD activity, LDH and GSH-Px activity (
N=8)
* P＜0.05vs M organizes,
#P＜0.05vs R group,
@P＜0.05vs S group,
﹠amp;P＜0.05vs L group, $ P＜0.05vsRS group,! P＜0.05vs SL
As shown in table 6, for the CIR mice, to compare with puppet operation group, the generation of CIR model group MDA obviously increases, active obviously reduce (P＜0.05) of SOD, LDH and GSH-Px.Compare with model group, seven kinds of drug candidates all can be able to significantly suppress the increase (P＜0.05) that the CIR mouse brain organizes MDA to generate.In addition, compare with the Radix Salviae Miltiorrhizae group, the red-rooted-salvia-root chuanxiong-rhizome azine group reduces the effect more obvious (P＜0.05) that MDA increases.Compare with Radix Ginseng group, Radix Salviae Miltiorrhizae group, ligustrazine group, Radix Ginseng Radix Salviae Miltiorrhizae group, Radix Ginseng red-rooted-salvia-root chuanxiong-rhizome azine group reduces the effect more obvious (P＜0.05) that MDA increases.Compare with model group, Radix Ginseng group, ligustrazine group, Radix Ginseng ligustrazine group, red-rooted-salvia-root chuanxiong-rhizome azine group, Radix Ginseng red-rooted-salvia-root chuanxiong-rhizome azine group significantly suppress the reduction (P＜0.05) of SOD, LDH and GSH-Px activity.Compare with the Radix Salviae Miltiorrhizae group, the red-rooted-salvia-root chuanxiong-rhizome azine group increases the effect more obvious (P＜0.05) of SOD and LDH activity.Compare with Radix Salviae Miltiorrhizae group, Radix Ginseng Radix Salviae Miltiorrhizae group, Radix Ginseng red-rooted-salvia-root chuanxiong-rhizome azine group increases the effect more obvious (P＜0.05) of SOD and LDH activity.Compare with the Radix Ginseng group, the effect that Radix Ginseng ligustrazine group increases the GSH-Px activity is more obvious, compares with the Radix Salviae Miltiorrhizae group, and the effect that the red-rooted-salvia-root chuanxiong-rhizome azine group increases the GSH-Px activity is more obvious.Compare with Radix Ginseng, Radix Salviae Miltiorrhizae, ligustrazine, Radix Ginseng Radix Salviae Miltiorrhizae and red-rooted-salvia-root chuanxiong-rhizome azine group, Radix Ginseng red-rooted-salvia-root chuanxiong-rhizome azine group increases the effect more obvious (P＜0.05) of GSH-Px activity.
4, conclusion:
(1) Radix Ginseng red sage and chuanxiong rhizome injection all has protective effect to acute brain damage following complete and global cerebral ischemia/reperfusion mice, and therefore three medicine compatibilities all have good therapeutic effect in early days to acute phase of cerebral ischemia, recovery.And single medicinal material people Danshen injection, Rhizoma Chuanxiong injection or two medicine composition of prescription red sage and chuanxiong rhizome injections, Radix Ginseng Danshen root injection, Radix Ginseng Rhizoma Chuanxiong injection are only effective in cure to acute cerebral ischemia, perhaps only effective in cure to cerebral ischemia reperfusion injury, the effect of its anti-cerebral infarction or reperfusion injury is more single.
(2) on anti-global cerebral ischemia/reperfusion effect, two medicine compatibilities are better than single medicine prescription, and three medicine compatibilities are better than two medicine compatibilities.Experimental result shows, three medicine compatibilities alleviate cerebral edema, alleviate radical damage, the comprehensive function of the reaction that reduces inflammation is better than two medicine compatibilities or single medicine prescription.
In summary, the present invention's's " Radix Ginseng+Radix Salviae Miltiorrhizae+Rhizoma Chuanxiong " combination reaches " Radix Ginseng ", " Radix Salviae Miltiorrhizae " with the combination of " Radix Ginseng+Radix Salviae Miltiorrhizae ", " Radix Ginseng+Rhizoma Chuanxiong ", " Radix Salviae Miltiorrhizae+Rhizoma Chuanxiong ", " Rhizoma Chuanxiong " folk prescription is compared, play a role at many levels, multipath, many target spots, to ischemic cerebrovascular/apoplexy acute stage, recover all can play preferably curative effect in early days, prompting said composition more in twos compatibility, single preparations of ephedrine is compared and has been obtained beyond thought technique effect.
Claims (13)
1. the pharmaceutical composition with benefiting QI for activating blood circulation effect is characterized in that, it is comprised of the active substance of following weight portion: Radix Ginseng extract 1-100 part, Radix Salviae Miltiorrhizae extract 1-60 part, Rhizoma Chuanxiong extract 1-60 part.
2. pharmaceutical composition according to claim 1 is characterized in that, it is comprised of the active substance of following weight portion: Radix Ginseng extract 3-80 part, Radix Salviae Miltiorrhizae extract 5-55 part, Rhizoma Chuanxiong extract 3-50 part.
3. pharmaceutical composition according to claim 2 is characterized in that, it is comprised of the active substance of following weight portion: Radix Ginseng extract 10-60 part, Radix Salviae Miltiorrhizae extract 7-40 part, Rhizoma Chuanxiong extract 5-40 part.
4. the described pharmaceutical composition of any one is characterized in that according to claim 1-3, and described Radix Ginseng extract refers to Radix Ginseng total saponins; Radix Salviae Miltiorrhizae extract refers to Radix Salviae Miltiorrhizae total phenolic acids; Rhizoma Chuanxiong extract refers to ligustrazine or ligustrazine hydrochloride or ligustrazine phosphate or its pharmaceutical salts.
5. according to claim 1 and 2 or 3 or 4 described pharmaceutical compositions, it is characterized in that it is comprised of the active substance of following weight portion: Radix Ginseng total saponins 20-50 part, Radix Salviae Miltiorrhizae total phenolic acids 10-30 part, ligustrazine or ligustrazine hydrochloride or ligustrazine phosphate or its pharmaceutical salts 8-30 part.
6. pharmaceutical composition according to claim 5 is characterized in that,
Radix Ginseng total saponins is like this preparation: the people participates in the alcohol reflux of variable concentrations, merge extractive liquid,, concentrating under reduced pressure Recycled ethanol, upper macroporous resin column absorption, washing resin is used ethanol elution, collect ethanol elution, Recycled ethanol adds the suitable quantity of water dissolving, filter, filtrate adds organic solvent extraction, collects extract, dehydration, reclaim organic solvent, drying under reduced pressure, and get final product;
Radix Salviae Miltiorrhizae total phenolic acids is like this preparation: Radix Salviae Miltiorrhizae powder is broken into coarse powder, the acid adding aqueous solution soaking, and percolation extracts, collect percolate, filter, macroporous resin column absorption on the filtrate, use respectively alcoholic solution, the ethanol elution of aqueous acid, acidify, collect eluent, Recycled ethanol, suitably concentrated, and adjust pH is to acidity, organic solvent extraction, collect extract, organic solvent is reclaimed in dehydration, drying under reduced pressure, and get final product;
Rhizoma Chuanxiong extract is like this preparation: gets Rhizoma Chuanxiong power and is broken into coarse powder, and the water saturated organic solvent extraction of acid adding, merge extractive liquid,, the reclaim under reduced pressure organic solvent, residue adds dissolve with ethanol, decompression recycling ethanol, drying under reduced pressure, and get final product.
7. pharmaceutical composition according to claim 6 is characterized in that,
Radix Ginseng total saponins is like this preparation: the people participates in 6-12 and doubly measures the 50-95% alcohol reflux 1-4 time, each 1-3 hour, merge extractive liquid,, concentrating under reduced pressure Recycled ethanol, upper macroporous resin column absorption, 10-50% alcoholic solution washing resin with alkalization, and be washed till neutrality with purified water, and use the 50-95% ethanol elution, collect ethanol elution, Recycled ethanol, add the suitable quantity of water dissolving, ultrafiltrate is collected in ultrafiltration, add n-butanol extraction 1-7 time, collect n-butyl alcohol liquid, n-butyl alcohol is reclaimed in dehydration, drying under reduced pressure, and get final product;
Radix Salviae Miltiorrhizae total phenolic acids is like this preparation: Radix Salviae Miltiorrhizae powder is broken into coarse powder, adds 2-6 and doubly measures aqueous acid immersion 2-6 hour, and the aqueous acid percolation extracts, collect 10-20 and doubly measure percolate, filter, macroporous resin column absorption on the filtrate, use respectively 10-50% alcoholic solution, the 50-95% ethanol elution of aqueous acid, acidify, collect eluent, Recycled ethanol, suitably concentrated, and adjust pH adds ethyl acetate extraction 1-7 time to 1-2, collect acetic acid ethyl fluid, ethyl acetate is reclaimed in dehydration, drying under reduced pressure, and get final product;
Rhizoma Chuanxiong extract is like this preparation: get Rhizoma Chuanxiong power and be broken into coarse powder, add the water saturated ethyl acetate backflow of pH=3.0 acid and extract each 1-3 hour 1-4 time, merge extractive liquid,, the reclaim under reduced pressure ethyl acetate, residue adds the 50-95% dissolve with ethanol, decompression recycling ethanol, drying under reduced pressure, and get final product.
8. the described pharmaceutical composition of any one is characterized in that according to claim 1-4, and Radix Ginseng total saponins accounts for more than 65% of Radix Ginseng extract total solids content; Radix Salviae Miltiorrhizae total phenolic acids accounts for more than 75% of Radix Salviae Miltiorrhizae extract total solids content; Ferulic acid is that the phenol of representative and phthalide-type sum that ligustilide is representative account for more than 50% of Rhizoma Chuanxiong extract total solids content.
9. the described pharmaceutical composition of any one according to claim 1-5, it is characterized in that described Radix Ginseng extract, Radix Salviae Miltiorrhizae extract, Rhizoma Chuanxiong extract, Radix Ginseng total saponins, Radix Salviae Miltiorrhizae total phenolic acids, ligustrazine or ligustrazine hydrochloride or ligustrazine phosphate or its pharmaceutical salts are by commercially available direct acquisition.
10. the preparation method of the described pharmaceutical composition of any one is characterized in that according to claim 1-5, and the method is: get Radix Ginseng extract, Radix Salviae Miltiorrhizae extract, Rhizoma Chuanxiong extract routinely technique be prepared into ejection preparation.
11. the preparation method of pharmaceutical composition according to claim 10 is characterized in that, described ejection preparation refers to injection, injectable sterile powder, Injectable sterile block, concentrated solution for injection.
12. the preparation method of pharmaceutical composition according to claim 11 is characterized in that, injectable sterile powder is like this preparation:
Get Rhizoma Chuanxiong extract and add an amount of water for injection dissolving, get solution A; Get Radix Salviae Miltiorrhizae extract and add the dissolving of an amount of water for injection, and adjust pH is to 6-7, stirring and dissolving gets solution B; Keep stirring, solution A is added in the solution B, and adjust pH gets solution C to 6-7; Gets Radix Ginseng extract and an amount of mannitol injects the dissolving of blunging, mixes with solution C, stir, and adjust pH is to 6-7, inject water to quantitative, activated carbon adsorption, filtration, filtering with microporous membrane, packing, lyophilization, and get final product.
13. the described pharmaceutical composition of any one is characterized in that according to claim 1-4, for the preparation of the application in treatment suffering from acute stroke, the early stage disease medicament of recovery.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210118717 CN103372053A (en) | 2012-04-20 | 2012-04-20 | Medicinal composition for treating cardiovascular and cerebrovascular diseases and preparation method of medicament |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201210118717 CN103372053A (en) | 2012-04-20 | 2012-04-20 | Medicinal composition for treating cardiovascular and cerebrovascular diseases and preparation method of medicament |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN103372053A true CN103372053A (en) | 2013-10-30 |
Family
ID=49458299
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201210118717 Pending CN103372053A (en) | 2012-04-20 | 2012-04-20 | Medicinal composition for treating cardiovascular and cerebrovascular diseases and preparation method of medicament |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103372053A (en) |
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104304624A (en) * | 2014-10-31 | 2015-01-28 | 烟台星之手生物医药有限公司 | Compound radix salviae miltiorrhizae sugar for patient with hypertension |
| CN105213580A (en) * | 2015-10-19 | 2016-01-06 | 遵义医学院 | Pharmaceutical composition of a kind of resisting cardiac hypertrophy and preparation method thereof |
| CN105852130A (en) * | 2016-05-24 | 2016-08-17 | 朱启标 | Preparation method of ginseng health care product and product of preparation method |
| CN110680845A (en) * | 2018-07-05 | 2020-01-14 | 北京盈科瑞创新医药股份有限公司 | Pharmaceutical composition for treating stroke and preparation method and application thereof |
-
2012
- 2012-04-20 CN CN 201210118717 patent/CN103372053A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104304624A (en) * | 2014-10-31 | 2015-01-28 | 烟台星之手生物医药有限公司 | Compound radix salviae miltiorrhizae sugar for patient with hypertension |
| CN105213580A (en) * | 2015-10-19 | 2016-01-06 | 遵义医学院 | Pharmaceutical composition of a kind of resisting cardiac hypertrophy and preparation method thereof |
| CN105213580B (en) * | 2015-10-19 | 2019-04-05 | 遵义医学院 | A kind of pharmaceutical composition of resisting cardiac hypertrophy and preparation method thereof |
| CN105852130A (en) * | 2016-05-24 | 2016-08-17 | 朱启标 | Preparation method of ginseng health care product and product of preparation method |
| CN110680845A (en) * | 2018-07-05 | 2020-01-14 | 北京盈科瑞创新医药股份有限公司 | Pharmaceutical composition for treating stroke and preparation method and application thereof |
| CN110680845B (en) * | 2018-07-05 | 2022-05-24 | 浙江维康药业股份有限公司 | Pharmaceutical composition for treating stroke and preparation method and application thereof |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103705594B (en) | Chinese medicine composition for the treatment of hyperlipemia and preparation method thereof | |
| CN101972353A (en) | Medicine composition for preventing and treating heart cerebrovascular diseases | |
| CN103372054A (en) | Medicament for treating cardiovascular and cerebrovascular diseases and preparation method of medicament | |
| CN103372053A (en) | Medicinal composition for treating cardiovascular and cerebrovascular diseases and preparation method of medicament | |
| CN102475830B (en) | Medicinal composition for treating coronary disease and angina pectoris, preparation method thereof and preparation thereof | |
| CN102657834A (en) | Traditional Chinese medical composition for treatment of alcoholism and preparation process thereof | |
| CN103006838A (en) | Traditional Chinese medicine composition for treating cardiovascular and cerebrovascular diseases | |
| CN101172155A (en) | Novel dosage forms of pulse-activating gallbladder warming soup and method of preparing the same | |
| CN101590102A (en) | A kind of medicine for the treatment of cardiovascular and cerebrovascular disease and preparation method thereof | |
| CN104645015A (en) | Traditional Chinese medicine compound preparation for treating vascular dementia and preparation method of traditional Chinese medicine compound preparation | |
| CN101744993B (en) | Extraction method for ginseng, ophiopogon root and schisandra chinensis and preparation thereof | |
| CN103933195A (en) | Traditional Chinese medicinal composition for treating liver diseases, and its application in preparation of liver disease prevention and treatment medicines | |
| CN1762410B (en) | Chinese dodder seed extract, its preparation method, Chinese proprietary medicine containing extracts thereof and use thereof | |
| CN104707023A (en) | Traditional Chinese medicinal composition for treating polycystic ovary syndrome, and preparation method thereof | |
| CN101085070B (en) | Traditional Chinese medicinal composition containing notoginseng and haw and its preparation | |
| CN102120000B (en) | Composition of effective parts of traditional Chinese medicine preparation for resisting Coxsackie virus B and preparation method thereof | |
| CN101744991B (en) | Single extraction method of ginseng, ophiopogon root and shiandra and preparation thereof | |
| CN101745011B (en) | Method for extracting ginseng, dwarf lilyturf tuber and schisandra chinensis and preparation thereof | |
| CN100577185C (en) | Chinese medicine red sage-astragalus root preparation for treating liver fibrosis and liver cirrhosis and its preparation process | |
| CN101129431A (en) | Traditional Chinese medicine composition for preventing and controlling cardiovascular disease and relative disease, method of preparing the same and application of the same | |
| CN104398677B (en) | A kind of tartary buckwheat general flavone and Gynostemma Pentaphyllum compound | |
| CN101084965A (en) | Safflower compound preparation and its preparation technology | |
| CN100493535C (en) | Compounding traditional Chinese medicine-Xueyaping for treating hypertension, and its preparation method | |
| CN101745001B (en) | Extraction method of ophiopogon root, ginseng and shiandra and preparation thereof | |
| CN101647858B (en) | Preparation method of water-soluble extract of red sage root |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information |
Address after: 100088 Beijing city Xicheng District, New Street No. 2 Tiancheng Technology building block B room 4002 Applicant after: BEIJING INCREASE PHARMACEUTICAL INSTITUTE Co.,Ltd. Address before: 100088 Beijing city Xicheng District, New Street No. 2 Tiancheng Technology building block B room 4002 Applicant before: BEIJING INCREASE PHARMACEUTICAL RESEARCH INSTITUTE Co.,Ltd. Address after: 100088 Beijing city Xicheng District, New Street No. 2 Tiancheng Technology building block B room 4002 Applicant after: BEIJING INCREASE PHARMACEUTICAL RESEARCH INSTITUTE Co.,Ltd. Address before: 100088 Beijing city Xicheng District, New Street No. 2 Tiancheng Technology building block B room 4002 Applicant before: BEIJING INCREASE PHARMACEUTICAL TECHNOLOGY Co.,Ltd. |
|
| COR | Change of bibliographic data | ||
| CB02 | Change of applicant information |
Address after: Double camp 102299 West Road Beijing city Changping District Science Park No. 79, No. 24 building 6 layer cloud Valley Park Applicant after: Beijing Increasepharm Co.,Ltd. Address before: 100088 Beijing city Xicheng District, New Street No. 2 Tiancheng Technology building block B room 4002 Applicant before: BEIJING INCREASE PHARMACEUTICAL INSTITUTE Co.,Ltd. |
|
| CB02 | Change of applicant information | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20131030 |
|
| RJ01 | Rejection of invention patent application after publication |