CN1915294A - Medicinal composition, preparation method and quality control method - Google Patents
Medicinal composition, preparation method and quality control method Download PDFInfo
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- CN1915294A CN1915294A CN 200510093138 CN200510093138A CN1915294A CN 1915294 A CN1915294 A CN 1915294A CN 200510093138 CN200510093138 CN 200510093138 CN 200510093138 A CN200510093138 A CN 200510093138A CN 1915294 A CN1915294 A CN 1915294A
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Abstract
A composite medicine in the form of injection or orally taken medicine for treating cardiovascular and cerebrovascular diseases, such as coronary heart disease, angina pectoris, apoplexy sequelae, cerebral thrombus, etc, is prepared from red sage root or its extract and dipyridamole. Its preparing process and quality control method are also disclosed.
Description
Technical field
The invention provides a kind of pharmaceutical composition that is used for the treatment of cardiovascular and cerebrovascular disease, the preparation method and the method for quality control of said composition is provided simultaneously, belong to technical field of medicaments.
Technical background
Cardiovascular and cerebrovascular disease such as coronary heart disease, cerebral thrombosis, alzheimer disease etc. have become the No.1 killer of human health, have become human mortality's one of the main reasons in many countries; According to investigations, sickness rate in recent years has and increases trend year by year, and continuous rejuvenation trend is arranged, in, young patient constantly increases, cardiovascular and cerebrovascular disease has become commonly encountered diseases, the frequently-occurring disease of harm China people ' s health.And at present medicine mainly concentrates on pure Chinese medicinal preparation and Western medicine two aspects, and mostly the Chinese medicine and western medicine coupling is that the clinician selects suitable Chinese medicine preparation to cooperate the Western medicine diagnosis and treatment of corresponding function according to the disease situation, and the prescription of Western medicine is fairly simple and side effect is bigger; Though the pure Chinese medicinal preparation toxic and side effects is little, their onset is slow, influences therapeutic effect; The Chinese medicine and western medicine coupling is the rule of thumb bold compatibility of clinician, but lacks pharmacologic agent theoretical the support, lacks the support of compatibility theory simultaneously, has certain risk.In the prior art, Chinese patent application 03117115.X discloses ejection preparation of antiplatelet aggregation and preparation method thereof, in this product, be made into the pharmaceutical preparation of antiplatelet aggregation with dipyridamole and Semen Ginkgo extrac, some problems that present medication exists have been solved, we find but reach clinical research by experiment: though this compatibility is effective, but the main coronary artery dilating slight drag of dipyridamole blood vessel, and the compensatory ground expansion of myocardial ischemia district slight drag blood vessel, not only can not increase the ischemic region blood supply, can produce " steal-effect " phenomenon on the contrary, ischemic region is caused adverse effect; And Folium Ginkgo extract can not improve this drawback fully, and the curative effect that can make some patients is not remarkable especially; The clear 200410022286.X in Chinese patent Shen discloses a kind of Chinese medicine preparation that is used for the treatment of cardiovascular disease and preparation method thereof and method of quality control.In this invention, form by Radix Salviae Miltiorrhizae and ligustrazine hydrochloride, although this medicine has solved some problems of clinical application, but because the acidity of ligustrazine hydrochloride is stronger, zest is stronger during acupoint injection therapy, and Radix Salviae Miltiorrhizae adopts water extraction, this water extract also to be acid among the present invention, so can have a negative impact to some patient.In view of such circumstances, searching better, compatibility is simple, therapeutic effect is desirable, and effective medicine that toxic and side effects is little has just become people's urgent problem.
Summary of the invention
The object of the present invention is to provide a kind of pharmaceutical composition for the treatment of cardiovascular disease and preparation method thereof and method of quality control; At prior art, the present invention adopts the preparation that Radix Salviae Miltiorrhizae or Radix Salviae Miltiorrhizae extract and dipyridamole compatibility are made to be needed, Radix Salviae Miltiorrhizae has coronary blood flow increasing, reduces myocardial excitability and conductivity, microcirculation improvement, antiplatelet aggregation and thrombosis, and blood viscosity is descended, effectively avoided " steal-effect " phenomenon of dipyridamole; Dipyridamole is capable of inhibiting cell to the picked-up of adenosine and the enzymolysis of adenosine, suppresses phosphodiesterase, and cAMP is increased, and coronary artery dilator increases its blood flow, improves blood oxygen saturation, improves the blood supply and the oxygen supply of cardiac muscle; The two share, and has synergism.The present invention has curative effect preferably for treating cardiovascular and cerebrovascular disease such as coronary heart disease, angina pectoris, cerebral thrombosis, apoplexy etc.; Another object of the present invention is the method for Chinese medicinal of these treatment cardiovascular and cerebrovascular diseases of open preparation; The present invention also aims to provide its method of quality control; To overcome the problem that prior art exists.
Preparation of the present invention is to constitute like this: it by 1～20 part of 10～10000 parts of Radix Salviae Miltiorrhizaes and dipyridamole through extracting refining forming; Or the Radix Salviae Miltiorrhizae extract and the corresponding weight portion dipyridamole that are obtained after extracting by corresponding weight portion medical material are made.The pharmaceutical composition of described treatment cardiovascular and cerebrovascular disease is characterized in that: calculate according to components by weight percent, it by 1～15 part of 100～5000 parts of Radix Salviae Miltiorrhizaes and dipyridamole through extracting refining forming; Or the Radix Salviae Miltiorrhizae extract and the corresponding weight portion dipyridamole that are obtained after extracting by corresponding weight portion medical material are made.Say exactly: calculate according to parts by weight, it by 1～10 part of 100～2000 parts of Radix Salviae Miltiorrhizaes and dipyridamole through extracting refining forming; Or the Radix Salviae Miltiorrhizae extract and the corresponding weight portion dipyridamole that are obtained after extracting by corresponding weight portion medical material are made.
The described preparation of the pharmaceutical composition of described treatment cardiovascular and cerebrovascular disease is injection and oral formulations; Injection comprises: little liquid drugs injection, powder pin or infusion solutions; Oral formulations comprises: all acceptable dosage forms on the pharmaceuticss such as tablet, dispersible tablet, effervescent tablet, oral cavity disintegration tablet, capsule, soft capsule, microcapsule, granule, pill, powder, drop pill, slow releasing preparation, controlled release preparation, oral liquid, soft extract, extractum, gel, membrane; Preferred preparation is liquid drugs injection, powder pin, infusion solutions, oral liquid, drop pill, capsule, soft capsule, oral cavity disintegration tablet, tablet, capsule, dispersible tablet, buccal tablet, oral gel or granule.
The pharmaceutical composition of described treatment cardiovascular and cerebrovascular disease: count by weight percentage: the content of phenols component be not less than in the preparation deduction adjuvant amount, water quantities and dipyridamole amount total solid 1%; The component content sum that derives from red rooted salvia that all can be surveyed in the injection be not less than in the preparation deduction adjuvant amount, water quantities and dipyridamole amount total solid 20%; Dipyridamole should be 90.0%～110.0% of labelled amount.
The preparation of drug combination method of described treatment cardiovascular and cerebrovascular disease is: get Radix Salviae Miltiorrhizae, add entry or ethanol extraction, the extracting solution concentrate drying gets the Radix Salviae Miltiorrhizae crude extract, one or more that also can further adopt precipitate with ethanol, organic solvent extraction, alkali extraction and acid precipitation, column chromatography carry out suitably refining, get the Radix Salviae Miltiorrhizae extract, with Radix Salviae Miltiorrhizae crude extract or Radix Salviae Miltiorrhizae extract and dipyridamole mixing, be prepared into the preparation that needs with diverse ways.
Radix Salviae Miltiorrhizae extract can also be commercially available or adopt other preparation methoies to prepare in the preparation of drug combination method of described treatment cardiovascular and cerebrovascular disease.
The pharmaceutical composition of described treatment cardiovascular and cerebrovascular disease has antiplatelet aggregation, reduces myocardial oxygen consumption, microcirculation improvement, increases the functions such as blood supply of ischemic region; Be used for the treatment of cardiovascular and cerebrovascular diseases such as coronary heart disease, angina pectoris, cerebral thrombosis, apoplexy.
Its assay is to adopt in high performance liquid chromatography, spectrophotography, thin layer chromatography scanning, the titrimetry one or more to record in the method for quality control of the pharmaceutical composition of described treatment cardiovascular and cerebrovascular disease.
Compared with prior art, Radix Salviae Miltiorrhizae or Radix Salviae Miltiorrhizae extract and dipyridamole all are active drugs of cardiovascular and cerebrovascular diseases, because its effective ingredient purity is higher, and the intravenous administrations that adopt in the acute disease treatment more.Arbitrarily with both combinations, though can obtain potentiation, its preparation stability and safety can't guarantee clinically.The applicant plans Radix Salviae Miltiorrhizae extract and dipyridamole and is combined into novel formulation and develops research, brings into play both cooperative compensating effects in angina pectoris, cerebral thrombosis, apoplexy by compatibility, is that the treatment of cardiovascular and cerebrovascular disease increases a new medication and selects.Simultaneously, can system further investigate Radix Salviae Miltiorrhizae or the safety of Radix Salviae Miltiorrhizae extract and dipyridamole compatibility and the controllability of quality, for data for clinical drug use is given security.By antiplatelet aggregation test, inhibition mouse tail thrombotest and the anti-protective effect test that lacks sugared anoxia to the In vitro culture myocardial cell injury; to these two kinds of medicines (Radix Salviae Miltiorrhizae extract: dipyridamole) carried out the prescription screening test of system; found that with Radix Salviae Miltiorrhizae extract: the prescription pharmacological action of dipyridamole=3: 1 is strong and consumption is lower, preparations shaping and having good stability, and both compatibilities can reach the effect of efficacy enhancing and toxicity reducing.The result shows; after the two herbal medicine use in conjunction; the obvious synergistic effect is arranged aspect blood circulation promoting and blood stasis dispelling; aspect the treatment cerebral ischemia obvious synergistic effect is being arranged also; the increase that can obviously increase blood flow coronarius simultaneously, reduce the Ischemic Heart load, resist myocardial oxygen consumption, thereby better protection ischemic myocardium.
Pharmaceutical preparation of the present invention, with respect to the independent preparation of Radix Salviae Miltiorrhizae, dipyridamole better efficacy not only, and use and carry all easily, the preparation method of multiple different oral formulations is provided, be suitable for different crowd and use, avoided dosage form single to hospitalized patients bring unfavorable.
The applicant has also carried out following experiment, to prove effective effect of medicine provided by the invention.
(1) the prescription screening experimental study conclusion of drug regimen compatibility
We are by antiplatelet aggregation test, inhibition mouse tail thrombotest and the anti-protective effect test that lacks sugared anoxia to the In vitro culture myocardial cell injury; Radix Salviae Miltiorrhizae extract and dipyridamole have been carried out the prescription screening test of system in varing proportions; found that strong and consumption is lower with the pharmacological action of Radix Salviae Miltiorrhizae extract and dipyridamole combination (3: 1) prescription, so determine that this ratio prescription is best prescription.
The prescription research conclusion
| Formula number | Prescription proportion of composing Radix Salviae Miltiorrhizae extract: dipyridamole | The screening and assessment index | |||
| Platelet suppression ratio (%) | Thrombosis suppression ratio (%) | The test of cultivation myocardial cell injury | |||
| LDH reduces % | CK reduces % | ||||
| 1 2 3 4 5 6 7 | 1∶3 1∶2 1∶1 2∶1 3∶1 5∶1 8∶1 | 77.8％ 73.7％ 74.2％ 73.2％ 74.3％ 68.5％ 67.9％ | 48.4％ 33.5％ 46.7％ 44.5％ 46.7％ 31.8％ 47.3％ | 41.8％ 52.9％ 39.1％ 41.2％ 44.23％ 38.6％ 38.9％ | 31.8％ 41.8％ 46.5％ 28.1％ 37.4％ 48.1％ 42.1％ |
From above-mentioned prescription screening result as can be seen, the compatible combination of different Radix Salviae Miltiorrhizae extracts and dipyridamole all can produce certain curative effect, but through system thinking, determine to reach potentiation antidotal effect with Radix Salviae Miltiorrhizae extract and dipyridamole by force and consumption is lower, preparations shaping and having good stability with 3: 1 ratio compatibility pharmacological action.
(2) Radix Salviae Miltiorrhizae extract: affirmation and the side's of tearing open research conclusion of dipyridamole=3: 1 combination prescription effectiveness
Drug efficacy study through system shows; after two medication combined application; aspect blood circulation promoting and blood stasis dispelling, has the obvious synergistic effect; at aspects such as treatment cerebral thrombosis, apoplexy the obvious synergistic effect is arranged also; simultaneously; obviously coronary blood flow increasing, improve the blood supply of ischemic region, thereby the better protection ischemic myocardium.
The affirmation of prescription effectiveness and the side's of tearing open research conclusion
| Pilot project | Prescription of the present invention | The Radix Salviae Miltiorrhizae extract group | The dipyridamole group |
| Improve mouse microcirculation test platelet aggregation-against and test the test promoting blood circulation and removing blood stasis of anti-mouse tail thrombotest rabbit fibrin solubility test | Effect is remarkable, the effect reinforced effects is remarkable, the effect reinforced effects is remarkable, the effect reinforced effects is remarkable, and the effect reinforced effects is remarkable | Effect positive effect positive effect positive effect positive effect is obvious | The general effect of effect positive effect positive effect positive effect is obvious |
Concrete embodiment
Embodiment 1: the preparation Radix Salviae Miltiorrhizae extract: get 10 parts of Radix Salviae Miltiorrhizaes (part is: kilogram or gram)
Get Radix Salviae Miltiorrhizae, add 10 times of water gagings after the pulverizing and decoct 3 times, each 1.5 hours, merge extractive liquid,, concentrate, filter, filtrate is crossed the D-101 macroporous adsorptive resins, earlier with 6 times of resinite hydrops and 4 times of resin volume 5% ethanol elution impurity, reuse 30% ethanol is resolved, collect stripping liquid, reclaim the ethanol concentrate drying, pulverize and promptly get Radix Salviae Miltiorrhizae extract.
Embodiment 2: the preparation Radix Salviae Miltiorrhizae extract: 10000 parts of Radix Salviae Miltiorrhizaes (part is: kilogram or gram)
Get Radix Salviae Miltiorrhizae, add 12 times of decoctings and boil 3 times, 2 hours for the first time, second and third time 1.5 hours, merge extractive liquid,, relative density is 1.05～1.15 thick paste when being concentrated into 50～80 ℃, adds ethanol and makes and contain pure flow control and once reach 50～70%, for the second time reach 85%, cold preservation is spent the night, and filters filtrate recycling ethanol, drying under reduced pressure gets Radix Salviae Miltiorrhizae extract.
Embodiment 3: the preparation Radix Salviae Miltiorrhizae extract: 8000 parts of Radix Salviae Miltiorrhizaes (part is: kilogram or gram)
Extract: get Radix Salviae Miltiorrhizae, add 6 times of amount 50% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, decompression recycling ethanol, relative density is 1.05～1.15 thick paste when being concentrated into 80 ℃, adds 3 times of water gagings, heats 60 ℃ of stirring and dissolving, filter, filtrate is condensed into thick paste, and vacuum drying gets Radix Salviae Miltiorrhizae extract.
Embodiment 4: the preparation Radix Salviae Miltiorrhizae extract: 100 parts of Radix Salviae Miltiorrhizaes (part is: kilogram or gram)
Extract: get Radix Salviae Miltiorrhizae, add 10 times of decoctings and boil 3 times, 2 hours for the first time, second and third time 1.5 hours, merge extractive liquid,, relative density is about 1.05 clear paste when being concentrated into 70 ℃, adding 20% sulfuric acid solution adjustment pH value is 2～3, stir, add the equal-volume ethyl acetate extraction 4 times, isolate ethyl acetate layer, reclaim solvent, concentrate, drying under reduced pressure gets Radix Salviae Miltiorrhizae extract.
Embodiment 5: the preparation Radix Salviae Miltiorrhizae extract: 5000 parts of Radix Salviae Miltiorrhizaes (part is: kilogram or gram)
Get Radix Salviae Miltiorrhizae, add 8 times of decoctings and boil 3 times, each 1.5 hours, merge extractive liquid,, relative density is 1.10～1.15 thick paste when being concentrated into 80 ℃, with the sodium carbonate liquor stirring and dissolving of equal-volume 20%, filter, filtrate adds 20% sulfuric acid solution, and regulating pH value is 2～3, stir, cold preservation 24 hours is filtered, the precipitation water wash to pH value be 5～6, drying under reduced pressure promptly gets Radix Salviae Miltiorrhizae extract.
Embodiment 6: the preparation Radix Salviae Miltiorrhizae extract: 2000 parts of Radix Salviae Miltiorrhizaes (part is: kilogram or gram)
Get Radix Salviae Miltiorrhizae, pulverize the back and add 80% ethanol, soaked 12 hours, percolation extracts, merge extractive liquid,, decompression recycling ethanol and when being condensed into 80 ℃ relative density be 1.05～1.15 extractum, add 50 ℃ of stirring and dissolving of 3 times of water gaging heating, filter, filtrate is crossed the ZTC-1 macroporous resin column, with 20% ethanol elution impurity, reuse 60% alcohol desorption, collect stripping liquid, reclaim the ethanol concentrate drying, get Radix Salviae Miltiorrhizae extract.
Embodiment 7: 5000 parts of Radix Salviae Miltiorrhizaes, 5 parts of dipyridamoles (part is: kilogram or gram)
Get Radix Salviae Miltiorrhizae, add 10 times of water gagings after the pulverizing and decoct each 1.5 hours 3 times, merge extractive liquid, concentrates, and filters, filtrate is crossed the D-101 macroporous adsorptive resins, with 6 times of resinite hydrops and 4 times of resin volume 5% ethanol elution impurity, reuse 30% ethanol is resolved earlier, collects stripping liquid, reclaim ethanol, concentrate drying adds the injection water, stirs to make it dissolving; Get dipyridamole, add the stirring of water for injection and 1% tartaric acid solution and make it dissolving, 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining, three grades of microporous filter membrane: be sequentially: 0.8um-0.45um-0.22um filters, embedding is sealed sterilization and is promptly got hydro-acupuncture preparation in the 10ml ampoule.The content that records Radix Salviae Miltiorrhizae total phenols in the preparation with spectrophotography is 47%.
Embodiment 8: 10000 parts of Radix Salviae Miltiorrhizaes, 1 part of dipyridamole (part is: kilogram or gram)
Get Radix Salviae Miltiorrhizae, pulverize the back and add 70% ethanol, soaked 12 hours, heating and refluxing extraction 3 times, each 1 hour, merge extractive liquid,, decompression recycling ethanol and when being condensed into 60 ℃ relative density be 1.08～1.15 extractum, add 3 times of water gaging stirring and dissolving, filter, filtrate is crossed the D-101 macroporous adsorptive resins, earlier with 6 times of resinite hydrops and 4 times of resin volume 10% ethanol elution impurity, reuse 50% ethanol is resolved, collect stripping liquid, reclaim the ethanol concentrate drying, pulverize, join stir in an amount of water for injection make it the dissolving, standby; Get dipyridamole, add the injection water, add 1% tartaric acid solution again, stirring makes it dissolving, adds standby Radix Salviae Miltiorrhizae extract solution mix homogeneously, regulates pH value 4.2～5.5, stirring makes it to dissolve fully, the PEG400 that adds 30ml, the mannitol of 130g, stirring makes it to dissolve fully, the active carbon that adds 0.05% (g/ml), 60 ℃ of static absorption were filtered carbon removal after 20 minutes, and benefit adds to the full amount of water for injection, regulate pH value 4.8～5.8, fine straining, intermediate sampling, to be detected qualified after, quantitative filling is in cillin bottle, half moulding plug, the freeze dryer of packing into, lyophilization.After the end to be dried, the intrinsic pressure plug of case, outlet lock aluminium lid, packing promptly gets lyophilized injectable powder.The component content sum that derives from red rooted salvia that all can be surveyed be deduction adjuvant amount, water quantities and dipyridamole amount in the preparation total solid 63%.
Embodiment 9: 3000 parts of Radix Salviae Miltiorrhizaes, 20 parts of dipyridamoles (part is: kilogram or gram)
Get Radix Salviae Miltiorrhizae, be ground into the coarse powder of 10 mesh sieves, add 8 times of volume 70% alcohol reflux 2 times, each 1 hour, measuring relative density when merge extractive liquid,, decompression recycling ethanol to 60 ℃ is 1.05～1.15, adds the water dissolution of 3 times of medical material volumes, filter, filtrate is crossed D-101 type macroporous adsorbent resin, with 6 times of resinite hydrops flushing impurity, uses 30% alcohol desorption of 4 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, and drying is pulverized, add water for injection, stir and make it dissolving; Get dipyridamole, add water for injection, add 1% tartaric acid solution again, stir and make it dissolving; With above-mentioned two kinds of solution mixings, 4 ℃ of cold preservations are spent the night, and coarse filtration adds in an amount of glucose solution, add 0.2% active carbon and boil 15 minutes, and coarse filtration, fine straining promptly get the glucose infusion liquid agent with the water for injection dilution.
Embodiment 10: 100 parts of Radix Salviae Miltiorrhizae extracts, 15 parts of dipyridamoles (part is: kilogram or gram)
Get Radix Salviae Miltiorrhizae extract, add the water for injection stirring and make it dissolving, get dipyridamole, add the stirring of water for injection and 1% tartaric acid solution and make it dissolving, 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining, three grades of microporous filter membrane: be sequentially: 0.8um-0.45um-0.22um, filter, embedding is sealed sterilization and is promptly got hydro-acupuncture preparation in the 10ml ampoule.The component content sum that derives from red rooted salvia that all can be surveyed be deduction adjuvant amount, water quantities and dipyridamole amount in the preparation total solid 23%.
Embodiment 11: 2000 parts of Radix Salviae Miltiorrhizae extracts, 18 parts of dipyridamoles (part is: kilogram or gram)
Get Radix Salviae Miltiorrhizae extract, join in an amount of water for injection to stir and make it dissolving, standby; Get dipyridamole and add water for injection, add 1% tartaric acid solution again, be stirred to dissolving fully, add standby Radix Salviae Miltiorrhizae extract solution mix homogeneously, regulate pH value 4.8～5.8, stirring makes it to dissolve fully, adds an amount of PEG400 and an amount of mannitol, stirring makes it to dissolve fully, the active carbon that adds 0.05% (g/ml), 60 ℃ of static absorption filtered carbon removal after 20 minutes, benefit adds to the full amount of water for injection, regulate pH value 4.5～5.5, fine straining, intermediate sampling, to be detected qualified after, quantitatively; About 3ml fill in cillin bottle, half moulding plug, the freeze dryer of packing into, lyophilization.After the end to be dried, the intrinsic pressure plug of case, outlet lock aluminium lid, packing promptly gets lyophilized injectable powder.The component content sum that derives from red rooted salvia that all can be surveyed be deduction adjuvant amount, water quantities and dipyridamole amount in the preparation total solid 93%; The content of dipyridamole is 99% of labelled amount.
Embodiment 12: 100 parts of Radix Salviae Miltiorrhizae extracts, 8 parts of dipyridamoles (part is: kilogram or gram)
Get 500ml water for injection earlier and put in the liquid dispenser, add Radix Salviae Miltiorrhizae extract 500mg, stirring at room makes it dissolving, adds 1.2g sodium citrate and 50ml propylene glycol again, stirs evenly, and makes it to form clear and bright solution.Get 300ml water for injection again and put in the liquid dispenser, it is an amount of to add 1% tartaric acid solution, adds dipyridamole again, is stirred to form clear and bright solution, stirs down this solution is added in the above-mentioned Radix Salviae Miltiorrhizae extract solution, adds and injects water to ormal weight.Measure pH value, tartaric acid with 1% or 0.1M naOH solution are transferred pH to 4.8～5.8, add an amount of glucose, stirring and dissolving, adding 0.05% active carbon boils, stir insulation 20 minutes, filtered while hot, three grades of microporous filter membrane: be sequentially: 0.8um-0.45um-0.22um, filter, add an amount of water for injection dilution, embedding, 105 ℃ of sterilizations promptly got the glucose infusion liquid agent in 1 hour.The content that records Radix Salviae Miltiorrhizae total phenols in the preparation with spectrophotography is 2%.
Embodiment 13: 10000 parts of Radix Salviae Miltiorrhizaes, 20 parts of dipyridamoles (part is: kilogram or gram)
Get Radix Salviae Miltiorrhizae, add 12 times of water gagings and decoct 2 times, 2h for the first time, 1.5h merges decoction liquor for the second time, filters, and filtrate is concentrated into 1000ml.Add the ethanol precipitation secondary, for the first time the teacher contains the alcohol amount and reaches 50%, makes for the second time to contain the alcohol amount and reach 60%, all cold preservation is placed the back and is filtered filtrate recycling ethanol, the dry Radix Salviae Miltiorrhizae extract that gets at every turn, add dipyridamole, mixing adds PEG4000 and polyoxyethylene monostearate S-40 portion, mix homogeneously, water-bath is melted, and stirs evenly, drip and in dimethicone, to become ball, drip apart from 5cm bore 2.5mm, 70 ℃ of hybrid medicine temperature, liquid coolant height 60cm promptly gets drop pill.
Embodiment 14: 1000 parts of Radix Salviae Miltiorrhizae extracts, 10 parts of dipyridamoles (part is: kilogram or gram)
Get Radix Salviae Miltiorrhizae extract, dipyridamole mix homogeneously, press medication amount: substrate amount=1: 1.2 adding soybean oil, mixing; The prescription of rubber is a gelatin: glycerol: water: titanium dioxide=100g: 40g: 100g: 1g, batchingization adhesive tape part is: weigh batching, in the inputization glue jar, merceration is warming up to 60 ~ 70 ℃ gradually after 30 minutes, stir 5 hours third whiles evacuation and remove bubble, treat evenly back blowing of sizing material, incapsulate after the filtration in the sizing material bucket of machine; The debugging pellet press, 65 ℃ of gelatin box temperature controls, film rotating speed 2.0 is rolled in 45 ℃ of sprinkler body temperature controls, rubber thickness 0.8mm, 18～25 ℃ of indoor temperatures, relative humidity 40%, pelleting; The dry typing drying of rolling that adopts combined with two steps of tray dried, rolled qualitative dry 2 hours, and 22 ℃ of baking temperatures, dry relative humidity should be lower than 65%, and promptly got soft capsule at 24～48 hours drying time.
Embodiment 15: 50 parts of Radix Salviae Miltiorrhizae extracts, 12 parts of dipyridamoles (part is: kilogram or gram)
Get Radix Salviae Miltiorrhizae extract, dipyridamole mix homogeneously, add 7% polyvinylpolypyrrolidone PVPP and 2% mannitol, compacting promptly gets oral cavity disintegration tablet in flakes.
Embodiment 16: 100 parts of Radix Salviae Miltiorrhizaes, 15 parts of dipyridamoles (part is: kilogram or gram)
Get Radix Salviae Miltiorrhizae, add 70～95% alcohol reflux 1～8 hour, filter, filtrate recycling ethanol, medicinal residues decoct with water 1～5 hour, filter; Merge above-mentioned filtrate, being concentrated into relative density is the clear paste of 1.00～1.45 (60～95 ℃), adds dipyridamole, starch is an amount of, mixing, drying is granulated, compacting in flakes, coating, promptly.Promptly get tablet.
Embodiment 17: 3000 parts of Radix Salviae Miltiorrhizaes, 6 parts of dipyridamoles (part is: kilogram or gram)
Get Radix Salviae Miltiorrhizae and extract three times, add 95% alcohol reflux 1.5 hours for the first time, filter, filtrate is concentrated into the thick paste that relative density is 1.30 (55～60 ℃); Add for the second time 50% alcohol reflux 1.5 hours, filter; Add the water reflux, extract, for the third time 2 hours, and filtered, merge two, three times filtrate, filtrate is concentrated into the thick paste that relative density is 1.40 (55～60 ℃), adds concentrated solution for the first time, mixing, making relative density is 1.35～1.39 (55～60 ℃), adds dipyridamole, 4% carboxymethyl starch sodium, mix, drying is granulated granulate, incapsulate, promptly get capsule.
Embodiment 18: 10 parts of Radix Salviae Miltiorrhizae extracts, 2 parts of dipyridamoles (part is: kilogram or gram)
Get Radix Salviae Miltiorrhizae extract, the dipyridamole mix homogeneously, get polyvinylpolypyrrolidone PVPP3.35g and CMC-Na1.05g, add the lemon yellow mixing, get half and medicated powder mixing, K30 anhydrous alcohol solution with 1.5% is made binding agent, 40 order system material, granulate remain half polyvinylpolypyrrolidone PVPP3.35g and CMC-Na1.05g, and the mixed powder that adds the lemon yellow mixing is added in the particle that makes, tabletting promptly gets dispersible tablet.The content that records Radix Salviae Miltiorrhizae total phenols in the preparation with spectrophotography is 82%.
Embodiment 19: 100 parts of Radix Salviae Miltiorrhizaes, 4 parts of dipyridamoles (part is: kilogram or gram)
Get Radix Salviae Miltiorrhizae, add 10 times of water gagings and decoct 4 times, 2 hours for the first time, 1.5h for the second time, third and fourth time 1h, decoction liquor merges, and filters, and filtrate is concentrated into 100ml, adds dipyridamole, 15% lactose mixing, granulates, and sieves, and promptly gets granule.
Embodiment 20: 500 parts of Radix Salviae Miltiorrhizae extracts, 10 parts of dipyridamoles (part is: kilogram or gram)
Get Radix Salviae Miltiorrhizae extract, add dipyridamole, mixing, drying adds 2% magnesium stearate, stevioside is an amount of, and tabletting promptly gets buccal tablet.The content that records Radix Salviae Miltiorrhizae total phenols in the preparation with spectrophotography is 22%.
Embodiment 21: 100 parts of Radix Salviae Miltiorrhizae extracts, 20 parts of dipyridamoles (part is: kilogram or gram)
Get an amount of K-carrageenan, locust bean gum makes swelling with low amounts of water, and slight fever makes dissolving, slowly adds fluid extract, mix homogeneously, and warm macerating is 2 hours under 40 ℃ temperature.With Flos Carthami extract and dipyridamole mixing, add slowly in the colloid solution, mix; Other gets sucrose, citric acid and potassium sorbate, with an amount of water dissolution, filters, and adds in the above-mentioned colloid solution, adds water to ormal weight, and mix homogeneously is crossed colloid mill, and packing promptly gets oral gel.
Claims (11)
1, a kind of pharmaceutical composition that is used for the treatment of cardiovascular and cerebrovascular disease is characterized in that: calculate according to components by weight percent, it by 1～20 part of 10～10000 parts of Radix Salviae Miltiorrhizaes and dipyridamole through extracting refining forming; Or the Radix Salviae Miltiorrhizae extract and the corresponding weight portion dipyridamole that are obtained after extracting by corresponding weight portion medical material are made.
2, according to the pharmaceutical composition of the described treatment cardiovascular and cerebrovascular disease of claim 1, it is characterized in that: calculate according to components by weight percent, it by 1～15 part of 100～5000 parts of Radix Salviae Miltiorrhizaes and dipyridamole through extracting refining forming; Or the Radix Salviae Miltiorrhizae extract and the corresponding weight portion dipyridamole that are obtained after extracting by corresponding weight portion medical material are made.
3, according to the pharmaceutical composition of the described treatment cardiovascular and cerebrovascular disease of claim 2, it is characterized in that: calculate according to parts by weight, it by 1～10 part of 100～2000 parts of Radix Salviae Miltiorrhizaes and dipyridamole through extracting refining forming; Or the Radix Salviae Miltiorrhizae extract and the corresponding weight portion dipyridamole that are obtained after extracting by corresponding weight portion medical material are made.
4, according to the pharmaceutical composition of any described treatment cardiovascular and cerebrovascular disease among the claim 1-3, it is characterized in that: preparation of the present invention is injection and oral formulations; Injection comprises: little liquid drugs injection, powder pin or infusion solutions; Oral formulations comprises: all acceptable dosage forms on the pharmaceuticss such as tablet, dispersible tablet, effervescent tablet, oral cavity disintegration tablet, capsule, soft capsule, microcapsule, granule, pill, powder, drop pill, slow releasing preparation, controlled release preparation, oral liquid, soft extract, extractum, gel, membrane.
5, according to the pharmaceutical composition of the described treatment cardiovascular and cerebrovascular disease of claim 4, it is characterized in that: preparation of the present invention is liquid drugs injection, powder pin, infusion solutions, oral liquid, drop pill, capsule, soft capsule, oral cavity disintegration tablet, tablet, capsule, dispersible tablet, buccal tablet, oral gel or granule.
6, according to the pharmaceutical composition of claim 4 or 5 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: count by weight percentage: the content of phenols component be not less than in the preparation deduction adjuvant amount, water quantities and dipyridamole amount total solid 1%; The component content sum that derives from red rooted salvia that all can be surveyed in the injection be not less than in the preparation deduction adjuvant amount, water quantities and dipyridamole amount total solid 20%; Dipyridamole should be 90.0%～110.0% of labelled amount.
7, according to the preparation of drug combination method of claim 4 or 5 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: get Radix Salviae Miltiorrhizae, add entry or ethanol extraction, the extracting solution concentrate drying gets the Radix Salviae Miltiorrhizae crude extract, one or more that also can further adopt precipitate with ethanol, organic solvent extraction, alkali extraction and acid precipitation, column chromatography carry out suitably refining, get the Radix Salviae Miltiorrhizae extract,, be prepared into the preparation that needs with diverse ways Radix Salviae Miltiorrhizae crude extract or Radix Salviae Miltiorrhizae extract and dipyridamole mixing.
8, according to the preparation of drug combination method of the described treatment cardiovascular and cerebrovascular disease of claim 7, it is characterized in that: Radix Salviae Miltiorrhizae extract can also be commercially available or adopt other preparation methoies to prepare.
9, according to the pharmaceutical composition of any described treatment cardiovascular and cerebrovascular disease among the claim 1-3, it is characterized in that: the present invention has antiplatelet aggregation, reduces myocardial oxygen consumption, microcirculation improvement, the function of the blood supply of increase ischemic region etc.
10, according to the application in cardiovascular and cerebrovascular diseases medicaments such as preparation treatment coronary heart disease, angina pectoris, cerebral thrombosis, apoplexy of the pharmaceutical composition of any described treatment cardiovascular and cerebrovascular disease among the claim 1-3.
11, according to the method for quality control of the pharmaceutical composition of claim 4 or 5 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: its assay is to adopt in high performance liquid chromatography, spectrophotography, thin layer chromatography scanning, the titrimetry one or more to record.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510093138 CN1915294A (en) | 2005-08-19 | 2005-08-19 | Medicinal composition, preparation method and quality control method |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200510093138 CN1915294A (en) | 2005-08-19 | 2005-08-19 | Medicinal composition, preparation method and quality control method |
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| Publication Number | Publication Date |
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| CN1915294A true CN1915294A (en) | 2007-02-21 |
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| CN 200510093138 Pending CN1915294A (en) | 2005-08-19 | 2005-08-19 | Medicinal composition, preparation method and quality control method |
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| Country | Link |
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| CN (1) | CN1915294A (en) |
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