CN1954820A - Medical composite for treating curdio-cerebral vascular disease and its preparation method and application - Google Patents
Medical composite for treating curdio-cerebral vascular disease and its preparation method and application Download PDFInfo
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- CN1954820A CN1954820A CN 200510114736 CN200510114736A CN1954820A CN 1954820 A CN1954820 A CN 1954820A CN 200510114736 CN200510114736 CN 200510114736 CN 200510114736 A CN200510114736 A CN 200510114736A CN 1954820 A CN1954820 A CN 1954820A
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Abstract
A composite medicine in the form of injection or orally taken solid or liquid for treating ischemic cerebral apoplexy, coronary heart disease, angina pectoris, cardiac insufficiency, apoplexy sequelae, hepato-renal syndrome, cardiopulmonary disease, diabetes, etc is prepared from breviscapine and the general flavone and general lactone of gingko leaf. Its preparing process is also disclosed.
Description
Technical field
The present invention is a kind of pharmaceutical composition for the treatment of cardiovascular and cerebrovascular disease and its production and application, belongs to technical field of medicaments.
Technical background
Cardiovascular and cerebrovascular disease such as angina pectoris are commonly encountered diseases, the frequently-occurring diseases of middle-aged and elderly people.Mean that coronary atherosclerosis causes coronary insufficiency, the retrosternal pain that the rapid temporary transient hypoxic-ischemic of cardiac muscle causes.The category such as " thoracic obstruction ", " cardiopalmus ", " angina pectoris " that belongs to the traditional Chinese medical science.Primary disease Chang Fanfu outbreak, touching difficulty heals, and the healthy of people in serious harm.Prevent and treat purpose in order to reach, a large amount of research has been done by many inventors and medicine enterprise, and the product of some treatments also is provided; As: the number of patent application of the applicant's application is: 200410022510.5, name is called the patent application of " a kind of Chinese medicine preparation for the treatment of cardiovascular and cerebrovascular disease and preparation method thereof ", and the disease that it is used for the treatment for the treatment of cardiac and cerebral vascular diseases has definite curative effect; But in further investigation, find, adopt the effective site compatibility to improve curative effect greatly, be easy to preparations shaping, improved the safety of preparation and the controllability of quality.
Summary of the invention
The objective of the invention is to: a kind of pharmaceutical composition for the treatment of cardiovascular and cerebrovascular disease and its production and application is provided; The present invention is directed to prior art, according to cardiovascular and cerebrovascular disease such as coronary heart disease, cerebral thrombosis, alzheimer disease etc. all contract because of blood vessel is narrow, reason such as blood flow minimizing causes the diseases induced principle of blood supply insufficiency, on the basis of experiment screening, adopt breviscapine Folium Ginkgo total flavones and total lactone compatibility to make preparation, optimize best prescription and technology; The product that obtains, particularly ejection preparation product can play activating blood circulation to dissipate blood stasis, TONGMAI SHULUO, improve blood circulation and metabolism.For example coronary heart disease is that coronary atherosclerosis causes myocardial ischemia, anoxia and the heart disease that causes, and two medicines share, and can play to improve the myocardial metabolism effect, increase coronary flow, and the blood that improves cardiac muscle is provided with the effect of allevating angina pectoris.The present invention has curative effect preferably for treating cardiovascular and cerebrovascular disease such as coronary heart disease, angina pectoris, arrhythmia, cerebral thrombosis, alzheimer disease etc.And the present invention is pure Chinese medicinal preparation, but the little patients life-time service of its untoward reaction.
The present invention constitutes like this: calculate according to percentage by weight, it is to be made by breviscapine 1～99% and Folium Ginkgo total flavones and total lactone 99～1% and suitable adjuvant.Be preferably: calculate according to percentage by weight, it is to be made by breviscapine 10～60% and Folium Ginkgo total flavones and total lactone 90～40% and suitable adjuvant.Say accurately: calculate according to percentage by weight, it is to be made by Folium Ginkgo total flavones and total lactone 90～60% and breviscapine and total lactone 40～60% and suitable adjuvant.
Breviscapine in the described prescription can be the highly finished product of Herba Erigerontis alcohol extract, Herba Erigerontis water extract, Herba Erigerontis water extract-alcohol precipitation extract, Herba Erigerontis semi-bionic extraction thing, Herba Erigerontis supercritical extract or above each extract; Folium Ginkgo total flavones and total lactone can be the highly finished product of Folium Ginkgo alcohol extract, Folium Ginkgo water extract, Folium Ginkgo water extract-alcohol precipitation extract, Folium Ginkgo semi-bionic extraction thing, Folium Ginkgo supercritical extract or above each extract.Described preparation be directly used in the injection of drug administration by injection, directly for the venous transfusion of intravenous drip, need be used for the concentrated solution for injection of intravenous drip and injectable sterile powder and aseptic block and tablet, capsule, granule, drop pill, pill, soft capsule, oral liquid, oral cavity disintegration tablet or the dispersible tablet that makes with freeze-drying or spray drying method after the dilution.Contain flavones ingredient and lactone composition in the preparation, calculate by weight percentage, the breviscapine in the preparation and the flavones ingredient, the lactone component content sum that derive from Folium Ginkgo be not less than deduction adjuvant amount and water quantities in the preparation total solid 50%.
Folium Ginkgo total flavones and total lactone effective site are preparations like this: get the Folium Ginkgo medical material, adding entry or alcoholic solution after the pulverizing extracts, merge extractive liquid,, filter, concentrate ginkgo biloba crude extract, adopt in ethanol precipitation, column chromatography, extraction, the flocculent precipitation one or more to unite on this basis to use carry out suitably refining, Folium Ginkgo total flavones and total lactone effective site; Breviscapine is preparation like this: get the Herba Erigerontis medical material, adding entry or alcoholic solution after the pulverizing extracts, merge extractive liquid,, filter, concentrate the Herba Erigerontis crude extract, adopt in ethanol precipitation, column chromatography, extraction, the flocculent precipitation one or more to unite on this basis to use carry out suitably refining, breviscapine; With breviscapine and Folium Ginkgo total flavones and total lactone mix homogeneously, add adjuvant and make different preparations.
The Injectable sterile block of described compositions prepares like this: get breviscapine, Folium Ginkgo total flavones and total lactone, 120g mannitol, add 1800ml water for injection, stirring makes dissolving, with saturated sodium hydroxide solution adjust pH to 7.0～7.5, add the injection water to 2000ml, mixing, the needle-use activated carbon of adding 0.5% boiled coarse filtration 30 minutes, reuse 0.45 μ m and 0.22 μ m microporous filter membrane filter, the filtrate packing, every bottle of 2.0ml, lyophilization, equilibration time when the balance solidification point of phase I is 0 ℃ is 1.5 hours, i.e. the time of shelf temperature and product temperature basically identical; The second stage solidification point is from 0 ℃ during to minimum eutectic temperature-16 ℃, and shelf temperature and product temperature equilibration time are 2 hours; Phase III continues to be cooled to-40 ℃, needs 2 hours approximately, keeps this temperature 2 hours, freeze the jail fully until product, promptly begin evacuation, enter drying program, under-40 ℃ of constant temperature-and evacuation, slowly heat up 2～4 ℃/h, to the lowest total of the melting point temperature, the time is about 12 hours, after sublimation drying is finished, continuation is under the low pressure condition, and it is dry to remove residual moisture to heat up, and the time is about 14～16 hours, kept more than 35 ℃ dry 1.5 hours, gland, promptly.
The injection and the concentrated solution for injection of described compositions prepare like this: get breviscapine, Folium Ginkgo total flavones and total lactone, add an amount of water for injection dissolving, by volume add 0.5% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, with saturated sodium hydroxide solution adjust pH to 7.0～7.5, boils, 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining add the injection water, divide to install to ampoule bottle, seal sterilization, promptly.
The pharmaceutical composition of described treatment cardiovascular and cerebrovascular disease is mainly used in diseases such as treatment ischemia apoplexy, angina pectoris, cardiac insufficiency, apoplexy sequela, hepatorenal syndrome, heart and lung diseases, diabetes and complication thereof.
Compared with prior art, the applicant carried out lot of experiments, filtering out the prescription for the treatment of diseases such as angina pectoris is breviscapine, Folium Ginkgo total flavones and total lactone, and best proportion compatibility is Folium Ginkgo total flavones and total lactone 60-40% and breviscapine 40-60%.Adopt good, the steady quality of prepared product appearance of the present invention.
For proving that medicine provided by the invention has effective effect, the applicant has carried out a series of experiments.
Experimental example 1: to the comparative study of different proportioning pharmacodynamics
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; these two kinds of medicines (breviscapine, Folium Ginkgo total flavones and total lactone) are pressed 1: 99,10: 90,40: 60,60: 40,60: 40,99: 1 totally 6 combination and compatibilities prescriptions, carried out the prescription screening test of system.
The prescription research conclusion
The screening and assessment index
Prescription
Herba Erigerontis Folium Ginkgo total flavones platelet presses down thrombosis and cultivates the myocardial cell injury test
Numbering
Plain (mg) and total lactone (mg) system rate (%) suppression ratio (%) LDH reduce % CK and reduce %
1 1 99 52.1％ 49.1％ 42.5％ 49.7％
2 10 90 80.4％ 77.2％ 61.1％ 78.4％
3 40 60 82.4％ 75.3％ 60.2％ 76.5％
4 60 40 63.8％ 60.2％ 49.8％ 57.4％
5 80 20 70.5％ 60.4％ 48.6％ 65.5％
6 99 1 50.1％ 51.5％ 45.7％ 60.5％
By experimental result as can be known, the best proportion compatibility of breviscapine, Folium Ginkgo total flavones and total lactone is breviscapine 10-40% and Folium Ginkgo total flavones and total lactone 90-60%.
Experimental example 2: injection Study on Forming
2.1pH value is to the influence of injection
The applicant finds that in development suitable acid-base value is the stable key factor of medicine, and in order to improve the quality of this injection, the applicant placed 3 months for 40 ℃ the injection of 6 kinds of different pH value, investigated its stability respectively.The result shows that 7.0～7.5 pH value scope is the most reasonable.
0 month March
The total lactone of the total lactone of pH value clarity (mg/ml) clarity (mg/ml)
Differ from 1.00 5.0 differ from 1.15
5.5 clear and bright 1.12 differ from 1.08
6.0 clear and bright 1.11 differ from 1.10
6.5 clear and bright 1.13 differ from 1.07
7.0 clear and bright 1.16 clear and bright 1.12
7.5 clear and bright 1.18 clear and bright 1.13
Differ from 1.08 8.0 differ from 1.20
2.2pH value is to the influence of freeze-dried powder
Number 123456789
PH value of solution 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5 9.0 before the lyophilizing
The good good job difference of insufficient formability difference difference difference is poor
The yellowish yellowish yellowish-brown deep yellow palm fibre of color and luster
PH value of solution 4.5 5.2 5.5 6.0 6.8 7.3 7.4 8.1 8.5 after the lyophilizing
The result shows that the rational pH value scope of the present invention is 7.0-7.5, and product quality is good.
Concrete embodiment
Embodiments of the invention 1: breviscapine 10g Folium Ginkgo total flavones and total lactone 90g
Get breviscapine, Folium Ginkgo total flavones and total lactone and 120g mannitol, add 1800ml water for injection, stirring makes dissolving, with saturated sodium hydroxide solution adjust pH to 7.0～7.5, add the injection water to 2000ml, mixing, the needle-use activated carbon of adding 0.5% boiled coarse filtration 30 minutes, reuse 0.45 μ m and 0.22 μ m microporous filter membrane filter, the filtrate packing, every bottle of 2.0ml, lyophilization, equilibration time when the balance solidification point of phase I is 0 ℃ is 1.5 hours, i.e. the time of shelf temperature and product temperature basically identical; The second stage solidification point is from 0 ℃ during to minimum eutectic temperature-16 ℃, and shelf temperature and product temperature equilibration time are 2 hours; Phase III continues to be cooled to-40 ℃, need 2 hours approximately, kept this temperature 2 hours, freeze the jail fully until product, promptly begin evacuation, enter drying program, under-40 ℃ of constant temperature-evacuation, slowly heat up, 2～4 ℃/h, to the lowest total of the melting point temperature, the time is about 12 hours, after sublimation drying is finished, continuation is under the low pressure condition, heating up, dry the time is about 14～16 hours to remove residual moisture, keeps more than 35 ℃ dry 1.5 hours, gland, promptly get the Injectable sterile block, one time 2,1 time on the one, with using behind 250ml 0.9% physiological saline solution, after testing, calculate flavonoid in the injection by weight percentage, the lactone component content account in the preparation deduction adjuvant amount and water quantities total solid 85%.
Embodiments of the invention 2: breviscapine 40g Folium Ginkgo total flavones and total lactone 60g
Get breviscapine, Folium Ginkgo total flavones and total lactone, add an amount of water for injection dissolving, by volume add 0.5% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, with saturated sodium hydroxide solution adjust pH to 7.0～7.5, boils, 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining add the injection water, divide to install to ampoule bottle, seal sterilization, promptly get injection and concentrated solution for injection.
Embodiments of the invention 3: breviscapine 10g Folium Ginkgo total flavones and total lactone 90g
Get breviscapine, Folium Ginkgo total flavones and total lactone, add an amount of water for injection dissolving, add the glucose or the sodium chloride of ormal weight, by volume add 0.5% active carbon behind the mixed dissolution, boil, keep little 30min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, the saturated sodium hydroxide solution of reuse adjust pH to 7.0～7.5, boil, 4 ℃ of cold preservations are spent the night, and coarse filtration, fine straining add the injection water, packing, sterilization promptly gets glucose or sodium chloride intravenous infusion.
Embodiments of the invention 4: breviscapine 40g Folium Ginkgo total flavones and total lactone 60g
Get breviscapine, Folium Ginkgo total flavones and total lactone, add 1800ml water for injection, stirring makes dissolving, with saturated sodium hydroxide solution adjust pH to 7.0～7.5, add the injection water to 2000ml, mixing, the needle-use activated carbon of adding 0.5%, boiled 30 minutes, coarse filtration, reuse 0.45 μ m and 0.22 μ m microporous filter membrane filter, divide and install in the enamel tray, lyophilization, the equilibration time when the balance solidification point of phase I is 0 ℃ is 1.5 hours, i.e. the time of shelf temperature and product temperature basically identical; The second stage solidification point is from 0 ℃ during to minimum eutectic temperature-16 ℃, and shelf temperature and product temperature equilibration time are 2 hours; Phase III continues to be cooled to-40 ℃, need 2 hours approximately, kept this temperature 2 hours, freeze the jail fully until product, promptly begin evacuation, enter drying program, under-40 ℃ of constant temperature-evacuation, slowly heat up, 2～4 ℃/h, to the lowest total of the melting point temperature, time is about 12 hours, after sublimation drying is finished, continue under the low pressure condition, it is dry to remove residual moisture to heat up, time is about 14～16 hours, kept more than 35 ℃ dry 1.5 hours, and under aseptic condition, divided to install in the cillin bottle, promptly get injectable sterile powder.
Embodiments of the invention 5: breviscapine 40g Folium Ginkgo total flavones and total lactone 60g
Get breviscapine, Folium Ginkgo total flavones and total lactone, mixing adds an amount of water for injection dissolving, by volume add 0.5% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, with saturated sodium hydroxide solution adjust pH to 7.0～7.5, boil, 4 ℃ of cold preservations are spent the night, and coarse filtration, fine straining are 150 ℃ in inlet temperature, leaving air temp is 65 ℃, and air velocity is 25ms
-1Condition under spray drying get powder, packing promptly gets injectable sterile powder.
Embodiments of the invention 6: breviscapine 20g Folium Ginkgo total flavones and total lactone 80g
With breviscapine and Folium Ginkgo total flavones and total lactone mix homogeneously, add 4.5% polyvinylpolypyrrolidone PVPP and 1.5% mannitol, compacting promptly gets oral cavity disintegration tablet in flakes.
Embodiments of the invention 7: breviscapine 80g Folium Ginkgo total flavones and total lactone 20g
With breviscapine and Folium Ginkgo total flavones and total lactone mix homogeneously, to be that 1.5: 1 Macrogol 4000 is put in the rustless steel container with the principal agent ratio, add extract, mix homogeneously, be heated to 80-90 ℃, treat whole fusions after, 70-80 ℃ of insulation, mechanical high-speed stirs 10min to even, be transferred in the reservoir, the dropping liquid valve is regulated in 70～80 ℃ of insulations, splash in 30～40 ℃ the dimethicone, drip apart from 5～6cm, drip 40～45 droplets/minute of speed, to the greatest extent and wipe dimethicone the drop pill drop that forms, packing promptly gets drop pill.
Embodiments of the invention 8: breviscapine 99g Folium Ginkgo total flavones and total lactone 1g
With breviscapine and Folium Ginkgo total flavones and total lactone mix homogeneously, in principal agent: the ratio of adjuvant=1: 1 adds calcium sulfate, by principal agent: the ratio adding microcrystalline Cellulose of adjuvant=1: 1, evenly mixed, make soft material in right amount with 60% ethanol, cross 20 mesh sieve system granules, 60 ℃ of dryings, take out, cross 30 mesh sieve granulate, add an amount of Pulvis Talci, micropowder silica gel, evenly mixed, tabletting promptly gets dispersible tablet.
Embodiments of the invention 9: breviscapine 1g Folium Ginkgo total flavones and total lactone 99g
With breviscapine and Folium Ginkgo total flavones and total lactone mix homogeneously, add 2 times of amount starch, 0.8% stevioside, 2% microcrystalline Cellulose, with the alcoholic solution system soft material of an amount of polyvinylpyrrolidone k30, granulate 70 ℃ of forced air dryings, granulate, granulate promptly gets granule.
Embodiments of the invention 10: breviscapine 60g Folium Ginkgo total flavones and total lactone 40g
With breviscapine and Folium Ginkgo total flavones and total lactone mix homogeneously, add the starch of equivalent, mix homogeneously is granulated, and is encapsulated, promptly gets capsule.
Breviscapine among the above embodiment, Folium Ginkgo total flavones and total lactone can be with breviscapine, Folium Ginkgo total flavones and total lactones commercially available or that make by the inventive method, no matter be alcohol extract, water extract, water extract-alcohol precipitation extract, semi-bionic extraction thing or supercritical extract or the like, still: total flavones and total lactone glycoside content are greater than 50% in Folium Ginkgo total flavones and the total lactone.Can guarantee the therapeutic effect of product like this.
Claims (10)
1, a kind of pharmaceutical composition for the treatment of cardiovascular and cerebrovascular disease is characterized in that: calculate according to percentage by weight, it is to be made by breviscapine 1～99% and Folium Ginkgo total flavones and total lactone 99～1% and suitable adjuvant.
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 percentage by weight, it is to be made by breviscapine 10～60% and Folium Ginkgo total flavones and total lactone 90～40% and suitable adjuvant.
3, according to the pharmaceutical composition of claim 1 or 2 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: calculate according to percentage by weight, it is to be made by breviscapine 10～40% and Folium Ginkgo total flavones and total lactone 90～60% and suitable adjuvant.
4, according to the pharmaceutical composition of any described treatment cardiovascular and cerebrovascular disease of claim 1～3, it is characterized in that: the breviscapine in the described prescription can be the highly finished product of Herba Erigerontis alcohol extract, Herba Erigerontis water extract, Herba Erigerontis water extract-alcohol precipitation extract, Herba Erigerontis semi-bionic extraction thing, Herba Erigerontis supercritical extract or above each extract; Folium Ginkgo total flavones and total lactone can be the highly finished product of Folium Ginkgo alcohol extract, Folium Ginkgo water extract, Folium Ginkgo water extract-alcohol precipitation extract, Folium Ginkgo semi-bionic extraction thing, Folium Ginkgo supercritical extract or above each extract.
5, according to the pharmaceutical composition of any described treatment cardiovascular and cerebrovascular disease of claim 1～4, it is characterized in that: described preparation be directly used in the injection of drug administration by injection, directly for the venous transfusion of intravenous drip, need be used for the concentrated solution for injection of intravenous drip and injectable sterile powder and aseptic block and tablet, capsule, granule, drop pill, pill, soft capsule, oral liquid, oral cavity disintegration tablet or the dispersible tablet that makes with freeze-drying or spray drying method after the dilution.
6, according to the pharmaceutical composition of any described treatment cardiovascular and cerebrovascular disease in the claim 1～5, it is characterized in that: contain flavones ingredient and lactone composition in the preparation, calculate by weight percentage, the breviscapine in the preparation and the flavones ingredient, the lactone component content sum that derive from Folium Ginkgo be not less than deduction adjuvant amount and water quantities in the preparation total solid 50%.
7, according to the preparation of drug combination method of any described treatment cardiovascular and cerebrovascular disease in the claim 1～5, it is characterized in that:
A. Folium Ginkgo total flavones and total lactone effective site are preparations like this: get the Folium Ginkgo medical material, adding entry or alcoholic solution after the pulverizing extracts, merge extractive liquid,, filter, concentrate ginkgo biloba crude extract, adopt in ethanol precipitation, column chromatography, extraction, the flocculent precipitation one or more to unite on this basis to use carry out suitably refining, Folium Ginkgo total flavones and total lactone effective site;
B. breviscapine is preparation like this: get the Herba Erigerontis medical material, adding entry or alcoholic solution after the pulverizing extracts, merge extractive liquid,, filter, concentrate the Herba Erigerontis crude extract, adopt in ethanol precipitation, column chromatography, extraction, the flocculent precipitation one or more to unite on this basis to use carry out suitably refining, breviscapine;
C. with breviscapine and Folium Ginkgo total flavones and total lactone mix homogeneously, add adjuvant and make different preparations.
8, preparation of drug combination method according to the described treatment cardiovascular and cerebrovascular disease of claim 7, it is characterized in that: the Injectable sterile block of described compositions prepares like this: get breviscapine, Folium Ginkgo total flavones and total lactone, 120g mannitol, add 1800ml water for injection, stirring makes dissolving, with saturated sodium hydroxide solution adjust pH to 7.0～7.5, add the injection water to 2000ml, mixing, the needle-use activated carbon of adding 0.5%, boiled 30 minutes, coarse filtration, reuse 0.45 μ m and 0.22 μ m microporous filter membrane filter, the filtrate packing, every bottle of 2.0ml, lyophilization, the equilibration time when the balance solidification point of phase I is 0 ℃ is 1.5 hours, i.e. the time of shelf temperature and product temperature basically identical; The second stage solidification point is from 0 ℃ during to minimum eutectic temperature-16 ℃, and shelf temperature and product temperature equilibration time are 2 hours; Phase III continues to be cooled to-40 ℃, needs 2 hours approximately, keeps this temperature 2 hours, freeze the jail fully until product, promptly begin evacuation, enter drying program, evacuation under-40 ℃ of constant temperature slowly heats up 2～4 ℃/h, to the lowest total of the melting point temperature, the time is about 12 hours, after sublimation drying is finished, continuation is under the low pressure condition, and it is dry to remove residual moisture to heat up, and the time is about 14～16 hours, kept more than 35 ℃ dry 1.5 hours, gland, promptly.
9, preparation of drug combination method according to the described treatment cardiovascular and cerebrovascular disease of claim 7, it is characterized in that: the injection and the concentrated solution for injection of described compositions prepare like this: get breviscapine, Folium Ginkgo total flavones and total lactone, add an amount of water for injection dissolving, by volume add 0.5% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, with saturated sodium hydroxide solution adjust pH to 7.0～7.5, boil, coarse filtration is spent the night in 4 ℃ of cold preservations, fine straining, add the injection water, divide to install to ampoule bottle, seal sterilization, promptly.
10, as the application of the pharmaceutical composition of any described treatment cardiovascular and cerebrovascular disease in the claim 1～5, it is characterized in that: described pharmaceutical composition is used for the application at disease medicaments such as preparation treatment ischemia apoplexy, angina pectoris, cardiac insufficiency, apoplexy sequela, hepatorenal syndrome, heart and lung diseases, diabetes and complication thereof.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200510114736 CN1954820A (en) | 2005-10-26 | 2005-10-26 | Medical composite for treating curdio-cerebral vascular disease and its preparation method and application |
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| CN 200510114736 CN1954820A (en) | 2005-10-26 | 2005-10-26 | Medical composite for treating curdio-cerebral vascular disease and its preparation method and application |
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