CN1915268A - Medicinal composition, preparation method and quality control method - Google Patents

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 ginseng or its stem and leaf or red ginseng or their extract and troxerutin. Its preparing process and quality control method are also disclosed.

Description

A kind of pharmaceutical composition and preparation method thereof and method of quality control

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 is a big persistent ailment that threatens world's healthy population as coronary heart disease, myocardial infarction, rhomboembolia type cerebrovascular, and the trend that progressively rises is arranged in recent years.According to World Health Organization (WHO), the philtrum of per 3 death in the whole world just has 1 to die from cardiovascular and cerebrovascular disease, and its mortality rate is also in continuous increase, and cardiovascular and cerebrovascular disease has caused the extensive great attention of domestic and international medical circle.Therefore, invent a kind of determined curative effect, safe ready, side effect is little or the medicine that has no side effect seems particularly important.So far, existing a large amount of Chinese medicine and western medicine emerge, but because Western medicine does not have absolute advantages and side effect bigger at treating cardiac and cerebral vascular diseases, and Chinese medicine is because in the process of effective component extracting, other impurity components that produce produce adverse consequences to people's physical ability, under the prerequisite of strict quality method without comparison, produce, the constant product quality and the safety that obtain are unreliable, though and oral preparation of Chinese traditional medicinal is of a great variety, available property is big, but because bioavailability is low, the course of treatment is longer, and onset rapidly is so develop determined curative effect, have no adverse reaction, the medicine that can effectively control the quality of the pharmaceutical preparations simultaneously again just becomes the new focus of people.In the prior art, clinical and drug effect shows in a large number, and the extract of Radix Ginseng or its stem and leaf part or Radix Ginseng Rubra and described medical material demonstrates unique advantage aspect cardiovascular and cerebrovascular disease, and troxerutin also has aggressive posture in this regard, while does not have the report with both compatibility agents again up to now.So the inventor adopts conventional method to make suitable formulations the two compatibility and researchs and develops.

Summary of the invention

The objective of the invention is to disclose a kind of pharmaceutical composition for the treatment of cardiovascular and cerebrovascular disease, adopt the extract and the troxerutin compatibility of Radix Ginseng or Stem and leaf of Radix Ginseng part or Radix Ginseng Rubra or above-mentioned medical material to make the preparation that needs, test finds that this prescription compatibility does not have toxic and side effects through pharmacological effect, and given full play to the advantage of Chinese medicine and western medicine, rapid-action, curative effect affirms that the two share, and has the obvious synergistic synergistic function for treating cardiovascular and cerebrovascular disease such as coronary heart disease, angina pectoris, obliterated cerebral vascular disease etc.Effectively avoided using separately at present the drawback of Chinese medicine or Western medicine; Another object of the present invention is to disclose the preparation of drug combination method of this treatment cardiovascular and cerebrovascular disease, comprise multiple injection type and peroral dosage form, effectively avoid the single inconvenience that brings of dosage form of present doctors and patients' medication, satisfied the selection of clinician and extensive patients to a greater degree; The present invention also aims to provide its method of quality control,, and then overcome the variety of issue that prior art exists with assurance stability of formulation, safety and effectiveness.

Preparation of the present invention is to constitute like this: calculate according to components by weight percent, it by 1～50 part of 10～10000 parts of Radix Ginsengs and troxerutin through extracting refining forming; Or the Radix Ginseng extract and the corresponding weight portion troxerutin that are obtained after extracting by corresponding weight portion medical material are made; Specifically, calculate according to components by weight percent, it by 1～30 part of 100～5000 parts of Radix Ginsengs and troxerutin through extracting refining forming; Or the Radix Ginseng extract and the corresponding weight portion troxerutin that are obtained after extracting by corresponding weight portion medical material are made; Say exactly: calculate according to parts by weight, it by 1～20 part of 100～3000 parts of Radix Ginsengs and troxerutin through extracting refining forming; Or the Radix Ginseng extract and the corresponding weight portion troxerutin that are obtained after extracting by corresponding weight portion medical material are made.

Radix Ginseng in the pharmaceutical composition of described treatment cardiovascular and cerebrovascular disease and extract thereof can also be Stem and leaf of Radix Ginseng part or the Radix Ginseng Rubra and the extracts thereof of same ratio.

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: the content of saponin component be not less than in the preparation deduction adjuvant amount, water quantities and troxerutin amount total solid 5%; The component content sum that derives from ginseng crude drug or Stem and leaf of Radix Ginseng part or Radix Ginseng Rubra medical material that all can be surveyed in the injection is not less than 20% troxerutin of the total solid of deduction adjuvant amount, water quantities and troxerutin amount in the preparation; Troxerutin 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 Ginseng or Stem and leaf of Radix Ginseng part or Radix Ginseng Rubra, add entry or ethanol extraction, the extracting solution concentrate drying gets the medical material crude extract, one or more that also can further adopt precipitate with ethanol, organic solvent extraction, column chromatography carry out suitably refining, get the medical material extract, with medical material crude extract or medical material extract and troxerutin mixing, be prepared into the preparation that needs with conventional method.

Radix Ginseng or Stem and leaf of Radix Ginseng part or Radix Ginseng Rubra extract can also be commercially available or adopt other preparation methoies to prepare in the preparation of drug combination method of treatment cardiovascular and cerebrovascular disease.

The pharmaceutical composition of described treatment cardiovascular and cerebrovascular disease has anticoagulant; antithrombotic forms; protecting myocardial cell, blood flow increasing, antagonism myocardial oxygen consumption, functions such as blood pressure lowering are used for the treatment of cardiovascular and cerebrovascular diseases such as coronary heart disease, angina pectoris, vasculitis, obliterated cerebral vascular disease.

Its assay is to adopt in high performance liquid chromatography, spectrophotography, thin layer chromatography scanning, the titrimetry one or more to record in the pharmaceutical composition of described treatment cardiovascular and cerebrovascular disease.

In the prior art, the extract of Radix Ginseng or Stem and leaf of Radix Ginseng part or Radix Ginseng Rubra or above-mentioned medical material and troxerutin all demonstrate certain advantage in the treatment cardiovascular and cerebrovascular disease, because its effective ingredient purity is higher, the application of injection in the emergency and severe disease treatment of single medicinal material all arranged at present.The inventor finds clinically both to be made up, and can obtain potentiation, but up to now, does not have the preparation report of the two prescription.So, the applicant is combined into novel formulation with Radix Ginseng or its stem and leaf part or its Radix Ginseng Rubra extract and troxerutin and develops research, bring into play both cooperative compensating effects by compatibility, for new medication of treatment increase of cardiovascular and cerebrovascular disease is selected in coronary heart disease, angina pectoris, obliterated cerebral vascular disease, atherosclerosis etc.Simultaneously, can system extract and the safety of troxerutin compatibility and the controllability of quality of further investigation Radix Ginseng or its stem and leaf part or Radix Ginseng Rubra or above-mentioned medical material, 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 Ginseng extract: troxerutin) carried out the prescription screening test of system; found that with Radix Ginseng extract (Radix Ginseng total saponins content is 90%): the prescription pharmacological action of troxerutin=7: 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; can obviously increase simultaneously blood flow coronarius, reduce myocardial oxygen consumption, thus the better protection ischemic myocardium.

Pharmaceutical preparation of the present invention, with respect to the independent preparation of Radix Ginseng, troxerutin better efficacy not only, and use is carried all very convenient, the multiple different ejection preparation and the preparation method of oral formulations are 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 the effective effect of medicine provided by the invention.

(1) the prescription screening experimental study conclusion of drug regimen compatibility

We test by antiplatelet aggregation; suppress mouse tail thrombotest and the anti-protective effect test that lacks sugared anoxia to the In vitro culture myocardial cell injury; the Radix Ginseng extract of different content or Radix Paeoniae Alba extract and troxerutin have been carried out the prescription screening test of system in varing proportions; found that the curative effect after Radix Ginseng or Radix Ginseng extract and troxerutin compatibility use has remarkable potentiation with troxerutin more separately; it with Radix Ginseng total saponins content 90% Radix Ginseng extract: troxerutin=combination in 7: 1; the prescription pharmacological action is strong and consumption is lower, is best prescription so determine this ratio prescription.

Table 1 prescription research conclusion

Prescription is formed and ratio		The screening and assessment index
						Formula number	Radix Ginseng extract: troxerutin	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∶10 1∶5 1∶1 4∶1 7∶1 15∶1 20∶1	82.2％ 80.5％ 79.9％ 78.8％ 82.4％ 71.3％ 67.9％	55.4％ 47.8％ 52.5％ 58.5％ 62.5％ 57.5％ 52.1％					42.2％ 39.2％ 32.5％ 48.1％ 51.3％ 50.5％ 42.0％	50.5％ 48.8％ 40.7％ 43.5％ 51.2％ 49.1％ 43.5％

Annotate: the content of Radix Ginseng total saponins is 90% in the extract.

Table 2: prescription research conclusion

Prescription is formed and ratio		The screening and assessment index
						Formula number	Radix Ginseng extract: troxerutin	Platelet suppression ratio (%)	Thrombosis suppression ratio (%)	The test of cultivation myocardial cell injury
LDH reduces %	CK reduces %
		1 2 3 4 5 6 7	4∶1 7∶1 10∶1 20∶1 30∶1 50∶1 150∶1	55.2％ 59.5％ 53.9％ 55.8％ 51.4％ 45.3％ 40.9％	39.4％ 35.8％ 37.5％ 44.5％ 38.5％ 39.5％ 43.1％					31.2％ 37.2％ 35.9％ 32.1％ 39.3％ 34.5％ 38.0％	36.5％ 35.8％ 39.7％ 37.5％ 35.2％ 30.1％ 29.5％

Annotate: the content of Radix Ginseng total saponins is 60% in the extract.

Table 3: prescription research conclusion

	Prescription is formed and ratio	The screening and assessment index
						Formula number	Radix Ginseng extract: troxerutin	Platelet suppression ratio (%)	Thrombosis suppression ratio (%)	The test of cultivation myocardial cell injury
LDH reduces %	CK reduces %
		1 2 3 4 5 6 7	4∶1 7∶1 15∶1 50∶1 150∶1 400∶1 600∶1	32.1％ 35.4％ 30.2％ 32.7％ 36.3％ 32.7％ 25.7％	20.4％ 27.9％ 18.9％ 17.2％ 23.5％ 19.2％ 17.2％					21.1％ 25.5％ 23.9％ 20.9％ 19.4％ 22.9％ 20.9％	18.2％ 23.0％ 15.4％ 19.4％ 21.5％ 14.4％ 19.4％

Annotate: the content of Radix Ginseng total saponins is 30% in the extract.

Table 4: prescription research conclusion

Prescription is formed and ratio		The screening and assessment index
						Formula number	Radix Ginseng extract: troxerutin	Platelet suppression ratio (%)	Thrombosis suppression ratio (%)	The test of cultivation myocardial cell injury
LDH reduces %	CK reduces %
		1 2 3 4 5 6 7	7∶1 15∶1 50∶1 100∶1 300∶1 500∶1 800∶1	28.2％ 30.2％ 20.7％ 15.1％ 15.2％ 14.6％ 13.7％	21.5％ 18.9％ 15.2％ 10.5％ 13.2％ 15.3％ 10.2％					16.2％ 15.9％ 13.9％ 15.3％ 14.6％ 11.3％ 10.9％	18.5％ 15.4％ 12.4％ 11.2％ 13.9％ 12.2％ 10.4％

Annotate: the content of Radix Ginseng total saponins is 5% in the extract.

From above-mentioned prescription screening result as can be seen, the Radix Ginseng extract of different purity or Radix Paeoniae Alba extract and troxerutin compatibility all can produce certain curative effect, but through system thinking, determine with Radix Ginseng total saponins content be 90% Radix Ginseng extract with troxerutin with 7: 1 ratio compatibility pharmacological action by force and consumption is lower, preparations shaping and having good stability, can reach the effect of efficacy enhancing and toxicity reducing.

(2) Radix Ginseng extract: affirmation and the side's of tearing open research conclusion of troxerutin=7: 1 combination prescription effectiveness

Drug efficacy study through system shows; after the two herbal medicine use in conjunction; aspect blood circulation promoting and blood stasis dispelling, has the obvious synergistic effect; at aspects such as treatment coronary heart disease, angina pectoris, cerebral thrombosiss the obvious synergistic effect is arranged also; simultaneously; can obviously increase blood flow, reduction Ischemic Heart load, the antagonism myocardial oxygen consumption of arteria coronaria, thus the better protection ischemic myocardium.

The prescription research conclusion

Pilot project	Prescription of the present invention	The Radix Ginseng extract group	The troxerutin group
				Myocardial infarction model test improves blood stasis model rat blood rheology test platelet aggregation-against and tests anti-mouse tail thrombotest due to the dog CAL method	Effect is remarkable, the effect reinforced effects is remarkable, the effect reinforced effects is remarkable, the effect reinforced effects is remarkable, and effect strengthens	The general effect of effect positive effect positive effect is obvious	The general effect positive effect of effect positive effect is obvious

Concrete embodiment

Embodiment 1: the preparation Radix Ginseng extract: get 10 parts of Radix Ginsengs (part is: kilogram or gram)

The ginseng crude drug, add 8 times of amount 80% soak with ethanol 4 hours after the pulverizing, reflux, extract, 3 times, each 2 hours, merge extractive liquid,, filter, filtrate recycling ethanol to relative density is 1.05～1.10 (60 ℃), adds water dissolution, standing over night, filter, behind the saturated n-butanol extraction purification of filtrate water Radix Ginseng extract.

Embodiment 2: the preparation Radix Ginseng Rubra extract: 1000 parts of Radix Ginseng Rubra (part is: kilogram or gram)

Get the Radix Ginseng Rubra medical material, add 8 times of amount 80% soak with ethanol 4 hours after the pulverizing, reflux, extract, 3 times, each 2 hours, merge extractive liquid, filtered, during 60 ℃ of filtrate recycling ethanol relative densities is 1.05～1.10, adds water dissolution, centrifugal, rotating speed is 4000r/min, and centrifugal 10min, supernatant cross the D301 macroporous resin column, water and 10% ethanol elution remove impurity, reuse 70% alcohol desorption is collected stripping liquid, reclaim ethanol, concentrated solution is drying to obtain Radix Ginseng Rubra extract.

Embodiment 3: the preparation Radix Ginseng extract: 3000 parts of Radix Ginsengs (part is: kilogram or gram)

Get the ginseng crude drug, pulverized 40 mesh sieves, add 8 times of water gagings and soaked 12 hours, 100 ℃ decoct 3 times, and decocting time is little respectively to be 2h, 2h, and 1h, merge extractive liquid, is concentrated into certain volume.Concentrated solution gets Radix Ginseng extract after crossing purification by macroporous resin,

Embodiment 4: the preparation Radix Ginseng extract: 5000 parts of Radix Ginsengs (part is: kilogram or gram)

Take by weighing the ginseng crude drug, cross 40 orders and get coarse powder, add 8 times of water gagings and soak 12h, 60 ℃ of water-bath warm macerating 3 times, 3 times are respectively 2h, 2h, 1h.After the extraction, decompress filter.Get Radix Ginseng extract behind the n-butanol extraction purification that filtrate water is saturated.

Embodiment 5: the preparation Radix Ginseng extract: 100 parts of Radix Ginsengs (part is: kilogram or gram)

Take by weighing Radix Ginseng, pulverize coarse powder, put into triangular flask, measure with 10 times of amounts of ethanol of 50%, 8 times of amounts, 8 times respectively that low fire extracted 10 fens in microwave oven, filter with suction funnel, merging filtrate reclaims the ethanol evaporate to dryness, use water dissolution, aqueous solution is condensed into extractum, promptly get Radix Ginseng extract.

Embodiment 6: the preparation extract of Radix Ginseng leaf: 10000 parts of Folium Ginseng (part is: kilogram or gram)

Take by weighing the Radix Ginseng cured leaf, add 8 times of water gagings and soak 12h, put into ultrasound wave and extract, set extraction time and be 20 fens, power 100,30 ℃ of temperature, 8 times of quantity of solvent, number of times 3 times, after the extraction, decompress filter.With filtrate after with purification by macroporous resin extract of Radix Ginseng leaf.

Embodiment 7: 10 parts of Radix Ginsengs, 50 parts of troxerutins (part is: kilogram or gram)

Get the ginseng crude drug, add 8 times of amount 80% soak with ethanol 4 hours after the pulverizing, reflux, extract, 3 times, each 2 hours, merge extractive liquid, filtered, during 60 ℃ of filtrate recycling ethanol relative densities is 1.05～1.10, adds the water for injection of 0.8 times of medical material weight, and 4 ℃ of cold preservations are spent the night, filter, filtrate is 1.05～1.10 when concentrating 60 ℃ of relative densities, adds the injection water, filter, filtrate is boiled the active carbon of back by quality percent by volume adding 0.2%, keeps little and boils 30 minutes, cold slightly filtration, filtrate is used for dosing; Get troxerutin, stir in the adding water for injection and make it dissolving, with above-mentioned two kinds of solution mix homogeneously, adjust pH 5.2～6.5 boils, and 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining; Mannitol is added the injection dissolving of blunging, and with above-mentioned filtrate mixing, filtration adds to the full amount of water for injection, packing, pre-freeze temperature-45～-40 ℃, pre-freeze time 6～8h; 40～-35 ℃ of evacuation keep 6～8h; Be warming up to-30～-25 ℃ again, keep 6～8h; Be warming up to-20～15 ℃, keep 6～8h; Be warming up to-10～-5 ℃, keep 3～5h; Be warming up to 0 ℃, keep 3～5h; Be warming up to 15～20 ℃, keep 1～3h; Be warming up to 25～30 ℃, keep 1～3h, be warming up to 35～40 ℃, keep 1～3h, promptly get lyophilized injectable powder.

Embodiment 8: 3000 parts of troxerutins of Radix Ginseng Rubra: 5 parts (part is: kilogram or gram)

The Radix Ginseng Rubra medical material adds 8 times of amount 80% soak with ethanol 4 hours, reflux, extract, 3 times after the pulverizing, each 2 hours, merge extractive liquid, filtered, during 60 ℃ of filtrate recycling ethanol relative densities is 1.05～1.10, adds the water for injection of 0.8 times of medical material weight, and 4 ℃ of cold preservations are spent the night, filter, filtrate is 1.05～1.10 when concentrating 60 ℃ of relative densities, adds the injection water, filter, filtrate is boiled the active carbon of back by quality percent by volume adding 0.2%, keeps little and boils 30 minutes, cold slightly filtration, filtrate is used for dosing; Get troxerutin, add the injection blunge make it the dissolving, with above-mentioned two kinds of solution mix homogeneously, adjust pH 5.2～6.5 boils, 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining add to the full amount of water for injection, the branch install to ampoule bottle, seal sterilization and promptly get aqueous injection.

Embodiment 9: 700 parts of troxerutins of Folium Ginseng: 15 parts (part is: kilogram or gram)

Take by weighing the Radix Ginseng cured leaf, add 8 times of water gagings and soak 12h, put into ultrasound wave and extract, set extraction time and be 20 fens, power 100,30 ℃ of temperature, 8 times of quantity of solvent, number of times 3 times, after the extraction, decompress filter.With filtrate after with purification by macroporous resin extract of Radix Ginseng leaf, with the troxerutin mixing, add injection and blunge and make it dissolving, adjust pH 5.2～6.5, boil, 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining, add to the full amount of water for injection, divide to install to ampoule bottle, seal sterilization and promptly get aqueous injection.

Embodiment 10: Radix Ginseng extract: 1000 parts, and troxerutin: 20 parts (part is: kilogram or gram)

Get Radix Ginseng total saponins, add the injection water and make it dissolving, 4 ℃ of cold preservations are spent the night, and filter, and filtrate is boiled the active carbon of back by quality percent by volume adding 0.2%, and keep little and boiled 30 minutes, cold slightly filtration, filtrate is used for dosing; Get troxerutin, add and inject the dissolving of blunging, above-mentioned two kinds of solution mix homogeneously, adjust pH 5.2～6.5 boils, and 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining, mannitol is added the injection dissolving of blunging, with above-mentioned filtrate mixing, filtration, add to the full amount of water for injection, packing, pre-freeze temperature-45～-40 ℃, pre-freeze time 6～8h;-40～-35 ℃ of evacuation keep 6～8h; Be warming up to-30～-25 ℃ again, keep 6～8h; Be warming up to-20～-15 ℃, keep 6～8h; Be warming up to-10～-5 ℃, keep 3～5h; Be warming up to 0 ℃, keep 3～5h; Be warming up to 15～20 ℃, keep 1～3h; Be warming up to 25～30 ℃, keep 1～3h, be warming up to 35～40 ℃, keep 1～3h, promptly get lyophilized injectable powder.Record with spectrophotography that total saponin content is 12% in the preparation, the component content sum that derives from the ginseng crude drug that all can be surveyed be deduction adjuvant amount, water quantities and troxerutin amount in the preparation total solid 21%.

Embodiment 11: Radix Ginseng: 70 parts of troxerutins: 10 parts (part is: kilogram or gram)

Get the ginseng crude drug, add 8 times of amount 80% soak with ethanol 4 hours after the pulverizing, reflux, extract, 3 times, each 2 hours, merge extractive liquid, filtered, during 60 ℃ of filtrate recycling ethanol relative densities is 1.05～1.10, add water dissolution, centrifugal, rotating speed is 4000r/min, centrifugal 10min, supernatant is crossed the D301 macroporous resin column, water and 10% ethanol elution remove impurity, reuse 70% alcohol desorption, collect stripping liquid, reclaim ethanol, concentrated solution adds the water for injection of 0.8 times of medical material weight, and 4 ℃ of cold preservations are spent the night, filter, filtrate is 1.05～1.10 when concentrating 60 ℃ of relative densities, adds the injection water, filters, filtrate is boiled the active carbon of back by quality percent by volume adding 0.2%, keep little and boiled 30 minutes, cold slightly filtration, filtrate is used for dosing; Get troxerutin, add and inject the dissolving of blunging, with above-mentioned two kinds of solution mix homogeneously, adjust pH 5.2～6.5 boils, and 4 ℃ of cold preservations are spent the night, and coarse filtration, fine straining add in an amount of process glucose solution that boils, and promptly get the glucose infusion liquid agent with the water for injection dilution.The component content sum that derives from the ginseng crude drug that all can be surveyed be deduction adjuvant amount, water quantities and troxerutin amount in the preparation total solid 30%.

Embodiment 12: Radix Ginseng Rubra: 1000 parts of troxerutins: 40 parts (part is: kilogram or gram)

Get the Radix Ginseng Rubra medical material, add 8 times of amount 80% soak with ethanol 4 hours after the pulverizing, reflux, extract, 3 times, each 2 hours, merge extractive liquid, filtered, during 60 ℃ of filtrate recycling ethanol relative densities is 1.05～1.10, adds water dissolution, centrifugal, rotating speed is 4000r/min, centrifugal 10min, supernatant cross the D301 macroporous resin column, water and 10% ethanol elution remove impurity, reuse 70% alcohol desorption, collect stripping liquid, reclaim ethanol, the concentrated solution drying, add water for injection, 4 ℃ of cold preservations are spent the night, and filter, and filtrate is 1.05～1.10 when concentrating 60 ℃ of relative densities, add the injection water, filter, filtrate is boiled the active carbon of back by quality percent by volume adding 0.2%, keeps little and boils 30 minutes, cold slightly filtration, filtrate is used for dosing; , get troxerutin, add and inject the dissolving of blunging, with above-mentioned two kinds of solution mix homogeneously, adjust pH 5.0～6.5 boils, and 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining add in an amount of process sodium chloride solution that boils, and promptly get the sodium chloride infusion solution with the water for injection dilution.

Embodiment 13: Radix Ginseng extract: 300 parts of troxerutins: 45 parts (part is: kilogram or gram)

Get Radix Ginseng extract, add the injection water, filter, filtrate is boiled the active carbon of back by quality percent by volume adding 0.2%, and keep little and boiled 30 minutes, cold slightly filtration, filtrate is used for dosing; , get troxerutin, add and inject the dissolving of blunging, with above-mentioned two kinds of solution mix homogeneously, adjust pH 5.0～6.5 boils, and 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining add in an amount of process sodium chloride solution that boils, and promptly get the sodium chloride infusion solution with the water for injection dilution.The content of troxerutin is 102.8% of labelled amount, record with spectrophotography that total saponin content is 46% in the preparation, the component content sum that derives from the ginseng crude drug that all can be surveyed be deduction adjuvant amount, water quantities and troxerutin amount in the preparation total solid 59%.

Embodiment 14: extract of Radix Ginseng leaf: 10 parts of troxerutins: 1 part (part is: kilogram or gram)

Get extract of Radix Ginseng leaf, add the injection water, filter, filtrate is boiled the active carbon of back by quality percent by volume adding 0.2%, and keep little and boiled 30 minutes, cold slightly filtration, filtrate is used for dosing; Get troxerutin, add and inject the dissolving of blunging, with above-mentioned two kinds of solution mix homogeneously, adjust pH 5.2～6.5 boils, and 4 ℃ of cold preservations are spent the night, and coarse filtration, fine straining add in an amount of process glucose solution that boils, and promptly get the glucose infusion liquid agent with the water for injection dilution.Record with spectrophotography that total saponin content is 81% in the preparation, the component content sum that derives from the ginseng crude drug that all can be surveyed be deduction adjuvant amount, water quantities and troxerutin amount in the preparation total solid 96%.

Embodiment 15: Radix Ginseng Rubra extract: 3000 parts of troxerutins: 20 parts (part is: kilogram or gram)

Get Radix Ginseng Rubra extract, add the injection water, filter, filtrate is boiled the active carbon of back by quality percent by volume adding 0.2%, and keep little and boiled 30 minutes, cold slightly filtration, filtrate is used for dosing; Get troxerutin, stir in the adding water for injection and make it dissolving, with above-mentioned two kinds of solution mix homogeneously, adjust pH 5.2～6.5 boils, and 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining; Mannitol is added the injection dissolving of blunging, and with above-mentioned filtrate mixing, filtration adds to the full amount of water for injection, packing, pre-freeze temperature-45～-40 ℃, pre-freeze time 6～8h;-40～-35 ℃ of evacuation keep 6～8h; Be warming up to-30～-25 ℃ again, keep 6～8h; Be warming up to-20～-15 ℃, keep 6～8h; Be warming up to-10～-5 ℃, keep 3～5h; Be warming up to 0 ℃, keep 3～5h; Be warming up to 15～20 ℃, keep 1～3h; Be warming up to 25～30 ℃, keep 1～3h, be warming up to 35～40 ℃, keep 1～3h, promptly get lyophilized injectable powder.

Embodiment 16: Radix Ginseng extract: 1000 parts of troxerutins: 20 parts (part is: kilogram or gram)

Get Radix Ginseng extract, add water for injection, 4 ℃ of cold preservations are spent the night, and filter, filtrate is 1.05～1.10 when concentrating 60 ℃ of relative densities, adds the injection water, filters, and filtrate is boiled the back and added 0.2% active carbon by the quality percent by volume, keep little and boiled 30 minutes, cold slightly filtration, filtrate is used for dosing; Get troxerutin, add and inject the dissolving of blunging, with above-mentioned two kinds of solution mix homogeneously, adjust pH 5.0～6.5 boils, and 4 ℃ of cold preservations are spent the night, and coarse filtration, fine straining add in an amount of process sodium chloride solution that boils, and promptly get the sodium chloride infusion solution with the water for injection dilution.

Embodiment 17: 5000 parts of Radix Ginsengs, 30 parts of troxerutins (part is: kilogram or gram)

Get the ginseng crude drug, pulverized 40 mesh sieves, add 8 times of water gagings and soaked 12 hours, 100 ℃ decoct 3 times, and decocting time is little respectively to be 2h, 2h, and 1h, merge extractive liquid, is concentrated into certain volume.Concentrated solution gets Radix Ginseng extract after crossing purification by macroporous resin, with the troxerutin mix homogeneously, adds the Macrogol 4000 of 1～1.5 times of medicated powder weight, merges evenly, splashes into and promptly gets drop pill in the liquid paraffin.

Embodiment 18: 100 parts of Radix Ginseng extracts, 25 parts of troxerutins (part is: kilogram or gram)

Take by weighing the Radix Ginseng Rubra medical material, cross 40 orders and get coarse powder, add 8 times of water gagings and soak 12h, 60 ℃ of water-bath warm macerating 3 times, 3 times are respectively 2h, 2h, 1h.After the extraction, decompress filter.Get Radix Ginseng extract behind the n-butanol extraction purification that filtrate water is saturated.With Radix Ginseng Rubra extract and troxerutin mix homogeneously, add the soybean oil of 0.8～1.2 times of medicated powder weight and 2～5% Cera Flava again, mix homogeneously is pressed into soft capsule.

Embodiment 19: 10 parts of Radix Ginseng extracts, 2 parts of troxerutins (part is: kilogram or gram)

After pulverizing, Radix Ginseng adds 8 times of amount 80% alcohol reflux 3 times, each 2 hours, merge extractive liquid,, filtering, is 1.05～1.10 during 60 ℃ of filtrate recycling ethanol relative densities, and drying under reduced pressure is made Radix Ginseng extract, itself and bis ether are reached not mix homogeneously, the polyvinylpolypyrrolidone PVPP of adding 5%～8% and an amount of mannitol, compacting promptly gets oral cavity disintegration tablet in flakes.Record with spectrophotography that total saponin content is 6% in the preparation.

Embodiment 20: 10000 parts of Radix Ginsengs, 50 parts of troxerutins (part is: kilogram or gram)

The ginseng crude drug adds 8 times of amount 80% soak with ethanol 4 hours, reflux, extract, 3 times after the pulverizing, each 2 hours, merge extractive liquid, filtered, filtrate recycling ethanol to relative density is 1.05～1.10 (60 ℃), adds water dissolution, standing over night, filter, behind the saturated n-butanol extraction purification of filtrate water Radix Ginseng extract, with the troxerutin mix homogeneously, the carboxymethyl starch sodium that adds an amount of microcrystalline Cellulose and 1%～6%, mixing, tabletting promptly gets tablet.

Embodiment 21: 1000 parts of Radix Ginseng extracts, 18 parts of troxerutins (part is: kilogram or gram)

Get Radix Ginseng extract, add troxerutin, mixing, drying adds 1～2% magnesium stearate, mixed pelletization, granulate incapsulates, and promptly gets capsule.

Embodiment 22: 100 parts of extract of Radix Ginseng leafs, 32 parts of troxerutins (part is: kilogram or gram)

Get extract of Radix Ginseng leaf, the troxerutin mix homogeneously adds CMC-Na, an amount of and lemon yellow mixing, makes binding agent with 1.5% K30 anhydrous alcohol solution, 40 order system material, granulate, and tabletting promptly gets dispersible tablet.

Embodiment 23: 10 parts of Folium Ginseng, 20 parts of troxerutins (part is: kilogram or gram)

Take by weighing the Radix Ginseng cured leaf, add 8 times of water gagings and soak 12h, put into ultrasound wave and extract, set extraction time and be 20 fens, power 100,30 ℃ of temperature, 8 times of quantity of solvent, number of times 3 times, after the extraction, decompress filter.With filtrate after with purification by macroporous resin extract of Radix Ginseng leaf, add troxerutin, mixing, drying adds hydroxypropyl cellulose, steviosin is an amount of, tabletting promptly gets buccal tablet.

Embodiment 24: 300 parts of Radix Ginseng extracts, 8 parts of troxerutins (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 Radix Ginseng extract and troxerutin mixing, add slowly in the colloid solution, mix; Other gets lactose 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.The content of troxerutin is 96.4% of labelled amount in the preparation.

Embodiment 25: 140 parts of Radix Ginseng Rubra, 20 parts of troxerutins (part is: kilogram or gram)

Take by weighing Radix Ginseng Rubra, pulverize coarse powder, put into triangular flask, measure with 10 times of amounts of ethanol of 50%, 8 times of amounts, 8 times respectively that low fire extracted 10 fens in microwave oven, filter merging filtrate with suction funnel, reclaim the ethanol evaporate to dryness, use water dissolution, aqueous solution is condensed into extractum, dry, pulverize,, add an amount of stevioside and dextrin itself and troxerutin mix homogeneously, make granule, be drying to obtain granule.

Claims (12)

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 1～50 part of 10～10000 parts of Radix Ginsengs and troxerutin through extracting refining forming; Or the Radix Ginseng extract and the corresponding weight portion troxerutin that are obtained after extracting by corresponding weight portion medical material are made.

2, the pharmaceutical composition of treatment cardiovascular and cerebrovascular disease according to claim 1 is characterized in that: calculate according to components by weight percent, it by 1～30 part of 100～5000 parts of Radix Ginsengs and troxerutin through extracting refining forming; Or the Radix Ginseng extract and the corresponding weight portion troxerutin 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 1～20 part of 100～3000 parts of Radix Ginsengs and troxerutin through extracting refining forming; Or the Radix Ginseng extract and the corresponding weight portion troxerutin 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 of claim 1-3, it is characterized in that: Radix Ginseng in the described prescription and extract thereof can also be Stem and leaf of Radix Ginseng part or the Radix Ginseng Rubra and the extracts thereof of same ratio.

5, according to the pharmaceutical composition of any described treatment cardiovascular and cerebrovascular disease among the claim 1-4, 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.

6, according to the pharmaceutical composition of the described treatment cardiovascular and cerebrovascular disease of claim 5, 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.

7, according to the pharmaceutical composition of claim 5 or 6 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: the content of saponin component be not less than in the preparation deduction adjuvant amount, water quantities and troxerutin amount total solid 5%; The component content sum that all can be surveyed in the injection derives from ginseng crude drug or Stem and leaf of Radix Ginseng part or Radix Ginseng Rubra medical material be not less than deduction adjuvant amount, water quantities and troxerutin amount in the preparation total solid 20%; Troxerutin content should be 90.0%～110.0% of labelled amount.

8, according to the preparation of drug combination method of claim 5 or 6 described treatment cardiovascular and cerebrovascular diseases, it is characterized in that: get Radix Ginseng or Stem and leaf of Radix Ginseng part or Radix Ginseng Rubra, add entry or ethanol extraction, the extracting solution concentrate drying gets the medical material crude extract, one or more that also can further adopt precipitate with ethanol, organic solvent extraction, column chromatography carry out suitably refining, get the medical material extract,, be prepared into the preparation that needs with conventional method medical material crude extract or medical material extract and troxerutin mixing.

9, according to the preparation of drug combination method of the described treatment cardiovascular and cerebrovascular disease of claim 8, it is characterized in that: Radix Ginseng or Stem and leaf of Radix Ginseng part or Radix Ginseng Rubra extract can also be commercially available or adopt other preparation methoies to prepare.

10, 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 anticoagulant; antithrombotic forms, protecting myocardial cell, blood flow increasing, antagonism myocardial oxygen consumption, functions such as blood pressure lowering.

11, according to the application in cardiovascular and cerebrovascular diseases medicaments such as preparation treatment coronary heart disease, angina pectoris, arteriosclerosis, obliterated cerebral vascular disease of the pharmaceutical composition of any described treatment cardiovascular and cerebrovascular disease among the claim 1-3.

12, according to the pharmaceutical composition of claim 5 or 6 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.