CN1733039A - Compound preparation of breviscapinum for treating cardiovascular and cerebrovascular diseases and its preparing process - Google Patents

Abstract

The invention provides a compound preparation of breviscapinum for treating cardiovascular and cerebrovascular diseases and its preparing process, which is prepared from safflower and Erigeron Breviscapus, and can be made into oral preparation or injections, including power injection and freeze-dried powder injection.

Description

Compound formulation of breviscapine of treatment cardio-cerebrovascular diseases and preparation method thereof

Technical field: the present invention is a kind of compound formulation of breviscapine for the treatment of cardio-cerebrovascular diseases and preparation method thereof, belongs to technical field of Chinese medicine.

Technical background: cardiovascular and cerebrovascular disease such as coronary heart disease, cerebral thrombosis, hypertension, cerebral infarction etc. all are one of the most common and diseases that harm is maximum in the world today, also can cause the damage of organs such as the heart, brain, kidney, cause as diseases such as apoplexy, heart failure, renal failures, serious threat human beings'health and life, it was reported, sickness rate in recent years has and increases trend year by year, and in, young patient constantly increases.Prevent and treat purpose in order to reach, number of research projects has been done by many inventors and medicine enterprise, and the product of some treatments also is provided; As, number of patent application is: 01113880, and name is called the application of " the Chinese medicine wafer of treatment cardiovascular and cerebrovascular disease "; The applicant had also once submitted the application that name is called " a kind of Chinese medicine preparation for the treatment of cardiovascular and cerebrovascular disease and preparation method thereof ", 2004100403494.But the former prescription is very complicated, and the quality of restive medicine can not solve the actual needs of doctor and patient; And the latter has used oil lamp, Radix Salviae Miltiorrhizae, and the zest of Radix Salviae Miltiorrhizae tannin and anaphylaxis have influenced the quality of product and the operability of technology greatly, is difficult to promote product and produces greatly.And some are with Radix Salviae Miltiorrhizae, the erigeron breviscapus effective component preparation as prescription, and having ignored drug effect is the result of multiple interaction between component, and the independent effect of certain composition can be displaced anything but.In view of such circumstances, seek that a kind of medical material compatibility is simple, therapeutic effect is desirable, does not have toxic and side effects, preparation technology rationally effectively, the abundant thing of medicine preparation of preparation formulation to have satisfied the demand and to be badly in need of solving into people.

Summary of the invention: the objective of the invention is to: a kind of compound formulation of breviscapine for the treatment of cardio-cerebrovascular diseases and preparation method thereof is provided; The present invention is directed to prior art, according to cardiovascular and cerebrovascular disease such as coronary heart disease, cerebral thrombosis, hypertension, cerebral infarction etc. all contract because of blood vessel is narrow, reason such as blood flow minimizing causes the diseases induced principle of blood supply insufficiency, only select for use this two flavors medical material of Flos Carthami and Herba Erigerontis as prescription of the present invention, just can prepare the pharmaceutical preparation that has activating blood circulation to dissipate blood stasis, TONGMAI SHULUO, improves blood circulation and metabolic function by the preparation method that the applicant provides, Flos Carthami contains flavones ingredient, safe and effective, technology is rationally feasible.

The present invention constitutes like this: calculate according to components by weight percent, it is added after extracting with 1～99 part of Herba Erigerontis by 99～1 parts on Flos Carthami, and suitable adjuvant is refining to form; Or the Herba Erigerontis extract that obtains after extraction of the Flos Carthami extract that is obtained after extracting by corresponding weight portion medical material and corresponding weight portion medical material adds suitable adjuvant and is made.Be preferably: calculate according to parts by weight, it adds suitable adjuvant for 90～40 parts by 10～60 parts on Flos Carthami and Herba Erigerontis and is made, or the Herba Erigerontis extract that obtains after extraction of the Flos Carthami extract that is obtained after extracting by corresponding weight portion medical material and corresponding weight portion medical material adds suitable adjuvant and is made.More preferably: calculate according to parts by weight, it adds suitable adjuvant for 80～50 parts by 20～50 parts on Flos Carthami and Herba Erigerontis and is made, or the Herba Erigerontis extract that obtains after extraction of the Flos Carthami extract that is obtained after extracting by corresponding weight portion medical material and corresponding weight portion medical material adds suitable adjuvant and is made.Say accurately: calculate according to parts by weight, it adds suitable adjuvant for 75 parts by 25 parts on Flos Carthami and Herba Erigerontis and is made, or the Herba Erigerontis extract that obtains after extraction of the Flos Carthami extract that is obtained after extracting by corresponding weight portion medical material and corresponding weight portion medical material adds suitable adjuvant and is made.Among the present invention: the amount of adjuvant in the deduction preparation, the lamp-dish flower acetic content in the preparation is not less than 0.2%, and flavones content is not less than 5%, so just can reach the effect of invention.

Preparation of the present invention comprises: be directly used in the injection with small volume of drug administration by injection, directly for the venous transfusion of intravenous drip, need to be used for after the dilution concentrated solution for injection and injectable sterile powder, tablet, dispersible tablet, oral cavity disintegration tablet, capsule, soft capsule, granule, drop pill and the oral liquid of intravenous drip.Say accurately: preparation of the present invention is an injection, comprising: be directly used in the injection with small volume of drug administration by injection, directly for the venous transfusion of intravenous drip, need to be used for after the dilution concentrated solution for injection and the injectable sterile powder of intravenous drip.

The preparation method of described preparation: get the Herba Erigerontis medical material, add water or ethanol extraction, extracting solution gets the Herba Erigerontis crude extract after carrying out suitably concentrating, and also can further adopt one or more methods mixing in alcohol deposition method, acid-base precipitation method, column chromatography, the solvent extraction to use to such an extent that Herba Erigerontis is made with extra care extract; Get flos carthami, add water or ethanol extraction, extracting solution gets the Flos Carthami crude extract after carrying out suitably concentrating, also can further adopt one or more methods mixing in alcohol deposition method, acid-base precipitation method, column chromatography, the solvent extraction to use to such an extent that Flos Carthami is made with extra care extract, with Herba Erigerontis crude extract or refining extract and Flos Carthami crude extract or refining extract mixing, make different preparations then.

Say accurately: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 4-10 times of volume 50-80% alcohol reflux 1-4 time, each 0.5-3 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 1-5 times of medical material volume, filter, filtrate is crossed AB-8 type macroporous adsorbent resin with the speed of 0.3-0.8ml/g medical material .min, with 1-10 times of resinite hydrops and 1-6 times of resin volume 5-15% alcohol flushing impurity, then with the 30-70% alcohol desorption of 1-7 times of resin volume, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 5-15 times of decocting and boils 1-4 time, each 0.5-2.5 hour, collect extracting solution, filter, filtrate is crossed polyamide chromatography post with the speed of 0.3-0.8ml/g medical material .min, with 3-8 times of resinite hydrops and 2-6 times of resin volume 5-25% ethanol elution impurity, then with 2-7 times of resin volume 40-70% alcohol desorption, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.10～1.20, Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add different auxiliary material, make different preparations.

In other words: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, and added 4～10 times of volume decoctings and boil each 0.5～2.5 hour 1～4 time, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, adds ethanol and carries out ethanol precipitation twice, makes for the first time to contain the alcohol amount and reach 55～75%, make for the second time and contain the alcohol amount and reach 80～90%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 4～10 times of volume 50～90% alcohol reflux 1～4 time, each 0.5～2.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.15～1.25, drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, Flos Carthami extract mix homogeneously, add adjuvant and make different preparations.

Injectable sterile block in the described preparation prepares like this: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 3 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin, with 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity, use 40% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 10 times of decoctings and boils 3 times, each 1 hour, collect extracting solution, cross polyamide chromatography post, with 6 times of resinite hydrops and 4 times of resin volume 20% ethanol elution impurity, use 5 times of resin volume 60% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, get Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add an amount of water for injection dissolving, by volume add 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.0 ~ 7.0, boil, coarse filtration is spent the night in 4 ℃ of cold preservations, fine straining.Mannitol is added the injection water be mixed with 100mg/ml solution,, filter with above-mentioned filtrate mixing, packing, temperature-45 ℃, pre-freeze time 10h, the beginning evacuation, and be warming up to-40 ℃, and keep 8h, be warming up to-35 ℃ again, keep 8h; Be warming up to-25 ℃, keep 8h, be warming up to-15 ℃, keep 5h, be warming up to 0 ℃, keep 5h, be warming up to 10 ℃, keep 2h, be warming up to 20 ℃, keep 2h, promptly.

Injection with small volume or concentrated solution for injection in the described preparation prepare like this: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 3 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin, with 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity, use 40% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 10 times of decoctings and boils 3 times, each 1 hour, collect extracting solution, cross polyamide chromatography post, with 6 times of resinite hydrops and 4 times of resin volume 20% ethanol elution impurity, use 5 times of resin volume 60% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, get Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add an amount of water for injection dissolving, by volume add 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.0 ~ 7.0, boil, coarse filtration is spent the night in 4 ℃ of cold preservations, fine straining, add the injection water, divide to install to pacify and cut open bottle, seal sterilization, promptly.

Glucose infusion liquid agent in the described preparation prepares like this: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 3 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin, with 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity, use 40% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 10 times of decoctings and boils 3 times, each 1 hour, collect extracting solution, cross polyamide chromatography post, with 6 times of resinite hydrops and 4 times of resin volume 20% ethanol elution impurity, use 5 times of resin volume 60% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, get Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add an amount of water for injection dissolving, add the glucose of ormal weight again, by volume add 1.0% active carbon behind the mixed dissolution, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.0 ~ 7.0, boil, 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining, add the injection water, packing, sterilization is promptly.

Sodium chloride infusion solution in the described preparation prepares like this: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 3 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin, with 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity, use 40% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 10 times of decoctings and boils 3 times, each 1 hour, collect extracting solution, cross polyamide chromatography post, with 6 times of resinite hydrops and 4 times of resin volume 20% ethanol elution impurity, use 5 times of resin volume 60% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, get Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add an amount of water for injection dissolving, add the sodium chloride of ormal weight again, by volume add 1.0% active carbon behind the mixed dissolution, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.0 ~ 7.0, boil, 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining, add the injection water, packing, sterilization is promptly.

The sterilized powder that is used to inject in the described preparation prepares like this: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 3 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin, with 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity, use 40% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 10 times of decoctings and boils 3 times, each 1 hour, collects extracting solution, cross polyamide chromatography post,, use 5 times of resin volume 60% alcohol desorptions then with 6 times of resinite hydrops and 4 times of resin volume 20% ethanol elution impurity, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add an amount of water for injection dissolving, by volume add 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.5 ~ 7.5, boil, coarse filtration is spent the night in 4 ℃ of cold preservations, fine straining, divide and install in the enamel tray, temperature-45 ℃, pre-freeze time 10h, beginning evacuation, and be warming up to-40 ℃, keep 8h, be warming up to-35 ℃ again, keep 8h; Be warming up to-25 ℃, keep 8h, be warming up to-15 ℃, keep 5h, be warming up to 0 ℃, keep 5h, be warming up to 10 ℃, keep 2h, be warming up to 20 ℃, keep 2h, under aseptic condition, divide to install in the cillin bottle promptly.

The sterilized powder that is used to inject in the described preparation also can prepare like this: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 3 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin, with 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity, use 40% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 10 times of decoctings and boils 3 times, each 1 hour, collect extracting solution, cross polyamide chromatography post, with 6 times of resinite hydrops and 4 times of resin volume 20% ethanol elution impurity, use 5 times of resin volume 60% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add an amount of water for injection dissolving, by volume add 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, transfer pH value 5.5 ~ 7.5, boil, coarse filtration is spent the night in 4 ℃ of cold preservations, fine straining is 150 ℃ in inlet temperature, leaving air temp is 70 ℃, and air velocity is 18ms ^-1Condition under spray drying get powder, packing is promptly.

Injectable sterile block in the described preparation can also prepare like this: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, adding 4～10 times of volume decoctings boils 1～4 time, each 0.5～2.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, add ethanol and carry out ethanol precipitation twice, make for the first time and contain the alcohol amount and reach 55～75%, make for the second time and contain the alcohol amount and reach 80～90%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 4～10 times of volume 50～90% alcohol reflux 1～4 time, each 0.5～2.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.15～1.25, drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, Flos Carthami extract mix homogeneously, add an amount of water for injection dissolving, by volume add 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.0 ~ 7.0, boil, 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining.Mannitol is added the injection water be mixed with 100mg/ml solution,, filter with above-mentioned filtrate mixing, packing, temperature-45 ℃, pre-freeze time 10h, the beginning evacuation, and be warming up to-40 ℃, and keep 8h, be warming up to-35 ℃ again, keep 8h; Be warming up to-25 ℃, keep 8h, be warming up to-15 ℃, keep 5h, be warming up to 0 ℃, keep 5h, be warming up to 10 ℃, keep 2h, be warming up to 20 ℃, keep 2h, promptly.

Injection with small volume in the described preparation or concentrated solution for injection can also prepare like this: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, adding 4～10 times of volume decoctings boils 1～4 time, each 0.5～2.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, add ethanol and carry out ethanol precipitation twice, make for the first time and contain the alcohol amount and reach 55～75%, make for the second time and contain the alcohol amount and reach 80～90%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 4～10 times of volume 50～90% alcohol reflux 1～4 time, each 0.5～2.5 hour, measuring relative density when merge extractive liquid,, decompression recycling ethanol to 60 ℃ was 1.15～1.25, drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, the Flos Carthami extract mix homogeneously adds an amount of water for injection dissolving, by volume adds 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.0 ~ 7.0, boil, coarse filtration is spent the night in 4 ℃ of cold preservations, fine straining, add the injection water, divide to install to pacify and cut open bottle, seal sterilization, promptly.

Glucose infusion liquid agent in the described preparation can also prepare like this: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, adding 4～10 times of volume decoctings boils 1～4 time, each 0.5～2.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, add ethanol and carry out ethanol precipitation twice, make for the first time and contain the alcohol amount and reach 55～75%, make for the second time and contain the alcohol amount and reach 80～90%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 4～10 times of volume 50～90% alcohol reflux 1～4 time, each 0.5～2.5 hour, measuring relative density when merge extractive liquid,, decompression recycling ethanol to 60 ℃ was 1.15～1.25, drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, the Flos Carthami extract mix homogeneously adds an amount of water for injection dissolving, adds the glucose of ormal weight again, by volume add 1.0% active carbon behind the mixed dissolution, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.0 ~ 7.0, boil, 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining, add the injection water, packing, sterilization is promptly.

Sodium chloride infusion solution in the described preparation can also prepare like this: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, adding 4～10 times of volume decoctings boils 1～4 time, each 0.5～2.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, add ethanol and carry out ethanol precipitation twice, make for the first time and contain the alcohol amount and reach 55～75%, make for the second time and contain the alcohol amount and reach 80～90%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 4～10 times of volume 50～90% alcohol reflux 1～4 time, each 0.5～2.5 hour, measuring relative density when merge extractive liquid,, decompression recycling ethanol to 60 ℃ was 1.15～1.25, drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, the Flos Carthami extract mix homogeneously adds an amount of water for injection dissolving, adds the sodium chloride of ormal weight again, by volume add 1.0% active carbon behind the mixed dissolution, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.0 ~ 7.0, boil, 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining, add the injection water, packing, sterilization is promptly.

The sterilized powder that is used to inject in the described preparation can also prepare like this: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, adding 4～10 times of volume decoctings boils 1～4 time, each 0.5～2.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, add ethanol and carry out ethanol precipitation twice, make for the first time and contain the alcohol amount and reach 55～75%, make for the second time and contain the alcohol amount and reach 80～90%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 4～10 times of volume 50～90% alcohol reflux 1～4 time, each 0.5～2.5 hour, measuring relative density when merge extractive liquid,, decompression recycling ethanol to 60 ℃ was 1.15～1.25, drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, the Flos Carthami extract mix homogeneously adds an amount of water for injection dissolving, by volume adds 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.5 ~ 7.5, boil, coarse filtration is spent the night in 4 ℃ of cold preservations, fine straining, divide and install in the enamel tray, temperature-45 ℃, pre-freeze time 10h, beginning evacuation, and be warming up to-40 ℃, keep 8h, be warming up to-35 ℃ again, keep 8h; Be warming up to-25 ℃, keep 8h, be warming up to-15 ℃, keep 5h, be warming up to 0 ℃, keep 5h, be warming up to 10 ℃, keep 2h, be warming up to 20 ℃, keep 2h, under aseptic condition, divide to install in the cillin bottle promptly.

The sterilized powder that is used to inject in the described preparation also can prepare like this: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, adding 4～10 times of volume decoctings boils 1～4 time, each 0.5～2.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, add ethanol and carry out ethanol precipitation twice, make for the first time and contain the alcohol amount and reach 55～75%, make for the second time and contain the alcohol amount and reach 80～90%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 4～10 times of volume 50～90% alcohol reflux 1～4 time, each 0.5～2.5 hour, measuring relative density when merge extractive liquid,, decompression recycling ethanol to 60 ℃ is 1.15～1.25, and drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, the Flos Carthami extract mix homogeneously, add an amount of water for injection dissolving, by volume add 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, transfer pH value 5.5 ~ 7.5, boil, coarse filtration is spent the night in 4 ℃ of cold preservations, fine straining is 150 ℃ in inlet temperature, leaving air temp is 70 ℃, and air velocity is 18ms ^-1Condition under spray drying get powder, packing is promptly.

This method can be made tablet, dispersible tablet, oral cavity disintegration tablet, capsule, soft capsule, granule, drop pill or oral liquid.

Oral formulations in the described preparation prepares like this: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, and added 8 times of volume decoctings and boil each 1 hour 3 times, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, adds ethanol and carries out ethanol precipitation twice, makes for the first time to contain the alcohol amount and reach 70%, make for the second time and contain the alcohol amount and reach 85%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 8 times of volume 80% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.15～1.25, drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, Flos Carthami extract mix homogeneously, add adjuvant and make tablet, dispersible tablet, oral cavity disintegration tablet, capsule, soft capsule, granule, drop pill or oral liquid.

Compared with prior art, the Flos Carthami that the present invention uses has promoting blood flow to regulate menstruation, removing heat from blood eliminating carbuncle, the effect of calming the nerves, but human body immunity improving power, strengthen premunition, regulate the human body cholesterol metabolism, suppress the generation of hypercholesterolemia blood disorder, in addition, also can strengthen cardiac contractile force, excited people's nervous function, hemopoietic function etc.The Herba Erigerontis blood circulation promoting and blood stasis dispelling, dredge the meridian passage; Function with vasodilator, microcirculation improvement, raising cardiac and cerebral blood-supply flow; The scalable blood fat suppresses platelet and erythrocyte aggregation, and blood viscosity lowering promotes fibrinolytic, improves hemorheological property; But also formation or the release that can remove oxygen-derived free radicals, inhibition histamine medium.Therefore adopt Flos Carthami and Herba Erigerontis compatibility to make preparation, just have activating blood circulation to dissipate blood stasis, TONGMAI SHULUO, improve blood circulation and metabolic effect.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, hyperlipidemia etc.And this prescription blood circulation promoting and blood stasis dispelling, can also be used for the treatment of hepatorenal syndrome, diabetes and complication, pulmonary heart disease, raising immunity etc.The present invention is a pure Chinese medicinal preparation, and little, the other preparation variety of its untoward reaction is many, but the patients selection, can life-time service.Because prescription element is few, and the quality of production is controlled easily, product quality is guaranteed in addition.Injection of the present invention is called injection, injectable sterile powder, concentrated solution for injection according to 05 edition pharmacopeia, wherein

Injection: be used for intramuscular injection, intravenous injection or intravenous drip, wherein be used for the venous transfusion of title again of intravenous drip

Injectable sterile powder: refer to face sterilized powder or the aseptic block that is mixed with solution with the suitable sterile solution of preceding usefulness, wherein sterilized powder can make with freeze-drying or spray drying method, and aseptic block makes with freeze-drying

Concentrated solution for injection: refer to face the aseptic concentrated solution of using for intravenous drip with preceding dilution.

Compared with prior art, the applicant has carried out perfect medicament composing prescription compatibility experiment, not merely is simple stack; By antiplatelet aggregation test, myocardial cell culture experiment, to Flos Carthami: Herba Erigerontis divides the test of pesticide effectiveness of having carried out system screening by 1: 9,1: 4,1: 3,1: 1 and 3: 2 five combination prescriptions, found that the prescription pharmacological action of making up at 1: 3 with Flos Carthami, Herba Erigerontis is strong and consumption is lower, that is to say that both compatibilities can reach potentiation antidotal effect.Also to Flos Carthami: the carrying out of Herba Erigerontis=1: 3 combination prescription effectiveness confirm and the side's of tearing open experimental study, the result shows, improving myocardial ischemia, improve cardiac hemodynamic behind Herba Erigerontis and the Radix Salviae Miltiorrhizae compatibility, the effect of microcirculation improvement and hemorheological property is good than the two independent medication.

A lot of problems in the research of extraction and purification process, have been found.For example, the Flavonoid substances less stable of Flos Carthami, but make freeze-dried powder, both can guarantee clinical efficacy, can avoid simultaneously liquid drugs injection again because phenomenons such as the hydrolysis that long-time placement is taken place, oxidation, generation precipitations, make preparation more stable, help the storage of preparation, solid preparation is convenient to transportation simultaneously.In the process of trituration, find, the key of this product be make with extra care, moulding process.Because the paste-forming rate of this product is bigger, brings very big difficulty to molding, if without refining, dose is big, brings great inconvenience to the patient.Can cause loss of active ingredients again but make with extra care, affect the treatment.

The applicant has also studied other two kinds of technologies: technology 1: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, added 8 times of volume water boiling and extraction 3 times, each 1 hour, merge extractive liquid,, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, adds ethanol and carries out ethanol precipitation twice, makes for the first time to contain the alcohol amount and reach 70%, make for the second time and contain the alcohol amount and reach 85%, filter, measuring relative density during decompression filtrate recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 10 times of decoctings and boils 3 times, each 1 hour, collects extracting solution, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, add ethanol and carry out ethanol precipitation twice, make for the first time to contain the alcohol amount and reach 80%, make for the second time to contain the alcohol amount and reach 90%, filter, measuring relative density during decompression filtrate recycling ethanol to 60 ℃ is 1.05～1.15, Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add different auxiliary material, make different preparations.Technology 2: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 8 times of volume water boiling and extraction 3 times, each 1 hour, merge extractive liquid,, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, add the equal-volume ethyl acetate extraction 5 times, isolate acetic acid ethyl fluid, merge the back and reclaim solvent, get Herba Erigerontis extract; Flos Carthami adds 10 times of volumes, 70% alcohol reflux 3 times, each 1 hour, collect extracting solution, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, adds the equal-volume ethyl acetate extraction 5 times, isolate acetic acid ethyl fluid, merge the back and reclaim solvent, get Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract mixes evenly, add different auxiliary material, make different preparations.But it is relatively comprehensive, still the preparation technology below selecting is more reasonable: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, adds the water heating for dissolving of 3 times of medical material volumes, filters, filtrate is crossed AB-8 type macroporous adsorbent resin, with 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity, use 40% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 10 times of decoctings and boils 3 times, each 1 hour, collects extracting solution, cross polyamide chromatography post, with 6 times of resinite hydrops and 4 times of resin volume 20% ethanol elution impurity, use 5 times of resin volume 60% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Flos Carthami extract, and the lamp-dish flower acetic content that obtains is not less than 0.2%, flavones content is not less than 10%, both guarantee product quality, be beneficial to molding again.

Though above technology can be active constituent-enriched, but cost is higher, so we have further studied another kind of technology again: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, adding 8 times of volume decoctings boils 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, adds ethanol and carries out ethanol precipitation twice, makes for the first time to contain the alcohol amount and reach 70%, make for the second time and contain the alcohol amount and reach 85%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 8 times of volume 80% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.15～1.25, drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, Flos Carthami extract mix homogeneously, add different auxiliary material, make different preparations.This is simple for process, and cost is on the low side, and determined curative effect is beneficial to popularization.

And we study the adjuvant factor of most critical in the moulding process, for example the caffolding agent of injection, liquor strength, freeze-dry process condition.Because the kind of caffolding agent, freeze-dry process condition also can product can molding, and the liquor strength of this product is high more, mouldability is poor more; But if reduce liquor strength, then clinical usage quantity strengthens.

The applicant has carried out a series of experiments, can prove that medicine provided by the invention has effective effect;

The screening of experimental example 1 prescription

(1) effective ingredient prescription and prescription of the present invention

Influence to stasis syndrome rat blood rheological characteristic

Test 1 group: the capsule that Carthamus yellow, breviscapine are made;

Test 2 groups: capsule group of the present invention

60 of rats, male and female half and half, body weight 270 ± 25g.Successive administration 12 days, 1h after the last administration, all the other respectively organize equal sc injection epinephrine 0.8mg/kg, totally twice, two minor tick 4h except that the normal control group.(front and back each 2 hours at interval) immerse 5min in the frozen water, fasting with rat between twice.Femoral artery blood sampling in morning next day, each index of hemorheology is measured in the heparin sodium anticoagulant.

Group dosage (g/kg) whole blood viscosity plasma viscosity packed cell volume reduced viscosity

Height hits to hang down and cuts

Normal control-5.30 ± 1.02 7.81 ± 1.12 14.71 ± 1.40 1.51 ± 0.13 0.41 ± 0.11 7.63 ± 1.81

Model contrast-6.82 ± 1.14 8.62 ± 1.43 16.15 ± 1.43 2.12 ± 0.11 0.52 ± 0.76 8.50 ± 2.51

Test 1 6.0 5.90 ± 0.27 8.13 ± 1.34 14.82 ± 1.45 1.75 ± 0.16 0.46 ± 0.16 7.84 ± 1.26

Test 2 group 6.0 5.60 ± 1.11 7.79 ± 0.78 14.43 ± 1.31 1.70 ± 0.21 0.43 ± 0.05 7.68 ± 3.29

The result shows, can not being equal to of the curative effect of effective ingredient and effective site be not because the Chinese medicine comprehensive onset that is compound recipe is that certain ingredient can be displaced.

(2) prescription screening

To Flos Carthami: Herba Erigerontis divides the test of pesticide effectiveness of having carried out system screening by 1: 9,1: 4,1: 3,1: 1 and 3: 2 five combination prescriptions, found that the prescription pharmacological action of making up at 1: 3 with Flos Carthami, Herba Erigerontis is strong and consumption is lower, that is to say that both compatibilities can reach potentiation antidotal effect.Also to Flos Carthami: the carrying out of Herba Erigerontis=1: 3 combination prescription effectiveness confirm and the side's of tearing open experimental study, the result shows, improving myocardial ischemia, improve cardiac hemodynamic behind Herba Erigerontis and the Flos Carthami compatibility, the effect of microcirculation improvement and hemorheological property is good than the two independent medication.

The prescription screening experimental study conclusion of the red drug regimen compatibility of lamp

Formula number	Prescription is formed and ratio screening and assessment index
					Flos Carthami: Herba Erigerontis	Platelet aggregation rate (%)	The test of cultivation myocardial cell injury
	LDH reduces %	CK reduces %
			1 2 3 4 5	1∶9 1∶4 1∶3 1∶1 3∶2			66.9％ 56.6％ 50.4％ 58.1％ 53.7％	36.43％ 32.14％ 49.88％ 43.15％ 41.27％	28.16％ 35.17％ 42.19％ 35.42％ 30.11％

(2) Flos Carthami: affirmation and the side's of tearing open research of 1: 3 combination prescription of Herba Erigerontis effectiveness

Conclusion

Drug efficacy study through system shows; after two medication combined application; aspect blood circulation promoting and blood stasis dispelling, obvious role in synergism is arranged; aspect the treatment cerebral ischemia obvious role in synergism is being arranged also; can obviously increase simultaneously the afterload of blood flow coronarius, reduction Ischemic Heart, the increase of antagonism myocardial oxygen consumption, thus the better protection ischemic myocardium.The results are shown in following table.

Affirmation and the side's of tearing open research conclusion of combination prescription effectiveness

The pilot project prescription is formed and ratio

Compatibility uses single with the single Herba Erigerontis group of using of Flos Carthami group

Behind the two compatibility effect strengthen can significantly reduce animal pattern LDH and can obviously reduce animal pattern LDH and

CK and left ventricle infarction size, but CK and left ventricle infarction size can

Significantly or obviously reduce animal pattern and significantly or obviously reduce animal pattern

HR, obvious elevation model animal MAP, HR, obvious elevation model animal MAP,

The dog coronary artery is tied obvious elevation model animal CO, can obviously show to reduce animal pattern ST displacement,

Cardiac muscle due to the hypodesmus

The cerebral infarction models test shows or the remarkable obvious elevation model animal of elevation model animal CO,

-LV+dp/dt。LVSP obviously raises, and LVEDP obviously reduces, can be obviously or

Make the MVO2 of animal pattern significantly fall remarkable elevation model animal

Low.To animal pattern LV+dp/dt and-LV+dp/dt, to the MVO2 effect not

It is obvious that the ST displacement does not have obvious effect

It is not obvious to act on the no effect of description as a result of enhancing due to the medicine method behind the two compatibility of the heart

The examination of myocardial ischemia model

Test

Behind the two compatibility effect strengthen significantly increase model group Mice Auricle capillary to injection Adr after the Mice Auricle blood capillary

The open number of vasoganglion intersection point, increase model tubule net intersection point are opened number, Mice Auricle is little

Mus auricular microcirculation velocity of blood flow, obviously change that blood circulation fluidised form and Mice Auricle are little to be followed

The effect of Mice Auricle microcirculation hemal ring third level arteries caliber is not after improving that mice is little and following kind injection Adr

Ring test liquid stream attitude, promote behind the injection Adr mouse ear obviously, can be significantly or extremely significantly increase mould

Wide microcirculation third level arteries caliber type Mice Auricle microcirculation velocity of blood flow,

Obviously or significantly resisting Adr shrinks venous blood and has obviously or significantly resist Adr and shrink quiet

The pipe effect.The arteries and veins blood vessel function.

Improving behind the two compatibility of blood stasis model effect strengthens and can obviously, significantly or extremely significantly improve blood stasis and can obviously, significantly or extremely significantly improve blood

The rat blood rheology

Property test model rat serum rheological characteristic index stasis of blood rat model rheological property of blood index

Act on behind poly-the two compatibility of antiplatelet strengthening to have and extremely significantly reduce the no result's description of platelet aggregation rate do

The collection test is used

Effect strengthens behind anti-the two compatibility of mouse tail thrombosis that extremely significantly to suppress thrombosis effect effect not obvious

Form test

Effect strengthens behind the two compatibility has in the remarkable accelerate dissolution blood plasma fibration not obvious

Rabbit fibrin albumen, extremely significantly reduce fiber in the blood plasma

The effect of solubility test protein content

Experimental example 2 process for refining

Technology 1: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 3 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin, with 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity, use 40% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 10 times of decoctings and boils 3 times, each 1 hour, collect extracting solution, cross polyamide chromatography post, with 6 times of resinite hydrops and 4 times of resin volume 20% ethanol elution impurity, use 5 times of resin volume 60% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, get Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add different auxiliary material, make different preparations.

Technology 2: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, added 8 times of volume water boiling and extraction 3 times, each 1 hour, merge extractive liquid,, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, adds ethanol and carries out ethanol precipitation twice, makes for the first time to contain the alcohol amount and reach 70%, make for the second time and contain the alcohol amount and reach 85%, filter, measuring relative density during decompression filtrate recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 10 times of decoctings and boils 3 times, each 1 hour, collects extracting solution, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, add ethanol and carry out ethanol precipitation twice, make for the first time to contain the alcohol amount and reach 80%, make for the second time to contain the alcohol amount and reach 90%, filter, measuring relative density during decompression filtrate recycling ethanol to 60 ℃ is 1.05～1.15, Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add different auxiliary material, make different preparations.

Technology 3: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 8 times of volume water boiling and extraction 3 times, each 1 hour, merge extractive liquid,, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, add the equal-volume ethyl acetate extraction 5 times, isolate acetic acid ethyl fluid, merge the back and reclaim solvent, get Herba Erigerontis extract; Flos Carthami adds 10 times of volumes, 70% alcohol reflux 3 times, each 1 hour, collect extracting solution, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, adds the equal-volume ethyl acetate extraction 5 times, isolate acetic acid ethyl fluid, merge the back and reclaim solvent, get Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract mixes evenly, add different auxiliary material, make different preparations.

Technology 4: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, and added 8 times of volume decoctings and boil each 1 hour 3 times, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, adds ethanol and carries out ethanol precipitation twice, makes for the first time to contain the alcohol amount and reach 70%, make for the second time and contain the alcohol amount and reach 85%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 8 times of volume 80% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.15～1.25, drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, Flos Carthami extract mix homogeneously, add different auxiliary material, make different preparations.

Lamp-dish flower acetic % flavone % paste-forming rate %

Technology 1 23.01 35.51 6.57%

Technology 2 0.34 8.89 23.21%

Technology 3 5.50 27.94 15.42%

Technology 4 0.28 10.10 25.20%

The result shows that technology of the present invention had both kept effective ingredient, has reduced paste-forming rate again, creative selection result.

Experimental example 3 moulding processs

(1) freeze-dry process

1. the screening of caffolding agent kind

Whether caffolding agent adds and kind influences the molding of freeze-dried powder, so at first this is screened.Get the medicinal liquid that contains crude drug 4.5g/ml, respectively with the solution mix homogeneously of caffolding agent mannitol, glucose and lactose, with 0.22 μ m membrane filtration postlyophilization, every XiLin bottle-packaging solution 3ml.

Freeze dryer: Edwards SNL-3200 freezer dryer (the thermoelectric Thermo of the U.S.).Lyophilisation condition: temperature-45 ℃, pre-freeze time 10h, the beginning evacuation, and be warming up to-40 ℃, and keep 8h, be warming up to-35 ℃ again, keep 8h; Be warming up to-25 ℃, keep 8h, be warming up to-15 ℃, keep 5h, be warming up to 0 ℃, keep 5h, be warming up to 10 ℃, keep 2h, be warming up to 20 ℃, keep 2h,

The screening of caffolding agent kind

The caffolding agent kind	The caffolding agent solution concentration	Medicinal liquid: caffolding agent (v: v)	The finished product appearance character
				Mannitol	100mg/ml	1∶2 1∶1 2∶1	The moulding section atrophy of subsiding
Glucose	100mg/ml	1∶2 1∶1 2∶1	Not molding of not molding of not molding of atrophy atrophy atrophy
				Lactose	100mg/ml	1∶2 1∶1 2∶1	The part not molding of not molding of atrophy atrophy of subsiding
Blank medicinal liquid		3ml	Color and luster is inhomogeneous, not molding of atrophy

By Biao Kede, the lyophilizing medicinal liquid need add caffolding agent; Wherein the molding effect of mannitol is better, so caffolding agent is finally selected mannitol for use.

The screening of caffolding agent consumption

The mannitol solution (100mg/ml, 120mg/ml and 150mg/ml) of variable concentrations is mixed in varing proportions with the medicinal liquid that contains crude drug 4.5g/ml, filter every XiLin bottle-packaging solution 3ml, lyophilization.Lyophilisation condition: temperature-45 ℃, pre-freeze time 10h, the beginning evacuation, and be warming up to-40 ℃, and keep 8h, be warming up to-35 ℃ again, keep 8h; Be warming up to-25 ℃, keep 8h, be warming up to-15 ℃, keep 5h, be warming up to 0 ℃, keep 5h, be warming up to 10 ℃, keep 2h, be warming up to 20 ℃, keep 2h.The results are shown in following table.

The screening of mannitol consumption

Numbering	Mannitol concentration (mg/ml)	Mannitol: medicinal liquid (v: v)	Color and luster	Profile	Solubility	Clarity
							1 2 3	100	2∶1 1∶1 1∶2	Yellowish Huang	Inhomogeneous good atrophy	Well carefully	Up to specification up to specification
4 5 6	120	2∶1 1∶1 1∶2	Yellowish Huang	The inhomogeneous atrophy of atrophy	Well carefully	Up to specification up to specification
							7 8 9	150	2∶1 1∶1 1∶2	Yellowish Huang	The atrophy atrophy of partly subsiding	Well carefully	Up to specification up to specification

As seen from table, the consumption of mannitol is many more in the preparation of the present invention's preparation, and the mouldability of product is good more; In order to reach the least possible purpose of adjuvant under the condition of preparations shaping, through taking all factors into consideration, finally selecting mannitol concentration is 100mg/ml simultaneously, and the volume ratio of mannitol solution and medicinal liquid is 1: 1.

4. lyophilization conditional filtering

The lyophilization conditional filtering

Experimental result shows: spray bottle, atrophy phenomenon, the finished product appearance character that condition I and former lyophilisation condition make and the equal conformance with standard of moisture appear in condition II gained sample.Consider the practical situation of production, the condition I that the finally selected overall time spent is short, i.e. lyophilization condition is: temperature-45 ℃, pre-freeze time 10h, the beginning evacuation, and be warming up to-40 ℃, and keep 8h, be warming up to-35 ℃ again, keep 8h; Be warming up to-25 ℃, keep 8h, be warming up to-15 ℃, keep 5h, be warming up to 0 ℃, keep 5h, be warming up to 10 ℃, keep 2h, be warming up to 20 ℃, keep 2h,

(2) injection

The selection of dosing pH value: for adapting to the Human Physiology needs, also will consider the character of each constituents in the medicinal liquid simultaneously, when dosing, need suitably adjust to the pH value of medicinal liquid.Select the Radix Salviae Miltiorrhizae total phenol content as evaluation index.

Test method and result: after feeding intake and handle by recipe quantity by above-mentioned condition, with Herba Erigerontis extracting solution, Radix Salviae Miltiorrhizae extract mix homogeneously, filter, add water to 1000ml, adjust pH, when the different pH value that reaches shown in the following table, boil the back standing over night, observe the variation of appearance character under different pH condition.Experimental result sees the following form.

The investigation of dosing pH value

Sequence number	1	2	3	4	5	6	7	8	9
										Dosing pH	4.0	4.5	5.0	5.5	6.0	6.5	7.0	7.5	8.0
Boil pH	3.6	4.0	4.6	5.2	5.5	6.0	6.5	6.7	7.0
										Outward appearance	Precipitation appears			No significant change			Color burn

The result shows, medicinal liquid boils the back pH value and occurs precipitating at the sample 5.0 below, and pH value is obviously deepened in the color sample more than 7.0, and pH value is that 5.0～7.0 medicinal liquid is relatively stable, and outward appearance does not have significant change.Below its total saponin content is measured, be the results are shown in following table.

The situation of change table of index components before and after pH value is regulated

Sequence number	Dosing pH	Total phenol content during dosing (%)	Boil back pH	Boil back total phenol content (%)
					1 2 3 4	5.0 6.0 6.5 7.0	20.16 20.16 20.16 20.16	4.6 5.2 5.6 5.9	19.76 19.72 19.66 19.65

As seen from table, medicinal liquid is being adjusted the pH value front and back, the not too big variation of index components Radix Ginseng total saponins content.The appearance character of comprehensive above-mentioned medicinal liquid and the changes of contents of Radix Ginseng total saponins, the pH value of medicinal liquid is transferred between 5.0～7.0 when determining dosing

(3) spray drying

Numbering	Inlet temperature ℃	Leaving air temp ℃	Air velocity ms -1	Color and luster	Profile	Solubility	Clarity
								1 2 3	100 120 150	50 60 70	14 16 18	Yellowish Huang is yellowish	Inhomogeneous atrophy is good	Well carefully	Up to specification up to specification

4 5 6

160 180 200

80 90 100

20 22 24

Huang Huanghuang

Good inhomogeneous atrophy

Well carefully

Up to specification up to specification

(4) drop pill

Traditional Chinese Medicine Dropping Pill than higher, should be considered the dissolution characteristics of former medicated powder to the requirement of medicine, also will consider the paste-forming rate of medical material simultaneously, and medicated powder increases taking dose too much; Cross the low paste-forming rate that reduces, the dose of drop pill is reduced, but can lose too much effective ingredient like this, thereby reduce curative effect of medication, in order to take into account curative effect of medication, also will make sample drop make ball as far as possible simultaneously, we investigate drug matrices.

Matrix species	Evaluation index
			Mixing uniformity	Hardness
	Medicine: PEG4000=1: 0.5 medicine: PEG6000=1: 0.5 medicine: Macrogol 4000: polyoxyl 40 stearate: L-HPC=1: 0.5: 0.5: 0.1	The energy mixing, bubble energy mixing is arranged, a large amount of bubbles and caking energy mixing are arranged, no bubble			Moderate moderate inadequately

From top experimental data as can be seen, two kinds of substrate all can make the medicated powder mixing, but PEG6000 lumps sample easily, and the drop pill hardness of making is not enough, the main active of Radix Salviae Miltiorrhizae is a phenols simultaneously, by using substrate PEG4000 can improve the stability of effective ingredient, but the effective ingredient bioavailability is had much room for improvement, but, therefore take all factors into consideration the sample character we according to medicine: Macrogol 4000: polyoxyethylene monostearate: L-HPC=1: 0.5: 0.5: 0.1 part by weight mixing.

Concrete embodiment:

Embodiments of the invention 1: Flos Carthami 250g, Herba Erigerontis 750g

Get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 3 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin, with 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity, use 40% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 10 times of decoctings and boils 3 times, each 1 hour, collect extracting solution, cross polyamide chromatography post, with 6 times of resinite hydrops and 4 times of resin volume 20% ethanol elution impurity, use 5 times of resin volume 60% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, get Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add an amount of water for injection dissolving, by volume add 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.0 ~ 7.0, boil, coarse filtration is spent the night in 4 ℃ of cold preservations, fine straining.Mannitol is added the injection water be mixed with 100mg/ml solution,, filter with above-mentioned filtrate mixing, packing, temperature-45 ℃, pre-freeze time 10h, the beginning evacuation, and be warming up to-40 ℃, and keep 8h, be warming up to-35 ℃ again, keep 8h; Be warming up to-25 ℃, keep 8h, be warming up to-15 ℃, keep 5h, be warming up to 0 ℃, keep 5h, be warming up to 10 ℃, keep 2h, be warming up to 20 ℃, keep 2h, promptly get freeze-dried powder, once-a-day, one time one.

Embodiments of the invention 2: Flos Carthami 250g, Herba Erigerontis 750g

Get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 3 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin, with 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity, use 40% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 10 times of decoctings and boils 3 times, each 1 hour, collect extracting solution, cross polyamide chromatography post, with 6 times of resinite hydrops and 4 times of resin volume 20% ethanol elution impurity, use 5 times of resin volume 60% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, get Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add an amount of water for injection dissolving, by volume add 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.0 ~ 7.0, boil, coarse filtration is spent the night in cold preservation (4 ℃), fine straining.Mannitol is added the injection water be mixed with 100mg/ml solution,, filter with above-mentioned filtrate mixing, packing, temperature-45 ℃, pre-freeze time 10h, the beginning evacuation, and be warming up to-40 ℃, and keep 8h, be warming up to-35 ℃ again, keep 8h; Be warming up to-25 ℃, keep 8h, be warming up to-15 ℃, keep 5h, be warming up to 0 ℃, keep 5h, be warming up to 10 ℃, keep 2h, be warming up to 20 ℃, keep 2h, promptly get aseptic block.

Embodiments of the invention 3: Flos Carthami 250g, Herba Erigerontis 750g

Get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 3 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin, with 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity, use 40% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 10 times of decoctings and boils 3 times, each 1 hour, collect extracting solution, cross polyamide chromatography post, with 6 times of resinite hydrops and 4 times of resin volume 20% ethanol elution impurity, use 5 times of resin volume 60% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add an amount of water for injection dissolving, by volume add 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, transfer pH value 5.0 ~ 7.0, boil, coarse filtration is spent the night in cold preservation (4 ℃), fine straining adds the injection water, divide to install to pacify and cut open bottle, seal sterilization and promptly get injection with small volume or concentrated solution for injection.

Embodiments of the invention 4: Flos Carthami 250g, Herba Erigerontis 750g

Get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 3 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin, with 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity, use 40% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 10 times of decoctings and boils 3 times, each 1 hour, collect extracting solution, cross polyamide chromatography post, with 6 times of resinite hydrops and 4 times of resin volume 20% ethanol elution impurity, use 5 times of resin volume 60% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, get Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add an amount of water for injection dissolving, add the glucose of ormal weight again, by volume add 1.0% active carbon behind the mixed dissolution, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.0 ~ 7.0, boil, cold preservation (4 ℃) is spent the night, coarse filtration, fine straining, add the injection water, packing, sterilization promptly gets the glucose infusion liquid agent.

Embodiments of the invention 5: Flos Carthami 250g, Herba Erigerontis 750g

Get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 3 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin, with 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity, use 40% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 10 times of decoctings and boils 3 times, each 1 hour, collect extracting solution, cross polyamide chromatography post, with 6 times of resinite hydrops and 4 times of resin volume 20% ethanol elution impurity, use 5 times of resin volume 60% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, get Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add an amount of water for injection dissolving, add the sodium chloride of ormal weight again, by volume add 1.0% active carbon behind the mixed dissolution, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.0 ~ 7.0, boil, cold preservation (4 ℃) is spent the night, coarse filtration, fine straining, add the injection water, packing, sterilization promptly gets the sodium chloride infusion solution.

Embodiments of the invention 6: Flos Carthami 250g, Herba Erigerontis 750g

Get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 3 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin, with 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity, use 40% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 10 times of decoctings and boils 3 times, each 1 hour, collects extracting solution, cross polyamide chromatography post,, use 5 times of resin volume 60% alcohol desorptions then with 6 times of resinite hydrops and 4 times of resin volume 20% ethanol elution impurity, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add an amount of water for injection dissolving, by volume add 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.5 ~ 7.5, boil, coarse filtration is spent the night in cold preservation (4 ℃), fine straining, divide and install in the enamel tray, temperature-45 ℃, pre-freeze time 10h, beginning evacuation, and be warming up to-40 ℃, keep 8h, be warming up to-35 ℃ again, keep 8h; Be warming up to-25 ℃, keep 8h, be warming up to-15 ℃, keep 5h, be warming up to 0 ℃, keep 5h, be warming up to 10 ℃, keep 2h, be warming up to 20 ℃, keep 2h, under aseptic condition, divide to install to promptly to get sterilized powder in the cillin bottle.

Embodiments of the invention 7: Flos Carthami 250g, Herba Erigerontis 750g

Get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 3 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin, with 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity, use 40% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 10 times of decoctings and boils 3 times, each 1 hour, collect extracting solution, cross polyamide chromatography post, with 6 times of resinite hydrops and 4 times of resin volume 20% ethanol elution impurity, use 5 times of resin volume 60% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add an amount of water for injection dissolving, by volume add 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, transfer pH value 5.5 ~ 7.5, boil, coarse filtration is spent the night in cold preservation (4 ℃), fine straining is 150 ℃ in inlet temperature, leaving air temp is 70 ℃, and air velocity is 18ms ^-1Condition under spray drying get powder, packing promptly gets sterilized powder.

Embodiments of the invention 8: Flos Carthami 250g, Herba Erigerontis 750g

Get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, and added 4～10 times of volume decoctings and boil each 0.5～2.5 hour 1～4 time, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, adds ethanol and carries out ethanol precipitation twice, makes for the first time to contain the alcohol amount and reach 55～75%, make for the second time and contain the alcohol amount and reach 80～90%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 4～10 times of volume 50～90% alcohol reflux 1～4 time, each 0.5～2.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.15～1.25, drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, Flos Carthami extract mix homogeneously, add an amount of water for injection dissolving, by volume add 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.0 ~ 7.0, boil, coarse filtration, fine straining are spent the night in cold preservation (4 ℃).Mannitol is added the injection water be mixed with 100mg/ml solution,, filter with above-mentioned filtrate mixing, packing, temperature-45 ℃, pre-freeze time 10h, the beginning evacuation, and be warming up to-40 ℃, and keep 8h, be warming up to-35 ℃ again, keep 8h; Be warming up to-25 ℃, keep 8h, be warming up to-15 ℃, keep 5h, be warming up to 0 ℃, keep 5h, be warming up to 10 ℃, keep 2h, be warming up to 20 ℃, keep 2h, promptly get aseptic block.

Embodiments of the invention 9: Flos Carthami 250g, Herba Erigerontis 750g

Get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, and added 4～10 times of volume decoctings and boil each 0.5～2.5 hour 1～4 time, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, adds ethanol and carries out ethanol precipitation twice, makes for the first time to contain the alcohol amount and reach 55～75%, make for the second time and contain the alcohol amount and reach 80～90%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 4～10 times of volume 50～90% alcohol reflux 1～4 time, each 0.5～2.5 hour, measuring relative density when merge extractive liquid,, decompression recycling ethanol to 60 ℃ is 1.15～1.25, and drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, the Flos Carthami extract mix homogeneously, add an amount of water for injection dissolving, by volume add 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, transfer pH value 5.0 ~ 7.0, boil, coarse filtration is spent the night in cold preservation (4 ℃), fine straining adds the injection water, divide to install to pacify and cut open bottle, seal sterilization and promptly get injection with small volume or concentrated solution for injection.

Embodiments of the invention 10: Flos Carthami 250g, Herba Erigerontis 750g

Get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, and added 4～10 times of volume decoctings and boil each 0.5～2.5 hour 1～4 time, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, adds ethanol and carries out ethanol precipitation twice, makes for the first time to contain the alcohol amount and reach 55～75%, make for the second time and contain the alcohol amount and reach 80～90%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 4～10 times of volume 50～90% alcohol reflux 1～4 time, each 0.5～2.5 hour, measuring relative density when merge extractive liquid,, decompression recycling ethanol to 60 ℃ was 1.15～1.25, drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, the Flos Carthami extract mix homogeneously adds an amount of water for injection dissolving, adds the glucose of ormal weight again, by volume add 1.0% active carbon behind the mixed dissolution, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.0 ~ 7.0, boil, cold preservation (4 ℃) is spent the night, coarse filtration, fine straining, add the injection water, packing, sterilization promptly gets the glucose infusion liquid agent.

Embodiments of the invention 11: Flos Carthami 250g, Herba Erigerontis 750g

Get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, and added 4～10 times of volume decoctings and boil each 0.5～2.5 hour 1～4 time, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, adds ethanol and carries out ethanol precipitation twice, makes for the first time to contain the alcohol amount and reach 55～75%, make for the second time and contain the alcohol amount and reach 80～90%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 4～10 times of volume 50～90% alcohol reflux 1～4 time, each 0.5～2.5 hour, measuring relative density when merge extractive liquid,, decompression recycling ethanol to 60 ℃ was 1.15～1.25, drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, the Flos Carthami extract mix homogeneously adds an amount of water for injection dissolving, adds the sodium chloride of ormal weight again, by volume add 1.0% active carbon behind the mixed dissolution, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.0 ~ 7.0, boil, cold preservation (4 ℃) is spent the night, coarse filtration, fine straining, add the injection water, packing, sterilization promptly gets the sodium chloride infusion solution.

Embodiments of the invention 12: Flos Carthami 250g, Herba Erigerontis 750g

Get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, and added 4～10 times of volume decoctings and boil each 0.5～2.5 hour 1～4 time, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, adds ethanol and carries out ethanol precipitation twice, makes for the first time to contain the alcohol amount and reach 55～75%, make for the second time and contain the alcohol amount and reach 80～90%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 4～10 times of volume 50～90% alcohol reflux 1～4 time, each 0.5～2.5 hour, measuring relative density when merge extractive liquid,, decompression recycling ethanol to 60 ℃ was 1.15～1.25, drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, the Flos Carthami extract mix homogeneously adds an amount of water for injection dissolving, by volume adds 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.5 ~ 7.5, boil, coarse filtration is spent the night in cold preservation (4 ℃), fine straining, divide and install in the enamel tray, temperature-45 ℃, pre-freeze time 10h, beginning evacuation, and be warming up to-40 ℃, keep 8h, be warming up to-35 ℃ again, keep 8h; Be warming up to-25 ℃, keep 8h, be warming up to-15 ℃, keep 5h, be warming up to 0 ℃, keep 5h, be warming up to 10 ℃, keep 2h, be warming up to 20 ℃, keep 2h, under aseptic condition, divide to install to promptly to get sterilized powder in the cillin bottle.

Embodiments of the invention 13: Flos Carthami 250g, Herba Erigerontis 750g

Get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, and added 4～10 times of volume decoctings and boil each 0.5～2.5 hour 1～4 time, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, adds ethanol and carries out ethanol precipitation twice, makes for the first time to contain the alcohol amount and reach 55～75%, make for the second time and contain the alcohol amount and reach 80～90%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 4～10 times of volume 50～90% alcohol reflux 1～4 time, each 0.5～2.5 hour, measuring relative density when merge extractive liquid,, decompression recycling ethanol to 60 ℃ is 1.15～1.25, and drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, the Flos Carthami extract mix homogeneously, add an amount of water for injection dissolving, by volume add 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, transfer pH value 5.5 ~ 7.5, boil, coarse filtration is spent the night in cold preservation (4 ℃), fine straining is 150 ℃ in inlet temperature, leaving air temp is 70 ℃, and air velocity is 18ms ^-1Condition under spray drying get powder, packing promptly gets sterilized powder.

Embodiments of the invention 14: Flos Carthami 250g, Herba Erigerontis 750g

Get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, and added 8 times of volume decoctings and boil each 1 hour 3 times, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, adds ethanol and carries out ethanol precipitation twice, makes for the first time to contain the alcohol amount and reach 70%, make for the second time and contain the alcohol amount and reach 85%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 8 times of volume 80% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.15～1.25, drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, the Flos Carthami extract mix homogeneously, according to medicine: Macrogol 4000: polyoxyethylene monostearate: L-HPC=(1: 0.5: 0.5: part by weight mixing 0.1), 80 ℃ of insulations, drip and make ball, dripping the system condition is: the employing internal diameter is 4.0mm, external diameter is the dropper of 6.0mm, drips 70 ℃ of system temperature, dripping speed is 20～30d/min, drip apart from being 5cm, splash in the long cooling column of 100cm, be liquid coolant again with the dimethicone, the cooling of employing gradient: the Temperature Distribution of gradient liquid coolant is 10 ℃～30 ℃, 0 ℃～5 ℃, pill promptly gets drop pill.

Embodiments of the invention 15: Flos Carthami 200g, Herba Erigerontis 800g

Get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 4 times of volume decoctings and boiled 0.5 hour, measuring relative density when merge extractive liquid,, decompression recycling ethanol to 60 ℃ is 1.05～1.15, add ethanol and carry out ethanol precipitation twice, make for the first time to contain the alcohol amount and reach 55%, make for the second time to contain the alcohol amount and reach 80%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami added 4 times of volume 50% alcohol reflux 0.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.15～1.25, drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, Flos Carthami extract mix homogeneously, add distilled water, promptly get oral liquid.

Embodiments of the invention 16: Flos Carthami 500g, Herba Erigerontis 500g

Get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, and added 10 times of volume decoctings and boil each 2.5 hours 4 times, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, adds ethanol and carries out ethanol precipitation twice, makes for the first time to contain the alcohol amount and reach 75%, make for the second time and contain the alcohol amount and reach 90%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 10 times of volume 90% alcohol reflux 4 times, each 2.5 hours, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.15～1.25, and drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, Flos Carthami extract mix homogeneously, dry, pulverize, granulate, promptly get granule.

Embodiments of the invention 17: Flos Carthami 100g, Herba Erigerontis 900

Get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, added 4 times of volume 50% alcohol reflux 0.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 1-5 times of medical material volume, filter, filtrate is crossed AB-8 type macroporous adsorbent resin with the speed of 0.3ml/g medical material .min, with 1 times of resinite hydrops and 1 times of resin volume 5% alcohol flushing impurity, use 30% alcohol desorption of 1 times of resin volume then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 5 times of decoctings and boiled 0.5 hour, collect extracting solution, filter, filtrate is crossed polyamide chromatography post with the speed of 0.3ml/g medical material .min, with 3 times of resinite hydrops and 2 times of resin volume 5% ethanol elution impurity, use 2 times of resin volume 40% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.10～1.20, get Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add distilled water, promptly get oral liquid.

Embodiments of the invention 18: Flos Carthami 600g, Herba Erigerontis 400g

Get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 10 times of volume 80% alcohol reflux 4 times, each 3 hours, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 5 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin with the speed of 0.8ml/g medical material .min, with 10 times of resinite hydrops and 6 times of resin volume 15% alcohol flushing impurity, use 70% alcohol desorption of 7 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 15 times of decoctings and boils 4 times, each 2.5 hours, collect extracting solution, filter, filtrate is crossed polyamide chromatography post with the speed of 0.8ml/g medical material .min, with 8 times of resinite hydrops and 6 times of resin volume 25% ethanol elution impurity, use 7 times of resin volume 70% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.10～1.20, get Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, and drying is pulverized, tabletting promptly gets tablet.

Embodiments of the invention 19: Flos Carthami 990g, Herba Erigerontis 10g

Get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, added 4 times of volume 50% alcohol reflux 0.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 1-5 times of medical material volume, filter, filtrate is crossed AB-8 type macroporous adsorbent resin with the speed of 0.3ml/g medical material .min, with 1 times of resinite hydrops and 1 times of resin volume 5% alcohol flushing impurity, use 30% alcohol desorption of 1 times of resin volume then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 5 times of decoctings and boiled 0.5 hour, collects extracting solution, filters, filtrate is crossed polyamide chromatography post with the speed of 0.3ml/g medical material .min, with 3 times of resinite hydrops and 2 times of resin volume 5% ethanol elution impurity, use 2 times of resin volume 40% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.10～1.20, get Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly drying, pulverize, promptly get granule.

Embodiments of the invention 20: Flos Carthami 10g, Herba Erigerontis 990g

Get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, added 4 times of volume 50% alcohol reflux 0.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 1-5 times of medical material volume, filter, filtrate is crossed AB-8 type macroporous adsorbent resin with the speed of 0.3ml/g medical material .min, with 1 times of resinite hydrops and 1 times of resin volume 5% alcohol flushing impurity, use 30% alcohol desorption of 1 times of resin volume then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 5 times of decoctings and boiled 0.5 hour, collect extracting solution, filter, filtrate is crossed polyamide chromatography post with the speed of 0.3ml/g medical material .min, with 3 times of resinite hydrops and 2 times of resin volume 5% ethanol elution impurity, use 2 times of resin volume 40% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.10～1.20, Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, drying is pulverized, and adds soybean oil, pill promptly gets soft capsule.

Embodiments of the invention 21: Flos Carthami 10g, Herba Erigerontis 990g

Get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, added 4 times of volume 50% alcohol reflux 0.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 1-5 times of medical material volume, filter, filtrate is crossed AB-8 type macroporous adsorbent resin with the speed of 0.3ml/g medical material .min, with 1 times of resinite hydrops and 1 times of resin volume 5% alcohol flushing impurity, use 30% alcohol desorption of 1 times of resin volume then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 5 times of decoctings and boiled 0.5 hour, collects extracting solution, filters, filtrate is crossed polyamide chromatography post with the speed of 0.3ml/g medical material .min, with 3 times of resinite hydrops and 2 times of resin volume 5% ethanol elution impurity, uses 2 times of resin volume 40% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.10～1.20, Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, drying is pulverized, and granulates, encapsulated, promptly get capsule.

Embodiments of the invention 22: Flos Carthami 10g, Herba Erigerontis 990g

Get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, added 4 times of volume 50% alcohol reflux 0.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 1-5 times of medical material volume, filter, filtrate is crossed AB-8 type macroporous adsorbent resin with the speed of 0.3ml/g medical material .min, with 1 times of resinite hydrops and 1 times of resin volume 5% alcohol flushing impurity, use 30% alcohol desorption of 1 times of resin volume then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 5 times of decoctings and boiled 0.5 hour, collect extracting solution, filter, filtrate is crossed polyamide chromatography post with the speed of 0.3ml/g medical material .min, with 3 times of resinite hydrops and 2 times of resin volume 5% ethanol elution impurity, use 2 times of resin volume 40% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.10～1.20, Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, drying is pulverized, and adds 12% sodium carboxymethyl cellulose, tabletting promptly gets dispersible tablet.

Embodiments of the invention 23: Flos Carthami 10g, Herba Erigerontis 990g

Get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, added 4 times of volume 50% alcohol reflux 0.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 1-5 times of medical material volume, filter, filtrate is crossed AB-8 type macroporous adsorbent resin with the speed of 0.3ml/g medical material .min, with 1 times of resinite hydrops and 1 times of resin volume 5% alcohol flushing impurity, use 30% alcohol desorption of 1 times of resin volume then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 5 times of decoctings and boiled 0.5 hour, collect extracting solution, filter, filtrate is crossed polyamide chromatography post with the speed of 0.3ml/g medical material .min, with 3 times of resinite hydrops and 2 times of resin volume 5% ethanol elution impurity, use 2 times of resin volume 40% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.10～1.20, get Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, and drying is pulverized, add 12% sodium carboxymethyl cellulose, 2% magnesium stearate, tabletting promptly gets oral cavity disintegration tablet.

Claims (23)

1, a kind of compound formulation of breviscapine for the treatment of cardio-cerebrovascular diseases is characterized in that: calculate according to components by weight percent, it by 1～99 part of 99～1 parts on Flos Carthami and Herba Erigerontis through extracting refining forming; Or the Herba Erigerontis extract that obtains after extraction of the Flos Carthami extract that is obtained after extracting by corresponding weight portion medical material and corresponding weight portion medical material is equipped with suitable adjuvant and is made.

2, according to the compound formulation of breviscapine of the described treatment cardio-cerebrovascular diseases of claim 1, it is characterized in that: calculate according to parts by weight, it is made for 90～40 parts by 10～60 parts on Flos Carthami and Herba Erigerontis, or the Herba Erigerontis extract that obtains after extraction of the Flos Carthami extract that is obtained after extracting by corresponding weight portion medical material and corresponding weight portion medical material is equipped with suitable adjuvant and is made.

3, according to the compound formulation of breviscapine of the described treatment cardio-cerebrovascular diseases of claim 2, it is characterized in that: calculate according to parts by weight, it is made for 80～50 parts by 20～50 parts on Flos Carthami and Herba Erigerontis, or the Herba Erigerontis extract that obtains after extraction of the Flos Carthami extract that is obtained after extracting by corresponding weight portion medical material and corresponding weight portion medical material is equipped with suitable adjuvant and is made.

4, according to the compound formulation of breviscapine of the described treatment cardio-cerebrovascular diseases of claim 3, it is characterized in that: calculate according to parts by weight, it is made for 75 parts by 25 parts on Flos Carthami and Herba Erigerontis, or the Herba Erigerontis extract that obtains after extraction of the Flos Carthami extract that is obtained after extracting by corresponding weight portion medical material and corresponding weight portion medical material is equipped with suitable adjuvant and is made.

5, according to the compound formulation of breviscapine of any described treatment cardio-cerebrovascular diseases among the claim 1-4, it is characterized in that: the amount of adjuvant in the deduction preparation, the lamp-dish flower acetic content in the preparation is not less than 0.2%, and the content of flavones ingredient is not less than 5%.

6, according to the compound formulation of breviscapine of any described treatment cardio-cerebrovascular diseases among the claim 1-5, it is characterized in that: preparation of the present invention comprises: be directly used in the injection with small volume of drug administration by injection, directly for the venous transfusion of intravenous drip, need to be used for after the dilution concentrated solution for injection and injectable sterile powder, tablet, dispersible tablet, oral cavity disintegration tablet, capsule, soft capsule, granule, drop pill and the oral liquid of intravenous drip.

7, according to the compound formulation of breviscapine of the described treatment cardio-cerebrovascular diseases of claim 6, it is characterized in that: preparation of the present invention is an injection, comprising: be directly used in the injection with small volume of drug administration by injection, directly for the venous transfusion of intravenous drip, need to be used for after the dilution concentrated solution for injection and the injectable sterile powder of intravenous drip.

8, as the preparation method of the compound formulation of breviscapine of any described treatment cardio-cerebrovascular diseases among the claim 1-7, it is characterized in that: get the Herba Erigerontis medical material, add water or ethanol extraction, extracting solution gets the Herba Erigerontis crude extract after carrying out suitably concentrating, and also can further adopt one or more methods mixing in alcohol deposition method, acid-base precipitation method, column chromatography, the solvent extraction to use to such an extent that Herba Erigerontis is made with extra care extract; Get flos carthami, add water or ethanol extraction, extracting solution gets the Flos Carthami crude extract after carrying out suitably concentrating, also can further adopt one or more methods mixing in alcohol deposition method, acid-base precipitation method, column chromatography, the solvent extraction to use to such an extent that Flos Carthami is made with extra care extract, with Herba Erigerontis crude extract or refining extract and Flos Carthami crude extract or refining extract mixing, make different preparations then.

9, according to the preparation method of the compound formulation of breviscapine of the described treatment cardio-cerebrovascular diseases of claim 8, it is characterized in that: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 4-10 times of volume 50-80% alcohol reflux 1-4 time, each 0.5-3 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 1-5 times of medical material volume is filtered, and filtrate is with the 0.3-0.8ml/g medical material.The speed of min is crossed AB-8 type macroporous adsorbent resin, with 1-10 times of resinite hydrops and 1-6 times of resin volume 5-15% alcohol flushing impurity, then with the 30-70% alcohol desorption of 1-7 times of resin volume, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 5-15 times of decocting and boils 1-4 time, and each 0.5-2.5 hour, collect extracting solution, to filter, filtrate is with the 0.3-0.8ml/g medical material.The speed of min is crossed polyamide chromatography post, with 3-8 times of resinite hydrops and 2-6 times of resin volume 5-25% ethanol elution impurity, then with 2-7 times of resin volume 40-70% alcohol desorption, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.10～1.20, Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add different auxiliary material, make different preparations.

10, preparation method according to the compound formulation of breviscapine of the described treatment cardio-cerebrovascular diseases of claim 8, it is characterized in that: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, adding 4～10 times of volume decoctings boils 1～4 time, each 0.5～2.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, add ethanol and carry out ethanol precipitation twice, make for the first time to contain the alcohol amount and reach 55～75%, make for the second time to contain the alcohol amount and reach 80～90%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 4～10 times of volume 50～90% alcohol reflux 1～4 time, each 0.5～2.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.15～1.25, drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, Flos Carthami extract mix homogeneously, add adjuvant and make different preparations.

11, preparation method according to the compound formulation of breviscapine of the described treatment cardio-cerebrovascular diseases of claim 9, it is characterized in that: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 3 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin, with 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity, use 40% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 10 times of decoctings and boils 3 times, each 1 hour, collect extracting solution, cross polyamide chromatography post, with 6 times of resinite hydrops and 4 times of resin volume 20% ethanol elution impurity, use 5 times of resin volume 60% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, get Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add an amount of water for injection dissolving, by volume add 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.0～7.0, boil, coarse filtration is spent the night in 4 ℃ of cold preservations, fine straining; Mannitol is added the injection water be mixed with 100mg/ml solution,, filter with above-mentioned filtrate mixing, packing, temperature-45 ℃, pre-freeze time 10h, the beginning evacuation, and be warming up to-40 ℃, and keep 8h, be warming up to-35 ℃ again, keep 8h; Be warming up to-25 ℃, keep 8h, be warming up to-15 ℃, keep 5h, be warming up to 0 ℃, keep 5h, be warming up to 10 ℃, keep 2h, be warming up to 20 ℃, keep 2h, promptly get the Injectable sterile block.

12, preparation method according to the compound formulation of breviscapine of the described treatment cardio-cerebrovascular diseases of claim 9, it is characterized in that: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 3 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin, with 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity, use 40% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 10 times of decoctings and boils 3 times, each 1 hour, collect extracting solution, cross polyamide chromatography post, with 6 times of resinite hydrops and 4 times of resin volume 20% ethanol elution impurity, use 5 times of resin volume 60% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add an amount of water for injection dissolving, by volume add 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, transfer pH value 5.0～7.0, boil, coarse filtration is spent the night in 4 ℃ of cold preservations, fine straining adds the injection water, divide to install to pacify and cut open bottle, seal sterilization and promptly get injection with small volume or concentrated solution for injection.

13, preparation method according to the compound formulation of breviscapine of the described treatment cardio-cerebrovascular diseases of claim 9, it is characterized in that: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 3 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin, with 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity, use 40% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 10 times of decoctings and boils 3 times, each 1 hour, collect extracting solution, cross polyamide chromatography post, with 6 times of resinite hydrops and 4 times of resin volume 20% ethanol elution impurity, use 5 times of resin volume 60% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, get Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add an amount of water for injection dissolving, add the glucose of ormal weight again, by volume add 1.0% active carbon behind the mixed dissolution, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.0～7.0, boil, 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining, add the injection water, packing, sterilization promptly gets glucose intravenous infusion.

14, preparation method according to the compound formulation of breviscapine of the described treatment cardio-cerebrovascular diseases of claim 9, it is characterized in that: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 3 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin, with 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity, use 40% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 10 times of decoctings and boils 3 times, each 1 hour, collect extracting solution, cross polyamide chromatography post, with 6 times of resinite hydrops and 4 times of resin volume 20% ethanol elution impurity, use 5 times of resin volume 60% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, get Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add an amount of water for injection dissolving, add the sodium chloride of ormal weight again, by volume add 1.0% active carbon behind the mixed dissolution, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.0～7.0, boil, 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining, add the injection water, packing, sterilization promptly gets sodium chloride intravenous infusion.

15, preparation method according to the compound formulation of breviscapine of the described treatment cardio-cerebrovascular diseases of claim 9, it is characterized in that: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 3 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin, with 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity, use 40% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 10 times of decoctings and boils 3 times, each 1 hour, collects extracting solution, cross polyamide chromatography post,, use 5 times of resin volume 60% alcohol desorptions then with 6 times of resinite hydrops and 4 times of resin volume 20% ethanol elution impurity, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add an amount of water for injection dissolving, by volume add 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.5～7.5, boil, coarse filtration is spent the night in 4 ℃ of cold preservations, fine straining, divide and install in the enamel tray, temperature-45 ℃, pre-freeze time 10h, beginning evacuation, and be warming up to-40 ℃, keep 8h, be warming up to-35 ℃ again, keep 8h; Be warming up to-25 ℃, keep 8h, be warming up to-15 ℃, keep 5h, be warming up to 0 ℃, keep 5h, be warming up to 10 ℃, keep 2h, be warming up to 20 ℃, keep 2h, under aseptic condition, divide to install to promptly to get the lyophilization sterilized powder that is used to inject in the cillin bottle.

16, preparation method according to the compound formulation of breviscapine of the described treatment cardio-cerebrovascular diseases of claim 9, it is characterized in that: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 3 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin, with 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity, use 40% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Herba Erigerontis extract; Flos Carthami adds 10 times of decoctings and boils 3 times, each 1 hour, collect extracting solution, cross polyamide chromatography post, with 6 times of resinite hydrops and 4 times of resin volume 20% ethanol elution impurity, use 5 times of resin volume 60% alcohol desorptions then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, Flos Carthami extract, above-mentioned Herba Erigerontis extract and Flos Carthami extract is mixed evenly, add an amount of water for injection dissolving, by volume add 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, transfer pH value 5.5～7.5, boil, coarse filtration is spent the night in 4 ℃ of cold preservations, fine straining is 150 ℃ in inlet temperature, leaving air temp is 70 ℃, and air velocity is 18ms ^-1Condition under spray drying get powder, packing promptly gets the spray drying sterilized powder that is used to inject.

17, preparation method according to the compound formulation of breviscapine of the described treatment cardio-cerebrovascular diseases of claim 10, it is characterized in that: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, adding 4～10 times of volume decoctings boils 1～4 time, each 0.5～2.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, add ethanol and carry out ethanol precipitation twice, make for the first time to contain the alcohol amount and reach 55～75%, make for the second time to contain the alcohol amount and reach 80～90%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 4～10 times of volume 50～90% alcohol reflux 1～4 time, each 0.5～2.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.15～1.25, drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, Flos Carthami extract mix homogeneously, add an amount of water for injection dissolving, by volume add 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.0～7.0, boil, 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining.Mannitol is added the injection water be mixed with 100mg/ml solution,, filter with above-mentioned filtrate mixing, packing, temperature-45 ℃, pre-freeze time 10h, the beginning evacuation, and be warming up to-40 ℃, and keep 8h, be warming up to-35 ℃ again, keep 8h; Be warming up to-25 ℃, keep 8h, be warming up to-15 ℃, keep 5h, be warming up to 0 ℃, keep 5h, be warming up to 10 ℃, keep 2h, be warming up to 20 ℃, keep 2h, promptly get the Injectable sterile block.

18, preparation method according to the compound formulation of breviscapine of the described treatment cardio-cerebrovascular diseases of claim 10, it is characterized in that: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, adding 4～10 times of volume decoctings boils 1～4 time, each 0.5～2.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, add ethanol and carry out ethanol precipitation twice, make for the first time to contain the alcohol amount and reach 55～75%, make for the second time to contain the alcohol amount and reach 80～90%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 4～10 times of volume 50～90% alcohol reflux 1～4 time, each 0.5～2.5 hour, measuring relative density when merge extractive liquid,, decompression recycling ethanol to 60 ℃ is 1.15～1.25, and drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, the Flos Carthami extract mix homogeneously, add an amount of water for injection dissolving, by volume add 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, transfer pH value 5.0～7.0, boil, coarse filtration is spent the night in 4 ℃ of cold preservations, fine straining adds the injection water, divide to install to pacify and cut open bottle, seal sterilization and promptly get injection with small volume or concentrated solution for injection.

19, preparation method according to the compound formulation of breviscapine of the described treatment cardio-cerebrovascular diseases of claim 10, it is characterized in that: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, adding 4～10 times of volume decoctings boils 1～4 time, each 0.5～2.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, add ethanol and carry out ethanol precipitation twice, make for the first time to contain the alcohol amount and reach 55～75%, make for the second time to contain the alcohol amount and reach 80～90%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 4～10 times of volume 50～90% alcohol reflux 1～4 time, each 0.5～2.5 hour, measuring relative density when merge extractive liquid,, decompression recycling ethanol to 60 ℃ was 1.15～1.25, drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, the Flos Carthami extract mix homogeneously adds an amount of water for injection dissolving, adds the glucose of ormal weight again, by volume add 1.0% active carbon behind the mixed dissolution, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.0～7.0, boil, 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining, add the injection water, packing, sterilization promptly gets glucose intravenous infusion.

20, preparation method according to the compound formulation of breviscapine of the described treatment cardio-cerebrovascular diseases of claim 10, it is characterized in that: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, adding 4～10 times of volume decoctings boils 1～4 time, each 0.5～2.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, add ethanol and carry out ethanol precipitation twice, make for the first time to contain the alcohol amount and reach 55～75%, make for the second time to contain the alcohol amount and reach 80～90%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 4～10 times of volume 50～90% alcohol reflux 1～4 time, each 0.5～2.5 hour, measuring relative density when merge extractive liquid,, decompression recycling ethanol to 60 ℃ was 1.15～1.25, drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, the Flos Carthami extract mix homogeneously adds an amount of water for injection dissolving, adds the sodium chloride of ormal weight again, by volume add 1.0% active carbon behind the mixed dissolution, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.0～7.0, boil, 4 ℃ of cold preservations are spent the night, coarse filtration, fine straining, add the injection water, packing, sterilization promptly gets sodium chloride intravenous infusion.

21, preparation method according to the compound formulation of breviscapine of the described treatment cardio-cerebrovascular diseases of claim 10, it is characterized in that: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, adding 4～10 times of volume decoctings boils 1～4 time, each 0.5～2.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, add ethanol and carry out ethanol precipitation twice, make for the first time to contain the alcohol amount and reach 55～75%, make for the second time to contain the alcohol amount and reach 80～90%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 4～10 times of volume 50～90% alcohol reflux 1～4 time, each 0.5～2.5 hour, measuring relative density when merge extractive liquid,, decompression recycling ethanol to 60 ℃ was 1.15～1.25, drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, the Flos Carthami extract mix homogeneously adds an amount of water for injection dissolving, by volume adds 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.5～7.5, boil, coarse filtration is spent the night in 4 ℃ of cold preservations, fine straining, divide and install in the enamel tray, temperature-45 ℃, pre-freeze time 10h, beginning evacuation, and be warming up to-40 ℃, keep 8h, be warming up to-35 ℃ again, keep 8h; Be warming up to-25 ℃, keep 8h, be warming up to-15 ℃, keep 5h, be warming up to 0 ℃, keep 5h, be warming up to 10 ℃, keep 2h, be warming up to 20 ℃, keep 2h, under aseptic condition, divide to install to promptly to get the freeze dry sterile powder end that is used to inject in the cillin bottle.

22, preparation method according to the compound formulation of breviscapine of the described treatment cardio-cerebrovascular diseases of claim 10, it is characterized in that: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, adding 4～10 times of volume decoctings boils 1～4 time, each 0.5～2.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, add ethanol and carry out ethanol precipitation twice, make for the first time to contain the alcohol amount and reach 55～75%, make for the second time to contain the alcohol amount and reach 80～90%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 4～10 times of volume 50～90% alcohol reflux 1～4 time, each 0.5～2.5 hour, measuring relative density when merge extractive liquid,, decompression recycling ethanol to 60 ℃ is 1.15～1.25, and drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, the Flos Carthami extract mix homogeneously, add an amount of water for injection dissolving, by volume add 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, transfer pH value 5.5～7.5, boil, coarse filtration is spent the night in 4 ℃ of cold preservations, fine straining is 150 ℃ in inlet temperature, leaving air temp is 70 ℃, and air velocity is 18ms ^-1Condition under spray drying get powder, packing promptly gets the spray drying sterilized powder that is used to inject.

23, according to the preparation method of the compound formulation of breviscapine of the described treatment cardio-cerebrovascular diseases of claim 10, it is characterized in that: get Herba Erigerontis, be ground into the coarse powder of 10 mesh sieves, adding 8 times of volume decoctings boils 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, add ethanol and carry out ethanol precipitation twice, make for the first time to contain the alcohol amount and reach 70%, make for the second time to contain the alcohol amount and reach 85%, filter, measuring relative density during filtrate recycling ethanol to 60 ℃ is 1.05～1.15, and drying under reduced pressure gets Herba Erigerontis extract; Flos Carthami adds 8 times of volume 80% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.15～1.25, drying under reduced pressure gets Flos Carthami extract, with above-mentioned Herba Erigerontis extract, Flos Carthami extract mix homogeneously, add adjuvant and make tablet, dispersible tablet, oral cavity disintegration tablet, capsule, soft capsule, granule, drop pill or oral liquid.