CN1935234A - Chinese medicine injection preparation and its preparing method - Google Patents
Chinese medicine injection preparation and its preparing method Download PDFInfo
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- CN1935234A CN1935234A CN 200610111680 CN200610111680A CN1935234A CN 1935234 A CN1935234 A CN 1935234A CN 200610111680 CN200610111680 CN 200610111680 CN 200610111680 A CN200610111680 A CN 200610111680A CN 1935234 A CN1935234 A CN 1935234A
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Abstract
The present invention relates to a Chinese medicine injection preparation for raising immunity of human body and curing angiocardiopathy and cerebrovascular disease. Its prescription is formed from ophiopogon tube, ginseng or red ginseng or pilose asiabell root and erigeron breviscapus, and suid invention adopts the column chromatographic process to purify the extract of medicinal material. Said invention can be mainly used for curing the diseases of coronary heart disease, angina pectoris, arrhythmia, cerebral thrombosis and senile dementia, etc.
Description
Technical field
The present invention is a kind of traditional medicine Injectio with human body immunity improving power, treatment cardio-cerebrovascular diseases and preparation method thereof, belongs to technical field of Chinese medicine.
Technical background
We suit the medicine to the illness--and-cardiovascular and cerebrovascular disease is a big persistent ailment that threatens world's healthy population as coronary heart disease, myocardial infarction, rhomboembolia type cerebrovascular, and the trend that progressively rises is arranged in recent years.The height of cardiovascular and cerebrovascular disease mortality rate is to weigh a country, resident's quality of life, the important indicator of sanitary health career, along with the arriving of fairly comfortable life, and the change of meals spectrum, resident's longevity, healthy existence desire improve constantly.In order to prevent, control the generation of cardiovascular and cerebrovascular disease, exploitation cardiovascular and cerebrovascular disease class medicine has become a main trend.Therefore, it is low to seek a kind of cost, determined curative effect, and the natural Chinese medicines preparation that has no side effect is very urgent.
The medicine that is used for the treatment of at present cardiovascular and cerebrovascular disease clinically is generally Radix Salviae Miltiorrhizae Injection, SHENGMAI ZHUSHEYE, SHENMAI ZHUSHEYE, Breviscapini injection etc., yet these injection curative effects are very not desirable, and the report that untoward reaction is all arranged, the clinical reports of delivering in " clinical misdiagnosis wrong treatment " the 6th phase of calendar year 2001 at the above " giving birth to the untoward reaction of arteries and veins (and ginseng arteries and veins) injection ", Li Lanqing etc. of " Chinese patent medicine " 1999 the 8th phases as Zhuan Zhiquan such as " untoward reaction of Herba Erigerontis injection ".The applicant thinks that the reason that produces this situation may be: 1, the prescription of these preparations and proportioning thereof have much room for improvement, effect such as Breviscapini injection, Radix Salviae Miltiorrhizae Injection is single, can only be to a certain cause of disease pathological changes generation effect of cardiovascular and cerebrovascular disease, so curative effect is undesirable; 2, the processing extraction is impure, and some compositions such as pigment, tannin, starch, protein etc. are remained in the medicinal liquid with colloidal form, thereby untoward reaction takes place.Effective ingredient in Chinese or effective part group have multiple composition synergism, make its performance better therapeutic.Therefore, invent a kind of good effect, untoward reaction few, to the cardiovascular and cerebrovascular disease Different types of etiopathogenises produce the medicament composing prescription of synergistic therapeutic action and preparation thereof, technology is necessary.
The applicant drafts prescription: Radix Ophiopogonis, Radix Ginseng, breviscapine from the medicine of several respects researchs such as Chinese medicine traditional theory, pathomechanism treatment cardiovascular and cerebrovascular disease.From Chinese medicine theoretically, Radix Ginseng QI invigorating reinforcing the heart; Radix Ophiopogonis YIN nourishing and the production of body fluid promoting, Fu Mai; Breviscapine is the effective ingredient of Herba Erigerontis, and the effect of dredge the meridian passage, blood circulation promoting and blood stasis dispelling is arranged, and three medicine compatibilities are combined into a kind of pharmaceutical preparation that can effectively treat cardiovascular and cerebrovascular disease.From pathomechanism, vascular lesion is the main cause that causes at present known all cardiovascular and cerebrovascular vessel incident, and can be divided into ischemic and hemorrhagic two big classes from lesion nature, and the former sickness rate is far above the latter.In recent years, the free radical mechanism research of ischemic heart and brain damage is very active, has obtained bigger progress in many aspects.Prior art shows the effect that has breviscapine, Radix Ginseng, Radix Ophiopogonis good removing reactive oxygen free radical.Inventor's process discovers that three's compatibility result of use is better than the single medicine, and through the drug effective region that the process for refining that the present invention studies prepares, active ingredient has been carried out rich long-pending and purification, thereby made the effect of preparation better.
Summary of the invention
The object of the present invention is to provide a kind of ejection preparation and preparation method thereof with human body immunity improving power, treatment cardiovascular and cerebrovascular disease; The present invention utilizes the Radix Ginseng strongly invigorating primordial QI, and Radix Ophiopogonis, the effect and the breviscapine of YIN nourishing and the production of body fluid promoting were combined into a kind of preparation that can effectively treat cardiovascular and cerebrovascular disease.The present invention is directed to prior art, at different medical materials, adopt the mode of separately extracting, both can effectively extract active component, can under the situation that guarantees active component, remove impurity targetedly simultaneously, sample is made with extra care, make injection, make the faster performance curative effect of medicine performance, can be used for the treatment of cardiovascular and cerebrovascular disease acute attack stage.
Technical solution of the present invention is achieved in that according to components by weight percent and calculates, it is refiningly added suitable adjuvant and is made through extracting by 0.001～150 part of 10～1000 parts of 10～1000 parts of Radix Ophiopogonis, Radix Ginseng and breviscapine, or adds the injection that suitable adjuvant is made by corresponding weight portion medical material through extracting the extract and the corresponding weight portion breviscapine that obtain after refining.Specifically, calculate according to components by weight percent, it is refiningly added suitable adjuvant and is made through extracting by 0.01～100 part of 10～500 parts of 10～500 parts of Radix Ophiopogonis, Radix Ginseng and breviscapine, or adds the injection that suitable adjuvant is made by corresponding weight portion medical material through extracting the extract and the corresponding weight portion breviscapine that obtain after refining.In particular, calculate according to components by weight percent, it is refiningly added suitable adjuvant and is made through extracting by 0.05～50 part of 50～200 parts of 50～200 parts of Radix Ophiopogonis, Radix Ginseng and breviscapine,, or add suitable adjuvant and be made through extracting the extract that obtains after refining and corresponding weight portion breviscapine by corresponding weight portion medical material.
Preparation of the present invention is an injection, comprising: be directly used in drug administration by injection injection, need to be used for the concentrated solution for injection of intravenous drip after the dilution, directly for the venous transfusion of intravenous drip and injectable sterile powder and the aseptic block that makes with freeze-drying or spray drying method.
Traditional medicine Injectio with human body immunity improving power, treatment cardiovascular and cerebrovascular disease of the present invention: contain the multiple compositions of surveying such as saponin component and flavones ingredient in the preparation, calculate according to percentage by weight, wherein the content of saponin component is not less than 1% of the total solid after the deduction adjuvant amount and water quantities in the preparation; The content of scutellarin should be 80%～120% of labelled amount in the preparation.Saponin component in the preparation and flavones ingredient and and other all can survey the composition sum and be not less than 25% of the total solid after the deduction adjuvant amount and water quantities in the preparation.
Preparation method with traditional medicine Injectio of human body immunity improving power, treatment cardiovascular and cerebrovascular disease of the present invention: Radix Ophiopogonis, Radix Ginseng two flavor medical materials add water or ethanol extraction respectively, extracting solution carry out suitably concentrating crude extract or further adopt one or more methods in alcohol deposition method, water precipitating method, acid-base precipitation method, flocculent precipitation, column chromatography, the solvent extraction to mix to use refining extract, material crude extract or refining extract and the breviscapine adding different auxiliary material of getting it filled is made various ejection preparations.
Specifically: the preparation method with traditional medicine Injectio of human body immunity improving power, treatment cardiovascular and cerebrovascular disease of the present invention is:
A, Radix Ophiopogonis medical material, adding 5～15 times of volume decoctings boils 1～4 time, each 0.5～2.5 hour, merge extractive liquid,, merge extractive liquid,, filter, filtrate is crossed ZTC-1 type macroporous adsorptive resins with the speed of 0.3-0.8ml/g medical material .min, water with 3-10 times of resin volume washes with the speed of 0.5-1.5ml/g medical material .min earlier, the 5-25% ethanol of reuse 1-4 times of resin volume is with the speed eluting impurity of 0.5-1.5ml/g medical material .min, at last with the 50-70% ethanol of 2-6 times of resin volume speed eluting with 0.5-1.0ml/g medical material .min, collect stripping liquid, reclaiming and measuring relative density when ethanol is evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;
B, get the ginseng crude drug, add 5～15 times of volume 50～80% alcohol reflux 1～4 time, each 0.5～2.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water dissolution that adds 1-5 times of medical material volume, filter, filtrate is crossed ZTC-1 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, with the 30-70% alcohol desorption of 1-7 times of resin volume, collect stripping liquid then successively, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Radix Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add adjuvant and make different ejection preparations.
Injection of the present invention prepares like this:
A, get medical material Radix Ophiopogonis, adding 10 times of volume decoctings boils 3 times, each 1.5 hours, merge extractive liquid,, filter, filtrate is crossed ZTC-1 type macroporous adsorptive resins with the speed of 0.5ml/g medical material .min, water with 6 times of resin volumes washes with the speed of 1ml/g medical material .min earlier, 20% ethanol of 3 times of resin volumes of reuse is with the speed eluting impurity of 1ml/g medical material .min, use the speed eluting of 60% ethanol of 4 times of resin volumes at last with 0.8ml/g medical material .min, collect stripping liquid, reclaim the dry Radix Ophiopogonis extract that gets of ethanol;
B, get the ginseng crude drug, 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 dissolution that adds 4 times of medical material volumes, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.5ml/g medical material .min, use 7 times of resinite hydrops and 5 times of resin volume 10% alcohol flushing impurity successively, use 60% 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, dry Radix Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add adjuvant and make different ejection preparations.
Injection of the present invention specifically prepares like this:
A, get medical material Radix Ophiopogonis, adding 10 times of volume decoctings boils 3 times, each 1.5 hours, merge extractive liquid,, filter, filtrate is crossed ZTC-1 type macroporous adsorptive resins with the speed of 0.5ml/g medical material .min, water with 6 times of resin volumes washes with the speed of 1ml/g medical material .min earlier, 20% ethanol of 3 times of resin volumes of reuse is with the speed eluting impurity of 1ml/g medical material .min, use the speed eluting of 60% ethanol of 4 times of resin volumes at last with 0.8ml/g medical material .min, collect stripping liquid, reclaim the dry Radix Ophiopogonis extract that gets of ethanol;
B, get the ginseng crude drug, 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 dissolution that adds 4 times of medical material volumes, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.5ml/g medical material .min, use 7 times of resinite hydrops and 5 times of resin volume 10% alcohol flushing impurity successively, use 60% 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, dry Radix Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 0.1%～1.5% active carbon, boil, keep little 10～60min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfers pH value 5.5～7.5, boils, spend the night coarse filtration, fine straining 1～8 ℃ of cold preservation.Mannitol is added the injection water be mixed with 50～150mg/ml solution,, filter packing with above-mentioned filtrate mixing, temperature-55～-45 ℃, pre-freeze time 8～12h, the beginning evacuation, and be warming up to-43～-37 ℃, keep 6～10h, be warming up to-33～-27 ℃ again, keep 6～10h; Be warming up to-23～-17 ℃, keep 6～10h, be warming up to-13～-7 ℃, keep 4～6h, be warming up to-3～3 ℃, keep 4～6h, be warming up to 7～13 ℃, keep 1～3h, be warming up to 17～23 ℃, keep 1～3h, promptly get the aseptic block of lyophilizing.
Injection of the present invention is preparation like this:
A, get medical material Radix Ophiopogonis, adding 10 times of volume decoctings boils 3 times, each 1.5 hours, merge extractive liquid,, filter, filtrate is crossed ZTC-1 type macroporous adsorptive resins with the speed of 0.5ml/g medical material .min, water with 6 times of resin volumes washes with the speed of 1ml/g medical material .min earlier, 20% ethanol of 3 times of resin volumes of reuse is with the speed eluting impurity of 1ml/g medical material .min, use the speed eluting of 60% ethanol of 4 times of resin volumes at last with 0.8ml/g medical material .min, collect stripping liquid, reclaim the dry Radix Ophiopogonis extract that gets of ethanol;
B, get the ginseng crude drug, 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 dissolution that adds 4 times of medical material volumes, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.5ml/g medical material .min, use 7 times of resinite hydrops and 5 times of resin volume 10% alcohol flushing impurity successively, use 60% 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, dry Radix Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 0.1%～1.5% active carbon, boil, keep little 10～60min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.5～7.5, boil, spend the night 1～8 ℃ of cold preservation, coarse filtration, fine straining, dividing to install in the ampoule bottle, is 100～110 ℃ in vapor (steam) temperature, and actual pressure is at 100～120kN/m
3Pressure sterilizing is 40～60 minutes under the condition, promptly gets the injection with small volume or the concentrated solution for injection that are directly used in drug administration by injection.
Injection of the present invention is preparation like this:
A, get medical material Radix Ophiopogonis, adding 10 times of volume decoctings boils 3 times, each 1.5 hours, merge extractive liquid,, filter, filtrate is crossed ZTC-1 type macroporous adsorptive resins with the speed of 0.5ml/g medical material .min, water with 6 times of resin volumes washes with the speed of 1ml/g medical material .min earlier, 20% ethanol of 3 times of resin volumes of reuse is with the speed eluting impurity of 1ml/g medical material .min, use the speed eluting of 60% ethanol of 4 times of resin volumes at last with 0.8ml/g medical material .min, collect stripping liquid, reclaim the dry Radix Ophiopogonis extract that gets of ethanol;
B, get the ginseng crude drug, 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 dissolution that adds 4 times of medical material volumes, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.5ml/g medical material .min, use 7 times of resinite hydrops and 5 times of resin volume 10% alcohol flushing impurity successively, use 60% 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, dry Radix Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, add the glucose of ormal weight again, by volume add 0.1%～1.5% active carbon, boil, keep little 10～60min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, transfer pH value 5.5～7.5, boil, spend the night coarse filtration, fine straining 1～8 ℃ of cold preservation, add the injection water, packing is under 105～125 ℃ of conditions, sterilized 20～60 minutes, and promptly got the glucose intravenous infusion agent.
Injection of the present invention is preparation like this:
A, get medical material Radix Ophiopogonis, adding 10 times of volume decoctings boils 3 times, each 1.5 hours, merge extractive liquid,, filter, filtrate is crossed ZTC-1 type macroporous adsorptive resins with the speed of 0.5ml/g medical material .min, water with 6 times of resin volumes washes with the speed of 1ml/g medical material .min earlier, 20% ethanol of 3 times of resin volumes of reuse is with the speed eluting impurity of 1ml/g medical material .min, use the speed eluting of 60% ethanol of 4 times of resin volumes at last with 0.8ml/g medical material .min, collect stripping liquid, reclaim the dry Radix Ophiopogonis extract that gets of ethanol;
B, get the ginseng crude drug, 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 dissolution that adds 4 times of medical material volumes, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.5ml/g medical material .min, use 7 times of resinite hydrops and 5 times of resin volume 10% alcohol flushing impurity successively, use 60% 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, dry Radix Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, add the sodium chloride of ormal weight again, by volume add 0.1%～1.5% active carbon, boil, keep little 10～60min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, transfer pH value 5.5～7.5, boil, spend the night coarse filtration, fine straining 1～8 ℃ of cold preservation, add the injection water, packing is under 105～125 ℃ of conditions, sterilized 20～60 minutes, and promptly got the sodium chloride intravenous infusion agent.
Injection of the present invention is preparation like this:
A, get medical material Radix Ophiopogonis, adding 10 times of volume decoctings boils 3 times, each 1.5 hours, merge extractive liquid,, filter, filtrate is crossed ZTC-1 type macroporous adsorptive resins with the speed of 0.5ml/g medical material .min, water with 6 times of resin volumes washes with the speed of 1ml/g medical material .min earlier, 20% ethanol of 3 times of resin volumes of reuse is with the speed eluting impurity of 1ml/g medical material .min, use the speed eluting of 60% ethanol of 4 times of resin volumes at last with 0.8ml/g medical material .min, collect stripping liquid, reclaim the dry Radix Ophiopogonis extract that gets of ethanol;
B, get the ginseng crude drug, 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 dissolution that adds 4 times of medical material volumes, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.5ml/g medical material .min, use 7 times of resinite hydrops and 5 times of resin volume 10% alcohol flushing impurity successively, use 60% 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, dry Radix Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 0.1%～1.5% active carbon, boil, keep little 10～60min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfers pH value 5.5～7.5, boils, spend the night 1～8 ℃ of cold preservation, coarse filtration, fine straining divide to install in the enamel tray, temperature-55～-45 ℃, pre-freeze time 8～12h, the beginning evacuation, and be warming up to-43～-37 ℃, keep 6～10h, be warming up to-33～-27 ℃ again, keep 6～10h; Be warming up to-23～-17 ℃, keep 6～10h, be warming up to-13～-7 ℃, keep 4～6h, be warming up to-3～3 ℃, keep 4～6h, be warming up to 7～13 ℃, keep 1～3h, be warming up to 17～23 ℃, keep 1～3h, under aseptic condition, divide to install to promptly to get the freeze dry sterile powder end in the cillin bottle.
Injection of the present invention is preparation like this:
A, get medical material Radix Ophiopogonis, adding 10 times of volume decoctings boils 3 times, each 1.5 hours, merge extractive liquid,, filter, filtrate is crossed ZTC-1 type macroporous adsorptive resins with the speed of 0.5ml/g medical material .min, water with 6 times of resin volumes washes with the speed of 1ml/g medical material .min earlier, 20% ethanol of 3 times of resin volumes of reuse is with the speed eluting impurity of 1ml/g medical material .min, use the speed eluting of 60% ethanol of 4 times of resin volumes at last with 0.8ml/g medical material .min, collect stripping liquid, reclaim the dry Radix Ophiopogonis extract that gets of ethanol;
B, get the ginseng crude drug, 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 dissolution that adds 4 times of medical material volumes, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.5ml/g medical material .min, use 7 times of resinite hydrops and 5 times of resin volume 10% alcohol flushing impurity successively, use 60% 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, dry Radix Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 0.1%～1.5% active carbon, boil, keep little 10～60min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.5～7.5, boil, spend the night 1～8 ℃ of cold preservation, coarse filtration, fine straining, in inlet temperature is 140～160 ℃, and leaving air temp is 60～80 ℃, and air velocity is 16～20ms
-1Condition under spray drying get powder, packing promptly gets the spray drying sterilized powder.
Preparation method with traditional medicine Injectio of human body immunity improving power, treatment cardiovascular and cerebrovascular disease of the present invention: the adjuvant that is adopted in the preparation process comprises one or more in mannitol, galactose, glycine, glucose, sodium chloride, dextran, glycerol, ethanol, propylene glycol, Polyethylene Glycol, sorbitol, tween, the poloxamer.
The Radix Ginseng that the present invention relates to can also be the Radix Ginseng Rubra or the Radix Codonopsis of equivalent.
Experimentation shows, the prescription side effect that the applicant screened is little, cardiovascular and cerebrovascular disease is had tangible curative effect, and the formulation products that obtains is the good medicine of human body immunity improving power, treatment cardiovascular and cerebrovascular disease; The selected preparation technology of the present invention extracts the medical material effective ingredient when removing impurity; The selected moulding process of the present invention is rationally controlled.
The applicant has carried out a series of experiments, can prove that safety of medicine provided by the invention is effective, process stabilizing, quality controllable.
Experimental example 1: drug effectiveness research
The pharmacological research conclusion
| Pilot project | Of the present invention group | The Breviscapini injection group |
| Myocardial infarction model test due to the dog coronary artery ligation method | Effect is remarkable, and effect strengthens | Effect is general |
| Improve the rheology test of blood stasis model rat blood | Effect is remarkable, and effect strengthens | Effect is general |
| The antiplatelet aggregation test | Effect is remarkable, and effect strengthens | Effect is obvious |
| The rabbit fibrin solubility test | Effect is obvious, and effect strengthens | Effect is general |
From above-mentioned test as can be seen, therefore the combination preparation therapeutic effect proves that this prescription is reasonably, determined curative effect significantly better than the single preparation.
Experimental example 2: injection with small volume or concentrated solution for injection molding research
(1) activated carbon dosage is investigated:
Injection owing to solvent, raw material, container etc. have the pyrogen material, reduces the safety of injection in the process of producing, and therefore needs to remove the pyrogen material in the process of preparation injection.The method of depyrogenation mainly contains high temperature method, acid-base method, ultrafiltration and absorption method at present, active carbon adsorption not only can heat of adsorption originality composition, the effect that also has filter of helping and decolouring, when removing pyrogen, can improve the appearance character of preparation, therefore we select the active carbon adsorption depyrogenation for use, and its consumption is investigated.The results are shown in following table:
The activated carbon dosage investigation table
| Activated carbon dosage (%) | Cream heavy (g) | The rate of transform (%) | Outward appearance |
| 0.1 | 6.62 | 56.30 | Reddish brown |
| 1 | 6.37 | 54.65 | Red |
| 1.5 | 6.08 | 51.42 | Red |
From the medicinal liquid outward appearance, select activated carbon dosage be 1% and 1.5% proper; But judge that from the rate of transform 0.1% consumption and 1% consumption are slightly better, the three all can satisfy the related request of injection, but takes all factors into consideration above factor, so that be the best with the activated carbon decolorizing of medicine liquid volume 1%.
The bleaching time investigation table
| Time (minute) | Cream heavy (g) | The rate of transform (%) | Outward appearance |
| 10 | 6.75 | 55.82 | Reddish brown |
| 30 | 6.48 | 54.53 | Red |
| 60 | 6.10 | 52.59 | Pale red |
From top test as can be seen, along with the color of the prolongation medicinal liquid of time is thin out, but above-mentioned factor is taken all factors into consideration in the also corresponding minimizing of the rate of transform of effective ingredient, selects for use and boils 30 minutes for best.
(2) pH value of solution is investigated
For adapting to the Human Physiology needs, also to consider the character of each constituents in the medicinal liquid simultaneously, when dosing, need suitably adjust the pH value of medicinal liquid.Select scutellarin content as evaluation index.
Test method and result: after feeding intake and handle by recipe quantity,, filter with the concentrated solution mix homogeneously by above-mentioned condition, add water to 1000ml, adjust pH is 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 Table.
The investigation of dosing pH value
| Sequence number | 1 2 3 | 4 5 6 7 | 8 9 |
| Dosing pH | 4.5 5.0 5.5 | 6.0 6.5 7.0 7.5 | 8.0 8.5 |
| Boil pH | 4.1 4.6 5.3 | 5.7 6.2 6.6 7.1 | 7.6 8.0 |
| Outward appearance | Precipitation appears | No significant change | Color burn |
The result shows, the medicinal liquid pH value boils the back at the sample below 5.5 and precipitation occurs, and pH value is obviously deepened in the color sample more than 7.5, and pH value is that 5.5～7.5 medicinal liquid is relatively stable, and outward appearance does not have significant change.Below its scutellarin content is measured.The results are shown in Table:
The situation of change table of index components before and after pH value is regulated
| Sequence number | Dosing pH | Content during dosing (%) | Boil back pH | Boil back content (%) |
| 1 | 5.5 | 4.94 | 5.3 | 4.77 |
| 2 | 6.0 | 4.94 | 5.7 | 4.69 |
| 3 | 6.5 | 4.94 | 6.2 | 4.72 |
| 4 | 7.0 | 4.94 | 6.6 | 4.73 |
| 5 | 7.5 | 4.94 | 7.1 | 4.67 |
As seen from table, medicinal liquid is being adjusted the pH value front and back, the not too big variation of index components scutellarin content.The appearance character of comprehensive above-mentioned medicinal liquid and the changes of contents of scutellarin, the pH value of medicinal liquid is transferred between 5.5～7.5 when determining dosing.
Experimental example 3: the investigation of freeze-dry process
(1) screening of caffolding agent kind
The caffolding agent kind influences the molding of freeze-dried powder, so at first this is screened.Taking liquid mixes with caffolding agent mannitol, glucose and lactose solution respectively, 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 :-45 ℃, behind the pre-freeze 8h, the beginning evacuation, and be warming up to-40 ℃, keep 10h; Be warming up to-30 ℃, keep 10h; Be warming up to-20 ℃, keep 10h; Be warming up to-10 ℃, keep 5h; Be warming up to 0 ℃, keep 5h; Be warming up to 15 ℃, keep 3h; Be warming up to 25 ℃, keep 3h.The result is as showing:
The screening of caffolding agent kind
| The caffolding agent kind | Caffolding agent: medicinal liquid (V: V) | Solubility | The finished product outward appearance |
| Glucose | 2∶1 | Good | Part is subsided |
| Galactose | 2∶1 | Generally | Molding |
| Mannitol | 2∶1 | Good | Molding |
| Glycine | 2∶1 | Good | Molding, frangible |
| Dextran | 2∶1 | Generally | Molding |
| Mannitol, propylene glycol | 2∶1 | Good | Molding |
| Glycine, Polyethylene Glycol | 2∶1 | Good | Molding, frangible |
| Dextran, sorbitol, tween | 2∶1 | Good | Molding |
| Blank medicinal liquid | 3ml | Atrophy |
As seen from table, in the adjuvant that is screened, under the identical situation of other conditions, most of adjuvant all can be made into freeze-dried powder, but solubility angle integrated survey from yield rate, molding situation and sample, use the effect of mannitol to be better than other several adjuvants separately, can satisfy the every requirement of injection, reduce simultaneously as far as possible and add too much adjuvant.
(2) caffolding agent consumption screening
The mannitol solution (50mg/ml, 100mg/ml and 150mg/ml) of variable concentrations is mixed in varing proportions with medicinal liquid, filter, every cillin bottle loading amount is 3ml, lyophilization.Lyophilisation condition :-45 ℃, behind the pre-freeze 8h, the beginning evacuation, and be warming up to-40 ℃, keep 10h; Be warming up to-30 ℃, keep 10h; Be warming up to-20 ℃, keep 10h; Be warming up to-10 ℃, keep 5h; Be warming up to 0 ℃, keep 5h; Be warming up to 15 ℃, keep 3h; Be warming up to 25 ℃, keep 3h.The result is as showing:
The screening of mannitol consumption
| Numbering | Mannitol concentration (mg/ml) | Mannitol: medicinal liquid (v: v) | Color and luster | Profile | Solubility | Clarity |
| 1 | 50 | 2∶1 | Yellowish-brown | Part is subsided | Good | Up to specification |
| 2 | 100 | 2∶1 | Yellow | Intact | Good | Up to specification |
| 3 | 150 | 2∶1 | Yellowish | Intact | Good | Up to specification |
As seen from table, when the ratio of caffolding agent consumption and medicinal liquid is 2: 1, the sample character is that the sample of 100mg/ml and 150mg/ml is relatively good with the mannitol concentration, the sample of 50mg/ml has part to subside, but major part still is molding, but take all factors into consideration the consumption and the clinical dose of adjuvant, the optimum selection mannitol concentration is 100mg/ml, and the volume ratio of mannitol solution and medicinal liquid is 2: 1.
(3) lyophilization conditional filtering
Lyophilization is a veryer long dry run, needs to consume a large amount of energy.An ideal lyophilisation condition not only can be saved a large amount of energy, can also shorten man-hour simultaneously, so we are optimized screening to existing lyophilisation condition.The actual conditions screening sees Table:
The lyophilization conditional filtering
Time (h)
Condition I condition II condition III cold-trap
Temperature (℃)
-45 (pre-freezes) 8-8
-40 (pre-freeze)-10-
-40 (evacuation) 8-10
-35 (evacuation)-10-
-30 (evacuation) 8-10 keeps
-25 (evacuation)-8--70 ℃
-20 (evacuation) 8-10
-15 (evacuation)-8-
-10 (evacuation) 5-5
0 (evacuation) 555
10 (evacuation) 233
20 (evacuation) 233
Experimental result shows: finished product appearance character that condition I, II and III make and the equal conformance with standard of moisture.But comparatively speaking, condition II yield rate is low slightly, and condition III power consumption is bigger, considers the practical situation of production, short condition I of finally selected overall time spent, i.e. and lyophilization condition is: pre-freeze temperature-45 ℃, pre-freeze time 10h;-40 ℃ of evacuation keep 8h; Be warming up to-30 ℃ again, keep 8h; Be warming up to-20 ℃, keep 8h; Be warming up to-10 ℃, keep 5h; Be warming up to 0 ℃, keep 5h; Be warming up to 10 ℃, keep 2h; Be warming up to 20 ℃, keep 2h, get product.
Experimental example 4: spray drying conditional filtering
Spray drying technology can make sample dry rapidly under the situation of atomizing, and the protection effective ingredient can make the water content of sample reduce simultaneously, helps stability of formulation.It is bigger that but the air temperature and current speed that spray-dired effect is imported and exported influences, so we are that evaluation index is investigated these three factors with the loss of active ingredients rate.
Spray drying condition investigation table
| Inlet temperature (℃) | Outlet temperature (℃) | Air velocity (ms -1) | Loss rate (%) |
| 140 | 60 | 16 | 3.67 |
| 150 | 70 | 18 | 3.10 |
| 160 | 80 | 20 | 3.38 |
From above-mentioned result of the test as can be seen, three kinds of conditions all can obtain material preferably, but are 150 ℃ with inlet temperature by contrast, and outlet temperature is 70 ℃, and air velocity is 18ms
-1Condition be best.
Concrete embodiment
(part is represented weight portion, as: kilogram, gram etc.)
Embodiments of the invention 1: 150 parts of 1000 parts of breviscapines of 1000 parts of Radix Ginsengs Radix Ophiopogonis
A, get medical material Radix Ophiopogonis, adding 15 times of volume decoctings boils 4 times, each 2.5 hours, merge extractive liquid,, merge extractive liquid,, filter, filtrate is crossed ZTC-1 type macroporous adsorptive resins with the speed of 0.8ml/g medical material .min, water with 10 times of resin volumes washes with the speed of 1.5ml/g medical material .min earlier, 25% ethanol of 4 times of resin volumes of reuse is used the speed eluting of 70% ethanol of 6 times of resin volumes with 1.0ml/g medical material .min at last with the speed eluting impurity of 1.5ml/g medical material .min, collects stripping liquid, reclaiming and measuring relative density when ethanol is evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;
B, get the ginseng crude drug, add 15 times of volume 80% alcohol reflux 4 times, each 2.5 hours, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water dissolution that adds 5 times of medical material volumes, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.8ml/g medical material .min, use 10 times of resinite hydrops and 6 times of resin volume 15% alcohol flushing impurity successively, 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, dry Radix Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 1% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfers pH value 5.5～7.5, boils, spend the night coarse filtration, fine straining 4 ℃ of cold preservations.Mannitol is added the injection water be mixed with 100mg/m1 solution,, filter, packing, temperature-45 ℃, pre-freeze time 10h with above-mentioned filtrate mixing;-40 ℃ of evacuation keep 8h; Be warming up to-30 ℃ again, keep 8h; Be warming up to-20 ℃, keep 8h; Be warming up to-10 ℃, 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.After testing: the content of saponin component accounts in the preparation 30% of total solid after deduction adjuvant amount and the water quantities; The total solid that saponin component, scutellarin and other the content sum that can survey composition account in the preparation after deduction adjuvant amount and the water quantities is 85%.
Embodiments of the invention 2: 0.001 part of 10 parts of breviscapine of 10 parts of Radix Ginsengs Radix Ophiopogonis
A, get medical material Radix Ophiopogonis, adding 5 times of volume decoctings boiled 1 time 0.5 hour, merge extractive liquid,, merge extractive liquid,, filter, filtrate is crossed ZTC-1 type macroporous adsorptive resins with the speed of 0.3ml/g medical material .min, water with 3 times of resin volumes washes with the speed of 0.5ml/g medical material .min earlier, 5% ethanol of 1 times of resin volume of reuse is with the speed eluting impurity of 0.5ml/g medical material .min, use the speed eluting of 50% ethanol of 2 times of resin volumes at last with 0.5ml/g medical material .min, collect stripping liquid, reclaiming and measuring relative density when ethanol is evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;
B, get the ginseng crude drug, added 5 times of volumes, 50% alcohol reflux 1 time 0.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water dissolution that adds 1 times of medical material volume, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.3ml/g medical material .min, use 1 times of resinite hydrops and 1 times of resin volume 5% alcohol flushing impurity successively, 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, dry Radix Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 0.1% active carbon, boil, keep little 60min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, adjust pH 5.5～7.5 boils, and spends the night 8 ℃ of cold preservations, coarse filtration, fine straining, dividing to install in the ampoule bottle, is 110 ℃ in vapor (steam) temperature, and actual pressure is at 120kN/m
3Pressure sterilizing is 60 minutes under the condition, promptly gets the injection with small volume or the concentrated solution for injection that are directly used in drug administration by injection.After testing: the content of saponin component accounts in the preparation 16% of total solid after deduction adjuvant amount and the water quantities; The total solid that saponin component, scutellarin and other the content sum that can survey composition account in the preparation after deduction adjuvant amount and the water quantities is 25%.
Embodiments of the invention 3: 1.5 parts of 60 parts of breviscapines of 110 parts of Radix Ginsengs Radix Ophiopogonis
A, get medical material Radix Ophiopogonis, add 8 times of volume decoctings and boiled 1 time 0.5 hour, merge extractive liquid,, merge extractive liquid, filters, and measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, dry Radix Ophiopogonis extract;
B, get the ginseng crude drug, added 6 times of volumes, 50% alcohol reflux 1 time 0.5 hour, measuring relative density when merge extractive liquid,, decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Radix Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, add the glucose of ormal weight again, by volume add 0.1% active carbon, boil, keep little 10min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, transfer; PH value 5.5～7.5 boils, and spends the night 1 ℃ of cold preservation, and coarse filtration, fine straining add the injection water, and packing under 105 ℃ of conditions, was sterilized 20 minutes, promptly got the glucose intravenous infusion agent.
Embodiments of the invention 4: 0.05 part of 50 parts of breviscapine of 50 parts of Radix Ginsengs Radix Ophiopogonis
A, get medical material Radix Ophiopogonis, adding 10 times of volume decoctings boils 3 times, each 1 hour, merge extractive liquid,, filter, filtrate is crossed ZTC-1 type macroporous adsorptive resins with the speed of 0.4ml/g medical material .min, water with 6 times of resin volumes washes with the speed of 0.8m1/g medical material .min earlier, 10% ethanol of 3 times of resin volumes of reuse is with the speed eluting impurity of 1ml/g medical material .min, use the speed eluting of 60% ethanol of 4 times of resin volumes at last with 0.8ml/g medical material .min, collect stripping liquid, reclaim the dry Radix Ophiopogonis extract that gets of ethanol;
B, get the ginseng crude drug, add 8 times of volume 70% alcohol reflux 2 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water dissolution that adds 4 times of medical material volumes, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.5ml/g medical material .min, use 7 times of resinite hydrops and 5 times of resin volume 10% alcohol flushing impurity successively, use 60% 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, dry Radix Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, add the sodium chloride of ormal weight again, by volume add 1% 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, spend the night coarse filtration, fine straining 4 ℃ of cold preservations, add the injection water, packing is under 115 ℃ of conditions, sterilized 30 minutes, and promptly got the sodium chloride intravenous infusion agent.
Embodiments of the invention 5: 50 parts of 200 parts of breviscapines of 200 parts of Radix Ginseng Rubra Radix Ophiopogonis
A, add 8 times of volumes, 60% alcohol reflux Radix Ophiopogonis 3 times, each 1 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, filter merging filtrate, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, add the dissolving of 6 times of amount water for injection, filter, filtrate is crossed ZTC-1 type macroporous adsorptive resins with the speed of 0.5ml/g medical material .min, water with 5 times of resin volumes washes with the speed of 0.6ml/g medical material .min earlier, 10% ethanol of 4 times of resin volumes of reuse is used the speed eluting of 60% ethanol of 6 times of resin volumes with 0.8ml/g medical material .min at last with the speed eluting impurity of 0.8ml/g medical material .min, collects stripping liquid, reclaiming and measuring relative density when ethanol is evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;
B, get the Radix Ginseng Rubra medical material, adding 14 times of volume decoctings boils 2 times, each 1 hour, merge extractive liquid, is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.8ml/g medical material .min, with 6 times of resinite hydrops flushings, sample effluent and water lotion in the collection, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, adds ethanol precipitate with ethanol twice, makes that to contain the alcohol amount be 60% for the first time, make for the second time that to contain the alcohol amount be 80%, filter, twice precipitation merged the back add 2 times of water dissolutioies, filter, filtrate concentrate the Radix Ginseng Rubra polysaccharide, 4 times of resin volumes of reuse, 10% alcohol flushing impurity is used 60% alcohol desorption of 5 times of resin volumes then, collects stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Radix Ginseng Rubra extract;
Above-mentioned Radix Ophiopogonis extract, Radix Ginseng Rubra extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 0.4% active carbon, boil, keep little 50min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, adjust pH 5.5～7.5 boils, and spends the night 3 ℃ of cold preservations, coarse filtration, fine straining, divide to install in the enamel tray temperature-45 ℃, pre-freeze time 10h;-40 ℃ of evacuation keep 8h; Be warming up to-30 ℃ again, keep 8h; Be warming up to-20 ℃, keep 8h; Be warming up to-10 ℃, 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 in the cillin bottle.
Contain the multiple compositions of surveying such as saponin component and flavones ingredient in the preparation, calculate according to percentage by weight, wherein the content of saponin component accounts for 1% of the total solid after the deduction adjuvant amount and water quantities in the preparation; The content of scutellarin should be 80%～120% of labelled amount in the preparation.
Embodiments of the invention 6: 2 parts of 150 parts of breviscapines of 160 parts of Radix Codonopsis Radix Ophiopogonis
A, get medical material Radix Ophiopogonis, adding 10 times of volume decoctings boils 3 times, each 1 hour, merge extractive liquid,, merge extractive liquid,, filter, filtrate is crossed ZTC-1 type macroporous adsorptive resins with the speed of 0.5ml/g medical material .min, water with 5 times of resin volumes washes with the speed of 0.8ml/g medical material .min earlier, 15% ethanol of 4 times of resin volumes of reuse is used the speed eluting of 60% ethanol of 5 times of resin volumes with 0.8ml/g medical material .min at last with the speed eluting impurity of 1.2ml/g medical material .min, collects stripping liquid, reclaiming and measuring relative density when ethanol is evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;
B, get codonopsis pilosula, add 10 times of volume 70% alcohol reflux 2 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water dissolution that adds 4 times of medical material volumes, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.5ml/g medical material .min, use 7 times of resinite hydrops and 5 times of resin volume 10% alcohol flushing impurity successively, use 60% 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, dry Radix Codonopsis extract;
Above-mentioned Radix Ophiopogonis extract, Radix Codonopsis extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 0.8% active carbon, boil, keep little 40min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, adjust pH 5.5～7.5 boils, and spends the night 6 ℃ of cold preservations, coarse filtration, fine straining, in inlet temperature is 150 ℃, and leaving air temp is 70 ℃, and air velocity is 18ms
-1Condition under spray drying get powder, packing promptly gets the spray drying sterilized powder.
Contain the multiple compositions of surveying such as saponin component and flavones ingredient in the preparation, calculate according to percentage by weight, wherein the content of saponin component accounts for 2% of the total solid after the deduction adjuvant amount and water quantities in the preparation; The content of wild Radix Scutellariae former times should be 120% of labelled amount in the preparation.Calculate according to percentage by weight, saponin component in the preparation and flavones ingredient and and other all can survey the composition sum and account for 50% of the total solid after the deduction adjuvant amount and water quantities in the preparation.
Embodiments of the invention 7: 200 parts of 200 parts of breviscapines of 200 parts of Radix Ginseng Rubra Radix Ophiopogonis
A, get medical material Radix Ophiopogonis, adding 5 times of volume decoctings boiled 1 time 0.5 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, adds ethanol precipitate with ethanol twice, makes that to contain the alcohol amount be 50% for the first time, make for the second time that to contain the alcohol amount be 80%, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Radix Ophiopogonis extract;
B, get the Radix Ginseng Rubra medical material, added 5 times of volumes, 50% alcohol reflux 1 time 0.5 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, dry Radix Ginseng Rubra extract;
Above-mentioned Radix Ophiopogonis extract, Radix Ginseng Rubra extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 0.4% active carbon, boil, keep little 50min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, adjust pH 5.5～7.5 boils, and spends the night 3 ℃ of cold preservations, coarse filtration, fine straining, divide to install in the enamel tray temperature-45 ℃, pre-freeze time 10h;-40 ℃ of evacuation keep 8h; Be warming up to-30 ℃ again, keep 8h; Be warming up to-20 ℃, keep 8h; Be warming up to-10 ℃, 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 in the cillin bottle.The total solid that the content of saponin component accounts in the preparation after deduction adjuvant amount and the water quantities is 1.8%.
Claims (12)
1, a kind of ejection preparation with human body immunity improving power, treatment cardiovascular and cerebrovascular disease, it is characterized in that: calculate according to components by weight percent, it is refiningly added suitable adjuvant and is made through extracting by 0.001～150 part of 10～1000 parts of 10～1000 parts of Radix Ophiopogonis, Radix Ginseng and breviscapine, or adds the injection that suitable adjuvant is made by corresponding weight portion medical material through extracting the extract and the corresponding weight portion breviscapine that obtain after refining.
2, according to the described traditional medicine Injectio of claim 1 with human body immunity improving power, treatment cardiovascular and cerebrovascular disease, it is characterized in that: calculate according to components by weight percent, it is refiningly added suitable adjuvant and is made through extracting by 0.01～100 part of 10～500 parts of 10～500 parts of Radix Ophiopogonis, Radix Ginseng and breviscapine, or adds the injection that suitable adjuvant is made by corresponding weight portion medical material through extracting the extract and the corresponding weight portion breviscapine that obtain after refining.
3, according to claim 1 or 2 described traditional medicine Injectios with human body immunity improving power, treatment cardiovascular and cerebrovascular disease, it is characterized in that: calculate according to components by weight percent, it is refiningly added suitable adjuvant and is made through extracting by 0.05～50 part of 50～200 parts of 50～200 parts of Radix Ophiopogonis, Radix Ginseng and breviscapine, or is added suitable adjuvant and be made through extracting the extract that obtains after refining and corresponding weight portion breviscapine by corresponding weight portion medical material.
4, according to any described traditional medicine Injectio with human body immunity improving power, treatment cardiovascular and cerebrovascular disease of claim 1-3, it is characterized in that: injection comprises: be directly used in drug administration by injection injection, need to be used for the concentrated solution for injection of intravenous drip after the dilution, directly for the venous transfusion of intravenous drip and injectable sterile powder and the aseptic block that makes with freeze-drying or spray drying method.
5, according to the described traditional medicine Injectio of claim 4 with human body immunity improving power, treatment cardiovascular and cerebrovascular disease, it is characterized in that: contain the multiple compositions of surveying such as saponin component and flavones ingredient in the preparation, calculate according to percentage by weight, wherein the content of saponin component is not less than 1% of the total solid after the deduction adjuvant amount and water quantities in the preparation; The content of scutellarin should be 80%～120% of labelled amount in the preparation.
6, according to the described traditional medicine Injectio of claim 5 with human body immunity improving power, treatment cardiovascular and cerebrovascular disease, it is characterized in that: calculate according to percentage by weight, saponin component in the preparation and flavones ingredient and and other all can survey the composition sum and be not less than 25% of the total solid after the deduction adjuvant amount and water quantities in the preparation.
7, the preparation method with traditional medicine Injectio of human body immunity improving power, treatment cardiovascular and cerebrovascular disease as claimed in claim 4, it is characterized in that: Radix Ophiopogonis, Radix Ginseng two flavor medical materials add water or ethanol extraction respectively, extracting solution carry out suitably concentrating crude extract or further adopt one or more methods in alcohol deposition method, water precipitating method, acid-base precipitation method, flocculent precipitation, column chromatography, the solvent extraction to mix to use refining extract, material crude extract or refining extract and the breviscapine adding different auxiliary material of getting it filled is made various ejection preparations.
8, the preparation method with traditional medicine Injectio of human body immunity improving power, treatment cardiovascular and cerebrovascular disease as claimed in claim 7 is characterized in that:
A, get medical material Radix Ophiopogonis, adding 5～15 times of volume decoctings boils 1～4 time, each 0.5～2.5 hour, merge extractive liquid,, merge extractive liquid,, filter, filtrate is crossed ZTC-1 type macroporous adsorptive resins with the speed of 0.3-0.8ml/g medical material .min, water with 3-10 times of resin volume washes with the speed of 0.5-1.5ml/g medical material .min earlier, the 5-25% ethanol of reuse 1-4 times of resin volume is with the speed eluting impurity of 0.5-1.5ml/g medical material .min, with the 50-70% ethanol of the 2-6 times of resin volume speed eluting with 0.5-1.0ml/g medical material .min, collects stripping liquid at last, reclaiming and measuring relative density when ethanol is concentrated into 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;
B, get the ginseng crude drug, add 5～15 times of volume 50～80% alcohol reflux 1～4 time, each 0.5～2.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water dissolution that adds 1-5 times of medical material volume, filter, filtrate is crossed ZTC-1 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, with the 30-70% alcohol desorption of 1-7 times of resin volume, collect stripping liquid then successively, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Radix Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add adjuvant and make different ejection preparations.
9, according to the described preparation method of claim 8, it is characterized in that with traditional medicine Injectio of human body immunity improving power, treatment cardiovascular and cerebrovascular disease:
A, get medical material Radix Ophiopogonis, adding 10 times of volume decoctings boils 3 times, each 1.5 hours, merge extractive liquid,, filter, filtrate is crossed ZTC-1 type macroporous adsorptive resins with the speed of 0.5ml/g medical material .min, water with 6 times of resin volumes washes with the speed of 1ml/g medical material .min earlier, 20% ethanol of 3 times of resin volumes of reuse is with the speed eluting impurity of 1ml/g medical material .min, use the speed eluting of 60% ethanol of 4 times of resin volumes at last with 0.8ml/g medical material .min, collect stripping liquid, reclaim the dry Radix Ophiopogonis extract that gets of ethanol;
B, get the ginseng crude drug, 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 dissolution that adds 4 times of medical material volumes, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.5ml/g medical material .min, use 7 times of resinite hydrops and 5 times of resin volume 10% alcohol flushing impurity successively, use 60% 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, dry Radix Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add adjuvant and make different ejection preparations.
10, according to the described preparation method with traditional medicine Injectio of human body immunity improving power, treatment cardiovascular and cerebrovascular disease of claim 9, it is characterized in that: the aseptic block of lyophilizing is preparation like this:
A, get medical material Radix Ophiopogonis, adding 10 times of volume decoctings boils 3 times, each 1.5 hours, merge extractive liquid,, filter, filtrate is crossed ZTC-1 type macroporous adsorptive resins with the speed of 0.5ml/g medical material .min, water with 6 times of resin volumes washes with the speed of 1ml/g medical material .min earlier, 20% ethanol of 3 times of resin volumes of reuse is with the speed eluting impurity of 1ml/g medical material .min, use the speed eluting of 60% ethanol of 4 times of resin volumes at last with 0.8ml/g medical material .min, collect stripping liquid, reclaim the dry Radix Ophiopogonis extract that gets of ethanol;
B, get the ginseng crude drug, 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 dissolution that adds 4 times of medical material volumes, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.5ml/g medical material .min, use 7 times of resinite hydrops and 5 times of resin volume 10% alcohol flushing impurity successively, use 60% 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, dry Radix Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, 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, and adjust pH 5.5～7.5 boils, spend the night coarse filtration, fine straining 4 ℃ of cold preservations.With suitable adjuvant aqueous solution, with above-mentioned filtrate mixing, filter, packing, temperature-45 ℃, pre-freeze time 10h, the beginning evacuation, and in 12～72 hours differential gradient increased temperature to 10 ℃ progressively, keep 2h, be warming up to 20 ℃, keep 2h, promptly.
11, according to any described preparation method with traditional medicine Injectio of human body immunity improving power, treatment cardiovascular and cerebrovascular disease among the claim 7-10, it is characterized in that: the adjuvant that is adopted in the preparation process comprises one or more in mannitol, galactose, glycine, glucose, sodium chloride, dextran, glycerol, ethanol, propylene glycol, Polyethylene Glycol, sorbitol, tween, the poloxamer.
12, according to any described traditional medicine Injectio with human body immunity improving power, treatment cardiovascular and cerebrovascular disease of claim 1-10, it is characterized in that: Radix Ginseng can also be the Radix Ginseng Rubra or the Radix Codonopsis of equivalent.
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| CN104435658A (en) * | 2014-07-03 | 2015-03-25 | 罗国安 | Medicine for preventing and treating ischemic cerebral apoplexy and preparation method thereof |
| CN104435658B (en) * | 2014-07-03 | 2018-01-05 | 罗国安 | A kind of medicine for ischemia apoplexy prevention and treatment and preparation method thereof |
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