CN1911365A - Injection contg. traditional Chinese medicine, and its prepn. method - Google Patents
Injection contg. traditional Chinese medicine, and its prepn. method Download PDFInfo
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Abstract
A Chinese medicine in the form of injection for improving immunity and treating cardiovascular and cerebrovascular diseases, such as coronary heart disease, angina pectoris, arrhythmia, cerebral infarction and senile dementia, is prepared from ophiopogon root, ginseng or red ginseng or pilose asiabell root, schisandra fruit and breviscapine. Its preparing process is also disclosed, which features the extraction of polyose from ophiopogon root.
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.So far existing a large amount of Chinese medicine and western medicine emerge.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, contrast after deliberation, we develop a kind of traditional medicine Injectio for the treatment of cardio-cerebrovascular diseases, are made up of Radix Ophiopogonis, Radix Ginseng, Herba Erigerontis and Fructus Schisandrae Chinensis.Many inventors have also done number of research projects, as: number of patent application is " 02153750.X ", name is called the application of " a kind of Herba Erigerontis combination drug ", though the product of this part application has good clinical application effect, but the harm that cardiovascular and cerebrovascular disease acute attack at present brings to human health is bigger, oral formulations can't discharge medicine rapidly, lie in a comatose condition owing to the patient simultaneously, dysphagia, medicine disintegrate in gastrointestinal tract in addition, absorption are individual processes slowly, therefore can't reach better therapeutic.Because the continuing to optimize and develop of the process conditions of preparation breviscapine, a large amount of in addition clinical test results makes this raw materials quality controllability improve greatly.The inventor of present technique is by a large amount of experimental studies, invented with breviscapine and Chinese medicine Radix Ginseng, Radix Ophiopogonis, the crude extract of Fructus Schisandrae Chinensis or the ejection preparation of refining extract combination, modern extraction technique is combined with the Chinese medicine compound recipe, under safety, quality controllable prerequisite, make the effectiveness of the preparation after the combination improve greatly.
Summary of the invention
The object of the present invention is to provide a kind of traditional medicine Injectio and preparation method thereof with human body immunity improving power, treatment cardio-cerebrovascular diseases; The present invention is directed to prior art, at different medical materials, adopt the mode of separately extracting, can effectively extract active component, simultaneously can be under the situation that guarantees active component, remove impurity targetedly, sample is made with extra care, add that the treatment of cardiovascular and cerebrovascular disease acute attack stage is extremely important, preparation of the present invention is mainly injection, make medicine performance curative effect fast, the availability height is fit to cardiovascular and cerebrovascular vessel.There is the present invention to adopt nontoxic, non-corrosive solvent to extract and make with extra care again, makes that organic solvent-free is residual in the sample, improve the safety and the stability of preparation greatly, be convenient to production, packing, storage and the use of preparation.
Technical scheme of the present invention is achieved in that according to parts by weight and calculates, it by 50～1000 parts of 1～300 part of 0.1～30 part of breviscapine, 1～300 part of Radix Ophiopogonis, Fructus Schisandrae Chinensis and Radix Ginsengs through extracting refining and adding the injection that suitable adjuvant is made, or add the injection that suitable adjuvant is made through extracting the extract that obtains after refining and the breviscapine of corresponding weight portion by corresponding weight portion medical material, contain the various saccharides composition in the preparation, and do not extract the volatile oil composition of Fructus Schisandrae Chinensis separately.Described have human body immunity improving power, the traditional medicine Injectio of treatment cardio-cerebrovascular diseases, calculate according to components by weight percent, it is by 0.3～15 part of breviscapine, 10～100 parts of Radix Ophiopogonis, 200～500 parts of 10～100 parts of Fructus Schisandrae Chinensis and Radix Ginsengs are through extracting refining and adding the injection that suitable adjuvant is made, or add the injection that suitable adjuvant is made through extracting the extract that obtains after refining and the breviscapine of corresponding weight portion by corresponding weight portion medical material, contain various saccharides compositions such as Radix Ophiopogonis polysaccharide and monosaccharide in the preparation, and do not extract the volatile oil composition of Fructus Schisandrae Chinensis separately.Say exactly, it by 0.5～8 part of 30～80 parts of 250～350 parts of Radix Ginsengs, 30～80 parts of Radix Ophiopogonis, Fructus Schisandrae Chinensis and breviscapine through extracting refining and adding the injection that suitable adjuvant is made, or add the injection that suitable adjuvant is made through extracting the extract that obtains after refining by corresponding weight portion medical material, contain various saccharides compositions such as Radix Ophiopogonis polysaccharide and monosaccharide in the preparation, the total solid that the content of carbohydrate content accounts in the preparation after deduction adjuvant amount and the water quantities is not less than 4%, and does not extract the volatile oil composition of Fructus Schisandrae Chinensis separately.
Preparation of the present invention is an injection, comprising: be directly used in drug administration by injection injection, need to be used for after the dilution concentrated solution for injection of intravenous drip, directly for the glucose intravenous infusion of intravenous drip and sodium chloride intravenous infusion and the injectable sterile powder and the aseptic block that make with freeze-drying or spray drying method.
Contain saponin component, polysaccharide composition and flavones ingredient in the traditional medicine Injectio with human body immunity improving power, treatment cardio-cerebrovascular diseases of the present invention, wherein the content of saponin component is not less than in the preparation 1% of total solid after deduction adjuvant amount and the water quantities; The content of scutellarin should be 80%～120% of labelled amount in the preparation, and the content of polysaccharide composition is not less than 3% of the total solid after the deduction adjuvant amount and water quantities in the preparation.All the content sums that can survey composition of saponin component in the preparation, polysaccharide composition and flavones ingredient and other account for that the total solid after the deduction adjuvant amount and water quantities is not less than 25% in the preparation.
Preparation method with traditional medicine Injectio of human body immunity improving power, treatment cardio-cerebrovascular diseases of the present invention: Radix Ophiopogonis, Radix Ginseng, Fructus Schisandrae Chinensis three 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, acid-base precipitation method, 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 cardio-cerebrovascular diseases 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,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 50～70%, make that to contain the alcohol amount be 80～90% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, twice precipitation merged the back add 1～4 times of water dissolution, filter, the concentrated solution of filtrate and front merges, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;
B, schisandra chinensis medicinal material, add 5-15 times of volume water boiling and extraction 1-4 time, each 0.5-2.5 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time to contain the alcohol amount and be 50-70%, make for the second time to contain the alcohol amount and be 80-90%, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Fructus Schisandrae Chinensis extrat;
C, 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 when being concentrated into 60 ℃ is 1.05～1.15, dry Radix Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat, 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,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 60%, make that to contain the alcohol amount be 85% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, twice precipitation merged the back add 2 times of water dissolutioies, filter, the concentrated solution of filtrate and front merges, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;
B, schisandra chinensis medicinal material, add 10 times of volume water boiling and extraction 3 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 60%, make that to contain the alcohol amount be 85% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Fructus Schisandrae Chinensis extrat;
C, get the ginseng crude drug, add 10 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, dry Radix Ginseng extract.
Above-mentioned Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat, 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 freeze-dried powder.
The adjuvant that is adopted in the preparation of the present invention 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.
Injection with small volume of the present invention or concentrated solution for injection prepare like this:
A, get medical material Radix Ophiopogonis, adding 10 times of volume decoctings boils 3 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 60%, make that to contain the alcohol amount be 85% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, twice precipitation merged the back add 2 times of water dissolutioies, filter, the concentrated solution of filtrate and front merges, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;
B, schisandra chinensis medicinal material, add 10 times of volume water boiling and extraction 3 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 60%, make that to contain the alcohol amount be 85% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Fructus Schisandrae Chinensis extrat;
C, get the ginseng crude drug, add 10 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, dry Radix Ginseng extract.
Above-mentioned Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat, 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.
Glucose intravenous infusion agent 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,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 60%, make that to contain the alcohol amount be 85% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, twice precipitation merged the back add 2 times of water dissolutioies, filter, the concentrated solution of filtrate and front merges, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;
B, get schisandra chinensis medicinal material, add 10 times of volume water boiling and extraction 3 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 60%, make that to contain the alcohol amount be 85% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Fructus Schisandrae Chinensis extrat;
C, get the ginseng crude drug, add 10 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, dry Radix Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, the glucose that adds ormal weight again, 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, add the injection water, packing is under 105～125 ℃ of conditions, sterilized 20～60 minutes, and promptly got the glucose intravenous infusion agent.
Sodium chloride intravenous infusion agent 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,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 60%, make that to contain the alcohol amount be 85% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, twice precipitation merged the back add 2 times of water dissolutioies, filter, the concentrated solution of filtrate and front merges, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;
B, schisandra chinensis medicinal material, add 10 times of volume water boiling and extraction 3 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 60%, make that to contain the alcohol amount be 85% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Fructus Schisandrae Chinensis extrat;
C, get the ginseng crude drug, add 10 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, dry Radix Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, the sodium chloride that adds ormal weight again, 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, add the injection water, packing is under 105～125 ℃ of conditions, sterilized 20～60 minutes, and promptly got the sodium chloride intravenous infusion agent.
The preparation like this of freeze dry sterile powder of the present invention end:
A, get medical material Radix Ophiopogonis, adding 10 times of volume decoctings boils 3 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 60%, make that to contain the alcohol amount be 85% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, twice precipitation merged the back add 2 times of water dissolutioies, filter, the concentrated solution of filtrate and front merges, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;
B, schisandra chinensis medicinal material, add 10 times of volume water boiling and extraction 3 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 60%, make that to contain the alcohol amount be 85% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Fructus Schisandrae Chinensis extrat;
C, get the ginseng crude drug, add 10 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, dry Radix Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat, 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.
Spray drying sterilized powder 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,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 60%, make that to contain the alcohol amount be 85% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, twice precipitation merged the back add 2 times of water dissolutioies, filter, the concentrated solution of filtrate and front merges, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;
B, schisandra chinensis medicinal material, add 10 times of volume water boiling and extraction 3 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 60%, make that to contain the alcohol amount be 85% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Fructus Schisandrae Chinensis extrat;
C, get the ginseng crude drug, add 10 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, dry Radix Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat, 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.
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 SHENGMAI ZHUSHEYE group | The breviscapus pulse-engendering Capsules group |
| Improve blood stasis model rat blood rheology test platelet aggregation-against and test anti-mouse tail thrombotest rabbit fibrin solubility test small white mouse anti-fatigue test | Effect is remarkable, the effect reinforced effects is remarkable, the effect reinforced effects is remarkable, the effect reinforced effects is obvious, and the effect reinforced effects is remarkable | The general DeGrain of the general effect of effect positive effect positive effect | The general DeGrain of the effect general effect of general effect positive effect |
From above-mentioned test as can be seen, injection therapeutic effect of the present invention is significantly better than oral formulations and SHENGMAI ZHUSHEYE.
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 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 1 1.5 | 8.84 8.60 8.19 | 56.76 54.74 50.82 | Reddish brown 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 30 60 | 8.93 8.56 8.35 | 53.38 52.26 49.81 | Reddish brown red 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 boils pH | 4.5 4.2 | 5.0 4.5 | 5.5 5.1 | 6.0 5.6 | 6.5 6.1 | 7.0 6.5 | 7.5 7.3 | 8.0 7.7 | 8.5 8.1 |
| 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 5.5 below, 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, be 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 2 3 4 5 | 5.5 6.0 6.5 7.0 7.5 | 2.36 2.36 2.36 2.36 2.36 | 5.1 5.6 6.1 6.5 7.3 | 2.12 2.09 2.10 2.14 2.04 |
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 galactose mannitol glycine dextran mannitol, the propylene glycol glycine, the Polyethylene Glycol dextran, sorbitol, the blank medicinal liquid of tween | 2∶1 2∶1 2∶1 2∶1 2∶1 2∶1 2∶1 2∶1 3ml | Well generally carefully generally well carefully | The moulding of partly subsiding is moulding moulded; Frangible moulding moulded moulding, frangible moulding 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 2 3 | 50 100 150 | 2∶1 2∶1 2∶1 | Yellowish-brown Huang is yellowish | Part is subsided intact | Well carefully | Up to specification 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) temperature (℃) | Condition I | Condition II | Condition III | Cold-trap |
| -45 (pre-freeze)-40 (pre-freeze)-40 (vacuumizing)-35 (vacuumizing)-30 (vacuumizing)-25 (vacuumizing)-20 (vacuumizing)-15 (vacuumizing)-10 (vacuumizing) 0 (vacuumizing) 10 (vacuumizing) 20 (vacuumizing) | 8 - 8 - 8 - 8 - 5 5 2 2 | - 8 - 8 - 8 - 6 - 6 2 2 | 8 - 10 - 10 - 10 - 5 5 3 3 | Keep-70 ℃ |
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 (%) |
| 140 150 160 | 60 70 80 | 16 18 20 | 4.27 3.83 4.10 |
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: 1000 parts of 300 parts of Radix Ginsengs of breviscapine 300 parts of Fructus Schisandrae Chinensis, 30 parts of Radix Ophiopogonis
A, get medical material Radix Ophiopogonis, adding 15 times of volume decoctings boils 4 times, each 2.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 70%, make that to contain the alcohol amount be 90% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, twice precipitation merged the back add 1 times of water dissolution, filter, the concentrated solution of filtrate and front merges, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;
B, get schisandra chinensis medicinal material, add 15 times of volume water boiling and extraction 4 times, each 2.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 70%, make that to contain the alcohol amount be 90% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Fructus Schisandrae Chinensis extrat;
C, 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 when being concentrated into 60 ℃ is 1.05～1.15, dry Radix Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat, 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/ml 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 polysaccharide component content accounts in the preparation 67% of total solid after deduction adjuvant amount and the water quantities; The content of saponin component accounts in the preparation 12% of total solid after deduction adjuvant amount and the water quantities; Polysaccharide composition, saponin component and scutellarin and other can be surveyed the component content sum and account in the preparation 90% of total solid after deduction adjuvant amount and the water quantities.
Embodiments of the invention 2: 50 parts of 1 part of Radix Ginsengs of breviscapine 1 part of Fructus Schisandrae Chinensis, 0.1 part of 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, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 50%, 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, will twice precipitation merges the back and adds 1 times of water dissolution, filter, the concentrated solution of filtrate and front merges, and measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;
B, get schisandra chinensis medicinal material, added 5 times of volume water boiling and extraction 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 Fructus Schisandrae Chinensis extrat;
C, get the ginseng crude drug, 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 extract;
Above-mentioned Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat, 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, transfer pH value 5.5～7.5, boil, spend 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: Radix Ophiopogonis polysaccharide content accounts in the preparation 20% of total solid after deduction adjuvant amount and the water quantities; The content of saponin component accounts in the preparation 3.2% of total solid after deduction adjuvant amount and the water quantities; The content of flavones ingredient accounts in the preparation 1.8% of total solid after deduction adjuvant amount and the water quantities; The total solid that three's sum accounts in the preparation after deduction adjuvant amount and the water quantities is 25%.
Embodiments of the invention 3: 300 parts of 60 parts of Radix Ginsengs of breviscapine 60 parts of Fructus Schisandrae Chinensis, 2 parts of Radix Ophiopogonis
A, get medical material Radix Ophiopogonis, adding 8 times of volume decoctings boiled 1 time 2.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 60%, 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, will twice precipitation merges the back and adds 3 times of water dissolutioies, filter, the concentrated solution of filtrate and front merges, and measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;
B, get schisandra chinensis medicinal material, added 5 times of volume water boiling and extraction 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 85%, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Fructus Schisandrae Chinensis extrat;
C, get the ginseng crude drug, 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 extract;
Above-mentioned Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat, 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, boil, spend the night coarse filtration, fine straining 1 ℃ of cold preservation, add the injection water, packing is under 105 ℃ of conditions, sterilized 20 minutes, and promptly got the glucose intravenous infusion agent.After testing: the content of saponin component accounts in the preparation 1.1% of total solid after deduction adjuvant amount and the water quantities.
Embodiments of the invention 4: 300 parts of 60 parts of Radix Ginsengs of breviscapine 60 parts of Fructus Schisandrae Chinensis, 1 part of Radix Ophiopogonis
A, get medical material Radix Ophiopogonis, add 5 times of volume decoctings and boiled 1 time 0.5 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, dry Radix Ophiopogonis extract;
B, get schisandra chinensis medicinal material, add 8 times of volume water boiling and extraction 3 times, each 1 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 60%, make that to contain the alcohol amount be 85% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Fructus Schisandrae Chinensis extrat;
C, get the ginseng crude drug, 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 extract;
Above-mentioned Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat, Herba Erigerontis extract and Radix Ginseng extract 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: 30 parts of 6 parts of Radix Ginseng Rubra of breviscapine 6 parts of Fructus Schisandrae Chinensis, 0.6 part of Radix Ophiopogonis
A, add 12 times of volumes, 75% 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, add the dissolving of 3 times of amount water for injection, filter merging filtrate, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, and medicinal residues add 5 times of volume decoctings and boil 2 times, merge extractive liquid,, concentrating and measuring relative density when adding to 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 90%, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, will twice precipitation merges the back and adds 2 times of water dissolutioies, filter, the concentrated solution of filtrate and front merges, and measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;
B, get schisandra chinensis medicinal material, add 10 times of volume water boiling and extraction 2 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 60%, make that to contain the alcohol amount be 85% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Fructus Schisandrae Chinensis extrat;
C, get the Radix Ginseng Rubra medical material, adding 10 times of volume decoctings boils 2 times, each 1 hour, measuring relative density when merge extractive liquid, is concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 50%, make for the second time that to contain the alcohol amount be 85%, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, will twice precipitation merges the back and adds 3 times of water dissolutioies, filter, the concentrated solution of filtrate and front merges, and measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ginseng Rubra extract that gets;
Above-mentioned Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat, 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, 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.
Embodiments of the invention 6: 30 parts of 6 parts of Radix Codonopsis of breviscapine 6 parts of Fructus Schisandrae Chinensis, 0.5 part of Radix Ophiopogonis
A, get medical material Radix Ophiopogonis, adding 10 times of volume decoctings boils 3 times, each 1 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 60%, make that to contain the alcohol amount be 80% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, twice precipitation merged the back add 3 times of water dissolutioies, filter, the concentrated solution of filtrate and front merges, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;
B, get schisandra chinensis medicinal material, add 10 times of volume water boiling and extraction 2 times, per 1 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 70%, make that to contain the alcohol amount be 80% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Fructus Schisandrae Chinensis extrat;
C, get codonopsis pilosula, added 6 times of volumes, 50% alcohol reflux 1 time 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, dry Radix Codonopsis extract;
Above-mentioned Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat, 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, transfer pH value 5.5～7.5, boil, spend 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.
Embodiments of the invention 7: 50 parts of 1 part of Radix Ginsengs of breviscapine 1 part of Fructus Schisandrae Chinensis, 1 part of Radix Ophiopogonis
A, get medical material Radix Ophiopogonis, adding 7 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 60% 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 schisandra chinensis medicinal material, add 8 times of volume water boiling and extraction 3 times, each 1 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 50%, make that to contain the alcohol amount be 85% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Fructus Schisandrae Chinensis extrat;
C, get the ginseng crude drug, added 6 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 extract;
Above-mentioned Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat, 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, transfer pH value 5.5～7.5, boil, spend 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: Radix Ophiopogonis polysaccharide content accounts in the preparation 3.1% of total solid after deduction adjuvant amount and the water quantities.
Embodiments of the invention 8: 30 parts of 6 parts of Radix Ginsengs of breviscapine 6 parts of Fructus Schisandrae Chinensis, 0.2 part of Radix Ophiopogonis
A, get medical material Radix Ophiopogonis, adding 12 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 0.4ml/g medical material .min, water with 6 times of resin volumes washes with the speed of 0.7ml/g medical material .min earlier, and 15% ethanol of 4 times of resin volumes of reuse is used the speed eluting of 70% ethanol of 4 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, collect stripping liquid, reclaim ethanol, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;
B, get schisandra chinensis medicinal material, add 10 times of volume water boiling and extraction 2 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 60%, make that to contain the alcohol amount be 85% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Fructus Schisandrae Chinensis extrat;
C, get the ginseng crude drug, add 10 times of volume 70% alcohol reflux 2 times, each 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 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, Fructus Schisandrae Chinensis extrat, 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, 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.After testing: carbohydrate content content accounts in the preparation 4.2% of total solid after deduction adjuvant amount and the water quantities.
Claims (12)
1, a kind of traditional medicine Injectio with human body immunity improving power, treatment cardiovascular and cerebrovascular disease, it is characterized in that: calculate according to components by weight percent, it by 50～1000 parts of 1～300 part of 0.1～30 part of breviscapine, 1～300 part of Radix Ophiopogonis, Fructus Schisandrae Chinensis and Radix Ginsengs through extracting refining and adding the injection that suitable adjuvant is made, or add the injection that suitable adjuvant is made through extracting the extract that obtains after refining and the breviscapine of corresponding weight portion by corresponding weight portion medical material, contain the various saccharides composition in the preparation, and do not extract the volatile oil composition of Fructus Schisandrae Chinensis separately.
2, has human body immunity improving power according to claim 1 is described, the traditional medicine Injectio of treatment cardiovascular and cerebrovascular disease, it is characterized in that: calculate according to components by weight percent, it is by 0.3～15 part of breviscapine, 10～100 parts of Radix Ophiopogonis, 200～500 parts of 10～100 parts of Fructus Schisandrae Chinensis and Radix Ginsengs are through extracting refining and adding the injection that suitable adjuvant is made, or add the injection that suitable adjuvant is made through extracting the extract that obtains after refining and the breviscapine of corresponding weight portion by corresponding weight portion medical material, contain various saccharides compositions such as Radix Ophiopogonis polysaccharide and monosaccharide in the preparation, and do not extract the volatile oil composition of Fructus Schisandrae Chinensis separately.
3, describedly has human body immunity improving power according to claim 1 or 2, the traditional medicine Injectio of treatment cardiovascular and cerebrovascular disease, it is characterized in that: calculate according to components by weight percent, it is by 250～350 parts of Radix Ginsengs, 30～80 parts of Radix Ophiopogonis, 0.5～8 part of 30～80 parts of Fructus Schisandrae Chinensis and breviscapine are through extracting refining and adding the injection that suitable adjuvant is made, or add the injection that suitable adjuvant is made through extracting the extract that obtains after refining by corresponding weight portion medical material, contain various saccharides compositions such as Radix Ophiopogonis polysaccharide and monosaccharide in the preparation, the total solid that the content of carbohydrate content accounts in the preparation after deduction adjuvant amount and the water quantities is not less than 4%, and does not extract the volatile oil composition of Fructus Schisandrae Chinensis separately.
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 after the dilution concentrated solution for injection of intravenous drip, directly for the glucose intravenous infusion of intravenous drip and sodium chloride intravenous infusion and the injectable sterile powder and the aseptic block that make 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 saponin component, polysaccharide composition and flavones ingredient in the preparation, wherein the content of saponin component is not less than in the preparation 1% of total solid after deduction adjuvant amount and the water quantities; The content of scutellarin should be 80%～120% of labelled amount in the preparation, and the content of polysaccharide composition is not less than 3% of the total solid after the deduction adjuvant amount and water quantities in the preparation.
6, according to the described traditional medicine Injectio with human body immunity improving power, treatment cardiovascular and cerebrovascular disease of claim 5, it is characterized in that: all the content sums that can survey composition of the saponin component in the preparation, polysaccharide composition and flavones ingredient and other account for that the total solid after the deduction adjuvant amount and water quantities is not less than 25% 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, Fructus Schisandrae Chinensis three 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, acid-base precipitation method, 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,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add ethanol precipitate with ethanol twice, make that to contain the alcohol amount be 50～70% for the first time, make that to contain the alcohol amount be 80～90% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, will twice precipitation merges the back and adds 1～4 times of water dissolution, filters, the concentrated solution of filtrate and front merges, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, dry Radix Ophiopogonis extract, and this technology has been extracted the polysaccharide composition in medical material Radix Ophiopogonis;
B, get schisandra chinensis medicinal material, add 5～15 times of volume water boiling and extraction 1～4 time, each 0.5～2.5 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 50～70%, make for the second time that to contain the alcohol amount be 80～90%, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Fructus Schisandrae Chinensis extrat, and this technology is not extracted the volatile oil composition in the schisandra chinensis medicinal material separately;
C, 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 when being concentrated into 60 ℃ is 1.05～1.15, dry Radix Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat, 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,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 60%, make that to contain the alcohol amount be 85% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, twice precipitation merged the back add 2 times of water dissolutioies, filter, the concentrated solution of filtrate and front merges, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;
B, get schisandra chinensis medicinal material, add 10 times of volume water boiling and extraction 3 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 60%, make that to contain the alcohol amount be 85% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Fructus Schisandrae Chinensis extrat;
C, get the ginseng crude drug, add 10 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, dry Radix Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat, 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: lyophilized injectable powder 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,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 60%, make that to contain the alcohol amount be 85% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, twice precipitation merged the back add 2 times of water dissolutioies, filter, the concentrated solution of filtrate and front merges, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;
B, get schisandra chinensis medicinal material, add 10 times of volume water boiling and extraction 3 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 60%, make that to contain the alcohol amount be 85% for the second time, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Fructus Schisandrae Chinensis extrat;
C, get the ginseng crude drug, add 10 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, dry Radix Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, Fructus Schisandrae Chinensis extrat, 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 in the claim 7～10, it is characterized in that: the adjuvant that is adopted in the preparation 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 in claim 1～3 and 7～10, it is characterized in that: Radix Ginseng can also be the Radix Ginseng Rubra or the Radix Codonopsis of equivalent.
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| Publication number | Priority date | Publication date | Assignee | Title |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN102526494A (en) * | 2012-03-23 | 2012-07-04 | 徐玉文 | Ointment for treating burning |
| CN102526494B (en) * | 2012-03-23 | 2013-06-12 | 徐玉文 | Ointment for treating burning |
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