CN1919303A - Traditional medicine Injectio and its preparing method - Google Patents
Traditional medicine Injectio and its preparing method Download PDFInfo
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- CN1919303A CN1919303A CN 200510092850 CN200510092850A CN1919303A CN 1919303 A CN1919303 A CN 1919303A CN 200510092850 CN200510092850 CN 200510092850 CN 200510092850 A CN200510092850 A CN 200510092850A CN 1919303 A CN1919303 A CN 1919303A
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Abstract
The invention relates to a Chinese medicinal injection preparation for improving human body immunity and treating cardiovascular and cerebrovascular diseases and its preparing process, wherein the preparation is prepared from lilyturf root, ginseng, red ginseng, codonopsis pilosula and breviscapine. The preparation according to the invention has the function of improving human body immunity, increasing blood flow of coronary artery and brain blood vessel, improving blood supply of myocardial tissue and brain, treating cardiovascular and cerebrovascular diseases such as coronary disease, angina pectoris, arrhythmia, cerebral thrombus and senile dementia.
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.
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 the effect and the breviscapine of YIN nourishing and the production of body fluid promoting were combined into a kind of while and can effectively treat the preparation of cardiovascular and cerebrovascular disease Radix Ophiopogonis.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 weight ratio, 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, 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 of the ejection preparation of 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, dry Radix Ophiopogonis extract;
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 when being concentrated into 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,, 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 Radix Ophiopogonis extract;
B, 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, 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,, 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 Radix Ophiopogonis extract;
B, 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, 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, and adjust pH 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 aseptic block.
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.
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, dry Radix Ophiopogonis extract;
B, 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, 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 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, dry Radix Ophiopogonis extract;
B, 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, 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, adjust pH 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 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, dry Radix Ophiopogonis extract;
B, 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, 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, adjust pH 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 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, dry Radix Ophiopogonis extract;
B, 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, 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, and adjust pH 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 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, dry Radix Ophiopogonis extract;
B, 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, 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, adjust pH 5.5～7.5 boils, and spends 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 Breviscapini injection group |
| The myocardial infarction model test improves the anti-mouse tail thrombotest of mouse microcirculation test rabbit fibrin solubility test due to the dog CAL method | Effect is remarkable, the effect reinforced effects is obvious, the effect reinforced effects is remarkable, the effect reinforced effects is obvious, and effect strengthens | The general partial action of effect is obvious, and the general effect of the not obvious effect of partial action 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 1 1.5 | 8.90 8.67 8.12 | 55.46 53.21 50.08 | 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 | 8.85 8.61 8.24 | 55.47 53.69 51.15 | 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 4.0 | 5.0 4.6 | 5.5 5.2 | 6.0 5.7 | 6.5 6.1 | 7.0 6.6 | 7.5 7.0 | 8.0 7.5 | 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 | 3.68 3.68 3.68 3.68 3.68 | 5.2 5.7 6.1 6.6 7.0 | 3.52 3.47 3.49 3.55 3.53 |
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, 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 - 8 - 5 4 4 | 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: 45 ℃ of pre-freeze temperature, 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 | 4.17 3.54 4.01 |
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,, 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 Radix Ophiopogonis extract;
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 when being concentrated into 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, and adjust pH 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 content of saponin component accounts in the preparation 28% of total solid after deduction adjuvant amount and the water quantities, and saponin component and scutellarin and other can be surveyed the component content sum and account for 91% of the total solid after the deduction adjuvant amount and water quantities in the preparation.
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,, 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 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, 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; Saponin component and scutellarin content sum account in the preparation 25% of total solid after deduction adjuvant amount and the water quantities.
Embodiments of the invention 3: 2 parts of 100 parts of breviscapines of 100 parts of Radix Ginsengs Radix Ophiopogonis
A, get medical material Radix Ophiopogonis, adding 11 times of volume decoctings boiled 1 time 2 hours, 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 the ginseng crude drug, add 14 times of volume 60% alcohol reflux 2 times, each 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, 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.
Embodiments of the invention 4: 0.5 part of 50 parts of breviscapine of 50 parts of Radix Ginsengs Radix Ophiopogonis
A, get medical material Radix Ophiopogonis, adding 6 times of volume decoctings boils 2 times, each 0.5 hour, measuring relative density when extracting solution is concentrated into 60 ℃ is 1.05～1.15, adds ethanol precipitate with ethanol twice, makes that to contain the alcohol amount be 75% 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 Radix Ophiopogonis extract;
B, get the ginseng crude drug, added 8 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, 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 0.9% 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.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 5: 0.3 part of 100 parts of breviscapine of 150 parts of Radix Ginseng Rubra Radix Ophiopogonis
A, add 10 times of volumes, 60% alcohol reflux Radix Ophiopogonis 3 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add the dissolving of 4 times of amount water for injection, filter merging filtrate, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, medicinal residues add 6 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 the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 65%, make for the second time that to contain the alcohol amount be 85%, filter, merge with the concentrated solution of front, 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, adding 12 times of volume decoctings boils 2 times, each 2.5 hours, 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 65%, 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, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 0.6% 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 5 ℃ 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.
Embodiments of the invention 6: 1 part of 120 parts of breviscapine of 80 parts of Radix Codonopsis Radix Ophiopogonis
A, get medical material Radix Ophiopogonis, add 13 times of volume decoctings and boil 2 times, each 1 hour, merge extractive liquid, was measured relative density and is 1.05～1.15 dry Radix Ophiopogonis extracts when being concentrated into 60 ℃;
B, get codonopsis pilosula, added 7 times of volumes, 70% alcohol reflux 1 time 1 hour, 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, 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, saponin component accounts in the preparation 1.4% of total solid after deduction adjuvant amount and the water quantities after testing.
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 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.
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, it is characterized in that with human body immunity improving power, treatment cardiovascular and cerebrovascular disease: 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, 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 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, dry Radix Ophiopogonis extract;
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 when being concentrated into 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,, 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 Radix Ophiopogonis extract;
B, 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, 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 freeze-drying preparation is preparation like this:
A, get medical material Radix Ophiopogonis, get medical material Radix Ophiopogonis, add 10 times of volume decoctings and boil each 1.5 hours 3 times, 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 85%, filter merging filtrate, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Radix Ophiopogonis extract;
B, 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, 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.Suitable adjuvant is added the injection water is mixed with solution,, filter with above-mentioned filtrate mixing, 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 claim 1-3 and any described traditional medicine Injectio with human body immunity improving power, treatment cardiovascular and cerebrovascular disease of 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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| CN 200510092850 CN1919303A (en) | 2005-08-22 | 2005-08-22 | Traditional medicine Injectio and its preparing method |
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