CN1935232A - Chinese medicine injection preparation and its preparing method - Google Patents
Chinese medicine injection preparation and its preparing method Download PDFInfo
- Publication number
- CN1935232A CN1935232A CN 200610111678 CN200610111678A CN1935232A CN 1935232 A CN1935232 A CN 1935232A CN 200610111678 CN200610111678 CN 200610111678 CN 200610111678 A CN200610111678 A CN 200610111678A CN 1935232 A CN1935232 A CN 1935232A
- Authority
- CN
- China
- Prior art keywords
- extract
- add
- injection
- relative density
- radix ophiopogonis
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention relates to a Chinese medicine injection preparation for raising immunity of human body and curing angiocardiopathy and cerebrovascular disease. Said Chinese medicine injection preparation is made up by using the Chinese medicinal materials of ophiopogon tuber, ginseng or red ginseng of pilose asiabell root and erigeron breviscapus through a certain preparation process. Said invention also provides the concrete steps of said preparation process. Said Chinese medicine injection preparation can obtain good therapeutic effect for curing the diseases of coronary heart disease, angina pectoris, arrhythmia, cerebral thrombosis and senile dementia, etc.
Description
Technical field
The present invention is a kind of traditional medicine Injectio with human body immunity improving power, treatment cardio-cerebrovascular diseases and preparation method thereof, belongs to technical field of Chinese medicine.
Technical background
We's medical application---cardiovascular and cerebrovascular disease, as coronary heart disease, myocardial infarction, rhomboembolia type cerebrovascular etc. is sickness rate height, disability rate height and the also high disease of case fatality rate, with diabetes, tumor etc. is at present the mankind to be threatened maximum three major types disease, and wherein cardiovascular and cerebrovascular disease is positioned at first of this three big disease.There is 2,600,000 people every year in China because of cardiovascular and cerebrovascular disease death at present, so prevention and treatment cardiovascular and cerebrovascular disease have become a necessity and arduous problem.
The medicine that is used for the treatment of at present cardiovascular and cerebrovascular disease clinically is generally Radix Salviae Miltiorrhizae Injection, SHENGMAI ZHUSHEYE, SHENMAI ZHUSHEYE, Breviscapini injection etc., yet these injection curative effects are very not desirable, and the report that untoward reaction is all arranged, the clinical reports of delivering in " clinical misdiagnosis wrong treatment " the 6th phase of calendar year 2001 at the above " giving birth to the untoward reaction of arteries and veins (and ginseng arteries and veins) injection ", Li Lanqing etc. of " Chinese patent medicine " 1999 the 8th phases as Zhuan Zhiquan such as " untoward reaction of Herba Erigerontis injection ".The applicant thinks that the reason that produces this situation may be: 1, the prescription of these preparations and proportioning thereof have much room for improvement, effect such as Breviscapini injection, Radix Salviae Miltiorrhizae Injection is single, can only be to a certain cause of disease pathological changes generation effect of cardiovascular and cerebrovascular disease, so curative effect is undesirable; 2, the processing extraction is impure, and some compositions such as pigment, tannin, starch, protein etc. are remained in the medicinal liquid with colloidal form, thereby untoward reaction takes place.Effective ingredient in Chinese or effective part group have multiple composition synergism, make its performance better therapeutic.Therefore, invent a kind of good effect, untoward reaction few, to the cardiovascular and cerebrovascular disease Different types of etiopathogenises produce the medicament composing prescription of synergistic therapeutic action and preparation thereof, technology is necessary.
The applicant drafts prescription: Radix Ophiopogonis, Radix Ginseng, Herba Erigerontis from the medicine of several respects researchs such as Chinese medicine traditional theory, pathomechanism treatment cardiovascular and cerebrovascular disease.From Chinese medicine theoretically, Radix Ginseng QI invigorating reinforcing the heart; Radix Ophiopogonis YIN nourishing and the production of body fluid promoting, Fu Mai; Herba Erigerontis has the effect of dredge the meridian passage, blood circulation promoting and blood stasis dispelling, and three medicine compatibilities are combined into a kind of pharmaceutical preparation that can effectively treat cardiovascular and cerebrovascular disease.From pathomechanism, vascular lesion is the main cause that causes at present known all cardiovascular and cerebrovascular vessel incident, and can be divided into ischemic and hemorrhagic two big classes from lesion nature, and the former sickness rate is far above the latter.In recent years, the free radical mechanism research of ischemic heart and brain damage is very active, has obtained bigger progress in many aspects.Prior art shows the effect that has Herba Erigerontis, Radix Ginseng, Radix Ophiopogonis good removing reactive oxygen free radical.The applicant's process discovers that three's compatibility result of use is better than the single medicine, and through the drug effective region that the process for refining that the present invention studies prepares, active ingredient has been carried out rich long-pending and purification, thereby made the effect of preparation better.
Summary of the invention
The object of the present invention is to provide a kind of ejection preparation and preparation method thereof with human body immunity improving power, treatment cardiovascular and cerebrovascular disease; The present invention utilizes the Radix Ginseng strongly invigorating primordial QI, Radix Ophiopogonis YIN nourishing and the production of body fluid promoting, Herba Erigerontis relaxing muscles and tendons to promote blood circulation, analgesic effect are combined into a kind of preparation that can effectively treat cardiovascular and cerebrovascular disease.The present invention is directed to prior art,, adopt the mode of separately extracting at different medical materials, 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, the bioavailability height is particularly useful for the treatment of cardiovascular and cerebrovascular disease acute attack stage, while preparation of the present invention is human body immunity improving power effectively, the generation of prevention and resist the disease.
Technical solution of the present invention is achieved in that
The present invention is a kind of ejection preparation with human body immunity improving power, treatment cardiovascular and cerebrovascular disease, calculate according to components by weight percent, it is made through extracting refining and adding suitable adjuvant by 50～5000 parts of 10～1000 parts of 10～1000 parts of Radix Ophiopogonis, Radix Ginseng and Herba Erigerontiss, or adds the injection that suitable adjuvant is made by corresponding weight portion medical material through extracting the extract that obtains after refining; Say exactly, it through extracting refining and add the injection that suitable adjuvant is made, or adds the injection that suitable adjuvant is made by corresponding weight portion medical material through extracting the extract that obtains after refining by 50～1000 parts of 10～500 parts of 10～500 parts of Radix Ophiopogonis, Radix Ginseng and Herba Erigerontiss; More preferably 200～500 parts of 50～200 parts of 50～200 parts of Radix Ophiopogonis, Radix Ginseng and Herba Erigerontiss be through extracting refining and add the injection that suitable adjuvant is made, or add the injection that suitable adjuvant is made by corresponding weight portion medical material through extracting the extract that obtains after refining.
Contain the multiple compositions of surveying such as saponin component and flavones ingredient in the preparation 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 flavones ingredient is not less than in the preparation 1% of total solid after deduction adjuvant amount and the water quantities; The content sum that saponin component in the preparation and flavones ingredient and other can be surveyed composition is not less than 25% of the total solid after the deduction adjuvant amount and water quantities in the preparation.
Injection of the present invention 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.
Injection of the present invention can prepare by the following method:
Radix Ophiopogonis, people participate in Herba Erigerontis three flavor medical materials and add water or ethanol extraction respectively, extracting solution carry out suitably concentrating crude extract, or further adopt one or more methods in alcohol deposition method, water precipitating method, acid-base precipitation method, flocculent precipitation, column chromatography, the solvent extraction be used in combination refining extract, above-mentioned crude extract or extract are added different auxiliary material make various ejection preparations.
The preparation method of injection of the present invention is as follows:
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 Herba Erigerontis medical material, 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 Herba Erigerontis extract;
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, Herba Erigerontis extract and Radix Ginseng extract are merged, add adjuvant and make different ejection preparations.
The preparation method of injection of the present invention is preferably:
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 Herba Erigerontis medical material, 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 Herba Erigerontis extract;
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, Herba Erigerontis extract and Radix Ginseng extract are merged, add adjuvant and make different ejection preparations.
Aseptic block in the injection of the present invention 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 Herba Erigerontis medical material, 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 Herba Erigerontis extract;
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, Herba Erigerontis extract and Radix Ginseng extract 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, at 4 ℃ of cold preservations 12 hours, coarse filtration, fine straining.Suitable adjuvant is added the injection water be mixed with solution,, filter packing with above-mentioned filtrate mixing, temperature-45 ℃, pre-freeze time 10h, the beginning evacuation, and in 12～72 hours differential gradient increased temperature to 10 ℃ progressively, keep 2.5h, be warming up to 20 ℃, keep 2h, promptly.
Injection with small volume in the injection of the present invention or concentrated solution for injection can 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, dry Radix Ophiopogonis extract;
B, get the Herba Erigerontis medical material, 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 Herba Erigerontis extract;
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, Herba Erigerontis extract and Radix Ginseng extract 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, 1～8 ℃ of cold preservation 12 hours, 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 in the injection of the present invention can 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, dry Radix Ophiopogonis extract;
B, get the Herba Erigerontis medical material, 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 Herba Erigerontis extract;
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, Herba Erigerontis extract and Radix Ginseng extract 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, at 1～8 ℃ of cold preservation 12 hours, 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.
Freeze dry sterile powder end in the injection of the present invention can 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, dry Radix Ophiopogonis extract;
B, Herba Erigerontis medical material add 10 times of volume 70% alcohol reflux 3 times, and each 1 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, the dry Herba Erigerontis extract that gets;
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, 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 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, at 1～8 ℃ of cold preservation 12 hours, 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.
Freeze dry sterile powder of the present invention end can 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, dry Radix Ophiopogonis extract;
B, Herba Erigerontis medical material add 10 times of volume 70% alcohol reflux 3 times, and each 1 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, the dry Herba Erigerontis extract that gets;
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, Herba Erigerontis extract and Radix Ginseng extract 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, 1～8 ℃ of cold preservation 12 hours, 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 in the injection of the present invention can 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, dry Radix Ophiopogonis extract;
B, Herba Erigerontis medical material add 10 times of volume 70% alcohol reflux 3 times, and each 1 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, the dry Herba Erigerontis extract that gets;
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, Herba Erigerontis extract and Radix Ginseng extract 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 boiled, 1～8 ℃ of cold preservation 12 hours, 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 adjuvant that is adopted in the injection set-up procedure 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.
Radix Ginseng of the present invention can also be the Radix Ginseng Rubra or the Radix Codonopsis of equivalent.
Compared with prior art, salience progress of the present invention is:
The applicant filters out optimum prescription in conjunction with aspects such as traditional Chinese medicine theory, cardiovascular and cerebrovascular disease pathomechanism, each effective ingredient site of actions; make it possess effects such as the blood vessel of expansion, brain protection, anticoagulant, the healing of promotion myocardial damage; and respectively each flavor Effective Components of Chinese Herb is extracted; be prepared into compound preparation, pharmacodynamics test proves that this compound preparation has stronger curative effect to cardiovascular and cerebrovascular disease than other preparations and single medicinal substances extract.The three herbal medicine rational and effective prescription proportionings that the present invention filters out, can many-sided effect in the vascular lesion position, and enhancing human body immunity power had better effect.Find that simultaneously Herba Erigerontis, Radix Ophiopogonis, compatibility Radix Ginseng Rubra, Radix Codonopsis also had certain curative effect.
Each medical material of this prescription adopts and extracts separately and suitable process for refining, avoids occurring the complicated component that mixed extraction may cause, and the pigment that remove impurity does not totally cause, tannin, protein etc. remain in the medium problem of medicinal liquid.
The applicant finds that in injection with small volume or concentrated solution for injection molding research the effective ingredient breviscapine dissolubility of Herba Erigerontis is low, and chemical stability problems appears in preparation easily.Through repetition test; we adopt the ethanol extraction Herba Erigerontis of higher concentration; and the medicinal liquid pH value is adjusted to 5.5～7.5; this moment, medicinal liquid was relatively stable; do not produce microgranule or any cosmetic variation; index components scutellarin content does not have too big variation, has effectively solved the problem of Herba Erigerontis stability.
Lyophilized formulations provided by the invention because main component is saponin, flavonoid substance, situations such as spray bottle, lyophilizing are incomplete occurred in freezing dry process.Through our repetition test, adopt rational freeze-dry process, preferably resolve this difficult problem.The inventor finds that in research process 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, both can satisfy the every requirement of injection, and reduce simultaneously as far as possible and add too much adjuvant.
Experimentation shows, the prescription side effect that the applicant screened is little, cardiovascular and cerebrovascular disease is had tangible curative effect, and the formulation products that obtains is the good medicine of human body immunity improving power, treatment cardiovascular and cerebrovascular disease; The selected preparation technology of the present invention extracts the medical material effective ingredient when removing impurity; The selected moulding process of the present invention is rationally controlled.
The applicant has carried out a series of experiments, can prove that safety of medicine provided by the invention is effective, process stabilizing, quality controllable.
Experimental example 1: drug effectiveness research
The pharmacological research conclusion
| Pilot project | Of the present invention group | The Herba Erigerontis injection group |
| Myocardial infarction model test due to the dog coronary artery ligation method | Effect is remarkable, and effect strengthens | Effect is general |
| Improve the test of mice microcirculation | Effect is obvious, and effect strengthens | Partial action is obvious, and partial action is not obvious |
| Anti-mouse tail thrombotest | Effect is remarkable, and effect strengthens | Effect is general |
| The rabbit fibrin solubility test | Effect is obvious, and effect strengthens | Effect is general |
From above-mentioned test as can be seen, the combination preparation therapeutic effect is significantly better than single preparation group.
Experimental example 2: extraction process condition research
2.1 the Chinese medicine preparation curative effect depends primarily on extraction, and extraction effect is subjected to extracting the influence of factors such as solvent, extraction time and time.Saponins in Radix Ophiopogonis has fine solubility in water, therefore preliminary definite extraction solvent is a water.
2.1.1 extracting solvent load Radix Ophiopogonis investigates
Take by weighing 200g Radix Ophiopogonis, totally three parts, add not commensurability decocting respectively and boil 3 times, each 2 hours, filtrate was filtered, and concentrate drying is measured total saponin content and extraction ratio.
Solvent load is investigated
| Sequence number | Medical material amount (g) | Solvent load (doubly) | Cream heavy (g) | Content (%) | The rate of transform (%) |
| 1 | 200.03 | 8 | 11.86 | 7.15 | 84.80 |
| 2 | 200.07 | 10 | 12.74 | 7.22 | 91.98 |
| 3 | 200.02 | 12 | 13.81 | 6.68 | 92.25 |
From The above results as can be seen, not commensurability water can extract most of saponin component, but from the rate of transform and content, adopting 10 times of water gagings is optimized schemes.
2.1.2 extraction time is investigated
After determining to extract solvent load, we screen the number of times that extracts.
Take by weighing 200g Radix Ophiopogonis, totally three parts, add 10 times of water gagings respectively and decoct, each 2 hours, filtrate was filtered, and concentrate drying is measured total saponin content and extraction ratio.
Extraction time is investigated
| Sequence number | Medical material amount (g) | Extraction time (inferior) | Cream heavy (g) | Content (%) | The rate of transform (%) |
| 1 | 200.02 | 1 | 7.65 | 8.10 | 61.97 |
| 2 | 200.02 | 2 | 9.58 | 8.35 | 79.99 |
| 3 | 200.04 | 3 | 12.83 | 7.21 | 92.50 |
From The above results as can be seen, along with increasing of extraction time, the rate of transform increases, but the rate of transform has reached 92.5% after extracting three times, therefore considers the energy and cost, determines that at last extracting 3 times is preferred plan.
2.1.3 the precipitate with ethanol condition is investigated
Take by weighing 600g Radix Ophiopogonis, add 10 times of volume decoctings and boil 3 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, is divided into 3 parts, adds the ethanol precipitate with ethanol respectively twice, filter filtrate concentrate drying, the rate of transform of mensuration total saponins.
The precipitate with ethanol condition is investigated
| Sequence number | Alcohol precipitation concentration for the first time | Alcohol precipitation concentration for the second time | Content (%) | The total saponins rate of transform (%) |
| 1 | 50％ | 70％ | 11.65 | 85.14 |
| 2 | 60％ | 85％ | 13.58 | 85.06 |
| 3 | 70％ | 90％ | 13.72 | 83.65 |
Take all factors into consideration from the content and the rate of transform, condition 2 is more satisfactory.
2.2 Herba Erigerontis optimization for extracting condition
Experimental technique and data
Take by weighing Herba Erigerontis 300g, totally 9 parts, make solvent with alcoholic solution, respectively by orthogonal table L
9(3
4) test.
The factor level table
Horizontal factor A concentration of alcohol (%) B extraction time (inferior) C extraction time (h) D ethanol consumption (doubly)
1 50 1 1 10
2 70 2 1.5 12
3 90 3 2 14
Orthogonal design table
Factor
The A B C D rate of transform (%)
Level
1 1 1 1 1 73.45
2 1 2 2 2 80.12
3 1 3 3 3 88.25
4 2 1 2 3 79.82
5 2 2 3 1 85.84
6 2 3 1 2 90.06
7 3 1 3 2 78.61
8 3 2 1 3 84.66
9 3 3 2 1 91.29
I 241.82 231.88 248.17 250.58
II 255.72 250.62 251.23 248.79
III 254.56 269.60 252.70 252.73
I 80.61 77.29 82.72 83.53
II 85.24 83.54 83.74 82.93
III 84.85 89.87 84.23 84.24
R 4.63 12.57 1.51 1.31
I
2 58476.9 1 53768.33 61588.35 62790.34
II
2 65392.72 62810.38 63116.51 61896.46
III
2 64800.79 72684.16 63857.29 63872.45
K
2 188670.42 189262.88 188562.15 188559.25
S 39.65 237.14 3.56 2.59
From above table as can be seen, extraction time has the greatest impact, and therefore selects B3 for use; A2 and A3 are very approaching in the concentration of alcohol, all are better than A1, therefore consider cost and the preferred A2 of the rate of transform; Extracting solvent load and extraction time does not all have obvious influence, considers the working time and consume energy to select C1 and D1 respectively for use, determines that therefore extraction conditions is: add 10 times of amount 70% ethanol, heating and refluxing extraction 3 times, each 1 hour.
2.3 Radix Ginseng optimization for extracting condition
Experimental technique and data
Take by weighing Radix Ginseng 100g, totally 9 parts, respectively by orthogonal table L
9(3
4) test.
The factor level table
C extraction time is (little
Factor A ethanol consumption (doubly) B extraction time (inferior) D concentration of alcohol (%)
The time)
Level
1 8 1 1 70
2 10 2 2 80
3 12 3 3 90
Orthogonal test table
Factor
The A B C D rate of transform (%)
Level
1 1 1 1 1 74.15
2 1 2 2 2 80.82
3 1 3 3 3 88.95
4 2 1 2 3 80.52
5 2 2 3 1 86.54
6 2 3 1 2 90.76
7 3 1 3 2 79.31
8 3 2 1 3 85.36
9 3 3 2 1 91.99
I 243.92 233.98 250.27 252.68
II 257.82 252.72 253.33 250.89
III 256.66 271.70 254.80 254.83 T＝758.40
I 81.31 77.99 83.42 84.23 CT＝T2/9＝
II 85.94 84.24 84.44 83.63 63907.84
III 85.55 90.57 84.93 84.94
R 4.63 12.57 1.51 1.31
I
2 59496.97 54746.64 62635.07 63847.18
II
2 66471.15 63867.40 64176.09 62945.79
III
2 65874.36 73820.89 64923.04 64938.33
K
2 191842.47 192434.93 191734.20 191731.30
S 39.65 237.14 3.56 2.59
From above table as can be seen, extraction time has the greatest impact, and therefore selects for use and extracts 3 times; 10 times and 12 times of gained rates of transform were more approaching during the ethanol consumption was investigated, for the saving cost is preferably used 10 times of amounts; Extraction time does not have influence to the rate of transform, for saving man-hour, preferably uses 1 hour; Concentration of alcohol does not have obvious influence to the rate of transform yet, selects 70% ethanol for use for reducing the ethanol consumption; Therefore determine that extraction conditions is: add 10 times of amount 70% ethanol, heating and refluxing extraction 3 times, each 1 hour.
Experimental example 3: injection with small volume or concentrated solution for injection molding research
3.1 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 | 8.93 | 56.78 | Reddish brown |
| 1 | 8.71 | 54.82 | Red |
| 1.5 | 8.42 | 51.15 | 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 | 8.94 | 54.57 | Reddish brown |
| 30 | 8.76 | 53.22 | Red |
| 60 | 8.30 | 50.81 | 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.
3.2 pH value of solution is investigated
For adapting to the Human Physiology needs, also to consider the character of each constituents in the medicinal liquid simultaneously, when dosing, need suitably adjust the pH value of medicinal liquid.Select scutellarin content as evaluation index.
Test method and result: after feeding intake and handle by recipe quantity,, filter with the concentrated solution mix homogeneously by above-mentioned condition, add water to 1000ml, adjust pH is when the different pH value that reaches shown in the following table, boil the back standing over night, observe the variation of appearance character under different pH condition.Experimental result sees Table.
The investigation of dosing pH value
| Sequence number | 1 2 3 | 4 5 6 7 | 8 9 |
| Dosing pH | 4.5 5.0 5.5 | 6.0 6.5 7.0 7.5 | 8.0 8.5 |
| Boil pH | 4.1 4.7 5.2 | 5.7 6.2 6.6 7.2 | 7.6 8.0 |
| Outward appearance | Precipitation appears | No significant change | Color burn |
The result shows, the medicinal liquid pH value boils the back at the sample below 5.5 and precipitation occurs, and pH value is obviously deepened in the color sample more than 7.5, and pH value is that 5.5～7.5 medicinal liquid is relatively stable, and outward appearance does not have significant change.Below its scutellarin content is measured, 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 | 5.5 | 3.44 | 5.2 | 3.11 |
| 2 | 6.0 | 3.44 | 5.7 | 3.18 |
| 3 | 6.5 | 3.44 | 6.2 | 3.20 |
| 4 | 7.0 | 3.44 | 6.6 | 3.15 |
| 5 | 7.5 | 3.44 | 7.2 | 3.26 |
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 4: the investigation of lyophilized formulations moulding process
4.1 the 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 | 5∶3 | Good | Part is subsided |
| Galactose | 5∶3 | Generally | Molding |
| Mannitol | 5∶3 | Good | Molding |
| Glycine | 5∶3 | Good | Molding, frangible |
| Dextran | 5∶3 | Generally | Molding |
| Mannitol, propylene glycol | 5∶3 | Good | Molding |
| Glycine, Polyethylene Glycol | 5∶3 | Good | Molding, frangible |
| Dextran, sorbitol, tween | 5∶3 | Good | Molding |
| Blank medicinal liquid | 3ml | Atrophy |
As seen from table, in the adjuvant that is screened, under the identical situation of other conditions, most of adjuvant all can be made into freeze-dried powder, but solubility angle integrated survey from yield rate, molding situation and sample, use the effect of mannitol to be better than other several adjuvants separately, can satisfy the every requirement of injection, reduce simultaneously as far as possible and add too much adjuvant.
4.2 caffolding agent consumption screening
The mannitol solution (70mg/ml, 100mg/ml and 130mg/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 | 70 | 5∶3 | Yellowish-brown | Part is subsided | Good | Up to specification |
| 2 | 100 | 5∶3 | Yellow | Intact | Good | Up to specification |
| 3 | 130 | 5∶3 | Yellowish | Intact | Good | Up to specification |
As seen from table, when the ratio of caffolding agent consumption and medicinal liquid is 5: 3, the sample character is that the sample of 100mg/ml and 130mg/ml is relatively good with the mannitol concentration, the sample of 70mg/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 5: 3.
4.3 lyophilization conditional filtering
Lyophilization is a veryer long dry run, needs to consume a large amount of energy.An ideal lyophilisation condition not only can be saved a large amount of energy, can also shorten man-hour simultaneously, so we are optimized screening to existing lyophilisation condition.The actual conditions screening sees Table:
The lyophilization conditional filtering
Time (h)
Condition I condition II condition III cold-trap
Temperature (℃)
-45 (pre-freezes) 10-8
-40 (pre-freeze)-8-
-40 (evacuation) 8-10
-35 (evacuation)-8-
-30 (evacuation) 8-8
-25 (evacuation)-10-
-20 (evacuation) 8-10
-15 (evacuation)-8-maintenance
5-5-70 ℃ of-10 (evacuation)
0 (evacuation) 555
10 (evacuation) 2.5 33
20 (evacuation) 243
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 2.5h; Be warming up to 20 ℃, keep 2h, get product.
Experimental example 5: spray drying conditional filtering
Spray drying technology can make sample dry rapidly under the situation of atomizing, and the protection effective ingredient can make the water content of sample reduce simultaneously, helps stability of formulation.It is bigger that but the air temperature and current speed that spray-dired effect is imported and exported influences, so we are that evaluation index is investigated these three factors with the loss of active ingredients rate.
Spray drying condition investigation table
| Inlet temperature (℃) | Outlet temperature (℃) | Air velocity (ms -1) | Loss rate (%) |
| 140 | 60 | 16 | 3.79 |
| 150 | 70 | 18 | 3.10 |
| 160 | 80 | 20 | 3.42 |
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: 300 parts of 125 parts of Herba Erigerontiss of 125 parts of Radix Ginsengs Radix Ophiopogonis
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 Herba Erigerontis medical material, 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 Herba Erigerontis extract;
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, Herba Erigerontis extract and Radix Ginseng extract 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 regulating pH value is 6, boils, at 4 ℃ of cold preservations 12 hours, coarse filtration, fine straining.Suitable adjuvant is added the injection water be mixed with solution,, filter, packing, pre-freeze 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 2.5h; Be warming up to 20 ℃, keep 2h, promptly get aseptic block.After testing: the content of saponin component accounts in the preparation 42% of total solid after deduction adjuvant amount and the water quantities; The content of flavones ingredient accounts in the preparation 39% of total solid after deduction adjuvant amount and the water quantities; The total solid that sum of the two accounts in the preparation after deduction adjuvant amount and the water quantities is 81%.
Embodiments of the invention 2: 5000 parts of 1000 parts of Herba Erigerontiss 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 Herba Erigerontis medical material, 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 Herba Erigerontis extract;
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, Herba Erigerontis extract and Radix Ginseng extract 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 regulating pH value is 6.5, boils, at 4 ℃ of cold preservations 12 hours, coarse filtration, fine straining.Mannitol is added the injection water be mixed with 100mg/ml solution,, filter with above-mentioned filtrate mixing, packing, temperature-45 ℃, pre-freeze time 12h, the beginning evacuation, and be warming up to-37 ℃, and keep 10h, be warming up to-27 ℃ again, keep 10h; Be warming up to-17 ℃, keep 10h, be warming up to-7 ℃, keep 6h, be warming up to 3 ℃, keep 6h, be warming up to 13 ℃, keep 3h, be warming up to 23 ℃, keep 3h, promptly get freeze-dried powder.After testing: the content of saponin component accounts in the preparation 37% of total solid after deduction adjuvant amount and the water quantities; The content of flavones ingredient accounts in the preparation 53% of total solid after deduction adjuvant amount and the water quantities; The total solid that sum of the two accounts in the preparation after deduction adjuvant amount and the water quantities is 90%.
Embodiments of the invention 3: 50 parts of 10 parts of Herba Erigerontiss 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 Herba Erigerontis medical material, added 5 times of volumes, 50% alcohol reflux 1 time 0.5 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, dry Herba Erigerontis extract;
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, Herba Erigerontis extract and Radix Ginseng extract 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 is 5.5, boils, 1 ℃ of cold preservation 12 hours, coarse filtration, fine straining, dividing to install in the ampoule bottle, is 100 ℃ in vapor (steam) temperature, and actual pressure is at 100kN/m
3Pressure sterilizing is 20 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 12% of total solid after deduction adjuvant amount and the water quantities; The content of flavones ingredient accounts in the preparation 13% of total solid after deduction adjuvant amount and the water quantities; The total solid that sum of the two accounts in the preparation after deduction adjuvant amount and the water quantities is 25%.
Embodiments of the invention 4: 300 parts of 60 parts of Herba Erigerontiss of 110 parts of Radix Ginsengs Radix Ophiopogonis
A, get medical material Radix Ophiopogonis, adding 8 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 Herba Erigerontis medical material, added 8 times of volumes, 50% alcohol reflux 1 time 0.5 hour, measuring relative density when extracting solution is concentrated into 60 ℃ is 1.05～1.15, dry Herba Erigerontis extract;
C, get the ginseng crude drug, add 10 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, Herba Erigerontis extract and Radix Ginseng extract 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, and regulating pH value is 6, boil, at 1 ℃ of cold preservation 12 hours, coarse filtration, fine straining, 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% of total solid after deduction adjuvant amount and the water quantities.
Embodiments of the invention 5: 1000 parts of 500 parts of Herba Erigerontiss of 500 parts of Radix Ginsengs Radix Ophiopogonis
A, get medical material Radix Ophiopogonis, adding 10 times of volume decoctings boiled 1 time 2.5 hours, measuring relative density when extracting solution 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 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 Herba Erigerontis medical material, add 6 times of volume 70% 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 Herba Erigerontis extract;
C, get the ginseng crude drug, added 12 times of volumes, 60% 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 Ginseng extract;
Above-mentioned Radix Ophiopogonis extract, 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, and adjust pH is 7.0, boil, at 4 ℃ of cold preservations 12 hours, coarse filtration, fine straining, 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 flavones ingredient accounts in the preparation 1% of total solid after deduction adjuvant amount and the water quantities.
Embodiments of the invention 6: 800 parts of 200 parts of Herba Erigerontiss of 200 parts of Radix Ginseng Rubra Radix Ophiopogonis
A, add 8 times of volumes, 70% 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 3 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 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 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 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 Herba Erigerontis medical material, 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 Herba Erigerontis extract;
C, get the Radix Ginseng Rubra medical material, add 6 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water dissolution that adds 3 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 10 times of resinite hydrops and 5 times of resin volume 25% alcohol flushing impurity successively, use 60% alcohol desorption of 4 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 Rubra extract;
Above-mentioned Radix Ophiopogonis extract, Herba Erigerontis extract and Radix Ginseng Rubra extract 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, adjust pH is 7.2, boils, 5 ℃ of cold preservations 12 hours, 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 2.5h; 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, to account in the preparation total solid of deduction adjuvant amount and water quantities be 52% to saponin component.
Embodiments of the invention 7: 400 parts of 100 parts of Herba Erigerontiss of 150 parts of Radix Codonopsis Radix Ophiopogonis
A, get medical material Radix Ophiopogonis, adding 12 times of volume decoctings boils 2 times, each 0.8 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 Radix Ophiopogonis extract;
B, get the Herba Erigerontis medical material, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 4 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin with the speed of 0.5ml/g medical material .min, use 8 times of resinite hydrops and 6 times of resin volume 15% alcohol flushing impurity successively, use 40% alcohol desorption of 4 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Herba Erigerontis extract;
C, get codonopsis pilosula, add 6 times of volume 50% 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 Codonopsis extract;
Above-mentioned Radix Ophiopogonis extract, Herba Erigerontis extract and Radix Codonopsis extract 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, and adjust pH is 6.8, boils, 6 ℃ of cold preservations 12 hours, coarse filtration, fine straining are 150 ℃ in inlet temperature, and leaving air temp is 70 ℃, air velocity is that spray drying gets powder under the condition of 18ms-1, and packing promptly gets the spray drying sterilized powder.After testing, to account in the preparation total solid of deduction adjuvant amount and water quantities be 39% to the content of flavones ingredient.
Embodiments of the invention 8: 200 parts of 50 parts of Herba Erigerontiss of 50 parts of Radix Ginsengs Radix Ophiopogonis
A, get medical material Radix Ophiopogonis, adding 10 times of volume decoctings boils 3 times, each 1.5 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, Herba Erigerontis medical material add 10 times of volume 70% alcohol reflux 3 times, and each 1 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, the dry Herba Erigerontis extract that gets;
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, Herba Erigerontis extract and Radix Ginseng extract are merged, add an amount of water for injection dissolving, by volume add 0.5% active carbon, boil, keep little 50min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, adjust pH is 5.8, boils, 8 ℃ of cold preservations 12 hours, coarse filtration, fine straining divide to install in the enamel tray, temperature-55 ℃, pre-freeze time 8h, the beginning evacuation, and be warming up to-43 ℃, keep 6h, be warming up to-33 ℃ again, keep 6h; Be warming up to-23 ℃, keep 6h, be warming up to-13 ℃, keep 4h, be warming up to-3 ℃, keep 4h, be warming up to 7 ℃, keep 1h, be warming up to 17 ℃, keep 1h, under aseptic condition, divide to install to promptly to get the freeze dry sterile powder end in the cillin bottle.
Embodiments of the invention 9: 500 parts of 200 parts of Herba Erigerontiss of 200 parts of Radix Ginsengs Radix Ophiopogonis
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, Herba Erigerontis medical material add 10 times of volume 70% alcohol reflux 3 times, and each 1 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, the dry Herba Erigerontis extract that gets;
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, Herba Erigerontis extract and Radix Ginseng extract are merged, add an amount of water for injection dissolving, by volume add 0.8% active carbon, boil, keep little 60min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, adjust pH 7.5 boiled, 8 ℃ of cold preservations 12 hours, coarse filtration, fine straining, in inlet temperature is 160 ℃, and leaving air temp is 80 ℃, and air velocity is 20ms
-1Condition under spray drying get powder, packing promptly gets the spray drying sterilized powder.
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 made through extracting refining and adding suitable adjuvant by 50～5000 parts of 10～1000 parts of 10～1000 parts of Radix Ophiopogonis, Radix Ginseng and Herba Erigerontiss, or adds the injection that suitable adjuvant is made by corresponding weight portion medical material through extracting the extract that obtains 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 through extracting refining and add the injection that suitable adjuvant is made, or adds the injection that suitable adjuvant is made by corresponding weight portion medical material through extracting the extract that obtains after refining by 50～1000 parts of 10～500 parts of 10～500 parts of Radix Ophiopogonis, Radix Ginseng and Herba Erigerontiss.
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 through extracting refining and add the injection that suitable adjuvant is made, or adds the injection that suitable adjuvant is made by corresponding weight portion medical material through extracting the extract that obtains after refining by 200～500 parts of 50～200 parts of 50～200 parts of Radix Ophiopogonis, Radix Ginseng and Herba Erigerontiss.
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, 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 flavones ingredient is not less than in the preparation 1% of total solid after deduction adjuvant amount and the water quantities.
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: the content sum that saponin component in the preparation and flavones ingredient and other can be surveyed composition is 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, people participate in Herba Erigerontis three flavor medical materials and add water or ethanol extraction respectively, extracting solution carry out suitably concentrating crude extract, or further adopt one or more methods in alcohol deposition method, water precipitating method, acid-base precipitation method, flocculent precipitation, column chromatography, the solvent extraction be used in combination refining extract, above-mentioned crude extract or extract are added different auxiliary material make 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 Herba Erigerontis medical material, 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 Herba Erigerontis extract;
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, Herba Erigerontis extract and Radix Ginseng extract 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 Herba Erigerontis medical material, 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 Herba Erigerontis extract;
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, Herba Erigerontis extract and Radix Ginseng extract 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: aseptic block 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 Herba Erigerontis medical material, 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 Herba Erigerontis extract;
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, Herba Erigerontis extract and Radix Ginseng extract 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, at 4 ℃ of cold preservations 12 hours, coarse filtration, fine straining.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 any described traditional medicine Injectio with human body immunity improving power, treatment cardiovascular and cerebrovascular disease of claim 1-10, it is characterized in that: Radix Ginseng can also be the Radix Ginseng Rubra or the Radix Codonopsis of equivalent.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 200610111678 CN1935232A (en) | 2005-08-22 | 2006-08-22 | Chinese medicine injection preparation and its preparing method |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200510092842 | 2005-08-22 | ||
| CN200510092842.5 | 2005-08-22 | ||
| CN 200610111678 CN1935232A (en) | 2005-08-22 | 2006-08-22 | Chinese medicine injection preparation and its preparing method |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1935232A true CN1935232A (en) | 2007-03-28 |
Family
ID=37953092
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 200610111678 Pending CN1935232A (en) | 2005-08-22 | 2006-08-22 | Chinese medicine injection preparation and its preparing method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1935232A (en) |
-
2006
- 2006-08-22 CN CN 200610111678 patent/CN1935232A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1381236A (en) | Medicinal composition containing baicalin and caffoeoylchinic acid | |
| CN1951474A (en) | A Chinese medicinal injection and preparation method thereof | |
| CN1935235B (en) | Chinese medicine injection preparation and its preparing method | |
| CN1935232A (en) | Chinese medicine injection preparation and its preparing method | |
| CN1935234A (en) | Chinese medicine injection preparation and its preparing method | |
| CN1935231A (en) | Chinese medicine injection preparation and its preparing method | |
| CN1935230B (en) | Chinese medicine injection preparation and its preparing method | |
| CN102716231B (en) | A kind of Chinese medicine composition and application thereof for the treatment of brain injury and cerebral edema | |
| CN1935233A (en) | Chinese medicine injection preparation and its preparing method | |
| CN1935229A (en) | Chinese medicine injection preparation and its preparing method | |
| CN1969897A (en) | Pharmaceutical composition for treating cardiovascular and cerebrovascular diseases, preparation process and quality control method thereof | |
| CN101744991B (en) | Single extraction method of ginseng, ophiopogon root and shiandra and preparation thereof | |
| CN101745011B (en) | Method for extracting ginseng, dwarf lilyturf tuber and schisandra chinensis and preparation thereof | |
| CN101194996A (en) | Chinese medicine ejection preparation and method for preparing the same | |
| CN1969927A (en) | Pharmaceutical composition for treating cardiovascular and cerebrovascular diseases, preparation process and quality control method thereof | |
| CN1935183A (en) | Chinese medicine compound preparation and its preparing method | |
| CN1969939A (en) | Pharmaceutical composition for treating cardiovascular and cerebrovascular diseases, preparation process and quality control method thereof | |
| CN100455302C (en) | Danshen freeze-drying injection for treating cardiovascular and cerebrovascular diseases and preparation thereof | |
| CN1919301A (en) | Traditional medicine Injectio and its preparing method | |
| CN1883654A (en) | Pulse invigorating injection with astragalus root and preparation process thereof | |
| CN1969892A (en) | Pharmaceutical composition for treating cardiovascular and cerebrovascular diseases, preparation method and quality control method thereof | |
| CN1969938A (en) | Pharmaceutical composition for treating cardiovascular and cerebrovascular diseases, preparation process and quality control method thereof | |
| CN1969926A (en) | Pharmaceutical composition for treating cardiovascular and cerebrovascular diseases, preparation process and quality control method thereof | |
| CN115120657A (en) | Traditional Chinese medicine composition for anti-permeability dilatation in shock-resistant period of burn, pharmaceutical preparation and preparation method | |
| CN1919305A (en) | Traditional medicine Injectio and its preparing method |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |