CN1951474A

CN1951474A - A Chinese medicinal injection and preparation method thereof

Info

Publication number: CN1951474A
Application number: CN 200610111675
Authority: CN
Inventors: 于文风
Original assignee: Qiyuanyide Medicines Institute Beijing
Current assignee: Qiyuanyide Medicines Institute Beijing
Priority date: 2005-08-22
Filing date: 2006-08-22
Publication date: 2007-04-25

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 herba erigerontis, wherein organic solvent extraction method is employed to purify the herbal extract, and the process for preparing various dose forms is also provided. The preparation shows good effect in treating cardiovascular and cerebrovascular diseases such as coronary disease, angina pectoris, arrhythmia, cerebral thrombus and senile dementia.

Description

A kind of traditional medicine Injectio and preparation method thereof

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.Inventor's process discovers that three's compatibility result of use is better than the single medicine, and through the drug effective region that the process for refining that the present invention studies prepares, active ingredient has been carried out rich long-pending and purification, thereby made the effect of preparation better.

Summary of the invention

The object of the present invention is to provide a kind of ejection preparation and preparation method thereof with human body immunity improving power, treatment cardiovascular and cerebrovascular disease; The present invention utilizes the Radix Ginseng strongly invigorating primordial QI, 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 according to parts by weight and calculates, be to be made through extracting refining and adding suitable adjuvant, or add suitable adjuvant and be made through extracting the extract that obtains after refining by corresponding weight portion medical material by 50～5000 parts of 10～1000 parts of 10～1000 parts of Radix Ophiopogonis, Radix Ginseng and Herba Erigerontiss.Definite say a kind of traditional medicine Injectio with human body immunity improving power, treatment cardiovascular and cerebrovascular disease, be to be made through extracting refining and adding suitable adjuvant, or add suitable adjuvant and be made through extracting the extract that obtains after refining by corresponding weight portion medical material by 50～1000 parts of 10～500 parts of 10～500 parts of Radix Ophiopogonis, Radix Ginseng and Herba Erigerontiss.More definite say a kind of traditional medicine Injectio with human body immunity improving power, treatment cardiovascular and cerebrovascular disease, be to be made through extracting refining and adding suitable adjuvant, or add suitable adjuvant and be made through extracting the extract that obtains after refining by corresponding weight portion medical material by 200～500 parts of 50～200 parts of 50～200 parts of Radix Ophiopogonis, Radix Ginseng and Herba Erigerontiss.

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, 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 wherein 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.

Preparation method with traditional medicine Injectio of human body immunity improving power, treatment cardiovascular and cerebrovascular disease of the present invention: 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 the ejection preparation of treatment cardio-cerebrovascular diseases of the present invention is:

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, adds 1～4 times of amount n-butyl alcohol, shaking out 1～8 time, merge n-butyl alcohol liquid, measuring relative density during decompression and solvent recovery 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, measuring relative density when merge extractive liquid,, decompression and solvent recovery to 60 ℃ is 1.05～1.15, adds 1～4 times and measures ethyl acetate, shaking out 1～8 time, measuring relative density when combined ethyl acetate liquid, decompression and solvent recovery to 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, adds 1～4 times of amount n-butyl alcohol, shaking out 1～8 time, merge n-butyl alcohol liquid, measuring relative density during decompression and solvent recovery to 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.

Exactly, 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, adds 2 times of amount n-butyl alcohol, shaking out 5 times, merge n-butyl alcohol liquid, measuring relative density during decompression and solvent recovery 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, adds 2 times of amount ethyl acetate, shaking out 5 times, measuring relative density when combined ethyl acetate liquid, decompression and solvent recovery to 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, adds 2 times of amount n-butyl alcohol, shaking out 5 times, merge n-butyl alcohol liquid, measuring relative density during decompression and solvent recovery to 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.With suitable adjuvant aqueous solution, with above-mentioned filtrate mixing, filter, packing, temperature-45 ℃, pre-freeze time 10h, the beginning evacuation, and in 12～72 hours differential gradient increased temperature to 10 ℃ progressively, keep 2h, be warming up to 20 ℃, keep 3h, promptly.

Injection of the present invention is preparation like this:

A, Radix Ophiopogonis medical material, 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, adds 2 times of amount n-butyl alcohol, shaking out 5 times, merge n-butyl alcohol liquid, measuring relative density during decompression and solvent recovery to 60 ℃ is 1.05～1.15, dry Radix Ophiopogonis 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.

Injection of the present invention is preparation like this:

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.

Injection of the present invention is preparation like this:

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, transfer pH value 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.

Injection of the present invention prepares like this:

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% pH active carbon, boil, keep little 10～60min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, and tone pitch 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.

Injection of the present invention is preparation like this:

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 preparation process of the present invention comprises in mannitol, galactose, glycine, glucose, sodium chloride, dextran, glycerol, ethanol, propylene glycol, Polyethylene Glycol, sorbitol, tween, the poloxamer-kind or several.

The Radix Ginseng that the present invention relates to 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 great fall 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.Wherein 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

Of the present invention group of Herba Erigerontis injection group of pilot project

Heart effect is remarkable due to the dog coronary artery ligation method, and the effect reinforced effects is general

The muscle infarction model test

The antiplatelet aggregation test effect is remarkable, and the effect reinforced effects is obvious

Anti-mouse tail thrombotest effect is remarkable, and the effect reinforced effects is general

Rabbit fibrin solubility test effect is obvious, and the effect reinforced effects 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:

2.1 extraction conditions screening Radix Ophiopogonis:

2.1.1 determining of amount of water

Take by weighing three parts of 150g medical materials, decoct with water respectively 3 times, each 1.5 hours, merge extractive liquid, concentrated drying.The results are shown in following table:

The investigation of amount of water

Heavy (g) total saponins rate of transform (%) of medical material amount amount of water (doubly) cream

150 8 41.30 74.98

150 10 45.41 93.25

150 12 47.45 93.77

As seen from the experiment, add 10 times and 12 times of water, extraction effect is more or less the same, and is guaranteeing in order to save cost, to determine that amount of water is 10 times of amounts under the sufficient prerequisite of extracts active ingredients.

2.1.2 determining of extraction time

Take by weighing three parts of 150g medical materials, add 10 times of water gagings respectively and decoct, each 1.5 hours, merge extractive liquid, concentrated drying.The results are shown in following table:

The investigation of extraction time

Heavy (g) total saponins rate of transform (%) of medical material amount (g) extraction time (inferior) cream

150 2 36.92 62.56

150 3 45.93 91.34

150 4 50.37 92.09

As seen from the experiment, extract 3 times and 4 times, extraction effect is more or less the same, and is guaranteeing in order to save time, to determine that extraction time is 3 times under the sufficient prerequisite of extracts active ingredients.

2.1.3 determining of extraction time

Take by weighing three parts of 150g medical materials, add 10 times of water gagings respectively and decoct 3 times, merge extractive liquid, concentrates drying.The results are shown in following table:

The investigation of extraction time

Medical material amount each extraction time (hour) heavy (g) rate of transform (%) of cream

150 1 37.52 66.02

150 1.5 45.00 91.58

150 2 50.56 92.04

As seen from the experiment, extracted 1.5 hours and 2 hours, extraction effect is more or less the same at every turn, is guaranteeing in order to save time, to determine that each extraction time is 1.5 hours under the sufficient prerequisite of extracts active ingredients.

2.1.4 the screening of extractant:

Take by weighing two parts of 200g medical materials, add 10 times of water gagings and decoct 3 times, each 1.5 hours, merge extractive liquid, concentrated, and concentrated solution is divided into two parts, solubilizer extraction respectively.The results are shown in following table:

The investigation of extractant

Heavy (g) paste-forming rate (%) of medical material amount (g) extractant cream

200 ethyl acetate 10.37 10.37

200 n-butyl alcohol 15.62 15.62

As seen from the experiment, the effect of n-butanol extraction is better than ethyl acetate, therefore selects for use n-butyl alcohol to extract.

2.1.5 the screening of extractant consumption:

Take by weighing the 300g medical material, add 10 times of water gagings and decoct 3 times, each 1.5 hours, merge extractive liquid, concentrated, and concentrated solution is divided into three parts, and the n-butyl alcohol that adds different amounts respectively extracts.The results are shown in following table:

The investigation of extractant consumption

Heavy (g) paste-forming rate (%) of medical material amount (g) extractant consumption cream

100 1 times of amounts 11.08 11.08

100 2 times of amounts 15.81 15.81

100 3 times of amounts 16.66 16.66

As seen from the experiment, the n-butanol extraction effect of 2 times of consumptions and 3 times of consumptions is more or less the same, and is guaranteeing in order to save cost, to determine that the n-butanol extraction consumption is 2 times of amounts under the sufficient prerequisite of extracts active ingredients.

2.2 Herba Erigerontis extraction conditions screening:

2.2.1 extract the screening of solvent

Take by weighing four parts of 300g medical materials, add the different solvents of 15 times of volumes respectively, reflux, extract, 3 times, each 1 hour.Respectively extracting solution is filtered the filtrate concentrate drying.The results are shown in following table:

Extract the investigation of solvent

Heavy (g) rate of transform (%) of medical material amount (g) concentration of alcohol (%) cream

300 30 22.35 82.60

300 50 22.40 85.57

300 70 16.76 92.64

300 90 17.58 93.08

The result shows, during with 70% and 90% ethanol extraction, the scutellarin rate of transform is higher, but difference of them is little, therefore selects 70% ethanol to extract solvent as optimum.

2.2.2 determining of alcohol adding amount

Take by weighing three parts of 300g medical materials, add 70% not commensurability ethanol extraction 3 times respectively, each 1 hour, merge extractive liquid, concentrated drying.The results are shown in following table:

The investigation of alcohol adding amount

Heavy (g) rate of transform (%) of medical material amount (g) alcohol adding amount (doubly) cream

300 8 14.56 73.45

300 10 16.64 91.91

300 12 17.71 92.06

As seen from the experiment, add 10 times and 12 times of 70% ethanol, extraction effect is more or less the same, and is guaranteeing in order to save cost, to determine that alcohol adding amount is 10 times of amounts under the sufficient prerequisite of extracts active ingredients.

2.2.3 determining of extraction time

Take by weighing the 300g medical material, three parts, add 70% ethanol extraction of 10 times of amounts respectively, each 1 hour, merge extractive liquid, concentrated drying.The results are shown in following table:

The investigation of extraction time

Heavy (g) rate of transform (%) of medical material amount (g) extraction time (inferior) cream

300 2 13.10 76.99

300 3 15.74 91.59

300 4 18.78 92.22

As seen from the experiment, extract 3 times and 4 times, extraction effect is more or less the same, and is guaranteeing in order to save time, to determine that optimum extraction time is 3 times under the sufficient prerequisite of extracts active ingredients.

2.2.4 the screening of extractant

Take by weighing the 600g medical material, add 10 times of amount 70% ethanol extractions 3 times, each 1 hour, merge extractive liquid, concentrated, and concentrated solution is divided into two parts, solubilizer extraction respectively.The results are shown in following table:

The investigation of extractant

Heavy (g) scutellarin content (%) of medical material amount (g) extractant cream

300 ethyl acetate 1.36 53.06

300 n-butyl alcohol 1.24 43.24

As seen from the experiment, the effect of ethyl acetate extraction is better than n-butyl alcohol, therefore selects for use ethyl acetate to extract.

2.2.5 the screening of extractant consumption

Take by weighing the 600g medical material, add 10 times of amount 70% ethanol extractions 3 times, each 1 hour, merge extractive liquid, concentrated, and concentrated solution is divided into three parts, added the ethyl acetate extraction 5 times of different amounts respectively.The results are shown in following table:

The investigation of extractant consumption

Heavy (g) scutellarin content (%) of medical material amount (g) extractant consumption cream

200 1 times of amounts 0.62 37.54

200 2 times of amounts 0.96 54.25

200 3 times of amounts 1.03 50.67

As seen from the experiment, the ethyl acetate extraction effect of 2 times of consumptions and 3 times of consumptions is more or less the same, and is guaranteeing in order to save cost, to determine that the ethyl acetate extraction consumption is 2 times of amounts under the sufficient prerequisite of extracts active ingredients.

2.3 Radix Ginseng extraction conditions screening

2.3.1 extract the screening of solvent

Take by weighing four parts of 300g medical materials, add the different solvents of 15 times of volumes respectively, reflux, extract, 3 times, each 1 hour.Respectively with extracting liquid filtering, the filtrate concentrate drying.The results are shown in following table:

Extract the investigation of solvent

300 30 60.09 83.15

300 50 45.63 86.28

300 70 35.86 91.53

300 90 32.56 92.13

The result shows, during with 70% ethanol extraction, the total saponin content and the rate of transform all are higher than the ethanol of other concentration.So the ethanol of selection 70% is as extracting solvent.

2.3.2 determining of alcohol adding amount

The investigation of alcohol adding amount

Heavy (g) extraction ratio (%) of medical material amount (g) alcohol adding amount (doubly) cream

300 8 30.63 77.05

300 10 34.56 91.30

300 12 36.47 92.29

2.3.3 determining of extraction time

The investigation of extraction time

Heavy (g) extraction ratio (%) of medical material amount (g) extraction time (inferior) cream

300 2 31.42 76.31

300 3 35.08 91.91

300 4 37.76 92.38

2.3.4 determining of extraction time

Take by weighing three parts of 300g medical materials, add 70% ethanol extraction 3 times of 10 times of amounts respectively, merge extractive liquid, concentrates drying.The results are shown in following table:

The investigation of extraction time

Medical material amount (g) each extraction time (hour) heavy (g) extraction ratio (%) of cream

300 0.5 29.67 82.10

300 1.0 34.82 91.37

300 1.5 36.12 91.86

As seen from the experiment, extracted 1.0 hours and 1.5 hours, extraction effect is more or less the same at every turn, is guaranteeing in order to save time, to determine that each extraction time is 1 hour under the sufficient prerequisite of extracts active ingredients.

2.3.5 the screening of extractant

The investigation of extractant

Heavy (g) rate of transform (%) of medical material amount (g) extractant cream

300 n-butyl alcohol 2.79 59.93

300 ethyl acetate 2.51 48.26

2.3.6 the screening of extractant consumption:

Take by weighing the 900g medical material, add 10 times of amount 70% ethanol extractions 3 times, each 1 hour, merge extractive liquid, concentrated, and concentrated solution is divided into three parts, added the n-butanol extraction 5 times of different amounts respectively.The results are shown in following table:

The investigation of extractant consumption

Heavy (g) rate of transform (%) of medical material amount (g) extractant consumption cream

300 1 times of amounts 1.91 49.80

300 2 times of amounts 2.77 59.99

300 3 times of amounts 2.83 61.02

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 investigated, the results are shown in following table:

The activated carbon dosage investigation table

Heavy (g) rate of transform (%) outward appearance of activated carbon dosage (%) cream

0.1 7.53 55.69 is reddish brown

1 7.20 54.61 is red

1.5 6.84 51.18 is 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) heavy (g) rate of transform (%) outward appearance of cream

10 7.37 55.86 palm fibres

30 7.28 54.35 is red

60 7.06 51.28 is 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 123456789

Dosing pH 4.5 5.0 5.5 6.0 6.5 7.0 7.5 8.0 8.5

Boil pH 4.0 4.6 5.1 5.7 6.2 6.6 7.2 7.7 8.1

The no significant change color burn of precipitation appears in outward appearance

The result shows, the medicinal liquid pH value boils the back at the sample below 5.5 and precipitation occurs, and pH value is obviously deepened in the color sample more than 7.5, and pH value is that 5.5～7.5 medicinal liquid is relatively stable, and outward appearance does not have significant change.Below its scutellarin content is measured.The results are shown in Table:

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

Content (%) boils back pH and boils back content (%) during sequence number dosing pH dosing

1 5.5 4.51 5.1 4.30

2 6.0 4.51 5.7 4.35

3 6.5 4.51 6.2 4.29

4 7.0 4.51 6.6 4.31

5 7.5 4.51 7.2 4.40

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

Caffolding agent kind caffolding agent: medicinal liquid solubility finished product outward appearance

(V∶V)

3: 1 good parts of glucose subside

Galactose general molding in 3: 1

Mannitol good molding in 3: 1

Glycine good molding in 3: 1, frangible

Dextran general molding in 3: 1

Mannitol, propylene glycol good molding in 3: 1

Glycine, Polyethylene Glycol good molding in 3: 1, frangible

Dextran, Pyrusussuriensis good molding in 3: 1

Alcohol, tween

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 (65mg/ml, 100mg/ml and 135mg/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

Mannitol concentration mannitol: medicinal liquid

Numbering color and luster profile solubility clarity

(mg/ml) (V∶V)

1 65 3: 1 yellowish-brown part has been subsided up to specification

2 100 3: 1 is yellow intact good up to specification

3 135 3: 1 is yellowish intact good up to specification

As seen from table, when the ratio of caffolding agent consumption and medicinal liquid is 3: 1, the sample character is that the sample of 100mg/ml and 135mg/ml is relatively good with the mannitol concentration, the sample of 65mg/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 3: 1.

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

Experimental result shows: finished product appearance character that condition I, II and III make and the equal conformance with standard of moisture.But comparatively speaking, condition II yield rate is low slightly, and condition III power consumption is bigger, considers the practical situation of production, short condition I of finally selected overall time spent, i.e. and lyophilization condition is: pre-freeze temperature-45 ℃, pre-freeze time 10h;-40 ℃ of evacuation keep 8h; Be warming up to-30 ℃ again, keep 8h; Be warming up to-20 ℃, keep 8h; Be warming up to-10 ℃, keep 5h; Be warming up to 0 ℃, keep 5h; Be warming up to 10 ℃, keep 2h; Be warming up to 20 ℃, keep 3h, 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 4.42

150 70 18 3.75

160 80 20 4.08

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

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 1% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transferring pH value is 6, boils, 4 ℃ 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 2h; Be warming up to 20 ℃, keep 3h, under aseptic condition, divide to install to promptly to get the freeze dry sterile powder end in the cillin bottle.Cold preservation 12 hours is after testing: the content of saponin component accounts for 25% of the total solid after the deduction adjuvant amount and water quantities in the preparation; The content of flavones ingredient accounts in the preparation 58% 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 83%.

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, adds 4 times of amount n-butyl alcohol, shaking out 8 times, merge n-butyl alcohol liquid, measuring relative density during decompression and solvent recovery 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, measuring relative density when merge extractive liquid,, decompression and solvent recovery to 60 ℃ is 1.05～1.15, adds 4 times and measures ethyl acetate, shaking out 8 times, measuring relative density when combined ethyl acetate liquid, decompression and solvent recovery to 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, adds 4 times of amount n-butyl alcohol, shaking out 8 times, merge n-butyl alcohol liquid, measuring relative density during decompression and solvent recovery to 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 7.5, 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, 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 3h, 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; The content of flavones ingredient accounts in the preparation 62% 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, measuring relative density when extracting solution is concentrated into 60 ℃ is 1.05～1.15, add 1 times of amount n-butyl alcohol, shaking out 1 time, merge n-butyl alcohol liquid, measuring relative density during decompression and solvent recovery to 60 ℃ is 1.05～1.15, dry Radix Ophiopogonis extract;

B, get the Herba Erigerontis medical material, add 5 times of volume 50% alcohol reflux 1 time, each 0.5 hour, measuring relative density during extracting solution decompression and solvent recovery to 60 ℃ is 1.05～1.15, add 1 times of amount ethyl acetate, shaking out 1 time, combined ethyl acetate liquid, measuring relative density during decompression and solvent recovery to 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, measuring relative density when extracting solution is concentrated into 60 ℃ is 1.05～1.15, add 1 times of amount n-butyl alcohol, shaking out 1 time, merge n-butyl alcohol liquid, measuring relative density during decompression and solvent recovery to 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, regulating pH value is 5.8, boils, 8 ℃ of cold preservations 12 hours, 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 7% of total solid after deduction adjuvant amount and the water quantities; The content of flavones ingredient accounts in the preparation 18% 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 10 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, add 2 times of amount n-butyl alcohol, shaking out 3 times merges n-butyl alcohol liquid, measuring relative density during decompression and solvent recovery to 60 ℃ is 1.05～1.15, dry Radix Ophiopogonis extract;

B, get the Herba Erigerontis medical material, add 5 times of volume 60% alcohol reflux 2 times, each 0.5 hour, measuring relative density during extracting solution decompression and solvent recovery to 60 ℃ is 1.05～1.15, add 2 times of amount ethyl acetate, shaking out 2 times, combined ethyl acetate liquid, measuring relative density during decompression and solvent recovery to 60 ℃ is 1.05～1.15, dry Herba Erigerontis extract;

C, get the ginseng crude drug, add 12 times of volume 70% alcohol reflux 1 time, each 1.5 hours, measuring relative density when extracting solution is concentrated into 60 ℃ is 1.05～1.15, add 1 times of amount n-butyl alcohol, measuring relative density when shaking out 3 times, n-butyl alcohol liquid decompression and solvent recovery to 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 flavones ingredient accounts in the preparation 1.1% 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 9 times of volume decoctings boils 2 times, each 2 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, adds 3 times of amount n-butyl alcohol, shaking out 3 times, merge n-butyl alcohol liquid, measuring relative density during decompression and solvent recovery to 60 ℃ is 1.05～1.15, dry Radix Ophiopogonis extract;

B, get the Herba Erigerontis medical material, add 12 times of volume 70% alcohol reflux 3 times, each 1.5 hours, measuring relative density when merge extractive liquid,, decompression and solvent recovery to 60 ℃ is 1.05～1.15, adds 2 times and measures ethyl acetate, shaking out 5 times, measuring relative density when combined ethyl acetate liquid, decompression and solvent recovery to 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, 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 regulating pH value is 7, 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 saponin component accounts in the preparation 1.2% of total solid after deduction adjuvant amount and the water quantities.

Embodiments of the invention 6: 300 parts of 100 parts of Herba Erigerontiss of 150 parts of Radix Ginseng Rubra Radix Ophiopogonis

Add A, Radix Ophiopogonis 8 times of volumes, 60% alcohol reflux 2 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add 2 times of amount n-butyl alcohol, shaking out 3 times merges n-butyl alcohol liquid, measuring relative density during decompression and solvent recovery 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, measuring relative density when merge extractive liquid,, decompression and solvent recovery to 60 ℃ is 1.05～1.15, adds 3 times and measures ethyl acetate, shaking out 4 times, measuring relative density when combined ethyl acetate liquid, decompression and solvent recovery to 60 ℃ is 1.05～1.15, dry Herba Erigerontis extract;

C, get the Radix Ginseng Rubra medical material, add 10 times of volume 60% alcohol reflux 2 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, adds 2 times of amount n-butyl alcohol, shaking out 4 times, merge n-butyl alcohol liquid, measuring relative density during decompression and solvent recovery 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 1.5% active carbon, boil, keep little 50min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, regulating pH value is 6.5, boils, 4 ℃ 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 2h; Be warming up to 20 ℃, keep 3h, under aseptic condition, divide to install to promptly to get the freeze dry sterile powder end in the cillin bottle.After testing: the content of saponin component accounts in the preparation 1% of total solid after deduction adjuvant amount and the water quantities; 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 7: 400 parts of 100 parts of Herba Erigerontiss of 100 parts of Radix Codonopsis Radix Ophiopogonis

A, get medical material Radix Ophiopogonis, adding 10 times of volume decoctings boils 2 times, each 2 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, adds 2 times of amount n-butyl alcohol, shaking out 3 times, merge n-butyl alcohol liquid, measuring relative density during decompression and solvent recovery 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 2.5 hours, merge extractive liquid,, measuring relative density during decompression and solvent recovery to 60 ℃ is 1.05～1.15, add 1 times of amount ethyl acetate, shaking out 3 times, combined ethyl acetate liquid, measuring relative density during decompression and solvent recovery to 60 ℃ is 1.05～1.15, dry Herba Erigerontis extract;

C, get codonopsis pilosula, add 10 times of volume 60% alcohol reflux 2 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, adds 2 times of amount n-butyl alcohol, shaking out 4 times, merge n-butyl alcohol liquid, measuring relative density during decompression and solvent recovery to 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, regulating pH value is 5.5, boils, 6 ℃ 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.

Embodiments of the invention 8: 600 parts of 100 parts of Herba Erigerontiss of 150 parts of Radix Ginseng Rubra Radix Ophiopogonis

C, get the Radix Ginseng Rubra medical material, add 10 times of volume 60% alcohol reflux 2 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, adds 2 times of amount n-butyl alcohol, shaking out 4 times, merge n-butyl alcohol liquid, measuring relative density during decompression and solvent recovery to 60 ℃ is 1.05～1.15, dry Radix Codonopsis 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 0.8% active carbon, boil, keep little 40min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, adjust pH is 6.5, boils, 6 ℃ of cold preservations 12 hours, coarse filtration, fine straining, in inlet temperature is 140 ℃, and leaving air temp is 60 ℃, and air velocity is 16ms ^-1Condition under spray drying get powder, packing promptly gets the spray drying sterilized powder.After testing, it is 41% that the content of flavones ingredient accounts for the total solid of deducting adjuvant amount and water quantities in the preparation, and it is 32% that the content of saponin component accounts for the total solid of deducting adjuvant amount and water quantities in the preparation.

Embodiments of the invention 9: 200 parts of 50 parts of Herba Erigerontiss of 50 parts of Radix Ginsengs Radix Ophiopogonis

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 8 ℃ of cold preservations 12 hours, coarse filtration, fine straining, add the injection water, packing is under 125 ℃ of conditions, sterilized 60 minutes, and promptly got the glucose intravenous infusion agent.

Embodiments of the invention 10: 500 parts of 200 parts of Herba Erigerontiss of 200 parts of Radix Codonopsis Radix Ophiopogonis

C, get and work as codonopsis pilosula, 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, adds 2 times of amount n-butyl alcohol, shaking out 5 times, merge n-butyl alcohol liquid, measuring relative density during decompression and solvent recovery to 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, add the sodium chloride of ormal weight again, by volume add 0.5% active carbon, boil, keep little 10min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, and regulating pH value is 6.5, 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 sodium chloride intravenous infusion agent.

Embodiments of the invention 11: 500 parts of 200 parts of Herba Erigerontiss of 200 parts of Radix Ginsengs Radix Ophiopogonis

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 1.5% pH active carbon, boil, keep little 50min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, regulating pH value is 6, boils, 1 ℃ of cold preservation 12 hours, coarse filtration, fine straining divide to install in the enamel tray, temperature-45 ℃, pre-freeze time 12h, the beginning evacuation, and be warming up to-37 ℃, 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, under aseptic condition, divide to install to promptly to get the freeze dry sterile powder end in the cillin bottle.

Embodiments of the invention 12: 300 parts of 125 parts of Herba Erigerontiss of 125 parts of Radix Ginsengs Radix Ophiopogonis

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 1.5% active carbon, boil, keep little 60min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 7.5, boil, 8 ℃ of cold preservations 12 hours, 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.

Embodiments of the invention 13: 300 parts of 125 parts of Herba Erigerontiss of 125 parts of Radix Ginsengs Radix Ophiopogonis

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, adjust pH 5.5, 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.

Embodiments of the invention 14: 300 parts of 125 parts of Herba Erigerontiss of 125 parts of Radix Ginsengs Radix Ophiopogonis

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 1.5% active carbon, boil, keep little 60min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, transfer pH value 7.5, boil, at 8 ℃ of cold preservations 12 hours, coarse filtration, fine straining, add the injection water, packing is under 125 ℃ of conditions, sterilized 60 minutes, and promptly got the sodium chloride intravenous infusion agent.

Embodiments of the invention 15: 300 parts of 125 parts of Herba Erigerontiss of 125 parts of Radix Ginsengs Radix Ophiopogonis

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% pH active carbon, boil, keep little 10min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, tone pitch 5.5 boiled, 1 ℃ of cold preservation 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 16: 300 parts of 125 parts of Herba Erigerontiss of 125 parts of Radix Ginsengs Radix Ophiopogonis

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 1.5% 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

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 is added suitable adjuvant and be made through extracting the extract that obtains after refining by corresponding weight portion medical material.

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 made through extracting refining and adding suitable adjuvant by 50～1000 parts of 10～500 parts of 10～500 parts of Radix Ophiopogonis, Radix Ginseng and Herba Erigerontiss, or is added suitable adjuvant and be made through extracting the extract that obtains after refining by corresponding weight portion medical material.

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 made through extracting refining and adding suitable adjuvant by 200～500 parts of 50～200 parts of 50～200 parts of Radix Ophiopogonis, Radix Ginseng and Herba Erigerontiss, or is added suitable adjuvant and be made through extracting the extract that obtains after refining 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, 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:

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:

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:

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.With suitable adjuvant aqueous solution, with above-mentioned filtrate mixing, filter, packing, temperature-45 ℃, pre-freeze time 10h, the beginning evacuation, and in 12～72 hours differential gradient increased temperature to 10 ℃ progressively, keep 2h, be warming up to 20 ℃, keep 2h, promptly.

11, according to any described preparation method with traditional medicine Injectio of human body immunity improving power, treatment cardiovascular and cerebrovascular disease among the claim 7-10, it is characterized in that: the adjuvant that is adopted in the preparation process comprises one or more in mannitol, galactose, glycine, glucose, sodium chloride, dextran, glycerol, ethanol, propylene glycol, Polyethylene Glycol, sorbitol, tween, the poloxamer.

12, according to any described traditional medicine Injectio with human body immunity improving power, treatment cardiovascular and cerebrovascular disease among the claim 1-10, it is characterized in that: Radix Ginseng can also be the Radix Ginseng Rubra or the Radix Codonopsis of equivalent.