CN1935233A

CN1935233A - Chinese medicine injection preparation and its preparing method

Info

Publication number: CN1935233A
Application number: CN 200610111679
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: 2007-03-28

Abstract

The present invention relates to a Chinese medicine injection preparation for raising immunity of human body and curing angiocardiopathy and cerebrovascular disease and its preparation method. Said Chinese medicine injection preparation prescription is formed from ophiopogon tuber, ginseng or red ginseng or pilose asiabell root and erigeron breviscapus. Said invention adopts organic solvent extraction process to purify the extract of medicinal material. Said Chinese medicine injection preparation can be mainly used for curing the diseases of coronary heart disease, angina pectoris, arrhythmia, cerebral thrombosis and senile dementia, etc.

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 cardiovascular and cerebrovascular disease 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.And Chinese medicine is particular about the multicomponent synergism, makes its performance better therapeutic.Therefore, invent a kind of good effect, untoward reaction few, to the cardiovascular and cerebrovascular disease Different types of etiopathogenises produce the medicament composing prescription of synergistic therapeutic action and preparation thereof, technology is necessary.

The applicant drafts prescription: Radix Ophiopogonis, Radix Ginseng, breviscapine from the medicine of several respects researchs such as Chinese medicine traditional theory, pathomechanism treatment cardiovascular and cerebrovascular disease.From Chinese medicine theoretically, Radix Ginseng QI invigorating reinforcing the heart; Radix Ophiopogonis YIN nourishing and the production of body fluid promoting, Fu Mai; Herba Erigerontis have 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 breviscapine, Radix Ginseng, Radix Ophiopogonis good removing reactive oxygen free radical.Inventor's process discovers that three's compatibility result of use is better than the single medicine, and through the effective ingredient that extraction process of the present invention prepares, has removed impurity and kept plurality of active ingredients in the medicine, thereby made the effect of preparation better.

Summary of the invention

The object of the present invention is to provide a kind of ejection preparation and preparation method thereof with human body immunity improving power, treatment cardiovascular and cerebrovascular disease; The present invention utilizes the Radix Ginseng strongly invigorating primordial QI, and Radix Ophiopogonis, the effect and the breviscapine of YIN nourishing and the production of body fluid promoting were combined into a kind of preparation that can effectively treat cardiovascular and cerebrovascular disease.The present invention is directed to prior art, at different medical materials, adopt the mode of separately extracting, both can effectively extract active component, can under the situation that guarantees active component, remove impurity targetedly simultaneously, sample is made with extra care, make injection, make the faster performance curative effect of medicine performance, can be used for the treatment of cardiovascular and cerebrovascular disease acute attack stage.

Technical solution of the present invention is achieved in that according to components by weight percent and calculates, it is refiningly added suitable adjuvant and is made through extracting by 0.001～150 part of 10～1000 parts of 10～1000 parts of Radix Ophiopogonis, Radix Ginseng and breviscapine, or adds the injection that suitable adjuvant is made by corresponding weight portion medical material through extracting the extract and the corresponding weight portion breviscapine that obtain after refining.Described traditional medicine Injectio with human body immunity improving power, treatment cardiovascular and cerebrovascular disease, calculate according to components by weight percent, it is refiningly added suitable adjuvant and is made through extracting by 0.01～100 part of 10～500 parts of 10～500 parts of Radix Ophiopogonis, Radix Ginseng and breviscapine, or adds the injection that suitable adjuvant is made by corresponding weight portion medical material through extracting the extract and the corresponding weight portion breviscapine that obtain after refining.Specifically, calculate according to components by weight percent, it is refiningly added suitable adjuvant and is made through extracting by 0.05～50 part of 50～200 parts of 50～200 parts of Radix Ophiopogonis, Radix Ginseng and breviscapine, or is added suitable adjuvant and be made through extracting the extract that obtains after refining and corresponding weight portion breviscapine by corresponding weight portion medical material.

The Radix Ginseng that the present invention relates to can also be the Radix Ginseng Rubra or the Radix Codonopsis of equivalent.

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.

Of the present invention have human body immunity improving power, the treatment cardiovascular and cerebrovascular disease traditional medicine Injectio in contain saponin component, polysaccharide composition and flavones ingredient, calculate according to percentage by weight, wherein the content of saponin component is not less than 1% of the total solid after the deduction adjuvant amount and water quantities in the preparation; The content of scutellarin should be 80%～120% of labelled amount in the preparation, and all can survey the saponin component in the preparation, flavones ingredient and other the composition sum and be not less than 25% of the total solid after the deduction adjuvant amount and water quantities in the preparation.

Preparation method with traditional medicine Injectio of human body immunity improving power, treatment cardiovascular and cerebrovascular disease of the present invention: Radix Ophiopogonis, Radix Ginseng two flavor medical materials add water or ethanol extraction respectively, extracting solution carry out suitably concentrating crude extract or further adopt one or more methods in alcohol deposition method, water precipitating method, acid-base precipitation method, flocculent precipitation, column chromatography, the solvent extraction to mix to use refining extract, material crude extract or refining extract and the breviscapine adding different auxiliary material of getting it filled is made various ejection preparations.

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, add 1～4 times of amount n-butyl alcohol, shaking out 1～8 time merges n-butyl alcohol liquid, measuring relative density during decompression and solvent recovery to 60 ℃ is 1.05～1.15, water liquid after the extraction adds ethanol precipitate with ethanol twice, makes that to contain the alcohol amount be 50～70% for the first time, makes that to contain the alcohol amount be 80～90% for the second time, filter, the concentrated solution of filtrate and front merges, and measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;

B, get 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, Radix Ginseng extract and breviscapine are merged, add adjuvant and make different ejection preparations.

Injection of the present invention prepares like this:

A, get medical material Radix Ophiopogonis, adding 10 times of volume decoctings boils 3 times, each 1.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add 2 times of amount n-butyl alcohol, shaking out 5 times merges n-butyl alcohol liquid, measuring relative density during decompression and solvent recovery to 60 ℃ is 1.05～1.15, water liquid after the extraction adds ethanol precipitate with ethanol twice, makes that to contain the alcohol amount be 60% for the first time, makes that to contain the alcohol amount be 85% for the second time, filter, the concentrated solution of filtrate and front merges, and measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;

B, get 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;

Injection of the present invention specifically prepares like this:

Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 0.1%～1.5% active carbon, boil, keep little 10～60min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfers pH value 5.5～7.5, boils, at 1～8 ℃ of cold preservation 12 hours, coarse filtration, fine straining.Mannitol is added the injection water be mixed with 50～150mg/ml solution,, filter packing with above-mentioned filtrate mixing, temperature-55～-45 ℃, pre-freeze time 8～12h, the beginning evacuation, and be warming up to-43～-37 ℃, keep 6～10h, be warming up to-33～-27 ℃ again, keep 6～10h; Be warming up to-23～-17 ℃, keep 6～10h, be warming up to-13～-7 ℃, keep 4～6h, be warming up to-3～3 ℃, keep 4～6h, be warming up to 7～13 ℃, keep 1～3h, be warming up to 17～23 ℃, keep 1～3h, promptly get the aseptic block of lyophilizing.

Injection with small volume in the injection of the present invention or concentrated solution for injection are preparations 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, add 2 times of amount n-butyl alcohol, shaking out 5 times merges n-butyl alcohol liquid, measuring relative density during decompression and solvent recovery to 60 ℃ is 1.05～1.15, water liquid after the extraction adds ethanol precipitate with ethanol twice, makes that to contain the alcohol amount be 60% for the first time, makes that to contain the alcohol amount be 85% for the second time, filter, the concentrated solution of filtrate and front merges, and measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;

B, get 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, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 0.1%～1.5% active carbon, boil, keep little 10～60min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.5～7.5, boil, 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 comprises the glucose intravenous infusion agent, is to prepare like this:

Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, add the glucose of ormal weight again, by volume add 0.1%～1.5% active carbon, boil, keep little 10～60min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, transfer pH value 5.5～7.5, boil, 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 also comprises the sodium chloride intravenous infusion agent, is to prepare like this:

Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, add the sodium chloride of ormal weight again, by volume add 0.1%～1.5% active carbon, boil, keep little 10～60min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, transfer pH value 5.5～7.5, boil, 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 end in the injection of the present invention is preparation like this:

Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 0.1%～1.5% active carbon, boil, keep little 10～60min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfers pH value 5.5～7.5, boils, 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 is preparation like this:

Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 0.1%～1.5% active carbon, boil, keep little 10～60min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, and adjust pH 5.5～7.5 boils, 1～8 ℃ of cold preservation 12 hours, coarse filtration, fine straining are 140～160 ℃ in inlet temperature, and leaving air temp is 60～80 ℃, air velocity is that spray drying gets powder under the condition of 16～20ms-1, and packing promptly gets the spray drying sterilized powder.

Preparation method with traditional medicine Injectio of human body immunity improving power, treatment cardiovascular and cerebrovascular disease of the present invention: the adjuvant that is adopted in the preparation comprises one or more in mannitol, galactose, glycine, glucose, sodium chloride, dextran, glycerol, ethanol, propylene glycol, Polyethylene Glycol, sorbitol, tween, the poloxamer.

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 breviscapine, 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 breviscapine dissolubility is low, and chemical stability problems appears in preparation easily.Through repetition test, we are adjusted to 5.5～7.5 with the medicinal liquid pH value, and this moment, medicinal liquid was relatively stable, did not produce microgranule or any cosmetic variation, and index components scutellarin content does not have too big variation, has effectively solved the problem of breviscapine stability.

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; 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, and the formulation products that obtains is the good medicine of human body immunity improving power, treatment cardiovascular and cerebrovascular disease.

The applicant has carried out a series of experiments, can prove that safety of medicine provided by the invention is effective, process stabilizing, quality controllable.

Experimental example 1: drug effectiveness research

The pharmacological research conclusion

Pilot project	Of the present invention group	The Breviscapini injection group
Pilot project	Of the present invention group	The Breviscapini injection group	Improve the rheology test of blood stasis model rat blood	Effect is remarkable, and effect strengthens	Effect is general
The antiplatelet aggregation test	Effect is remarkable, and effect strengthens	Effect is obvious	Improve the rheology test of blood stasis model rat blood	Effect is remarkable, and effect strengthens	Effect is general
The antiplatelet aggregation test	Effect is remarkable, and effect strengthens	Effect is obvious	The rabbit fibrin solubility test	Effect is obvious, and effect strengthens	Effect is general
The white mice anti-fatigue test	Effect is remarkable	DeGrain	The rabbit fibrin solubility test	Effect is obvious, and effect strengthens	Effect is general

From above-mentioned test as can be seen, therefore the combination preparation therapeutic effect proves that this prescription is reasonably, determined curative effect significantly better than the single preparation.

Experimental example 2: the medicinal material extract purifying process is investigated

2.1 Radix Ophiopogonis, technology was investigated

2.1.1 Radix Ophiopogonis, extraction process was investigated

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.Main active component is polysaccharide and saponins in Radix Ophiopogonis, and the two all has fine solubility in water, and polysaccharide composition dissolubility in water is less, therefore takes into account both extractions, and preliminary definite extraction solvent is a water.The general investigation decocts when extracting, and chooses amount of water, decocting time, decoction number of times as factor, and the varying level of each factor of high spot reviews is to decocting the influence of extraction effect.According to knowhow and practical situation, the selection factor level.

Extract the experimental factor water-glass Radix Ophiopogonis

Factor level A decocting time (h) B decocts number of times (inferior) C amount of water (doubly)

1 1 1 10

2 1.5 2 12

3 2 3 14

Orthogonal table

Factor

The A B C D rate of transform (%)

Level

1 1 1 1 1 75.26

2 1 2 2 2 81.93

3 1 3 3 3 90.06

4 2 1 2 3 81.63

5 2 2 3 1 87.65

6 2 3 1 2 91.87

7 3 1 3 2 80.42

8 3 2 1 3 86.47

9 3 3 2 1 93.1

I 247.25 237.31 253.6 256.01

II 261.15 256.05 256.66 254.22

III 259.99 275.03 258.13 258.16

I ² 61132.56 56316.04 64312.96 65541.12

II ² 68199.32 65561.6 65874.36 64627.81

III ² 67594.8 75641.5 66631.1 66646.59

K ² 196926.7 197519.1 196818.4 196815.5

S 39. 65 237.14 3.56 2.59

Analysis of variance table

Soruces of variation	Deviation square profit	Degree of freedom	Variance	The F value
Soruces of variation	Deviation square profit	Degree of freedom	Variance	The F value	A	39.65	2	19.83	15.25
B	237.14	2	118.57	91.21	A	39.65	2	19.83	15.25
B	237.14	2	118.57	91.21	C	3.56	2	1.78	1.37
D	2.59	2	1.30		C	3.56	2	1.78	1.37

From The above results as can be seen, extraction time has a significant effect to the rate of transform, therefore selects B3; Also there is certain influence extraction time to the rate of transform, but is not very remarkable, can select A2 in conjunction with the intuitive analysis result; Solvent load does not have influence to the rate of transform, just can satisfy the needs of extraction with the level of C1, so determines that extraction conditions boils each 1.5 hours 3 times for adding 10 times of volume decoctings.

2.1.2 separation purifying technique is investigated

With extraction separation and purification Radix Ophiopogonis total saponins the time, the kind of the extractant of selecting for use, solvent load are bigger to isolating influential effect, so we have carried out optimizing screening to these two conditions.

2.1.2.1 the screening of extractant

Take by weighing medical material 400g 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, be divided into two parts, add 2 times of amount solvents, shaking out 5 times, combining extraction liquid, measuring relative density during decompression and solvent recovery to 60 ℃ is 1.05～1.15, drying.The results are shown in following table:

Extractant screening table

Medical material consumption (g)	Extractant	Cream heavy (g)	Paste-forming rate (%)
Medical material consumption (g)	Extractant	Cream heavy (g)	Paste-forming rate (%)	200g	Ethyl acetate	21.03	10.52
200g	N-butyl alcohol	31.65	15.78	200g	Ethyl acetate	21.03	10.52

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.

2.1.2.2 the screening of extractant consumption

Take by weighing medical material 600g 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, be divided into three parts, add n-butyl alcohol respectively, shaking out 5 times, combining extraction liquid, measuring relative density during decompression and solvent recovery to 60 ℃ is 1.05～1.15, drying.

Extractant consumption screening table

Medical material amount (g)	The extractant consumption	Cream heavy (g)	Paste-forming rate (%)
Medical material amount (g)	The extractant consumption	Cream heavy (g)	Paste-forming rate (%)	200	1 times of amount	17.20	8.60
200	2 times of amounts	32.06	16.03	200	1 times of amount	17.20	8.60
200	2 times of amounts	32.06	16.03	200	3 times of amounts	32.71	16.36

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 guaranteeing under the sufficient prerequisite of extracts active ingredients, in order to save cost, determines that the n-butanol extraction consumption is 2 amounts.

2.2 Radix Ginseng technology is investigated

2.2.1 the Radix Ginseng extraction conditions is investigated

Radix Ginseng contains multiple saponin, polysaccharide, volatilization wet goods composition, and wherein the ginsenoside is an effective ingredient.Radix Ginseng is generally used alcohol reflux, so Radix Ginseng also adopts alcohol reflux in this technology.

2.2.1.1 the examination of concentration of alcohol

Experimental technique and data: take by weighing Radix Ginseng 100g, totally 5 parts, add 6 times respectively and measure 10%, 30%, 50%, 70%, 90% alcohol reflux, each 1 hour, extract 3 times, filter.Reclaim ethanol, drying under reduced pressure is measured Radix Ginseng total saponins content.

Concentration of alcohol is to the influence of extraction effect

The experiment number	Concentration of alcohol	Medical material weight (g)	Cream heavy (g)	Total saponin content (%)	Extraction ratio (%)
The experiment number	Concentration of alcohol	Medical material weight (g)	Cream heavy (g)	Total saponin content (%)	Extraction ratio (%)	1	10％	100.03	17.26	10.31	86.83
2	30％	100.01	15.32	11.64	86.83	1	10％	100.03	17.26	10.31	86.83
2	30％	100.01	15.32	11.64	86.83	3	50％	100.02	13.57	13.01	86.35
4	70％	100.04	12.59	14.18	87.32	3	50％	100.02	13.57	13.01	86.35
4	70％	100.04	12.59	14.18	87.32	5	90％	100.02	12.25	14.25	85.37

By table as can be seen, the extraction ratio difference of total saponins is little, proves that the ginsenoside all has dissolubility preferably in ethanol.But analyze from the content of total saponins, higher with total saponin content in 70%, 90% ethanol extraction, take all factors into consideration two indexs of extraction ratio and content, select 70% ethanol extraction.

2.2.1.2 extraction conditions screening

Experimental technique and data: take by weighing Radix Ginseng 300g, totally 3 parts, add 70% alcohol reflux respectively and filter, reclaim ethanol, drying under reduced pressure.The results are shown in following table:

Extraction conditions screening table

Extraction conditions	Medical material amount (g)	Cream heavy (g)	Extraction ratio (%)
Extraction conditions	Medical material amount (g)	Cream heavy (g)	Extraction ratio (%)	8 times of 70% ethanol extraction 2 times, each 1.5	300.03	33.42	81.79
10 times of 70% ethanol extraction 3 times, each 1 hour	300.04	43.27	91.22	8 times of 70% ethanol extraction 2 times, each 1.5	300.03	33.42	81.79
10 times of 70% ethanol extraction 3 times, each 1 hour	300.04	43.27	91.22	12 times of 70% ethanol extraction 2 times, each 2 hours	300.05	40.63	86.41

From The above results as can be seen, condition 2 is optimized extraction conditions, and determine that therefore extraction conditions is: 70% alcohol heating reflux that adds 10 times of amounts extracts each 1 hour 3 times.

Test 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

Activated carbon dosage (%)	Cream heavy (g)	The rate of transform (%)	Outward appearance
Activated carbon dosage (%)	Cream heavy (g)	The rate of transform (%)	Outward appearance	0.1	7.57	54.28	Reddish brown
1	7.36	53.64	Red	0.1	7.57	54.28	Reddish brown
1	7.36	53.64	Red	1.5	7.15	50.89	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
Time (minute)	Cream heavy (g)	The rate of transform (%)	Outward appearance	10	7.68	52.99	Reddish brown
30	7.43	52.04	Red	10	7.68	52.99	Reddish brown
30	7.43	52.04	Red	60	7.19	50.38	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, left standstill after boiling 12 hours, and observed 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
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	3.9 4.4 5.1	5.5 6.0 6.6 7.1	7.5 8.0	Dosing pH	4.5 5.0 5.5	6.0 6.5 7.0 7.5	8.0 8.5
Boil pH	3.9 4.4 5.1	5.5 6.0 6.6 7.1	7.5 8.0	Outward appearance	Precipitation appears	No significant change	Color burn

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

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

Sequence number	Dosing pH	Content during dosing (%)	Boil back pH	Boil back content (%)
Sequence number	Dosing pH	Content during dosing (%)	Boil back pH	Boil back content (%)	1	5.5	4.53	5.1	4.28
2	6.0	4.53	5.5	4.19	1	5.5	4.53	5.1	4.28
2	6.0	4.53	5.5	4.19	3	6.5	4.53	6.0	4.22
4	7.0	4.53	6.6	4.27	3	6.5	4.53	6.0	4.22
4	7.0	4.53	6.6	4.27	5	7.5	4.53	7.1	4.20

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 lyophilizing 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
The caffolding agent kind	Caffolding agent: medicinal liquid (V: V)	Solubility	The finished product outward appearance	Glucose	2∶1	Good	Part is subsided
Galactose	2∶1	Generally	Molding	Glucose	2∶1	Good	Part is subsided
Galactose	2∶1	Generally	Molding	Mannitol	2∶1	Good	Molding
Glycine	2∶1	Good	Molding, frangible	Mannitol	2∶1	Good	Molding
Glycine	2∶1	Good	Molding, frangible	Dextran	2∶1	Generally	Molding
Mannitol, propylene glycol	2∶1	Good	Molding	Dextran	2∶1	Generally	Molding
Mannitol, propylene glycol	2∶1	Good	Molding	Glycine, Polyethylene Glycol	2∶1	Good	Molding, frangible
Dextran, sorbitol, tween	2∶1	Good	Molding	Glycine, Polyethylene Glycol	2∶1	Good	Molding, frangible
Dextran, sorbitol, tween	2∶1	Good	Molding	Blank medicinal liquid	3ml		Atrophy

As seen from table, in the adjuvant that is screened, under the identical situation of other conditions, most of adjuvant all can be made into freeze-dried powder, but solubility angle integrated survey from yield rate, molding situation and sample, use the effect of mannitol to be better than other several adjuvants separately, can satisfy the every requirement of injection, reduce simultaneously as far as possible and add too much adjuvant.

4.2 caffolding agent consumption screening

The mannitol solution (50mg/ml, 100mg/ml and 150mg/ml) of variable concentrations is mixed in varing proportions with medicinal liquid, filter, every cillin bottle loading amount is 3ml, lyophilization.Lyophilisation condition :-45 ℃, behind the pre-freeze 8h, the beginning evacuation, and be warming up to-40 ℃, keep 10h; Be warming up to-30 ℃, keep 10h; Be warming up to-20 ℃, keep 10h; Be warming up to-10 ℃, keep 5h; Be warming up to 0 ℃, keep 5h; Be warming up to 15 ℃, keep 3h; Be warming up to 25 ℃, keep 3h.The result is as showing:

The screening of mannitol consumption

Numbering	Mannitol concentration (mg/ml)	Mannitol: medicinal liquid (v: v)	Color and luster	Profile	Solubility	Clarity
Numbering	Mannitol concentration (mg/ml)	Mannitol: medicinal liquid (v: v)	Color and luster	Profile	Solubility	Clarity	1	50	2∶1	Yellowish-brown	Part is subsided	Good	Up to specification
2	100	2∶1	Yellow	Intact	Good	Up to specification	1	50	2∶1	Yellowish-brown	Part is subsided	Good	Up to specification
2	100	2∶1	Yellow	Intact	Good	Up to specification	3	150	2∶1	Yellowish	Intact	Good	Up to specification

As seen from table, when the ratio of caffolding agent consumption and medicinal liquid is 2: 1, the sample character is that the sample of 100mg/ml and 150mg/ml is relatively good with the mannitol concentration, the sample of 50mg/ml has part to subside, but major part still is molding, but take all factors into consideration the consumption and the clinical dose of adjuvant, the optimum selection mannitol concentration is 100mg/ml, and the volume ratio of mannitol solution and medicinal liquid is 2: 1.

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)-12-

-40 (evacuation) 8-10

-35 (evacuation)-8-

-30 (evacuation) 10-6 keeps

-25 (evacuation)-8--70 ℃

-20 (evacuation) 8-10

-15 (evacuation)-8-

-10 (evacuation) 5-5

0 (evacuation) 556

10 (evacuation) 243

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 10h; Be warming up to-20 ℃, keep 8h; Be warming up to-10 ℃, keep 5h; Be warming up to 0 ℃, keep 5h; Be warming up to 10 ℃, keep 2h; Be warming up to 20 ℃, keep 2h, get product.

Experimental example 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 (%)
Inlet temperature (℃)	Outlet temperature (℃)	Air velocity (ms ^-1)	Loss rate (%)	140	60	16	4.57
150	70	18	3.15	140	60	16	4.57
150	70	18	3.15	160	80	20	3.69

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.)

The embodiment of the invention 1: 25 parts of 125 parts of breviscapines of 125 parts of Radix Ginsengs Radix Ophiopogonis

Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 1% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, regulating pH value is 6, boils, 4 ℃ 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 30 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 15% of total solid after deduction adjuvant amount and the water quantities; All can be surveyed the component content sum and account in the preparation 47% of total solid after deduction adjuvant amount and the water quantities.

The embodiment of the invention 2: 25 parts of 125 parts of breviscapines of 125 parts of Radix Ginsengs Radix Ophiopogonis

Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, add the glucose of ormal weight again, by volume add 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 6.5, boil, at 4 ℃ of cold preservations 12 hours, coarse filtration, fine straining, add the injection water, packing is under 110 ℃ of conditions, sterilized 40 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; The content of scutellarin be in the preparation labelled amount 80%.

The embodiment of the invention 3: 25 parts of 125 parts of breviscapines of 125 parts of Radix Ginsengs Radix Ophiopogonis

Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 1% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transferring pH value is 7, boils, 4 ℃ of cold preservations 12 hours, coarse filtration, fine straining, divide to install in the enamel tray pre-freeze temperature-45 ℃, pre-freeze time 10h;-40 ℃ of evacuation keep 8h; Be warming up to-30 ℃ again, keep 10h; Be warming up to-20 ℃, keep 8h; Be warming up to-10 ℃, keep 5h; Be warming up to 0 ℃, keep 5h; Be warming up to 10 ℃, keep 2h; Be warming up to 20 ℃, keep 2h, under aseptic condition, divide to install to promptly to get the freeze dry sterile powder end in the cillin bottle.After testing: the content of saponin component accounts in the preparation 15% of total solid after deduction adjuvant amount and the water quantities; The content of scutellarin be in the preparation labelled amount 120%.

The embodiment of the invention 4: 25 parts of 125 parts of breviscapines of 125 parts of Radix Ginsengs Radix Ophiopogonis

Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 1% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, regulating pH value is 6, boils, 4 ℃ of cold preservations 12 hours, coarse filtration, fine straining, in inlet temperature is 150 ℃, and leaving air temp is 70 ℃, and air velocity is 18ms ^-1Condition under spray drying get powder, packing promptly gets the spray drying sterilized powder.After testing: the content of saponin component accounts in the preparation 17% of total solid after deduction adjuvant amount and the water quantities; All can be surveyed the component content sum and account in the preparation 45% of total solid after deduction adjuvant amount and the water quantities.

Embodiments of the invention 5: 150 parts of 1000 parts of breviscapines of 1000 parts of Radix Ginsengs Radix Ophiopogonis

A, get medical material Radix Ophiopogonis, adding 15 times of volume decoctings boils 4 times, each 2.5 hours, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add 4 times of amount n-butyl alcohol, shaking out 8 times merges n-butyl alcohol liquid, measuring relative density during decompression and solvent recovery to 60 ℃ is 1.05～1.15, water liquid after the extraction adds ethanol precipitate with ethanol twice, makes that to contain the alcohol amount be 70% for the first time, makes that to contain the alcohol amount be 90% for the second time, filter, the concentrated solution of filtrate and front merges, and measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;

B, get 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, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 1% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, and regulating pH value is 6, 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-55 ℃, pre-freeze time 12h with above-mentioned filtrate mixing;-43 ℃ of evacuation keep 10h; Be warming up to-33 ℃ again, keep 10h; Be warming up to-23 ℃, keep 10h; Be warming up to-13 ℃, keep 6h; Be warming up to-3 ℃, keep 6h; Be warming up to 7 ℃, keep 3h; Be warming up to 17 ℃, keep 3h, promptly get freeze-dried powder.After testing: the content of saponin component accounts in the preparation 33% of total solid after deduction adjuvant amount and the water quantities; All can be surveyed the component content sum and account in the preparation 80% of total solid after deduction adjuvant amount and the water quantities.

Embodiments of the invention 6: 0.001 part of 10 parts of breviscapine of 10 parts of Radix Ginsengs Radix Ophiopogonis

A, get medical material Radix Ophiopogonis, adding 5 times of volume decoctings boiled 1 time 0.5 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, 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, and the water liquid after the extraction adds the ethanol precipitate with ethanol twice, make for the first time that to contain the alcohol amount be 50%, make for the second time that to contain the alcohol amount be 80%, filter the concentrated solution merging of filtrate and front, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;

B, get the ginseng crude drug, added 5 times of volumes, 50% alcohol reflux 1 time 0.5 hour, 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, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 0.1% active carbon, boil, keep little 60min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, regulating pH value is 7.5, boils, 8 ℃ of cold preservations 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 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 1% of total solid after deduction adjuvant amount and the water quantities; All can be surveyed the component content sum and account in the preparation 25% of total solid after deduction adjuvant amount and the water quantities.

0.05 part of 50 parts of breviscapine of 50 parts of Radix Ginsengs, 7 Radix Ophiopogonis of embodiment

Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, add the sodium chloride of ormal weight again, by volume add 1.5% active carbon, boil, keep little 60min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, and regulating pH value is 7.5, boil, at 1 ℃ of cold preservation 12 hours, coarse filtration, fine straining, add the injection water, packing is under 125 ℃ of conditions, sterilized 20 minutes, and promptly got the sodium chloride intravenous infusion agent.After testing: the content of saponin component accounts in the preparation 5.6% of total solid after deduction adjuvant amount and the water quantities; All can be surveyed the component content sum and account in the preparation 37% of total solid after deduction adjuvant amount and the water quantities.

Embodiments of the invention 8: 50 parts of 200 parts of breviscapines of 200 parts of Radix Ginsengs Radix Ophiopogonis

A, get medical material Radix Ophiopogonis, adding 8 times of volume decoctings boils 2 times, each 0.5 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 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 ginseng crude drug, added 6 times of volumes, 70% 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, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 0.1% active carbon, boil, keep little 10min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, and regulating pH value is 6.5, boils, at 6 ℃ of cold preservations 12 hours, coarse filtration, fine straining.Mannitol is added the injection water be mixed with 50mg/ml solution,, filter with above-mentioned filtrate mixing, packing, temperature-45 ℃, pre-freeze time 8h, the beginning evacuation, and be warming up to-37 ℃, and keep 6h, be warming up to-27 ℃ again, keep 6h; Be warming up to-17 ℃, keep 6h, be warming up to-7 ℃, keep 4h, be warming up to 3 ℃, keep 4h, be warming up to 13 ℃, keep 1h, be warming up to 23 ℃, keep 1h, promptly get the aseptic block of lyophilizing.After testing: the content of saponin component accounts in the preparation 19% of total solid after deduction adjuvant amount and the water quantities; All can be surveyed the component content sum and account in the preparation 54% of total solid after deduction adjuvant amount and the water quantities.

Embodiments of the invention 9: 100 parts of 500 parts of breviscapines of 500 parts of Radix Ginseng Rubra Radix Ophiopogonis

A, get medical material Radix Ophiopogonis, adding 10 times of volume decoctings boils 2 times, each 1 hour, 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, water liquid after the extraction adds ethanol precipitate with ethanol twice, makes that to contain the alcohol amount be 65% for the first time, makes that to contain the alcohol amount be 80% for the second time, filter, the concentrated solution of filtrate and front merges, and measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;

B, get the Radix Ginseng Rubra 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 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 Ginseng Rubra extract.

Above-mentioned Radix Ophiopogonis extract, Radix Ginseng Rubra extract and breviscapine are merged, add an amount of water for injection dissolving, add the sodium chloride of ormal weight again, by volume add 0.8% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, adjust pH 5.5～7.5, 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 26% of total solid after deduction adjuvant amount and the water quantities; All can be surveyed the component content sum and account in the preparation 78% of total solid after deduction adjuvant amount and the water quantities.

Embodiments of the invention 10: 1 part of 100 parts of breviscapine of 80 parts of Radix Ginsengs Radix Ophiopogonis

Add A, Radix Ophiopogonis 8 times of volumes, 60% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, add 1 times of amount n-butyl alcohol, shaking out 5 times merges n-butyl alcohol liquid, measures relative density during decompression and solvent recovery to 60 ℃ and be 1.05～1.15 dry Radix Ophiopogonis extracts;

B, get the ginseng crude drug, adding 12 times of volume decoctings boils 3 times, each 0.5 hour, measuring relative density when merge extractive liquid, is concentrated into 60 ℃ is 1.05～1.15, add 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, and the water liquid after the extraction adds ethanol precipitate with ethanol twice, makes that to contain the alcohol amount be 55% 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, will twice precipitation merges the back and adds 1 times of water dissolution, filter, the concentrated solution of filtrate and front merges, and measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ginseng extract that gets.The dry Radix Ginseng extract that gets.

Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 0.8% active carbon, boil, keep little 40min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, adjust pH 5.5 boiled, 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 2h, under aseptic condition, divide to install to promptly to get the freeze dry sterile powder end in the cillin bottle.

Embodiments of the invention 11: 0.1 part of 120 parts of breviscapine of 100 parts of Radix Codonopsis Radix Ophiopogonis

A, get medical material Radix Ophiopogonis, adding 8 times of volume decoctings boils 3 times, each 1 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, 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 codonopsis pilosula, add 12 times of volume 60% 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 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, Radix Codonopsis extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 0.6% active carbon, boil, keep little 40min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, adjust pH 7.5 boiled, 6 ℃ of cold preservations 12 hours, coarse filtration, fine straining, in inlet temperature is 150 ℃, and leaving air temp is 70 ℃, and air velocity is 18ms ^-1Condition under spray drying get powder, packing promptly gets the spray drying sterilized powder.

Embodiments of the invention 12: 0.8 part of 150 parts of breviscapine of 180 parts of Radix Ginsengs Radix Ophiopogonis

A, get medical material Radix Ophiopogonis, add 6 times of volume decoctings and boil 3 times, each 0.5 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, dry Radix Ophiopogonis extract;

B, get the ginseng crude drug, added 8 times of volumes, 60% alcohol reflux 1 time 1.5 hours, measuring relative density when extracting solution is concentrated into 60 ℃ is 1.05～1.15, dry Radix Ginseng extract;

Above-mentioned Radix Ophiopogonis extract, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 0.3% active carbon, boil, keep little 60min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfer pH value 5.5, boil, 6 ℃ 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: 50 parts of 200 parts of breviscapines of 200 parts of Radix Ginseng Rubra Radix Ophiopogonis

A, get medical material Radix Ophiopogonis, adding 6 times of volume decoctings boils 3 times, each 2 hours, merge extractive liquid,, merge extractive liquid,, filter, filtrate is crossed ZTC-1 type macroporous adsorptive resins with the speed of 0.3ml/g medical material .min, water with 6 times of resin volumes washes with the speed of 0.4ml/g medical material .min earlier, and 15% ethanol of 4 times of resin volumes of reuse is used the speed eluting of 70% ethanol of 5 times of resin volumes with 0.8ml/g medical material .min at last with the speed eluting impurity of 1.0ml/g medical material .min, collect stripping liquid, reclaim ethanol, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis extract that gets;

B, get the Radix Ginseng Rubra medical material, add 10 times of volume 80% alcohol reflux 2 times, each 1.5 hours, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water dissolution that adds 4 times of medical material volumes, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.5ml/g medical material .min, use 5 times of resinite hydrops and 6 times of resin volume 10% alcohol flushing impurity successively, use 60% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Radix Ginseng Rubra extract;

Above-mentioned Radix Ophiopogonis extract, Radix Ginseng Rubra extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 0.6% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, adjust pH 7.5 boiled, 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 10h; Be warming up to-20 ℃, keep 8h; Be warming up to-10 ℃, keep 5h; Be warming up to 0 ℃, keep 5h; Be warming up to 10 ℃, keep 2h; Be warming up to 20 ℃, keep 2h, under aseptic condition, divide to install to promptly to get the freeze dry sterile powder end in the cillin bottle.The content of scutellarin is 99.6% of preparation labelled amount.

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 refiningly added suitable adjuvant and is made through extracting by 0.001～150 part of 10～1000 parts of 10～1000 parts of Radix Ophiopogonis, Radix Ginseng and breviscapine, or adds the injection that suitable adjuvant is made by corresponding weight portion medical material through extracting the extract and the corresponding weight portion breviscapine that obtain after refining.

2, according to the described traditional medicine Injectio of claim 1 with human body immunity improving power, treatment cardiovascular and cerebrovascular disease, it is characterized in that: calculate according to components by weight percent, it is refiningly added suitable adjuvant and is made through extracting by 0.01～100 part of 10～500 parts of 10～500 parts of Radix Ophiopogonis, Radix Ginseng and breviscapine, or adds the injection that suitable adjuvant is made by corresponding weight portion medical material through extracting the extract and the corresponding weight portion breviscapine that obtain after refining.

3, according to claim 1 or 2 described traditional medicine Injectios with human body immunity improving power, treatment cardiovascular and cerebrovascular disease, it is characterized in that: calculate according to components by weight percent, it is refiningly added suitable adjuvant and is made through extracting by 0.05～50 part of 50～200 parts of 50～200 parts of Radix Ophiopogonis, Radix Ginseng and breviscapine, or is added suitable adjuvant and be made through extracting the extract that obtains after refining and corresponding weight portion breviscapine by corresponding weight portion medical material.

4, according to any described traditional medicine Injectio with human body immunity improving power, treatment cardiovascular and cerebrovascular disease of claim 1-3, it is characterized in that: injection comprises: be directly used in drug administration by injection injection, need to be used for the concentrated solution for injection of intravenous drip after the dilution, directly for the venous transfusion of intravenous drip and injectable sterile powder and the aseptic block that makes with freeze-drying or spray drying method.

5, according to the described traditional medicine Injectio of claim 4 with human body immunity improving power, treatment cardiovascular and cerebrovascular disease, it is characterized in that: contain saponin component and flavones ingredient in the preparation, calculate according to percentage by weight, wherein the content of saponin component is not less than 1% of the total solid after the deduction adjuvant amount and water quantities in the preparation; The content of scutellarin should be 80%～120% of labelled amount in the preparation.

6, according to the described traditional medicine Injectio of claim 5 with human body immunity improving power, treatment cardiovascular and cerebrovascular disease, it is characterized in that: calculate according to percentage by weight, all can survey the saponin component in the preparation, flavones ingredient and other the composition sum and be not less than 25% of the total solid after the deduction adjuvant amount and water quantities in the preparation.

7, the preparation method with traditional medicine Injectio of human body immunity improving power, treatment cardiovascular and cerebrovascular disease as claimed in claim 4, it is characterized in that: Radix Ophiopogonis, Radix Ginseng two flavor medical materials add water or ethanol extraction respectively, extracting solution carry out suitably concentrating crude extract or further adopt one or more methods in alcohol deposition method, water precipitating method, acid-base precipitation method, flocculent precipitation, column chromatography, the solvent extraction to mix to use refining extract, material crude extract or refining extract and the breviscapine adding different auxiliary material of getting it filled is made various ejection preparations.

8, the preparation method with traditional medicine Injectio of human body immunity improving power, treatment cardiovascular and cerebrovascular disease as claimed in claim 7 is characterized in that:

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, Radix Ginseng extract and breviscapine are merged, add an amount of water for injection dissolving, by volume add 1.0% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, transfers pH value 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 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.