CN1935231A

CN1935231A - Chinese medicine injection preparation and its preparing method

Info

Publication number: CN1935231A
Application number: CN 200610111677
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. It is characterized by that the prescription of said Chinese medicine injection preparation is formed from the Chinese medicinal materials of ophiopogon tuber, ginseng or red ginseng or pilose asiabell root and erigeron breviscapus. Said invention also provides the concrete steps of its preparation method, and said Chinese medicine injection preparation can obtain good therapeutic effect for curing the diseases of coronary heart disease, angina pectoris, arrhythmia, cerebral thrombosis and senile dementia, etc.

Description

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.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, 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 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, 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, at different medical materials, adopt the mode of separately extracting, both can effectively extract active component, simultaneously can be under the situation that guarantees active component, remove impurity targetedly, sample is made with extra care, add that the treatment of cardiovascular and cerebrovascular disease acute attack stage is extremely important, preparation of the present invention is mainly injection, make medicine performance curative effect fast, the availability height is fit to the treatment of cardiovascular and cerebrovascular disease.

Technical solution of the present invention is achieved in that a kind of traditional medicine Injectio with human body immunity improving power, treatment cardiovascular and cerebrovascular disease: calculate according to parts by weight, 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.Described traditional medicine Injectio: calculate according to parts by weight with human body immunity improving power, treatment cardiovascular and cerebrovascular disease, 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.Specifically, it is made the present invention 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.

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 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, and 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.

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, crude extract or extract are added different auxiliary material make various ejection preparations.

Preparation method with traditional medicine Injectio of human body immunity improving power, treatment cardiovascular and cerebrovascular disease 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,, merge extractive liquid,, filter, filtrate is crossed ZTC-1 type macroporous adsorptive resins with the speed of 0.3～0.8ml/g medical material .min, water with 3～10 times of resin volumes washes with the speed of 0.5～1.5ml/g medical material .min earlier, 5～25% ethanol of 1～4 times of resin volume of reuse are with the speed eluting impurity of 0.5～1.5ml/g medical material .min, use the speed eluting of 50～70% ethanol of 2～6 times of resin volumes at last with 0.5～1.0ml/g medical material .min, collect stripping liquid, reclaiming and measuring relative density when ethanol is concentrated into 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis total saponins that gets;

B, get the Herba Erigerontis medical material, add 5～15 times of volume 50～80% alcohol reflux 1～4 time, each 0.5～2.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 1～5 times of medical material volume, filter, filtrate is crossed AB-8 type macroporous adsorbent resin with the speed of 0.1～0.8ml/g medical material .min, use 1～10 times of resinite hydrops and 1～6 times of resin volume 5～15% alcohol flushing impurity successively, use 30～70% alcohol desorptions of 1～7 times of resin volume then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Herba Erigerontis total flavones;

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 during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water dissolution that adds 1～5 times of medical material volume, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.3～1.5ml/g medical material .min, use 1～10 times of resinite hydrops and 1～6 times of resin volume 5～15% alcohol flushing impurity successively, use 30～70% alcohol desorptions of 1～7 times of resin volume then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Radix Ginseng total saponins;

Above-mentioned Radix Ophiopogonis total saponins, Herba Erigerontis total flavones and Radix Ginseng total saponins are merged, add adjuvant and make different ejection preparations.

Exactly, aseptic block 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,, filter, filtrate is crossed ZTC-1 type macroporous adsorptive resins with the speed of 0.5ml/g medical material .min, water with 6 times of resin volumes washes with the speed of 1ml/g medical material .min earlier, 20% ethanol of 3 times of resin volumes of reuse is with the speed eluting impurity of 1ml/g medical material .min, use the speed eluting of 60% ethanol of 4 times of resin volumes at last with 0.8ml/g medical material .min, collect stripping liquid, reclaim the dry Radix Ophiopogonis total saponins that gets of ethanol;

B, get the Herba Erigerontis medical material, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 3 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin with the speed of 0.2ml/g medical material .min, use 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity successively, use 40% 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 Herba Erigerontis total flavones;

C, get the ginseng crude drug, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water dissolution that adds 4 times of medical material volumes, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 1ml/g medical material .min, use 7 times of resinite hydrops and 5 times of resin volume 10% alcohol flushing impurity successively, use 60% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Radix Ginseng total saponins;

Above-mentioned Radix Ophiopogonis total saponins, Herba Erigerontis total flavones and Radix Ginseng total saponins 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.

Injection with small volume of the present invention or concentrated solution for injection are preparations like this:

Above-mentioned Radix Ophiopogonis total saponins, Herba Erigerontis total flavones and Radix Ginseng total saponins 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.

The glucose intravenous infusion agent is preparation like this in the injection of the present invention:

Above-mentioned Radix Ophiopogonis total saponins, Herba Erigerontis total flavones and Radix Ginseng total saponins 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.

The sodium chloride intravenous infusion agent is preparation like this in the injection of the present invention:

B, the Herba Erigerontis medical material, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 3 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin with the speed of 0.2ml/g medical material .min, use 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity successively, use 40% 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 Herba Erigerontis total flavones;

Above-mentioned Radix Ophiopogonis total saponins, Herba Erigerontis total flavones and Radix Ginseng total saponins 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 total saponins, Herba Erigerontis total flavones and Radix Ginseng total saponins 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 total saponins, Herba Erigerontis total flavones and Radix Ginseng total saponins 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, 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.

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

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

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.

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 Herba Erigerontis injection group
Pilot project	Of the present invention group	The Herba Erigerontis injection group	Myocardial infarction model test due to the dog coronary artery ligation method	Effect is remarkable, and effect strengthens	Effect is general
Improve the rheology test of blood stasis model rat blood	Effect is remarkable, and effect strengthens	Effect is general		Effect is remarkable, and effect strengthens	Effect is general
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 antiplatelet aggregation test	Effect is remarkable, and effect strengthens	Effect is obvious

From above-mentioned test as can be seen, the combination preparation therapeutic effect is significantly better than single preparation group.

Experimental example 2: medical material separation condition screening

2.1 Herba Erigerontis separation condition screening

The curative effect of medicine depends primarily on the content of effective site in the raw material, therefore need separate alcoholization to effective site.Because the Chinese medicine extract complicated component, and the more close composition of character is more, and therefore the separation and purification to effective site brings big difficulty.In order to investigate the optimum condition of separation and purification Herba Erigerontis total flavones from the resin column, we investigate the principal element eluant strength, eluant consumption, the rate of outflow that influence separating effect, adopt L ₉(3 ⁴) orthogonal table tests the scientific and reasonable condition that filters out ideal separation and purification Herba Erigerontis total flavones.Get Herba Erigerontis medical material 2700g, add 8 times of volume 70% alcohol heating reflux and extract 3 times, each 1 hour, filter.Decompression filtrate recycling ethanol (60 ℃ ,-0.09MPa), being concentrated into relative density is the concentrated solution of 1.05～1.15 (60 ℃), adds the water for injection heating for dissolving of 3 times of medical material weight behind the mix homogeneously, filter.Filtrate is divided into 9 parts (are every part and are equivalent to contain medical material 300g), crosses resin column post (interior diameter: post height=50mm: 600mm, weight resin 450g, volume 600ml).Begin to wash with the speed of 0.2ml/g medical material .min medical material .h, press L then with the water for injection of 4 times of resin volumes and 15% ethanol of 4 times of resin volumes ₉(3 ⁴) orthogonal table carries out eluting, collects ethanol elution, decompression recycling ethanol, vacuum drying (60 ℃ ,-0.09Mpa).The rate of transform with total flavones serves as to investigate index.

The factor level table

Factor flow velocity (L/kg medical material .h) concentration of alcohol (%) eluant consumption (doubly)

Horizontal A B C

1 8 40 3

2 10 50 4

3 12 60 5

Annotate: the eluant consumption is represented the weight resin multiple

The elution requirement orthogonal table

Gauge outfit

The A B C D total flavones rate of transform (%)

Tested number

1 1 1 1 1 42.95

2 1 2 2 2 46.03

3 1 3 3 3 59.99

4 2 1 2 3 45.03

5 2 2 3 1 52.98

6 2 3 1 2 38.05

7 3 1 3 2 57.77

8 3 2 1 3 41.4

9 3 3 2 1 46.49

I 148.97 145.75 122.4 142.42

II 136.06 140.41 137.55 141.85

III 145.66 144.53 170.74 146.42

I ² 22192.06 21243.06 14981.76 20283.46

II ² 18512.32 19714.97 18920 20121.42

III ² 21216.84 20888.92 29152.15 21438.82

K ² 61921.22 61846.95 63053.91 61843.7

S 29.98 5.22 407.54 4.13

Eluting is analysis of variance table as a result

Soruces of variation	S	V	The F ratio	Significance
Soruces of variation	S	V	The F ratio	Significance	A	29.98	2	7.25
B	5.22	2	1.26		A	29.98	2	7.25
B	5.22	2	1.26		C	407.54	2	98.57	*
D	4.13	2			C	407.54	2	98.57	*

By intuitive analysis as can be known, A3＞A2＞A1, B1＞B3＞B2, C3＞C2＞C1, solvent load (factor C) is the principal element that influences the total flavones rate of transform, secondly is flow velocity (factor A) and concentration of alcohol (factor B).ANOVA showed significant: solvent load has the significance influence to the scutellarin rate of transform, selects best condition C 3; Concentration of alcohol does not have the significance influence to the rate of transform, considers that the cost of factory selects B1; Flow velocity does not have the significance influence yet, selects condition A3 for use in order to shorten man-hour; So determine that elution requirement is A3B1C3, promptly, be 0.2ml/g medical material .min with the speed eluting of 5 times of resin volume 40% ethanol with 12L/kg medical material .h.

2.2 Radix Ginseng separation condition screening

In order to investigate the optimum condition of desorbing Radix Ginseng total saponins from the resin, select eluant strength, eluant consumption, three factors of effluent speed, each factor is respectively got three levels, adopts L ₉(3 ⁴) orthogonal table tests, get ginseng crude drug 2700g, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water dissolution that adds 4 times of medical material volumes, filter, filtrate is divided into 9 parts of speed with 0.5ml/g medical material .min and crosses ZTC-1 type macroporous adsorbent resin, uses 7 times of resinite hydrops and 5 times of resin volume 10% alcohol flushing impurity successively, carries out eluting with alcoholic solution then, collect ethanol elution, be concentrated into dried.With must measuring of total saponins is index.

The factor level table

Factor B eluant consumption

Level

A concentration of alcohol (%) C effluent speed (ml/g medical material .min)

(doubly)

1 20 5 0.6

2 40 7 0.8

3 60 9 1.0

The elution requirement orthogonal table

Gauge outfit

A B C D total saponins amount (g)

Tested number

1 1 1 1 1 2.3

2 1 2 2 2 2.32

3 1 3 3 3 2.33

4 2 1 2 3 3.2

5 2 2 3 1 3.29

6 2 3 1 2 3.62

7 3 1 3 2 3.51

8 3 2 1 3 3.79

9 3 3 2 1 4.2

I 6.95 9.01 9.71 9.79

II 10.11 9.4 9.72 9.45

III 11.5 10.15 9.13 9.32

I ² 48.30 81.18 94.28 95.84

II ² 102.21 88.36 94.48 89.30

III ² 132.25 103.02 83.36 86.86

K ² 282.76 272.56 272.12 272.01

S 3.62 0.22 0.08 0.04

The separation condition analysis of variance table

Soruces of variation	SS	V	MS	The F ratio	Significance
Soruces of variation	SS	V	MS	The F ratio	Significance	A	3.62	2	1.81	91	*
B	0.22	2	0.11	6		A	3.62	2	1.81	91	*
B	0.22	2	0.11	6		C	0.08	2	0.04	2
D	0.04	2	0.02			C	0.08	2	0.04	2

By intuitive analysis as can be known, A ₃＞A ₂＞A ₁, B ₃＞B ₂＞B ₁, C ₁=C ₂＞C ₃, elution volume (factor A) has certain influence to the separation of total saponins, and concentration of alcohol (factor B) and flow velocity (factor C) influence are little.ANOVA showed significant, elution volume has appreciable impact to the separation of total saponins, selects best condition A ₃, concentration of alcohol does not have influence, considers that the cost of factory selects B ₁, flow velocity does not have influence, selects condition C for use in order to shorten man-hour ₃So, determine the A that is combined as of elution requirement ₃B ₁C ₃, promptly with 5 times of column volume 60% ethanol with 1ml/g medical material .min speed eluting.

2.3 separation condition screening Radix Ophiopogonis

Get medical material 2700g Radix Ophiopogonis, add 10 times of volume decoctings and boil each 1.5 hours 3 times, merge extractive liquid,, filter, filtrate is crossed ZTC-1 type macroporous adsorptive resins with the speed of 0.5ml/g medical material .min, and the water with 6 times of resin volumes washes with the speed of 1ml/g medical material .min earlier, 20% ethanol of 3 times of resin volumes of reuse is with the speed eluting impurity of 1ml/g medical material .min, use the alcoholic solution eluting at last, collect stripping liquid, concentrate drying, measure total saponin content, calculate the rate of transform.

The factor level table

A effluent speed (ml/g

Factor

B eluant consumption (doubly) C concentration of alcohol (%)

Horizontal medical material .min)

1 0.4 4 40

2 0.6 6 50

3 0.8 8 60

The elution requirement orthogonal table

The factor rate of transform

A B C D

Experiment number (%)

1 1 1 1 1 39.18

2 1 2 2 2 54.17

3 1 3 3 3 56.85

4 2 1 2 3 47.85

5 2 2 3 1 63.42

6 2 3 1 2 46.46

7 3 1 3 2 53.77

8 3 2 1 3 43.69

9 3 3 2 1 46.26

I 150.2 140.8 129.33 148.86

II 157.73 161.28 148.28 154.4

III 143.72 149.57 174.04 148.39

I ² 22560.04 19824.64 16726.25 22159.30

II ² 24878.75 26011.24 21986.96 23839.36

III ² 20655.44 22371.18 30289.92 22019.59

K ² 68094.23 68207.06 69003.13 68018.25

S 32.77 70.39 335.74 7.45

Analysis of variance table

Soruces of variation	Sum of deviation square	Degree of freedom	Mean square	The F ratio
Soruces of variation	Sum of deviation square	Degree of freedom	Mean square	The F ratio	A	32.77	2	16.39	4.39
B	70.39	2	35.20	9.43	A	32.77	2	16.39	4.39
B	70.39	2	35.20	9.43	C	335.74	2	167.87	51.97
D	7.45	2	3.73		C	335.74	2	167.87	51.97

From above-mentioned variance analysis and orthogonal table as can be seen, the concentration of alcohol influence is bigger, gets 60% alcohol desorption; Volume and flow velocity do not have influence, consider production cost and working time, select 4 times of volumes and 0.8ml/g medical material .min respectively for use.

Experimental example 3: injection with small volume or concentrated solution for injection molding research

3.1 activated carbon dosage is investigated:

Injection owing to solvent, raw material, container etc. have the pyrogen material, reduces the safety of injection in the process of producing, and therefore needs to remove the pyrogen material in the process of preparation injection.The method of depyrogenation mainly contains high temperature method, acid-base method, ultrafiltration and absorption method at present, active carbon adsorption not only can heat of adsorption originality composition, the effect that also has filter of helping and decolouring, when removing pyrogen, can improve the appearance character of preparation, therefore we select the active carbon adsorption depyrogenation for use, and its consumption is investigated.The results are shown in following table:

The activated carbon dosage investigation table

Activated carbon dosage (%)	Cream heavy (g)	The rate of transform (%)	Outward appearance
Activated carbon dosage (%)	Cream heavy (g)	The rate of transform (%)	Outward appearance	0.1	6.40	56.81	Reddish brown
1	6.26	55.16	Red	0.1	6.40	56.81	Reddish brown
1	6.26	55.16	Red	1.5	5.85	51.93	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	6.51	56.94	Reddish brown
30	6.23	55.65	Red	10	6.51	56.94	Reddish brown
30	6.23	55.65	Red	60	5.87	53.76	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	3.8 4.3 5.1	5.6 6.2 6.5 7.0	7.5 8.1	Dosing pH	4.5 5.0 5.5	6.0 6.5 7.0 7.5	8.0 8.5
Boil pH	3.8 4.3 5.1	5.6 6.2 6.5 7.0	7.5 8.1	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	5.18	5.1	4.95
2	6.0	5.18	5.6	5.07	1	5.5	5.18	5.1	4.95
2	6.0	5.18	5.6	5.07	3	6.5	5.18	6.2	5.10
4	7.0	5.18	6.5	5.02	3	6.5	5.18	6.2	5.10
4	7.0	5.18	6.5	5.02	5	7.5	5.18	7.0	4.93

As seen from table, medicinal liquid is being adjusted the pH value front and back, the not too big variation of index components scutellarin content.The appearance character of comprehensive above-mentioned medicinal liquid and the changes of contents of scutellarin, the pH value of medicinal liquid is transferred between 5.5～7.5 when determining dosing.

Experimental example 4: the investigation of lyophilized formulations moulding process

4.1 the screening of caffolding agent kind

The caffolding agent kind influences the molding of freeze-dried powder, so at first this is screened.Taking liquid mixes with caffolding agent mannitol, glucose and lactose solution respectively, 0.22 μ m membrane filtration postlyophilization, every XiLin bottle-packaging solution 3ml.Freeze dryer: Edwards SNL-3200 freezer dryer (the thermoelectric Thermo of the U.S.).Lyophilisation condition :-45 ℃, behind the pre-freeze 8h, the beginning evacuation, and be warming up to-40 ℃, keep 10h; Be warming up to-30 ℃, keep 10h; Be warming up to-20 ℃, keep 10h; Be warming up to-10 ℃, keep 5h; Be warming up to 0 ℃, keep 5h; Be warming up to 15 ℃, keep 3h; Be warming up to 25 ℃, keep 3h.The result is as showing:

The screening of caffolding agent kind

The caffolding agent kind	Caffolding agent: medicinal liquid (V: V)	Solubility	The finished product outward appearance
The caffolding agent kind	Caffolding agent: medicinal liquid (V: V)	Solubility	The finished product outward appearance	Glucose	3∶1	Good	Part is subsided
Galactose	3∶1	Generally	Molding	Glucose	3∶1	Good	Part is subsided
Galactose	3∶1	Generally	Molding	Mannitol	3∶1	Good	Molding
Glycine	3∶1	Good	Molding, frangible	Mannitol	3∶1	Good	Molding
Glycine	3∶1	Good	Molding, frangible	Dextran	3∶1	Generally	Molding
Mannitol, propylene glycol	3∶1	Good	Molding	Dextran	3∶1	Generally	Molding
Mannitol, propylene glycol	3∶1	Good	Molding	Glycine, Polyethylene Glycol	3∶1	Good	Molding, frangible
Dextran, sorbitol, tween	3∶1	Good	Molding	Glycine, Polyethylene Glycol	3∶1	Good	Molding, frangible
Dextran, sorbitol, tween	3∶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 (70mg/ml, 100mg/ml and 130mg/ml) of variable concentrations is mixed in varing proportions with medicinal liquid, filter, every cillin bottle loading amount is 3ml, lyophilization.Lyophilisation condition :-45 ℃, behind the pre-freeze 8h, the beginning evacuation, and be warming up to-40 ℃, keep 10h; Be warming up to-30 ℃, keep 10h; Be warming up to-20 ℃, keep 10h; Be warming up to-10 ℃, keep 5h; Be warming up to 0 ℃, keep 5h; Be warming up to 15 ℃, keep 3h; Be warming up to 25 ℃, keep 3h.The result is as showing:

The screening of mannitol consumption

Numbering	Mannitol concentration (mg/ml)	Mannitol: medicinal liquid (v: v)	Color and luster	Profile	Solubility	Clarity
Numbering	Mannitol concentration (mg/ml)	Mannitol: medicinal liquid (v: v)	Color and luster	Profile	Solubility	Clarity	1	70	3∶1	Yellowish-brown	Part is subsided	Good	Up to specification
2	100	3∶1	Yellow	Intact	Good	Up to specification	1	70	3∶1	Yellowish-brown	Part is subsided	Good	Up to specification
2	100	3∶1	Yellow	Intact	Good	Up to specification	3	130	3∶1	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 130mg/ml is relatively good with the mannitol concentration, the sample of 70mg/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 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

Time (h)

Condition I condition II condition III cold-trap

Temperature (℃)

-45 (pre-freezes) 10-8

-40 (pre-freeze)-12-

-40 (evacuation) 10-10

-35 (evacuation)-10-

-30 (evacuation) 8-10 keeps

-25 (evacuation)-8--70 ℃

-20 (evacuation) 8-10

-15 (evacuation)-8-

-10 (evacuation) 5-6

0 (evacuation) 556

10 (evacuation) 233

20 (evacuation) 233

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 10h; Be warming up to-30 ℃ again, keep 8h; Be warming up to-20 ℃, keep 8h; Be warming up to-10 ℃, keep 5h; Be warming up to 0 ℃, keep 5h; Be warming up to 10 ℃, keep 2h; Be warming up to 20 ℃, keep 2h, get product.

Experimental example 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	5.34
150	70	18	5.16	140	60	16	5.34
150	70	18	5.16	160	80	20	5.20

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.)

Embodiment 1: 350 parts of 120 parts of Herba Erigerontiss of 120 parts of Radix Ginsengs Radix Ophiopogonis

Above-mentioned Radix Ophiopogonis total saponins, Herba Erigerontis total flavones and Radix Ginseng total saponins 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 6.5, 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 10h; Be warming up to-30 ℃ again, keep 8h; Be warming up to-20 ℃, keep 8h; Be warming up to-10 ℃, keep 5h; Be warming up to 0 ℃, keep 5h; Be warming up to 10 ℃, keep 2h; Be warming up to 20 ℃, keep 2h, get product.After testing: the content of saponin component accounts in the preparation 24% of total solid after deduction adjuvant amount and the water quantities; The content of flavones ingredient accounts in the preparation 26% 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 50%.

Embodiment 2: 350 parts of 120 parts of Herba Erigerontiss of 120 parts of Radix Ginsengs Radix Ophiopogonis

Above-mentioned Radix Ophiopogonis total saponins, Herba Erigerontis total flavones and Radix Ginseng total saponins 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 7, 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 31% of total solid after deduction adjuvant amount and the water quantities; The content of flavones ingredient accounts in the preparation 21% 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 52%.

Embodiment 3: 350 parts of 120 parts of Herba Erigerontiss of 120 parts of Radix Ginsengs Radix Ophiopogonis

Above-mentioned Radix Ophiopogonis total saponins, Herba Erigerontis total flavones and Radix Ginseng total saponins 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 the joint pH value is 5.5, 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 29% of total solid after deduction adjuvant amount and the water quantities; The content of flavones ingredient accounts in the preparation 27% 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 56%.

Embodiment 4: 350 parts of 120 parts of Herba Erigerontiss of 120 parts of Radix Ginsengs Radix Ophiopogonis

B, the Herba Erigerontis medical material, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 3 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin with the speed of 0.5ml/g medical material .min, use 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity successively, use 40% 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 Herba Erigerontis total flavones;

C, get the ginseng crude drug, add 8 times of volume 70% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water dissolution that adds 4 times of medical material volumes, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.5ml/g medical material .min, use 7 times of resinite hydrops and 5 times of resin volume 10% alcohol flushing impurity successively, use 60% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Radix Ginseng total saponins;

Total soap former times above-mentioned Radix Ophiopogonis, Herba Erigerontis total flavones and Radix Ginseng total saponins 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, adjust pH is 5.5, 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 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 25% of total solid after deduction adjuvant amount and the water quantities; The content of flavones ingredient accounts in the preparation 23% 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 48%.

Embodiments of the invention 5: 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,, merge extractive liquid,, filter, filtrate is crossed ZTC-1 type macroporous adsorptive resins with the speed of 0.8ml/g medical material .min, water with 10 times of resin volumes washes with the speed of 1.5ml/g medical material .min earlier, 25% ethanol of 4 times of resin volumes of reuse is used the speed eluting of 70% ethanol of 6 times of resin volumes with 1.0ml/g medical material .min at last with the speed eluting impurity of 1.5ml/g medical material .min, collects stripping liquid, reclaiming and measuring relative density when ethanol is evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis total saponins that gets;

B, get the Herba Erigerontis medical material, add 15 times of volume 80% alcohol reflux 4 times, each 2.5 hours, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 5 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin with the speed of 0.8ml/g medical material .min, use 10 times of resinite hydrops and 6 times of resin volume 15% alcohol flushing impurity successively, use 70% alcohol desorption of 7 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Herba Erigerontis total flavones;

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 during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water dissolution that adds 5 times of medical material volumes, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 1.5ml/g medical material .min, use 10 times of resinite hydrops and 6 times of resin volume 15% alcohol flushing impurity successively, use 70% alcohol desorption of 7 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 total saponins;

Above-mentioned Radix Ophiopogonis total saponins, Herba Erigerontis total flavones and Radix Ginseng total saponins 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, adjust pH is 6, boils, 4 ℃ of cold preservations 12 hours, coarse filtration, fine straining divide to install in the enamel tray, temperature-55 ℃, pre-freeze time 12h, the beginning evacuation, and be warming up to-43 ℃, 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, 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 38% of total solid after deduction adjuvant amount and the water quantities; The content of flavones ingredient accounts in the preparation 52% 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 6: 50 parts of 10 parts of Herba Erigerontiss of 10 parts of Radix Ginsengs Radix Ophiopogonis

A, get medical material Radix Ophiopogonis, adding 5 times of volume decoctings boiled 1 time 0.5 hour, merge extractive liquid,, 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 3 times of resin volumes washes with the speed of 0.5ml/g medical material .min earlier, 5% ethanol of 1 times of resin volume of reuse is with the speed eluting impurity of 0.5ml/g medical material .min, use the speed eluting of 50% ethanol of 2 times of resin volumes at last with 0.5ml/g medical material .min, collect stripping liquid, reclaiming and measuring relative density when ethanol is evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis total saponins that gets;

B, get the Herba Erigerontis medical material, added 5 times of volumes, 50% alcohol reflux 1 time 0.5 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 1 times of medical material volume, filter, filtrate is crossed AB-8 type macroporous adsorbent resin with the speed of 0.1ml/g medical material .min, use 1 times of resinite hydrops and 1 times of resin volume 5% alcohol flushing impurity successively, use 30% alcohol desorption of 1 times of resin volume then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Herba Erigerontis total flavones;

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 during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water dissolution that adds 1 times of medical material volume, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.3ml/g medical material .min, use 1 times of resinite hydrops and 1 times of resin volume 5% alcohol flushing impurity successively, use 30% alcohol desorption of 1 times of resin volume then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Radix Ginseng total saponins;

Above-mentioned Radix Ophiopogonis total saponins, Herba Erigerontis total flavones and Radix Ginseng total saponins are merged, add an amount of water for injection dissolving, by volume add 1% active carbon, boil, keep little 60min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, adjust pH is 6, 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 40 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 sum of saponins and flavones ingredient accounts in the preparation 25% of total solid after deduction adjuvant amount and the water quantities.

Embodiments of the invention 7: 500 parts of 200 parts of Herba Erigerontiss of 200 parts of Radix Ginseng Rubra Radix Ophiopogonis

A, get medical material Radix Ophiopogonis, add 6 times of volume decoctings and boiled 1 time 0.5 hour, merge extractive liquid,, merge extractive liquid, filters, and measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, dry Radix Ophiopogonis total saponins;

B, get the Herba Erigerontis medical material, add 12 times of volume 60% alcohol reflux 3 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 2 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin with the speed of 0.3ml/g medical material .min, use 3 times of resinite hydrops and 1 times of resin volume 5% alcohol flushing impurity successively, use 50% alcohol desorption of 4 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Herba Erigerontis total flavones;

C, get the Radix Ginseng Rubra medical material, added 5 times of volumes, 50% alcohol reflux 1 time 0.5 hour, measuring relative density when merge extractive liquid,, decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Radix Ginseng Rubra total saponins;

Above-mentioned Radix Ophiopogonis total saponins, Herba Erigerontis total flavones and Radix Ginseng Rubra total saponins 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 5.5～7.5, 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.After testing: the content of saponin component accounts in the preparation 1% of total solid after deduction adjuvant amount and the water quantities.

Embodiments of the invention 8: 5000 parts of 1000 parts of Herba Erigerontiss of 1000 parts of Radix Ginsengs Radix Ophiopogonis

A, get medical material Radix Ophiopogonis, adding 12 times of volume decoctings boils 3 times, each 1.5 hours, merge extractive liquid,, filter, filtrate is crossed ZTC-1 type macroporous adsorptive resins with the speed of 0.5ml/g medical material .min, water with 6 times of resin volumes washes with the speed of 1ml/g medical material .min earlier, 20% ethanol of 3 times of resin volumes of reuse is with the speed eluting impurity of 1ml/g medical material .min, use the speed eluting of 60% ethanol of 4 times of resin volumes at last with 0.8ml/g medical material .min, collect stripping liquid, reclaim the dry Radix Ophiopogonis total saponins that gets of ethanol;

B, get the Herba Erigerontis medical material, added 5 times of volumes, 50% alcohol reflux 1 time 0.5 hour, measuring relative density when merge extractive liquid,, decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Herba Erigerontis total flavones;

C, get the ginseng crude drug, add 7 times of volume 70% alcohol reflux 3 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 6 times of resinite hydrops and 5 times of resin volume 10% alcohol flushing impurity successively, use 60% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Radix Ginseng total saponins;

Above-mentioned Radix Ophiopogonis total saponins, Herba Erigerontis total flavones and Radix Ginseng total saponins are merged, add an amount of water for injection dissolving, add the sodium chloride of ormal weight again, by volume add 1% active carbon, boil, keep little 30min that boils, cold slightly filtration, filtrate add the injection water to ormal weight, transfer pH value 5.5～7.5, boil, at 4 ℃ of cold preservations 12 hours, coarse filtration, fine straining, add the injection water, packing is under 115 ℃ of conditions, sterilized 30 minutes, and promptly got the sodium chloride intravenous infusion agent.After testing: the content of flavones ingredient accounts in the preparation 13% of total solid after deduction adjuvant amount and the water quantities.

Embodiments of the invention 9: 500 parts of 200 parts of Herba Erigerontiss of 200 parts of Radix Codonopsis Radix Ophiopogonis

A, add 10 times of volumes, 70% alcohol reflux Radix Ophiopogonis 2 times, each 1 hour, merge extractive liquid,, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, filter merging filtrate, measuring relative density when being evaporated to 60 ℃ is 1.05～1.15, add the dissolving of 5 times of amount water for injection, filter, filtrate is crossed ZTC-1 type macroporous adsorptive resins with the speed of 0.5ml/g medical material .min, water with 5 times of resin volumes washes with the speed of 0.6ml/g medical material .min earlier, 10% ethanol of 4 times of resin volumes of reuse is used the speed eluting of 60% ethanol of 5 times of resin volumes with 0.6ml/g medical material .min at last with the speed eluting impurity of 1ml/g medical material .min, collects stripping liquid, reclaiming and measuring relative density when ethanol is evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis total saponins that gets;

B, get the Herba Erigerontis medical material, add 6 times of volume 70% 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 heating for dissolving that adds 3 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin with the speed of 0.5ml/g medical material .min, use 5 times of resinite hydrops and 4 times of resin volume 10% alcohol flushing impurity successively, use 40% 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 Herba Erigerontis total flavones;

C, get codonopsis pilosula, adding 10 times of volume decoctings boils 3 times, each 2 hours, merge extractive liquid, is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.5ml/g medical material .min, with 6 times of resinite hydrops flushings, sample effluent and water lotion in the collection, measuring relative density when being concentrated into 60 ℃ is 1.05～1.15, adds ethanol precipitate with ethanol twice, makes that to contain the alcohol amount be 60% for the first time, make for the second time that to contain the alcohol amount be 85%, filter, twice precipitation merged the back add 2 times of water dissolutioies, filter, filtrate concentrate the Radix Ginseng Rubra polysaccharide, 4 times of resin volumes of reuse, 10% alcohol flushing impurity is used 50% alcohol desorption of 5 times of resin volumes then, collects stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Radix Codonopsis total saponins;

Above-mentioned Radix Ophiopogonis total saponins, Herba Erigerontis total flavones and Radix Codonopsis total saponins are merged, add an amount of water for injection dissolving, by volume add 0.5% active carbon, boil, keep little 50min that boils, cold slightly filtration, filtrate adds the injection water to ormal weight, adjust pH is 7.5, 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 10h; 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 10: 200 parts of 50 parts of Herba Erigerontiss of 50 parts of Radix Codonopsis Radix Ophiopogonis

A, get medical material Radix Ophiopogonis, adding 8 times of volume decoctings boils 3 times, each 1.5 hours, merge extractive liquid,, merge extractive liquid,, filter, filtrate is crossed ZTC-1 type macroporous adsorptive resins with the speed of 0.4ml/g medical material .min, water with 6 times of resin volumes washes with the speed of 0.7ml/g medical material .min earlier, 15% ethanol of 4 times of resin volumes of reuse is used the speed eluting of 70% ethanol of 4 times of resin volumes with 0.8ml/g medical material .min at last with the speed eluting impurity of 1.2ml/g medical material .min, collects stripping liquid, reclaiming and measuring relative density when ethanol is evaporated to 60 ℃ is 1.05～1.15, the dry Radix Ophiopogonis total saponins that gets;

B, get the Herba Erigerontis medical material, add 15 times of volume 60% alcohol reflux 2 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water heating for dissolving that adds 4 times of medical material volumes, filter, filtrate is crossed AB-8 type macroporous adsorbent resin with the speed of 0.6ml/g medical material .min, use 5 times of resinite hydrops and 5 times of resin volume 8% alcohol flushing impurity successively, use 50% alcohol desorption of 7 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Herba Erigerontis total flavones;

C, get codonopsis pilosula, add 8 times of volume 70% alcohol reflux 2 times, each 1 hour, merge extractive liquid,, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, the water dissolution that adds 3 times of medical material volumes, filter, filtrate is crossed ZTC-1 type macroporous adsorbent resin with the speed of 0.5ml/g medical material .min, use 7 times of resinite hydrops and 5 times of resin volume 10% alcohol flushing impurity successively, use 60% alcohol desorption of 5 times of resin volumes then, collect stripping liquid, measuring relative density during decompression recycling ethanol to 60 ℃ is 1.05～1.15, dry Radix Codonopsis extract;

Above-mentioned Radix Ophiopogonis total saponins, Herba Erigerontis total flavones 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, adjust pH 5.5～7.5 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.After testing, wherein the content of flavones ingredient be in the preparation total solid after deduction adjuvant amount and the water quantities 1%.

Claims

1, a kind of traditional medicine Injectio with human body immunity improving power, treatment cardiovascular and cerebrovascular disease, it is characterized in that: calculate according to components by weight percent, it 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:

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

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