CN102600071A - Method for preparing sinomenine hydrochloride infusion solutions and freeze-dried powder injections - Google Patents
Method for preparing sinomenine hydrochloride infusion solutions and freeze-dried powder injections Download PDFInfo
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Abstract
The invention discloses a method for preparing sinomenine hydrochloride infusion solutions and freeze-dried powder injections. The method disclosed by the invention adopts adsorption technique of cation exchange resin or macroporous adsorption resin to replace traditional benzene extraction and chloroform extraction technique that are more toxic, and is high in extraction rate and simpler in operation; and harm and pollution to operators and the environment produced by the large-quantity high-toxicity organic solvent can be overcame, the method reduces processes for treating the organic solvent, is more beneficial for environmental protection, reduces investment in environmental protection facilities of plants, and is beneficial for environment-friendly production. Sinomenine hydrochloride extracted and separated by the method disclosed by the invention is used as a raw material in pharmaceutical preparations, has higher purity and no residual solvent, and reduces the potential hazards to human body.
Description
Technical field
The present invention relates to the method for preparing of a kind of sinomenine hydrochloride infusion solutions and lyophilized injectable powder, be specifically related to a kind of non-organic solvent and extract the method that effective ingredient sinomenine hydrochloride in the Caulis Sinomenii is processed sinomenine hydrochloride infusion solutions and lyophilized injectable powder.
Background technology
Caulis Sinomenii is a conventional Chinese medicine; Dry rattan for menispermaceous plants Sinomenium acutum and hair Sinomenium acutum; Just on the books in Compendium of Material Medica, record in Pharmacopoeia of the People's Republic of China version in 2010 at present, have dispel the wind, the effect of the meridian dredging, diuresis; Be used to treat rheumatic arthralgia, arthroncus, paralysis pruritus, also have effects such as anti-arrhythmia and blood pressure lowering.
Main component is an alkaloid in the Caulis Sinomenii; The composition of having found at present has sinomenine (Sinomenine); Isosinomenine (Igoginomenine), magnificent sinomenine (SinoAcutine), short Sinomenium acutum time alkali (Acutumidine); Point sinomenine (Sinaetine) and disinomenine (Diginomenine), ethyl sinomenine (ethylsinomenine), tetrahydrochysene epiberberine (sinactine), tetrahydrochysene epiberberine, Caulis menispermi ripple phenol alkali, bianfugenine, Tetrahydropalmatine etc.
Sinomenine (Sinomenine) is a kind of alkaloid monomer that extracts in the Caulis Sinomenii, is the main effective ingredient of Caulis Sinomenii performance analgesia, antiinflammatory action, from Japanese Caulis Sinomenii, is separated obtaining the earliest by Ishiwari etc.The sixties in 20th century, Chinese scholar Zhu Renhong also found sinomenine from homemade Caulis Sinomenii.Its hydrochlorate preparation commonly used clinically such as ZHENGQINGFENGTONGNING PIAN, ZHENGQINGFENGTONGNING slow releasing tablet, ZHENGQINGFENGTONGNING injection are used to treat rheumatic, rheumatoid arthritis, and treatment ankylosing spondylitis, arrhythmia etc. are evident in efficacy.
At present the commercial production sinomenine hydrochloride adopts the alkalization water extraction process more, and it is for adding entry and a certain amount of Calx in Caulis Sinomenii, alkalization a period of time, add a certain amount of technical benzene then, reflux, extract,, last acidify, leave standstill, crystallize.Caulis Sinomenii dilute sulfuric acid percolate is transferred pH value 9 with lime water, and benzene carries out counter-current extraction at 50 ℃, and benzene extraction liquid carries out anti-phase counter-current extraction, activated carbon decolorizing, crystallization with 1% hydrochloric acid.In hot water, carry out recrystallization, get pure article.(Chen Yukun " extracting technique of Chinese medicine ", 1992), existing method all use very big benzene of toxicity or chloroform as extracting solvent; Benzene is the one-level toxic solvent; System cancer rate is very high, and is disabled at pharmaceutical industry, and needing just to reach environmental requirement through very cumbersome technology aspect the recycling of solvent; And chloroform is the secondary toxic reagent, thereby in Chinese medicine extraction, should avoid the use of benzene and chloroform solvent as far as possible.
Summary of the invention
The object of the invention is to provide the method for preparing of a kind of sinomenine hydrochloride infusion solutions and lyophilized injectable powder.
The present invention seeks to realize that through following technical scheme the method for preparing of sinomenine hydrochloride infusion solutions of the present invention comprises the preparation of sodium chloride infusion solutions and the preparation of glucose infusion solutions, concrete grammar comprises the steps:
Method one: the preparation of sodium chloride infusion solutions
The method for preparing of step 1, sinomenine hydrochloride
A, extraction: Caulis Sinomenii coarse powder 100～1000 weight portions, with 0.1～1mol/L HCl moistening of 60～1000 parts by volume 0.5～8 hour, the dress percolator; Adding 0.1～1mol/L HCl again makes liquid level cover medicated powder 2cm; Flood after 6～48 hours, begin percolation, stop percolation after 6～24 hours by the speed of 2～5ml/min; Get percolate, subsequent use;
B, upper prop eluting: with cation exchange resin of having handled well on the percolate or 152 type resins, blade diameter length ratio 1: 8-12, last appearance speed be 2-5 times of column volume/hour; With silico-tungstic acid test solution inspection deposition is arranged to effluent, and thin layer chromatography stops to go up kind when detecting inanimate object alkaline spot point, be eluted to purified water and stop when eluent does not have color; Soaked resin 12 hours with 8-15% ammonia solution immersion resin or 152 type resins with the 3-10% hydrochloric acid solution, the ammonia of reuse pH8-11-alcoholic solution eluting or 152 type macroporous adsorbent resins are with 3-10% hydrochloric acid solution eluting, and elution speed is 2-5BV/h; Eluent receives when with the inspection of silico-tungstic acid test solution deposition being arranged, and does not receive when eluent has deposition with the inspection of silico-tungstic acid test solution to stop, and merges eluent; Be neutralized to pH=6-8 with hydrochloric acid or ammonia; Desalination, concentrate drying gets the sinomenine hydrochloride bullion.
C, refining: get sinomenine hydrochloride bullion 5～10 weight portions,, add the active carbon of 3-6% times of weight with 10～95% ethanol or the dissolving extremely fully of purified water reflux of 30～120 parts by volume; Insulation refluxed 10～30 minutes, filtered while hot, and filtrating concentrates; Cooling, crystallize; Filter, colourless with the ethanol cleaning filter cake of 75-95% to filtrating, get sinomenine hydrochloride;
The preparation of step 2, sodium chloride infusion solutions
It is an amount of to take by weighing sinomenine hydrochloride 0.3-2 weight portion, sodium chloride 6-15 weight portion, water for injection, gets the sodium chloride of above-mentioned amount, and the water for injection stirring and dissolving that adds dosing amount 60%-80% makes into concentrated solution; The sinomenine hydrochloride that other takes by weighing recipe quantity adds in the above-mentioned concentrated solution; Stirring makes dissolving, adds the needle-use activated carbon of 0.05%-0.5%, stirs; 35～45 ℃ are incubated 10 minutes, filter carbon removal; Replenish water for injection to 1000 parts by volume, stir, check filters with the filter element of 0.35-0.55 μ m and 0.1-0.3 μ m respectively after qualified, and sampling checks pH value, content, bacterial endotoxin, visible foreign matters to meeting national injection standard, sterilizes, and promptly gets.
Method two: the preparation of glucose infusion solutions
Step 1, with step 1 in the method one;
The preparation of step 2, glucose infusion solutions
It is an amount of to take by weighing sinomenine hydrochloride 0.3-2 weight portion, glucose 40-60 weight portion, water for injection, gets the glucose of above-mentioned amount, and the water for injection stirring and dissolving that adds dosing amount 60%-80% makes into concentrated solution; The sinomenine hydrochloride that other takes by weighing recipe quantity adds in the above-mentioned concentrated solution; Stirring makes dissolving, adds the needle-use activated carbon of 0.05%-0.5%, stirs; 35～45 ℃ are incubated 10 minutes, filter carbon removal; Replenish water for injection to 1000 parts by volume; Stir, check filters with the filter element of 0.35-0.55 μ m and 0.1-0.3 μ m respectively after qualified, and sampling checks pH value, content, bacterial endotoxin, visible foreign matters to National standard, sterilizes, and promptly gets.
The method for preparing of sinomenine hydrochloride lyophilized injectable powder of the present invention comprises the steps:
Step 1, with step 1 in the above-mentioned method one;
Step 2,
Get sinomenine hydrochloride 50-150 weight portion and proper amount of water for injection, add the stirring of recipe quantity sinomenine hydrochloride and make dissolving; The active carbon that adds 0.05-0.5%, 35～45 ℃ are incubated 5-20 minute, filter carbon removal; Replenish water for injection to 1000 parts by volume, stir, check filters with the filter element of 0.35-0.55 μ m and 0.1-0.3 μ m respectively after qualified, takes a sample, and checks pH value, content, bacterial endotoxin, visible foreign matters to National standard, packing, and lyophilization promptly gets.
Parametric optimization in sinomenine hydrochloride infusion solutions of the present invention and the lyophilized injectable powder method for preparing is following:
In the B step, the preferred 001*2.5 of strong cation-exchanging resin, 001*4 type resin, preferred 152 types of macroporous adsorbent resin; Preferred 1: 10 of resin path height ratio; The preferred 3 times of column volumes of last appearance speed/hour; Soak preferred 10% ammonia solution of resin or 5% hydrochloric acid solution; With ammonia-alcoholic solution of pH8-11 elute soln as cation exchange resin, eluent is neutralized to pH=6～8 with hydrochloric acid; 5%HCl solution is as the elute soln of 152 type macroporous adsorbent resins;
The C step preferably adds the active carbon of 4% times of weight; Preferred 40%, 55%, 60%, 75% during reflux, 80% ethanol.
Step 2 in the sinomenine hydrochloride infusion solutions method for preparing of the present invention in the method one can be preferably:
It is an amount of to take by weighing sinomenine hydrochloride 0.5 weight portion, sodium chloride 6 weight portions, water for injection, gets the sodium chloride of above-mentioned amount, and the water for injection stirring and dissolving that adds dosing amount 70% makes into concentrated solution; The sinomenine hydrochloride that other gets recipe quantity adds in the above-mentioned concentrated solution; Stirring makes dissolving, adds 0.1% needle-use activated carbon, stirs; 35～45 ℃ are incubated 10 minutes, filter carbon removal; Replenish water for injection to 1000 parts by volume, stir, check filters with the filter element of 0.45 μ m and 0.22 μ m respectively after qualified, sampling, and check pH value, content, bacterial endotoxin, visible foreign matters are sterilized to meeting national injection standard, promptly get;
Or it is an amount of to take by weighing sinomenine hydrochloride 1 weight portion, sodium chloride 10 weight portions, water for injection, gets the sodium chloride of above-mentioned amount, and the water for injection stirring and dissolving that adds dosing amount 70% makes into concentrated solution; The sinomenine hydrochloride that other gets recipe quantity adds in the above-mentioned concentrated solution; Stirring makes dissolving, adds 0.2% needle-use activated carbon, stirs; 35～45 ℃ are incubated 10 minutes, filter carbon removal; Replenish water for injection to 1000 parts by volume, stir, check filters with the filter element of 0.35 μ m and 0.15 μ m respectively after qualified, sampling, and check pH value, content, bacterial endotoxin, visible foreign matters are sterilized to meeting national injection standard, promptly get.
Step 2 in the sinomenine hydrochloride infusion solutions method for preparing of the present invention in the method two can be preferably:
It is an amount of to take by weighing sinomenine hydrochloride 0.5 weight portion, glucose 45 weight portions, water for injection, gets the glucose of recipe quantity, and the water for injection stirring and dissolving that adds dosing amount 70% makes into concentrated solution; The sinomenine hydrochloride that other gets recipe quantity adds in the above-mentioned concentrated solution; Stirring makes dissolving, adds 0.1% needle-use activated carbon, stirs; 35～45 ℃ are incubated 10 minutes, filter carbon removal; Replenish water for injection to 1000 parts by volume, stir, check filters with the filter element of 0.45 μ m and 0.22 μ m respectively after qualified, sampling, and check pH value, content, bacterial endotoxin, visible foreign matters are sterilized to National standard, promptly get;
Or it is an amount of to take by weighing sinomenine hydrochloride 1 weight portion, glucose 55 weight portions, water for injection, gets the glucose of recipe quantity, and the water for injection stirring and dissolving that adds dosing amount 60% makes into concentrated solution; The sinomenine hydrochloride that other gets recipe quantity adds in the above-mentioned concentrated solution; Stirring makes dissolving, adds 0.2% needle-use activated carbon, stirs; 35～45 ℃ are incubated 10 minutes, filter carbon removal; Replenish water for injection to 1000 parts by volume, stir, check filters with the filter element of 0.35 μ m and 0.15 μ m respectively after qualified, sampling, and check pH value, content, bacterial endotoxin, visible foreign matters are sterilized to National standard, promptly get.
Step 2 in the sinomenine hydrochloride lyophilized injectable powder method for preparing of the present invention in the method two can be preferably:
Get sinomenine hydrochloride 100 weight portions and proper amount of water for injection, add the stirring of recipe quantity sinomenine hydrochloride and make dissolving; The active carbon of adding 0.1%, 35～45 ℃ are incubated 10 minutes, filter carbon removal; Replenish water for injection to 1000 parts by volume, stir, check filters with the filter element of 0.45 μ m and 0.22 μ m respectively after qualified, and sampling checks pH value, content, bacterial endotoxin, visible foreign matters to National standard, packing, and lyophilization promptly gets;
Perhaps get sinomenine hydrochloride 140 weight portions and proper amount of water for injection, add the stirring of recipe quantity sinomenine hydrochloride and make dissolving; The active carbon of adding 0.2%, 35～45 ℃ are incubated 6 minutes, filter carbon removal; Replenish water for injection to 1000 parts by volume, stir, check filters with the filter element of 0.35 μ m and 0.3 μ m respectively after qualified, and sampling checks pH value, content, bacterial endotoxin, visible foreign matters to National standard, packing, and lyophilization promptly gets.
The weight portion in the method for preparing of above-mentioned sinomenine hydrochloride infusion solutions and lyophilized injectable powder and the relation of parts by volume are the relation of g/ml.
The inventive method adopts through cation exchange resin or absorption with macroporous adsorbent resin and replaces traditional bigger benzene extraction and chloroform extraction (extraction) technology of toxicity; Extract yield is high, operates easylier, the harm and the pollution that overcome that consumption of organic solvent is big, toxicity cause to operator ' s health and environment greatly; Reduced the processing procedure of organic solvent; More help environmental conservation, reduced the input of the environmental protection facility of factory, help environmental friendliness production.The sinomenine hydrochloride of this method extraction separation, as the raw material of pharmaceutical preparation, purity is higher, and no solvent residue has reduced the potential hazard to human body.
Following experimental example and embodiment are used to further specify but are not limited to the present invention.
Experimental example one: the Study on extraction of Caulis Sinomenii non-organic solvent
1, experimental technique
1.1 material and instrument
Caulis Sinomenii medicinal material coarse powder, macroporous adsorbent resin, sinomenine hydrochloride reference substance, hydrochloric acid, ammonia, sodium hydroxide, ethanol, sodium chloride etc.
Glass column (diameter 3cm, high by 30～40cm), HPLC high performance liquid chromatogram detector, rotary evaporimeter.
1.2 method and result
1.2.1 decision method
(1) the alkaloid indicator is selected
Press a method preparation of Chinese Pharmacopoeia version in 2010 bismuth potassium iodide weak solution, basic iron potassium cyanide, three kinds of alkaloid indicators of silico-tungstic acid test solution; Getting 1～2 respectively drips in inspection liquid; Precipitate, chromogenic reaction; Experiment contrast premenstruum shows that the indication of silico-tungstic acid test solution is the most directly perceived, sensitive.This experimental design adopts the indicator of silico-tungstic acid test solution as endpoint.
(2) thin layer chromatography: immobile phase: silica gel thin-layer plate; Developing solvent: methanol: water: ammonia=8: 1: 1; Developer: rare bismuth potassium iodide solution.
(3) HPLC
Use octadecylsilane chemically bonded silica to be filler; With acetonitrile-0.78% sodium dihydrogen phosphate (12: 88) is mobile phase; The detection wavelength is 265nm.30 ℃ of column temperatures, flow velocity 1.0ml/min.
1.2.2. the type selecting of resin
(1) resin model
The D-101 type, nonpolar macroporous adsorption resin, manufacturer: Tianjin sea light chemical industry;
The LSD001 type, polar macroporous adsorption resin, manufacturer: Xi'an Lanxiao Sci-Tech Co., Ltd.;
The D-312 type, macroporous adsorbent resin, manufacturer: Shandong Lukang Record Pharmaceuticals Co., Ltd.;
The DM21 type, macroporous adsorbent resin, manufacturer: Shandong Lukang Record Pharmaceuticals Co., Ltd.;
The HPD722 type, low pole macroporous adsorbent resin, manufacturer: Cangzhou Bon Adsorption Material Science and Technology Co., Ltd.
152 types, cation exchange resin, manufacturer: Shandong Lukang Record Pharmaceuticals Co., Ltd.;
732 types, sodium type cation exchange resin, manufacturer: Cangzhou Bon Adsorption Material Science and Technology Co., Ltd.
001 * 2.5 type, H type cation exchange resin, manufacturer: Shandong Lukang Record Pharmaceuticals Co., Ltd.;
001 * 4 type, H type cation exchange resin, manufacturer: Shandong Lukang Record Pharmaceuticals Co., Ltd.;
(2) method
Choose the macroporous resin or the ion exchange resin 10g～20g of above-mentioned different manufacturers, different model, go up 30mm*300mm glass exchange column after the pretreatment, get the percolate (pH is transferred to 3) of 1000g medical material; Be divided into 7 equal portions; Flow through resin by certain speed, general to go up appearance speed be 2～3BV/h, the special resin reference velocity of pressing; Have deposition to stop to go up appearance with silico-tungstic acid test solution inspection to effluent, water is washed till eluent not to be had till the color basically.The applied sample amount and the absorbability of contrast different resins, the resin model of selected good best producer is chosen the adsorbing material of 2～3 kinds of resins as this product.
The absorption situation of table 1 different model resin upper prop
Only investigate the absorption situation from indicator, thin layer and observe phenomena because of above experiment, can't accurately judge the absorption situation of resin, the later stage uses liquid chromatograph instead associated resin is investigated.
1, sinomenine hydrochloride raw material absorption: the sinomenine hydrochloride solution of preparation 2% (2g → 100ml); Get D101,001*4, three kinds of each 2g of resin of DM21 respectively in conical flask, add the above-mentioned obtain solution of 10ml, wave on the agitator at repeatedly and shake 12 hours; Liquid Detection, the result sees the following form
Table 2: the absorption HPLC result of different resins static adsorption sinomenine hydrochloride material liquid
2, extract stock solution absorption; Getting 001*2.5,001*4,152 types, AB-8 type, HPD600 type, 732 types, DM21 type, the treated good resin 2g of D101 type respectively puts in the 100ml conical flask; Add the percolation stock solution 25ml that extracts, Liquid Detection, the result sees the following form:
Table 3: the absorption HPLC result of the percolate that different resins static adsorption Caulis Sinomenii extracts
Above result shows that above-mentioned several kinds of resin absorption abilities compare: 001*2.5＞001*4＞152 types.AB-8, HPD600 type, DM21 type, D101 type, 732 types etc. because of absorbability in percolate too a little less than.
1.2.3 desorbing or eluting
According to above experimental result, selected 001*2.5,001*4,152 3 kinds of resins.Each resin experimentizes by following design.
(1) cation-adsorption resin (001*4,001*2.5)
1. 5% ammonia liquid.
2. 10% ammonia liquid.
3. 95% alcoholic solution.
4. transfer the alcoholic solution of PH to 8-11 with ammonia.
5. salt, diluted acid.(the 5%HCl solution of NH4Cl)
6. salt, rare alcohol.(20%NaCl+ alcoholic solution)
Get sour water percolate 500ml, through resin column, be washed till neutrality with purified water, more respectively with the speed eluting of different eluents, till the inanimate object alkali reaction with 2-3BV/h with the flow velocity of 2-3BV/h.Measure the sinomenine hydrochloride content in each duplicate samples, calculate eluting rate.The contrast elute effect.
The different eluents of table 4 are to the influence of sinomenine hydrochloride elute effect
Above experimental result shows: ammonia-alcoholic solution of pH8-11 is adopted in cationic resin absorption back, can obtain elute effect preferably.
(2) macroporous adsorbent resin (152 type)
1. 50% alcoholic solution.
2. 75% alcoholic solution.
3. 95% alcoholic solution.
4. 5%HCl solution.
Get sour water percolate 500ml, through resin column, be washed till neutrality with purified water, more respectively with the speed eluting of different eluents, till the inanimate object alkali reaction with 2～3BV/h with the flow velocity of 2～3BV/h.Measure the sinomenine hydrochloride content in each duplicate samples, calculate eluting rate.The contrast elute effect.
Table 5 152 types adopt the influence of different eluents to the sinomenine hydrochloride elute effect
Experimental result shows: adopt different eluents that the adsorption liquid of 152 type resins is carried out desorbing, only HCl has desorption effect, so this resin adopts 5%HCl to carry out eluting.
1.2.3 static adsorption is confirmed desorption condition
Through the selected good eluent of above-mentioned experiment, adopt the mode of static adsorption, after absorption 12 hours, with resin with the purified water rinsing to water during inanimate object alkali, adding 12ml stripping liquid shook Liquid Detection 12 hours.The result is following:
The percolate adsorption and desorption HPLC result that table 6 static adsorption Caulis Sinomenii extracts
Above result shows, adopts the stripping liquid of confirming to carry out desorbing, all can separate the sinomenine hydrochloride of sucking-off resin absorption.
1.3 conclusion
Adopt macroporous adsorbent resin and cation exchange resin; Sinomenine hydrochloride there is big adsorption; Through experiment; The optimum resin that selected 001*2.5, two kinds of cation exchange resiies of 001*4,152 type macroporous adsorbent resins extract as this sinomenine hydrochloride purification adopts the elute soln of ammonia-alcoholic solution (pH8～11) as cation exchange resin, and 5%HCl is as the elute soln of 152 type macroporous adsorbent resins.
Following embodiment all can realize the effect of above-mentioned experimental example.
Embodiment one: a kind of method for preparing of sinomenine hydrochloride infusion solutions, this method comprises the steps:
A, extraction: Caulis Sinomenii coarse powder 500kg, with the 0.5mol/L HCl moistening of 500L 3 hours, the dress percolator; Add 0.5mol/L HCl again and make liquid level cover medicated powder 2cm, flood after 12 hours, begin percolation by the speed of 3ml/min; Stop percolation after 12 hours, get percolate, subsequent use;
B, upper prop eluting: with cation exchange resin of having handled well on the percolate or 152 type resins, blade diameter length ratio 1: 10, last appearance speed be 3 times of column volumes/hour; With silico-tungstic acid test solution inspection deposition is arranged to effluent, and thin layer chromatography stops to go up kind when detecting inanimate object alkaline spot point, be eluted to purified water and stop when eluent does not have color; Soak resin 12h with 10% ammonia solution immersion resin or 152 type resins with 5% hydrochloric acid solution, the alcoholic solution eluting of reuse 10% ammonia accent PH to 9 or 152 type resins are with 5% hydrochloric acid solution eluting, and elution speed is 3BV/h; Eluent receives when with the inspection of silico-tungstic acid test solution deposition being arranged, and does not receive when eluent has deposition with the inspection of silico-tungstic acid test solution to stop, and merges eluent; Be neutralized to pH=6～8 with hydrochloric acid or with ammonia; Desalination, concentrate drying gets the sinomenine hydrochloride bullion.
C, refining: get sinomenine hydrochloride bullion 8kg, 75% ethanol or the dissolving extremely fully of purified water reflux with 100L add 5% bulking value active carbon doubly; Insulation refluxed 20 minutes, filtered while hot, and filtrating concentrates; Cooling, crystallize; Filter, it is colourless to filtrating that the ethanol with 80% cleans filter cake, gets sinomenine hydrochloride.
It is an amount of to take by weighing sinomenine hydrochloride 1g, sodium chloride 9g, water for injection, processes 1000ml; The water for injection stirring and dissolving that sodium chloride is added dosing amount 70% makes into concentrated solution, and the sinomenine hydrochloride that other takes by weighing recipe quantity adds in the above-mentioned concentrated solution, stirs to make dissolving, adds 0.1% needle-use activated carbon, stirs, and 35～45 ℃ are incubated 10 minutes, filter carbon removal; Replenish water for injection to full dose, stir, check, qualified after respectively with the filter element filtration of 0.45 μ m and 0.22 μ m; Sampling, check pH value, content, bacterial endotoxin, visible foreign matters are packed in the clean infusion bottle of 100ml by 100ml/ bottle branch, seal; Gland, sterilization promptly gets; Specification is 100ml: 100mg.
Embodiment two: a kind of method for preparing of sinomenine hydrochloride infusion solutions, this method comprises the steps:
A, extraction: Caulis Sinomenii coarse powder 800kg, with the 0.9mol/L HCl moistening of 1000L 5 hours, the dress percolator; Add 0.9mol/L HCl again and make liquid level cover medicated powder 2cm, flood after 20 hours, begin percolation by the speed of 5ml/min; Stop percolation after 24 hours, get percolate, subsequent use;
B, upper prop eluting: with cation exchange resin 001*4 type of having handled well on the percolate or 152 type resins, blade diameter length ratio 1: 10, last appearance speed be 5 times of column volumes/hour; With silico-tungstic acid test solution inspection deposition is arranged to effluent, and thin layer chromatography stops to go up kind when detecting inanimate object alkaline spot point, be eluted to purified water and stop when eluent does not have color; Soaked resin 12 hours with 10% ammonia solution immersion resin or 152 type resins with 8% hydrochloric acid solution, reuse 12% ammonia is transferred alcoholic solution eluting or 152 type resins, the 8% hydrochloric acid solution eluting of PH to 9, and elution speed is 5BV/h; Eluent receives when with the inspection of silico-tungstic acid test solution deposition being arranged, and does not receive when eluent has deposition with the inspection of silico-tungstic acid test solution to stop, and merges eluent; Be neutralized to pH=7 with the hydrochloric acid neutralization or with ammonia; Desalination, concentrate drying gets the sinomenine hydrochloride bullion.
C, refining: get sinomenine hydrochloride bullion 10kg, 85% ethanol or the dissolving extremely fully of purified water reflux with 120L add 5% bulking value active carbon doubly; Insulation refluxed 30 minutes, filtered while hot, and filtrating concentrates; Cooling, crystallize; Filter, it is colourless to filtrating that the ethanol with 75% cleans filter cake, gets sinomenine hydrochloride.
It is an amount of to take by weighing sinomenine hydrochloride 0.4g, sodium chloride 12g, water for injection, processes 1000ml; The water for injection stirring and dissolving that sodium chloride is added dosing amount 70% makes into concentrated solution, and the sinomenine hydrochloride that other takes by weighing recipe quantity adds in the above-mentioned concentrated solution, stirs to make dissolving, adds 0.1% needle-use activated carbon, stirs, and 35～45 ℃ are incubated 10 minutes, filter carbon removal; Replenish water for injection to full dose, stir, check, qualified after respectively with the filter element filtration of 0.45 μ m and 0.22 μ m; Sampling, check pH value, content, bacterial endotoxin, visible foreign matters are packed in the clean infusion bottle of 250ml by 250ml/ bottle branch, seal; Gland, sterilization promptly gets; Specification is 250ml: 100mg.
Embodiment three: a kind of method for preparing of sinomenine hydrochloride freeze-dried powder, this method comprises the steps:
A, extraction: Caulis Sinomenii coarse powder 800kg, with the 0.7mol/L HCl moistening of 900L 6 hours, the dress percolator; Add 0.8mol/L HCl again and make liquid level cover medicated powder 2cm, flood after 24 hours, begin percolation by the speed of 3ml/min; Stop percolation after 24 hours, get percolate, subsequent use;
B, upper prop eluting: with cation exchange resin of having handled well on the percolate or 152 type resins, blade diameter length ratio 1: 10, last appearance speed is 3 times of column volume/h; With silico-tungstic acid test solution inspection deposition is arranged to effluent, and thin layer chromatography stops to go up kind when detecting inanimate object alkaline spot point, be eluted to purified water and stop when eluent does not have color; Soaked resin 12 hours with 10% ammonia solution immersion resin or 152 type resins with 7% hydrochloric acid solution, reuse 12% ammonia is transferred alcoholic solution eluting or 152 type resins, the 5% hydrochloric acid solution eluting of PH to 9, and elution speed is 4BV/h; Eluent receives when with the inspection of silico-tungstic acid test solution deposition being arranged, and does not receive when eluent has deposition with the inspection of silico-tungstic acid test solution to stop, and merges eluent; Be neutralized to pH=7 with hydrochloric acid or with ammonia; Desalination, concentrate drying gets the sinomenine hydrochloride bullion.
C, refining: get sinomenine hydrochloride bullion 6kg, 55% ethanol or the dissolving extremely fully of purified water reflux with 80L add 3% bulking value active carbon doubly; Insulation refluxed 10～30 minutes, filtered while hot, and filtrating concentrates; Cooling, crystallize; Filter, it is colourless to filtrating that the ethanol with 80% cleans filter cake, gets sinomenine hydrochloride.
Get sinomenine hydrochloride 100g and proper amount of water for injection, add the sinomenine hydrochloride stirring and make dissolving; The active carbon of adding 0.1%, 35～45 ℃ are incubated 10 minutes, filter carbon removal; Replenish water for injection to 1000ml, stir, check; Respectively with the filter element filtration of 0.45 μ m and 0.22 μ m, sampling checks pH value, content, bacterial endotoxin, visible foreign matters to national standard after qualified; Prop up branch by 100mg/ and pack in ampoule or the cillin bottle, lyophilization promptly gets.
Embodiment four:
A, extraction: Caulis Sinomenii coarse powder 800kg, with the 0.7mol/L HCl moistening of 900L 6 hours, the dress percolator; Add 0.8mol/L HCl again and make liquid level cover medicated powder 2cm, flood after 24 hours, begin percolation by the speed of 3ml/min; Stop percolation after 24 hours, get percolate, subsequent use;
B, upper prop eluting: with cation exchange resin of having handled well on the percolate or 152 type resins, blade diameter length ratio 1: 10, last appearance speed is 3 times of column volume/h; With silico-tungstic acid test solution inspection deposition is arranged to effluent, and thin layer chromatography stops to go up kind when detecting inanimate object alkaline spot point, be eluted to purified water and stop when eluent does not have color; Soaked resin 12 hours with 10% ammonia solution immersion resin or 152 type resins with 7% hydrochloric acid solution, reuse 12% ammonia is transferred alcoholic solution eluting or 152 type resins, the 5% hydrochloric acid solution eluting of PH to 9, and elution speed is 4BV/h; Eluent receives when with the inspection of silico-tungstic acid test solution deposition being arranged, and does not receive when eluent has deposition with the inspection of silico-tungstic acid test solution to stop, and merges eluent; Be neutralized to pH=7 with hydrochloric acid or with ammonia; Desalination, concentrate drying gets the sinomenine hydrochloride bullion.
C, refining: get sinomenine hydrochloride bullion 6kg, 55% ethanol or the dissolving extremely fully of purified water reflux with 80L add 3% bulking value active carbon doubly; Insulation refluxed 10～30 minutes, filtered while hot, and filtrating concentrates; Cooling, crystallize; Filter, it is colourless to filtrating that the ethanol with 80% cleans filter cake, gets sinomenine hydrochloride.
It is an amount of to take by weighing sinomenine hydrochloride 1g, glucose 50g, water for injection, processes 1000ml;
The water for injection stirring and dissolving that adds dosing amount 70% earlier makes into concentrated solution, and the sinomenine hydrochloride that other takes by weighing recipe quantity adds in the above-mentioned concentrated solution, stirs to make dissolving, adds 0.1% needle-use activated carbon, stirs, and 35～45 ℃ are incubated 10 minutes, filter carbon removal; Replenish water for injection to full dose, stir, check, qualified after respectively with the filter element filtration of 0.45 μ m and 0.22 μ m; Sampling, check pH value, content, bacterial endotoxin, visible foreign matters are packed in the clean infusion bottle of 100ml by 100ml/ bottle branch, seal; Gland, sterilization promptly gets; Specification: 100ml: 100mg.
Embodiment five:
A, extraction: Caulis Sinomenii coarse powder 800kg, with the 0.9mol/L HCl moistening of 1000L 5 hours, the dress percolator; Add 0.9mol/L HCl again and make liquid level cover medicated powder 2cm, flood after 20 hours, begin percolation by the speed of 5ml/min; Stop percolation after 24 hours, get percolate, subsequent use;
B, upper prop eluting: with cation exchange resin 001*4 type of having handled well on the percolate or 152 type resins, blade diameter length ratio 1: 10, last appearance speed be 5 times of column volumes/hour; With silico-tungstic acid test solution inspection deposition is arranged to effluent, and thin layer chromatography stops to go up kind when detecting inanimate object alkaline spot point, be eluted to purified water and stop when eluent does not have color; Soaked resin 12 hours with 10% ammonia solution immersion resin or 152 type resins with 8% hydrochloric acid solution, reuse 12% ammonia is transferred alcoholic solution eluting or 152 type resins, the 8% hydrochloric acid solution eluting of PH to 9, and elution speed is 5BV/h; Eluent receives when with the inspection of silico-tungstic acid test solution deposition being arranged, and does not receive when eluent has deposition with the inspection of silico-tungstic acid test solution to stop, and merges eluent; Be neutralized to pH=7 with the hydrochloric acid neutralization or with ammonia; Desalination, concentrate drying gets the sinomenine hydrochloride bullion.
C, refining: get sinomenine hydrochloride bullion 10kg, 85% ethanol or the dissolving extremely fully of purified water reflux with 120L add 5% bulking value active carbon doubly; Insulation refluxed 30 minutes, filtered while hot, and filtrating concentrates; Cooling, crystallize; Filter, it is colourless to filtrating that the ethanol with 75% cleans filter cake, gets sinomenine hydrochloride.
It is an amount of to take by weighing sinomenine hydrochloride 0.4g, glucose 60g, water for injection, processes 1000ml;
The water for injection stirring and dissolving that adds dosing amount 70% earlier makes into concentrated solution, and the sinomenine hydrochloride that other takes by weighing recipe quantity adds in the above-mentioned concentrated solution, stirs to make dissolving, adds 0.1% needle-use activated carbon, stirs, and 35～45 ℃ are incubated 10 minutes, filter carbon removal; Replenish water for injection to full dose, stir, check, qualified after respectively with the filter element filtration of 0.45 μ m and 0.22 μ m; Sampling, check pH value, content, bacterial endotoxin, visible foreign matters are packed in the clean infusion bottle of 250ml by 250ml/ bottle branch, seal; Gland, sterilization promptly gets; Specification: 250ml: 100mg.
Embodiment six:
A, extraction: Caulis Sinomenii coarse powder 500kg, with the 0.5mol/L HCl moistening of 500L 3 hours, the dress percolator; Add 0.5mol/L HCl again and make liquid level cover medicated powder 2cm, flood after 12 hours, begin percolation by the speed of 3ml/min; Stop percolation after 12 hours, get percolate, subsequent use;
B, upper prop eluting: with cation exchange resin of having handled well on the percolate or 152 type resins, blade diameter length ratio 1: 10, last appearance speed be 3 times of column volumes/hour; With silico-tungstic acid test solution inspection deposition is arranged to effluent, and thin layer chromatography stops to go up kind when detecting inanimate object alkaline spot point, be eluted to purified water and stop when eluent does not have color; Soak resin 12h with 10% ammonia solution immersion resin or 152 type resins with 5% hydrochloric acid solution, the alcoholic solution eluting of reuse 10% ammonia accent PH to 9 or 152 type resins are with 5% hydrochloric acid solution eluting, and elution speed is 3BV/h; Eluent receives when with the inspection of silico-tungstic acid test solution deposition being arranged, and does not receive when eluent has deposition with the inspection of silico-tungstic acid test solution to stop, and merges eluent; Be neutralized to pH=6～8 with hydrochloric acid or with ammonia; Desalination, concentrate drying gets the sinomenine hydrochloride bullion.
C, refining: get sinomenine hydrochloride bullion 8kg, 75% ethanol or the dissolving extremely fully of purified water reflux with 100L add 5% bulking value active carbon doubly; Insulation refluxed 20 minutes, filtered while hot, and filtrating concentrates; Cooling, crystallize; Filter, it is colourless to filtrating that the ethanol with 80% cleans filter cake, gets sinomenine hydrochloride.
Get sinomenine hydrochloride 100g and proper amount of water for injection, add the sinomenine hydrochloride stirring and make dissolving; The active carbon of adding 0.1%, 35～45 ℃ are incubated 10 minutes, filter carbon removal; Replenish water for injection to 1000ml, stir, check; Respectively with the filter element filtration of 0.45 μ m and 0.22 μ m, sampling checks pH value, content, bacterial endotoxin, visible foreign matters to national standard after qualified; Prop up branch by 100mg/ and pack in ampoule or the cillin bottle, lyophilization promptly gets.
Embodiment seven:
A, extraction: Caulis Sinomenii coarse powder 800kg, with the 0.7mol/L HCl moistening of 900L 6 hours, the dress percolator; Add 0.8mol/L HCl again and make liquid level cover medicated powder 2cm, flood after 24 hours, begin percolation by the speed of 3ml/min; Stop percolation after 24 hours, get percolate, subsequent use;
B, upper prop eluting: with cation exchange resin of having handled well on the percolate or 152 type resins, blade diameter length ratio 1: 10, last appearance speed is 3 times of column volume/h; With silico-tungstic acid test solution inspection deposition is arranged to effluent, and thin layer chromatography stops to go up kind when detecting inanimate object alkaline spot point, be eluted to purified water and stop when eluent does not have color; Soaked resin 12 hours with 10% ammonia solution immersion resin or 152 type resins with 7% hydrochloric acid solution, reuse 12% ammonia is transferred alcoholic solution eluting or 152 type resins, the 5% hydrochloric acid solution eluting of PH to 9, and elution speed is 4BV/h; Eluent receives when with the inspection of silico-tungstic acid test solution deposition being arranged, and does not receive when eluent has deposition with the inspection of silico-tungstic acid test solution to stop, and merges eluent; Be neutralized to pH=7 with hydrochloric acid or with ammonia; Desalination, concentrate drying gets the sinomenine hydrochloride bullion.
C, refining: get sinomenine hydrochloride bullion 6kg, 55% ethanol or the dissolving extremely fully of purified water reflux with 80L add 3% bulking value active carbon doubly; Insulation refluxed 10～30 minutes, filtered while hot, and filtrating concentrates; Cooling, crystallize; Filter, it is colourless to filtrating that the ethanol with 80% cleans filter cake, gets sinomenine hydrochloride.
Get sinomenine hydrochloride 100g and proper amount of water for injection, add the sinomenine hydrochloride stirring and make dissolving; The active carbon of adding 0.1%, 35～45 ℃ are incubated 10 minutes, filter carbon removal; Replenish water for injection to 1000ml, stir, check; Respectively with the filter element filtration of 0.45 μ m and 0.22 μ m, sampling checks pH value, content, bacterial endotoxin, visible foreign matters to national standard after qualified; Prop up branch by 100mg/ and pack in ampoule or the cillin bottle, lyophilization promptly gets.
Attach:
1, silico-tungstic acid test solution inspection method
Silico-tungstic acid test solution preparation: press appendix 109 of Chinese Pharmacopoeia version in 2010.
Get 1ml and be examined liquid in color comparison tube, add 1 to 2 silico-tungstic acid test solution, observe.
2, thin layer chromatography
Thin layer chromatography condition immobile phase: silica gel thin-layer plate
Developing solvent: methanol: water: ammonia=8: 1: 1
Developer: bismuth potassium iodide weak solution
Point sample amount: 5ul
3, ammonia-alcoholic solution of pH8-11 is promptly transferred the alcoholic solution of pH to 8～11 with the ammonia of 8-15%.
Claims (9)
1. the method for preparing of a sinomenine hydrochloride infusion solutions is characterized in that this method comprises following arbitrary method:
Method one:
The method for preparing of step 1, sinomenine hydrochloride
A, extraction: Caulis Sinomenii coarse powder 100～1000 weight portions, with 0.1～1mol/L HCl moistening of 60～1000 parts by volume 0.5～8 hour, the dress percolator; Adding 0.1～1mol/L HCl again makes liquid level cover medicated powder 2cm; Flood after 6～48 hours, begin percolation, stop percolation after 6～24 hours by the speed of 2～5ml/min; Get percolate, subsequent use;
B, upper prop eluting: with cation exchange resin of having handled well on the percolate or 152 type resins, blade diameter length ratio 1: 8-12, last appearance speed be 2-5 times of column volume/hour; With silico-tungstic acid test solution inspection deposition is arranged to effluent, and thin layer chromatography stops to go up kind when detecting inanimate object alkaline spot point, be eluted to purified water and stop when eluent does not have color; Soaked resin 12 hours with 8-15% ammonia solution immersion resin or 152 type resins with the 3-10% hydrochloric acid solution, the ammonia of reuse pH8-11-alcoholic solution eluting or 152 type macroporous adsorbent resins are with 3-10% hydrochloric acid solution eluting, and elution speed is 2-5BV/h; Eluent receives when with the inspection of silico-tungstic acid test solution deposition being arranged, and does not receive when eluent has deposition with the inspection of silico-tungstic acid test solution to stop, and merges eluent; Be neutralized to pH=6-8 with hydrochloric acid or ammonia; Desalination, concentrate drying gets the sinomenine hydrochloride bullion.
C, refining: get sinomenine hydrochloride bullion 5～10 weight portions,, add the active carbon of 3-6% times of weight with 10～95% ethanol or the dissolving extremely fully of purified water reflux of 30～120 parts by volume; Insulation refluxed 10～30 minutes, filtered while hot, and filtrating concentrates; Cooling, crystallize; Filter, colourless with the ethanol cleaning filter cake of 75-95% to filtrating, get sinomenine hydrochloride;
The preparation of step 2, sodium chloride infusion solutions
It is an amount of to take by weighing sinomenine hydrochloride 0.3-2 weight portion, sodium chloride 6-15 weight portion, water for injection, gets the sodium chloride of above-mentioned amount, and the water for injection stirring and dissolving that adds dosing amount 60%-80% makes into concentrated solution; The sinomenine hydrochloride that other takes by weighing recipe quantity adds in the above-mentioned concentrated solution; Stirring makes dissolving, adds the needle-use activated carbon of 0.05%-0.5%, stirs; 35～45 ℃ are incubated 10 minutes, filter carbon removal; Replenish water for injection to 1000 parts by volume, stir, check filters with the filter element of 0.35-0.55 μ m and 0.1-0.3 μ m respectively after qualified, and sampling checks pH value, content, bacterial endotoxin, visible foreign matters to meeting national injection standard, sterilizes, and promptly gets.
Method two:
Step 1, with step 1 in the method one;
The preparation of step 2, glucose infusion solutions
It is an amount of to take by weighing sinomenine hydrochloride 0.3-2 weight portion, glucose 40-60 weight portion, water for injection, gets the glucose of above-mentioned amount, and the water for injection stirring and dissolving that adds dosing amount 60%-80% makes into concentrated solution; The sinomenine hydrochloride that other takes by weighing recipe quantity adds in the above-mentioned concentrated solution; Stirring makes dissolving, adds the needle-use activated carbon of 0.05%-0.5%, stirs; 35～45 ℃ are incubated 10 minutes, filter carbon removal; Replenish water for injection to 1000 parts by volume; Stir, check filters with the filter element of 0.35-0.55 μ m and 0.1-0.3 μ m respectively after qualified, and sampling checks pH value, content, bacterial endotoxin, visible foreign matters to National standard, sterilizes, and promptly gets.
2. the method for preparing of a sinomenine hydrochloride lyophilized injectable powder is characterized in that this method comprises the steps:
The method for preparing of step 1, sinomenine hydrochloride
A, extraction: Caulis Sinomenii coarse powder 100～1000 weight portions, with 0.1～1mol/L HCl moistening of 60～1000 parts by volume 0.5～8 hour, the dress percolator; Adding 0.1～1mol/L HCl again makes liquid level cover medicated powder 2cm; Flood after 6～48 hours, begin percolation, stop percolation after 6～24 hours by the speed of 2～5ml/min; Get percolate, subsequent use;
B, upper prop eluting: with cation exchange resin of having handled well on the percolate or 152 type resins, blade diameter length ratio 1: 8-12, last appearance speed be 2-5 times of column volume/hour; With silico-tungstic acid test solution inspection deposition is arranged to effluent, and thin layer chromatography stops to go up kind when detecting inanimate object alkaline spot point, be eluted to purified water and stop when eluent does not have color; Soaked resin 12 hours with 8-15% ammonia solution immersion resin or 152 type resins with the 3-10% hydrochloric acid solution, the ammonia of reuse pH8-11-alcoholic solution eluting or 152 type macroporous adsorbent resins are with 3-10% hydrochloric acid solution eluting, and elution speed is 2-5BV/h; Eluent receives when with the inspection of silico-tungstic acid test solution deposition being arranged, and does not receive when eluent has deposition with the inspection of silico-tungstic acid test solution to stop, and merges eluent; Be neutralized to pH=6-8 with hydrochloric acid or ammonia; Desalination, concentrate drying gets the sinomenine hydrochloride bullion.
C, refining: get sinomenine hydrochloride bullion 5～10 weight portions,, add the active carbon of 3-6% times of weight with 10～95% ethanol or the dissolving extremely fully of purified water reflux of 30～120 parts by volume; Insulation refluxed 10～30 minutes, filtered while hot, and filtrating concentrates; Cooling, crystallize; Filter, colourless with the ethanol cleaning filter cake of 75-95% to filtrating, get sinomenine hydrochloride;
Step 2,
Get sinomenine hydrochloride 50-150 weight portion and proper amount of water for injection, add the stirring of recipe quantity sinomenine hydrochloride and make dissolving; The active carbon that adds 0.05-0.5%, 35～45 ℃ are incubated 5-20 minute, filter carbon removal; Replenish water for injection to 1000 parts by volume, stir, check filters with the filter element of 0.35-0.55 μ m and 0.1-0.3 μ m respectively after qualified, takes a sample, and checks pH value, content, bacterial endotoxin, visible foreign matters to National standard, packing, and lyophilization promptly gets.
3. the method for preparing of sinomenine infusion solutions as claimed in claim 1 is characterized in that step 2 is any of following steps in the method one:
It is an amount of to take by weighing sinomenine hydrochloride 0.5 weight portion, sodium chloride 6 weight portions, water for injection, gets the sodium chloride of above-mentioned amount, and the water for injection stirring and dissolving that adds dosing amount 70% makes into concentrated solution; The sinomenine hydrochloride that other gets recipe quantity adds in the above-mentioned concentrated solution; Stirring makes dissolving, adds 0.1% needle-use activated carbon, stirs; 35～45 ℃ are incubated 10 minutes, filter carbon removal; Replenish water for injection to 1000 parts by volume, stir, check filters with the filter element of 0.45 μ m and 0.22 μ m respectively after qualified, sampling, and check pH value, content, bacterial endotoxin, visible foreign matters are sterilized to meeting national injection standard, promptly get;
Or it is an amount of to take by weighing sinomenine hydrochloride 1 weight portion, sodium chloride 10 weight portions, water for injection, gets the sodium chloride of above-mentioned amount, and the water for injection stirring and dissolving that adds dosing amount 70% makes into concentrated solution; The sinomenine hydrochloride that other gets recipe quantity adds in the above-mentioned concentrated solution; Stirring makes dissolving, adds 0.2% needle-use activated carbon, stirs; 35～45 ℃ are incubated 10 minutes, filter carbon removal; Replenish water for injection to 1000 parts by volume, stir, check filters with the filter element of 0.35 μ m and 0.15 μ m respectively after qualified, sampling, and check pH value, content, bacterial endotoxin, visible foreign matters are sterilized to meeting national injection standard, promptly get.
4. the method for preparing of sinomenine infusion solutions as claimed in claim 1 is characterized in that step 2 is any of following steps in the method two:
It is an amount of to take by weighing sinomenine hydrochloride 0.5 weight portion, glucose 45 weight portions, water for injection, gets the glucose of recipe quantity, and the water for injection stirring and dissolving that adds dosing amount 70% makes into concentrated solution; The sinomenine hydrochloride that other gets recipe quantity adds in the above-mentioned concentrated solution; Stirring makes dissolving, adds 0.1% needle-use activated carbon, stirs; 35～45 ℃ are incubated 10 minutes, filter carbon removal; Replenish water for injection to 1000 parts by volume, stir, check filters with the filter element of 0.45 μ m and 0.22 μ m respectively after qualified, sampling, and check pH value, content, bacterial endotoxin, visible foreign matters are sterilized to National standard, promptly get;
Or it is an amount of to take by weighing sinomenine hydrochloride 1 weight portion, glucose 55 weight portions, water for injection, gets the glucose of recipe quantity, and the water for injection stirring and dissolving that adds dosing amount 60% makes into concentrated solution; The sinomenine hydrochloride that other gets recipe quantity adds in the above-mentioned concentrated solution; Stirring makes dissolving, adds 0.2% needle-use activated carbon, stirs; 35～45 ℃ are incubated 10 minutes, filter carbon removal; Replenish water for injection to 1000 parts by volume, stir, check filters with the filter element of 0.35 μ m and 0.15 μ m respectively after qualified, sampling, and check pH value, content, bacterial endotoxin, visible foreign matters are sterilized to National standard, promptly get.
5. the method for preparing of sinomenine lyophilized injectable powder as claimed in claim 2 is characterized in that step 2 is any of following steps:
Get sinomenine hydrochloride 100 weight portions and proper amount of water for injection, add the stirring of recipe quantity sinomenine hydrochloride and make dissolving; The active carbon of adding 0.1%, 35～45 ℃ are incubated 10 minutes, filter carbon removal; Replenish water for injection to 1000 parts by volume, stir, check filters with the filter element of 0.45 μ m and 0.22 μ m respectively after qualified, and sampling checks pH value, content, bacterial endotoxin, visible foreign matters to National standard, packing, and lyophilization promptly gets;
Perhaps get sinomenine hydrochloride 140 weight portions and proper amount of water for injection, add the stirring of recipe quantity sinomenine hydrochloride and make dissolving; The active carbon of adding 0.2%, 35～45 ℃ are incubated 6 minutes, filter carbon removal; Replenish water for injection to 1000 parts by volume, stir, check filters with the filter element of 0.35 μ m and 0.3 μ m respectively after qualified, and sampling checks pH value, content, bacterial endotoxin, visible foreign matters to National standard, packing, and lyophilization promptly gets.
6. like the method for preparing of arbitrary described sinomenine hydrochloride infusion solutions of claim 1-5 or lyophilized injectable powder, it is characterized in that in this method that in the step 1 B step, strong cation-exchanging resin is 001*2.5,001*4 type resin, macroporous adsorbent resin is 152 types; The resin path height ratio is 1: 10.
7. like the method for preparing of arbitrary described sinomenine hydrochloride infusion solutions of claim 1-5 or lyophilized injectable powder, it is characterized in that in this method adding the active carbon of 4% times of weight in the step 1 C step; Concentration of alcohol is 40%, 55%, 60%, 75% or 80% during reflux.
8. like the method for preparing of arbitrary described sinomenine hydrochloride infusion solutions of claim 1-5 or lyophilized injectable powder, it is characterized in that in this method in the step 1 B step, last appearance speed be 3 times of column volumes/hour; Soak resin with 10% ammonia solution or 5% hydrochloric acid solution.
9. like the method for preparing of arbitrary described sinomenine hydrochloride infusion solutions of claim 1-5 or lyophilized injectable powder; It is characterized in that in this method in the step 1 B step; With ammonia-alcoholic solution of pH8-11 elute soln as cation exchange resin, eluent is neutralized to pH=6～8 with hydrochloric acid; 5%HCl solution is as the elute soln of 152 type macroporous adsorbent resins.
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