CN102603632A - Method for preparing sinomenine hydrochloride by using non-organic solvent - Google Patents
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Abstract
The invention provides a preparation method of sinomenine hydrochloride. The method comprises the steps of: A) extraction: wetting caulis sinomenii coarse powder by using hydrochloric acid (HCl), installing a percolator, adding HCl for impregnation and percolation to obtain percolate; B) eluting treated cation exchange resin or 152 resin on the percolate by using ammonia water-ethanol solution or HCl with concentration being 3-10 percent, desalting, condensing and drying to obtain sinomenine hydrochloride crude products; and C) taking the sinomenine hydrochloride crude products, heating the crude products in ethanol or purified water for back flowing, condensing filtrate, cooling, crystallizing, filtering and using ethanol to wash a filter cake to obtain the sinomenine hydrochloride. Since the method adopts an absorbing process through the cation exchange resin or large-pore absorbing resin to replace the traditional extraction process through high-toxicity benzene and chloroform, the extraction rate is high, the method is simpler and convenient to operate, the harm and the pollution caused by high quantity of high-toxicity organic solvent to operator health and the environment can be avoided, the treatment process of the organic solvent is reduced, the environmental protection is further facilitated, the investment in environmental protection facilities of a factory is reduced and the environmental-friendly production is facilitated. The sinomenine hydrochloride prepared by adopting the method through extraction and separation can be used as a raw material for pharmaceutical preparations, the purity is higher, solvent residue does not exists and the potential harm to human bodies is reduced.
Description
Technical field
The present invention relates to a kind of preparation method of sinomenine hydrochloride, be specifically related to the method that a kind of non-organic solvent extracts effective constituent sinomenine hydrochloride in the Stem of Orientoine.
Background technology
Stem of Orientoine 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 itch, also have effects such as anti-heart disorder and step-down.
Staple is a vegeto-alkali in the Stem of Orientoine; The composition of having found at present has tuduranine (Sinomenine); Isosinomenine (Igoginomenine), magnificent tuduranine (SinoAcutine), short sinomenium acutum time alkali (Acutumidine); Point tuduranine (Sinaetine) and disinomenine (Diginomenine), ethyl tuduranine (ethylsinomenine), tetrahydrochysene epiberberine (sinactine), tetrahydrochysene epiberberine, yellow parilla ripple phenol alkali, bianfugenine, Tetrahydropalmatine etc.
Tuduranine (Sinomenine) is a kind of alkaloid monomer that extracts in the Stem of Orientoine, is the main effective constituent of Stem of Orientoine performance analgesia, anti-inflammatory action, from Japanese Stem of Orientoine, is separated obtaining the earliest by Ishiwari etc.The sixties in 20th century, Chinese scholar Zhu Renhong also found tuduranine from homemade Stem of Orientoine.Its hydrochloride preparation commonly used clinically such as ZHENGQINGFENGTONGNING PIAN, ZHENGQINGFENGTONGNING slow releasing tablet, ZHENGQINGFENGTONGNING injection liquid are used to treat rheumatic, rheumatoid arthritis, and treatment ankylosing spondylitis, irregular pulse etc. are evident in efficacy.
At present the industrial production sinomenine hydrochloride adopts the alkalization water extraction process more, and it is for adding entry and a certain amount of white lime in Stem of Orientoine, alkalization for some time, add a certain amount of technical benzene then, refluxing extraction, last acidifying, leave standstill, crystallization.Stem of Orientoine dilute sulphuric acid percolate is transferred pH value 9 with liming, 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 noxious 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 traditional Chinese medicine extraction, should avoid the use of benzene and chloroform solvent as far as possible.
Summary of the invention
The invention provides a kind of preparation method of sinomenine hydrochloride of non-organic solvent.
The present invention seeks to realize through following technical scheme:
A kind of preparation method of sinomenine hydrochloride of non-organic solvent, this method comprises the steps:
A, extraction: Stem of Orientoine meal 100～1000 weight parts, wetting 0.5～8 hour, dress percolator with 0.1～1mol/L HCl of 60～1000 parts by volume; Adding 0.1～1mol/L HCl again makes liquid level cover medicinal powder 2cm; Flood after 6～48 hours, begin diacolation, stop diacolation after 6～24 hours by the speed of 2～5ml/min; Get percolate, subsequent use;
B, upper prop wash-out: with Zeo-karb 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 silicotungstic acid test solution inspection deposition is arranged to effluent, and thin-layer chromatography stops to go up kind when detecting lifeless matter alkaline spot point, be eluted to purified water and stop when elutriant does not have color; Soak resin or 152 type resins with 3-10% hydrochloric acid soln immersion resin 12 hours with the 8-15% ammonia solution, again with ammoniacal liquor-ethanolic soln wash-out of pH8-11 or 152 type resins with 3-10% hydrochloric acid soln wash-out, elution speed is 2-5BV/h; Elutriant receives when with the inspection of silicotungstic acid test solution deposition being arranged, and does not receive when elutriant has deposition with the inspection of silicotungstic acid test solution to stop, and merges elutriant; Be neutralized to pH=6-8 with hydrochloric acid or ammoniacal liquor; Desalination, concentrate drying gets the sinomenine hydrochloride bullion.
C, refining: get sinomenine hydrochloride bullion 5～10 weight parts,, add the gac 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, crystallization; Filter, colourless with the ethanol cleaning filter cake of 75-95% to filtrating, get sinomenine hydrochloride.
Parametric optimization among the preparation method of sinomenine hydrochloride of the present invention is following:
In the B step, the preferred 001*2.5 of strong cation-exchanging resin, 001*4, 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 soln; With ammoniacal liquor-ethanolic soln of pH8-11 elute soln as Zeo-karb, elutriant 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 gac of 4% times of weight; Preferred 40%, 55%, 60%, 75% during reflux, 80% ethanol.
The weight part among the preparation method of above-mentioned sinomenine hydrochloride and the relation of parts by volume are the relation of g/ml.
The inventive method adopts through Zeo-karb 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 treating processes of organic solvent; More help environment protection, reduced the input of the environmental protection facility of factory, help environmental friendliness production.The sinomenine hydrochloride of present 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 Stem of Orientoine non-organic solvent
1, experimental technique
1.1 material and instrument
Stem of Orientoine medicinal material coarse powder, macroporous adsorbent resin, sinomenine hydrochloride reference substance, hydrochloric acid, ammoniacal liquor, sodium hydroxide, ethanol, sodium-chlor etc.
Glass column (diameter 3cm, high by 30～40cm), HPLC performance liquid detector, rotary evaporimeter.
1.2 method and result
1.2.1 decision method
(1) the vegeto-alkali indicator is selected
Press a method preparation of Chinese Pharmacopoeia version in 2010 bismuth potassium iodide dilute solution, basic iron Potssium Cyanide, three kinds of vegeto-alkali indicator of silicotungstic acid test solution; Getting 1～2 respectively drips in inspection liquid; Precipitate, coupling reaction; Experiment contrast premenstruum shows that the indication of silicotungstic acid test solution is the most directly perceived, sensitive.The indicator of silicotungstic acid test solution as endpoint adopted in this experimental design.
(2) thin-layer chromatography: stationary phase: silica gel thin-layer plate; Developping agent: methyl alcohol: water: ammoniacal liquor=8: 1: 1; Developer: rare bismuth potassium iodide solution.
(3) HPLC
Use octadecylsilane chemically bonded silica to be weighting agent; With acetonitrile-0.78% sodium dihydrogen phosphate (12: 88) is moving 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, Zeo-karb, manufacturer: Shandong Lukang Record Pharmaceuticals Co., Ltd.;
732 types, sodium type Zeo-karb, manufacturer: Cangzhou Bon Adsorption Material Science and Technology Co., Ltd.
001 * 2.5 type, H type Zeo-karb, manufacturer: Shandong Lukang Record Pharmaceuticals Co., Ltd.;
001 * 4 type, H type Zeo-karb, 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 pre-treatment, get the percolate (pH is transferred to 3) of 1000g medicinal 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 silicotungstic acid test solution inspection to effluent, water is washed till elutriant not to be had till the color basically.The applied sample amount and the adsorptive power of contrast different resins, the resin model of selected good best producer is chosen the sorbing 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 chromatography 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 Erlenmeyer flask, add the above-mentioned obtain solution of 10ml, wave on the vibrator 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 liquid stock
2, extract stoste 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 Erlenmeyer flask; Add the diacolation stoste 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 Stem of Orientoine is extracted
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 adsorptive power in percolate too a little less than.
1.2.3 desorb or wash-out
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% ammoniacal liquor liquid.
2. 10% ammoniacal liquor liquid.
3. 95% ethanolic soln.
4. transfer the ethanolic soln of PH to 8-11 with ammoniacal liquor.
5. salt, diluted acid.(the 5%HCl solution of NH4Cl)
6. salt, rare alcohol.(20%NaCl+ ethanolic soln)
Get sour water percolate 500ml, through resin column, be washed till neutrality with purified water, more respectively with the speed wash-out of different elutriants, till the lifeless matter 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 elutriants of table 4 are to the influence of sinomenine hydrochloride elute effect
Above experiment table really shows: ammoniacal liquor-ethanolic soln of pH8-11 is adopted in resin cation(R.C.) absorption back, can obtain elute effect preferably.
(2) macroporous adsorbent resin (152 type)
1. 50% ethanolic soln.
2. 75% ethanolic soln.
3. 95% ethanolic soln.
4. 5%HCl solution.
Get sour water percolate 500ml, through resin column, be washed till neutrality with purified water, more respectively with the speed wash-out of different elutriants, till the lifeless matter 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 elutriants to the sinomenine hydrochloride elute effect
Experimental result shows: adopt different elutriants that the adsorption liquid of 152 type resins is carried out desorb, only HCl has desorption effect, so this resin adopts 5%HCl to carry out wash-out.
1.2.3 Static Adsorption is confirmed desorption condition
Through the selected good elutriant of above-mentioned experiment, adopt the mode of Static Adsorption, after absorption 12 hours, with resin with the purified water rinsing to water during lifeless matter 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 Stem of Orientoine is extracted
Above result shows, adopts the stripping liquid of confirming to carry out desorb, all can separate the sinomenine hydrochloride of sucking-off resin absorption.
1.3 conclusion
Adopt macroporous adsorbent resin and Zeo-karb; Sinomenine hydrochloride there is big adsorption; Through experiment; The optimum resin that selected 001*2.5, two kinds of Zeo-karbs of 001*4,152 type macroporous adsorbent resins extract as this sinomenine hydrochloride purifying adopts the elute soln of ammoniacal liquor-ethanolic soln (pH8～11) as Zeo-karb, 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 preparation method of sinomenine hydrochloride of non-organic solvent, this method comprises the steps:
A, extraction: Stem of Orientoine meal 500kg, wetting 3 hours, dress percolator with the 0.5mol/L HCl of 500L; Add 0.5mol/L HCl again and make liquid level cover medicinal powder 2cm, flood after 12 hours, begin diacolation by the speed of 3ml/min; Stop diacolation after 12 hours, get percolate, subsequent use;
B, upper prop wash-out: with Zeo-karb 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 silicotungstic acid test solution inspection deposition is arranged to effluent, and thin-layer chromatography stops to go up kind when detecting lifeless matter alkaline spot point, be eluted to purified water and stop when elutriant does not have color; Soak resin or 152 type resins soak resin 12h with 5% hydrochloric acid soln with 10% ammonia solution, again with the ethanolic soln wash-out of 10% ammoniacal liquor accent PH to 9 or 152 type resins with 5% hydrochloric acid soln wash-out, elution speed is 3BV/h; Elutriant receives when with the inspection of silicotungstic acid test solution deposition being arranged, and does not receive when elutriant has deposition with the inspection of silicotungstic acid test solution to stop, and merges elutriant; Be neutralized to pH=6～8 with hydrochloric acid or with ammoniacal liquor; 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 gac doubly; Insulation refluxed 20 minutes, filtered while hot, and filtrating concentrates; Cooling, crystallization; Filter, it is colourless to filtrating that the ethanol with 80% cleans filter cake, gets sinomenine hydrochloride.
Embodiment two: a kind of preparation method of sinomenine hydrochloride of non-organic solvent, this method comprises the steps:
A, extraction: Stem of Orientoine meal 800kg, wetting 5 hours, dress percolator with the 0.9mol/L HCl of 1000L; Add 0.9mol/L HCl again and make liquid level cover medicinal powder 2cm, flood after 20 hours, begin diacolation by the speed of 5ml/min; Stop diacolation after 24 hours, get percolate, subsequent use;
B, upper prop wash-out: with Zeo-karb 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 silicotungstic acid test solution inspection deposition is arranged to effluent, and thin-layer chromatography stops to go up kind when detecting lifeless matter alkaline spot point, be eluted to purified water and stop when elutriant does not have color; Soaked resin 12 hours with 10% ammonia solution immersion resin or 152 type resins with 8% hydrochloric acid soln, transfer ethanolic soln wash-out or 152 type resins, the 8% hydrochloric acid soln wash-out of PH to 9 again with 12% ammoniacal liquor, elution speed is 5BV/h; Elutriant receives when with the inspection of silicotungstic acid test solution deposition being arranged, and does not receive when elutriant has deposition with the inspection of silicotungstic acid test solution to stop, and merges elutriant; Be neutralized to pH=7 with the hydrochloric acid neutralization or with ammoniacal liquor; 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 gac doubly; Insulation refluxed 30 minutes, filtered while hot, and filtrating concentrates; Cooling, crystallization; Filter, it is colourless to filtrating that the ethanol with 75% cleans filter cake, gets sinomenine hydrochloride.
Embodiment three: a kind of preparation method of sinomenine hydrochloride of non-organic solvent, this method comprises the steps:
A, extraction: Stem of Orientoine meal 800kg, wetting 6 hours, dress percolator with the 0.7mol/L HCl of 900L; Add 0.8mol/L HCl again and make liquid level cover medicinal powder 2cm, flood after 24 hours, begin diacolation by the speed of 3ml/min; Stop diacolation after 24 hours, get percolate, subsequent use;
B, upper prop wash-out: with Zeo-karb 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 silicotungstic acid test solution inspection deposition is arranged to effluent, and thin-layer chromatography stops to go up kind when detecting lifeless matter alkaline spot point, be eluted to purified water and stop when elutriant does not have color; Soaked resin 12 hours with 10% ammonia solution immersion resin or 152 type resins with 7% hydrochloric acid soln, transfer ethanolic soln wash-out or 152 type resins, the 5% hydrochloric acid soln wash-out of PH to 9 again with 12% ammoniacal liquor, elution speed is 4BV/h; Elutriant receives when with the inspection of silicotungstic acid test solution deposition being arranged, and does not receive when elutriant has deposition with the inspection of silicotungstic acid test solution to stop, and merges elutriant; Be neutralized to pH=7 with hydrochloric acid or with ammoniacal liquor; 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 gac doubly; Insulation refluxed 10～30 minutes, filtered while hot, and filtrating concentrates; Cooling, crystallization; Filter, it is colourless to filtrating that the ethanol with 80% cleans filter cake, gets sinomenine hydrochloride.
Attach: 1, silicotungstic acid test solution inspection method
Silicotungstic acid test solution preparation: press appendix 109 of Chinese Pharmacopoeia version in 2010.
Get 1ml and be examined liquid in tube comparison tubes, add 1 to 2 silicotungstic acid test solution, observe.
2, thin layer chromatography
Thin-layer chromatography condition stationary phase: silica gel thin-layer plate
Developping agent: methyl alcohol: water: ammoniacal liquor=8: 1: 1
Developer: bismuth potassium iodide dilute solution
Point sample amount: 5ul
3, ammoniacal liquor-ethanolic soln of pH8-11 is promptly transferred the ethanolic soln of pH to 8～11 with the ammoniacal liquor of 8-15%.
Claims (9)
1. a non-organic solvent prepares the method for sinomenine hydrochloride, it is characterized in that this method comprises the steps:
A, extraction: Stem of Orientoine meal 100～1000 weight parts, wetting 0.5～8 hour, dress percolator with 0.1～1mol/L HCl of 60～1000 parts by volume; Adding 0.1～1mol/L HCl again makes liquid level cover medicinal powder 2cm; Flood after 6～48 hours, begin diacolation, stop diacolation after 6～24 hours by the speed of 2～5ml/min; Get percolate, subsequent use;
B, upper prop wash-out: with Zeo-karb 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 silicotungstic acid test solution inspection deposition is arranged to effluent, and thin-layer chromatography stops to go up kind when detecting lifeless matter alkaline spot point, be eluted to purified water and stop when elutriant does not have color; Soak resin or 152 type resins with 3-10% hydrochloric acid soln immersion resin 12 hours with the 8-15% ammonia solution, again with ammoniacal liquor-ethanolic soln wash-out of pH8-11 or 152 type resins with 3-10% hydrochloric acid soln wash-out, elution speed is 2-5BV/h; Elutriant receives when with the inspection of silicotungstic acid test solution deposition being arranged, and does not receive when elutriant has deposition with the inspection of silicotungstic acid test solution to stop, and merges elutriant; Be neutralized to pH=6-8 with hydrochloric acid or ammoniacal liquor; Desalination, concentrate drying gets the sinomenine hydrochloride bullion.
C, refining: get sinomenine hydrochloride bullion 5～10 weight parts,, add the gac 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, crystallization; Filter, colourless with the ethanol cleaning filter cake of 75-95% to filtrating, get sinomenine hydrochloride.
2. the method for preparing sinomenine hydrochloride as claimed in claim 1 is characterized in that in this method B step that strong cation-exchanging resin is 001*2.5 or 001*4 type resin; Macroporous adsorbent resin is 152 types.
3. according to claim 1 or claim 2 the method for preparing sinomenine hydrochloride is characterized in that the resin path height ratio is 1: 10 in this method B step; Last appearance speed be 3 times of column volumes/hour.
4. according to claim 1 or claim 2 the method for preparing sinomenine hydrochloride is characterized in that in this method B step, soaks resin with 10% ammonia solution or 5% hydrochloric acid soln; With ammoniacal liquor-ethanolic soln of pH8-11 elute soln as Zeo-karb; 5%HCl solution is as the elute soln of 152 type macroporous adsorbent resins.
5. according to claim 1 or claim 2 the method for preparing sinomenine hydrochloride is characterized in that in this method B step, soaks resin with 10% ammonia solution or 5% hydrochloric acid soln; With ammoniacal liquor-ethanolic soln of pH8-11 elute soln as Zeo-karb; 5%HCl solution is as the elute soln of 152 type macroporous adsorbent resins.
6. according to claim 1 or claim 2 the method for preparing sinomenine hydrochloride is characterized in that adding the gac of 4% times of weight in this method C step; Alcohol concn is 40%, 55%, 60%, 75% or 80% during reflux.
7. the method for preparing sinomenine hydrochloride as claimed in claim 3 is characterized in that adding the gac of 4% times of weight in this method C step; Alcohol concn is 40%, 55%, 60%, 75% or 80% during reflux.
8. the method for preparing sinomenine hydrochloride as claimed in claim 3 is characterized in that adding the gac of 4% times of weight in this method C step; Alcohol concn is 40%, 55%, 60%, 75% or 80% during reflux.
9. the method for preparing sinomenine hydrochloride as claimed in claim 3 is characterized in that adding the gac of 4% times of weight in this method C step; Alcohol concn is 40%, 55%, 60%, 75% or 80% during reflux.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN106137949A (en) * | 2016-08-04 | 2016-11-23 | 长沙原道医药科技开发有限公司 | Sinomenine hydrochloride ointment prepared by a kind of inorganic solvent and preparation method thereof |
| CN106176578A (en) * | 2016-08-04 | 2016-12-07 | 长沙原道医药科技开发有限公司 | Sinomenine hydrochloride gel prepared by a kind of organic solvent and preparation method thereof |
| CN106176577A (en) * | 2016-08-04 | 2016-12-07 | 长沙原道医药科技开发有限公司 | Sinomenine hydrochloride gel prepared by a kind of inorganic solvent and preparation method thereof |
| CN106236700A (en) * | 2016-08-04 | 2016-12-21 | 长沙原道医药科技开发有限公司 | Sinomenine hydrochloride ointment prepared by a kind of organic solvent and preparation method thereof |
| CN106265516A (en) * | 2016-08-04 | 2017-01-04 | 长沙原道医药科技开发有限公司 | Sinomenine hydrochloride spray prepared by a kind of inorganic solvent and preparation method thereof |
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