CN102614149A - Method for preparing sinomenine capsules - Google Patents
Method for preparing sinomenine capsules Download PDFInfo
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- CN102614149A CN102614149A CN2012100889914A CN201210088991A CN102614149A CN 102614149 A CN102614149 A CN 102614149A CN 2012100889914 A CN2012100889914 A CN 2012100889914A CN 201210088991 A CN201210088991 A CN 201210088991A CN 102614149 A CN102614149 A CN 102614149A
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Abstract
The invention provides a method for preparing sinomenine capsules and has the advantages that a displacement method is adopted for preparing sinomenine, the operation is simple, during the extraction process, heating is not needed and cold treatment is adopted; the yield is high, and treatment of mother liquid is simple; and the method is safe and reliable and low-pollution and plays a positive role in environmental protection.
Description
Technical field
The present invention relates to a kind of method for preparing of sinomenine hydrochloride capsule, be specifically related to a kind of percolation and extract the method that effective ingredient sinomenine hydrochloride in the Caulis Sinomenii is processed the sinomenine hydrochloride capsule.
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, in water-bath, last acidify, leave standstill, crystallize.
Document has report to introduce the extraction and the purification process of sinomenine at present, and Caulis Sinomenii dilute sulfuric acid percolate is with lime water adjust pH 9; Benzene carries out counter-current extraction at 50 ℃, and benzene extraction liquid carries out the extraction of regurgitation stream, activated carbon decolorizing with 1% hydrochloric acid; Recrystallization is carried out in crystallization in hot water, get pure article.(Chen Yukun " extracting technique of Chinese medicine ", 1992)
This several method all uses the very big benzene of toxicity as extracting solvent; Benzene is I class toxic solvent; Murder by poisoning to human body is main with blood system and neurasthenia's disease crowd, shows as blood leukocytes, platelet and erythrocytopenia, dizziness, headache, hypomnesis, insomnia etc.Aplastic anemia can take place in severe patient, even leukemia, death, and is disabled at pharmaceutical industry.And the recovery of benzene is comparatively cumbersome, and the discharging difficulty reaches environmental requirement.Thereby in Chinese medicine extraction, replace the key that the raw material that contains benzene is the prevention benzolism with the raw material that does not contain benzene.
Summary of the invention
The object of the invention is to provide a kind of method for preparing of sinomenine hydrochloride capsule.
The present invention seeks to realize that through following technical scheme the method for preparing of sinomenine hydrochloride capsule of the present invention comprises the steps:
The method for preparing of step 1, sinomenine hydrochloride
A, preparation sinomenine hydrochloride bullion
1, extract: 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, adorn percolator; Adding 0.1～1mol/L HCl again makes liquid level cover medicated powder 2～6cm; Flood after 6～48 hours, begin percolation, stop percolation after 6～24 hours by the speed of 2～6ml/min; Get percolate, subsequent use;
2, extraction: above-mentioned percolate is added lime cream transfer pH to 10.5～12.0, filter, filtrating adds hydrochloric acid and transfers pH to 7.0～9.5, with chloroform extraction 2～5 times; Combined chloroform layer water is washed till neutrality, adds the anhydrous Na of 3%～6% times of weight
2The SO4 dehydration, concentrating under reduced pressure reclaims chloroform;
3, crystallization: concentrated solution splashes into 6mol/L HCl and transfers pH to 2～4, and be stirred to the come-up solids and disperse, cold preservation, sucking filtration discards filtrating, and 60 ℃～70 ℃ oven dry filter cakes get yellow sinomenine hydrochloride bullion;
B, sinomenine hydrochloride process for refining
Get sinomenine hydrochloride bullion 5～10 weight portions,, add the active carbon of 4% 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, it is colourless to filtrating that the ethanol with 95% cleans filter cake, gets sinomenine hydrochloride;
Sinomenine hydrochloride 5-45 weight portion, sucrose 25-65 weight portion, starch 25-45 weight portion, microcrystalline Cellulose 15-45 weight portion, magnesium stearate 0.5-1.5 weight portion, 5% polyvidone aqueous solution 30-50 parts by volume;
The preparation of step 3, capsule
Get above-mentioned amount sinomenine hydrochloride, with sucrose, starch, microcrystalline Cellulose, 5% polyvidone aqueous solution, magnesium stearate, process granule with 5% polyvidone aqueous solution, drying incapsulates, and promptly gets.
A, preparation sinomenine hydrochloride bullion
1, extract: Caulis Sinomenii coarse powder 500 weight portions, with the 0.5mol/L HCl moistening of 500 parts by volume 2 hours, adorn percolator; Add 0.5mol/L HCl again and make liquid level cover medicated powder 3cm, flood after 24 hours, begin percolation by the speed of 3ml/min; Stop percolation after 15 hours, get percolate, subsequent use;
2, extraction: above-mentioned percolate is added lime cream transfer pH to 11.6, filter, filtrating adds hydrochloric acid and transfers pH to 8, with chloroform extraction 4 times; Combined chloroform layer water is washed till neutrality, adds the anhydrous Na of 3% times of weight
2SO
4Dehydration, concentrating under reduced pressure reclaims chloroform;
3, crystallization: concentrated solution splashes into 6mol/L HCl and transfers pH to 3, and be stirred to the come-up solids and disperse, cold preservation, sucking filtration discards filtrating, and 65 ℃ of oven dry filter cakes get yellow sinomenine hydrochloride bullion;
B, sinomenine hydrochloride process for refining
Get sinomenine hydrochloride bullion 7 weight portions, the concentration of using 60 parts by volume is 75% alcohol heating reflux dissolving extremely fully, adds the active carbon of 4% times of weight; Insulation refluxed 20 minutes, filtered while hot, and filtrating concentrates; Cooling, crystallize; Filter, it is colourless to filtrating that the ethanol with 95% cleans filter cake, gets sinomenine hydrochloride.
A, preparation sinomenine hydrochloride bullion
1, extract: Caulis Sinomenii coarse powder 400 weight portions, with the 0.3mol/L HCl moistening of 320 parts by volume 3.5 hours, adorn percolator; Add 0.3mol/L HCl again and make liquid level cover medicated powder 4cm, flood after 6 hours, begin percolation by the speed of 6ml/min; Stop percolation after 8 hours, get percolate, subsequent use;
2, extraction: above-mentioned percolate is added lime cream transfer pH to 11.3, filter, filtrating adds hydrochloric acid and transfers pH to 8.5, with chloroform extraction 2 times; Combined chloroform layer water is washed till neutrality, adds the anhydrous Na of 5% times of weight
2SO
4Dehydration, concentrating under reduced pressure reclaims chloroform;
3, crystallization: concentrated solution splashes into 6mol/L HCl and transfers pH to 4, and be stirred to the come-up solids and disperse, cold preservation, sucking filtration discards filtrating, and 62 ℃ of oven dry filter cakes get yellow sinomenine hydrochloride bullion;
B, sinomenine hydrochloride process for refining
Get sinomenine hydrochloride bullion 10 weight portions,, add the active carbon of 4% times of weight with the 95% alcohol heating reflux dissolving extremely fully of 120 parts by volume; Insulation refluxed 25 minutes, filtered while hot, and filtrating concentrates; Cooling, crystallize; Filter, it is colourless to filtrating that the ethanol with 95% cleans filter cake, gets sinomenine hydrochloride.
A, preparation sinomenine hydrochloride bullion
1, extract: Caulis Sinomenii coarse powder 200 weight portions, with the 0.2mol/L HCl moistening of 900 parts by volume 3.5 hours, adorn percolator; Adding 0.8mol/L HCl again makes liquid level cover medicated powder 4cm; Flood after 15 hours, begin percolation, stop percolation after 20 hours by the speed of 4ml/min; Get percolate, subsequent use;
2, extraction: above-mentioned percolate is added lime cream transfer pH to 11.3, filter, filtrating adds hydrochloric acid and transfers pH to 9, with chloroform extraction 2 times; Combined chloroform layer water is washed till neutrality, adds the anhydrous Na of 5% times of weight
2SO
4Dehydration, concentrating under reduced pressure reclaims chloroform;
3, crystallization: concentrated solution splashes into 6mol/L HCl and transfers pH to 4, and be stirred to the come-up solids and disperse, cold preservation, sucking filtration discards filtrating, and 62 ℃ of oven dry filter cakes get yellow sinomenine hydrochloride bullion;
B, sinomenine hydrochloride process for refining
Get sinomenine hydrochloride bullion 8 weight portions,, add the active carbon of 4% times of weight with 50% ethanol or the dissolving extremely fully of purified water reflux of 12 parts by volume; Insulation refluxed 25 minutes, filtered while hot, and filtrating concentrates; Cooling, crystallize; Filter, it is colourless to filtrating that the ethanol with 95% cleans filter cake, gets sinomenine hydrochloride.
A, preparation sinomenine hydrochloride bullion
1, extract: Caulis Sinomenii coarse powder 800 weight portions, with the 0.8mol/L HCl moistening of 300 parts by volume 1 hour, adorn percolator; Add 0.2mol/L HCl again and make liquid level cover medicated powder 5cm, flood after 36 hours, begin percolation by the speed of 5ml/min; Stop percolation after 8 hours, get percolate, subsequent use;
2, extraction: above-mentioned percolate is added lime cream transfer pH to 11.3, filter, filtrating adds hydrochloric acid and transfers pH to 7, with chloroform extraction 5 times; Combined chloroform layer water is washed till neutrality, adds the anhydrous Na of 6% times of weight
2SO
4Dehydration, concentrating under reduced pressure reclaims chloroform;
3, crystallization: concentrated solution splashes into 6mol/L HCl and transfers pH to 2, and be stirred to the come-up solids and disperse, cold preservation, sucking filtration discards filtrating, and 68 ℃ of oven dry filter cakes get yellow sinomenine hydrochloride bullion;
B, sinomenine hydrochloride process for refining
Get sinomenine hydrochloride bullion 6 weight portions,, add the active carbon of 4% times of weight with 80% ethanol or the dissolving extremely fully of purified water reflux of 40 parts by volume; Insulation refluxed 15 minutes, filtered while hot, and filtrating concentrates; Cooling, crystallize; Filter, it is colourless to filtrating that the ethanol with 95% cleans filter cake, gets sinomenine hydrochloride.
Sinomenine hydrochloride 20 weight portions, sucrose 45 weight portions, starch 36 weight portions, microcrystalline Cellulose 27 weight portions, magnesium stearate 0.9 weight portion, 5% polyvidone aqueous solution, 40 parts by volume;
Or sinomenine hydrochloride 10 weight portions, sucrose 20 weight portions, starch 30 weight portions, microcrystalline Cellulose 20 weight portions, magnesium stearate 0.6 weight portion, 5% polyvidone aqueous solution, 30 parts by volume;
Or sinomenine hydrochloride 40 weight portions, sucrose 60 weight portions, starch 40 weight portions, microcrystalline Cellulose 40 weight portions, magnesium stearate 1.4 weight portions, 5% polyvidone aqueous solution, 35 parts by volume;
The weight portion in the method for preparing of above-mentioned sinomenine hydrochloride capsule and the relation of parts by volume are the relation of g/ml.
The method for preparing of sinomenine hydrochloride capsule provided by the invention, advantage are wherein to have adopted percolation to prepare sinomenine hydrochloride, and be simple to operate, and leaching process need not heat, and is cold treatment; Yield is high, and mother solution is handled simple; Safe and reliable, pollute lowly, environmental conservation is played a positive role.
Description of drawings
Fig. 1: 0.1mol/L hydrochloric acid extraction 2,4,6,10,12,24,28,30, Ultraluminescence thin layer collection of illustrative plates after 48 hours and colour developing thin layer collection of illustrative plates
Fig. 2: 0.3mol/L hydrochloric acid extraction 2,4,6,10,12,24,28,30, Ultraluminescence thin layer collection of illustrative plates after 48 hours and colour developing thin layer collection of illustrative plates
Fig. 3: 0.7mol/L hydrochloric acid extraction 2,4,6,10,12,24,28,30, the colour developing thin layer collection of illustrative plates after 48 hours
Fig. 4: 1.0mol/L hydrochloric acid extraction 2,4,6,10,12,24,28,30, the colour developing thin layer collection of illustrative plates after 48 hours
0.1,0.3,0.7, the colour developing thin layer collection of illustrative plates of 1.0mol/L concentration hydrochloric acid extraction after 12 hours Fig. 5:
Fig. 6: the percolation time is 2,4,6,10,12,14 hours colour developing thin layer collection of illustrative plates
Fig. 7: it is 7,8,9,10 that aqueous alkali is transferred pH, 11 fluorescence and colour developing thin layer collection of illustrative plates
Fig. 8: with the extract fluorescence and the colour developing thin layer chromatography of chloroform extraction 1 time, 2 times, 3 times, 4 times
Fig. 9: percolate, aqueous alkali, weak lye, extract, elaboration, mother solution, elaboration fluorescence and colour developing thin layer chromatography
Figure 10: sinomenine hydrochloride reference substance high-efficient liquid phase chromatogram
Figure 11: the liquid chromatogram of sinomenine hydrochloride
Figure 12: the thin-layer chromatogram of sinomenine hydrochloride, the 1st speckle are reference substance, and the 2nd, 3,4,5 speckles are respectively 4 samples of the present invention.
Following experimental example and embodiment are used to further specify but are not limited to the present invention.
Experimental example one: Caulis Sinomenii Study on extraction
1, test objective
Through this test, confirm the technological parameter of this extraction process, like dip time, percolation time, extraction times, pH regulator scope etc., optimize technology.
2, test material
2.1 raw material: the Caulis Sinomenii that the Baoji provides
2.2 instrument:
Percolator;
PHS-2F PH meter: go up Electronic Instruments Plant of Nereid section
ZF-2 type three is used ultraviolet device: go up Hai'an booth Electronic Instruments Plant
RE-52A Rotary Evaporators: Shanghai Yarong Biochemical Instrument Plant
SHB-3 recirculated water is used vacuum pump more: Zhengzhou Tu Fu instrument plant
2.3 reagent: the quartzy chemical company limited in hydrochloric acid Zhuzhou
The safe and sound fine chemistry industry of ammonia Changsha Industrial Co., Ltd.
Chloroform Chemical Reagent Co., Ltd., Sinopharm Group
Silica gel G: Qingdao Marine Chemical Co., Ltd.
Ca (OH)
2, Na
2SO4, bismuth potassium iodide weak solution, ethanol etc.
2.4 detection method: colour developing 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, method
3.1 concentration of hydrochloric acid and dip time are investigated
Take by weighing 4 parts of mistakes, 20 purpose Caulis Sinomenii coarse powder, every part of 50g is respectively charged in 4 l00ml beakers; Prepare 0.1mol/L, 0.3mol/L, 0.7mol/L, 1.0mol/L hydrochloric acid; Added in 4 beakers moistening respectively 0.5 hour with the hydrochloric acid of the above-mentioned concentration of 40ml; In each beaker, add hydrochloric acid 50ml again with concentration, dipping, sampling in per 2 hours is taken a sample respectively 1 time.
Judgment basis:
1, by same concentration, different dip time sample is put in chronological order on same lamellae respectively, compared with the reference substance speckle, the maximum time point of principal spot is a dip time;
2, the sample of same time period, variable concentrations is put on same lamellae by the concentration order, the concentration point maximum with principal spot is optium concentration;
When 3, representing concentration result not have significant difference, show that then the hydrochloric acid of 0.1～1.0mol/L all is fit to this extraction as if 4.
3.2 the percolation time is investigated
The hydrochloric acid of getting 3.1 said definite concentration is as solvent; Cross 20 purpose sinomenine coarse powder 0.5 hour with 160ml moistening 200g, after flooding by above-mentioned definite dip time, beginning is carried out percolation with the speed of 2～3ml/min; Carried out primary sample in per 2 hours; Sample spot on same lamellae, when no sinomenine principal spot, is stopped percolation.Confirm as the terminal time of percolation.
3.3pH the value scope is investigated
After above-mentioned 3.2 percolates that obtain are regulated that pH value to 11 is above and are filtered with lime water; Obtain 5 parts of 50ml percolates; Every part extracts respectively with the 16ml chloroform after transferring to different pH value with hydrochloric acid is counter, gets extract, puts on same lamellae; Minimum with impure speckle, the maximum pH value point of principal spot is the optimal pH range of accommodation.
3.4 extractant consumption and number of times are investigated
Get above-mentioned 3.3 percolates after filtering, the optimal pH of transferring pH to 3.3 to confirm adopts chloroform to extract; Press 1/2 percolate volume first, the consumption of each 1/3 percolation liquid extracts later on, gets extract after each extraction; Sample spot is on same lamellae; When no sinomenine speckle, end extraction, confirm that this consumption and number of times are this technological parameter.
3.5 finger printing is investigated
Extract Caulis Sinomenii coarse powder 200g by above-mentioned 3.1,3.2,3.3,3.4 definite good parameters; Respectively at percolation, alkalization filter, sour water is instead transferred, extraction, acidify crystallize, operation stage such as refining are got percolate, aqueous alkali, weak lye, extract, bullion, mother solution, elaboration; Sample spot is analyzed on same lamellae.
3.6 thin layer chromatography point plate: get the sample 5ul of above-mentioned test respectively with 5ul point sample capillary tube, put on silica gel g thin-layer plate in order.
4, result
4.1 confirming of the selection of concentration of hydrochloric acid and dip time seen table one and Fig. 1 to Fig. 5.
Table one: the solvent extraction of variable concentrations is in the thin layer situation of different time
Brief summary: the hydrochloric acid with above 4 groups of concentration floods, and can obtain 8-9 material (observing after ultraviolet light and the bismuth potassium iodide colour developing).And the hydrochloric acid extraction that adopts 0.1mol/L to obvious low than other three groups of concentration of main constituent, all be rational so choose the above concentration of 0.3mol/L (containing 0.3mol/L).0.3mol/L tentatively confirming as 12 hours, the dip time of hydrochloric acid reaches Cmax; 0.7mol/L tentatively confirming as 10 hours, the dip time of hydrochloric acid reaches maximum concentration; 1.0mol/L tentatively confirming as 8 hours, the dip time of hydrochloric acid reaches maximum concentration.
4.2 confirming of percolation time seen table two and Fig. 6.
Table two: the thin layer situation of different time sections during percolation
Brief summary: 6 hours is that percolation is complete.Confirm to end percolation in 6-8 hour.
4.3 confirming of pH value scope seen table three and Fig. 7.
Table three: different PH chromatogram situation
Brief summary: confirming the 3rd point, is best pH during pH=8 promptly, is that pH=7-9 regulates allowed band between the 2nd and 4.
4.4 confirming of extractant consumption and number of times seen table four and Fig. 8.
Table four: the thin layer situation of different extraction times
Brief summary: Fig. 8 is followed successively by the sample that extracts 1,2,3,4 times from left to right, and under the ultraviolet, speck point is strengthened successively, and the non-main constituent amount of extraction increases.Though because of all also containing micro-main constituent in the extract of third and fourth time, by-product volume increases, and can consider to extract 2 times, the method for each 1/2 consumption extracts.
5, table five and Fig. 9 are seen in the research of finger printing.
Table five: different process stage chromatogram situation
Annotate: this extract is the sample that extracts first.
Brief summary: this adopts the hydrochloric acid percolation; Can extract hydrochloric sinomenine at interior totally 9 kinds of material compositions; 7 kinds of materials are wherein arranged under ultraviolet, and the bismuth potassium iodide following 2 kinds of materials that develop the color filter weak baseization, extraction through alkalization again; Effectively a kind of non-main constituent alkaloid under observed 6 kinds of materials and the colour developing under the removal ultraviolet obtains single sinomenine hydrochloride through making with extra care again.Proof this method is scientific and reasonable, simple and feasible.
Experimental example two: contrast experiment
Chloroform reflux, extract, technology in the table six: attach the sinomenine hydrochloride standard for one one 622 pages by Chinese Pharmacopoeia version in 2010.
Benzene reflux, extract, technology in the table six: raw material pulverizing, oven dry add the alkalization of Calx mix homogeneously; Insert and add in the extraction pot that the close reflux, extract, of the full envelope of benzene concentrates, filters, cooling, separate; Obtain free sinomenine; In free sinomenine, add HCl and transform generation sinomenine hydrochloride solution, carry out recrystallization with water again and obtain the product sinomenine hydrochloride.
The result sees table six.
Table six: contrast and experiment
Following embodiment all can realize the effect of above-mentioned experimental example.
Embodiment one:
The 200g Caulis Sinomenii is dried, was pulverized 20 orders, adds 0.3mol/L HCl 160ml and in beaker, stirs, and moistening was put in the percolator after 6 hours; Add the hydrochloric acid of 0.3mol/L, make it cover liquid level 10cm, flood after 24 hours, beginning is carried out percolation with the speed of 2～3ml/min; Collect percolate after 24 hours, add lime cream and regulate pH value to 11.3, filter; Filtrating reuse HCl regulates pH value to 8.8, with chloroform extraction 4 times, lower floor's chloroform solution through dewater, concentrating under reduced pressure; Reclaim solvent, concentrated solution is regulated pH value to 2 with the hydrochloric acid of 6mol/L, and stirring, cold filtration get the sinomenine hydrochloride bullion;
Get sinomenine hydrochloride bullion 5.8g, be heated to backflow, add the 0.24g active carbon after the stirring and dissolving with 95% ethanol 90ml; Insulation refluxed 30 minutes, filtered while hot, and filtrating is concentrated into 1/5; Cooling, crystallize filter, and it is colourless to filtrating to clean filter cake with ethanol; Sinomenine hydrochloride elaboration 2.22g, relative medical material yield more than 1.11%, content 97.9%;
Get sinomenine hydrochloride 20g, with adjuvants such as sucrose 45g, starch 36g, microcrystalline Cellulose 27g, 5% polyvidone aqueous solution 40ml, magnesium stearate 0.9g, process granule with 5% polyvidone aqueous solution, drying incapsulates 1000, promptly gets specification: the 20mg/ grain.
Embodiment two:
The 400g Caulis Sinomenii is dried, was pulverized 20 orders, adds 1.0mol/L HCl 300ml and in beaker, stirs, and moistening was put in the percolator after 0.5 hour; Add the hydrochloric acid of 1N, make it cover liquid level 5cm, dipping, beginning is carried out percolation with the speed of 5ml/min after 48 hours; Collect percolate after 8 hours, add lime cream and regulate pH value to 10.8, filter, filtrating reuse HCl regulates pH value to 9.2; With chloroform extraction 3 times, lower floor's chloroform solution reclaims solvent through dehydration, concentrating under reduced pressure; Concentrated solution is regulated pH value to 3.5 with the hydrochloric acid of 6mol/L, the hydrochlorate that stir, cold filtration gets sinomenine, and recrystallization gets the sinomenine hydrochloride bullion in ethanol;
Get sinomenine hydrochloride bullion 11.2g, be heated to backflow, add the 0.5g active carbon after the stirring and dissolving with 95% ethanol 110ml; Insulation refluxed 30 minutes, filtered while hot, and filtrating is concentrated into 1/4; Cooling, crystallize filter, and it is colourless to filtrating to clean filter cake with ethanol; Get sinomenine hydrochloride elaboration 4.61g, relative medical material yield 1.15%, content 96.4%.
Get sinomenine hydrochloride 10g, with adjuvants such as sucrose 20g, starch 30g, microcrystalline Cellulose 20g, magnesium stearate 0.6g, 5% polyvidone aqueous solution 30ml, process granule with 5% polyvidone aqueous solution, drying incapsulates, and promptly gets specification: the 20mg/ grain.
Embodiment three:
The 300g Caulis Sinomenii is dried, was pulverized 10 orders, adds 0.1mol/L HCl 240ml and in beaker, stirs, and moistening was put in the percolator after 2 hours; Add the hydrochloric acid of 0.1mol/L, make it cover liquid level 8cm, flood after 36 hours, beginning is carried out percolation with the speed of 3ml/min; Collect percolate after 12 hours, add lime cream and regulate pH value to 11.5, filter, filtrating reuse HCl regulates pH value to 9.5; With chloroform extraction 5 times, lower floor's chloroform solution washing through concentrating under reduced pressure, is reclaimed solvent to neutral; Concentrated solution is regulated pH value to 2 with the hydrochloric acid of 6mol/L, the hydrochlorate that stir, cold filtration gets sinomenine, and recrystallization gets the sinomenine hydrochloride bullion in ethanol;
Get sinomenine hydrochloride bullion 7.5g, be heated to backflow, add the 0.3g active carbon after the stirring and dissolving with 95% ethanol 60ml; Insulation refluxed 30 minutes, filtered while hot, and filtrating is concentrated into 1/3; Cooling, crystallize filter, and it is colourless to filtrating to clean filter cake with ethanol; Get sinomenine hydrochloride elaboration 3.3g, relative medical material yield 1.1%, content 96.5%.
Get sinomenine hydrochloride 20g, with adjuvants such as sucrose 45g, starch 36g, microcrystalline Cellulose 27g, 5% polyvidone aqueous solution 40ml, magnesium stearate 0.9g, process granule with 5% polyvidone aqueous solution, drying incapsulates 1000, promptly gets specification: the 20mg/ grain.
Embodiment four:
The 1000g Caulis Sinomenii is dried, was pulverized 20 orders, adds 0.3mol/L HCl 800ml and in beaker, stirs, and moistening was put in the percolator after 5 hours; Add the hydrochloric acid of 0.3mol/L, make it cover liquid level 2cm, flood after 6 hours, beginning is carried out percolation with the speed of 2～3ml/min; Collect percolate after 24 hours, add lime cream and regulate pH value to 11.3, filter; Filtrating reuse HCl regulates pH value to 8.8, with chloroform extraction 3 times, lower floor's chloroform solution through dewater, concentrating under reduced pressure; Reclaim solvent, concentrated solution is regulated pH value to 2 with the hydrochloric acid of 6mol/L, and stirring, cold filtration get the sinomenine hydrochloride bullion;
Get sinomenine hydrochloride bullion 4g, to dissolving fully, add the 0.16g active carbon with 75% ethanol 40ml reflux, insulation refluxed 20 minutes; Filter while hot, filtrating concentrates, cooling, crystallize; Filter, it is colourless to filtrating to clean filter cake with ethanol, gets sinomenine hydrochloride elaboration 1.62g.
Get sinomenine hydrochloride 40g, with sucrose 60g, starch 40g, microcrystalline Cellulose 40g,, adjuvant such as magnesium stearate 1.4g, 5% polyvidone aqueous solution 40ml, process granule with 5% polyvidone aqueous solution, drying incapsulates, and promptly gets specification: the 20mg/ grain.
Embodiment five:
The 1000g Caulis Sinomenii is dried, was pulverized 20 orders, adds 0.3mol/L HCl 900ml and in beaker, stirs, and moistening was put in the percolator after 8 hours; Add the hydrochloric acid of 0.3mol/L, make it cover liquid level 3cm, flood after 12 hours, beginning is carried out percolation with the speed of 2～3ml/min; Collect percolate after 6 hours, add lime cream and regulate pH value to 11.4, filter; Filtrating reuse HCl regulates pH value to 8.8, with chloroform extraction 2 times, lower floor's chloroform solution through dewater, concentrating under reduced pressure; Reclaim solvent, concentrated solution is regulated pH value to 2 with the hydrochloric acid of 6mol/L, and stirring, cold filtration get the sinomenine hydrochloride bullion;
Get sinomenine hydrochloride bullion 5g, to dissolving fully, add the 0.2g active carbon with 50% ethanol 37ml reflux, insulation refluxed 10 minutes; Filter while hot, filtrating concentrates, cooling, crystallize; Filter, it is colourless to filtrating to clean filter cake with ethanol, gets sinomenine hydrochloride elaboration 1.71g.
Get sinomenine hydrochloride 20g, with adjuvants such as sucrose 45g, starch 36g, microcrystalline Cellulose 27g, 5% polyvidone aqueous solution 40ml, magnesium stearate 0.9g, process granule with 5% polyvidone aqueous solution, drying incapsulates, and promptly gets specification: the 20mg/ grain.
Embodiment six:
The 1000g Caulis Sinomenii is dried, was pulverized 20 orders, adds 0.3mol/L HCl 700ml and in beaker, stirs, and moistening was put in the percolator after 3 hours; Add the hydrochloric acid of 0.3mol/L, make it cover liquid level 5cm, flood after 16 hours, beginning is carried out percolation with the speed of 2～3ml/min; Collect percolate after 10 hours, add lime cream and regulate pH value to 11.1, filter; Filtrating reuse HCl regulates pH value to 8.8, with chloroform extraction 3 times, lower floor's chloroform solution through dewater, concentrating under reduced pressure; Reclaim solvent, concentrated solution is regulated pH value to 2 with the hydrochloric acid of 6mol/L, and stirring, cold filtration get the sinomenine hydrochloride bullion;
Get sinomenine hydrochloride bullion 6g, to dissolving fully, add the 0.16g active carbon with 10% ethanol 30ml reflux, insulation refluxed 16 minutes; Filter while hot, filtrating concentrates, cooling, crystallize; Filter, it is colourless to filtrating to clean filter cake with ethanol, gets sinomenine hydrochloride elaboration 1.87g.
Get sinomenine hydrochloride 40g, with sucrose 60g, starch 40g, microcrystalline Cellulose 40g,, adjuvant such as magnesium stearate 1.4g, 5% polyvidone aqueous solution 40ml, process granule with 5% polyvidone aqueous solution, drying incapsulates, and promptly gets specification: the 20mg/ grain.
Embodiment seven:
The 1000g Caulis Sinomenii is dried, was pulverized 20 orders, adds 0.3mol/L HCl 700ml and in beaker, stirs, and moistening was put in the percolator after 1 hour; Add the hydrochloric acid of 0.3mol/L, make it cover liquid level 10cm, flood after 12 hours, beginning is carried out percolation with the speed of 2～3ml/min; Collect percolate after 10 hours, add lime cream and regulate pH value to 11.3, filter; Filtrating reuse HCl regulates pH value to 8.8, with chloroform extraction 4 times, lower floor's chloroform solution through dewater, concentrating under reduced pressure; Reclaim solvent, concentrated solution is regulated pH value to 2 with the hydrochloric acid of 6mol/L, and stirring, cold filtration get the sinomenine hydrochloride bullion;
Get sinomenine hydrochloride bullion 7.8g, be heated to 80 ℃ of insulations with the 30ml purified water, the dissolving back adds the active carbon of 0.32g fully, is incubated 30 minutes; Filter while hot, filtrating concentrates, cooling, crystallize; Filter, it is colourless to filtrating to clean filter cake with ethanol, gets sinomenine hydrochloride elaboration 2.55g.
Get sinomenine hydrochloride 40g, with sucrose 60g, starch 40g, microcrystalline Cellulose 40g,, adjuvant such as magnesium stearate 1.4g, 5% polyvidone aqueous solution 40ml, process granule with 5% polyvidone aqueous solution, drying incapsulates, and promptly gets specification: the 20mg/ grain.
Above embodiment all no longer contains sinomenine in the raw material slag after with the hydrochloric acid percolation.The yield of sinomenine is more than 1.1% of material quantity, content 94～99%.
Claims (8)
1. the method for preparing of a sinomenine hydrochloride capsule is characterized in that this method comprises the steps:
The method for preparing of step 1, sinomenine hydrochloride
A, preparation sinomenine hydrochloride bullion
Extract: Caulis Sinomenii coarse powder 100～1000 weight portions, with the 0.11mol/L HCl moistening of 60～1000 parts by volume 0.5～8 hour, adorn percolator; Adding 0.1～1mol/L HCl again makes liquid level cover medicated powder 2～6cm; Flood after 6～48 hours, begin percolation, stop percolation after 6～24 hours by the speed of 2～6ml/min; Get percolate, subsequent use;
Extraction: above-mentioned percolate is added lime cream transfer pH to 10.5～12.0, filter, filtrating adds hydrochloric acid and transfers pH to 7.0～9.5, with chloroform extraction 2～5 times; Combined chloroform layer water is washed till neutrality, adds the anhydrous Na of 3%～6% times of weight
2The SO4 dehydration, concentrating under reduced pressure reclaims chloroform;
Crystallization: concentrated solution splashes into 6mol/L HCl and transfers pH to 2～4, and be stirred to the come-up solids and disperse, cold preservation, sucking filtration discards filtrating, and 60 ℃～70 ℃ oven dry filter cakes get yellow sinomenine hydrochloride bullion;
B, sinomenine hydrochloride process for refining
Get sinomenine hydrochloride bullion 5～10 weight portions,, add the active carbon of 4% 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, it is colourless to filtrating that the ethanol with 95% cleans filter cake, gets sinomenine hydrochloride;
Step 2, get raw material
Sinomenine hydrochloride 5-45 weight portion, sucrose 25-65 weight portion, starch 25-45 weight portion, microcrystalline Cellulose 15-45 weight portion, magnesium stearate 0.5-1.5 weight portion, 5% polyvidone aqueous solution 30-50 parts by volume;
The preparation of step 3, capsule
Get sinomenine hydrochloride, with sucrose, starch, microcrystalline Cellulose, 5% polyvidone aqueous solution, magnesium stearate, process granule with 5% polyvidone aqueous solution, drying incapsulates, and promptly gets.
2. the method for preparing of sinomenine hydrochloride capsule as claimed in claim 1 is characterized in that step 1 is in this method:
A, preparation sinomenine hydrochloride bullion
Extract: Caulis Sinomenii coarse powder 500 weight portions, with the 0.5mol/L HCl moistening of 500 parts by volume 2 hours, adorn percolator; Add 0.5mol/L HCl again and make liquid level cover medicated powder 3cm, flood after 24 hours, begin percolation by the speed of 3ml/min; Stop percolation after 15 hours, get percolate, subsequent use;
Extraction: above-mentioned percolate is added lime cream transfer pH to 11.6, filter, filtrating adds hydrochloric acid and transfers pH to 8, with chloroform extraction 4 times; Combined chloroform layer water is washed till neutrality, adds the anhydrous Na of 3% times of weight
2SO
4Dehydration, concentrating under reduced pressure reclaims chloroform;
Crystallization: concentrated solution splashes into 6mol/L HCl and transfers pH to 3, and be stirred to the come-up solids and disperse, cold preservation, sucking filtration discards filtrating, and 65 ℃ of oven dry filter cakes get yellow sinomenine hydrochloride bullion;
B, sinomenine hydrochloride process for refining
Get sinomenine hydrochloride bullion 7 weight portions, the concentration of using 60 parts by volume is 75% alcohol heating reflux dissolving extremely fully, adds the active carbon of 4% times of weight; Insulation refluxed 20 minutes, filtered while hot, and filtrating concentrates; Cooling, crystallize; Filter, it is colourless to filtrating that the ethanol with 95% cleans filter cake, gets sinomenine hydrochloride.
3. the method for preparing of sinomenine hydrochloride capsule as claimed in claim 1 is characterized in that step 1 is in this method:
A, preparation sinomenine hydrochloride bullion
Extract: Caulis Sinomenii coarse powder 400 weight portions, with the 0.3mol/L HCl moistening of 320 parts by volume 3.5 hours, adorn percolator; Add 0.3mol/L HCl again and make liquid level cover medicated powder 4cm, flood after 6 hours, begin percolation by the speed of 6ml/min; Stop percolation after 8 hours, get percolate, subsequent use;
Extraction: above-mentioned percolate is added lime cream transfer pH to 11.3, filter, filtrating adds hydrochloric acid and transfers pH to 8.5, with chloroform extraction 2 times; Combined chloroform layer water is washed till neutrality, adds the anhydrous Na of 5% times of weight
2SO
4Dehydration, concentrating under reduced pressure reclaims chloroform;
Crystallization: concentrated solution splashes into 6mol/L HCl and transfers pH to 4, and be stirred to the come-up solids and disperse, cold preservation, sucking filtration discards filtrating, and 62 ℃ of oven dry filter cakes get yellow sinomenine hydrochloride bullion;
B, sinomenine hydrochloride process for refining
Get sinomenine hydrochloride bullion 10 weight portions,, add the active carbon of 4% times of weight with the 95% alcohol heating reflux dissolving extremely fully of 120 parts by volume; Insulation refluxed 25 minutes, filtered while hot, and filtrating concentrates; Cooling, crystallize; Filter, it is colourless to filtrating that the ethanol with 95% cleans filter cake, gets sinomenine hydrochloride.
4. the method for preparing of sinomenine hydrochloride capsule as claimed in claim 1 is characterized in that step 1 is in this method:
A, preparation sinomenine hydrochloride bullion
Extract: Caulis Sinomenii coarse powder 200 weight portions, with the 0.2mol/L HCl moistening of 900 parts by volume 3.5 hours, adorn percolator; Add 0.8mol/L HCl again and make liquid level cover medicated powder 4cm, flood after 15 hours, begin percolation by the speed of 4ml/min; Stop percolation after 20 hours, get percolate, subsequent use;
Extraction: above-mentioned percolate is added lime cream transfer pH to 11.3, filter, filtrating adds hydrochloric acid and transfers pH to 9, with chloroform extraction 2 times; Combined chloroform layer water is washed till neutrality, adds the anhydrous Na of 5% times of weight
2SO
4Dehydration, concentrating under reduced pressure reclaims chloroform;
Crystallization: concentrated solution splashes into 6mol/L HCl and transfers pH to 4, and be stirred to the come-up solids and disperse, cold preservation, sucking filtration discards filtrating, and 62 ℃ of oven dry filter cakes get yellow sinomenine hydrochloride bullion;
B, sinomenine hydrochloride process for refining
Get sinomenine hydrochloride bullion 8 weight portions,, add the active carbon of 4% times of weight with 50% ethanol or the dissolving extremely fully of purified water reflux of 12 parts by volume; Insulation refluxed 25 minutes, filtered while hot, and filtrating concentrates; Cooling, crystallize; Filter, it is colourless to filtrating that the ethanol with 95% cleans filter cake, gets sinomenine hydrochloride.
5. the method for preparing of sinomenine hydrochloride capsule as claimed in claim 1 is characterized in that step 1 is in this method:
A, preparation sinomenine hydrochloride bullion
Extract: Caulis Sinomenii coarse powder 800 weight portions, with the 0.8mol/L HCl moistening of 300 parts by volume 1 hour, adorn percolator; Add 0.2mol/L HCl again and make liquid level cover medicated powder 5cm, flood after 36 hours, begin percolation by the speed of 5ml/min; Stop percolation after 8 hours, get percolate, subsequent use;
Extraction: above-mentioned percolate is added lime cream transfer pH to 11.3, filter, filtrating adds hydrochloric acid and transfers pH to 7, with chloroform extraction 5 times; Combined chloroform layer water is washed till neutrality, adds the anhydrous Na of 6% times of weight
2SO
4Dehydration, concentrating under reduced pressure reclaims chloroform;
Crystallization: concentrated solution splashes into 6mol/L HCl and transfers pH to 2, and be stirred to the come-up solids and disperse, cold preservation, sucking filtration discards filtrating, and 68 ℃ of oven dry filter cakes get yellow sinomenine hydrochloride bullion;
B, sinomenine hydrochloride process for refining
Get sinomenine hydrochloride bullion 6 weight portions,, add the active carbon of 4% times of weight with 80% ethanol or the dissolving extremely fully of purified water reflux of 40 parts by volume; Insulation refluxed 15 minutes, filtered while hot, and filtrating concentrates; Cooling, crystallize; Filter, it is colourless to filtrating that the ethanol with 95% cleans filter cake, gets sinomenine hydrochloride.
6. like the method for preparing of the arbitrary described sinomenine hydrochloride capsule of claim 1---5, it is characterized in that step 2 is in this method:
Sinomenine hydrochloride 20 weight portions, sucrose 45 weight portions, starch 3 weight portions, microcrystalline Cellulose 27 weight portions, magnesium stearate 0.9 weight portion, 5% polyvidone aqueous solution, 40 parts by volume.
7. like the method for preparing of the arbitrary described sinomenine hydrochloride capsule of claim 1---5, it is characterized in that step 2 is in this method:
Sinomenine hydrochloride 10 weight portions, sucrose 20 weight portions, starch 30 weight portions, microcrystalline Cellulose 20 weight portions, magnesium stearate 0.6 weight portion, 5% polyvidone aqueous solution, 30 parts by volume.
8. like the method for preparing of the arbitrary described sinomenine hydrochloride capsule of claim 1---5, it is characterized in that step 2 is in this method:
Sinomenine hydrochloride 40 weight portions, sucrose 60 weight portions, starch 40 weight portions, microcrystalline Cellulose 40 weight portions, magnesium stearate 1.4 weight portions, 5% polyvidone aqueous solution, 50 parts by volume.
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101289469A (en) * | 2007-04-18 | 2008-10-22 | 代龙 | Process for separating total alkaloids form Chinese medicament extracting solution |
| CN102172361A (en) * | 2008-08-13 | 2011-09-07 | 北京和润创新医药科技发展有限公司 | Method for separating traditional Chinese medicine total alkaloids by ion exchange resin |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101289469A (en) * | 2007-04-18 | 2008-10-22 | 代龙 | Process for separating total alkaloids form Chinese medicament extracting solution |
| CN102172361A (en) * | 2008-08-13 | 2011-09-07 | 北京和润创新医药科技发展有限公司 | Method for separating traditional Chinese medicine total alkaloids by ion exchange resin |
Non-Patent Citations (1)
| Title |
|---|
| 李海滨: "青藤生物碱成分的研究", 《贵阳医学院学报》, vol. 31, no. 4, 31 August 2006 (2006-08-31), pages 344 - 345 * |
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