CN102614149B - Method for preparing sinomenine capsules - Google Patents
Method for preparing sinomenine capsules Download PDFInfo
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- CN102614149B CN102614149B CN 201210088991 CN201210088991A CN102614149B CN 102614149 B CN102614149 B CN 102614149B CN 201210088991 CN201210088991 CN 201210088991 CN 201210088991 A CN201210088991 A CN 201210088991A CN 102614149 B CN102614149 B CN 102614149B
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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 preparation method 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 made the sinomenine hydrochloride capsule.
Background technology
Caulis Sinomenii is traditional conventional Chinese medicine, dry rattan for menispermaceous plants Sinomenium acutum and hair Sinomenium acutum, just on the books in Compendium of Material Medica, now record in Pharmacopoeia of the People's Republic of China version in 2010, have dispel the wind, the effect of the meridian dredging, diuresis, be used for the treatment of rheumatic arthralgia, arthroncus, paralysis pruritus, also have the effects such as anti-arrhythmia and blood pressure lowering.
Main component is alkaloid in the Caulis Sinomenii, the composition of having found at present has sinomenine (Sinomenine), isosinomenine (Igoginomenine), China's 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, is separated the earliest obtaining from Japanese Caulis Sinomenii by Ishiwari etc.The sixties in 20th century, Chinese scholar Zhu Renhong also found sinomenine from domestic Caulis Sinomenii.Its hydrochlorate preparation commonly used such as ZHENGQINGFENGTONGNING PIAN, Zhengqing Fengtongning Retard Tablets, ZHENGQINGFENGTONGNING injection are used for the treatment of rheumatic, rheumatoid arthritis clinically, 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, then add a certain amount of technical benzene, reflux, extract, in water-bath, last acidify, leave standstill, crystallize.
Document has report to introduce 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 Anticountra flow extraction, activated carbon decolorizing with 1% hydrochloric acid, recrystallization is carried out in crystallization in hot water, get sterling.(Chen Yukun " extracting technique of Chinese medicine ", 1992)
This several method all uses the very large benzene of toxicity as extracting solvent, benzene is I class toxic solvent, the murder by poisoning of human body take blood system and neurasthenia's disease group as main, is shown as blood leukocytes, platelet and erythrocytopenia, dizziness, headache, hypomnesis, insomnia etc.Aplastic anemia can occur in severe patient, even leukemia, death, and is disabled at pharmaceutical industry.And the recovery of benzene is comparatively cumbersome, discharges difficult meet the requirement of environmental protection.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 preparation method of sinomenine hydrochloride capsule.
The present invention seeks to be achieved through the following technical solutions, the preparation method of sinomenine hydrochloride capsule of the present invention comprises the steps:
The preparation method of step 1, sinomenine hydrochloride
A, preparation sinomenine hydrochloride crude product
1, extracts: 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 makes liquid level cover medicated powder 2～6cm again, flood after 6～48 hours, begin percolation by the speed of 2～6ml/min, stop percolation after 6～24 hours, get percolate, for subsequent use;
2, extract: above-mentioned percolate is added lime cream transfer pH to 10.5～12.0, filter, filtrate adds hydrochloric acid and transfers pH to 7.0～9.5, uses chloroform extraction 2～5 times; The combined chloroform layer washes with water to 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 floating solids and disperse, cold preservation, sucking filtration discards filtrate, and 60 ℃～70 ℃ oven dry filter cakes get yellow sinomenine hydrochloride crude product;
B, sinomenine hydrochloride process for refining
Get sinomenine hydrochloride crude product 5～10 weight portions, 10～95% ethanol or the extremely fully dissolving of purified water reflux with 30～120 parts by volume, the active carbon that adds 4% times of weight, insulation refluxed 10～30 minutes, filtered while hot, and filtrate is concentrated, cooling, crystallize, filter, it is colourless to filtrate 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, with 5% polyvidone aqueous solution granulation, drying incapsulates, and get final product.
A, preparation sinomenine hydrochloride crude product
1, extract: Caulis Sinomenii coarse powder 500 weight portions with the 0.5mol/L HCl moistening of 500 parts by volume 2 hours, fill percolator, add again 0.5mol/L HCl 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, for subsequent use;
2, extract: above-mentioned percolate is added lime cream transfer pH to 11.6, filter, filtrate adds hydrochloric acid and transfers pH to 8, uses chloroform extraction 4 times; The combined chloroform layer washes with water to 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 floating solids and disperse, cold preservation, sucking filtration discards filtrate, and 65 ℃ of oven dry filter cakes get yellow sinomenine hydrochloride crude product;
B, sinomenine hydrochloride process for refining
Get sinomenine hydrochloride crude product 7 weight portions, be that 75% alcohol heating reflux is to fully dissolving with the concentration of 60 parts by volume, the active carbon that adds 4% times of weight, insulation refluxed 20 minutes, filtered while hot, and filtrate is concentrated, cooling, crystallize, filter, it is colourless to filtrate that the ethanol with 95% cleans filter cake, gets sinomenine hydrochloride.
A, preparation sinomenine hydrochloride crude product
1, extract: Caulis Sinomenii coarse powder 400 weight portions with the 0.3mol/L HCl moistening of 320 parts by volume 3.5 hours, fill percolator, add again 0.3mol/L HCl 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, for subsequent use;
2, extract: above-mentioned percolate is added lime cream transfer pH to 11.3, filter, filtrate adds hydrochloric acid and transfers pH to 8.5, uses chloroform extraction 2 times; The combined chloroform layer washes with water to 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 floating solids and disperse, cold preservation, sucking filtration discards filtrate, and 62 ℃ of oven dry filter cakes get yellow sinomenine hydrochloride crude product;
B, sinomenine hydrochloride process for refining
Get sinomenine hydrochloride crude product 10 weight portions, extremely fully dissolving of 95% alcohol heating reflux with 120 parts by volume, the active carbon that adds 4% times of weight, insulation refluxed 25 minutes, filtered while hot, and filtrate is concentrated, cooling, crystallize, filter, it is colourless to filtrate that the ethanol with 95% cleans filter cake, gets sinomenine hydrochloride.
A, preparation sinomenine hydrochloride crude product
1, extracts: Caulis Sinomenii coarse powder 200 weight portions, with the 0.2mol/L HCl moistening of 900 parts by volume 3.5 hours, the dress percolator, adding 0.8mol/L HCl makes liquid level cover medicated powder 4cm again, flood after 15 hours, begin percolation by the speed of 4ml/min, stop percolation after 20 hours, get percolate, for subsequent use;
2, extract: above-mentioned percolate is added lime cream transfer pH to 11.3, filter, filtrate adds hydrochloric acid and transfers pH to 9, uses chloroform extraction 2 times; The combined chloroform layer washes with water to 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 floating solids and disperse, cold preservation, sucking filtration discards filtrate, and 62 ℃ of oven dry filter cakes get yellow sinomenine hydrochloride crude product;
B, sinomenine hydrochloride process for refining
Get sinomenine hydrochloride crude product 8 weight portions, 50% ethanol or the extremely fully dissolving of purified water reflux with 12 parts by volume, the active carbon that adds 4% times of weight, insulation refluxed 25 minutes, filtered while hot, and filtrate is concentrated, cooling, crystallize, filter, it is colourless to filtrate that the ethanol with 95% cleans filter cake, gets sinomenine hydrochloride.
A, preparation sinomenine hydrochloride crude product
1, extract: Caulis Sinomenii coarse powder 800 weight portions with the 0.8mol/L HCl moistening of 300 parts by volume 1 hour, fill percolator, add again 0.2mol/L HCl 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, for subsequent use;
2, extract: above-mentioned percolate is added lime cream transfer pH to 11.3, filter, filtrate adds hydrochloric acid and transfers pH to 7, uses chloroform extraction 5 times; The combined chloroform layer washes with water to 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 floating solids and disperse, cold preservation, sucking filtration discards filtrate, and 68 ℃ of oven dry filter cakes get yellow sinomenine hydrochloride crude product;
B, sinomenine hydrochloride process for refining
Get sinomenine hydrochloride crude product 6 weight portions, 80% ethanol or the extremely fully dissolving of purified water reflux with 40 parts by volume, the active carbon that adds 4% times of weight, insulation refluxed 15 minutes, filtered while hot, and filtrate is concentrated, cooling, crystallize, filter, it is colourless to filtrate 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;
Weight portion in the preparation method of above-mentioned sinomenine hydrochloride capsule and the pass of parts by volume are the relation of g/ml.
The preparation method 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 liquid disposal is 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, the 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, the 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: the extract fluorescence that the usefulness chloroform extraction is 1 time, 2 times, 3 times, 4 times and colour developing thin layer chromatography
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 for further specifying but are not limited to the present invention.
Experimental example one: Caulis Sinomenii Study on extraction
1, test objective
By this test, determine the technological parameter of this extraction process, such as dip time, percolation time, extraction times, pH regulator scope etc., Optimization Technology.
2, test material
2.1 raw material: the Caulis Sinomenii that the Baoji provides
2.2 instrument:
Percolator;
PHS-2F PH meter: Electronic Instruments Plant of upper Nereid section
ZF-2 type three is used ultraviolet device: Town in Shanghai booth Electronic Instruments Plant
RE-52A Rotary Evaporators: Shanghai Yarong Biochemical Instrument Plant
The multiplex vacuum pump of SHB-3 recirculated water: 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 respectively in 4 beakers moistening 0.5 hour with the hydrochloric acid of the above-mentioned concentration of 40ml, add again the hydrochloric acid 50ml with concentration in each beaker, 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 the same thin laminate respectively, compared with the reference substance speckle, the time point of principal spot maximum is dip time;
2, the sample of same time period, variable concentrations is put on the same thin laminate by the concentration order, take the concentration point of principal spot maximum as optium concentration;
If 34 results that represent concentration during without significant difference, show that then the hydrochloric acid of 0.1～1.0mol/L all is fit to this extraction.
3.2 the percolation time is investigated
Get the hydrochloric acid of 3.1 described definite concentration 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 the same thin laminate, when without the sinomenine principal spot, is stopped percolation.Be defined as the terminal time of percolation.
3.3pH the value scope is investigated
After above-mentioned 3.2 percolates that obtain are regulated the above filtration of pH value to 11 with lime water, divide and get 5 parts of 50ml percolates, every part extracts respectively with the 16ml chloroform after transferring to different pH value with hydrochloric acid is counter, get extract, point is on the same thin laminate, minimum with impure speckle, the pH value point of principal spot maximum is the optimal pH range of accommodation.
3.4 Solvent quantity and number of times are investigated
Get above-mentioned 3.3 percolates after filtering, the optimal pH of transferring pH to 3.3 to determine, adopt chloroform to extract, press first 1/2 percolate volume, the consumption of each 1/3 percolation liquid extracts later on, gets extract after each extraction, sample spot is on the same thin laminate, when without the sinomenine speckle, end extraction, determine 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 parameters that determine, respectively at percolation, alkalization filter, sour water is instead transferred, extraction, acidify crystallize, the operation stage such as refining are got percolate, aqueous alkali, weak lye, extract, crude product, mother solution, elaboration, sample spot is analyzed on the same thin laminate.
3.6 thin layer chromatography point plate: get respectively the sample 5ul of above-mentioned test with 5ul point sample capillary tube, put on silica gel g thin-layer plate in order.
4, result
4.1 determining of the selection of concentration of hydrochloric acid and dip time sees 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 therefore choose the above concentration of 0.3mol/L (containing 0.3mol/L).0.3mol/L the dip time of hydrochloric acid tentatively is defined as reaching in 12 hours Cmax; 0.7mol/L the dip time of hydrochloric acid tentatively is defined as reaching in 10 hours maximum concentration; 1.0mol/L the dip time of hydrochloric acid tentatively is defined as reaching in 8 hours maximum concentration.
4.2 determining of percolation time sees 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.Determine to end percolation in 6-8 hour.
4.3 determining of pH value scope sees Table three and Fig. 7.
Table three: different PH chromatogram situation
Brief summary: determining the 3rd point, is best pH during pH=8 namely, is that pH=7-9 regulates allowed band between the 2nd and 4.
4.4 determining of Solvent quantity and number of times sees Table four and Fig. 8.
Table four: the thin layer situation of different extraction times
Brief summary: Fig. 8 is followed successively by and extracts 1,2,3,4 times sample from left to right, and under the ultraviolet, speck point is strengthened successively, and the non-main constituent amount of extraction increases.Though because 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, the research of finger printing sees Table five and Fig. 9.
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, the bismuth potassium iodide lower 2 kinds of materials that develop the color, filter again weak base, extraction by alkalization, effectively remove 6 kinds of materials and the a kind of lower non-main constituent alkaloid of colour developing observed under the ultraviolet, obtain single sinomenine hydrochloride by making with extra care again.Proof this method is scientific and reasonable, simple and feasible.
Experimental example two: contrast experiment
Percolation extraction process 3 in the table six: standby according to the tripartite legal system of embodiment
Chloroform Effect of Alcohol Extracting Procedureto Total in the table six: press 622 pages of attached sinomenine hydrochloride standards of Chinese Pharmacopoeia version in 2010.
Benzene Effect of Alcohol Extracting Procedureto Total in the table six: raw material pulverizing, oven dry add the alkalization of Calx mix homogeneously, insert add in the extraction pot benzene entirely be sealed reflux, extract, concentrated, filter, 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 results are shown in Table six.
Table six: contrast and experiment
Following embodiment all can realize the effect of above-mentioned experimental example.
Embodiment one:
The oven dry of 200g Caulis Sinomenii, pulverized 20 orders, adding 0.3mol/L HCl 160ml stirs in beaker, after the moistening 6 hours, put in the percolator, 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, filtrate is regulated pH value to 8.8 with HCl again, with chloroform extraction 4 times, lower floor's chloroform solution is through dehydration, concentrating under reduced pressure reclaims solvent, concentrated solution is regulated pH value to 2 with the hydrochloric acid of 6mol/L, stirs, cold filtration gets the sinomenine hydrochloride crude product;
Get sinomenine hydrochloride crude product 5.8g, be heated to backflow with 95% ethanol 90ml, add the 0.24g active carbon after the stirring and dissolving, insulation refluxed 30 minutes, filter while hot, filtrate is concentrated into 1/5, and cooling, crystallize filter, clean filter cake with ethanol colourless to filtrate, sinomenine hydrochloride elaboration 2.22g, relative medical material yield more than 1.11%, content 97.9%;
Get sinomenine hydrochloride 20g, with sucrose 45g, starch 36g, microcrystalline Cellulose 27g, the adjuvants such as 5% polyvidone aqueous solution 40ml, magnesium stearate 0.9g, with 5% polyvidone aqueous solution granulation, drying incapsulates 1000, and get final product, specification: the 20mg/ grain.
Embodiment two:
The oven dry of 400g Caulis Sinomenii, pulverized 20 orders, adding 1.0mol/L HCl 300ml stirs in beaker, after the moistening 0.5 hour, put in the percolator, 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, collects percolate after 8 hours, adds lime cream and regulates pH value to 10.8, filter, filtrate is regulated pH value to 9.2 with HCl again, uses chloroform extraction 3 times, and lower floor's chloroform solution is through dehydration, concentrating under reduced pressure, reclaim solvent, concentrated solution is regulated pH value to 3.5 with the hydrochloric acid of 6mol/L, stirs, cold filtration gets the hydrochlorate of sinomenine, and recrystallization gets the sinomenine hydrochloride crude product in ethanol;
Get sinomenine hydrochloride crude product 11.2g, be heated to backflow with 95% ethanol 110ml, add the 0.5g active carbon after the stirring and dissolving, insulation refluxed 30 minutes, filter while hot, filtrate is concentrated into 1/4, and cooling, crystallize filter, clean filter cake with ethanol colourless to filtrate, 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, with 5% polyvidone aqueous solution granulation, drying incapsulates, and get final product, specification: the 20mg/ grain.
Embodiment three:
The oven dry of 300g Caulis Sinomenii, pulverized 10 orders, adding 0.1mol/L HCl 240ml stirs in beaker, after the moistening 2 hours, put in the percolator, 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, collects percolate after 12 hours, adds lime cream and regulates pH value to 11.5, filter, filtrate is regulated pH value to 9.5 with HCl again, uses chloroform extraction 5 times, and lower floor's chloroform solution is washed to neutral through concentrating under reduced pressure, reclaim solvent, concentrated solution is regulated pH value to 2 with the hydrochloric acid of 6mol/L, stirs, cold filtration gets the hydrochlorate of sinomenine, and recrystallization gets the sinomenine hydrochloride crude product in ethanol;
Get sinomenine hydrochloride crude product 7.5g, be heated to backflow with 95% ethanol 60ml, add the 0.3g active carbon after the stirring and dissolving, insulation refluxed 30 minutes, filter while hot, filtrate is concentrated into 1/3, and cooling, crystallize filter, clean filter cake with ethanol colourless to filtrate, get sinomenine hydrochloride elaboration 3.3g, relative medical material yield 1.1%, content 96.5%.
Get sinomenine hydrochloride 20g, with sucrose 45g, starch 36g, microcrystalline Cellulose 27g, the adjuvants such as 5% polyvidone aqueous solution 40ml, magnesium stearate 0.9g, with 5% polyvidone aqueous solution granulation, drying incapsulates 1000, and get final product, specification: the 20mg/ grain.
Embodiment four:
The oven dry of 1000g Caulis Sinomenii, pulverized 20 orders, adding 0.3mol/L HCl 800ml stirs in beaker, after the moistening 5 hours, put in the percolator, 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, filtrate is regulated pH value to 8.8 with HCl again, with chloroform extraction 3 times, lower floor's chloroform solution is through dehydration, concentrating under reduced pressure reclaims solvent, concentrated solution is regulated pH value to 2 with the hydrochloric acid of 6mol/L, stirs, cold filtration gets the sinomenine hydrochloride crude product;
Get sinomenine hydrochloride crude product 4g, to fully dissolving, add the 0.16g active carbon with 75% ethanol 40ml reflux, insulation refluxed 20 minutes, filter while hot, filtrate is concentrated, cooling, crystallize, filter, clean filter cake with ethanol colourless to filtrate, get sinomenine hydrochloride elaboration 1.62g.
Get sinomenine hydrochloride 40g, with sucrose 60g, starch 40g, microcrystalline Cellulose 40g,, the adjuvants such as magnesium stearate 1.4g, 5% polyvidone aqueous solution 40ml, with 5% polyvidone aqueous solution granulation, drying incapsulates, and get final product, specification: the 20mg/ grain.
Embodiment five:
The oven dry of 1000g Caulis Sinomenii, pulverized 20 orders, adding 0.3mol/L HCl 900ml stirs in beaker, after the moistening 8 hours, put in the percolator, 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, filtrate is regulated pH value to 8.8 with HCl again, with chloroform extraction 2 times, lower floor's chloroform solution is through dehydration, concentrating under reduced pressure reclaims solvent, concentrated solution is regulated pH value to 2 with the hydrochloric acid of 6mol/L, stirs, cold filtration gets the sinomenine hydrochloride crude product;
Get sinomenine hydrochloride crude product 5g, to fully dissolving, add the 0.2g active carbon with 50% ethanol 37ml reflux, insulation refluxed 10 minutes, filter while hot, filtrate is concentrated, cooling, crystallize, filter, clean filter cake with ethanol colourless to filtrate, get sinomenine hydrochloride elaboration 1.71g.
Get sinomenine hydrochloride 20g, with sucrose 45g, starch 36g, microcrystalline Cellulose 27g, the adjuvants such as 5% polyvidone aqueous solution 40ml, magnesium stearate 0.9g, with 5% polyvidone aqueous solution granulation, drying incapsulates, and get final product, specification: the 20mg/ grain.
Embodiment six:
The oven dry of 1000g Caulis Sinomenii, pulverized 20 orders, adding 0.3mol/L HCl 700ml stirs in beaker, after the moistening 3 hours, put in the percolator, 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, filtrate is regulated pH value to 8.8 with HCl again, with chloroform extraction 3 times, lower floor's chloroform solution is through dehydration, concentrating under reduced pressure reclaims solvent, concentrated solution is regulated pH value to 2 with the hydrochloric acid of 6mol/L, stirs, cold filtration gets the sinomenine hydrochloride crude product;
Get sinomenine hydrochloride crude product 6g, to fully dissolving, add the 0.16g active carbon with 10% ethanol 30ml reflux, insulation refluxed 16 minutes, filter while hot, filtrate is concentrated, cooling, crystallize, filter, clean filter cake with ethanol colourless to filtrate, get sinomenine hydrochloride elaboration 1.87g.
Get sinomenine hydrochloride 40g, with sucrose 60g, starch 40g, microcrystalline Cellulose 40g,, the adjuvants such as magnesium stearate 1.4g, 5% polyvidone aqueous solution 40ml, with 5% polyvidone aqueous solution granulation, drying incapsulates, and get final product, specification: the 20mg/ grain.
Embodiment seven:
The oven dry of 1000g Caulis Sinomenii, pulverized 20 orders, adding 0.3mol/L HCl 700ml stirs in beaker, after the moistening 1 hour, put in the percolator, 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, filtrate is regulated pH value to 8.8 with HCl again, with chloroform extraction 4 times, lower floor's chloroform solution is through dehydration, concentrating under reduced pressure reclaims solvent, concentrated solution is regulated pH value to 2 with the hydrochloric acid of 6mol/L, stirs, cold filtration gets the sinomenine hydrochloride crude product;
Get sinomenine hydrochloride crude product 7.8g, be heated to 80 ℃ of insulations with the 30ml purified water, add the active carbon of 0.32g fully after the dissolving, be incubated 30 minutes, filter while hot, filtrate is concentrated, cooling, crystallize, filter, clean filter cake with ethanol colourless to filtrate, get sinomenine hydrochloride elaboration 2.55g.
Get sinomenine hydrochloride 40g, with sucrose 60g, starch 40g, microcrystalline Cellulose 40g,, the adjuvants such as magnesium stearate 1.4g, 5% polyvidone aqueous solution 40ml, with 5% polyvidone aqueous solution granulation, drying incapsulates, and get final product, 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 (7)
1. the preparation method of a sinomenine hydrochloride capsule is characterized in that the method comprises the steps:
The preparation method of step 1, sinomenine hydrochloride
A, preparation sinomenine hydrochloride crude product
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, the dress percolator, adding 0.1～1mol/L HCl makes liquid level cover medicated powder 2～6cm again, flood after 6～48 hours, begin percolation by the speed of 2～6ml/min, stop percolation after 6～24 hours, get percolate, for subsequent use;
Extract: above-mentioned percolate is added lime cream transfer pH to 10.5～12.0, filter, filtrate adds hydrochloric acid and transfers pH to 7.0～9.5, uses chloroform extraction 2～5 times; The combined chloroform layer washes with water to neutrality, adds the anhydrous Na of 3%～6% times of weight
2SO
4Dehydration, concentrating under reduced pressure reclaims chloroform;
Crystallization: concentrated solution splashes into 6mol/L HCl and transfers pH to 2～4, and be stirred to the floating solids and disperse, cold preservation, sucking filtration discards filtrate, and 60 ℃～70 ℃ oven dry filter cakes get yellow sinomenine hydrochloride crude product;
B, sinomenine hydrochloride process for refining
Get sinomenine hydrochloride crude product 5～10 weight portions, 10～95% ethanol or the extremely fully dissolving of purified water reflux with 30～120 parts by volume, the active carbon that adds 4% times of weight, insulation refluxed 10～30 minutes, filtered while hot, and filtrate is concentrated, cooling, crystallize, filter, it is colourless to filtrate 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, with 5% polyvidone aqueous solution granulation, drying incapsulates, and get final product.
2. the preparation method of sinomenine hydrochloride capsule as claimed in claim 1 is characterized in that step 1 is in the method:
A, preparation sinomenine hydrochloride crude product
Extract: Caulis Sinomenii coarse powder 500 weight portions with the 0.5mol/L HCl moistening of 500 parts by volume 2 hours, fill percolator, add again 0.5mol/L HCl 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, for subsequent use;
Extract: above-mentioned percolate is added lime cream transfer pH to 11.6, filter, filtrate adds hydrochloric acid and transfers pH to 8, uses chloroform extraction 4 times; The combined chloroform layer washes with water to 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 floating solids and disperse, cold preservation, sucking filtration discards filtrate, and 65 ℃ of oven dry filter cakes get yellow sinomenine hydrochloride crude product;
B, sinomenine hydrochloride process for refining
Get sinomenine hydrochloride crude product 7 weight portions, be that 75% alcohol heating reflux is to fully dissolving with the concentration of 60 parts by volume, the active carbon that adds 4% times of weight, insulation refluxed 20 minutes, filtered while hot, and filtrate is concentrated, cooling, crystallize, filter, it is colourless to filtrate that the ethanol with 95% cleans filter cake, gets sinomenine hydrochloride.
3. the preparation method of sinomenine hydrochloride capsule as claimed in claim 1 is characterized in that step 1 is in the method:
A, preparation sinomenine hydrochloride crude product
Extract: Caulis Sinomenii coarse powder 400 weight portions with the 0.3mol/L HCl moistening of 320 parts by volume 3.5 hours, fill percolator, add again 0.3mol/L HCl 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, for subsequent use;
Extract: above-mentioned percolate is added lime cream transfer pH to 11.3, filter, filtrate adds hydrochloric acid and transfers pH to 8.5, uses chloroform extraction 2 times; The combined chloroform layer washes with water to 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 floating solids and disperse, cold preservation, sucking filtration discards filtrate, and 62 ℃ of oven dry filter cakes get yellow sinomenine hydrochloride crude product;
B, sinomenine hydrochloride process for refining
Get sinomenine hydrochloride crude product 10 weight portions, with the extremely fully dissolving of 95% alcohol heating reflux of 120 parts by volume, add the active carbon of 4% times of weight, insulation refluxed 25 minutes, filter while hot, filtrate is concentrated, cooling, crystallize, filter, it is colourless to filtrate that the ethanol with 95% cleans filter cake, gets sinomenine hydrochloride.
4. the preparation method of sinomenine hydrochloride capsule as claimed in claim 1 is characterized in that step 1 is in the method:
A, preparation sinomenine hydrochloride crude product
Extract: Caulis Sinomenii coarse powder 800 weight portions with the 0.8mol/L HCl moistening of 300 parts by volume 1 hour, fill percolator, add again 0.2mol/L HCl 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, for subsequent use;
Extract: above-mentioned percolate is added lime cream transfer pH to 11.3, filter, filtrate adds hydrochloric acid and transfers pH to 7, uses chloroform extraction 5 times; The combined chloroform layer washes with water to 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 floating solids and disperse, cold preservation, sucking filtration discards filtrate, and 68 ℃ of oven dry filter cakes get yellow sinomenine hydrochloride crude product;
B, sinomenine hydrochloride process for refining
Get sinomenine hydrochloride crude product 6 weight portions, 80% ethanol or the extremely fully dissolving of purified water reflux with 40 parts by volume, the active carbon that adds 4% times of weight, insulation refluxed 15 minutes, filtered while hot, and filtrate is concentrated, cooling, crystallize, filter, it is colourless to filtrate that the ethanol with 95% cleans filter cake, gets sinomenine hydrochloride.
5. such as the preparation method of the arbitrary described sinomenine hydrochloride capsule of claim 1---4, it is characterized in that step 2 is in the method:
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.
6. such as the preparation method of the arbitrary described sinomenine hydrochloride capsule of claim 1---4, it is characterized in that step 2 is in the 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.
7. such as the preparation method of the arbitrary described sinomenine hydrochloride capsule of claim 1---4, it is characterized in that step 2 is in the 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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Citations (2)
| 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 |
|---|---|---|---|---|
| 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 (2)
| Title |
|---|
| 李海滨.青藤生物碱成分的研究.《贵阳医学院学报》.2006,第31卷(第4期),第344-345页. |
| 青藤生物碱成分的研究;李海滨;《贵阳医学院学报》;20060831;第31卷(第4期);第344-345页 * |
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