CN111269181B - Method and device for purifying sinomenine hydrochloride - Google Patents
Method and device for purifying sinomenine hydrochloride Download PDFInfo
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- CN111269181B CN111269181B CN201911420818.8A CN201911420818A CN111269181B CN 111269181 B CN111269181 B CN 111269181B CN 201911420818 A CN201911420818 A CN 201911420818A CN 111269181 B CN111269181 B CN 111269181B
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- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
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Abstract
The invention discloses a purification method of sinomenine hydrochloride extracting solution, which comprises the following specific steps: (1) Regulating pH value of sinomenine hydrochloride extract to 12-13 with lime cream, and centrifuging to obtain clear liquid A; (2) Adjusting the pH value of the clear liquid A to 10-11 by hydrochloric acid, and preprocessing to obtain clear liquid B; (3) Sending the clear liquid B into an ultrafiltration system to obtain ultrafiltration membrane permeate C; (4) Sending the permeate C into a nanofiltration system to obtain nanofiltration concentrated solution D; (5) The pH value of the concentrated solution D is adjusted back to 8-9 by hydrochloric acid, and after the concentrated solution D is fully stirred, the concentrated solution D is concentrated by a ceramic membrane, and then a sinomenine crude product is obtained by drying; (6) Heating and refluxing crude sinomenine hydrochloride with ethanol until the sinomenine hydrochloride is dissolved, adding active carbon, filtering, cooling, crystallizing, filtering, and washing a filter cake with ethanol until the filtrate is colorless to obtain sinomenine hydrochloride.
Description
Technical Field
The invention relates to a method and a device for purifying sinomenine hydrochloride, belonging to the technical field of plant extraction.
Background
Sinomenine (Sinomenine) is an alkaloid monomer extracted from Sinomenine, and has needle-like crystal and molecular weight of 329. Sinomenine, the main component of which was separated from sinomenine by Japanese scholars in the early 20 th century, has the effects of anti-inflammatory, immunity, cough relieving, blood pressure reducing and myocardial ischemia resisting, and in recent years, scholars research has found that sinomenine also has the effects of oxidation resistance, drug withdrawal and various antitumor activities. The hydrochloride preparation such as ZHENGQINGFENGTONGNING tablet, ZHENGQINGFENGTONGNING sustained release tablet and ZHENGQINGFENGTONGNING injection is used for treating rheumarthritis and rheumatoid arthritis, ankylosing spondylitis, arrhythmia, etc.
At present, the industrial production of sinomenine hydrochloride mostly adopts chloroform extraction technology with larger toxicity. Chloroform is a toxic solvent and can enter the body through the contact of the alimentary canal, the respiratory tract and the skin; has anesthetic effect on central nervous system, and has stimulating effect on eyes and skin, and can damage heart, liver and kidney; taking 10ml (140 mg/kg) in the human mouth can be fatal. Acute poisoning of chloroform is manifested by: headache, dizziness, debilitation, nausea and vomiting, the patients are excited first and then anesthetized, liver and kidney injury and the like occur, and serious patients can die due to respiratory paralysis and ventricular fibrillation. Erythema, edema, blisters, frostbite, etc. can occur when the skin is exposed to chloroform. Liver damage can occur when chloroform is contacted for a long time, and the phenomena such as dyspepsia, depression, insomnia and ataxia are accompanied. In addition, chloroform is recovered in industrial production, and the emission is difficult to reach the environmental protection requirement. Therefore, extraction with non-toxic substances in traditional Chinese medicine extraction is a key for preventing poisoning.
Disclosure of Invention
The purpose of the invention is that: the invention provides a process capable of replacing the traditional method, which can avoid using organic solvent and can achieve better product quality.
The technical proposal is as follows:
a method for purifying sinomenine hydrochloride comprises the following steps:
step 1, regulating the pH value of sinomenine hydrochloride extracting solution to 12-13 by lime cream, and then carrying out solid-liquid separation treatment to obtain clear liquid A;
step 2, the pH value of the clear liquid A is adjusted back to 10-11 by hydrochloric acid, and the clear liquid B is obtained after solid-liquid separation treatment;
step 3, sending the clear liquid B into an ultrafiltration membrane for ultrafiltration treatment to obtain an ultrafiltration membrane permeate;
step 4, sending the ultrafiltration membrane permeate into a nanofiltration membrane for nanofiltration treatment to obtain nanofiltration concentrated solution;
step 5, the pH value of the nanofiltration concentrated solution is adjusted back to 8-9 by hydrochloric acid, and the nanofiltration concentrated solution is fully stirred, concentrated by a ceramic membrane, and then dried to obtain a sinomenine crude product;
and step 6, taking a sinomenine hydrochloride crude product, adding ethanol, heating and refluxing until the sinomenine hydrochloride crude product is dissolved, adding active carbon, filtering, cooling, crystallizing, filtering, and washing a filter cake with the ethanol until the filtrate is colorless to obtain sinomenine hydrochloride.
In one embodiment, in the step 1, solid-liquid separation means a centrifugation method.
In one embodiment, in the step 2, the solid-liquid separation refers to one of plate-frame filtration, coarse filtration and membrane filtration.
In one embodiment, in the step 3, the molecular weight cut-off of an ultrafiltration membrane adopted in the ultrafiltration treatment is 1000-20000 Da, and the filtration pressure is 0.2-2.0Mpa; in the ultrafiltration process, water is needed to be supplemented in the later period to dialyze the concentrated solution, and the water adding amount is generally 0.1-2 times of the stock solution amount.
In one embodiment, in the step 4, the molecular weight cut-off of the nanofiltration membrane adopted in the nanofiltration treatment is 200-400 Da, the filtration pressure is 0.4-4.0Mpa, and in the nanofiltration filtration process, the concentrate is required to be dialyzed by water supplement in the later stage, and the water addition amount is generally 0.1-2 times of the original liquid amount.
In one embodiment, the ceramic membrane has a pore size of 1-1200nm, preferably a pore size of 5-500nm; the temperature of the feed liquid in the ceramic membrane filtration process is 5-60 ℃; the pressure is 0.1-0.5Mpa; the flow rate of the membrane surface is 2-5m/s; the concentration multiple is 1-30 times.
In one embodiment, in the ceramic membrane concentration process, water is needed to be supplemented in the later period to dialyze the concentrated solution, and the water adding amount is generally 0.1-2 times of the original liquid amount.
A sinomenine hydrochloride purification device, comprising:
the extraction tank is used for extracting sinomenine hydrochloride from sinomenine;
a first hydrochloric acid adding tank connected to the extraction tank for adding a hydrochloric acid solution to the extraction tank;
an alkalizing tank connected to the extracting tank for alkalizing the extracted sinomenine solution with lime milk;
a lime milk adding tank connected to the alkalizing tank for adding lime milk into the alkalizing tank;
the first centrifugal machine is connected with the alkalizing tank and is used for carrying out centrifugal impurity removal treatment on the feed liquid subjected to the lime milk alkalization treatment;
the adjusting tank is connected with the first centrifugal machine and is used for carrying out pH adjustment treatment on clear liquid obtained by the first centrifugal machine;
a second hydrochloric acid adding tank connected to the adjusting tank for adding hydrochloric acid into the adjusting tank;
the plate frame filter is connected with the adjusting tank and is used for filtering and impurity removing treatment of the feed liquid obtained in the adjusting tank;
the ultrafiltration membrane is connected to the permeation side of the plate frame filter and is used for carrying out ultrafiltration purification treatment on the permeate of the plate frame filter;
the nanofiltration membrane is connected to the permeation side of the ultrafiltration membrane and is used for carrying out nanofiltration concentration treatment on filtrate of the ultrafiltration membrane;
the ceramic membrane is connected to the concentration side of the nanofiltration membrane and is used for concentrating the concentrated solution obtained by the nanofiltration membrane;
the third hydrochloric acid adding tank is connected to the liquid inlet of the ceramic membrane and is used for regulating the pH value of the concentrated liquid obtained by the nanofiltration membrane;
the first drying box is connected with the concentrated side of the ceramic membrane and is used for drying the concentrated solution of the ceramic membrane;
the alcohol dissolving tank is used for alcohol dissolving the crude product obtained in the first drying box;
an ethanol adding tank connected to the alcohol dissolving tank for adding ethanol into the alcohol dissolving tank;
the decoloring kettle is connected with the alcohol dissolving tank and is used for decoloring the solution obtained from the alcohol dissolving tank;
an activated carbon adding tank connected to the decoloring kettle and used for adding activated carbon into the decoloring kettle;
the crystallization kettle is connected with the activated carbon adding tank and is used for carrying out crystallization treatment on the decolored material;
the second centrifugal machine is connected with the crystallization kettle and is used for carrying out centrifugal separation on sinomenine hydrochloride obtained by crystallization;
and the drying box is connected with the second centrifugal machine and is used for drying sinomenine hydrochloride obtained by the second centrifugal machine.
In one embodiment, the ultrafiltration membrane has a molecular weight cut-off of 1000 to 20000Da.
In one embodiment, the nanofiltration membrane has a molecular weight cut-off of 200 to 400Da.
In one embodiment, the ceramic membrane has a pore size of 5-500nm.
In one embodiment, the method further comprises: the first water adding port is connected with the liquid inlet of the ultrafiltration membrane and is used for carrying out dialysis water adding treatment on the ultrafiltration membrane.
In one embodiment, the method further comprises: the second water adding port is connected with the liquid inlet of the nanofiltration membrane and is used for carrying out dialysis water adding treatment on the nanofiltration membrane.
In one embodiment, the method further comprises: the third water adding port is connected with the liquid inlet of the ceramic membrane and is used for carrying out dialysis water adding treatment on the ceramic membrane.
Advantageous effects
The purification method of sinomenine hydrochloride extracting solution provided by the invention replaces the chloroform extraction process in the prior art by a membrane integration technology. The new process avoids the consumption and the residue of the organic solvent, improves the quality of the product, has higher automation level, shortens the production period and realizes the green, environment-friendly and energy-saving manufacture of sinomenine hydrochloride.
Drawings
Fig. 1 is a diagram of the apparatus of the present invention.
Wherein, 1, an extraction tank; 2. a first hydrochloric acid addition tank; 3. an alkalizing tank; 4. lime milk is added into the tank; 5. a first centrifuge; 6. an adjustment tank; 7. adding second hydrochloric acid into the tank; 8. a plate frame filter; 9. an ultrafiltration membrane; 10. a first water inlet; 11. nanofiltration membrane; 12. a second water inlet; 13. a ceramic membrane; 14. adding third hydrochloric acid into the tank; 15. a first drying oven; 16. an alcohol dissolution tank; 17. ethanol is added into the tank; 18. a decoloring kettle; 19. adding activated carbon into a tank; 20. a crystallization kettle; 21. a second centrifuge; 22. a second drying oven; 23. and a third water adding port.
Detailed Description
The invention discloses a purification method of sinomenine hydrochloride extracting solution, which comprises the following specific steps: (1) Regulating pH value of sinomenine hydrochloride extract to 12-13 with lime cream, and centrifuging to obtain clear liquid A; (2) Adjusting the pH value of the clear liquid A to 10-11 by hydrochloric acid, and preprocessing to obtain clear liquid B; (3) Sending the clear liquid B into an ultrafiltration system to obtain ultrafiltration membrane permeate C; (4) Sending the permeate C into a nanofiltration system to obtain nanofiltration concentrated solution D; (5) The pH value of the concentrated solution D is adjusted back to 8-9 by hydrochloric acid, and after the concentrated solution D is fully stirred, the concentrated solution D is concentrated by a ceramic membrane, and then a sinomenine crude product is obtained by drying; (6) Heating and refluxing crude sinomenine hydrochloride with ethanol until the sinomenine hydrochloride is dissolved, adding active carbon, filtering, cooling, crystallizing, filtering, and washing a filter cake with ethanol until the filtrate is colorless to obtain sinomenine hydrochloride. The invention has the advantages that: the traditional chloroform extraction is replaced by the membrane integration technology, so that the consumption and the residue of toxic organic solvents are avoided, and the quality of products is improved; and the automation level is higher, the production period is shortened, and the green, environment-friendly and energy-saving manufacturing of sinomenine hydrochloride is realized.
The method of the invention is described in detail as follows:
step 1, regulating the pH value of sinomenine hydrochloride extracting solution to 12-13 by lime cream, and centrifuging to obtain clear liquid A; the purpose of the step is to alkalize the extracting solution, dissolve sinomenine and separate the sinomenine from impurities by centrifugation;
step 2, the pH value of the clear liquid A is adjusted back to 10-11 by hydrochloric acid, and clear liquid B is obtained through pretreatment; the aim of the step is to reduce certain pH and further filter and purify;
step 3, sending the clear liquid B into an ultrafiltration system to obtain ultrafiltration membrane permeate C; the aim of the step is to carry out the purification treatment of the macromolecular impurities through an ultrafiltration membrane.
Step 4, sending the penetrating fluid C into a nanofiltration system to obtain nanofiltration concentrated solution D; the aim of the step is to concentrate sinomenine through a nanofiltration membrane, and enable inorganic salt and micromolecular impurities to permeate the nanofiltration membrane so as to realize the purification of sinomenine;
and step 5, adjusting the pH value of the concentrated solution D to 8-9 by using hydrochloric acid, fully stirring, concentrating by using a ceramic membrane, and drying to obtain a sinomenine crude product. The method aims at reducing the solubility of sinomenine by adjusting back the pH value, so that the sinomenine can be separated out and concentrated by a ceramic membrane, and the pH value in the step is a key parameter, and after the pH value is controlled to be 8-9, the solubility of sinomenine can be reduced, and the sinomenine is slightly dissolved in water, so that the purpose of concentrating and purifying the sinomenine by adopting a large-aperture ceramic membrane is realized, and the problem of using chloroform is avoided; the method has the advantages that the method plays a role in reducing the solubility of sinomenine and separating sinomenine from impurities, can greatly reduce the impurities, can realize further purification of sinomenine hydrochloride by adding water to dialyze the ceramic membrane, and can improve the purity of products.
And step 6, taking a sinomenine hydrochloride crude product, adding ethanol, heating and refluxing until the sinomenine hydrochloride crude product is dissolved, adding active carbon, filtering, cooling, crystallizing, filtering, and washing a filter cake with the ethanol until the filtrate is colorless to obtain sinomenine hydrochloride. In this step, the activated carbon is used for decoloring.
In one embodiment, the sinomenine hydrochloride extracting solution is obtained by wetting and percolating sinomenine coarse powder with hydrochloric acid.
In one embodiment, the pretreatment may include a cartridge filter, a plate frame, a hollow fiber membrane, and the like.
In one embodiment, the ultrafiltration is an ultrafiltration membrane made of ceramic or organic materials, the molecular weight cut-off is 1000-20000 Da, and the filtration pressure is 0.2-2.0Mpa.
In one embodiment, in the ultrafiltration process, water is added to dialyze the concentrated solution in the later stage, and the water addition amount is generally 0.1-2 times of the original liquid amount.
In one embodiment, the nanofiltration is a ceramic nanofiltration membrane or an organic nanofiltration membrane, the molecular weight cut-off is 100-1000 Da, and the filtration pressure is 0.4-4.0Mpa.
In one embodiment, in the nanofiltration filtration process, water is needed to be supplemented in the later stage to dialyze the concentrated solution, and the water adding amount is generally 0.1-2 times of the original liquid amount.
In one embodiment, the ceramic membrane has a pore size of 1-1200nm, preferably a pore size of 5-500nm; the temperature of the feed liquid in the ceramic membrane filtration process is 5-60 ℃; the pressure is 0.1-0.5Mpa; the flow rate of the membrane surface is 2-5m/s; the concentration multiple is 1-30 times.
In one embodiment, in the ceramic membrane concentration process, water is needed to be supplemented in the later period to dialyze the concentrated solution, and the water adding amount is generally 0.1-2 times of the original liquid amount.
Based on the method, the invention also provides a sinomenine hydrochloride purifying device, which comprises the following steps:
an extraction tank 1 for extracting sinomenine hydrochloride from caulis Sinomenii;
a first hydrochloric acid addition tank 2 connected to the extraction tank 1 for adding a hydrochloric acid solution to the extraction tank 1;
an alkalizing tank 3 connected to the extracting tank 1 for alkalizing the extracted sinomenine solution with lime milk;
a lime milk adding tank 4 connected to the alkalizing tank 3 for adding lime milk into the alkalizing tank 3;
the first centrifugal machine 5 is connected with the alkalizing tank 3 and is used for carrying out centrifugal impurity removal treatment on the feed liquid subjected to lime milk alkalization treatment;
an adjusting tank 6 connected to the first centrifuge 5 for performing pH adjustment treatment on the clear liquid obtained by the first centrifuge 5;
a second hydrochloric acid addition tank 7 connected to the adjustment tank 6 for adding hydrochloric acid to the adjustment tank 6;
the plate frame filter 8 is connected with the regulating tank 6 and is used for filtering and impurity removing the feed liquid obtained in the regulating tank 6;
an ultrafiltration membrane 9 connected to the permeate side of the plate-and-frame filter 8 for performing ultrafiltration purification treatment on the permeate of the plate-and-frame filter 8;
a nanofiltration membrane 11 connected to the permeation side of the ultrafiltration membrane 9 for performing nanofiltration concentration treatment on the filtrate of the ultrafiltration membrane 9;
a ceramic membrane 13 connected to the concentration side of the nanofiltration membrane 11 for concentrating the concentrated solution obtained by the nanofiltration membrane 11;
a third hydrochloric acid adding tank 14 connected to the liquid inlet of the ceramic membrane 13 for adjusting the pH of the concentrated liquid obtained from the nanofiltration membrane 11;
a first drying box 15 connected to the concentrated side of the ceramic membrane 13 for drying the concentrated solution of the ceramic membrane 13;
an alcohol-dissolving tank 16 for alcohol-dissolving the crude product obtained in the first drying oven 15;
an ethanol adding tank 17 connected to the alcohol dissolving tank 16 for adding ethanol to the alcohol dissolving tank 16;
a decoloring kettle 18 connected to the alcohol tank 16 for decoloring the solution obtained from the alcohol tank 16;
an activated carbon adding tank 19 connected to the decoloring kettle 18 for adding activated carbon to the decoloring kettle 18;
a crystallization kettle 20 connected to the activated carbon adding tank 19 for crystallizing the decolorized material;
a second centrifuge 21 connected to the crystallization kettle 20 for centrifuging the sinomenine hydrochloride obtained by crystallization;
the drying box 22 is connected to the second centrifuge 21, and is used for drying sinomenine hydrochloride obtained by the second centrifuge 21.
In one embodiment, the ultrafiltration membrane 9 has a molecular weight cut-off of 1000 to 20000Da.
In one embodiment, the nanofiltration membrane 11 has a molecular weight cut-off of 200 to 400Da.
In one embodiment, the ceramic membrane 13 has a pore size of 5-500nm.
In one embodiment, the method further comprises: the first water adding port 10 is connected with a liquid inlet of the ultrafiltration membrane 9 and is used for carrying out dialysis water adding treatment in the ultrafiltration membrane 9.
In one embodiment, the method further comprises: the second water adding port 12 is connected with the liquid inlet of the nanofiltration membrane 11 and is used for carrying out dialysis water adding treatment in the nanofiltration membrane 11.
In one embodiment, the method further comprises: the third water adding port 14 is connected with the liquid inlet of the ceramic membrane 13 and is used for carrying out dialysis water adding treatment in the ceramic membrane 13.
Example 1
Firstly, taking a sinomenine solution 80L extracted by 0.3mol/L hydrochloric acid, regulating the pH value to 12.5 by lime milk, and centrifuging to obtain a clear liquid 1; secondly, the pH value of the clear liquid 1 is adjusted back to 10.5 by using 6mol/L hydrochloric acid, and then the clear liquid 2 is obtained by plate frame filtration; taking 60L clear liquid 2, entering an ultrafiltration membrane device with a molecular weight cut-off of about 5000Da, controlling the experimental temperature at 30-40 ℃, controlling the filtering pressure at 0.8Mpa, concentrating to 6 times, and then starting to add softened water for washing and filtering, wherein the water adding amount is 20L, thus obtaining an ultrafiltration membrane permeate 3; then, 60L of ultrafiltration membrane permeate 3 is taken and sent into a filter membrane device with the molecular weight cut-off of about 300Da sodium, the experimental temperature is controlled at 30-40 ℃, the filtering pressure is 2.6Mpa, after the concentration is 10 times, the filtration is started to be added with softened water for washing filtration, and the water addition amount is 12L, so as to obtain nanofiltration concentrated solution 4; finally, taking 60L concentrated solution 4, adjusting the pH value to 8-9 by hydrochloric acid, standing for 4 hours, then sending the concentrated solution into a 200nm ceramic membrane device for concentration, controlling the experimental temperature to be 30-40 ℃, controlling the filtering pressure to be 0.25Mpa, concentrating to 10 times, then starting to add softened water for washing and filtering, adding water with the volume of 12L, and finally drying the ceramic membrane concentrated solution to obtain a sinomenine crude product. Finally, taking 11g of sinomenine hydrochloride crude product, heating to reflux by using 110ml of 95% ethanol, stirring and dissolving, adding 0.5g of active carbon, preserving heat and refluxing for 30 minutes, filtering while the active product is hot, concentrating the filtrate to 1/4, cooling, crystallizing, filtering, washing the filter cake with ethanol until the filtrate is colorless, and obtaining 4.48g of sinomenine hydrochloride refined product, wherein the yield of the sinomenine hydrochloride refined product is 81.2% and the content is 95.9% relative to the sinomenine hydrochloride extract.
Comparative example 1
This control example is a conventional chloroform extraction process.
Regulating the pH value of the 60L clear liquid 2 left after plate-frame filtration in the embodiment to 9.0 by using a 6mol/L hydrochloric acid solution, extracting for 3 times by using chloroform, dehydrating the lower chloroform solution, concentrating under reduced pressure, recovering a solvent, regulating the pH value of the concentrated solution to 3.5 by using the 6mol/L hydrochloric acid, stirring, cooling and filtering to obtain sinomenine hydrochloride, and recrystallizing in ethanol to obtain a sinomenine hydrochloride crude product; taking 11g of sinomenine hydrochloride crude product, heating to reflux with 110ml of 95% ethanol, stirring for dissolving, adding 0.5g of active carbon, preserving heat and refluxing for 30 minutes, filtering while the active carbon is hot, concentrating the filtrate to 1/4, cooling, crystallizing, filtering, washing the filter cake with ethanol until the filtrate is colorless, and obtaining 4.53g of sinomenine hydrochloride refined product, wherein the yield of the sinomenine hydrochloride refined product is 82.3% and the content of the sinomenine hydrochloride extracted solution is 96.4%.
Comparative example 2
The differences from example 1 are: the dialysis treatment with water is not adopted in the concentration process of the ceramic membrane.
Firstly, taking a sinomenine solution 80L extracted by 0.3mol/L hydrochloric acid, regulating the pH value to 12.5 by lime milk, and centrifuging to obtain a clear liquid 1; secondly, the pH value of the clear liquid 1 is adjusted back to 10.5 by using 6mol/L hydrochloric acid, and then the clear liquid 2 is obtained by plate frame filtration; taking 60L clear liquid 2, entering an ultrafiltration membrane device with a molecular weight cut-off of about 5000Da, controlling the experimental temperature at 30-40 ℃, controlling the filtering pressure at 0.8Mpa, concentrating to 6 times, and then starting to add softened water for washing and filtering, wherein the water adding amount is 20L, thus obtaining an ultrafiltration membrane permeate 3; then, 60L of ultrafiltration membrane permeate 3 is taken and sent into a filter membrane device with the molecular weight cut-off of about 300Da sodium, the experimental temperature is controlled at 30-40 ℃, the filtering pressure is 2.6Mpa, after the concentration is 10 times, the filtration is started to be added with softened water for washing filtration, and the water addition amount is 12L, so as to obtain nanofiltration concentrated solution 4; finally, the pH value of the 60L concentrated solution 4 is adjusted back to 8-9 by hydrochloric acid, and after the solution is kept for 4 hours, the solution is sent into a 200nm ceramic membrane device for concentration, the experimental temperature is controlled at 30-40 ℃, the filtering pressure is 0.25Mpa, the solution is concentrated to 10 times, and finally the ceramic membrane concentrated solution is dried to obtain a sinomenine crude product. Finally, taking 11g of sinomenine hydrochloride crude product, heating to reflux by using 110ml of 95% ethanol, stirring and dissolving, adding 0.5g of active carbon, preserving heat and refluxing for 30 minutes, filtering while the active product is hot, concentrating the filtrate to 1/4, cooling, crystallizing, filtering, washing the filter cake with ethanol until the filtrate is colorless, and obtaining 4.48g of sinomenine hydrochloride refined product, wherein the yield of the sinomenine hydrochloride refined product is 82.4% and the content of the sinomenine hydrochloride extracted solution is 93.1%.
As can be seen from comparative example 1 and example 1, the novel process has a similar treatment effect to the chloroform extraction process, the content of sinomenine hydrochloride finished products can reach more than 95%, and the yield is also more than 80%. In conclusion, the sinomenine hydrochloride extracting solution is clarified through a membrane integration technology, so that the sinomenine hydrochloride extracting solution can completely replace the extraction of toxic reagent chloroform, the consumption and the residue of an organic solvent are avoided, the quality of a product is improved, and the green, environment-friendly and energy-saving manufacturing of sinomenine hydrochloride is realized. As can be seen from comparative example 2 and example 1, the purpose of concentrating the precipitate by the ceramic membrane is achieved after the pH of sinomenine hydrochloride is adjusted to 8.5-9, and the product is washed in the dialysis process of the ceramic membrane by adding water for dialysis, so that the purity of the product is improved from 93.1% to 96.4%.
Claims (5)
1. The purification method of sinomenine hydrochloride is characterized by comprising the following steps:
step 1, regulating the pH value of sinomenine hydrochloride extracting solution to 12-13 by lime cream, and then carrying out solid-liquid separation treatment to obtain clear liquid A;
step 2, the pH value of the clear liquid A is adjusted back to 10-11 by hydrochloric acid, and the clear liquid B is obtained after solid-liquid separation treatment;
step 3, sending the clear liquid B into an ultrafiltration membrane for ultrafiltration treatment to obtain an ultrafiltration membrane permeate;
step 4, sending the ultrafiltration membrane permeate into a nanofiltration membrane for nanofiltration treatment to obtain nanofiltration concentrated solution;
step 5, the pH value of the nanofiltration concentrated solution is adjusted back to 8-9 by hydrochloric acid, and the nanofiltration concentrated solution is fully stirred, concentrated by a ceramic membrane, and then dried to obtain a sinomenine crude product;
step 6, taking a sinomenine hydrochloride crude product, adding ethanol, heating and refluxing until the sinomenine hydrochloride crude product is dissolved, adding active carbon, filtering, cooling, crystallizing, filtering, and washing a filter cake with ethanol until the filter cake is colorless to obtain sinomenine hydrochloride;
in the step 3, the interception molecular weight of an ultrafiltration membrane adopted in the ultrafiltration treatment is 1000-20000 Da;
in the step 4, the molecular weight cut-off of a nanofiltration membrane adopted in the nanofiltration treatment is 200-400 Da;
the aperture of the ceramic membrane is 5-500nm.
2. The method for purifying sinomenine hydrochloride according to claim 1, wherein in the step 1, the solid-liquid separation means a centrifugation method; in the step 2, solid-liquid separation refers to one of plate-frame filtration and membrane filtration; in the step 3, the filtering pressure in the ultrafiltration treatment is 0.2-2.0Mpa; in the ultrafiltration process, water is needed to be supplemented in the later period to dialyze the concentrated solution, and the water adding amount is 0.1-2 times of the stock solution amount.
3. The method for purifying sinomenine hydrochloride according to claim 1, wherein in the step 4, the filtration pressure is 0.4-4.0Mpa, and in the nanofiltration process, the concentrated solution is dialyzed by water supplement in the later stage, and the water addition amount is generally 0.1-2 times of the original solution amount.
4. The purification method of sinomenine hydrochloride according to claim 1, wherein the temperature of the feed liquid in the ceramic membrane filtration process is 5-60 ℃; the pressure is 0.1-0.5Mpa; the flow rate of the membrane surface is 2-5m/s; the concentration multiple is 1-30 times.
5. The method for purifying sinomenine hydrochloride according to claim 1, wherein the later-stage water supplement is needed to dialyze the concentrated solution in the ceramic membrane concentration process, and the water addition amount is 0.1-2 times of the original liquid amount.
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| CN115504936A (en) * | 2021-06-22 | 2022-12-23 | 湖南正清制药集团股份有限公司 | Alkalization equipment and method for sinomenine hydrochloride |
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