CN111269181A - Purification method and device of sinomenine hydrochloride - Google Patents
Purification method and device of sinomenine hydrochloride Download PDFInfo
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- CN111269181A CN111269181A CN201911420818.8A CN201911420818A CN111269181A CN 111269181 A CN111269181 A CN 111269181A CN 201911420818 A CN201911420818 A CN 201911420818A CN 111269181 A CN111269181 A CN 111269181A
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Abstract
The invention discloses a method for purifying sinomenine hydrochloride extracting solution, which comprises the following specific steps: (1) regulating pH of sinomenine hydrochloride extractive solution to 12-13 with lime milk, and centrifuging to obtain clear liquid A; (2) adjusting the pH value of the clear liquid A to 10-11 by hydrochloric acid, and performing pretreatment to obtain clear liquid B; (3) sending the clear liquid B into an ultrafiltration system to obtain an ultrafiltration membrane penetrating liquid C; (4) sending the penetrating fluid C into a nanofiltration system to obtain nanofiltration concentrated solution D; (5) adjusting the pH value of the concentrated solution D to 8-9 by hydrochloric acid, fully stirring, concentrating by using a ceramic membrane, and drying to obtain a sinomenine crude product; (6) taking the crude sinomenine hydrochloride product, adding ethanol, heating and refluxing to dissolve, adding activated carbon, filtering, cooling, crystallizing, filtering, and washing a filter cake with ethanol until the filtrate is colorless to obtain the 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 caulis Sinomenii, and has needle-like crystal structure and molecular weight of 329. Sinomenium acutum is used for treating rheumatic diseases more than 1000 years ago, and a Japanese scholar is used for separating sinomenine which is a main component from sinomenine at the beginning of 20 th century, wherein sinomenine has the effects of resisting inflammation, immunizing, relieving cough, reducing blood pressure and resisting myocardial ischemia. The hydrochloride preparation commonly used in clinic, such as Zhengqing Fengtongning tablet, Zhengqing Fengtongning sustained release tablet and Zhengqing Fengtongning injection, is used for treating rheumatic arthritis and rheumatoid arthritis, and treating ankylosing spondylitis, arrhythmia and the like, and has obvious curative effect.
At present, the industrial production of sinomenine hydrochloride mostly adopts a chloroform extraction process with high toxicity. Chloroform is a toxic solvent and can enter the body through contact with the digestive tract, respiratory tract and skin; has anesthetic effect on central nervous system, eye and skin irritation, and can damage heart, liver, and kidney; oral administration of 10ml (140 mg/kg) to humans can be fatal. Acute poisoning of chloroform is manifested by: headache, dizziness, hypodynamia, nausea and vomiting, patients are excited and then anesthetized, liver and kidney injuries and the like occur, and severe patients can die due to respiratory paralysis and ventricular fibrillation. Contact of chloroform with the skin can cause erythema, edema, blisters, frostbite, etc. When the patient is exposed to chloroform for a long time, liver damage can occur, and phenomena such as dyspepsia, depression, insomnia, ataxia and the like are accompanied. In addition, the recovery of chloroform in industrial production is complicated, and the emission is difficult to meet the environmental protection requirement. Therefore, the key point of preventing poisoning is that the traditional Chinese medicine is extracted without toxic substances.
Disclosure of Invention
The purpose of the invention is: the invention solves the problem that organic solvent (such as chloroform) is needed to be adopted for extraction in the purification process of sinomenine hydrochloride in the prior art, and provides a process which can replace the traditional method, so that the use of organic solvent can be avoided, and better product quality can be achieved.
The technical scheme 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 using lime milk, and performing solid-liquid separation treatment to obtain clear solution A;
step 2, regulating the pH value of the clear liquid A to 10-11 by hydrochloric acid, and carrying out solid-liquid separation treatment to obtain a clear liquid B;
step 3, feeding the clear liquid B into an ultrafiltration membrane for ultrafiltration treatment to obtain ultrafiltration membrane penetrating liquid;
5, adjusting the pH value of the nanofiltration concentrated solution to 8-9 by using hydrochloric acid, fully stirring, concentrating by using a ceramic membrane, and drying to obtain a sinomenine crude product;
and 6, taking the crude sinomenine hydrochloride product, adding ethanol, heating and refluxing to dissolve, adding activated carbon, filtering, cooling, crystallizing, filtering, and washing a filter cake with ethanol until the filtrate is colorless to obtain sinomenine hydrochloride.
In one embodiment, in step 1, the solid-liquid separation is performed by centrifugation.
In one embodiment, the solid-liquid separation in step 2 is one of plate-and-frame filtration, coarse filtration and membrane filtration.
In one embodiment, in the step 3, the molecular weight cut-off of an ultrafiltration membrane used in the ultrafiltration treatment is 1000 to 20000Da, and the filtration pressure is 0.2 to 2.0 MPa; in the ultrafiltration 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, in the step 4, the intercepted molecular weight of the nanofiltration membrane used in the nanofiltration treatment is 200-400 Da, the filtration pressure is 0.4-4.0Mpa, and during the nanofiltration filtration process, water is required to be replenished at the later stage to dialyze the concentrated solution, 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 membrane pore size of 5-500 nm; the temperature of the feed liquid in the ceramic membrane filtration process is 5-60 ℃; the pressure is 0.1-0.5 Mpa; the flow velocity of the membrane surface is 2-5 m/s; the concentration times are 1-30 times.
In one embodiment, in the ceramic membrane concentration process, water is required to be added 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's purification device includes:
the extraction tank is used for extracting sinomenine hydrochloride from the caulis sinomenii;
the first hydrochloric acid adding tank is connected to the extraction tank and is used for adding a hydrochloric acid solution into the extraction tank;
the alkalization tank is connected with the extraction tank and is used for adding lime milk into the extracted sinomenine solution for alkalization treatment;
the lime milk adding tank is connected with the alkalization tank and is used for adding lime milk into the alkalization tank;
the first centrifuge is connected with the alkalization tank and is used for carrying out centrifugal impurity removal treatment on the feed liquid subjected to lime milk alkalization treatment;
the adjusting tank is connected with the first centrifugal machine and is used for adjusting the pH of the clear liquid obtained by the first centrifugal machine;
the second hydrochloric acid adding tank is connected with the adjusting tank and is used for adding hydrochloric acid into the adjusting tank;
the plate frame filter is connected with the adjusting tank and is used for filtering and purifying 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 the filtrate of the ultrafiltration membrane;
the ceramic membrane is connected to the concentration side of the nanofiltration membrane and is used for concentrating 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 adjusting the pH of the concentrated solution obtained by the nanofiltration membrane;
the first drying box is connected with the concentration side of the ceramic membrane and used for drying the concentrated solution of the ceramic membrane;
the alcohol dissolving tank is used for carrying out alcohol dissolving on the crude product obtained in the first drying box;
the ethanol adding tank is connected with the alcohol dissolving tank and is used for adding ethanol into the alcohol dissolving tank;
the decoloring kettle is connected with the alcohol dissolving tank and is used for decoloring solution obtained by the alcohol dissolving tank;
the activated carbon adding tank is connected with the decoloring kettle and is 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 the sinomenine hydrochloride obtained by crystallization;
and the drying box is connected to the second centrifugal machine and used for drying the sinomenine hydrochloride obtained by the second centrifugal machine.
In one embodiment, the ultrafiltration membrane has a molecular weight cut-off of 1000 to 20000 Da.
In one embodiment, the nanofiltration membrane has a molecular weight cut-off of 200-400 Da.
In one embodiment, the ceramic membrane has a pore size of 5 to 500 nm.
In one embodiment, further comprising: and the first water adding port is connected with a liquid inlet of the ultrafiltration membrane and is used for dialysis water adding treatment in the ultrafiltration membrane.
In one embodiment, further comprising: and the second water filling port is connected with the liquid inlet of the nanofiltration membrane and is used for dialysis water adding treatment in the nanofiltration membrane.
In one embodiment, further comprising: and the third water filling port is connected with the liquid inlet of the ceramic membrane and is used for dialysis and water adding treatment in 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 the 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 alkalization tank; 4. adding lime milk into a tank; 5. a first centrifuge; 6. a conditioning tank; 7. a second hydrochloric acid addition tank; 8. a plate frame filter; 9. ultrafiltration membranes; 10. a first water addition port; 11. a nanofiltration membrane; 12. a second water filling port; 13. a ceramic membrane; 14. a third hydrochloric acid addition tank; 15. a first drying oven; 16. an alcohol dissolving tank; 17. adding ethanol into the tank; 18. a decoloring kettle; 19. adding activated carbon into the tank; 20. a crystallization kettle; 21. a second centrifuge; 22. a second drying oven; 23. and a third water filling port.
Detailed Description
The invention discloses a method for purifying sinomenine hydrochloride extracting solution, which comprises the following specific steps: (1) regulating pH of sinomenine hydrochloride extractive solution to 12-13 with lime milk, and centrifuging to obtain clear liquid A; (2) adjusting the pH value of the clear liquid A to 10-11 by hydrochloric acid, and performing pretreatment to obtain clear liquid B; (3) sending the clear liquid B into an ultrafiltration system to obtain an ultrafiltration membrane penetrating liquid C; (4) sending the penetrating fluid C into a nanofiltration system to obtain nanofiltration concentrated solution D; (5) adjusting the pH value of the concentrated solution D to 8-9 by hydrochloric acid, fully stirring, concentrating by using a ceramic membrane, and drying to obtain a sinomenine crude product; (6) taking the crude sinomenine hydrochloride product, adding ethanol, heating and refluxing to dissolve, adding activated carbon, filtering, cooling, crystallizing, filtering, and washing a filter cake with ethanol until the filtrate is colorless to obtain the 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 the product is improved; and the automation level is higher, the production period is shortened, and the green, environment-friendly and energy-saving manufacture of the sinomenine hydrochloride is realized.
The method of the invention is detailed as follows:
step 1, regulating the pH value of sinomenine hydrochloride extracting solution to 12-13 by using lime milk, and then centrifuging to obtain clear solution A; the purpose of the step is to alkalize the extracting solution, so that the sinomenine can be dissolved and can be separated from impurities in a centrifugal mode;
step 2, adjusting the pH value of the clear liquid A to 10-11 by hydrochloric acid, and performing pretreatment to obtain clear liquid B; the purpose of this step is to lower a certain pH and further filter and purify;
step 3, sending the clear liquid B into an ultrafiltration system to obtain ultrafiltration membrane penetrating liquid C; the aim of the step is to carry out the mesh purification treatment on the impurities of the macromolecules through an ultrafiltration membrane.
and 5, adjusting the pH value of the concentrated solution D to 8-9 by hydrochloric acid, fully stirring, concentrating by using a ceramic membrane, and drying to obtain a sinomenine crude product. The purpose of the step is to reduce the solubility of the sinomenine by adjusting back the pH value so that the sinomenine can be separated out and concentrated by a ceramic membrane, wherein the pH value is a key parameter, and the sinomenine can be reduced in solubility and slightly soluble in water after being controlled to be 8-9, 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 step plays a role in reducing the solubility of the sinomenine and separating the sinomenine from impurities, so that the impurities can be greatly reduced, the sinomenine hydrochloride can be further purified by adding water to dialyze the ceramic membrane, and the product purity can be improved.
And 6, taking the crude sinomenine hydrochloride product, adding ethanol, heating and refluxing to dissolve, adding activated carbon, filtering, cooling, crystallizing, filtering, and washing a filter cake with ethanol until the filtrate is colorless to obtain sinomenine hydrochloride. In this step, the decolorization treatment is performed by activated carbon.
In one embodiment, the sinomenine hydrochloride extract is obtained by wetting and percolating sinomenine coarse powder with hydrochloric acid.
In one embodiment, the pretreatment may include treatment with a cartridge filter, a plate frame, a hollow fiber membrane, or the like.
In one embodiment, the ultrafiltration membrane is a ceramic or organic ultrafiltration membrane, the molecular weight cut-off is 1000-20000 Da, and the filtration pressure is 0.2-2.0 MPa.
In one embodiment, during the ultrafiltration process, water is required to be added for dialysis of the concentrated solution at a later stage, and the added water amount is generally 0.1-2 times of the original liquid amount.
In one embodiment, the nanofiltration membrane is a ceramic or organic nanofiltration membrane, the molecular weight cut-off is 100-1000 Da, and the filtration pressure is 0.4-4.0 MPa.
In one embodiment, during the nanofiltration filtration process, water is required to be added at the later stage to dialyze the concentrated solution, 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 membrane pore size of 5-500 nm; the temperature of the feed liquid in the ceramic membrane filtration process is 5-60 ℃; the pressure is 0.1-0.5 Mpa; the flow velocity of the membrane surface is 2-5 m/s; the concentration times are 1-30 times.
In one embodiment, in the ceramic membrane concentration process, water is required to be added 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 purification device, which comprises the following steps:
the extraction tank 1 is used for extracting sinomenine hydrochloride from the caulis sinomenii;
the first hydrochloric acid adding tank 2 is connected to the extraction tank 1 and is used for adding a hydrochloric acid solution into the extraction tank 1;
the alkalization tank 3 is connected to the extraction tank 1 and is used for adding lime milk into the extracted sinomenine solution for alkalization;
a lime milk adding tank 4 connected to the alkalization tank 3 for adding lime milk into the alkalization tank 3;
the first centrifuge 5 is connected with the alkalization 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 processing 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 into the adjustment tank 6;
the plate frame filter 8 is connected to the adjusting tank 6 and is used for filtering and purifying the feed liquid obtained in the adjusting tank 6;
the ultrafiltration membrane 9 is connected to the permeation side of the plate-frame filter 8 and is used for performing ultrafiltration purification treatment on the permeate of the plate-frame filter 8;
the nanofiltration membrane 11 is connected to the permeation side of the ultrafiltration membrane 9 and is used for performing nanofiltration concentration treatment on the filtrate of the ultrafiltration membrane 9;
the ceramic membrane 13 is connected to the concentration side of the nanofiltration membrane 11 and is used 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 and used for adjusting the pH of the concentrated solution obtained by the nanofiltration membrane 11;
a first drying box 15 connected to the concentration side of the ceramic membrane 13 for drying the concentrated solution of the ceramic membrane 13;
a 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 into the alcohol dissolving tank 16;
the decoloring kettle 18 is connected to the alcohol-soluble tank 16 and is used for decoloring the solution obtained by the alcohol-soluble 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 performing crystallization treatment on the decolored material;
a second centrifuge 21 connected to the crystallization kettle 20 for performing centrifugal separation on sinomenine hydrochloride obtained by crystallization;
and the drying box 22 is connected to the second centrifuge 21 and is used for drying the sinomenine hydrochloride obtained by the second centrifuge 21.
In one embodiment, the ultrafiltration membrane 9 has a molecular weight cut-off of 1000 to 20000 Da.
In one embodiment, the nanofiltration membrane 11 has a molecular weight cut-off of 200-400 Da.
In one embodiment, the ceramic membrane 13 has a pore size of 5 to 500 nm.
In one embodiment, further comprising: and a first water adding port 10 connected to a liquid inlet of the ultrafiltration membrane 9 and used for dialysis water adding treatment in the ultrafiltration membrane 9.
In one embodiment, further comprising: and the second water adding port 12 is connected to the liquid inlet of the nanofiltration membrane 11 and is used for dialysis water adding treatment in the nanofiltration membrane 11.
In one embodiment, further comprising: and a third water adding port 14 connected to a liquid inlet of the ceramic membrane 13 for dialysis water adding treatment in the ceramic membrane 13.
Example 1
Firstly, 80L of sinomenine solution extracted by 0.3mol/L hydrochloric acid is taken, the pH value of the sinomenine solution is adjusted to 12.5 by lime milk, and then the sinomenine solution is centrifuged to obtain clear liquid 1; secondly, adjusting the pH value of the clear liquid 1 to 10.5 by using 6mol/L hydrochloric acid, and filtering by using a plate frame to obtain a clear liquid 2; taking 60L of clear liquid 2, introducing into an ultrafiltration membrane device with a cut-off molecular weight of about 5000Da, controlling the experimental temperature at 30-40 ℃, controlling the filtration pressure at 0.8Mpa, concentrating to 6 times, adding softened water, washing and filtering, and adding 20L of water to obtain an ultrafiltration membrane penetrating liquid 3; then, 60L of ultrafiltration membrane penetrating fluid 3 is taken and sent into a filtration membrane device with the molecular weight cut-off of about 300Da, the experimental temperature is controlled at 30-40 ℃, the filtration pressure is 2.6Mpa, after the concentration is 10 times, softened water is added for washing and filtration, and the water addition amount is 12L, so as to obtain nanofiltration concentrated solution 4; and finally, adjusting the pH value of the 60L concentrated solution 4 to 8-9 by hydrochloric acid, standing for 4h, then feeding the concentrated solution into a 200nm ceramic membrane device for concentration, controlling the experimental temperature to be 30-40 ℃, controlling the filtration pressure to be 0.25Mpa, concentrating to 10 times, adding softened water for washing and filtering, wherein the water addition amount is 12L, and finally drying the ceramic membrane concentrated solution to obtain a sinomenine crude product. And finally, taking 11g of crude sinomenine hydrochloride, heating the crude sinomenine hydrochloride by using 110ml of 95% ethanol to reflux, stirring the solution for dissolution, adding 0.5g of activated carbon, preserving the temperature and refluxing for 30 minutes, filtering the solution while the solution is hot, concentrating the filtrate to 1/4, cooling the solution, crystallizing the solution, filtering the solution, and washing a filter cake by using ethanol until the filtrate is colorless to obtain 4.48g of refined sinomenine hydrochloride, wherein the yield of the sinomenine hydrochloride relative to the sinomenine hydrochloride extracting solution is 81.2 percent, and the content of the sinomenine hydrochloride.
Comparative example 1
This comparative example is a conventional chloroform extraction process.
Adjusting pH value of 60L of clear liquid 2 remained after plate-frame filtration in the embodiment to 9.0 with 6mol/L hydrochloric acid solution, extracting for 3 times with chloroform, dehydrating lower layer chloroform solution, concentrating under reduced pressure, recovering solvent, adjusting pH value of concentrated solution to 3.5 with 6mol/L hydrochloric acid, stirring, cooling, filtering to obtain sinomenine hydrochloride, and recrystallizing in ethanol to obtain sinomenine crude product; taking 11g of sinomenine hydrochloride crude product, heating to reflux by using 110ml of 95% ethanol, stirring to dissolve, adding 0.5g of activated carbon, preserving heat and refluxing for 30 minutes, filtering while hot, concentrating the filtrate to 1/4, cooling, crystallizing, filtering, and cleaning the filter cake by using ethanol until the filtrate is colorless to obtain 4.53g of sinomenine hydrochloride refined product, wherein the yield is 82.3% relative to sinomenine hydrochloride extracting solution, and the content is 96.4%.
Comparative example 2
The differences from example 1 are: no dialysis treatment with water was used in the concentration of the ceramic membranes.
Firstly, 80L of sinomenine solution extracted by 0.3mol/L hydrochloric acid is taken, the pH value of the sinomenine solution is adjusted to 12.5 by lime milk, and then the sinomenine solution is centrifuged to obtain clear liquid 1; secondly, adjusting the pH value of the clear liquid 1 to 10.5 by using 6mol/L hydrochloric acid, and filtering by using a plate frame to obtain a clear liquid 2; taking 60L of clear liquid 2, introducing into an ultrafiltration membrane device with a cut-off molecular weight of about 5000Da, controlling the experimental temperature at 30-40 ℃, controlling the filtration pressure at 0.8Mpa, concentrating to 6 times, adding softened water, washing and filtering, and adding 20L of water to obtain an ultrafiltration membrane penetrating liquid 3; then, 60L of ultrafiltration membrane penetrating fluid 3 is taken and sent into a filtration membrane device with the molecular weight cut-off of about 300Da, the experimental temperature is controlled at 30-40 ℃, the filtration pressure is 2.6Mpa, after the concentration is 10 times, softened water is added for washing and filtration, and the water addition amount is 12L, so as to obtain nanofiltration concentrated solution 4; and finally, adjusting the pH value of the 60L concentrated solution 4 to 8-9 by hydrochloric acid, standing for 4h, then feeding 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, and finally drying the ceramic membrane concentrated solution to obtain a sinomenine crude product. And finally, taking 11g of crude sinomenine hydrochloride, heating the crude sinomenine hydrochloride by using 110ml of 95% ethanol to reflux, stirring the solution for dissolution, adding 0.5g of activated carbon, preserving the temperature and refluxing for 30 minutes, filtering the solution while the solution is hot, concentrating the filtrate to 1/4, cooling the solution, crystallizing the solution, filtering the solution, and washing a filter cake by using ethanol until the filtrate is colorless to obtain 4.48g of refined sinomenine hydrochloride, wherein the yield of the sinomenine hydrochloride relative to the sinomenine hydrochloride extracting solution is 82.4 percent and the content of the sinomenine hydrochloride extracting.
As can be seen from comparison of example 1 and example 1, the treatment effect of the new process is similar to the purification effect of the chloroform extraction process, the content of the sinomenine hydrochloride finished product can reach more than 95%, and the yield is also more than 80%. In conclusion, the sinomenine hydrochloride extracting solution is clarified by the membrane integration technology, so that toxic reagent chloroform can be completely replaced for extraction, the consumption and the residue of organic solvent are avoided, the quality of the product is improved, and the green, environment-friendly and energy-saving production of sinomenine hydrochloride is realized. As can be seen from the comparison of example 2 and example 1, the purpose of concentrating the precipitate by the ceramic membrane is achieved by adjusting the pH of the sinomenine hydrochloride to 8.5-9, and the product purity is improved from 93.1% to 96.4% by washing the product in the ceramic membrane dialysis process by adding water for dialysis.
Claims (10)
1. A method for purifying sinomenine hydrochloride is characterized by comprising the following steps:
step 1, regulating the pH value of sinomenine hydrochloride extracting solution to 12-13 by using lime milk, and performing solid-liquid separation treatment to obtain clear solution A;
step 2, regulating the pH value of the clear liquid A to 10-11 by hydrochloric acid, and carrying out solid-liquid separation treatment to obtain a clear liquid B;
step 3, feeding the clear liquid B into an ultrafiltration membrane for ultrafiltration treatment to obtain ultrafiltration membrane penetrating liquid;
step 4, sending the penetrating fluid of the ultrafiltration membrane into a nanofiltration membrane for nanofiltration treatment to obtain nanofiltration concentrated solution;
5, adjusting the pH value of the nanofiltration concentrated solution to 8-9 by using hydrochloric acid, fully stirring, concentrating by using a ceramic membrane, and drying to obtain a sinomenine crude product;
and 6, taking the crude sinomenine hydrochloride product, adding ethanol, heating and refluxing to dissolve, adding activated carbon, filtering, cooling, crystallizing, filtering, and washing a filter cake with ethanol until the filtrate is colorless to obtain sinomenine hydrochloride.
2. The method for purifying sinomenine hydrochloride according to claim 1, wherein in one embodiment, in the step 1, the solid-liquid separation is performed by centrifugation; in one embodiment, in the step 2, the solid-liquid separation is 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 used in the ultrafiltration treatment is 1000 to 20000Da, and the filtration pressure is 0.2 to 2.0 MPa; in the ultrafiltration 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.
3. The method for purifying sinomenine hydrochloride according to claim 1, wherein in the step 4, the nanofiltration membrane used in the nanofiltration treatment has a molecular weight cut-off of 200 to 400Da and a filtration pressure of 0.4 to 4.0Mpa, and during the nanofiltration filtration, water is required to be added at a later stage for dialysis of the concentrated solution, and the amount of added water is generally 0.1 to 2 times of the amount of the original solution.
4. The method of claim 1, wherein the pore size of the ceramic membrane is 1-1200nm, preferably 5-500 nm; the temperature of the feed liquid in the ceramic membrane filtration process is 5-60 ℃; the pressure is 0.1-0.5 Mpa; the flow velocity of the membrane surface is 2-5 m/s; the concentration times are 1-30 times.
5. The method for purifying sinomenine hydrochloride according to claim 1, wherein in one embodiment, during the ceramic membrane concentration process, water is required to be added for dialysis of the concentrated solution at a later stage, and the amount of the added water is generally 0.1-2 times of the amount of the original solution.
6. A purification device of sinomenine hydrochloride is characterized by comprising:
the extraction tank (1) is used for extracting sinomenine hydrochloride from the caulis sinomenii;
the first hydrochloric acid adding tank (2) is connected to the extraction tank (1) and is used for adding a hydrochloric acid solution into the extraction tank (1);
the alkalization tank (3) is connected to the extraction tank (1) and is used for adding lime milk into the extracted sinomenine solution for alkalization;
a lime milk adding tank (4) connected to the alkalization tank (3) and used for adding lime milk into the alkalization tank (3);
the first centrifugal machine (5) is connected with the alkalization tank (3) and is used for carrying out centrifugal impurity removal treatment on the feed liquid subjected to lime milk alkalization treatment;
a regulating tank (6) connected to the first centrifuge (5) for performing pH regulation 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 into the adjustment tank (6);
the plate frame filter (8) is connected to the adjusting tank (6) and is used for filtering and purifying the feed liquid obtained in the adjusting tank (6);
the ultrafiltration membrane (9) is connected to the permeation side of the plate frame filter (8) and is used for carrying out ultrafiltration purification treatment on the permeate of the plate frame filter (8);
the nanofiltration membrane (11) is connected to the permeation side of the ultrafiltration membrane (9) and is used for carrying out nanofiltration concentration treatment on the filtrate of the ultrafiltration membrane (9);
a ceramic membrane (13) which is connected to the concentration side of the nanofiltration membrane (11) and is used 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) and used for adjusting the pH of the concentrated solution obtained by the nanofiltration membrane (11);
a first drying box (15) connected to the concentration side of the ceramic membrane (13) and used for drying the concentrated solution of the ceramic membrane (13);
a alcohol dissolving tank (16) for alcohol dissolving the crude product obtained in the first drying oven (15);
the ethanol adding tank (17) is connected with the alcohol dissolving tank (16) and is used for adding ethanol into the alcohol dissolving tank (16);
the decoloring kettle (18) is connected with the alcohol dissolving tank (16) and is used for decoloring the solution obtained by the alcohol dissolving tank (16);
the activated carbon adding tank (19) is connected with the decoloring kettle (18) and is used for adding activated carbon into the decoloring kettle (18);
the crystallization kettle (20) is connected with the activated carbon adding tank (19) and is used for carrying out crystallization treatment on the decolored material;
the second centrifugal machine (21) is connected with the crystallization kettle (20) and is used for carrying out centrifugal separation on the sinomenine hydrochloride obtained by crystallization;
and the drying box (22) is connected to the second centrifugal machine (21) and is used for drying the sinomenine hydrochloride obtained by the second centrifugal machine (21).
7. The sinomenine hydrochloride purification device according to claim 6, wherein in one embodiment, the ultrafiltration membrane (9) has a molecular weight cut-off of 1000 to 20000 Da; in one embodiment, the nanofiltration membrane (11) has a molecular weight cut-off of 200-400 Da.
8. The apparatus for purifying sinomenine hydrochloride as claimed in claim 6, wherein the ceramic membrane (13) has a pore size of 5 to 500nm in one embodiment.
9. The apparatus for purifying sinomenine hydrochloride of claim 6, further comprising: the first water adding port (10) is connected with a liquid inlet of the ultrafiltration membrane (9) and is used for dialysis water adding treatment in the ultrafiltration membrane (9); in one embodiment, further comprising: and the second water adding port (12) is connected with the liquid inlet of the nanofiltration membrane (11) and is used for dialysis water adding treatment in the nanofiltration membrane (11).
10. The apparatus for purifying sinomenine hydrochloride of claim 6, further comprising: and the third water filling port (14) is connected with the liquid inlet of the ceramic membrane (13) and is used for dialysis water adding treatment in the ceramic membrane (13).
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN114957118A (en) * | 2021-02-22 | 2022-08-30 | 湖南正清制药集团股份有限公司 | Extraction method of sinomenine hydrochloride |
| 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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| GB791146A (en) * | 1954-11-26 | 1958-02-26 | Int Minerals & Chem Corp | Improvements in or relating to production of betaine hydrochloride |
| CZ2002570A3 (en) * | 1999-08-19 | 2002-11-13 | Tate & Lyle Sugar Holdings, Inc. | Sugar beet membrane filtration process |
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| CN114957118A (en) * | 2021-02-22 | 2022-08-30 | 湖南正清制药集团股份有限公司 | Extraction method of sinomenine hydrochloride |
| 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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