阅读说明：本技术 一种n-乙酰-l-半胱氨酸的电渗析提取方法 (Electrodialysis extraction method of N-acetyl-L-cysteine ) 是由 林海波 丛林川 于 2020-06-12 设计创作，主要内容包括：本发明属于氨基酸生产技术领域,公开了一种N-乙酰-L-半胱氨酸的电渗析的提取方法。本发明采用陶瓷膜分离、电渗析脱盐、活性炭脱色、膜浓缩、减压蒸发浓缩结晶及重结晶工艺的组合,有效实现了N-乙酰-L-半胱氨酸的清洁高效生产；该工艺的关键点为用电渗析取代了离子交换,有机溶剂萃取等传统脱盐浓缩提取工艺；大大提高了产品提取率,提高了产品纯度,同时减少了原有工艺的酸碱用量和水耗,降低了后续工艺的活性炭用量,大大减少了环境污染。(The invention belongs to the technical field of amino acid production, and discloses an electrodialysis extraction method of N-acetyl-L-cysteine. The method adopts the combination of ceramic membrane separation, electrodialysis desalination, activated carbon decoloration, membrane concentration, reduced pressure evaporation concentration crystallization and recrystallization processes, and effectively realizes the clean and efficient production of the N-acetyl-L-cysteine; the key point of the process is that the traditional desalination, concentration and extraction processes such as ion exchange, organic solvent extraction and the like are replaced by electrodialysis; greatly improves the extraction rate of the product, improves the purity of the product, reduces the acid-base dosage and water consumption of the prior process, reduces the dosage of activated carbon of the subsequent process and greatly reduces the environmental pollution.)

1. An electrodialysis extraction method of N-acetyl-L-cysteine is characterized by comprising the following steps:

A. filtering by a ceramic membrane; filtering the electrolytic reaction liquid by a ceramic membrane to remove solid impurities in the electrolytic reaction liquid to obtain a ceramic filter clarifying liquid containing N-acetyl-L-cysteine, wherein the conductivity of the ceramic filter clarifying liquid is 10000-100000 mu S/cm; the aperture of the ceramic membrane is 100-500nm, the operation pressure difference is 0.15-0.40MPa, and the membrane surface flow rate is 2.0-4.0 m/s;

B. continuous electrodialysis desalination: adjusting the filtered clear liquid containing the N-acetyl-L-cysteine obtained in the step A to an isoelectric point pH of 1.0-2.0, adding the filtered clear liquid into an electrodialysis membrane separator for desalting treatment, wherein the operation temperature is 10-40 ℃;

C. activated carbon decolorization: heating the electrodialysis desalination solution obtained in the step B to 50-70 ℃, violently stirring, adding decolorizing active carbon, and carrying out heat preservation and decolorization treatment for 40-60min until decolorization is achieved to obtain decolorized clear solution;

D. pre-concentrating a reverse osmosis membrane: concentrating the decolorized clear liquid obtained in the step C by a reverse osmosis membrane until the content of N-acetyl-L-cysteine is 12% -15%, and obtaining reverse osmosis preconcentrated liquid;

E. and (3) reduced pressure evaporation, concentration and crystallization: d, performing reduced pressure evaporation concentration on the reverse osmosis preconcentration solution obtained in the step D, cooling the concentrated solution to room temperature, and growing crystals at the temperature of 0-10 ℃ for 5-10 hours; filtering to obtain wet N-acetyl-L-cysteine crystal;

F. and (3) recrystallization: and E, dissolving the wet N-acetyl-L-cysteine crystal product obtained in the step E in water, recrystallizing and drying to obtain a purified dry N-acetyl-L-cysteine product.

2. The electrodialytic extraction method of N-acetyl-L-cysteine according to claim 1, wherein: in the step A, the electrolytic reaction solution is obtained by acetylating L-cystine and then carrying out electrolytic reduction on the L-cystine.

3. An electrodialysis extraction process for extracting N-acetyl-L-cysteine according to claim 1, wherein: in the step A, the solid impurities mainly refer to solid shedding of a cathode electrode in the electrolytic reduction reaction process, and comprise graphite, carbon, lead and silver.

4. The electrodialytic extraction method of N-acetyl-L-cysteine according to claim 1, wherein: in the step B, the electrodialysis membrane separator adopts a heterogeneous alloy membrane or a homogeneous phase mould, a Ru-Ti-Sn ternary oxide coating titanium electrode is used as an anode, a titanium plate is used as a cathode, and the water adding amount in a concentration chamber is 0.5-4 times of the volume of the feed liquid of the filtered clear liquid.

5. The electrodialytic extraction method of N-acetyl-L-cysteine according to claim 1, wherein: in the step B, the operating voltage of the electrodialysis membrane separator is 5-35V, the current variation range is 0.1-25A, the electrode solution is 0.5-2.5% of sodium sulfate aqueous solution, and the pH value is maintained at 6.0-7.0; the conductivity x of the desalted clear liquid obtained after electrodialysis electric drive membrane treatment is lower than 2000 mu S/cm, and the loss rate is less than 5%.

6. The electrodialytic extraction method of N-acetyl-L-cysteine according to claim 1, wherein: in the step C, the mass ratio of the activated carbon to the electrodialysis desalination liquid is 1: 0.005-0.015.

7. The electrodialysis extraction method of N-acetyl-L-cysteine according to claim 1, wherein in step D, the reverse osmosis membrane is operated at 0.5-2.5MPa and 20-60 ℃ to obtain concentrated feed liquid with solid content of 5% -10%, and pure water is used as water for production process.

8. The process for electrodialytic extraction of N-acetyl-L-cysteine according to claim 1, wherein in step E, said reduced pressure evaporation is performed at a temperature of 60-80 ℃ and the volume of the evaporated solution is 20-40% of the original volume.

9. The electrodialytic extraction method of N-acetyl-L-cysteine according to claim 1, wherein: and step F, drying the wet N-acetyl-L-cysteine crystal product through double cones, and drying for 5 hours at the temperature of 80 ℃ and the vacuum degree of-0.08 Mpa to obtain a dry product with the water content of less than 0.5 percent.

Technical Field

The invention belongs to the technical field of amino acid derivative production, and particularly relates to an electrodialysis extraction method of N-acetyl-L-cysteine, which has important application in the fields of medicine, cosmetics and biochemical raw material purification.

Technical Field

N-acetyl-L-cysteine (NAC) is an acetylated derivative of cysteine, has high medicinal value, contains sulfhydryl group in molecule, can break disulfide bond in mucin peptide bond, can be widely used for treating respiratory diseases, and can be made into eye drops for treating various keratitis. Meanwhile, the sulfhydryl of the N-acetyl-L-cysteine can react with the oxidative group, and can be used for treating, preventing or delaying alopecia caused by oxidative damage or in the chemotherapy process; can participate in various important metabolisms, promote the synthesis of glutathione and maintain the reduction state of cells; can also be used as inhibitor for inhibiting tissue and cell necrosis caused by canceration; it can also be used for treating external injury, central nervous system injury, visual tissue injury, and Parkinson's disease caused by lipid peroxidation. The N-acetyl-L-cysteine is used as a pharmaceutical auxiliary agent, a raw material medicine, a synthetic medicine raw material and an intermediate, has wide application in the aspects of producing anti-AIDS drugs, anti-cancer drugs, cosmetics and the like, and has great practical value.

In the industrial production of N-acetyl-L-cysteine, the separation and purification process of N-acetyl-L-cysteine is very complicated and high in cost, and the separation and purification cost of N-acetyl-L-cysteine usually accounts for more than half of the total cost. The traditional separation method comprises a precipitation method, an ion exchange method and the like, but a large amount of toxic, flammable and explosive solvents (methanol, ethanol and the like) are usually adopted for solvent precipitation or extraction, a large amount of energy is consumed for recovering the reagent, a large amount of waste water and waste gas are generated, and the environment is seriously polluted; the ion exchange resin method needs to repeatedly carry out ion exchange, then elute and regenerate, has troublesome operation, low yield, easy resin breakage, high cost and high consumption of a large amount of anion and cation resin, and can also generate a large amount of waste acid alkali liquor in the process and seriously cause environmental impact.

In recent years, with the continuous progress of biochemical separation technology, various advanced separation devices and methods play an increasingly important role in production, and especially, the application of electrodialysis desalination technology is developed, so that various biochemical separation methods are greatly improved. In the prior art, electrodialysis membrane separation technology is used for separating and refining amino acid and derivative products thereof, but a method for separating and extracting N-acetyl-L-cysteine from an electrolytic reaction liquid by using the electrodialysis technology is not reported. The subject group provides a method for electrochemically synthesizing N-acetyl-L-cysteine from L-cystine, which comprises the following specific steps: firstly acetylating L-cystine to obtain N, N '-diacetyl-L-cystine, and then electrolytically reducing the N, N' -diacetyl-L-cystine to obtain N-acetyl-L-cysteine. In view of the above, it is desirable to develop a method for purifying N-acetyl-L-cysteine by ion membrane electrodialysis, which can effectively avoid the disadvantages of the conventional separation method.

Disclosure of Invention

The invention aims to provide a method for separating and extracting N-acetyl-L-cysteine from electrolytic reaction liquid by adopting an electrodialysis mode, so as to overcome the defects of high cost, complex operation, low extraction rate and easy environmental pollution of the traditional separation mode. Compared with the traditional extraction process, the process for extracting the N-acetyl-L-cysteine by the electrodialysis method has the advantages that the product purity and the yield are obviously improved, the operation cost is greatly reduced, the process is green and environment-friendly, and the national green and economic requirements are met.

The purpose of the invention is realized by the following technical scheme:

an electrodialysis extraction method of N-acetyl-L-cysteine comprises the following steps: firstly, leading the electrolytic reaction solution to pass through a ceramic filter membrane to thoroughly remove solid impurities to obtain filtered clear solution; then, separating inorganic salt from the obtained filtered clear liquid by using continuous electrodialysis equipment; then carrying out pre-concentration by using a reverse osmosis membrane, carrying out reduced pressure evaporation concentration, crystallizing and the like to obtain a crude product, and recrystallizing the crude product to obtain a high-purity N-acetyl-L-cysteine product.

The electrodialysis extraction method of the N-acetyl-L-cysteine specifically comprises the following steps:

A. ceramic membrane filtration: filtering the electrolytic reaction liquid by a ceramic membrane to remove solid impurities in the electrolytic reaction liquid to obtain a ceramic filter clarifying liquid containing N-acetyl-L-cysteine, wherein the conductivity of the ceramic filter clarifying liquid is 10000-100000 mu S/cm; the specific conditions of the ceramic membrane filtration are as follows: the aperture of the ceramic membrane is 100-500nm, the operation pressure difference is 0.15-0.40MPa, and the flow rate of the membrane surface is 2.0-4.0 m/s;

B. continuous electrodialysis desalination: adjusting the pH value of the pottery filter clarified liquid containing the N-acetyl-L-cysteine obtained in the step A to be 1.0-2.0 at the isoelectric point, adding the pottery filter clarified liquid into an electrodialysis membrane separator for desalting treatment, wherein the operation temperature is 10-40 ℃;

C. activated carbon decolorization: heating the electrodialysis desalination solution obtained in the step B to 50-70 ℃, violently stirring, adding decolorizing active carbon, and carrying out heat preservation and decolorization treatment for 40-60min until decolorization is achieved to obtain decolorized clear solution;

D. pre-concentrating a reverse osmosis membrane: concentrating the decolorized clear liquid obtained in the step C by a reverse osmosis membrane until the content of N-acetyl-L-cysteine is 12% -15%, and obtaining reverse osmosis preconcentrated liquid;

E. and (3) reduced pressure evaporation, concentration and crystallization: d, performing reduced pressure evaporation concentration on the reverse osmosis preconcentration solution obtained in the step D, cooling the concentrated solution to room temperature, and growing crystals for 5-10 hours at the temperature of 0-10 ℃; filtering to obtain wet N-acetyl-L-cysteine crystal;

F. and (3) recrystallization: and E, dissolving the wet N-acetyl-L-cysteine crystal product obtained in the step E in water, recrystallizing and drying to obtain a purified dry N-acetyl-L-cysteine product.

As a more excellent technical scheme of the invention: step A, the electrolytic reaction solution is obtained by acetylating L-cystine and then carrying out electrolytic reduction, wherein the solution contains N-acetyl-L-cysteine, sodium ions, chloride ions, acetate ions, acetic acid, pigments and other impurities.

As a more excellent technical scheme of the invention: step A, the solid impurities mainly refer to solid shedding of a cathode electrode in the electrolytic reduction reaction process, and comprise graphite, carbon, lead and silver.

As a more excellent technical scheme of the invention: and step B, adopting a heterogeneous alloy membrane or a homogeneous phase mould as the electrodialysis membrane separator, taking a Ru-Ti-Sn ternary oxide coating titanium electrode as an anode and a titanium plate as a cathode, and adding water into the concentrated chamber with the volume 0.5-4 times that of the filtered clear solution (dilute chamber solution).

As a more excellent technical scheme of the invention: step B, the specific operating conditions of the desalination treatment of the electrodialysis membrane separator are as follows: the electrodialytic membrane separator has the operating voltage of 5-35V, the current variation range of 0.1-25A, the electrode liquid is 0.5-2.5% sodium sulfate aqueous solution, and the pH value is maintained at 6.0-7.0; the conductivity of the desalted clear liquid obtained after the electrodialysis electric driving membrane treatment is lower than 2000 mu S/cm, and the loss rate is less than 5 percent.

As a more excellent technical scheme of the invention: and C, the mass ratio of the using amount of the activated carbon to the electrodialysis desalination liquid is 1: 0.005-0.015.

As a more excellent technical scheme of the invention: and D, operating the reverse osmosis membrane at the pressure of 0.5-2.5MPa and the temperature of 20-60 ℃ to obtain concentrated feed liquid with the solid content of 5-10%, and using the seeped pure water as water for the production process.

As a more excellent technical scheme of the invention: and E, the temperature of the reduced pressure evaporation is 60-80 ℃, and the volume of the evaporated solution is 20-40% of the original volume.

As a more excellent technical scheme of the invention: and F, drying the wet N-acetyl-L-cysteine crystal product through double cones, and drying for 5 hours at the vacuum degree of-0.08 Mpa and the temperature of 80 ℃ to obtain a dry product with the water content of less than 0.5 percent.

Compared with the prior art, the invention has the beneficial effects that:

the method adopts electrodialysis to replace the traditional desalination, concentration and extraction processes such as ion exchange, organic solvent extraction and the like; the extraction rate of the product is greatly improved, and the purity of the product is improved; meanwhile, the acid-base dosage and the water consumption of the original process are reduced, the dosage of activated carbon of the subsequent process is reduced, and the environmental pollution is greatly reduced; the electric power is adopted as clean energy, normal temperature desalination is realized, the energy consumption is low, the investment is low, and the cost is obviously reduced; the method is easy to automatically control, high-quality N-acetyl-L-cysteine and byproducts can be obtained, and racemization of products in the heating process is avoided; no toxic solvent and no three wastes, realizes clean and high-efficiency production, and embodies dual effects of economy and environmental protection.

Drawings

FIG. 1 is a process flow diagram of an embodiment.

Detailed Description

The invention is further illustrated by the following examples, without restricting its scope to the examples described.

Preparing an electrolytic reaction solution: dissolving 1200g L-cystine into 5.5L 2 mol. L^-1Then placing the mixture in a double-layer reaction kettle, vigorously stirring the mixture in a circulating ice water (0 ℃) bath, then slowly adding 1.5L of acetic anhydride, and continuously adding 2 mol.L of acetic anhydride in the process of dropwise adding the acetic anhydride^-1Sodium hydroxide of (2) toThe pH of the reaction solution was maintained at about 10, and after the completion of the dropwise addition of the acid anhydride, the reaction solution was stirred for 60min, and 1 mol. L of the acylation solution was used as a catholyte^-1H₂SO₄As an anolyte, a plate-frame type flowing electrolytic tank with a Nafion film as a diaphragm is adopted, a Ru-Ti-Sn ternary oxide coating titanium electrode (Ru-Ti-Sn) anode (30x50cm) is used, a self-made vapor deposition carbon electrode is used as a cathode (30x50cm), constant current electrolytic reduction is carried out, and the current density is 80mA cm^-2And electrolyzing for 4 hours to obtain an electrolytic reaction solution.