CN118126113A - Recycling method and application of reduced glutathione production waste liquid - Google Patents
Recycling method and application of reduced glutathione production waste liquid Download PDFInfo
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- RWSXRVCMGQZWBV-WDSKDSINSA-N glutathione Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@@H](CS)C(=O)NCC(O)=O RWSXRVCMGQZWBV-WDSKDSINSA-N 0.000 title claims abstract description 165
- 108010024636 Glutathione Proteins 0.000 title claims abstract description 53
- 239000007788 liquid Substances 0.000 title claims abstract description 39
- 238000000034 method Methods 0.000 title claims abstract description 33
- 239000002699 waste material Substances 0.000 title claims abstract description 30
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 26
- 238000004064 recycling Methods 0.000 title claims abstract description 13
- 108010053070 Glutathione Disulfide Proteins 0.000 claims abstract description 62
- YPZRWBKMTBYPTK-BJDJZHNGSA-N glutathione disulfide Chemical compound OC(=O)[C@@H](N)CCC(=O)N[C@H](C(=O)NCC(O)=O)CSSC[C@@H](C(=O)NCC(O)=O)NC(=O)CC[C@H](N)C(O)=O YPZRWBKMTBYPTK-BJDJZHNGSA-N 0.000 claims abstract description 62
- 239000012535 impurity Substances 0.000 claims abstract description 49
- 238000002425 crystallisation Methods 0.000 claims abstract description 20
- 230000008025 crystallization Effects 0.000 claims abstract description 20
- YPZRWBKMTBYPTK-UHFFFAOYSA-N oxidized gamma-L-glutamyl-L-cysteinylglycine Natural products OC(=O)C(N)CCC(=O)NC(C(=O)NCC(O)=O)CSSCC(C(=O)NCC(O)=O)NC(=O)CCC(N)C(O)=O YPZRWBKMTBYPTK-UHFFFAOYSA-N 0.000 claims abstract description 14
- 239000000047 product Substances 0.000 claims description 42
- 150000001879 copper Chemical class 0.000 claims description 17
- 238000000605 extraction Methods 0.000 claims description 16
- 239000006228 supernatant Substances 0.000 claims description 14
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 238000000926 separation method Methods 0.000 claims description 10
- 238000001556 precipitation Methods 0.000 claims description 8
- 239000011347 resin Substances 0.000 claims description 8
- 229920005989 resin Polymers 0.000 claims description 8
- 239000003480 eluent Substances 0.000 claims description 4
- 230000035484 reaction time Effects 0.000 claims description 2
- 229960003180 glutathione Drugs 0.000 abstract description 61
- 238000000746 purification Methods 0.000 abstract description 12
- VHJLVAABSRFDPM-QWWZWVQMSA-N dithiothreitol Chemical compound SC[C@@H](O)[C@H](O)CS VHJLVAABSRFDPM-QWWZWVQMSA-N 0.000 abstract description 9
- DNJIEGIFACGWOD-UHFFFAOYSA-N ethyl mercaptane Natural products CCS DNJIEGIFACGWOD-UHFFFAOYSA-N 0.000 abstract description 8
- DGVVWUTYPXICAM-UHFFFAOYSA-N β‐Mercaptoethanol Chemical compound OCCS DGVVWUTYPXICAM-UHFFFAOYSA-N 0.000 abstract description 8
- 108090000765 processed proteins & peptides Proteins 0.000 abstract description 3
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- 238000005516 engineering process Methods 0.000 abstract description 2
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- 239000000243 solution Substances 0.000 description 21
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 15
- PZBFGYYEXUXCOF-UHFFFAOYSA-N TCEP Chemical compound OC(=O)CCP(CCC(O)=O)CCC(O)=O PZBFGYYEXUXCOF-UHFFFAOYSA-N 0.000 description 14
- 239000003814 drug Substances 0.000 description 8
- 230000009467 reduction Effects 0.000 description 8
- 230000000052 comparative effect Effects 0.000 description 7
- 229940079593 drug Drugs 0.000 description 6
- 239000003638 chemical reducing agent Substances 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 239000010865 sewage Substances 0.000 description 4
- PBVAJRFEEOIAGW-UHFFFAOYSA-N 3-[bis(2-carboxyethyl)phosphanyl]propanoic acid;hydrochloride Chemical compound Cl.OC(=O)CCP(CCC(O)=O)CCC(O)=O PBVAJRFEEOIAGW-UHFFFAOYSA-N 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 238000011160 research Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000012295 chemical reaction liquid Substances 0.000 description 2
- 238000007599 discharging Methods 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 229940126534 drug product Drugs 0.000 description 2
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- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- -1 sulfhydryl compound Chemical class 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 206010061623 Adverse drug reaction Diseases 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 102000004190 Enzymes Human genes 0.000 description 1
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- 241001465754 Metazoa Species 0.000 description 1
- 238000001042 affinity chromatography Methods 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000007123 defense Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
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- 238000009776 industrial production Methods 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
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- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
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- 230000035790 physiological processes and functions Effects 0.000 description 1
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- 238000003908 quality control method Methods 0.000 description 1
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- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 125000003396 thiol group Chemical group [H]S* 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- Peptides Or Proteins (AREA)
Abstract
The invention discloses a recycling method and application of reduced glutathione production waste liquid, and belongs to the technical field of peptide purification. The invention utilizes the triphosphonate to reduce the oxidized glutathione in GSH production waste liquid, the molar ratio of the triphosphonate to the oxidized glutathione reaches 1:2, thus the oxidized glutathione can be quantitatively converted completely accurately, and the common mercaptoethanol and dithiothreitol can not be reduced completely even if the triphosphonate is excessively added. The technology of the invention is used for reducing the extracting intermediate liquid, especially the concentrated liquid before crystallization, can greatly reduce the level of oxidized glutathione generated in each procedure before crystallization, obviously reduce the content of impurity C and total impurities in the glutathione product and improve the quality of the glutathione product while improving the yield of the product. The scheme of the invention not only greatly improves the product yield and reduces the product production cost, but also saves the environmental treatment cost, thereby being beneficial to popularization and application of enterprises.
Description
Technical Field
The invention relates to the technical field of peptide purification, in particular to a recycling method and application of reduced glutathione production waste liquid.
Background
The chemical name of reduced Glutathione (GSH) is N- (N-L-gamma-glutamyl-L-cysteinyl) glycine, the chemical formula is C 10H17N3O6 S, and the glutathione is a sulfhydryl compound widely existing in animals, plants and microorganisms, plays an important role in a biochemical defense system in human bodies, has various physiological functions of resisting free radicals, aging, oxidization and the like, and has wide market prospect in the fields of drug treatment and health-care foods. At present, the industrialized production method of GSH is an enzyme method and a fermentation method, and oxygen is needed to participate in the two production methods, so that carbon source substances are oxidized to generate ATP energy required by peptide bond synthesis, and therefore GSH generated in the synthesis process is inevitably partially oxidized into oxidized glutathione (GSSG). GSSG has similar properties to GSH, and GSH is possibly oxidized into GSSG at any time in the process of extraction and purification, so GSSG has quite high content level in GSH products, and GSSG is one of main impurities in reduced glutathione products. GSSG is named as impurity C in Chinese and foreign pharmacopoeia; the US Pharmacopeia (USP) standard requires: GSSG is less than or equal to 1.5 percent ¸ percent and total impurities are less than or equal to 2 percent. Thus, impurity C is a main factor affecting the impurity content of glutathione and the quality of the product.
At present, the extraction and purification methods of the reduced glutathione mainly comprise a resin separation method, an ion exchange method, an organic mercury affinity chromatography method, a double water phase method, a copper salt method and the like, the methods with industrial production values are the resin separation method and the copper salt method, and in the extraction and purification process, the extraction waste liquid refers to a resin separation low-purity eluent, a copper salt precipitation supernatant and a crystallization mother liquor. The resin separation method is to separate the reduced glutathione and other impurities by utilizing the affinity difference of the reduced glutathione and other impurities to resin filler, collect eluent with high purity and high content, and discharge the rest waste liquid into a sewage system. The copper salt method is to separate and purify the specific affinity of glutathione sulfhydryl by using cuprous ions, the glutathione cuprous forms a precipitate due to extremely low solubility, GSSG and most other impurities remain in the supernatant, and the supernatant is generally used as extraction waste liquid to be directly discharged into a sewage treatment system. Although GSSG has small market demand, the preparation of GSSG products is realized by directly oxidizing GSH with high purity, if GSSG in waste liquid is directly extracted and purified, the extraction and purification cost is high and the quality is difficult to meet the requirement because other impurity peptides with similar properties in the waste liquid are complex. Therefore, for both the resin separation method and the copper salt method, the supernatant liquid in the production process contains the GSSG with higher concentration in most of the treatment modes of directly discharging the GSSG into a sewage system, which not only causes great waste of resources, but also increases the environmental protection treatment cost.
The national formulary has the standard of reduced glutathione, wherein the impurity C is less than or equal to 1.2 percent, and the total impurity is less than or equal to 1.8 percent. In the conventional GSH production process, even if the whole extraction process is under the protection of nitrogen, the content of GSSG in the crude drug product can only be controlled at the level of 0.8-1.0%, and repeated extraction and purification or special purification means are required for further reducing the content of GSSG. For the raw material medicine production enterprises, the production cost is obviously increased, the factory price is increased, and the sales of the products is influenced, so that the content of impurity C in the reduced glutathione raw material medicine products in the market at present is at a higher level. For a downstream drug enterprise for further production of the purchased reduced glutathione bulk drug, the high impurity content means that one step of purification is required to be advanced after purchasing, which increases the production cost per se; if the raw material medicines with higher purity are directly purchased, the purchasing cost is increased. This has led to a problem of opposition between the high purity requirements and the resulting high purification costs, which has plagued the production enterprises of reduced glutathione bulk drugs and pharmaceutical plants as downstream purchasing enterprises, and it is therefore particularly important to find a method which is relatively rapid and significantly reduces the impurity C content of reduced glutathione products.
Disclosure of Invention
Aiming at the prior art, the invention aims to provide a recycling method and application of reduced glutathione production waste liquid.
In order to achieve the above purpose, the invention adopts the following technical scheme:
in a first aspect of the present invention, there is provided a method for recycling waste liquid from reduced glutathione production, comprising the steps of:
Collecting reduced glutathione extraction waste liquid, detecting the content of oxidized glutathione, adding triphosphonate for reaction, and separating to obtain reduced glutathione;
the addition amount of the triphosphonate is 2 times of the molar amount of the oxidized glutathione.
Further, the reduced glutathione extraction waste liquid comprises a resin separation low-purity eluent, a copper salt precipitation supernatant or a crystallization mother liquor.
Further, the reaction time is 4-6 hours.
Further, the reaction temperature is 15-35 ℃.
In a second aspect of the present invention, there is provided the use of the method for recycling reduced glutathione production waste in (1) or (2) as follows:
(1) Reducing the impurity C content of the reduced glutathione product;
(2) The total impurity content of the reduced glutathione product is reduced.
The invention has the beneficial effects that:
according to the invention, the triphosphonate is used for carrying out reduction treatment on the oxidized glutathione in the GSH production waste liquid, and the molar ratio of the triphosphonate to the oxidized glutathione is 1:2, so that the oxidized glutathione can be accurately and quantitatively converted completely, the oxidized glutathione can be thoroughly converted into GSH for recycling, meanwhile, the COD discharge amount of sewage is reduced, and the environmental-friendly treatment cost is reduced. However, the conventional mercaptoethanol and dithiothreitol cannot be completely reduced even if they are excessively added.
The technology of the invention is used for reducing the extracting intermediate liquid, especially the concentrated liquid before crystallization, can greatly reduce the level of oxidized glutathione generated in each procedure before crystallization, obviously reduce the content of impurity C and total impurities in the glutathione product and improve the quality of the glutathione product while improving the yield of the product. The solution before crystallization is reduced, so that the impurity C of the product can be controlled to be about 0.1%, the total impurity is controlled to be below 0.5%, and the main indexes of the product are far better than those of some reagent-grade reduced glutathione products in the market, therefore, the product has strong international market competitiveness.
Drawings
Fig. 1 is a high performance liquid chromatogram of the product of example 1, GSH in fig. 1 is a signal peak of reduced glutathione, and C is a signal peak of impurity C.
FIG. 2 is a high performance liquid chromatogram of reduced glutathione product (reagent grade) of Shanghai microphone company, GSH in FIG. 2 is signal peak of reduced glutathione, and C is signal peak of impurity C.
Fig. 3 is a high performance liquid spectrum of a reduced glutathione original research reference reagent Tationil Ⓡ injection published by the national drug administration (soliciting opinion), and GSH in fig. 3 is a signal peak of reduced glutathione, and C is a signal peak of impurity C.
Detailed Description
It should be noted that the following detailed description is illustrative and is intended to provide further explanation of the application. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs.
In order to enable those skilled in the art to more clearly understand the technical scheme of the present application, the technical scheme of the present application will be described in detail with reference to specific embodiments.
The test materials used in the examples of the present invention, which are not specifically described, are all conventional in the art and are commercially available.
Tris (2-carboxyethyl) phosphine hydrochloride (triphosphonate, tris (2-carboxyethyl) phosphine hydrochloride, TCEP) used in the present application was purchased from Shanghai Michelin Biochemical technologies Co., ltd., CAS:51805-45-9.
Referring to the method in the "fermentation method for producing Glutathione (GSH) separation and purification process optimization" of university of Beijing Industrial science and university of Shuoshi research, the method (Lin Zhixing, 2007) is adopted to purify glutathione extract by copper salt separation method, copper salt precipitation supernatant and reducing solution are respectively collected, and 4427ml of copper salt precipitation supernatant and 1256ml of reducing solution are obtained in the same batch of experiments.
Example 1
Taking a reducing solution, wherein the GSH content is 32.42mg/ml, the GSSG content is 0.32mg/ml, concentrating in vacuum, adding triphosphonate with the GSSG molar quantity being 2 times into the concentrated solution, reacting for 5 hours at room temperature to obtain a reaction solution, and detecting the reaction solution, wherein the GSH content is 325.7mg/ml and the GSSG content is 0.021mg/ml;
And (3) dropwise adding ethanol into the reaction liquid for crystallization to obtain a GSH product, wherein the GSH content is 99.69%, the GSSG content is 0.084% and the total impurity is 0.31%.
Example 2
4427Ml of copper salt precipitate supernatant was taken, wherein GSH content was 0.094mg/ml and GSSG content was 1.63mg/ml, TCEP 6.78g was added thereto, and the reaction was stirred at room temperature for 4.5 hours. Separating the reaction liquid by copper salt separation, concentrating the secondary reduction liquid in vacuum, then dripping ethanol for crystallization, filtering and drying to obtain 6.12g of GSH product, and detecting: GSH content 98.94%, GSSG content 0.76% and total impurity 1.06%.
Comparative example 1
Taking a reducing solution, wherein the GSH content is 32.42mg/ml, the GSSG content is 0.32mg/ml, dropwise adding ethanol for crystallization after vacuum concentration, filtering and drying to obtain a GSH product, and detecting: GSH content 98.88%, GSSG content 0.82%, total impurities 1.12%;
Comparative example 2
Taking a reducing solution, wherein the GSH content is 32.42mg/ml, the GSSG content is 0.32mg/ml, concentrating in vacuum, adding mercaptoethanol with the molar quantity being 2 times that of the GSSG into the concentrated solution, reacting for 5 hours at room temperature, and detecting the GSH content 322.9mg/ml and the GSSG content 1.57mg/ml of the reaction solution;
And (3) dropwise adding ethanol for crystallization to obtain a GSH product, wherein the GSH content is detected to be 99.18%, the GSSG content is detected to be 0.52%, and the total impurity is detected to be 0.82%.
Comparative example 3
Taking a reducing solution, wherein the GSH content is 32.42mg/ml, the GSSG content is 0.32mg/ml, concentrating in vacuum, adding dithiothreitol with the GSSG molar quantity being 2 times, reacting for 5 hours at room temperature, and detecting the GSH content 323.9mg/ml and the GSSG content 1.46mg/ml of a reaction solution;
And (3) dropwise adding ethanol for crystallization to obtain a GSH product, wherein the GSH content is detected to be 99.14%, the GSSG content is detected to be 0.56%, and the total impurity is detected to be 0.86%.
Comparative example 4
Taking a reducing solution, wherein the GSH content is 32.42mg/ml, the GSSG content is 0.32mg/ml, concentrating in vacuum, adding mercaptoethanol with the molar quantity of GSSG being 3.5 times, reacting for 5 hours at room temperature, and detecting the GSH content of the reaction solution to be 342.9mg/ml and the GSSG content to be 0.84mg/ml;
And (3) dropwise adding ethanol for crystallization to obtain a GSH product, wherein the GSH content is detected to be 99.24%, the GSSG content is detected to be 0.42%, and the total impurity is detected to be 0.76%.
Comparative example 5
Taking a reducing solution, wherein the GSH content is 32.42mg/ml, the GSSG content is 0.32mg/ml, concentrating in vacuum, adding dithiothreitol with the GSSG molar quantity being 3.5 times, reacting for 5 hours at room temperature, and detecting the GSH content 332.8mg/ml and the GSSG content 0.81mg/ml of a reaction solution;
And (3) dropwise adding ethanol for crystallization to obtain a GSH product, wherein the GSH content is detected to be 99.28%, the GSSG content is detected to be 0.39%, and the total impurity is detected to be 0.72%.
The reduction efficiency of TCEP and mercaptoethanol, dithiothreitol was compared by example 1 (fig. 1) and comparative examples 1-5. The mercaptoethanol and dithiothreitol cannot reduce all GSSG in the waste liquid into GSH even if excessive mercaptoethanol and dithiothreitol are added, and the GSSG cannot be recovered and extracted into products, so the recovery rate of GSSG in the reducing liquid is low.
In the existing treatment mode for GSSG, dithiothreitol or mercaptoethanol is generally used as a mercapto reducing agent, and as can be seen in comparative examples 1-5, the disulfide bond in GSSG cannot be completely reduced by adding excessive reducing agent. Unlike TCEP, a 2-fold molar amount of TCEP is able to completely reduce disulfide bonds in GSSG. Besides TCEP, other sulfhydryl reducing agents have little significance in the production of reduced glutathione, because the addition of excessive sulfhydryl ethanol, dithiothreitol and other reducing agents not only brings difficulty to the later extraction and purification, but also the recovery rate of GSSG can not achieve the effect of using TCEP, so that the use of TCEP as the reducing agent of the reducing solution is a better scheme.
Due to low utilization value, the supernatant of copper salt precipitation is generally directly discharged as waste liquid. In the same batch of experiments 4427ml of copper salt precipitate supernatant and 1256ml of reducing solution were obtained. 4427ml of copper salt precipitate supernatant was treated by using the method of example 2 to give GSH product 6.12g. If 1256ml of the reducing solution were treated using the method of example 1, 37.31g of GSH product would be obtained; compared with directly discharging the copper salt precipitation supernatant as waste liquid, the method has the advantages that 6.12g of GSH product is additionally obtained besides 37.31g of GSH product, namely, the copper salt precipitation supernatant used as waste liquid in the prior art is recycled, and the total yield of the GSH product can be improved by about 16.4 percent. Example 1 the reduction solution was subjected to TCEP reduction treatment before crystallization, so impurity C was very low and best quality; in example 2, although TCEP reduction treatment was performed on the waste liquid, further extraction and concentration were still required due to the larger total volume of the waste liquid and lower GSH concentration, and part of GSH was oxidized to GSSG in the subsequent extraction process, TCEP reduction was not performed before crystallization, so that the recovered product impurity C was slightly higher, but the yield was improved compared with direct discharge.
The national formulary has the standard of reduced glutathione, wherein the impurity C is less than or equal to 1.2 percent, and the total impurity is less than or equal to 1.8 percent. For the raw materials, the higher the content of the product and the lower the content of impurities, the higher the quality of the product, the more stable the curative effect, the lower the possibility of adverse drug reaction and the stronger the market competitiveness. Therefore, the control of the impurity content is particularly important, the TCEP is important in controlling the impurity C in the product, and the addition of TCEP in an amount 2 times the molar amount relative to GSSG at any step of the extraction stage can effectively reduce the impurity C content.
The invention uses TCEP to reduce the crystallization liquid before crystallization, the impurity C in the product can be controlled below 0.1% until trace, which is not achieved by the similar crude drug products in the market at present as crude drugs, and the invention even exceeds the quality control standard of the same type of products: the detection of the reduced glutathione product (reagent grade) of the commercial Shanghai microphone company is shown in figure 2, wherein the GSH content is 99.56%, the impurity C content is 0.34% and the total impurity is 0.44%; the detection of the reduced glutathione original research reference reagent Tationil Ⓡ injection published by the national drug administration (solicited opinion manuscript) shows that the GSH content is 99.06%, the impurity C content is 0.29% and the total impurity is 0.94% in figure 3. The impurity C in the crystallized product is kept at a low level, and particularly, the reduction treatment is carried out before crystallization, so that the impurity C in the product can be controlled below 0.1% until trace detection is not carried out.
The above description is only of the preferred embodiments of the present application and is not intended to limit the present application, but various modifications and variations can be made to the present application by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application should be included in the protection scope of the present application.
Claims (5)
1. The method for recycling the reduced glutathione production waste liquid is characterized by comprising the following steps of:
Collecting reduced glutathione extraction waste liquid, detecting the content of oxidized glutathione, adding triphosphonate for reaction, and separating to obtain reduced glutathione;
the addition amount of the triphosphonate is 2 times of the molar amount of the oxidized glutathione.
2. The method for recycling reduced glutathione production waste liquid according to claim 1, wherein the reduced glutathione extraction waste liquid comprises a resin separation low-purity eluent, a copper salt precipitation supernatant or a crystallization mother liquid.
3. The method for recycling a reduced glutathione production waste liquid according to claim 1, wherein the reaction time is 4-6 hours.
4. The method for recycling a reduced glutathione production waste liquid according to claim 1, wherein the reaction temperature is 15-35 ℃.
5. Use of the method for recycling a reduced glutathione production waste as claimed in any one of claims 1 to 4 in (1) or (2) as follows:
(1) Reducing the impurity C content of the reduced glutathione product;
(2) The total impurity content of the reduced glutathione product is reduced.
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| CN105566445A (en) * | 2016-01-13 | 2016-05-11 | 浙江海正药业股份有限公司 | Method for separating and purifying reduced glutathione |
| WO2019187534A1 (en) * | 2018-03-26 | 2019-10-03 | 株式会社カネカ | Method for producing reduced glutathione |
| CN113545996A (en) * | 2020-02-29 | 2021-10-26 | 西安曼特思生物科技有限公司 | Protein product capable of fixing target and removing according to need |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105566445A (en) * | 2016-01-13 | 2016-05-11 | 浙江海正药业股份有限公司 | Method for separating and purifying reduced glutathione |
| WO2019187534A1 (en) * | 2018-03-26 | 2019-10-03 | 株式会社カネカ | Method for producing reduced glutathione |
| CN113545996A (en) * | 2020-02-29 | 2021-10-26 | 西安曼特思生物科技有限公司 | Protein product capable of fixing target and removing according to need |
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| Title |
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| 申刚义: "固定化酶微反应器", 31 May 2018, 中央民族大学出版社, pages: 69 * |
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