CN115850134B - Method for preparing cystine disodium salt - Google Patents
Method for preparing cystine disodium salt Download PDFInfo
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- CN115850134B CN115850134B CN202211659072.8A CN202211659072A CN115850134B CN 115850134 B CN115850134 B CN 115850134B CN 202211659072 A CN202211659072 A CN 202211659072A CN 115850134 B CN115850134 B CN 115850134B
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- Prior art keywords
- cystine
- disodium salt
- stirring
- dripping
- crystallization
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- PLVPMKWGXOOSKL-RGVONZFCSA-L disodium;(2r)-2-amino-3-[[(2r)-2-amino-2-carboxylatoethyl]disulfanyl]propanoate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](N)CSSC[C@H](N)C([O-])=O PLVPMKWGXOOSKL-RGVONZFCSA-L 0.000 title claims abstract description 20
- 238000000034 method Methods 0.000 title claims abstract description 13
- 229960003067 cystine Drugs 0.000 claims abstract description 43
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 42
- 238000003756 stirring Methods 0.000 claims abstract description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000000047 product Substances 0.000 claims abstract description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000013078 crystal Substances 0.000 claims abstract description 12
- 238000001035 drying Methods 0.000 claims abstract description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 10
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 10
- 239000000706 filtrate Substances 0.000 claims abstract description 10
- 238000002425 crystallisation Methods 0.000 claims abstract description 8
- 230000008025 crystallization Effects 0.000 claims abstract description 8
- 235000019441 ethanol Nutrition 0.000 claims abstract description 7
- 238000005185 salting out Methods 0.000 claims abstract description 7
- 239000008213 purified water Substances 0.000 claims abstract description 6
- 238000001914 filtration Methods 0.000 claims abstract description 5
- 230000001105 regulatory effect Effects 0.000 claims abstract description 5
- 239000012043 crude product Substances 0.000 claims abstract description 3
- LEVWYRKDKASIDU-QWWZWVQMSA-N D-cystine Chemical compound OC(=O)[C@H](N)CSSC[C@@H](N)C(O)=O LEVWYRKDKASIDU-QWWZWVQMSA-N 0.000 claims abstract 14
- 239000007788 liquid Substances 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 3
- 239000012528 membrane Substances 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 235000011121 sodium hydroxide Nutrition 0.000 abstract description 11
- 239000003814 drug Substances 0.000 abstract description 3
- LEVWYRKDKASIDU-IMJSIDKUSA-N L-cystine Chemical compound [O-]C(=O)[C@@H]([NH3+])CSSC[C@H]([NH3+])C([O-])=O LEVWYRKDKASIDU-IMJSIDKUSA-N 0.000 description 29
- 239000000243 solution Substances 0.000 description 10
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
- 238000004448 titration Methods 0.000 description 6
- XWNSFEAWWGGSKJ-UHFFFAOYSA-N 4-acetyl-4-methylheptanedinitrile Chemical compound N#CCCC(C)(C(=O)C)CCC#N XWNSFEAWWGGSKJ-UHFFFAOYSA-N 0.000 description 4
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 4
- 239000004153 Potassium bromate Substances 0.000 description 4
- 229940094037 potassium bromate Drugs 0.000 description 4
- 235000019396 potassium bromate Nutrition 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- -1 disodium cystine salts Chemical class 0.000 description 3
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 239000001963 growth medium Substances 0.000 description 2
- 229910052740 iodine Inorganic materials 0.000 description 2
- 239000011630 iodine Substances 0.000 description 2
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 2
- 235000019345 sodium thiosulphate Nutrition 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 239000008107 starch Substances 0.000 description 2
- 239000012085 test solution Substances 0.000 description 2
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 235000016709 nutrition Nutrition 0.000 description 1
- 230000035764 nutrition Effects 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for preparing cystine disodium salt, belonging to the field of biological medicine. Stirring and dissolving a cystine crude product in a hydrochloric acid solution, adding active carbon for decoloring, slowly adding caustic soda into a decoloring solution for regulating the pH value to 3.0, stirring and slowly crystallizing, and drying to obtain a cystine finished product; adding cystine finished product and sodium hydroxide into purified water, adjusting pH to 11.0-11.5 with cystine after dissolving, vacuum filtering, and collecting filtrate; alcohol precipitation crystallization: dripping the filtrate into absolute ethyl alcohol, stirring for crystallization, centrifuging after dripping to obtain wet crystals, and drying the wet crystals to obtain the cystine disodium salt. The quality of the cystine disodium salt obtained by the method meets the pharmaceutical grade standard, and the quality is higher.
Description
Technical Field
The invention relates to a method for preparing cystine disodium salt, belonging to the field of biological medicine.
Background
Cystine in cystine disodium salt is an essential amino acid in human body, and can be widely used in medicine, food, cosmetics, culture medium, etc. for regulating human nutrition balance and promoting metabolism. However, the solubility of cystine is extremely low, so that the application value of cystine is greatly reduced, the solubility of cystine disodium salt is extremely high, the application value is higher, the requirements of some cosmetic and culture medium manufacturers are larger, and the additional value is higher.
The preparation of disodium cystine salts also presents several challenges. The solubility of the disodium cystine salt is extremely high and can not be crystallized and separated out in the aqueous solution, the pH value of the disodium cystine aqueous solution is about 10, and the pH value of the decolorized active carbon ranges to be less than 7, so that the disodium cystine aqueous solution can not be decolorized, and the quality of the product is difficult to control.
Disclosure of Invention
Aiming at the difficult problem of low solubility of cystine, the invention provides a method for preparing cystine disodium salt with higher solubility.
The method for preparing cystine disodium salt mainly comprises the following steps:
(1) Stirring and dissolving the cystine crude product in hydrochloric acid solution, adding active carbon for decoloring, slowly adding liquid alkali into the decolored solution for regulating the pH value to 3.0, stirring and slowly crystallizing, and drying to obtain a cystine finished product;
(2) Adding cystine product and sodium hydroxide into purified water, adjusting pH to 11.0-11.5 with cystine after dissolving,
(3) Then vacuum filtering and collecting filtrate;
(4) Alcohol precipitation crystallization: dripping the filtrate into absolute ethyl alcohol, stirring for crystallization, centrifuging after dripping to obtain wet crystals, and drying the wet crystals to obtain the cystine disodium salt.
In one embodiment of the invention, step (1) is to add 3L of water into 150g of crude cystine, add 180ml of 36% analytical pure hydrochloric acid, stir and dissolve at 30 ℃, add 22.5g of active carbon, decolorize at 30 ℃ for 30min, then remove the active carbon by using filter paper and filter membrane to obtain decolorized solution, slowly adding caustic soda (30%) into the decolorized solution to adjust pH to 3.0, stir and slowly crystallize, and dry to obtain cystine finished product.
In one embodiment of the invention, the step (2) is to add the cystine finished product and sodium hydroxide into purified water according to the mol ratio of 1:2, and after the cystine finished product and sodium hydroxide are dissolved, the pH value is adjusted to 11.0-11.5 by cystine.
In one embodiment of the present invention, step (4) alcohol precipitation crystallization: dripping the filtrate into absolute ethanol, stirring for crystallization, centrifuging after dripping to obtain wet crystals, and drying the wet crystals at 50-60 ℃ for 16-20h to obtain cystine disodium salt.
In the invention, when the cystine is dissolved, the solubility of the cystine is increased by utilizing the hydrochloric acid. The quality of the cystine disodium salt obtained by the method meets the pharmaceutical grade standard, and the quality is higher.
Detailed Description
The detection method of cystine comprises the following steps: 80mg of sample is precisely weighed, placed in an iodine bottle, added with 2ml of sodium hydroxide test solution and 10ml of water for shaking and dissolving, added with 10ml of potassium bromide solution (20 g of potassium bromide is used for fixing the volume to 100 ml), precisely added with 50ml of potassium bromate titration solution (0.01667 mol/L) and 15ml of dilute hydrochloric acid, sealed, placed in the dark place in an ice bath for 10 minutes, added with 1.5g of potassium iodide, evenly shaken, titrated with sodium thiosulfate titration solution (0.1 mol/L) after 1 minute, added with 2ml of starch indicator until reaching a near end point, continuously titrated until blue disappears, and the titration result is corrected by a blank test. Each 1ml of potassium bromate titrant (0.01667 mol/L) corresponds to 2.403mg of C 6H12N2O4S2.
The detection method of the disodium cystine salt comprises the following steps: 94.6mg of sample is precisely weighed, placed in an iodine bottle, added with 2ml of sodium hydroxide test solution and 10ml of water for shaking and dissolving, added with 10ml of potassium bromide solution (20-100), precisely added with 50ml of potassium bromate titration solution (0.01667 mol/L) and 15ml of dilute hydrochloric acid, sealed, placed in an ice bath in the dark place for 10 minutes, added with 1.5g of potassium iodide, shaken evenly, titrated with sodium thiosulfate titration solution (0.1 mol/L) after 1 minute, added with 2ml of starch indicator until near the end point, continuously titrated until blue disappears, and the titration result is corrected by a blank test. Each 1ml of potassium bromate titrant (0.01667 mol/L) corresponds to 2.403mg of C 6H12N2O4S2. The detection methods of cystine and disodium cystine are basically consistent, the content of cystine is measured, and the measurement result is 98.5-101.5% and is qualified.
The crude cystine used in the following examples is prepared by hair hydrolysis or fermentation, and the impurities are pigments and proteins.
Example 1
The process route is as follows: crude cystine, finished cystine, sodium hydroxide dissolution, filtration and alcohol precipitation crystallization.
In particular, the method comprises the steps of,
(1) Adding 3L of water into 150g of crude cystine, adding 180ml of 36% analytical pure hydrochloric acid, stirring at 30 ℃ for dissolution, adding 22.5g of active carbon, decoloring at 30 ℃ for 30min, removing active carbon by using filter paper and a filter membrane to obtain decolored liquid, slowly adding dropwise caustic soda (30%) into the decolored liquid for regulating pH to 3.0, stirring for slow crystallization, and drying to obtain a cystine finished product;
(2) Adding the cystine finished product and sodium hydroxide into purified water according to the mol ratio of 1:2, adjusting the pH value to 11.0-11.5 by using cystine after dissolving,
(3) Then vacuum filtering and collecting filtrate;
(4) Alcohol precipitation crystallization: dripping the filtrate into absolute ethanol, stirring for crystallization, centrifuging after dripping to obtain wet crystals, and drying the wet crystals at 50-60 ℃ for 16-20h to obtain cystine disodium salt.
The quality of the disodium salt of cystine is shown in table 1.
TABLE 1
While the invention has been described with reference to the preferred embodiments, it is not limited thereto, and various changes and modifications can be made therein by those skilled in the art without departing from the spirit and scope of the invention as defined in the appended claims.
Claims (4)
1. A process for the preparation of cystine disodium salt, characterized in that it essentially comprises the steps of:
(1) Stirring and dissolving the cystine crude product in hydrochloric acid solution, adding active carbon for decoloring, slowly adding liquid alkali into the decolored solution for regulating the pH value to 3.0, stirring and slowly crystallizing, and drying to obtain a cystine finished product;
(2) Adding cystine product and sodium hydroxide into purified water, adjusting pH to 11.0-11.5 with cystine after dissolving,
(3) Then vacuum filtering and collecting filtrate;
(4) Alcohol precipitation crystallization: dripping the filtrate into absolute ethyl alcohol, stirring for crystallization, centrifuging after dripping to obtain wet crystals, and drying the wet crystals to obtain the cystine disodium salt.
2. The method for preparing cystine disodium salt according to claim 1, wherein in the step (1), 150g of crude cystine is taken, 3L of water is added, 180ml of 36% analytically pure concentrated hydrochloric acid is added, stirring and dissolving are carried out at 30 ℃, 22.5g of active carbon is added, decoloring is carried out at 30 ℃ for 30min, then filter paper and a filter membrane are used for removing the active carbon to obtain decolored liquid, alkali is slowly added dropwise into the decolored liquid to adjust the pH value to 3.0, stirring and slow crystallization are carried out, and finally, the cystine finished product is obtained after drying.
3. The method for preparing cystine disodium salt according to claim 1, wherein the final cystine product and sodium hydroxide are added into purified water according to a molar ratio of 1:2 in the step (2), and after the final cystine product and sodium hydroxide are dissolved, the final cystine product is adjusted to pH11.0-11.5 by cystine.
4. The method for producing cystine disodium salt according to claim 1, wherein the step (4) comprises alcohol precipitation crystallization: dripping the filtrate into absolute ethanol, stirring for crystallization, centrifuging after dripping to obtain wet crystals, and drying the wet crystals at 50-60 ℃ for 16-20h to obtain cystine disodium salt.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211659072.8A CN115850134B (en) | 2022-12-22 | 2022-12-22 | Method for preparing cystine disodium salt |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211659072.8A CN115850134B (en) | 2022-12-22 | 2022-12-22 | Method for preparing cystine disodium salt |
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| Publication Number | Publication Date |
|---|---|
| CN115850134A CN115850134A (en) | 2023-03-28 |
| CN115850134B true CN115850134B (en) | 2024-06-04 |
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| CN202211659072.8A Active CN115850134B (en) | 2022-12-22 | 2022-12-22 | Method for preparing cystine disodium salt |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4436910A (en) * | 1981-02-12 | 1984-03-13 | Degussa Aktiengesellschaft | Process for the production of aqueous solutions of sodium salts of α-a |
| CN1041153A (en) * | 1988-09-19 | 1990-04-11 | 陈学政 | Produce the novel process of Gelucystine |
| CN106674070A (en) * | 2015-11-05 | 2017-05-17 | 罗江晨明生物制品有限公司 | Method for extracting amino acid from hair |
| CN115461326A (en) * | 2020-04-28 | 2022-12-09 | 联合利华知识产权控股有限公司 | Process for the preparation of N, N' -diacetyl-L-cystine disodium salt from cystine and acetyl chloride in methanol in the presence of sodium hydroxide |
-
2022
- 2022-12-22 CN CN202211659072.8A patent/CN115850134B/en active Active
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4436910A (en) * | 1981-02-12 | 1984-03-13 | Degussa Aktiengesellschaft | Process for the production of aqueous solutions of sodium salts of α-a |
| CN1041153A (en) * | 1988-09-19 | 1990-04-11 | 陈学政 | Produce the novel process of Gelucystine |
| CN106674070A (en) * | 2015-11-05 | 2017-05-17 | 罗江晨明生物制品有限公司 | Method for extracting amino acid from hair |
| CN115461326A (en) * | 2020-04-28 | 2022-12-09 | 联合利华知识产权控股有限公司 | Process for the preparation of N, N' -diacetyl-L-cystine disodium salt from cystine and acetyl chloride in methanol in the presence of sodium hydroxide |
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| CN115850134A (en) | 2023-03-28 |
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