CN115850134A - Method for preparing cystine disodium salt - Google Patents
Method for preparing cystine disodium salt Download PDFInfo
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- CN115850134A CN115850134A CN202211659072.8A CN202211659072A CN115850134A CN 115850134 A CN115850134 A CN 115850134A CN 202211659072 A CN202211659072 A CN 202211659072A CN 115850134 A CN115850134 A CN 115850134A
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- China
- Prior art keywords
- cystine
- disodium salt
- dripping
- crystallization
- drying
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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 26
- 238000000034 method Methods 0.000 title claims abstract description 13
- 229960003067 cystine Drugs 0.000 claims abstract description 39
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 27
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000003756 stirring Methods 0.000 claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-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 12
- 239000000047 product Substances 0.000 claims abstract description 12
- 238000002425 crystallisation Methods 0.000 claims abstract description 10
- 230000008025 crystallization Effects 0.000 claims abstract description 10
- 239000000706 filtrate Substances 0.000 claims abstract description 10
- 239000007788 liquid Substances 0.000 claims abstract description 8
- 235000019441 ethanol Nutrition 0.000 claims abstract description 7
- 239000003513 alkali Substances 0.000 claims abstract description 6
- 239000008213 purified water Substances 0.000 claims abstract description 6
- 238000001556 precipitation Methods 0.000 claims abstract description 4
- 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 12
- 239000000203 mixture Substances 0.000 claims description 6
- 238000004090 dissolution Methods 0.000 claims description 4
- 239000012528 membrane Substances 0.000 claims description 3
- 238000005185 salting out Methods 0.000 claims description 3
- 238000003828 vacuum filtration Methods 0.000 claims description 3
- 238000004042 decolorization Methods 0.000 claims description 2
- 239000012467 final product Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 3
- 238000001914 filtration Methods 0.000 abstract description 2
- 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 27
- 239000000243 solution Substances 0.000 description 12
- 238000004448 titration Methods 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
- XWNSFEAWWGGSKJ-UHFFFAOYSA-N 4-acetyl-4-methylheptanedinitrile Chemical compound N#CCCC(C)(C(=O)C)CCC#N XWNSFEAWWGGSKJ-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
- 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
- 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
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical class [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 description 1
- 239000012043 crude product Substances 0.000 description 1
- -1 disodium cystine salt Chemical class 0.000 description 1
- 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
- 230000004060 metabolic process Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 238000002360 preparation method Methods 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
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000007789 sealing Methods 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Abstract
The invention discloses a method for preparing cystine disodium salt, belonging to the field of biological medicine. Dissolving a crude cystine product in a hydrochloric acid solution by stirring, adding activated carbon for decoloring, slowly adding liquid alkali into a decoloring solution to adjust the pH to 3.0, slowly crystallizing by stirring, and drying to obtain a finished cystine product; adding the finished product of cystine and sodium hydroxide into purified water, adjusting pH to 11.0-11.5 with cystine after dissolving, vacuum filtering, and collecting filtrate; alcohol precipitation and 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 medical grade standard and 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 used as effective component, and cystine is an essential amino acid in human body, and can be widely used in medicine, food, cosmetic, culture medium, etc., and has the functions of regulating nutrient balance of human body and promoting metabolism. However, the application value of the cystine is greatly reduced due to extremely low solubility of the cystine, the solubility of the disodium cystine salt is extremely high, the application value is higher, and the requirements of some cosmetic and culture medium manufacturers are higher, so that the application value is higher.
The preparation of the disodium salt of cystine also faces some difficulties. The solubility of the cystine disodium salt is extremely low, the cystine disodium salt cannot be crystallized and separated out from the aqueous solution, the pH value of the cystine disodium salt aqueous solution is about 10, and the pH value of the activated carbon decoloration range is less than 7, so that the cystine disodium salt aqueous solution cannot be decolored, and the product quality is difficult to control.
Disclosure of Invention
The invention aims at the problem of low solubility of cystine and provides a method for preparing cystine disodium salt with high solubility.
The method for preparing the cystine disodium salt mainly comprises the following steps:
(1) Dissolving the crude cystine in hydrochloric acid solution under stirring, adding activated carbon for decolorization, slowly adding liquid alkali into the decolorized solution to adjust pH to 3.0, slowly crystallizing under stirring, and drying to obtain the final product cystine;
(2) Adding the cystine product and sodium hydroxide into purified water, dissolving, adjusting pH to 11.0-11.5 with cystine,
(3) Then carrying out vacuum filtration, and collecting filtrate;
(4) Alcohol precipitation and 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, 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, the mixture is stirred and dissolved at 30 ℃, 22.5g of activated carbon is added, the mixture is decolorized for 30min at 30 ℃, then the activated carbon is removed by using filter paper and a filter membrane to obtain decolorized liquid, liquid alkali (30%) is slowly dropped into the decolorized liquid to adjust the pH value to 3.0, the mixture is stirred and slowly crystallized, and the finished cystine product is obtained after drying.
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 molar ratio of 1:2, and after dissolution, adjust the pH value to 11.0-11.5 by cystine.
In one embodiment of the present invention, step (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 at 50-60 ℃ for 16-20h to obtain the cystine disodium salt.
When the invention dissolves the cystine, the cystine is dissolved, hydrochloric acid was used to increase the solubility of cystine. The quality of the cystine disodium salt obtained by the method meets the medical grade standard and is higher.
Detailed Description
The detection method of cystine comprises the following steps: sampling 80mg, precisely weighing, placing in an iodine bottle, shaking and dissolving 2ml of sodium hydroxide test solution and 10ml of water, adding 10ml of potassium bromide solution (20 g of potassium bromide is constant volume to 100ml with water), precisely adding 50ml of potassium bromate titration solution (0.01667 mol/L) and 15ml of dilute hydrochloric acid, sealing, placing in an ice bath in the dark for 10 minutes, adding 1.5g of potassium iodide, shaking uniformly, after 1 minute, titrating with sodium thiosulfate titration solution (0.1 mol/L), adding 2ml of starch indicator when the end point is reached, continuing to titrate until blue disappears, and correcting the titration result by a blank test. Each 1ml of potassium bromate titration solution (0.01667 mol/L) is equivalent to 2.403mg of C 6 H 12 N 2 O 4 S 2 。
The detection method of cystine disodium salt comprises the following steps: a sample of 94.6mg is precisely weighed and placed in an iodine bottle, 2ml of sodium hydroxide test solution and 10ml of water are added for shaking dissolution, 10ml of potassium bromide solution (20 → 100) is added, 50ml of potassium bromate titration solution (0.01667 mol/L) and 15ml of dilute hydrochloric acid are precisely added, a plug is sealed, the mixture is placed in an ice bath in the dark for 10 minutes, 1.5g of potassium iodide is added, the mixture is shaken up for 1 minute, sodium thiosulfate titration solution (0.1 mol/L) is used for titration, when the end point is reached, 2ml of starch indicator is added, the titration is continued until the blue color disappears, and the titration result is corrected by a blank test. Each 1ml of potassium bromate titration solution (0.01667 mol/L) is equivalent to 2.403mg of C 6 H 12 N 2 O 4 S 2 . The detection methods of the cystine and the cystine disodium are basically consistent, the content of the cystine is determined, and the result is qualified when the calculation result is 98.5-101.5%.
The following examples used crude cystine which was prepared by hair hydrolysis or fermentation method, and the impurities were pigments and proteins.
Example 1
The process route is as follows: cystine crude product → cystine finished product → sodium hydroxide dissolution → filtration → alcohol precipitation crystallization.
In particular, the amount of the solvent to be used,
(1) Adding 150g of crude cystine into 3L of water, adding 180ml of 36% analytical pure concentrated hydrochloric acid, stirring and dissolving at 30 ℃, adding 22.5g of activated carbon, decoloring at 30 ℃ for 30min, removing the activated carbon by using filter paper and a filter membrane to obtain a decolored solution, slowly adding liquid alkali (30%) into the decolored solution, adjusting the pH value to 3.0, stirring and slowly crystallizing, and drying to obtain a finished cystine product;
(2) Adding the cystine finished product and sodium hydroxide into purified water according to the molar ratio of 1:2, after dissolving, adjusting pH to 11.0-11.5 by cystine,
(3) Then carrying out vacuum filtration, and collecting filtrate;
(4) Alcohol precipitation and crystallization: dripping the filtrate into absolute ethyl alcohol, stirring for crystallization, centrifuging after dripping to obtain wet crystals, and drying the wet crystals at 50-60 ℃ for 16-20h to obtain the cystine disodium salt.
The quality of the cystine disodium salt is shown in table 1.
TABLE 1
Although the present invention has been described with reference to the preferred embodiments, it should be understood that 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. The method for preparing the cystine disodium salt is characterized by mainly comprising the following steps of:
(1) Dissolving the crude cystine in hydrochloric acid solution under stirring, adding activated carbon for decolorization, slowly adding liquid alkali into the decolorized solution to adjust pH to 3.0, slowly crystallizing under stirring, and drying to obtain the final product cystine;
(2) Adding the cystine product and sodium hydroxide into purified water, dissolving, adjusting pH to 11.0-11.5 with cystine,
(3) Then carrying out vacuum filtration, and collecting filtrate;
(4) Alcohol precipitation and 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, characterized in that, in step (1), 150g of crude cystine is taken and added with 3L of water, 180ml of 36% analytical pure concentrated hydrochloric acid is added, stirred and dissolved at 30 ℃, 22.5g of activated carbon is added, decoloration is carried out for 30min at 30 ℃, then the activated carbon is removed by using filter paper and a filter membrane to obtain decolored solution, liquid alkali is slowly dropped into the decolored solution to adjust the pH value to 3.0, and the mixture is stirred and slowly crystallized, and the finished cystine is obtained after drying.
3. The method for preparing cystine disodium salt according to claim 1, characterized in that, in step (2), the final cystine product and sodium hydroxide are added into purified water according to the molar ratio of 1:2, and after dissolution, the pH is adjusted to 11.0-11.5 by cystine.
4. The process for preparing cystine disodium salt according to claim 1, characterized in that, step (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 at 50-60 ℃ for 16-20h to obtain the cystine disodium salt.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211659072.8A CN115850134A (en) | 2022-12-22 | 2022-12-22 | Method for preparing cystine disodium salt |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202211659072.8A CN115850134A (en) | 2022-12-22 | 2022-12-22 | Method for preparing cystine disodium salt |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115850134A true CN115850134A (en) | 2023-03-28 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202211659072.8A Pending CN115850134A (en) | 2022-12-22 | 2022-12-22 | Method for preparing cystine disodium salt |
Country Status (1)
| Country | Link |
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| CN (1) | CN115850134A (en) |
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/CN115850134A/en active Pending
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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