CN113307756A - Method for purifying proline bulk drug - Google Patents
Method for purifying proline bulk drug Download PDFInfo
- Publication number
- CN113307756A CN113307756A CN202110584419.6A CN202110584419A CN113307756A CN 113307756 A CN113307756 A CN 113307756A CN 202110584419 A CN202110584419 A CN 202110584419A CN 113307756 A CN113307756 A CN 113307756A
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- Prior art keywords
- proline
- crude product
- suction filtration
- effluent liquid
- purifying
- Prior art date
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- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 title claims abstract description 35
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 title claims abstract description 32
- 239000003814 drug Substances 0.000 title claims abstract description 14
- 238000000034 method Methods 0.000 title claims abstract description 14
- 229940079593 drug Drugs 0.000 title claims description 9
- 239000012043 crude product Substances 0.000 claims abstract description 29
- 238000000967 suction filtration Methods 0.000 claims abstract description 19
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000011347 resin Substances 0.000 claims abstract description 16
- 229920005989 resin Polymers 0.000 claims abstract description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 14
- 238000001035 drying Methods 0.000 claims abstract description 14
- 239000002253 acid Substances 0.000 claims abstract description 8
- 238000005119 centrifugation Methods 0.000 claims abstract description 7
- 239000003480 eluent Substances 0.000 claims abstract description 7
- 239000002994 raw material Substances 0.000 claims abstract description 7
- 125000002091 cationic group Chemical group 0.000 claims abstract description 6
- 230000002378 acidificating effect Effects 0.000 claims abstract description 5
- 238000001914 filtration Methods 0.000 claims abstract description 5
- 238000005374 membrane filtration Methods 0.000 claims abstract 2
- 239000007788 liquid Substances 0.000 claims description 25
- 150000001768 cations Chemical class 0.000 claims description 10
- 238000010438 heat treatment Methods 0.000 claims description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 238000001816 cooling Methods 0.000 claims description 9
- 238000000855 fermentation Methods 0.000 claims description 7
- 230000004151 fermentation Effects 0.000 claims description 7
- 239000013078 crystal Substances 0.000 claims description 6
- 238000003756 stirring Methods 0.000 claims description 6
- 238000002425 crystallisation Methods 0.000 claims description 4
- 230000008025 crystallization Effects 0.000 claims description 4
- 238000004042 decolorization Methods 0.000 claims description 4
- 239000012528 membrane Substances 0.000 claims description 4
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims description 3
- 239000003729 cation exchange resin Substances 0.000 claims description 3
- 238000010828 elution Methods 0.000 claims description 2
- 238000001471 micro-filtration Methods 0.000 claims 1
- WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 abstract description 14
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 abstract description 14
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 abstract description 14
- 239000004472 Lysine Substances 0.000 abstract description 14
- 235000004279 alanine Nutrition 0.000 abstract description 14
- 235000013922 glutamic acid Nutrition 0.000 abstract description 14
- 239000004220 glutamic acid Substances 0.000 abstract description 14
- 235000018977 lysine Nutrition 0.000 abstract description 14
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 abstract description 3
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 abstract description 3
- 239000012982 microporous membrane Substances 0.000 abstract description 2
- 229960002429 proline Drugs 0.000 description 21
- 239000000523 sample Substances 0.000 description 8
- 229940024606 amino acid Drugs 0.000 description 4
- 235000001014 amino acid Nutrition 0.000 description 4
- 150000001413 amino acids Chemical class 0.000 description 4
- 239000011964 heteropoly acid Substances 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 230000000813 microbial effect Effects 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- 229930182821 L-proline Natural products 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 235000018102 proteins Nutrition 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000013074 reference sample Substances 0.000 description 2
- 241000251468 Actinopterygii Species 0.000 description 1
- 208000018522 Gastrointestinal disease Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 208000002720 Malnutrition Diseases 0.000 description 1
- 108010064851 Plant Proteins Proteins 0.000 description 1
- 208000008425 Protein deficiency Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 206010053615 Thermal burn Diseases 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 231100000481 chemical toxicant Toxicity 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 235000000824 malnutrition Nutrition 0.000 description 1
- 230000001071 malnutrition Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- FEMOMIGRRWSMCU-UHFFFAOYSA-N ninhydrin Chemical compound C1=CC=C2C(=O)C(O)(O)C(=O)C2=C1 FEMOMIGRRWSMCU-UHFFFAOYSA-N 0.000 description 1
- 208000015380 nutritional deficiency disease Diseases 0.000 description 1
- 235000021118 plant-derived protein Nutrition 0.000 description 1
- 229940116540 protein supplement Drugs 0.000 description 1
- 235000005974 protein supplement Nutrition 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Pyrrole Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for purifying proline raw material medicine, and belongs to the field of biological medicine. The method comprises the steps of enabling proline eluent to pass through 335 type weakly alkaline cationic resin and 110 type weakly acidic cationic resin, decoloring by using activated carbon, performing suction filtration and microporous membrane filtration, performing vacuum concentration to crystallize, suction filtration, centrifugation and drying to obtain a crude product; and dissolving the crude product by using ethanol, recrystallizing, filtering, centrifuging and drying to obtain a proline sample. The sample obtained by the invention has no alanine, glutamic acid and lysine, and the removal rate of the mixed acid is 100%.
Description
Technical Field
The invention relates to a method for purifying proline raw material medicine, belonging to the field of biological medicine.
Background
Proline is a cyclic imino acid, the only imino acid among the common 20 amino acids that make up proteins. Proline is one of the components of plant proteins and can be widely present in plants in the free state.
Proline can be used as amino acid medicine for treating malnutrition, protein deficiency, severe gastrointestinal diseases, protein supplement after scald and surgical operation, and has no obvious toxic and side effects.
The traditional production mode of L-proline is a hydrolysis method, and after the protein is subjected to acid, alkali or enzymolysis, a mixture of various amino acids is obtained, and the required L-proline can be extracted from the mixture. The raw materials used are rubber fish, gelatin, hair and the like, but the final yield is low and the utilization rate of the raw materials is low due to multiple production and purification steps, and a large amount of toxic chemical raw materials are added in the production process, so that large-scale production cannot be realized.
With the continuous development of microbial biotechnology research, the innovation of biological downstream industry and the continuous introduction of various chemical industrial technologies, the cost of amino acid microbial fermentation is lower and lower, and the microbial fermentation method provides a powerful support for realizing the industrial mass production of L-proline. Nowadays, most of the proline on the market is obtained by industrial microbial fermentation. However, when proline is used as a drug substance, the content of the heteropolyacid needs to be controlled.
Disclosure of Invention
[ problem ] to
The invention aims to solve the technical problem of purifying proline obtained by fermentation and controlling the content of the heteropolyacid to meet the requirements of raw material medicines.
[ solution ]
The invention provides a method for purifying proline bulk drugs, which comprises the following steps:
(1) after the proline fermentation liquor is loaded on 732 cation exchange resin, proline eluent obtained by elution of sodium hydroxide is processed by 335 type weak alkaline cation resin, and effluent liquid is collected;
(2) enabling the effluent liquid obtained in the step (1) to pass through a 110 type weak acid cation resin to obtain secondary effluent liquid;
(3) heating the secondary effluent liquid obtained in the step (2) to 55-60 ℃, adding 10-15% of activated carbon for decoloring for 30min, performing suction filtration, filtering with a microporous filter membrane, performing vacuum concentration until crystallization occurs, pouring out crystals, cooling to room temperature, performing suction filtration, centrifuging, and drying to obtain a crude product 1;
(4) and (3) taking the crude product 1, heating by using 90% ethanol to dissolve the crude product, cooling and crystallizing at 80 ℃ while stirring until the temperature is cooled to 15 ℃, and performing suction filtration, centrifugation and drying to obtain a proline sample.
In one embodiment of the invention, step (1) is carried out by passing 10L of proline eluent over 2L of type 335 weakly basic cationic resin at a flow rate of 1.2L/h to obtain 10L of effluent.
In one embodiment of the present invention, step (2) is to pass the effluent liquid obtained in step (1) through a 110 type weakly acidic cation resin at a flow rate of 1.2L/h to obtain 10L of a secondary effluent liquid.
In one embodiment of the invention, the secondary effluent liquid obtained in the step (2) is heated to 60 ℃ in the step (3), 10% activated carbon is added for decolorization for 30min, after being filtered by suction and filtered by a microporous membrane, the secondary effluent liquid is subjected to vacuum concentration until crystallization occurs, the crystals are poured out and cooled to room temperature, and the crude product 1 is obtained after suction filtration, centrifugation and drying.
In one embodiment of the invention, the crude product 1 is taken in the step (4), added with 90% ethanol and heated to 80 ℃ to dissolve the crude product, and then cooled and crystallized at 80 ℃ while stirring until the temperature is cooled to 15 ℃, and finally the proline sample is obtained after suction filtration, centrifugation and drying at 60 ℃ for 4 hours.
[ advantageous effects ]
The method combines 335 type alkalescent cation resin, 110 type weak acid cation resin, and activated carbon for decolorization and crystallization purification, so that no alanine, no glutamic acid and no lysine exist in a sample, and the removal rate of the mixed acid is 100%.
Detailed Description
The present invention will be further illustrated below with reference to specific examples and comparative examples.
The detection method of alanine, glutamic acid and lysine is thin-layer chromatography: taking alanine, glutamic acid and lysine reference substances, placing in the same volumetric flask, adding water to dilute to the concentration of 0.05%, 0.1%, 0.2%, 0.3%, 0.4% and 0.5% to be used as a reference sample, sucking 2 mul of the sample to be detected and the reference sample to be respectively spotted on the same silica gel G thin layer plate, taking n-butyl alcohol-absolute ethyl alcohol-concentrated ammonia solution-water (8: 8:1:3) as a developing agent, developing, airing, spraying acetone solution (1 → 50) of ninhydrin, heating at 80 ℃ until spots appear, and immediately inspecting.
The proline eluate used in the examples described below was a proline eluate obtained by eluting with sodium hydroxide after passing the fermentation broth through a 732 cation exchange resin.
Example 1
(1) Passing 10L of proline eluent (glutamic acid content 0.1%, alanine 0.5%, lysine 0.2%) through 2L of 335 type weakly alkaline cationic resin at a flow rate of 1.2L/h to obtain 10L of effluent; through detection, the effluent liquid does not contain glutamic acid, the alanine content is 0.5%, and the lysine content is 0.2%;
(2) enabling the effluent liquid obtained in the step (1) to pass through a 110 type weakly acidic cation resin, and enabling the flow rate to be 1.2L/h to obtain 10L of secondary effluent liquid, wherein the secondary effluent liquid does not contain glutamic acid and lysine, and the alanine content is 0.5%;
(3) heating the secondary effluent liquid obtained in the step (2) to 60 ℃, adding 10% (10g/100mL) of activated carbon for decoloring for 30min for one time, performing suction filtration, filtering by a microporous filter membrane, performing vacuum concentration to crystallize, pouring out crystals, cooling to room temperature, performing suction filtration, centrifuging, and drying to obtain a crude product 1; the alanine content of the crude product 1 is 0.5%, and the crude product does not contain glutamic acid or lysine;
(4) taking 100g of the crude product 1, adding 200mL of 90% ethanol, heating to 80 ℃ to dissolve the crude product, placing the crude product into a water bath kettle at 80 ℃, cooling and crystallizing while stirring until the crude product is cooled to 15 ℃, performing suction filtration, centrifuging, and drying at 60 ℃ for 4 hours to obtain 40g of a sample, wherein the sample has no alanine, no glutamic acid or lysine, and the removal rate of the heteropolyacid is 100%.
Example 2
(1) Passing 10L of proline eluent (glutamic acid content 0.1%, alanine 0.5%, lysine 0.2%) through 2L of 335 type weakly alkaline cationic resin at a flow rate of 1.0L/h to obtain 10L of effluent; through detection, the effluent liquid does not contain glutamic acid, the alanine content is 0.5%, and the lysine content is 0.2%;
(2) enabling the effluent liquid obtained in the step (1) to pass through a 110 type weakly acidic cation resin, and enabling the flow rate to be 1.0L/h to obtain 10L of secondary effluent liquid, wherein the secondary effluent liquid does not contain glutamic acid and lysine, and the alanine content is 0.5%;
(3) heating the secondary effluent liquid obtained in the step (2) to 55 ℃, adding 15% (15g/100mL) of activated carbon for decoloring for 30min for one time, performing suction filtration, filtering by a microporous filter membrane, performing vacuum concentration to crystallize, pouring out crystals, cooling to room temperature, performing suction filtration, centrifuging, and drying to obtain a crude product 1; the alanine content of the crude product 1 is 0.5%, and the crude product does not contain glutamic acid or lysine;
(4) taking 100g of the crude product 1, adding 200mL of 85% ethanol, heating to 80 ℃ to dissolve the crude product, placing the crude product into a water bath kettle at 80 ℃, cooling and crystallizing while stirring until the crude product is cooled to 15 ℃, performing suction filtration and centrifugation, drying at 60 ℃ for 4 hours to obtain 39g of a sample, wherein the sample has no alanine, no glutamic acid or lysine, and the removal rate of the heteropolyacid is 100%.
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 (5)
1. A method for purifying proline bulk drugs is characterized by comprising the following steps:
(1) after the proline fermentation liquor is loaded on 732 cation exchange resin, proline eluent obtained by elution of sodium hydroxide is processed by 335 type weak alkaline cation resin, and effluent liquid is collected;
(2) enabling the effluent liquid obtained in the step (1) to pass through a 110 type weak acid cation resin to obtain secondary effluent liquid;
(3) heating the secondary effluent liquid obtained in the step (2) to 55-60 ℃, adding 10-15% of activated carbon for decolorization, performing suction filtration, filtering with a microporous filter membrane, performing vacuum concentration to crystallize, pouring out crystals, cooling to room temperature, performing suction filtration, centrifuging, and drying to obtain a crude product 1;
(4) and (3) taking the crude product 1, heating by using 90% ethanol to dissolve the crude product, cooling and crystallizing at 80 ℃ while stirring until the temperature is cooled to 15 ℃, and performing suction filtration, centrifugation and drying to obtain a proline sample.
2. The method for purifying a proline raw material drug according to claim 1, characterized in that in step (1), 10L of proline eluent is passed through 2L of type 335 weak basic cationic resin at a flow rate of 1.2L/h to obtain 10L of effluent.
3. The method for purifying proline bulk drug according to claim 1, characterized in that the effluent liquid obtained in step (1) is passed through 110 type weakly acidic cation resin in step (2) at a flow rate of 1.2L/h to obtain 10L secondary effluent liquid.
4. The method for purifying proline bulk drug according to claim 1, characterized in that, in the step (3), the secondary effluent liquid obtained in the step (2) is heated to 60 ℃, 10% activated carbon is added for decolorization for 30min, and after being subjected to suction filtration and microfiltration membrane filtration, vacuum concentration is performed until crystallization occurs, the crystal is poured out and cooled to room temperature, and the crude product 1 is obtained after suction filtration, centrifugation and drying.
5. The method for purifying the proline bulk drug according to claim 1 or 4, characterized in that the proline sample is obtained by taking the crude product 1 in the step (4), adding the crude product into 90% ethanol, heating to 80 ℃ to dissolve the crude product, cooling and crystallizing at 80 ℃ while stirring until the temperature is cooled to 15 ℃, performing suction filtration, centrifuging, and drying at 60 ℃ for 4 hours.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110584419.6A CN113307756A (en) | 2021-05-27 | 2021-05-27 | Method for purifying proline bulk drug |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110584419.6A CN113307756A (en) | 2021-05-27 | 2021-05-27 | Method for purifying proline bulk drug |
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| Publication Number | Publication Date |
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| CN113307756A true CN113307756A (en) | 2021-08-27 |
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| CN202110584419.6A Pending CN113307756A (en) | 2021-05-27 | 2021-05-27 | Method for purifying proline bulk drug |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103333094A (en) * | 2013-06-19 | 2013-10-02 | 广东肇庆星湖生物科技股份有限公司 | Process method for crystallization purification of proline |
| CN108640865A (en) * | 2018-07-02 | 2018-10-12 | 无锡晶海氨基酸股份有限公司 | A kind of preparation method of medicinal proline |
| CN108658827A (en) * | 2018-07-02 | 2018-10-16 | 无锡晶海氨基酸股份有限公司 | A kind of preparation method of proline crude product |
| CN112608266A (en) * | 2020-12-30 | 2021-04-06 | 南通紫琅生物医药科技有限公司 | Preparation method of L-proline |
-
2021
- 2021-05-27 CN CN202110584419.6A patent/CN113307756A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103333094A (en) * | 2013-06-19 | 2013-10-02 | 广东肇庆星湖生物科技股份有限公司 | Process method for crystallization purification of proline |
| CN108640865A (en) * | 2018-07-02 | 2018-10-12 | 无锡晶海氨基酸股份有限公司 | A kind of preparation method of medicinal proline |
| CN108658827A (en) * | 2018-07-02 | 2018-10-16 | 无锡晶海氨基酸股份有限公司 | A kind of preparation method of proline crude product |
| CN112608266A (en) * | 2020-12-30 | 2021-04-06 | 南通紫琅生物医药科技有限公司 | Preparation method of L-proline |
Non-Patent Citations (3)
| Title |
|---|
| 彭阳峰等: "离子交换法从醋酸溶液中提取脯氨酸的研究", 《离子交换与吸附》 * |
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| 曹稳根等: "L-脯氨酸在大孔强酸阳离子交换树脂上的吸附性能研究", 《宿州学院学报》 * |
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Application publication date: 20210827 |
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