CN111410627A - production method of pharmaceutical-grade L-tryptophan - Google Patents
production method of pharmaceutical-grade L-tryptophan Download PDFInfo
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- CN111410627A CN111410627A CN202010257637.4A CN202010257637A CN111410627A CN 111410627 A CN111410627 A CN 111410627A CN 202010257637 A CN202010257637 A CN 202010257637A CN 111410627 A CN111410627 A CN 111410627A
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- Prior art keywords
- tryptophan
- grade
- namely
- activated carbon
- filtering
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- QIVBCDIJIAJPQS-VIFPVBQESA-N L-tryptophane Chemical compound C1=CC=C2C(C[C@H](N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-VIFPVBQESA-N 0.000 title claims abstract description 66
- 229960004799 tryptophan Drugs 0.000 title claims abstract description 35
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 44
- 239000013078 crystal Substances 0.000 claims abstract description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 19
- 238000001914 filtration Methods 0.000 claims abstract description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000008213 purified water Substances 0.000 claims abstract description 13
- 239000012043 crude product Substances 0.000 claims abstract description 10
- 238000001035 drying Methods 0.000 claims abstract description 10
- 238000005406 washing Methods 0.000 claims abstract description 10
- 238000000053 physical method Methods 0.000 claims abstract description 9
- 239000002023 wood Substances 0.000 claims abstract description 9
- LXAHHHIGZXPRKQ-UHFFFAOYSA-N 5-fluoro-2-methylpyridine Chemical compound CC1=CC=C(F)C=N1 LXAHHHIGZXPRKQ-UHFFFAOYSA-N 0.000 claims abstract description 7
- 238000010438 heat treatment Methods 0.000 claims abstract description 7
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 7
- 238000003756 stirring Methods 0.000 claims abstract description 7
- 239000000706 filtrate Substances 0.000 claims abstract description 3
- 229910001385 heavy metal Inorganic materials 0.000 claims abstract description 3
- 238000005119 centrifugation Methods 0.000 claims description 2
- 238000002425 crystallisation Methods 0.000 claims description 2
- 230000008025 crystallization Effects 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims description 2
- IFGCUJZIWBUILZ-UHFFFAOYSA-N sodium 2-[[2-[[hydroxy-(3,4,5-trihydroxy-6-methyloxan-2-yl)oxyphosphoryl]amino]-4-methylpentanoyl]amino]-3-(1H-indol-3-yl)propanoic acid Chemical compound [Na+].C=1NC2=CC=CC=C2C=1CC(C(O)=O)NC(=O)C(CC(C)C)NP(O)(=O)OC1OC(C)C(O)C(O)C1O IFGCUJZIWBUILZ-UHFFFAOYSA-N 0.000 abstract description 4
- 238000002834 transmittance Methods 0.000 description 8
- 238000000034 method Methods 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 241001465754 Metazoa Species 0.000 description 5
- 230000004913 activation Effects 0.000 description 5
- 229910021645 metal ion Inorganic materials 0.000 description 4
- 238000003828 vacuum filtration Methods 0.000 description 4
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 2
- 206010029400 Nicotinic acid deficiency Diseases 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 239000003963 antioxidant agent Substances 0.000 description 2
- 230000003078 antioxidant effect Effects 0.000 description 2
- 235000015872 dietary supplement Nutrition 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 229910001873 dinitrogen Inorganic materials 0.000 description 2
- 239000012452 mother liquor Substances 0.000 description 2
- 238000006864 oxidative decomposition reaction Methods 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 102000004169 proteins and genes Human genes 0.000 description 2
- 108090000623 proteins and genes Proteins 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- SBNOTUDDIXOFSN-UHFFFAOYSA-N 1h-indole-2-carbaldehyde Chemical compound C1=CC=C2NC(C=O)=CC2=C1 SBNOTUDDIXOFSN-UHFFFAOYSA-N 0.000 description 1
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 description 1
- 125000002707 L-tryptophyl group Chemical group [H]C1=C([H])C([H])=C2C(C([C@](N([H])[H])(C(=O)[*])[H])([H])[H])=C([H])N([H])C2=C1[H] 0.000 description 1
- 208000002141 Pellagra Diseases 0.000 description 1
- 102000004142 Trypsin Human genes 0.000 description 1
- 108090000631 Trypsin Proteins 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 238000000498 ball milling Methods 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 238000003763 carbonization Methods 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 235000013365 dairy product Nutrition 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 235000020776 essential amino acid Nutrition 0.000 description 1
- 239000003797 essential amino acid Substances 0.000 description 1
- 210000003754 fetus Anatomy 0.000 description 1
- 239000003546 flue gas Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000037406 food intake Effects 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000006651 lactation Effects 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 230000009965 odorless effect Effects 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000003938 response to stress Effects 0.000 description 1
- 230000033764 rhythmic process Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229940125725 tranquilizer Drugs 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 230000003313 weakening effect Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/04—Indoles; Hydrogenated indoles
- C07D209/10—Indoles; Hydrogenated indoles with substituted hydrocarbon radicals attached to carbon atoms of the hetero ring
- C07D209/18—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D209/20—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals substituted additionally by nitrogen atoms, e.g. tryptophane
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Indole Compounds (AREA)
Abstract
the invention discloses a production method of pharmaceutical-grade L-tryptophan, which comprises the following specific steps of a dissolving, namely adding feed-grade L-tryptophan crude product into purified water, heating to dissolve, adding EDTA-disodium to remove heavy metals, b decoloring and filtering, namely adsorbing the dissolved solution by wood activated carbon (the conductivity is less than or equal to 25S/m) through a physical method, vacuumizing to remove the activated carbon, c crystallizing and centrifuging, namely uniformly stirring and slowly crystallizing the filtered filtrate under the protection of nitrogen, d centrifuging and washing, namely centrifuging and filtering the crystallized solution to obtain white crystals, washing the crystals with purified water, and e drying, namely drying the washed crystals at the temperature of 60-70 ℃ to obtain pure L-tryptophan.
Description
Technical Field
the invention relates to the technical field of production methods of amino acids, in particular to a production method of pharmaceutical-grade L-tryptophan.
Background
L-tryptophan is also called alpha-amino indole propionic acid, the molecular formula is C11H12N2O2, white to yellow white crystal or crystalline powder, odorless or slightly odorous, colored after long-time illumination, stable when heated in dark with acid, easy to decompose when coexisting with other amino acids, saccharides and aldehydes, used as food enhancer and antioxidant, used in medicine, and synthesized from indole aldehyde, or decomposed and synthesized from trypsin.
Human: the nutritional supplement, antioxidant, tryptophan is the precursor of the important neurotransmitter-5-hydroxytryptamine of the human body, and is one of the essential amino acids of the human body; is used as nutritional supplement for pregnant women and special milk powder for infants; a remedy for nicotinic acid deficiency (pellagra); can be used as tranquilizer for regulating mental rhythm and improving sleep.
Animals: promoting the ingestion of animals, weakening stress response, improving the sleep of animals, increasing the antibodies of fetuses and young animals, improving the lactation of dairy animals, reducing the dosage of high-quality protein in daily ration, saving the feed cost, reducing the dosage of protein feed in daily ration, saving the formula space and the like.
therefore, the pharmaceutical grade L-tryptophan which is required to improve the production efficiency and the purity, the light transmittance and the yield of the product meets the market demand.
Disclosure of Invention
the invention aims to overcome the technical defects and provide a method for producing pharmaceutical-grade L-tryptophan, which improves the production efficiency, the product purity, the light transmittance and the yield.
in order to solve the technical problems, the technical scheme provided by the invention is that the production method of the pharmaceutical-grade L-tryptophan comprises the following specific steps:
dissolving, namely adding the feed-grade L-tryptophan crude product into purified water, heating to dissolve, and adding EDTA-disodium to remove heavy metals;
b, decoloring and filtering: adsorbing the dissolved solution by using wood activated carbon (the conductivity is less than or equal to 25S/m) activated by a physical method, and then vacuumizing and filtering the activated carbon;
c, crystallization and centrifugation: stirring the filtered filtrate at a constant speed under the protection of nitrogen, and slowly crystallizing;
d, centrifuging and washing: centrifuging and filtering the crystal liquid to obtain white crystals, and washing the crystals with purified water;
and e, drying, namely drying the washed crystal at the temperature of 60-70 ℃ to obtain the pure L-tryptophan.
compared with the prior art, the method has the advantages that EDTA is used for chelating metal ions in feed-grade L-tryptophan to reduce the metal ions in the solution, the wood activated carbon activated by a physical method is used for ensuring the conductivity (less than or equal to 25S/m), the activated carbon has a developed micropore structure and can better adsorb impurities of the feed-grade L-tryptophan, and the activated carbon is vacuumized to filter out the activated carbon and crystallized under the protection of nitrogen, so that the oxidative decomposition of the L-tryptophan can be better placed.
The activated carbon is prepared by activating raw materials such as charcoal, coal and the like, the activation has chemical and physical modes, the physical method is usually also called as a gas activation method, the carbonized raw materials are contacted with activated gases such as water vapor, flue gas (mixed gas of the water vapor, CO2, N2 and the like), CO or air and the like at the high temperature of 800-1000 ℃, so as to carry out an activation reaction process, the basic process of the physical activation method mainly comprises the processes of carbonization, activation, impurity removal, crushing (ball milling), refining and the like, the preparation process is clean, and the liquid phase pollution is less.
the process can ensure the quantity and quality of products, shorten the production time and improve the efficiency, and the purity of the prepared L-tryptophan is more than 99.2 percent, the light transmittance can reach more than 97.8 percent, and the yield can reach 90 to 93 percent.
Detailed Description
The present invention will be described in further detail with reference to examples.
A production method of pharmaceutical-grade L-tryptophan comprises the steps of adding feed-grade L-tryptophan crude products into purified water, heating to 65-75 ℃ to dissolve the feed-grade L-tryptophan crude products, adding EDTA-disodium, decoloring the dissolved solution with wood activated carbon (the conductivity is less than or equal to 25S/m) activated by a physical method, completing decoloring, performing vacuum filtration, filtering out the activated carbon, slowly crystallizing the filtered solution with cold water under the protection of nitrogen gas with uniform stirring, performing centrifugal filtration on the crystallized solution to obtain white crystals, washing the crystals with purified water, and drying the washed crystals at the temperature of 60-70 ℃ to obtain the pharmaceutical-grade L-tryptophan.
EDTA is used for chelating metal ions in feed-grade L-tryptophan to reduce the metal ions in the solution, wood activated carbon activated by a physical method is used for ensuring the conductivity (less than or equal to 25S/m), the activated carbon has a developed microporous structure and can better adsorb impurities of the feed-grade L-tryptophan, and the activated carbon is vacuumized to filter out the activated carbon and crystallized under the protection of nitrogen, so that the L-tryptophan can be better placed for oxidative decomposition to prepare the medical-grade L-tryptophan.
the preparation process has simple operation, short production flow, no organic solvent, capacity of ensuring the product amount and quality, short production period and high efficiency, and can prepare L-tryptophan product with purity over 99.2, light transmittance over 97.8% and yield up to 90-93%.
Example 1
adding 70g of feed-grade L-tryptophan crude product with the content of 98% and the light transmittance of 52% into 1200ml of purified water, heating to 65-75 ℃ to dissolve the feed-grade L-tryptophan crude product, adding 0.5g of EDTA-disodium and 10g of wood activated carbon (the conductivity is less than or equal to 25S/m) through a physical method, preserving heat and decoloring for 30 minutes, filtering the activated carbon through vacuum filtration after the decoloring is finished, slowly crystallizing the filtered solution under the protection of cold water and nitrogen and constant-speed stirring, centrifugally filtering the crystallized solution to obtain white crystals, washing the purified water with the crystals, and drying the washed crystals at the temperature of 60-70 ℃ to obtain the pharmaceutical-grade L-tryptophan.
EXAMPLE 2
adding 70g of feed-grade L-tryptophan crude product with the content of 98% and the light transmittance of 52% into 1200ml of purified water, heating to 65-75 ℃ to dissolve the feed-grade L-tryptophan crude product, adding 1g of EDTA-disodium and 10g of wood activated carbon (the conductivity is less than or equal to 25S/m) through a physical method, preserving heat and decoloring for 30 minutes, filtering out the activated carbon through vacuum filtration after decoloring, slowly crystallizing the filtered solution under the protection of cold water and nitrogen gas and constant-speed stirring, centrifugally filtering the crystallized solution to obtain white crystals, washing the crystals with purified water, and drying the washed crystals at the temperature of 60-70 ℃ to obtain the medical-grade L-tryptophan.
Example 3
adding 30g of feed-grade L-tryptophan crude product with the content of 98% and the light transmittance of 52% into 1200ml of tryptophan mother liquor subjected to centrifugal filtration in the example 1, heating to 65-75 ℃ to dissolve the tryptophan mother liquor, adding 0.5g of EDTA-disodium and 5g of physically activated wood activated carbon (the conductivity is less than or equal to 25S/m), preserving heat and decoloring for 30 minutes, filtering the activated carbon through vacuum filtration after decoloring, slowly crystallizing the filtered solution under the protection of cold water and nitrogen and uniform stirring, performing centrifugal filtration on the crystallized solution to obtain white crystals, washing the crystals with purified water, and drying the washed crystals at the temperature of 60-70 ℃ to obtain the pharmaceutical-grade L-tryptophan.
The results of the examples show that:
| Product(s) | Example 1 | Example 2 | Example 3 |
| Purity of | 99.21％ | 99.23％ | 99.31％ |
| Light transmittance | 97.76％ | 97.82％ | 98.21％ |
Claims (1)
1. A production method of pharmaceutical-grade L-tryptophan is characterized by comprising the following specific steps:
dissolving, namely adding the feed-grade L-tryptophan crude product into purified water, heating to dissolve, and adding EDTA-disodium to remove heavy metals;
b, decoloring and filtering: adsorbing the dissolved solution by using wood activated carbon (the conductivity is less than or equal to 25S/m) activated by a physical method, and then vacuumizing and filtering the activated carbon;
c, crystallization and centrifugation: stirring the filtered filtrate at a constant speed under the protection of nitrogen, and slowly crystallizing;
d, centrifuging and washing: centrifuging and filtering the crystal liquid to obtain white crystals, and washing the crystals with purified water;
and e, drying, namely drying the washed crystal at the temperature of 60-70 ℃ to obtain the pure L-tryptophan.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010257637.4A CN111410627A (en) | 2020-04-03 | 2020-04-03 | production method of pharmaceutical-grade L-tryptophan |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010257637.4A CN111410627A (en) | 2020-04-03 | 2020-04-03 | production method of pharmaceutical-grade L-tryptophan |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN111410627A true CN111410627A (en) | 2020-07-14 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010257637.4A Pending CN111410627A (en) | 2020-04-03 | 2020-04-03 | production method of pharmaceutical-grade L-tryptophan |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN111410627A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113354569A (en) * | 2021-06-04 | 2021-09-07 | 无锡晶海氨基酸股份有限公司 | Method for purifying tryptophan |
| CN116283711A (en) * | 2023-02-21 | 2023-06-23 | 黑龙江新和成生物科技有限公司 | Preparation method of high-purity cake-shaped L-tryptophan crystal and product thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5057615A (en) * | 1989-06-27 | 1991-10-15 | Mitsui Toatsu Chamicals, Inc. | Process for purifying tryptophan |
| CN102304077A (en) * | 2011-06-24 | 2012-01-04 | 南通诚信氨基酸有限公司 | Method for purifying tryptophan |
| CN103232037A (en) * | 2013-05-09 | 2013-08-07 | 江西碧林实业有限公司 | Process for producing active carbon by using steam physical method |
| CN105061289A (en) * | 2015-07-28 | 2015-11-18 | 蚌埠丰原医药科技发展有限公司 | Preparation method of pharmaceutical grade L-tryptophan |
-
2020
- 2020-04-03 CN CN202010257637.4A patent/CN111410627A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5057615A (en) * | 1989-06-27 | 1991-10-15 | Mitsui Toatsu Chamicals, Inc. | Process for purifying tryptophan |
| CN102304077A (en) * | 2011-06-24 | 2012-01-04 | 南通诚信氨基酸有限公司 | Method for purifying tryptophan |
| CN103232037A (en) * | 2013-05-09 | 2013-08-07 | 江西碧林实业有限公司 | Process for producing active carbon by using steam physical method |
| CN105061289A (en) * | 2015-07-28 | 2015-11-18 | 蚌埠丰原医药科技发展有限公司 | Preparation method of pharmaceutical grade L-tryptophan |
Non-Patent Citations (1)
| Title |
|---|
| 李建颖主编: "《食品添加剂速查手册》", 30 November 2017, 南开大学出版社 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113354569A (en) * | 2021-06-04 | 2021-09-07 | 无锡晶海氨基酸股份有限公司 | Method for purifying tryptophan |
| CN116283711A (en) * | 2023-02-21 | 2023-06-23 | 黑龙江新和成生物科技有限公司 | Preparation method of high-purity cake-shaped L-tryptophan crystal and product thereof |
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