EP1756055A1 - Process for the purification of tryptophan - Google Patents
Process for the purification of tryptophanInfo
- Publication number
- EP1756055A1 EP1756055A1 EP05740139A EP05740139A EP1756055A1 EP 1756055 A1 EP1756055 A1 EP 1756055A1 EP 05740139 A EP05740139 A EP 05740139A EP 05740139 A EP05740139 A EP 05740139A EP 1756055 A1 EP1756055 A1 EP 1756055A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- tryptophan
- solution
- acetic acid
- ammonium hydroxide
- demineralised water
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 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 34
- QIVBCDIJIAJPQS-UHFFFAOYSA-N Tryptophan Natural products C1=CC=C2C(CC(N)C(O)=O)=CNC2=C1 QIVBCDIJIAJPQS-UHFFFAOYSA-N 0.000 title claims abstract description 34
- 238000000034 method Methods 0.000 title claims abstract description 19
- 238000000746 purification Methods 0.000 title claims description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 51
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 23
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical group [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 claims description 14
- 239000000908 ammonium hydroxide Substances 0.000 claims description 7
- 239000000047 product Substances 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 6
- 239000002244 precipitate Substances 0.000 claims description 5
- 230000001580 bacterial effect Effects 0.000 claims description 2
- 239000000203 mixture Substances 0.000 claims description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims 1
- 238000010521 absorption reaction Methods 0.000 claims 1
- 239000001110 calcium chloride Substances 0.000 claims 1
- 229910001628 calcium chloride Inorganic materials 0.000 claims 1
- 238000005406 washing Methods 0.000 claims 1
- 238000000855 fermentation Methods 0.000 abstract description 3
- 230000004151 fermentation Effects 0.000 abstract description 3
- 239000000243 solution Substances 0.000 description 27
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 17
- 150000001413 amino acids Chemical class 0.000 description 6
- 239000012452 mother liquor Substances 0.000 description 4
- 239000000725 suspension Substances 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 3
- 238000001728 nano-filtration Methods 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- 238000005119 centrifugation Methods 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 239000005909 Kieselgur Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- LLSDKQJKOVVTOJ-UHFFFAOYSA-L calcium chloride dihydrate Chemical compound O.O.[Cl-].[Cl-].[Ca+2] LLSDKQJKOVVTOJ-UHFFFAOYSA-L 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 238000011097 chromatography purification Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- RXKJFZQQPQGTFL-UHFFFAOYSA-N dihydroxyacetone Chemical compound OCC(=O)CO RXKJFZQQPQGTFL-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000001471 micro-filtration Methods 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000001179 sorption measurement Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 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
Definitions
- the present invention relates to the field of tryptophan purification. STATE OF THE ART
- Tryptophan is an amino acid known to be used widely in both the human and animal food industry.
- the various methods for purifying tryptophan derived from bacterial cultures include chromatographic purification, which involves the use of columns of sizeable dimensions and is very costly on an industrial scale.
- the invention relates to a process for the purification of tryptophan which comprises treating a solution of semi-crude tryptophan with acetic acid in the presence of a base.
- the present invention enables the aforesaid problems to be overcome by means of a process which comprises a passage whereby the solution containing tryptophan is acidified with acetic acid in the presence of a base.
- the culture broth containing the tryptophan is filtered to separate the culture impurities (cells etc.) by means of known systems (centrifugation, microfiltration, filtration with the aid of diatomaceous earth etc.).
- the solution of crude tryptophan thus obtained is treated, again in substantially known manner, with an adsorption medium (generally activated carbon or dicalite, preferably the latter). Said medium is then removed by filtration and washed to recover as much tryptophan as possible.
- an adsorption medium generally activated carbon or dicalite, preferably the latter.
- the semi-crude tryptophan in aqueous solution thus obtained is then suitably diluted in demineralised water in the presence of acetic acid and base at a temperature between 20°C and 80°C and the solution is left to crystallize.
- acetic acid and base at a temperature between 20°C and 80°C and the solution is left to crystallize.
- the addition of a base is necessary to partially neutralize the acetic acid and to enable crystallization of the amino acid.
- the solid is then re-suspended in water, the pH is corrected to the isoelectric point (pH 5.9) by adding base and finally the crystals are collected by filtration and dried.
- the tryptophan thus obtained has a purity above 99% and the yield with respect to the starting product (crude tryptophan) is calculated to be about 55-65%.
- the preferred acid is acetic acid and the base is ammonium hydroxide.
- 80% commercial acetic acid is used in a quantity between 10% by volume and a volume equivalent to the solution containing tryptophan, a 30% ammonium hydroxide solution then being added until the pH stabilizes at around a value of between 3.0 and 5.0.
- ammonium acetate can be used to bring the pH to around a value between 3.0 and 5.0 then diluting the solution with 80% commercial acetic acid in a quantity to bring the total concentration of acetic/acetate within a range between 5% and 40%.
- the wet mass of about 3.2 litres in volume, was re-suspended in 1.6 litres of demineralised water and the pH was brought to pH 5.9 with 280 ml of 30% NH 4 OH.
- the crystalline mass was filtered off with the aid of filter paper and washed with demineralised water.
- the suspension was then filtered and the carbon residue was washed with 500 litres of demineralised water.
- the wet mass of about 90 litres in volume, was re-suspended in 45 litres of demineralised water and the pH was brought to pH 5.9 with 5 litres of 30%
- the solution was brought to pH 5.0 by adding 150 g of ammonium acetate.
- 150 ml of 80% acetic acid, technical grade, and 450 ml of demineralised water were added to the solution and the entirety was brought to 60°C while under agitation.
- the precipitate was filtered off with the aid of filter paper and washed with demineralised water.
- the wet mass of about 100 ml in volume, was re-suspended in 80 ml of demineralised water and the pH was brought to pH 5.9 with 30% NH 4 OH.
- the crystalline mass was filtered off with the aid of filter paper and washed with demineralised water.
- the product obtained was finally oven dried at 70°C for 3 days.
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
A process is described enabling tryptophan, obtained from biological fermentation processes, to be purified by simple means and with very good yields.
Description
PROCESS FOR THE PURIFICATION OF TRYPTOPHAN
FIELD OF THE INVENTION
The present invention relates to the field of tryptophan purification. STATE OF THE ART
Tryptophan is an amino acid known to be used widely in both the human and animal food industry.
Its production is normally carried out by fermentation processes in which the carbon source in the culture substrate is commonly glucose. As with all fermentation processes, the product obtained has a considerable degree of impurity and so the main problem to be solved is obtaining the amino acid in a sufficiently pure manner without compromising total process yields.
The various methods for purifying tryptophan derived from bacterial cultures include chromatographic purification, which involves the use of columns of sizeable dimensions and is very costly on an industrial scale.
In US patent 4,820,825 a process is described for the purification of tryptophan in which an aqueous solution of crude tryptophan is treated at pH 1-4 with activated carbon and with highly porous non-polar resins. The solution is then. neutralized with alkaline substances and the tryptophan is finally crystallised by adding an aliphatic alcohol or a lower aliphatic ketone to the solution.
In US patent 5,057,615 a process is described for the purification of tryptophan in which the amino acid is purified by re-crystallization from a solution of water and acetic acid without using an alkaline neutral izer.
In this process however the acetate corresponding to the amino acid forms and thus, in order to obtain the amino acid, a final passage of drying under reduced pressure must be added, with the expense that such a passage clearly involves.
In US patent 6,284,897 a purification process is described in which a solution of tryptophan at pH 8-13 is maintained at a temperature between ambient and 100°C for a period between 0.5 hours and a week. In the light of the aforegoing, there is evident interest in establishing a process which involves less costly passages in terms of time and/or energy.
SUMMARY
The invention relates to a process for the purification of tryptophan which comprises treating a solution of semi-crude tryptophan with acetic acid in the presence of a base. DETAILED DESCRIPTION OF THE INVENTION
The present invention enables the aforesaid problems to be overcome by means of a process which comprises a passage whereby the solution containing tryptophan is acidified with acetic acid in the presence of a base. According to the invention the culture broth containing the tryptophan is filtered to separate the culture impurities (cells etc.) by means of known systems (centrifugation, microfiltration, filtration with the aid of diatomaceous earth etc.). The solution of crude tryptophan thus obtained is treated, again in substantially known manner, with an adsorption medium (generally activated carbon or dicalite, preferably the latter). Said medium is then removed by filtration and washed to recover as much tryptophan as possible.
The semi-crude tryptophan in aqueous solution thus obtained is then suitably diluted in demineralised water in the presence of acetic acid and base at a temperature between 20°C and 80°C and the solution is left to crystallize. The addition of a base is necessary to partially neutralize the acetic acid and to enable crystallization of the amino acid.
The solid is then re-suspended in water, the pH is corrected to the isoelectric point (pH 5.9) by adding base and finally the crystals are collected by filtration and dried. The tryptophan thus obtained has a purity above 99% and the yield with respect to the starting product (crude tryptophan) is calculated to be about 55-65%. According to the invention the preferred acid is acetic acid and the base is ammonium hydroxide.
In the first passage preferably 80% commercial acetic acid is used in a quantity between 10% by volume and a volume equivalent to the solution containing tryptophan, a 30% ammonium hydroxide solution then being added until the pH stabilizes at around a value of between 3.0 and 5.0.
According to a particular embodiment of the invention, instead of using acetic acid and ammonium hydroxide, ammonium acetate can be used to bring the pH to around a value between 3.0 and 5.0 then diluting the solution with 80% commercial acetic acid in a quantity to bring the total concentration of acetic/acetate within a range between 5% and 40%.
The invention can be further and better understood in the light of the examples given hereinafter.
Example 1
745 g of tryptophan, contained in a solution concentrated to 74.5 g/l by nanofiltration of mother liquor derived from a suitably microfiltered culture broth, were treated with 60 g of activated carbon at 60°C for 6 hours. The suspension was then filtered and the carbon residue was washed with 900 ml of demineralised water.
3.6 litres of 80% acetic acid, technical grade, were added to the solution while still hot. The solution was brought to pH 3.0 by adding 30% NH4OH solution and was then left to crystallize overnight. The precipitate was filtered off with the aid of filter paper and washed with demineralised water.
The wet mass, of about 3.2 litres in volume, was re-suspended in 1.6 litres of demineralised water and the pH was brought to pH 5.9 with 280 ml of 30% NH4OH.
The crystalline mass was filtered off with the aid of filter paper and washed with demineralised water.
Finally, the product obtained was oven dried at 70°C for 3 days.
445 g of tryptophan were obtained. Purity: 98.8%, yield 59.7%. Example 2
310 litres of a solution concentrated to 74.9 g/l by nanofiltration of mother liquor derived from a suitably microfiltered culture broth, were diluted with 360 litres of an aqueous solution consisting of the wash water of a crystalline mass of tryptophan previously produced in a similar manner to that described in example 1. The mixture was treated with 2.1 kg of activated carbon at 60°C for 4 hours.
The suspension was then filtered and the carbon residue was washed with 500
litres of demineralised water.
200 litres of 80% acetic acid, technical grade, were added to the solution while still hot. The solution was brought to pH 3.0 by the addition of a 30% NH4OH solution and was then left to crystallize overnight. The precipitate was filtered off with the aid of a pressure filter and washed with demineralised water.
The wet mass, of about 90 litres in volume, was re-suspended in 45 litres of demineralised water and the pH was brought to pH 5.9 with 5 litres of 30%
NH4OH. The crystalline mass was again filtered off and washed with demineralised water.
Finally, the product obtained was dried by means of a fluidized-bed dryer.
16.7 kg of tryptophan were obtained. Purity: 99.2%, yield 72.0%.
Example 3
750 ml of a tryptophan solution concentrated to 72.3 g/l by nanofiltration of mother liquor derived from a suitably microfiltered culture broth, were treated with 4 g of activated carbon at ambient temperature for 6 hours. The suspension was then filtered and the carbon residue was washed with 350 ml of demineralised water.
The solution was brought to pH 5.0 by adding 150 g of ammonium acetate. 150 ml of 80% acetic acid, technical grade, and 450 ml of demineralised water were added to the solution and the entirety was brought to 60°C while under agitation.
The solution was then left to crystallize overnight.
The precipitate was filtered off with the aid of filter paper and washed with demineralised water.
The wet mass, of about 100 ml in volume, was re-suspended in 80 ml of demineralised water and the pH was brought to pH 5.9 with 30% NH4OH. The crystalline mass was filtered off with the aid of filter paper and washed with demineralised water.
The product obtained was finally oven dried at 70°C for 3 days.
35.3 g of tryptophan were obtained. Purity: 98.9%, yield 65.1%. Example 4
300 litres of a solution, concentrated to 74.7 g/l by heating under vacuum of
mother liquor derived from a culture broth deprived of cells by centrifugation, were treated with 2.0 kg of activated carbon at ambient temperature for 4 hours in the presence of 4 kg of calcium chloride, dihydrate. The suspension was then filtered and the carbon residue was washed with 500 litres of demineralised water. The solution was brought to 70°C and 200 litres of 80% acetic acid, technical grade, were added while the pH was brought to 3.0 by adding a solution of 30% NH4OH. The solution was then left to cool and crystallise overnight. The precipitate was filtered off with the aid of a pressure filter and washed with demineralised water. The wet mass, of about 90 litres in volume, was re-suspended in 45 litres of demineralised water and the pH was brought to pH 5.9 with 5 litres of 30% NH4OH.
The crystalline mass was again filtered and washed with demineralised water. Finally, the product obtained was dried by means of a fluidized-bed dryer. 17.3 kg of tryptophan were obtained. Purity: 99.1 %, yield 77.2%.
Claims
1. Process for the purification of tryptophan comprising the treatment of a crude tryptophan solution with acetic acid and base.
2. Process as claimed in claim 1 wherein said crude tryptophan is tryptophan obtained from bacterial cultures after filtering the culture broth and treating the remaining solution with an absorption medium and calcium chloride, filtering and washing in accordance with known techniques.
3. Process as claimed in claim 2 wherein the base is ammonium hydroxide.
4. Process as claimed in claim 3 wherein the acetic acid is 80% acetic acid.
5. Process as claimed in claim 4 wherein the ammonium hydroxide is used in a sufficient quantity to bring the pH of the solution to a value of about pH 3.0.
6. Process as claimed in claims 1-5 wherein: a) semi-crude tryptophan is dissolved in demineralised water in the presence of
80% acetic acid; b) a solution of ammonium hydroxide is added until the pH is 3; c) the mixture is left to crystallise; d) the precipitated crystalline product is re-suspended in water and the pH is corrected to a value of about 6.0 by adding ammonium hydroxide; e) the precipitate is collected by filtration and dried.
7. Tryptophan of a purity above 98%, obtained by a process claimed in claims 1-6.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| ITFI20040063 ITFI20040063A1 (en) | 2004-03-19 | 2004-03-19 | TRIPTOFANO PURIFICATION PROCESS |
| PCT/EP2005/051271 WO2005090306A1 (en) | 2004-03-19 | 2005-03-18 | Process for the purification of tryptophan |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP1756055A1 true EP1756055A1 (en) | 2007-02-28 |
Family
ID=34965835
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP05740139A Withdrawn EP1756055A1 (en) | 2004-03-19 | 2005-03-18 | Process for the purification of tryptophan |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP1756055A1 (en) |
| IT (1) | ITFI20040063A1 (en) |
| WO (1) | WO2005090306A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015104464A1 (en) | 2014-01-07 | 2015-07-16 | Novasep Process | Process for purifying aromatic amino acids |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102146052B (en) * | 2010-12-24 | 2013-08-21 | 山东鲁抗医药股份有限公司 | Method for preparing tryptophan |
| CN103641766B (en) * | 2013-12-18 | 2016-05-18 | 江苏江山制药有限公司 | From zymotic fluid, extract continuously the method for L-Trp |
| CN110759849A (en) * | 2019-11-18 | 2020-02-07 | 河南巨龙生物工程股份有限公司 | Tryptophan secondary mother liquor recovery process |
| CN110713452B (en) * | 2019-11-18 | 2021-09-24 | 河南巨龙生物工程股份有限公司 | Process for directly extracting L-tryptophan by fermentation method |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2799684A (en) * | 1954-06-18 | 1957-07-16 | Food Chemical And Res Lab Inc | Crystalline compounds of tryptophane and methods of manufacturing them |
| US4769474A (en) * | 1985-04-10 | 1988-09-06 | Mitsui Toatsu Chemicals, Inc. | Process for purifying tryptophane |
| JPH0784441B2 (en) * | 1986-11-19 | 1995-09-13 | 三菱化学株式会社 | Purification method of tryptophan |
| JPH0813801B2 (en) * | 1989-06-27 | 1996-02-14 | 三井東圧化学株式会社 | Method for purifying tryptophan |
-
2004
- 2004-03-19 IT ITFI20040063 patent/ITFI20040063A1/en unknown
-
2005
- 2005-03-18 EP EP05740139A patent/EP1756055A1/en not_active Withdrawn
- 2005-03-18 WO PCT/EP2005/051271 patent/WO2005090306A1/en not_active Ceased
Non-Patent Citations (1)
| Title |
|---|
| See references of WO2005090306A1 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015104464A1 (en) | 2014-01-07 | 2015-07-16 | Novasep Process | Process for purifying aromatic amino acids |
Also Published As
| Publication number | Publication date |
|---|---|
| ITFI20040063A1 (en) | 2004-06-19 |
| WO2005090306A1 (en) | 2005-09-29 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN109180745B (en) | Method for preparing N-acetylneuraminic acid by separating and purifying polysialic acid-containing material | |
| US20170369920A1 (en) | Separation of 2'-fl from a fermentation broth | |
| CN109265498B (en) | An integrated method for separating and purifying polysialic acid to prepare N-acetylneuraminic acid | |
| CN109369730B (en) | Sialic acid and extraction method thereof | |
| KR20130062913A (en) | Crystalline oxidized glutathione and production method therefor | |
| CN101717360A (en) | Method for extracting L-tryptophan from fermentation liquid | |
| KR20180127347A (en) | Crystallization of reduced glutathione and its preparation method | |
| HU202282B (en) | Process for separating 2-keto-l-gulonic acid from fermentation juice | |
| EP0274728B1 (en) | Method for purifying tryptophan | |
| WO2005090306A1 (en) | Process for the purification of tryptophan | |
| JP4361641B2 (en) | Separation and recovery method of optically active amino acid and optically active amino acid amide | |
| CN120309665A (en) | A method for separating and purifying citicoline sodium from Bacillus subtilis fermentation broth | |
| JP2001258583A (en) | Method for purifying shikimic acid | |
| CN1035333C (en) | Production method of salinomycin and its sodium salt crystalline product | |
| CN115650872B (en) | Separation and purification method of L-homoserine fermentation liquor | |
| US4588818A (en) | Method for recovery of optically active tryptophane | |
| JPS61145150A (en) | Manufacture of glutamic acid in crystal state | |
| CN117050021B (en) | Method for separating and extracting tetrahydropyrimidine from fermentation liquor | |
| CN116162665B (en) | Method and device for preparing L-glufosinate-ammonium from D, L-glufosinate-ammonium reaction solution | |
| JPS61126070A (en) | Method of decoloring and purifying l-tryptophan | |
| JP3719309B2 (en) | Manufacturing method of ribitol | |
| JPS604168A (en) | Crystallization of tryptophan | |
| WO2014097221A1 (en) | Process for the purification of biapenem | |
| JPS6013758A (en) | Purification of tryptophan | |
| CN111517973B (en) | Production process for preparing 5-aminolevulinic acid hydrochloride from fermentation broth and application of production process |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
| 17P | Request for examination filed |
Effective date: 20061018 |
|
| AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU MC NL PL PT RO SE SI SK TR |
|
| DAX | Request for extension of the european patent (deleted) | ||
| 17Q | First examination report despatched |
Effective date: 20071129 |
|
| STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
| 18D | Application deemed to be withdrawn |
Effective date: 20080410 |