CN102146052B - Method for preparing tryptophan - Google Patents
Method for preparing tryptophan Download PDFInfo
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- CN102146052B CN102146052B CN 201010603780 CN201010603780A CN102146052B CN 102146052 B CN102146052 B CN 102146052B CN 201010603780 CN201010603780 CN 201010603780 CN 201010603780 A CN201010603780 A CN 201010603780A CN 102146052 B CN102146052 B CN 102146052B
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- tryptophane
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Abstract
The invention relates to a method for preparing tryptophan, in particular to a simple, convenient and high-efficiency method for high-transparency tryptophan. The method comprises the following steps of: adding crude tryptophan into mixed solution, heating to fully dissolve the crude tryptophan, adding active carbon, adsorbing for half an hour, filtering out the active carbon, and performing membrane filtration on a filter membrane, wherein the mixed solution is mixed solution of purified water, low molecular weight fatty alcohols or low-grade aliphatic ketones and low-grade fatty acids; stirring the filtrate for slow crystallization, and further reducing temperature by using a physical method for full crystallization; and filtering crystalline liquid to obtain white crystals, fully washing the crystals, regulating the PH value, filtering again, and drying to obtain a pure product, wherein all mother solution can be recycled. The tryptophan product prepared by the method accords with various indexes specified by the medicinal grade standard in pharmacopeia in 2010 version, such as the transparency of 95 percent and the like; moreover, in the method, a single solvent is used and is not needed to be separately recovered, and the mother solution is simply treated and can be recycled so as to avoid pollution.
Description
Technical field
The present invention relates to a kind of amino acid whose preparation method, specifically is the method for preparing the high transmission rate tryptophane.
Background technology
The molecular formula C of L-tryptophane
11H
12N
2O
2, molecular weight 204.23, another name amino indole propionic acid, structural formula is as follows:
The L-tryptophane is white or little yellow crystal or crystalline powder; Odorless or little smelly has bitter taste slightly, 289 ℃ of decomposition, and slightly soluble in water is insoluble to ethanol; Dissolve in diluted acid or diluted alkaline, long-time illumination is then painted, is total to a small amount of indoles of thermogenesis with water, as heating in the presence of sodium hydroxide, copper sulfate, then produce a large amount of indoles, in the dark heat to cry with acid and stablize, very easily decompose during with other amino acid, carbohydrate, aldehydes coexistence.
Tryptophane is that humans and animals is kept one of indispensable amino acid of growth, and the natural origin tryptophane is the second or the 3rd limiting amino acid of cereals feed normally, especially seems more obvious in the feed based on jowar and corn.Tryptophane has been subjected to paying close attention to widely as the amino acid with different physiological roles.Research is significant as the high-quality tryptophane product of medicine.
The tryptophane purification technique mainly adopts resin method at present, carries out ion-exchange and purifies.Use resin can produce a large amount of acid alkali containing waste liquids, cause environmental protection pressure, also increased production cost.Also needing through loaded down with trivial details step productions such as gac activation, condensing crystals of minority dissolving extraction arranged.
Japanese patent specification JP895/1983 adopts tryptophane solution earlier by nonpolar porous resin, pass through the method purification tryptophane of ultrafiltration again, but Impurity removal is undesirable, does not reach the high transmission rate requirement.Patent specification JP39857/1984 proposes tryptophane and dissolves with alkali lye, in the presence of lower aliphatic alcohols or ketone in and crystallization, improve purity, but Impurity removal is still insufficient, transmittance is difficult to reach 95%, and, use a large amount of solvents, need recovery and aftertreatment.JP126070/1986 is dissolved in tryptophane in 95-100 ℃ the acidic aqueous solution, uses charcoal absorption, and the filter charcoal adsorbs by nonpolar porous resin, the wash-out tryptophane, in the presence of lower aliphatic alcohols in and crystallization.Higher because of its use temperature, indole ring instability generation coloring matter causes transmittance undesirable.
US Patent specification US5057615 primary study only with the dissolving situation of acetic acid to tryptophane.Proposing its recrystallization process can lower the temperature in acetum, yield 89%, content 98.9%, not mentioned transmittance.After US Patent specification US4820825 dissolves the crude product tryptophane, use the absorption through the gac 3%-25% of acid activation, pass through nonpolar porous resin again, obtain finished product transmittance 90% at last, do not reach the requirement of transmittance 95%.US5776740 has introduced the method for the synthetic L-tryptophane of chemical method; US5756345 is the Escherichia coli fermentation method, and US 5624828 and US 5605818 also are the fermentation using bacteria methods, have simply set forth thick extracting method.
Domestic patent specification is rare mentioning aspect refining high-quality tryptophane, ZL200710068130.9 has announced the leaching process from fermenting to concentrating, ZL97113051.5 directly sprays the method that dry granulation is made additive from fermented liquid, and ZL96197716 is that Japanese aginomoto is about the patent of fermented bacterium preparation.Patent specification ZL200810065762.4 is with the charcoal absorption of tryptophane solution after with activation, filters back substep condensing crystal, can obtain transmittance and be higher than 95% product.But this method complex steps, not only gac needs multistep to handle, and also will divide and carry out condensing crystal several times, and the utmost point is not easy to suitability for industrialized production.And it requires more than 95% content in crude product, has reduced the scope of application of extracting purification technique.
Summary of the invention
The purpose of this invention is to provide the method that a kind of simple and effective prepares the high transmission rate tryptophane, the tryptophane product that this method obtains meets every indexs such as transmittance 95% of medicinal grade standard regulation in 2010 editions pharmacopeia.
For achieving the goal, the present invention has adopted following technical scheme:
A kind of preparation method of high transmission rate tryptophane may further comprise the steps:
Step 1, the crude product tryptophane is added in the mixed dissolution liquid, heating makes its whole dissolvings, add charcoal absorption half an hour after, remove by filter gac, carry out membrane filtration with filter membrane again, wherein mixed dissolution liquid is the mixed solution of purified water, lower aliphatic alcohols or lower aliphatic ketone and lower fatty acid;
Step 2, with filtrate slowly crystallization under agitation, and use physical method further cooling make its sufficient crystallising;
Step 3, crystal solution filtered the white crystal obtain through fully washing, filter again after regulating pH value, dry pure product;
Wherein, mother liquor can recycle.
As preferably, the crude product tryptophane described in the step 1 is solid or liquid state, obtains via fermentation or building-up process, does not wherein contain fermentation mycelium, and content is at 30 weight %-100 weight %.
Further, the consumption of the crude product tryptophane described in the step 1 is for can form the settled solution that weight concentration is the 30-75 grams per liter.
Further, the ratio of mixed dissolution liquid consumption is in the step 1, lower aliphatic alcohols or lower aliphatic ketone: lower fatty acid=2-7: 1; Lower aliphatic alcohols or lower aliphatic ketone: water=0.5-5: 1.
Further, lower aliphatic alcohols described in the step 1 or lower aliphatic ketone are ethanol, Virahol or acetone; Lower fatty acid is formic acid, acetic acid or propionic acid.
Further, mixed dissolution reagent that liquid adds can mix in advance in the step 1, also can add respectively, and not have the sequencing requirement, can arrange according to the physical device situation.
Further, the temperature of heating for dissolving described in the step 1 is 30-70 ℃, makes dissolving crude product and does not destroy the tryptophane component.
Further, adding gac in the step 1 is that gac is used in general industry production, and it goes without doing, and handle any early stage, and according to crude product tryptophane difference, consumption is 1 weight %-10 weight % of add crude product weight.
Further, the time of crystallisation process described in the step 2 is at 2-5 hour, and further the outlet temperature of cooling is down to-10 ℃-10 ℃.
Further, described in the step 3 fully washing comprise washing and mixing solutions is washed step.
Further, mixing solutions described in the step 3 is the mixing solutions of lower aliphatic alcohols or lower aliphatic ketone and water, and blending ratio is 0.1-3.5: 1.
Further, the pH value of adjusting described in the step 3 refers to be alkaline matter pH value is transferred to 5-8.
Further, the described alkaline matter that is is sodium hydroxide or ammoniacal liquor.
Further, drying process described in the step 3 refers to wet product are put into air dry oven or vacuum drying oven, or mixes slurry and carry out drying with the dried tower of spray.
Further, described recycle refers to water that mother liquor distillation is obtained and the mixing solutions of alcohol or ketone, measures wherein alcohol or ketone concentration, reuses when the next batch purifying.
A kind of preparation method of high transmission rate tryptophane is characterized in that, may further comprise the steps:
Step 1: the crude product tryptophane adds water in the mixed dissolution liquid with lower aliphatic alcohols or lower aliphatic ketone, add acetic acid, be heated to and make its whole dissolvings more than 30 ℃, forming concentration is the solution of 30-75 grams per liter, the 1 weight %-10 weight % that presses tryptophane weight adds gac, whip attachment removes by filter gac after half an hour under keeping warm mode, carries out membrane filtration with millipore filtration again;
Step 2: filtrate is slow decrease temperature crystalline under agitation, and uses water-bath, ice bath further to be cooled to about-5 ℃-10 ℃, makes its sufficient crystallising, and temperature-fall period is more than 2 hours;
Step 3: crystal solution is filtered the white crystal that obtains, fully wash with purified water, mixing solutions respectively, ammoniacal liquor is regulated pH value and is filtered again to the 4-9 and drain, put into vacuum drying oven, 30 ℃ of-90 ℃ of dryings got pure product in 3 hours, wherein mixing solutions is the mixing solutions of lower aliphatic alcohols or lower aliphatic ketone and water, and blending ratio is 0.1-3.5: 1;
Step 4: mother liquor obtains the mixing solutions of lower aliphatic alcohols or lower aliphatic ketone and water through distillation, measures wherein lower aliphatic alcohols or lower aliphatic ketone concentration, recycle.
Solvent used herein is single, does not need independent recovery, can will reuse after the mother liquor simple process, does not cause any three-waste pollution; Used gac need not activation, and the market is namely available, saves cost and time; Do not have enrichment step, reduced the requirement to power system, be easy to realize suitability for industrialized production.
Embodiment
Embodiment one:
The tryptophane crude product 50g of content 95%, transmittance 38%, add Virahol 280ml, formic acid 50ml, water 503.33ml is heated to 50 ℃ and makes its whole dissolvings, and forming concentration is the solution of 60g/L, add the 2.5g gac, whip attachment removes by filter gac after half an hour under keeping warm mode, carries out membrane filtration with 0.5 μ m millipore filtration again;
Filtrate is slow decrease temperature crystalline under agitation, and further is cooled to about 0 ℃, makes its sufficient crystallising, and temperature-fall period amounts to three hours;
Crystal solution is filtered the white crystal that obtains, and filters again after fully washing, regulating pH value and drains, and puts into vacuum drying oven, and drying got pure product in 3 hours.Yield 78%, tryptophane 99%, transmittance 97%, other indexs are qualified.
Embodiment two:
The tryptophane crude product 50g of content 89%, transmittance 32%, add propyl alcohol 350ml, acetic acid 200ml, water 219.23ml is heated to 70 ℃ and makes its whole dissolvings, and forming concentration is the solution of 65g/L, add the 3g gac, whip attachment removes by filter gac after half an hour under keeping warm mode, carries out membrane filtration with 0.5 μ m millipore filtration again;
Filtrate is slow decrease temperature crystalline under agitation, and uses waters, ice territory further to be cooled to about 5 ℃, makes its sufficient crystallising, and temperature-fall period amounts to three hours;
The white crystal that the crystal solution filtration obtains filters again after fully washing, ammoniacal liquor are regulated pH value and drains, and puts into vacuum drying oven, and drying got pure product in 3 hours.Yield 71%, tryptophane 98%, transmittance 95%, other indexs are qualified.
Embodiment three:
The tryptophane crude product 50g of content 98%, transmittance 39%, add acetone 100ml, propionic acid 50ml, water 961.11ml is heated to 50 ℃ and makes its whole dissolvings, and forming concentration is the solution of 45g/L, add the 2g gac, whip attachment removes by filter gac after half an hour under keeping warm mode, carries out membrane filtration with 0.5 μ m millipore filtration again;
Filtrate is slow decrease temperature crystalline under agitation, and uses waters, ice territory further to be cooled to about 0 ℃, makes its sufficient crystallising, and temperature-fall period amounts to three hours;
The white crystal that the crystal solution filtration obtains filters again after fully washing, ammoniacal liquor are regulated pH value and drains, and puts into vacuum drying oven, and drying got pure product in 3 hours.Yield 82%, tryptophane 99%, transmittance 95%, other indexs are qualified.
Embodiment four:
Present embodiment is used for the mother liquor of explanation recycle.Mother liquor 800ml is at 50 ℃, and vacuum-0.1MPa rotary evaporation concentrates, and steams the mixing solutions of 650ml acetone and water, checks acetone concentration 28%.Crystallization appears in dense back mother liquor, uses as crude product behind the filtration drying.
Claims (8)
1. the preparation method of a high transmission rate tryptophane is characterized in that, may further comprise the steps:
Step 1, the crude product tryptophane is added in the mixed dissolution liquid, heating makes its whole dissolvings, add charcoal absorption half an hour after, remove by filter gac, carry out membrane filtration with filter membrane again, wherein mixed dissolution liquid is the mixed solution of purified water, lower aliphatic alcohols or lower aliphatic ketone and lower fatty acid;
Step 2, with filtrate slowly crystallization under agitation, and use physical method further cooling make its sufficient crystallising;
Step 3, crystal solution filtered the white crystal obtain through fully washing, filter again after regulating pH value, dryly get pure product;
Wherein, mother liquor energy recycle;
Crude product tryptophane described in the step 1 is solid or liquid state, obtains via fermentation or building-up process, does not wherein contain fermentation mycelium, and content is at 30 weight %-100 weight %; Its consumption is for can form the settled solution that weight concentration is the 30-75 grams per liter; The ratio of mixed dissolution liquid consumption is lower aliphatic alcohols or lower aliphatic ketone: lower fatty acid=2-7: 1; Lower aliphatic alcohols or lower aliphatic ketone: water=0.5-5: 1; Described lower aliphatic alcohols or lower aliphatic ketone are ethanol, Virahol or acetone; Lower fatty acid is formic acid, acetic acid or propionic acid; Mixed dissolution reagent that liquid adds can mix in advance, also can add respectively, and not have the sequencing requirement, can arrange according to the physical device situation; Described heating for dissolving temperature is 30-70 ℃, makes dissolving crude product and does not destroy the tryptophane component;
The time of crystallisation process described in the step 2, further the outlet temperature of cooling was down to-10 ℃-10 ℃ at 2-5 hour.
2. the preparation method of tryptophane according to claim 1, it is characterized in that: adding gac in the step 1 is general industry production gac, and it goes without doing, and handle any early stage, and according to crude product tryptophane difference, consumption is 1 weight %-10 weight % of add crude product weight.
3. the preparation method of tryptophane according to claim 1, it is characterized in that: abundant washing described in the step 3 comprises washing and mixing solutions is washed step, wherein said mixing solutions is the mixing solutions of lower aliphatic alcohols or lower aliphatic ketone and water, and blending ratio is 0.1-3.5: 1.
4. the preparation method of tryptophane according to claim 1 is characterized in that: regulate the pH value described in the step 3 and refer to be alkaline matter the pH value is transferred to 5-8.
5. the preparation method of tryptophane according to claim 4, it is characterized in that: the described alkaline matter that is is sodium hydroxide or ammoniacal liquor.
6. the preparation method of tryptophane according to claim 1, it is characterized in that: drying process described in the step 3 refers to wet product are put into air dry oven or vacuum drying oven, or mixes slurry and carry out drying with spraying dried tower.
7. the preparation method of tryptophane according to claim 1 is characterized in that: described recycle refers to water that the mother liquor distillation is obtained and the mixing solutions of alcohol or ketone, measures wherein alcohol or ketone concentration, reuses when the next batch purifying.
8. the preparation method of a high transmission rate tryptophane is characterized in that, may further comprise the steps:
Step 1: the crude product tryptophane adds water in the mixed dissolution liquid with lower aliphatic alcohols or lower aliphatic ketone, add acetic acid, be heated to and make its whole dissolvings more than 30 ℃, forming concentration is the solution of 30-75 grams per liter, the 1 weight %-10 weight % that presses tryptophane weight adds gac, whip attachment removes by filter gac after half an hour under keeping warm mode, carries out membrane filtration with millipore filtration again;
Step 2: filtrate is slow decrease temperature crystalline under agitation, and uses water-bath, ice bath further to be cooled to about-5 ℃-10 ℃, makes its sufficient crystallising, and temperature-fall period is more than 2 hours;
Step 3: crystal solution is filtered the white crystal that obtains, fully wash with purified water, mixing solutions respectively, ammoniacal liquor is regulated the pH value and is filtered again to the 4-9 and drain, put into vacuum drying oven, 30 ℃ of-90 ℃ of dryings got pure product in 3 hours, wherein mixing solutions is the mixing solutions of lower aliphatic alcohols or lower aliphatic ketone and water, and blending ratio is 01-3.5: 1;
Step 4: mother liquor obtains the mixing solutions of lower aliphatic alcohols or lower aliphatic ketone and water through distillation, measures wherein lower aliphatic alcohols or lower aliphatic ketone concentration, recycle.
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| Application Number | Priority Date | Filing Date | Title |
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| CN 201010603780 CN102146052B (en) | 2010-12-24 | 2010-12-24 | Method for preparing tryptophan |
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| CN 201010603780 CN102146052B (en) | 2010-12-24 | 2010-12-24 | Method for preparing tryptophan |
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| CN102146052B true CN102146052B (en) | 2013-08-21 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN103044309A (en) * | 2012-09-07 | 2013-04-17 | 赵立地 | Method for purifying tryptophan |
| JP6303017B2 (en) | 2014-01-07 | 2018-03-28 | ノヴァセプ プロセスＮｏｖａｓｅｐ Ｐｒｏｃｅｓｓ | Method for purifying aromatic amino acids |
| CN104829519A (en) * | 2015-05-15 | 2015-08-12 | 南通荣泰生物科技有限公司 | Purification process of L-tryptophan |
| CN105061289B (en) * | 2015-07-28 | 2017-11-17 | 蚌埠丰原医药科技发展有限公司 | A kind of method for preparing pharmaceutical grade L tryptophans |
| CN105481749B (en) * | 2015-12-10 | 2017-12-08 | 河南巨龙生物工程股份有限公司 | A kind of method for efficiently removing impurity in tryptophan zymotic fluid |
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| DE2850074A1 (en) * | 1978-11-18 | 1980-05-22 | Degussa | METHOD FOR PURIFYING TRYPTOPHANE AND DERIVATIVES OF TRYPTOPHANE |
| ITFI20040063A1 (en) * | 2004-03-19 | 2004-06-19 | Biosphere S P A | TRIPTOFANO PURIFICATION PROCESS |
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