CN1184193C - Film technological extracting method for L-phenylalanine - Google Patents
Film technological extracting method for L-phenylalanine Download PDFInfo
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- CN1184193C CN1184193C CNB021572127A CN02157212A CN1184193C CN 1184193 C CN1184193 C CN 1184193C CN B021572127 A CNB021572127 A CN B021572127A CN 02157212 A CN02157212 A CN 02157212A CN 1184193 C CN1184193 C CN 1184193C
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
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Abstract
The present invention relates to a film technology separating and extracting method for L-phenylalanine which is used as a medicinal intermediate body. In the preparing process of L-phenylalanine solution by a phenylphruvic acid enzyme method, the present invention makes use of the following film separation technique: the removal of thalluses and cell debris, the ultra-filtration and the removal of hybridprotein, nanofiltration, desalination, decolorization and condensation; goal products are separated and extracted, and the extraction yield of the L-phenylalanine is greater than 85%. Compared with ion exchange and the precipitation extraction method of metal salts, the extraction yield of the integral extraction process is obviously increased, and acid base, water and steam consumption used in the extraction process are greatly reduced.
Description
Technical field
The present invention relates to the membrane separation technique extracting method of medicine intermediate L-phenylalanine, promptly prepare the L-phenylalanine and transform solution, utilize membrane separation process to realize high yield, the less energy-consumption separation and Extraction of L-phenylalanine at enzyme process.
Background technology
The L-phenylalanine promptly is one of eight kinds of indispensable amino acids.This amino acid is mainly used in: (1) as foodstuff additive or additive synthesis material, promptly is the L-phenylalanine as one of main raw material of new type of health type sweeting agent aspartame; (2) as medical material, as synthesis material of amino acid transfusion, amino acids cancer therapy drug and antiviral etc.Wherein aspartame has obtained using widely at food, beverage industry as nineteen nineties world market popular sweetener product the most, becomes the most basic power that stimulates L-phenylalanine rush of demand.
The suitability for industrialized production route of L-phenylalanine mainly contains fermentation method and enzyme process (cinnamic acid enzymatic and phenyl-pyruvic acid enzyme process).Fermentation method mainly comprises general fermentation method and genetic engineering fungus fermentation method: general fermentation method is because the pathways metabolism of microorganism itself is comparatively complicated, therefore the fermentation production rate of bacterial strain is generally lower, low and the refining cost of product separation is too high to the utilization ratio of matrix, therefore verifiedly can't carry out suitability for industrialized production; Genetic engineering fungus fermentation method is produced, because the plasmid stability of entrained target gene is relatively poor usually, the fermentation production rate fluctuation is bigger, therefore from production cost is higher in general.Production by Enzymes L-phenylalanine is because of having advantages such as production concentration height, purification step is few, throughput is strong, it is the main production route of at present domestic and international L-phenylalanine, be cinnamic acid enzymatic and phenyl-pyruvic acid enzyme process, the phenyl-pyruvic acid enzyme process no matter in technology, still aspect production cost and the project investment, compare with the cinnamic acid enzymatic route and to have bigger advantage, so the phenyl-pyruvic acid enzyme process is thought direct and the most most economical L-phenylalanine production method by industrial research department both at home and abroad.
In phenyl-pyruvic acid enzymatic conversion method liquid, except that main components such as substrate phenyl-pyruvic acid, L-aspartic acid, target product L-phenylalanine and pyruvic acid, also have microorganism cells and plurality of impurities compositions such as fragment, foreign protein and partial pigment thereof, so the extraction process difficulty of L-phenylalanine is bigger.The extracting method of forefathers' report mainly contains:
1. ion exchange resin extraction method: under pH＜3 and pH＞10 situations, utilize the L-phenylalanine in Zeo-karb or the anionite-exchange resin absorption conversion fluid respectively, through alkalescence and acidic solution wash-out, the concentrated L-phenylalanine that obtains;
2. calcium salt precipitation method: utilize calcium ion (CaCl
2) and phenylalanine formation infusible precipitate, forming precipitation at pH8.5-11, the phenylalanine calcium salt obtains phenylalanine through hydrochloric acid neutralization, crystallization;
3. the zinc salt precipitator method: transfer pH value of solution 7-9 with sodium hydroxide, in solution, add the zinc sulfate solid and obtain phenylalanine zinc salt precipitation, in acid and crystallization obtain the L-phenylalanine;
But from operating procedure and extraction economic analysis, the equal defectiveness of above method.The activation of ion-exchange techniques resin, regeneration and cleaning need consume a large amount of soda acids, and required equipment and resin cost are higher simultaneously; The metal salt precipitate method all produces a large amount of salt and waste water, and the yield of Ti Quing (generally being lower than 80%) and the purity of product are lower simultaneously; Therefore develop high yield, L-phenylalanine extracting method seems very urgent to the industrialization that promotes the L-phenylalanine cheaply.
Summary of the invention
The objective of the invention is to improve extract yield, the reduction extraction cost of product, adopt membrane technique to carry out the extraction of L-phenylalanine.
Purpose of the present invention can reach by following measure:
In extracting method of the present invention, enzymatic conversion liquid at first utilizes inorganic ceramic film or organic membrane filter to remove microorganism cells and fragment thereof, utilize polysulfone membrane to carry out ultrafiltration then and remove foreign protein, obtain L-phenylalanine crystal through polysulfone membrane decolouring and desalination and concentration, crystallization.
Purpose of the present invention can also reach by following measure:
The material of inorganic ceramic film is aluminum oxide or zirconium white, and membrane pore size is 0.2-1 μ m.
Organic membrane selects for use polysulfone membrane to filter, and the membrane molecule amount is 30000-100000.
The utilization polysulfone membrane is carried out ultrafiltration and is removed foreign protein, and the membrane molecule amount is 5000-30000.
The employing molecular weight is that the polysulfone membrane of 1000-3000 is decoloured, and destainer is carried out the desalination concentration thereupon, and the polysulfone membrane molecular weight is 200-1000.
The present invention has following advantage compared to existing technology:
1. this extraction process all adopts the membrane technique separating technology, and is simple to operate and easily realize automatization, extract yield height, product purity height;
2. leaching process all adopts physical separation method, and soda acid, water and steam that process consumes are low, and the cost of extraction greatly reduces;
3. employing membrane separation process, film and support equipment long service life thereof, convenience for device maintenance, less investment.
Embodiment
Embodiment 1.
Get 10 liters enzymatic conversion method solution, the concentration of L-phenylalanine is 20 grams per liters, selects 0.1m for use
2Inorganic ceramic film filter 0.1MPa, 25 ℃, the transmittance that filters back solution is 86%, the material of mineral membrane is aluminum oxide or zirconium white, membrane pore size is 0.2-1 μ m.Filtered liquid utilizes polysulfone membrane to carry out the removal of foreign protein, the solution filter pressure is 0.15-0.25MPa, the membrane molecule amount is 5000-30000, obtain proteinic clearance and be first 11 liters of the extracting solutions of L-phenylalanine more than 95%, the concentration of L-phenylalanine is 17.6 grams per liters, and the yield of L-phenylalanine is 96.7%.
Embodiment 2.
Get 10 liters enzymatic conversion method solution, the concentration of L-phenylalanine is 20 grams per liters, selects for use polysulfone membrane to filter, and the transmittance of solution has reached 82%, and the membrane molecule amount is 30000-100000.Filtered liquid utilizes polysulfone membrane to carry out the removal of foreign protein, the solution filter pressure is 0.15-0.25MPa, the membrane molecule amount is 5000-30000, obtain proteinic clearance and be 94% L-phenylalanine, 12 liters of extracting solutions just, the concentration of L-phenylalanine is 16.2 grams per liters, and the yield of L-phenylalanine is 97.2%.
Embodiment 3
Getting 10 liters of the first extracting solutions (concentration of L-phenylalanine is 17.6 grams per liters) of embodiment 1, is filtering membrane with the polysulfone membrane, and the molecular weight of film is 1000-3000, under 1.5-3.5MPa, 25-40 ℃ condition, filter decolouring, the color decreasing ratio is more than 97%, and the yield of L-phenylalanine is 97.5%; Destainer is that 200-800 polysulfone membrane desalination and concentration is handled through molecular weight, the decreasing ratio of sodium-chlor is 91%, and solution is regulated pH5.0-6.0 with sodium hydroxide when being concentrated to the 50-70 grams per liter, crystalline deposit obtains L-phenylalanine crystal 159.1 grams, and purity is 96.7%.
Embodiment 4.
Getting 10 liters of the first extracting solutions (concentration of L-phenylalanine is 16.2 grams per liters) of example 2, is filtering membrane with the polysulfone membrane, and the molecular weight of film is 1000-3000, under 1.5-2.5MPa, 25-40 ℃ condition, filter decolouring, the color decreasing ratio is 96%, and the yield of L-phenylalanine is 96.2%; Destainer is that 200-800 polysulfone membrane desalination and concentration is handled through molecular weight, the decreasing ratio of sodium-chlor is 91%, and solution is regulated pH5.0-6.0 with sodium hydroxide when being concentrated to the 50-70 grams per liter, crystalline deposit obtains L-phenylalanine crystal 157.1 grams, and purity is 97.3%.
Claims (5)
1, a kind of membrane technique extracting method of L-phenylalanine, prepare in the enzymatic conversion liquid reaction system of L-phenylalanine at the phenyl-pyruvic acid enzyme process, adopt membrane technique to carry out the separation and Extraction of L-phenylalanine, it is characterized in that enzymatic conversion liquid at first utilizes inorganic ceramic film or organic membrane filter to remove microorganism cells and fragment thereof, utilize polysulfone membrane to carry out ultrafiltration then and remove foreign protein, obtain L-phenylalanine crystal through polysulfone membrane decolouring and desalination and concentration, crystallization.
2, the membrane technique extracting method of L-phenylalanine according to claim 1, the material that it is characterized in that inorganic ceramic film is aluminum oxide or zirconium white, membrane pore size is 0.2-1 μ m.
3, the membrane technique extracting method of L-phenylalanine according to claim 1 is characterized in that organic membrane selects for use polysulfone membrane to filter, and the membrane molecule amount is 30000-100000.
4, the membrane technique extracting method of L-phenylalanine according to claim 1 is characterized in that using polysulfone membrane to carry out ultrafiltration and removes foreign protein, and the membrane molecule amount is 5000-30000.
5, the membrane technique extracting method of L-phenylalanine according to claim 1, it is characterized in that adopting molecular weight is that the polysulfone membrane of 1000-3000 is decoloured, and destainer is carried out the desalination concentration thereupon, the polysulfone membrane molecular weight is 200-1000.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021572127A CN1184193C (en) | 2002-12-23 | 2002-12-23 | Film technological extracting method for L-phenylalanine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB021572127A CN1184193C (en) | 2002-12-23 | 2002-12-23 | Film technological extracting method for L-phenylalanine |
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| Publication Number | Publication Date |
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| CN1425645A CN1425645A (en) | 2003-06-25 |
| CN1184193C true CN1184193C (en) | 2005-01-12 |
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| Application Number | Title | Priority Date | Filing Date |
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| CNB021572127A Expired - Fee Related CN1184193C (en) | 2002-12-23 | 2002-12-23 | Film technological extracting method for L-phenylalanine |
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Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101709038A (en) * | 2009-11-18 | 2010-05-19 | 太仓市欣兰生物科技有限公司 | Method for extracting L-phenylalanine from fermentation broth |
| CN101773786B (en) * | 2009-12-17 | 2013-07-10 | 杭州天创环境科技股份有限公司 | Method for desalination and concentration of medical intermediate |
| CN102344383B (en) * | 2011-08-18 | 2014-05-14 | 丽珠集团福州福兴医药有限公司 | Method for concentrating and crystallizing L-phenylalanine |
| CN102659612A (en) * | 2012-05-10 | 2012-09-12 | 杭州蓝然环境技术有限公司 | Process for purifying L-phenylalanine |
| CN103193664B (en) * | 2013-05-08 | 2015-04-22 | 孟州市华兴有限责任公司 | Purifying method of L-phenylalanine |
| CN108504671A (en) * | 2018-03-28 | 2018-09-07 | 宁波市医疗中心李惠利医院 | A kind of PTEN-Long protein purifications preparation method |
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2002
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| CN1425645A (en) | 2003-06-25 |
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| EE01 | Entry into force of recordation of patent licensing contract |
Assignee: Jiangsu Han Kuang Biological Engineering Co., Ltd. Assignor: Nanjing University of Technology Contract fulfillment period: 2007.1.1 to 2014.12.31 contract change Contract record no.: 2009320001086 Denomination of invention: Film technological extracting method for L-phenylalanine Granted publication date: 20050112 License type: Exclusive license Record date: 2009.7.13 |
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Free format text: EXCLUSIVE LICENSE; TIME LIMIT OF IMPLEMENTING CONTACT: 2007.1.1 TO 2014.12.31; CHANGE OF CONTRACT Name of requester: JIANGSU HANGUANG BIO-ENGINEERING CO., LTD. Effective date: 20090713 |
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Granted publication date: 20050112 Termination date: 20100125 |