CN101817762B - Preparation method of L-glutamine nitrate - Google Patents
Preparation method of L-glutamine nitrate Download PDFInfo
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- CN101817762B CN101817762B CN 201010172387 CN201010172387A CN101817762B CN 101817762 B CN101817762 B CN 101817762B CN 201010172387 CN201010172387 CN 201010172387 CN 201010172387 A CN201010172387 A CN 201010172387A CN 101817762 B CN101817762 B CN 101817762B
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Abstract
The invention discloses a preparation method of L-glutamine nitrate, comprising the following steps of: adding nitric acid into L-glutamine while stirring under the temperature of 10 to 25 DEG C, wherein the mol ratio of the L-glutamine to the nitric acid is 1: 1-1.1; gradually clarifying the solution at the reaction temperature of 40 to 60 DEG C; regulating the pH value of the solution to be 1 to 2 by using the nitric acid; then adding ethanol into a decompressed and dehydrated reactant, wherein the weight ratio of the L-glutamine to the ethanol is 1:1; evenly stirring, gradually cooling to 10 to 25 DEG C, and carrying out solid-liquid separation on precipitated crystals; drying the crystals at 60 to 70 DEG C to obtain an L-glutamine nitrate finished product; taking liquid subjected to solid-liquid separation as a mother solution, and continuously recycling. By adopting the reaction of the food-grade L-glutamine and the chemical-reagent-grade nitric acid under the ordinary pressure, the invention has mild reaction conditions as well as reasonable and simple process and can be suitable for industrial large production. The product prepared by adopting the preparation method has good quality, high purity up to more than 99 percent and high yield coefficient up to more than 95 percent.
Description
Technical field
The invention belongs to the preparation method of a seed amino acid nitrate, specifically is a kind of good product quality, yield height, the preparation method of L-glutaminate nitrate that cost is low.
Background technology
Amino acid is the base substance that constitutes the Animal nutrition desired protein.General people self generate or can obtain to satisfy by food each seed amino acid of somagenic need.But under the special situation as under the situation of sick, injured or large amount of exercise exercise, in order to recover the balance of various metabolism in the body, strengthening immunity and sportsmen increase muscle strength and regain one's strength as early as possible, just need extra additional each seed amino acid.
L-glutaminate (glutamine) another name: L-L-glutamic acid-5-acid amides; The L-glutamine.It is the 5-position acid amides of L-L-glutamic acid.Naturally occurring glutamine is the L type, is neutral non-toxic substance, easily permeate through cell membranes.The ammonia that organism intracellular metabolite process produces toxic property generally is combined the formation glutamine by glutamine synthetase catalysis with L-glutamic acid, be transported to liver with the glutamine form by blood, resolve into L-glutamic acid and ammonia through enzyme catalysis, again through ornithine cycle, making ammonia be converted into nontoxic urea and excrete, therefore is the main types of transportation of ammonia in the organism.
L-glutaminate is the rich in amino acid of people's in-vivo content, accounts for 60% of the whole free amino acids of skeletal muscle, accounts for 20% of whole body.Usually L-glutaminate is mainly synthetic in muscle, liver, and the normal function of intestinal cells, nephrocyte, immunocyte need be kept by consuming L-glutaminate.Additional L-glutaminate can improve the self-sow hormonal readiness in the human body, suppresses mytolin and decomposes the Synthesis that helps to alleviate sore muscle and repair the further strengthen muscle of muscle injury.Simultaneously, owing to guaranteed the supply of immunocyte L-glutaminate, thus guaranteed the function of immunocyte, improve human motion ability and immunologic function, reduce the incidence of infectious diseases.In addition, immediate postexercise is united and is replenished the recovery that L-glutaminate and carbohydrate are conducive to muscle glycogen.
L-glutaminate is not indispensable amino acid, and it can be synthesized by L-L-glutamic acid, L-Xie Ansuan, L-Isoleucine in human body.Sick and wounded, nutritional status is not good or stress situation such as high-intensity exercise under, body increases the demand of glutamine, so that self synthetic can not satisfying the demand, and needs external complement.
L-glutaminate is one of constituent of gastrointestinal mucosal albumen.It is the active drug for the treatment of intestine gastric ulcer.L-alanyl L-glutamy is the drug of first choice for the treatment of stomach ulcer and duodenal ulcer.It can promote metabolism by hemato encephalic barrier, improves the brain function, is the important nutrition agent of brain metabolism.Be usually used in the gastrointestinal ulceration reparation, aspects such as children ' s intelligence development is bad, alcoholism, epileptics, human brain function recovery.
The U.S. parties concerned discover that amino acid whose nitrate more is conducive to the amino acid absorption in vivo recently, therefore L-glutaminate are made into L-glutaminate nitrate, with the easier L-glutaminate that changes into, are absorbed by health.Dosage can be littler when therefore it used, and oral absorption efficient can be higher.But the producer that does not also have suitability for industrialized production L-glutaminate nitrate product at present in the world.
Summary of the invention
Be to solve the problem of L-glutaminate nitrate large-scale production, the invention provides a kind of can suitability for industrialized production and yield height, the preparation method of the glutamine nitrate that product purity is high.
The technical solution used in the present invention is: in 1. stirring under 10 ℃～25 ℃ temperature nitric acid is joined in the L-glutaminate, the mol ratio of L-glutaminate and nitric acid is 1: 1～1.1; Temperature of reaction is at 40 ℃～65 ℃, and solution is clarified gradually; Be 1～2 with nitric acid regulator solution pH; Add ethanol in the solution behind the decompression dehydration subsequently, the weight ratio of L-glutaminate and ethanol is 1: 1; Stir, progressively be cooled to 10 ℃～25 ℃, solid-liquid separation is carried out in the crystallization of separating out; 60 ℃～70 ℃ dryings of crystallisate get L-glutaminate nitrate finished product, and the liquid after the solid-liquid separation is that mother liquor continues to recycle; 2. in stirring under 10 ℃～25 ℃ temperature L-glutaminate joined in the mother liquor that 1. step produce, stir, add nitric acid, the mol ratio of L-glutaminate and nitric acid is 1: 1～1.1; Temperature of reaction is at 40 ℃～65 ℃, and solution is clarified gradually; Be 1～2 with nitric acid regulator solution pH; Add ethanol in the solution behind the decompression dehydration subsequently, the weight ratio of L-glutaminate and ethanol is 1: 1; Stir, be cooled to 10 ℃～25 ℃ gradually, solid-liquid separation is carried out in the crystallization of separating out; 60 ℃～70 ℃ dryings of crystallisate get L-glutaminate nitrate finished product, and the liquid after the solid-liquid separation is that mother liquor continues to recycle.
The preparation method of described L-glutaminate nitrate: 1. in the time of 20 ℃ ± 2 ℃ nitric acid is joined in the L-glutaminate, the mol ratio of L-glutaminate and nitric acid is 1: 1; Temperature of reaction is at 55 ℃ ± 5 ℃, and solution is clarified gradually, is 2 with nitric acid regulator solution pH; Add ethanol in the solution behind the decompression dehydration subsequently, the weight ratio of L-glutaminate and ethanol is 1: 1; Stir, be cooled to 20 ℃ ± 2 ℃ gradually, solid-liquid separation is carried out in the crystallization of separating out; 60 ℃～70 ℃ dryings of crystallisate get L-glutaminate nitrate finished product.Liquid after the solid-liquid separation is that mother liquor continues to recycle.2. in stirring under 20 ℃ ± 2 ℃ temperature L-glutaminate joined in the mother liquor that 1. step produce, stir, add nitric acid, the mol ratio of L-glutaminate and nitric acid is 1: 1; Temperature of reaction is 55 ℃ ± 5 ℃, and solution is clarified gradually, is 2 with nitric acid regulator solution pH; Add ethanol in the solution behind the decompression dehydration subsequently, the weight ratio of L-glutaminate and ethanol is 1: 1; Stir, be cooled to 20 ℃ ± 2 ℃ gradually, solid-liquid separation is carried out in the crystallization of separating out; 60 ℃～70 ℃ dryings of crystallisate get L-glutaminate nitrate finished product, and the liquid after the solid-liquid separation is that mother liquor continues to recycle.
Above-mentioned steps 1. middle decompression dehydration amount is moisture contained in the nitric acid, and step 2. middle decompression dehydration amount is the weight of mother liquor.
The temperature of decompression is below 65 ℃, and pressure is more than 500 mmhg.
1. and 2. step adds concentration of ethanol more than 95% in.
Advantage and positively effect that the present invention has are: the present invention adopts L-glutaminate and nitric acid to react the reaction conditions gentleness under normal pressure.The raw material that the present invention adopts is L-glutaminate and the highly purified nitric acid of food grade, so the good product quality of producing, impurity is few, just reach more than 99% without recrystallization purity, both guarantee quality, saved operation and production time again, improved production efficiency.The mother liquor that produces when utilization of the present invention is produced first recycles repeatedly, has improved the yield of product, reaches more than 98%.Reduced cost.Preparation were established of the present invention rationally, simply is fit to industrialized production.
Embodiment
The present invention has adopted high-quality raw material for the quality that guarantees L-glutaminate nitrate, the L-glutaminate of instant grade and the nitric acid of chemical reagent-grade, impurities is few in the raw material, the L-glutaminate nitrate good product quality that assurance is produced just reaches more than 99% without recrystallization purity.
The mol ratio of L-glutaminate and nitric acid is 1: 1 among the preparation method of the present invention, but for L-glutaminate is reacted completely, the comparable L-glutaminate of the input amount of nitric acid is more bigger.Scope is 1～1.1.The concentration of nitric acid that the present invention adopts is 65～68%, for guarantee and the mol ratio of 1 mole of L-glutaminate substantially between 1 to 1.1 mole, the add-on of nitric acid is along with the concentration difference has certain variation.
Because the solubleness of L-glutaminate in water is big, the water in the nitric acid just can be molten entirely with L-glutaminate, and therefore reaction need not add water.The reaction of L-glutaminate and nitric acid is thermopositive reaction, avoids reaction violent in order to allow, and it is too fast to heat up, and untimely the causing of dispel the heat caught fire, and should control the speed that nitric acid adds, and reacts that temperature must be between 10 ℃～25 ℃ when beginning, preferably 20 ℃ ± 2 ℃.Because the low temperature effect speed of response, in order to add fast response, add the temperature of the back rising reaction soln that finishes at nitric acid, general temperature is preferably in 55 ℃ ± 5 ℃ below 65 ℃.Temperature of reaction can not surpass 65 ℃, otherwise L-glutaminate can be damaged, and influences the yield of final product.Along with temperature raises, speed of response is accelerated, and solution is more and more clarified, and stirs all the time in this process, makes reactant distribution even, and reaction is accelerated.Reaction finishes when solution is clarified fully.Along with temperature raises, speed of response is accelerated, and solution is more and more clarified, and clarifies fully to solution.This moment, reaction finished.
It is acid that product L-glutaminate nitrate of the present invention is, and pH should be 2.Generally finishing before measurement pH in reaction, if acidity is little, drip nitric acid, is 2 with nitric acid control pH value of solution, because the mol ratio of nitric acid is slightly larger than L-glutaminate when producing, so if pH allows, can not influence quality product between 2 and 1.
Because the solubleness of L-glutaminate in ethanol is very little, so utilize alcohol to analyse L-glutaminate nitrate is separated.Determined that by product property and industrial production cost alcohol of the present invention is analysed employing is ethanol more than 95%, is preferably dehydrated alcohol.The weight ratio of L-glutaminate and ethanol is 1: 1.Separate out in order to accelerate crystallization, adopt and reduce method of temperature, cooling temperature is 10 ℃～25 ℃.The present embodiment cooling temperature is at 20 ℃ ± 2 ℃.
In order to guarantee alcohol concn, need after reaction finishes, moisture (mother liquor) be removed, be with the moisture removal in the nitric acid when producing first, producing later on is that the mother liquor that will add is removed.Dehydration method of the present invention is not limit, and embodiment adopts the decompression method that water and mother liquor are separated.The temperature of decompression dehydration is 50 ℃～65 ℃, and vacuum tightness is more than 500 mmhg.
The present invention to separation method without limits, the method that every suitable L-glutaminate nitrate separates can be used, the present invention adopts centrifugal method to carry out solid-liquid separation.
The present invention to the method for drying without limits, the method for every suitable L-glutaminate nitrate drying can be used, dry temperature can not surpass 70 ℃, otherwise L-glutaminate nitrate can decompose, quality is affected.
The present invention is because the solubleness of L-glutaminate nitrate in reaction soln is big, after separating, crystallisate also contains many L-glutaminate nitrate in the remaining mother liquor, therefore mother liquor can continue to recycle, yield has only more than 30% when producing so first, but yield can reach nearly 100% when utilizing mother liquor to produce later on.Greatly improved productivity.
For further understanding summary of the invention of the present invention, characteristics and effect, enumerate following examples now and be described in detail as follows:
Embodiment 1
In container, pour the double centner L-glutaminate into, in the time of 20 ℃ ± 2 ℃, add 66 kilogram 66% nitric acid while stirring, mix.Progressively heat to 55 ℃ ± 5 ℃ after adding nitric acid, solution is clarified gradually along with temperature raises.Detecting pH, is 2 with nitric acid regulator solution pH.Solution clarification back is at 50 ℃ of decompression dehydrations, and vacuum tightness is more than 500 mmhg.Add the double centner dehydrated alcohol in the solution after the dehydration, stir.Reduce the temperature to 21 ℃ ± 2 ℃ gradually, crystallisate occurs, crystallisate is separated with centrifugal.70 ℃ of dryings of isolated crystallisate get L-glutaminate nitrate finished product.Liquid continues to recycle as mother liquor.
Embodiment 2
Add the double centner L-glutaminate in the about double centner mother liquor that produces in the embodiment 1 under 20 ℃ ± 2 ℃ conditions, the nitric acid of 66 kilogram 66% of the back adding of stirring mixes.Progressively heat to 45 ℃ ± 5 ℃ after adding nitric acid, solution detects pH along with the temperature clarification gradually that raises, and is 2 with the pH of nitric acid regulator solution.Solution clarification back is at 60 ℃ of decompression dehydration double centners, and vacuum tightness is more than 500 mmhg.Add 100 gram dehydrated alcohols in the solution after the dehydration.Stir, reduce the temperature to 18 ℃ ± 2 ℃ gradually, crystallisate occurs, crystallisate is separated with centrifugal, 65 ℃ of dryings of isolated crystallisate get L-glutaminate nitrate finished product.Liquid continues to recycle repeatedly as mother liquor,
Embodiment 3
Add the double centner L-glutaminate in the about double centner mother liquor that produces in the embodiment 2 under 20 ℃ ± 2 ℃ conditions, the nitric acid of 66 kilogram 66% of the back adding of stirring mixes.Control nitric acid adds speed and temperature of reaction, makes temperature of reaction reach 40 ℃ gradually, need not heat the outside, and solution detects pH along with stirring clarification gradually, is 2 with the pH of nitric acid regulator solution.Solution clarification back is at 55 ℃ of decompression dehydration double centners, and vacuum tightness is more than 500 mmhg.Add 100 gram dehydrated alcohols in the solution after the dehydration.Stir, after reduce the temperature to 13 ℃ ± 2 ℃, engender crystallisate, crystallisate is separated with centrifugal, the isolated L-glutaminate nitrate 60 ℃ of dryings of product that wet get L-glutaminate nitrate finished product.Liquid continues to recycle repeatedly as mother liquor.
Claims (5)
1. the preparation method of a L-glutaminate nitrate is characterized in that: in 1. stirring under 10 ℃ ~ 25 ℃ temperature nitric acid is joined in the L-glutaminate, the mol ratio of L-glutaminate and nitric acid is 1:1 ~ 1.1; Temperature of reaction is at 40 ℃ ~ 60 ℃, and solution is clarified gradually; Be 1 ~ 2 with nitric acid regulator solution pH; Add ethanol in the reactant behind the decompression dehydration subsequently, the weight ratio of L-glutaminate and ethanol is 1:1; Stir, be cooled to 10 ℃ ~ 25 ℃ gradually, solid-liquid separation is carried out in the crystallization of separating out; 60 ℃ ~ 70 ℃ dryings of crystallisate get L-glutaminate nitrate finished product; Liquid after the solid-liquid separation is that mother liquor continues to recycle; 2. in stirring under 10 ℃ ~ 25 ℃ temperature L-glutaminate joined in the mother liquor that 1. step produce, stir, add nitric acid, the mol ratio of L-glutaminate and nitric acid is 1:1 ~ 1. 1; Temperature of reaction is at 40 ℃ ~ 60 ℃, and solution is clarified gradually; Be 1 ~ 2 with nitric acid regulator solution pH; Add ethanol in the solution behind the decompression dehydration subsequently, the weight ratio of L-glutaminate and ethanol is 1:1; Stir, be cooled to 10 ℃ ~ 25 ℃ gradually, solid-liquid separation is carried out in the crystallization of separating out; 60 ℃ ~ 70 ℃ dryings of crystallisate get L-glutaminate nitrate finished product, and the liquid after the solid-liquid separation is that mother liquor continues to recycle.
2. the preparation method of L-glutaminate nitrate according to claim 1 is characterized in that: 1. when 2 ℃ of 20 ℃ of scholars nitric acid is joined in the L-glutaminate, the mol ratio of L-glutaminate and nitric acid is 1:1; Temperature of reaction is 5 ℃ of 55 ℃ of scholars, and solution is clarified gradually, is 2 with nitric acid regulator solution pH; Add ethanol in the solution behind the decompression dehydration subsequently, the weight ratio of L-glutaminate and ethanol is 1:1; Stir, be cooled to 2 ℃ of 20 ℃ of scholars gradually, crystallization occurs, solid-liquid separation is carried out in the crystallization of separating out; 60 ℃ ~ 70 ℃ dryings of crystallisate get L-glutaminate nitrate finished product, and the liquid after the solid-liquid separation is that mother liquor continues to recycle; 2. in stirring under 2 ℃ of temperature of 20 ℃ of scholars L-glutaminate joined in the mother liquor that 1. step produce, stir, add nitric acid, the mol ratio of L-glutaminate and nitric acid is 1:1; Temperature of reaction is 5 ℃ of 55 ℃ of scholars, and solution is clarified gradually, is 2 with nitric acid regulator solution pH; Add ethanol in the solution behind the decompression dehydration subsequently, the weight ratio of L-glutaminate and ethanol is 1:1; Stir, be cooled to 2 ℃ of 20 ℃ of scholars gradually, solid-liquid separation is carried out in the crystallization of separating out; 60 ℃ ~ 70 ℃ dryings of crystallisate get L-glutaminate nitrate finished product, and the liquid after the solid-liquid separation is that mother liquor continues to recycle.
3. according to the preparation method of claim 1 or the described L-glutaminate nitrate of claim 2, it is characterized in that the decompression dehydration amount is moisture contained in the nitric acid during step 1.; Step 2. middle decompression dehydration amount is the weight of mother liquor.
4. the preparation method of L-glutaminate nitrate according to claim 3, the temperature that it is characterized in that decompression dehydration is 50 ℃ ~ 60 ℃, vacuum tightness is more than 500 mmhg.
5. according to the preparation method of claim 1 or the described L-glutaminate nitrate of claim 2, it is characterized in that step 1. and 2. in add concentration of ethanol more than 95%.
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| CN 201010172387 CN101817762B (en) | 2010-05-14 | 2010-05-14 | Preparation method of L-glutamine nitrate |
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Non-Patent Citations (2)
| Title |
|---|
| L-谷氨酰胺乙酯盐酸盐的合成;刘昭;《中国优秀硕士学位论文全文数据库工程科技Ⅰ辑》;20071015(第4期);第12页第1-2段 * |
| 刘昭.L-谷氨酰胺乙酯盐酸盐的合成.《中国优秀硕士学位论文全文数据库工程科技Ⅰ辑》.2007,(第4期),第12页第1-2段. |
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