CN112979482B - High-purity L-valine as well as preparation method and application thereof - Google Patents
High-purity L-valine as well as preparation method and application thereof Download PDFInfo
- Publication number
- CN112979482B CN112979482B CN202110276027.3A CN202110276027A CN112979482B CN 112979482 B CN112979482 B CN 112979482B CN 202110276027 A CN202110276027 A CN 202110276027A CN 112979482 B CN112979482 B CN 112979482B
- Authority
- CN
- China
- Prior art keywords
- valine
- drying
- resin
- acid
- purity
- 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.)
- Active
Links
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 title claims abstract description 117
- 229960004295 valine Drugs 0.000 title claims abstract description 61
- 238000002360 preparation method Methods 0.000 title claims abstract description 7
- 239000011347 resin Substances 0.000 claims abstract description 58
- 229920005989 resin Polymers 0.000 claims abstract description 58
- 238000000034 method Methods 0.000 claims abstract description 30
- 239000013078 crystal Substances 0.000 claims abstract description 26
- 238000001035 drying Methods 0.000 claims abstract description 20
- 239000002253 acid Substances 0.000 claims abstract description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000001914 filtration Methods 0.000 claims abstract description 15
- 238000001816 cooling Methods 0.000 claims abstract description 12
- 239000000706 filtrate Substances 0.000 claims abstract description 12
- 230000002378 acidificating effect Effects 0.000 claims abstract description 7
- 238000000926 separation method Methods 0.000 claims abstract description 7
- 150000001768 cations Chemical class 0.000 claims abstract description 6
- 230000001105 regulatory effect Effects 0.000 claims abstract description 6
- 238000005406 washing Methods 0.000 claims abstract description 5
- 239000003480 eluent Substances 0.000 claims abstract description 4
- 239000007788 liquid Substances 0.000 claims description 33
- 229940024606 amino acid Drugs 0.000 claims description 17
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 13
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 13
- 239000012528 membrane Substances 0.000 claims description 13
- 238000002425 crystallisation Methods 0.000 claims description 12
- 230000008025 crystallization Effects 0.000 claims description 12
- -1 hetero amino acid Chemical class 0.000 claims description 12
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 9
- 125000002091 cationic group Chemical group 0.000 claims description 7
- 238000004042 decolorization Methods 0.000 claims description 7
- 238000001728 nano-filtration Methods 0.000 claims description 7
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- 229920001467 poly(styrenesulfonates) Polymers 0.000 claims description 4
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
- 238000005119 centrifugation Methods 0.000 claims description 2
- 229910017604 nitric acid Inorganic materials 0.000 claims description 2
- 239000002904 solvent Substances 0.000 claims description 2
- 238000001694 spray drying Methods 0.000 claims description 2
- 238000000108 ultra-filtration Methods 0.000 claims description 2
- 238000001291 vacuum drying Methods 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims 1
- 239000012141 concentrate Substances 0.000 claims 1
- 239000000463 material Substances 0.000 claims 1
- 239000000047 product Substances 0.000 abstract description 5
- 230000009286 beneficial effect Effects 0.000 abstract description 3
- 238000004065 wastewater treatment Methods 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 28
- 235000001014 amino acid Nutrition 0.000 description 16
- 150000001413 amino acids Chemical class 0.000 description 5
- 229910052799 carbon Inorganic materials 0.000 description 5
- 239000011549 crystallization solution Substances 0.000 description 5
- 239000003814 drug Substances 0.000 description 5
- 238000000855 fermentation Methods 0.000 description 5
- 230000004151 fermentation Effects 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 238000002386 leaching Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000001212 derivatisation Methods 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 3
- 239000012752 auxiliary agent Substances 0.000 description 3
- 235000015872 dietary supplement Nutrition 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 239000004474 valine Substances 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 2
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 2
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 2
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 2
- 229960003767 alanine Drugs 0.000 description 2
- 235000004279 alanine Nutrition 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- 235000020776 essential amino acid Nutrition 0.000 description 2
- 239000003797 essential amino acid Substances 0.000 description 2
- 238000005342 ion exchange Methods 0.000 description 2
- 229960000310 isoleucine Drugs 0.000 description 2
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 2
- 229960003136 leucine Drugs 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 239000002243 precursor Substances 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- CVLHGLWXLDOELD-UHFFFAOYSA-N 4-(Propan-2-yl)benzenesulfonic acid Chemical compound CC(C)C1=CC=C(S(O)(=O)=O)C=C1 CVLHGLWXLDOELD-UHFFFAOYSA-N 0.000 description 1
- 239000004072 C09CA03 - Valsartan Substances 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
- KJHKTHWMRKYKJE-SUGCFTRWSA-N Kaletra Chemical compound N1([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=2C=CC=CC=2)NC(=O)COC=2C(=CC=CC=2C)C)CC=2C=CC=CC=2)CCCNC1=O KJHKTHWMRKYKJE-SUGCFTRWSA-N 0.000 description 1
- UAQVHNZEONHPQG-ZETCQYMHSA-N N-benzoyl-L-alanine Chemical compound OC(=O)[C@H](C)NC(=O)C1=CC=CC=C1 UAQVHNZEONHPQG-ZETCQYMHSA-N 0.000 description 1
- NCDNCNXCDXHOMX-UHFFFAOYSA-N Ritonavir Natural products C=1C=CC=CC=1CC(NC(=O)OCC=1SC=NC=1)C(O)CC(CC=1C=CC=CC=1)NC(=O)C(C(C)C)NC(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-UHFFFAOYSA-N 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000003674 animal food additive Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 239000000490 cosmetic additive Substances 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 235000020774 essential nutrients Nutrition 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 235000013373 food additive Nutrition 0.000 description 1
- 239000002778 food additive Substances 0.000 description 1
- 235000013355 food flavoring agent Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 230000002394 glycogenic effect Effects 0.000 description 1
- 230000002363 herbicidal effect Effects 0.000 description 1
- 239000004009 herbicide Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000036039 immunity Effects 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- 238000011068 loading method Methods 0.000 description 1
- 229960004525 lopinavir Drugs 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000012452 mother liquor Substances 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 229940054441 o-phthalaldehyde Drugs 0.000 description 1
- ZWLUXSQADUDCSB-UHFFFAOYSA-N phthalaldehyde Chemical compound O=CC1=CC=CC=C1C=O ZWLUXSQADUDCSB-UHFFFAOYSA-N 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 235000018102 proteins Nutrition 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- NCDNCNXCDXHOMX-XGKFQTDJSA-N ritonavir Chemical compound N([C@@H](C(C)C)C(=O)N[C@H](C[C@H](O)[C@H](CC=1C=CC=CC=1)NC(=O)OCC=1SC=NC=1)CC=1C=CC=CC=1)C(=O)N(C)CC1=CSC(C(C)C)=N1 NCDNCNXCDXHOMX-XGKFQTDJSA-N 0.000 description 1
- 229960000311 ritonavir Drugs 0.000 description 1
- 239000010865 sewage Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- SJSNUMAYCRRIOM-QFIPXVFZSA-N valsartan Chemical compound C1=CC(CN(C(=O)CCCC)[C@@H](C(C)C)C(O)=O)=CC=C1C1=CC=CC=C1C1=NN=N[N]1 SJSNUMAYCRRIOM-QFIPXVFZSA-N 0.000 description 1
- 229960004699 valsartan Drugs 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/38—Separation; Purification; Stabilisation; Use of additives
- C07C227/40—Separation; Purification
Abstract
The invention relates to a preparation method of high-purity L-valine, which comprises the following steps: (1) Filtering the L-valine solution to be purified, and collecting filtrate, wherein the concentration of the L-valine solution to be purified is not lower than 50g/L; (2) And (3) after regulating the pH value of the filtrate to be acidic, placing the filtrate in weak acidic cation resin for separation, and decoloring, concentrating, cooling, crystallizing, separating, washing and drying the collected effluent to obtain the product. The invention effectively separates L-valine and the heteroamino acid, the content of single heteroamino acid in the product is not higher than 0.01 percent, and the purity of the L-valine crystal is not lower than 99.9 percent. And pure water is used as an eluent, so that the method is environment-friendly and pollution-free, and is beneficial to subsequent wastewater treatment.
Description
Technical Field
The invention relates to the technical field of biology, in particular to high-purity L-valine, a preparation method and application thereof.
Background
Valine is essential amino acid and nutrient substance of organism, is widely applied to the fields of food, medicine, cosmetics, feed and the like, is widely used as food additive, feed additive, nutritional supplement, flavoring agent, cosmetic additive, preparation precursor of medicine (such as antibiotics, herbicide and the like) and the like, and has huge market demand.
L-valine is an essential amino acid and a glycogenic amino acid of the body, has effects of maintaining normal operation of nervous system functions, enhancing immunity, promoting liver regeneration and the like, and is widely used as a nutritional supplement or a key precursor for preparing medicines (such as valsartan, ritonavir, lopinavir and the like). However, the purity of L-valine is difficult to meet the requirements for pharmaceutical grade valine (purity of not less than 99%).
The method for preparing the L-valine by microbial fermentation has the advantages of bio-based raw materials, high-efficiency conversion, mild reaction, environmental protection, economy and the like, and is widely applied to industries. The method takes glucose as a raw material, and L-valine fermentation liquor is obtained through microbial fermentation. The fermentation broth is subjected to sterilization, decolorization, concentration, crystallization, separation and the like to obtain L-valine crystals and L-valine crystallization mother liquor. Impurity components such as proteins, pigments, sugars, and hetero amino acids (e.g., alanine, leucine, isoleucine, etc.) in the fermentation broth and the content thereof become key factors affecting the purity of L-valine.
Purification methods of L-valine include recrystallization, an auxiliary agent method and an ion exchange method. Because the structure and molecular weight of the hetero amino acid (such as alanine, leucine, isoleucine, etc.) are close to those of L-valine, the recrystallization method is difficult to effectively remove the hetero amino acid, and the energy consumption is high. An auxiliary agent-L-valine compound is formed in the purification method of the auxiliary agent (p-isopropylbenzenesulfonic acid or N-benzoyl-L-alanine), and the L-valine is obtained through decomposition, but the recovery of the organic auxiliary agent is difficult, and the safety of the product is affected by the residual organic matters. The ion exchange method has the problems of high resin consumption, more sewage in the elution process and the like. Therefore, a method for purifying L-valine with higher purification efficiency and environmental protection needs to be studied.
Disclosure of Invention
The invention aims to provide a preparation method of high-purity L-valine, which comprises the following steps:
(1) Filtering the L-valine solution to be purified, and collecting filtrate, wherein the concentration of the L-valine solution to be purified is not lower than 50g/L;
(2) And (3) after regulating the pH value of the filtrate to be acidic, placing the filtrate in a weak acidic cation resin column for separation, and decoloring, concentrating, cooling, crystallizing, separating, washing and drying the collected effluent to obtain the product.
According to the preferred technical scheme, the L-valine solution to be purified is prepared from L-valine to be purified, and the purity of the L-valine to be purified is not higher than 98%.
In a preferred embodiment of the present invention, the filtration in step (1) is selected from any one of ordinary filtration, nanofiltration and ultrafiltration, or a combination thereof.
According to the preferable technical scheme, the acid-base substance for regulating the pH value of the filtrate in the step (2) is selected from any one or combination of sulfuric acid, phosphoric acid, acetic acid, hydrochloric acid and nitric acid.
According to a preferred embodiment of the present invention, the filtrate in step (2) has a pH of 1 to 6, preferably a pH of 2 to 5, more preferably a pH of 3 to 4.
In a preferred embodiment of the present invention, in the step (2), the weakly acidic cationic resin has a carboxylic acid group or a phosphoric acid group, preferably JK110, HD-2, DK110, D152, D113, HZD-2, HD-1, DOWEX TM MAC-3、DOWEX TM Any one of UPCORE MAC-3 or a combination thereof.
In a preferred embodiment of the present invention, at least 1, preferably 2 to 6, more preferably 3 to 4, of the weakly acidic cationic resin columns in step (2) are connected in series.
According to a preferred embodiment of the present invention, the working temperature of the resin in step (2) is 15-50 ℃, preferably 25-30 ℃.
In a preferred embodiment of the present invention, the ratio of the height to the diameter of the resin in the step (2) is (3-10): 1, preferably (5-6): 1.
According to the preferred technical scheme of the invention, the flow rate of the L-valine solution to be purified in the step (2) is 1-4 column volumes/h.
According to the preferred technical scheme of the invention, the eluent of the resin in the step (2) is pure water, and the flow rate is 1-4 column volumes/h.
According to the preferred technical scheme of the invention, in the step (3), the decolorization is activated carbon decolorization, the using amount of the activated carbon is 0.1-5%, and the preferable using amount is 0.2-1%.
According to a preferred embodiment of the present invention, in the step (3), the decoloring temperature is 30-80 ℃, preferably 40-60 ℃.
According to a preferred embodiment of the present invention, the decoloring time is 0.1 to 2 hours, preferably 0.5 to 1.5 hours.
In a preferred embodiment of the present invention, the concentration is selected from any one of vacuum concentration, reduced pressure concentration, film concentration, and normal pressure concentration, or a combination thereof.
In a preferred embodiment of the present invention, the concentration temperature is 40-90 ℃, preferably 50-80 ℃, and most preferably 60-70 ℃.
According to the preferable technical scheme, the concentration of L-valine in the concentrated solution is more than or equal to 400g/L.
According to the preferable technical scheme, the crystallization is selected from any one or combination of natural cooling crystallization and forced cooling crystallization.
According to the preferable technical scheme, the crystallization temperature is 10-15 ℃, and the crystallization time is 1-2 hours.
In a preferred embodiment of the present invention, the separation is selected from any one of filtration, centrifugation, membrane treatment, or a combination thereof.
According to the preferred technical scheme of the invention, the washing solvent is pure water.
According to a preferred technical scheme of the invention, the drying is selected from any one or combination of vacuum drying, reduced pressure drying, normal pressure drying, spray drying, boiling drying and air flow drying, and the drying temperature is not lower than 120 ℃.
In the preferred technical scheme of the invention, the purity of the prepared L-valine crystal is not lower than 99.9%, and the content of single hetero amino acid is not higher than 0.01%.
The invention aims at the application of high-purity L-valine in preparing any one of medicines, medical intermediates, medical raw materials, nutritional supplements and amino acid medicines.
Unless otherwise indicated, when the invention relates to a percentage between liquids, the percentages are volume/volume percentages; the invention relates to the percentage between liquid and solid, said percentage being volume/weight percentage; the invention relates to the percentage between solids and liquids, the percentage being weight/volume percentage; the balance being weight/weight percent.
The resin volume in the invention is the loading of the weak acid cation resin, and the unit is BV.
The present invention employs the following detection methods, unless otherwise indicated:
crystalline purity of L-valine
The branched amino acids were quantitatively analyzed by high performance liquid chromatography using the method disclosed in document 1 (He Chenguang, et al, in 2009, volume 20, phase 4) and the method was used for detection.
2. Amount of hetero amino acids
Instrument and reagent: the Shimadzu LC-16 liquid chromatograph and the C18 chromatographic group are characterized in that the derivatization agent is 5% of o-phthalaldehyde ethanol water solution and 30% of methanol mobile phase, the valine standard is a sigma analysis standard, and the hetero amino acid is other amino acid with the content of 99% in the market.
The experimental steps are as follows: and (3) diluting the product to 0.5-2g/L, filtering, adding a derivatization agent for derivatization for 2 minutes, introducing samples after derivatization, and calculating the concentration of amino acids in the sample according to the peak area of the standard substance, wherein the wavelength is 234nm and the sample introduction amount is 10 ul.
Amount of heteroamino acid = heteroamino acid standard peak area/heteroamino acid peak area × heteroamino acid standard concentration.
Compared with the prior art, the invention has the following beneficial technical effects:
1. the invention effectively separates L-valine and the heteroamino acid, the purity of the L-valine crystal is not lower than 99.9%, and the content of single heteroamino acid is not higher than 0.01%.
2. The invention adopts pure water as the eluent, is environment-friendly and pollution-free, and is beneficial to the subsequent wastewater treatment.
3. The invention adopts continuous operation, has high resin utilization rate and high separation efficiency, and has the technical prospect of industrial production.
Drawings
FIG. 1 purity of L-valine crystals of examples 1-4 and comparative example 1
Detailed Description
The invention is further illustrated by the following examples.
Example 1
(1) Dissolving 1200g of L-valine with the purity of 98 percent in water, preparing the solution into 20L of solution with the concentration of 60g/L, heating the solution to 35-40 ℃, then passing through a nanofiltration membrane with the molecular weight of 800, passing through the inlet pressure of the membrane of 1.5Mpa, and collecting clear liquid;
(2) After the pH of the clear liquid is regulated to 2.5 by adding 85% phosphoric acid, the clear liquid enters a No. 1 resin column, a No. 2 resin column, a No. 3 resin column and a No. 4 resin column which are sequentially connected in series at a flow rate of 4 column volumes/h, the resin column is filled with JK110 type weak acid cationic resin, the working temperature of the resin column is 40 ℃, and the height-diameter ratio of the resin column is 4:1, collecting effluent liquid;
(3) Adding 0.5% active carbon into the collected effluent, stirring and decoloring for 60 minutes at 50 ℃, filtering, collecting decolored liquid, and concentrating the decolored liquid under reduced pressure at 65 ℃ until the concentration of L-valine is more than or equal to 400 g/L;
(4) Cooling the concentrated solution to 10-15 ℃, crystallizing for 1.5 hours, centrifuging the crystallization solution, centrifugally collecting crystals, leaching the crystals with water, collecting crystals, and drying to obtain 967.8g of L-valine crystals (the purity is shown in figure 1, and the single hetero amino acid is less than or equal to 0.01%).
Example 2
(1) Dissolving 1200g of L-valine with the purity of 98 percent in water, preparing the solution into 20L of solution with the concentration of 60g/L, heating the solution to 35-40 ℃, then passing through a nanofiltration membrane with the molecular weight of 800, passing through the inlet pressure of the membrane of 1.5Mpa, and collecting clear liquid;
(2) After the pH of the clear liquid is regulated to 3 by adding 85% phosphoric acid, the clear liquid enters a No. 1 resin column, a No. 2 resin column, a No. 3 resin column and a No. 4 resin column which are sequentially connected in series at a flow rate of 4 column volumes/h, DK110 type weak acid cationic resin is filled in the resin column, the working temperature of the resin column is 40 ℃, and the height-diameter ratio of the resin column is 4:1, collecting effluent liquid;
(3) Adding 0.5% active carbon into the collected effluent, stirring and decoloring for 60 minutes at 50 ℃, filtering, collecting decolored liquid, and concentrating the decolored liquid under reduced pressure at 65 ℃ until the concentration of L-valine is more than or equal to 400 g/L;
(4) Cooling the concentrated solution to 10-15 ℃, crystallizing for 1.5 hours, centrifuging the crystallization solution, centrifugally collecting crystals, leaching the crystals with water, collecting the crystals, and drying to obtain 955.4g of L-valine crystals (the purity is shown in figure 1, and the single hetero amino acid is less than or equal to 0.01%).
Example 3
(1) Dissolving 1200g of L-valine with the purity of 98 percent in water, preparing the solution into 20L of solution with the concentration of 60g/L, heating the solution to 35-40 ℃, then passing through a nanofiltration membrane with the molecular weight of 800, passing through the inlet pressure of the membrane of 1.5Mpa, and collecting clear liquid;
(2) Adding 85% phosphoric acid into the clear solution to adjust pH to 4, allowing the clear solution to enter a No. 1 resin column, a No. 2 resin column, a No. 3 resin column and a No. 4 resin column which are sequentially connected in series at a flow rate of 4 column volumes/h, and filling DOWEX into the resin columns TM MAC-3 weak acid cation resin, the working temperature of the resin column is 40 ℃, and the height-diameter ratio of the resin column is 4:1, collecting effluent liquid;
(3) Adding 0.5% active carbon into the collected effluent, stirring and decoloring for 60 minutes at 50 ℃, filtering, collecting decolored liquid, and concentrating the decolored liquid under reduced pressure at 65 ℃ until the concentration of L-valine is more than or equal to 400 g/L;
(4) Cooling the concentrated solution to 10-15 ℃, crystallizing for 1.5 hours, centrifuging the crystallization solution, centrifugally collecting crystals, leaching the crystals with water, collecting crystals, and drying to obtain 929.1g of L-valine crystals (the purity is shown in figure 1, and the single hetero amino acid is less than or equal to 0.01%).
Example 4
(1) Dissolving 1200g of L-valine with the purity of 98 percent in water, preparing the solution into 20L of solution with the concentration of 60g/L, heating the solution to 35-40 ℃, then passing through a nanofiltration membrane with the molecular weight of 800, passing through the inlet pressure of the membrane of 1.5Mpa, and collecting clear liquid;
(2) After adding acetic acid to the clear liquid to adjust the pH=3, the clear liquid enters a No. 1 resin column, a No. 2 resin column, a No. 3 resin column and a No. 4 resin column which are sequentially connected in series, the resin column is filled with HD-1 weak acid cationic resin, the working temperature of the resin column is 40 ℃, and the height-diameter ratio of the resin column is 4:1, collecting effluent liquid;
(3) Adding 0.5% active carbon into the collected effluent, stirring and decoloring for 60 minutes at 50 ℃, filtering, collecting decolored liquid, and concentrating the decolored liquid under reduced pressure at 65 ℃ until the concentration of L-valine is more than or equal to 400 g/L;
(4) Cooling the concentrated solution to 10-15 ℃, crystallizing for 1.5 hours, centrifuging the crystallization solution, centrifugally collecting crystals, leaching the crystals with water, collecting crystals, and drying to obtain 965.2g of L-valine crystals (the purity is shown in figure 1, and the single hetero amino acid is less than or equal to 0.01%).
Comparative example 1
(1) Dissolving 1200g of L-valine with the purity of 98 percent in water, preparing the solution into 20L of solution with the concentration of 60g/L, heating the solution to 35-40 ℃, then passing through a nanofiltration membrane with the molecular weight of 800, passing through the inlet pressure of the membrane of 1.5Mpa, and collecting clear liquid;
(2) Adding 85% phosphoric acid into clear liquid to adjust pH=4, and allowing the clear liquid to enter a No. 1 resin column, a No. 2 resin column, a No. 3 resin column and a No. 4 resin column which are sequentially connected in series at a flow rate of 4 column volumes/h, wherein the resin column is filled with HD-8 type strong acid cationic resin, the working temperature of the resin column is 40 ℃, and the height-diameter ratio of the resin column is 4:1, collecting effluent liquid;
(3) Adding 0.5% active carbon into the collected effluent, stirring and decoloring for 60 minutes at 50 ℃, filtering, collecting decolored liquid, and concentrating the decolored liquid under reduced pressure at 65 ℃ until the concentration of L-valine is more than or equal to 400 g/L;
(4) Cooling the concentrated solution to 10-15 ℃, crystallizing for 1.5 hours, centrifuging the crystallization solution, centrifugally collecting crystals, leaching the crystals with water, collecting crystals, and drying to obtain 921.1g of L-valine crystals (the purity is shown in figure 1, and the single hetero amino acid is less than or equal to 0.01%).
The above description of the embodiments of the present invention is not intended to limit the present invention, and those skilled in the art can make various changes or modifications according to the present invention without departing from the spirit of the present invention, and shall fall within the scope of the claims of the present invention.
Claims (18)
1. The preparation method of the high-purity L-valine is characterized by comprising the following steps:
(1) Filtering the L-valine solution to be purified, and collecting filtrate, wherein the concentration of the L-valine solution to be purified is not lower than 50g/L;
(2) After regulating the pH value of the filtrate to 3-4, placing the filtrate in weak acid cation resin for separation, wherein the flow rate of the L-valine solution to be purified is 1-4 column volumes/h, the working temperature of the resin is 15-50 ℃, and the height-diameter ratio of the resin is 3-10:1, decoloring, concentrating, cooling, crystallizing, separating, washing and drying the collected effluent liquid to obtain the catalyst;
the weak acid cation resin is JK110, DK110, DOWEX TM Any one of MAC-3 and HD-1 or a combination thereof.
2. The method of claim 1, wherein the L-valine solution to be purified is formulated for L-valine to be purified, and the L-valine to be purified has a purity of no greater than 98%.
3. The method of claim 1, wherein the filtering in step (1) is selected from any one of conventional filtering, nanofiltration, ultrafiltration, or a combination thereof.
4. The method of claim 1, wherein the acid-base material that adjusts the pH of the filtrate in step (2) is selected from any one of sulfuric acid, phosphoric acid, acetic acid, hydrochloric acid, nitric acid, or a combination thereof.
5. The method of claim 1, wherein the weakly acidic cationic resin in step (2) is a series of 2-6 resin columns.
6. The method of claim 1, wherein the eluent for the resin in step (2) is pure water at a flow rate of 1 to 4 column volumes/h.
7. The method of claim 1, wherein in step (3), the decolorization is activated carbon decolorization, and the amount of activated carbon used is 0.1 to 5%.
8. The method of claim 1, wherein in step (3), the decolorization temperature is 30 to 80 ℃.
9. The method of claim 1, wherein the decolorization time is 0.1 to 2 hours.
10. The method of claim 1, wherein the concentrating is selected from any one of vacuum concentrating, membrane concentrating, atmospheric concentrating, or a combination thereof.
11. The method of claim 1, wherein the concentration temperature is 40-90 ℃.
12. The method of claim 1, wherein the concentration of L-valine in the concentrate is greater than or equal to 400g/L.
13. The method of claim 1, wherein the crystallization is selected from any one of natural cooling crystallization, forced cooling crystallization, or a combination thereof.
14. The method of claim 1, wherein the crystallization temperature is 10-15 ℃ and the crystallization time is 1-2 hours.
15. The method of claim 1, wherein the separation is selected from any one of filtration, centrifugation, membrane treatment, or a combination thereof.
16. The method of claim 1, wherein the washing solvent is pure water.
17. The method of claim 1, wherein the drying is selected from any one or a combination of vacuum drying, reduced pressure drying, atmospheric pressure drying, spray drying, ebullient drying, air flow drying, and drying temperatures greater than or equal to 120 ℃.
18. The process according to claim 1, wherein the purity of the produced L-valine crystals is not less than 99.9% and the single hetero amino acid is not more than 0.01%.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202011556424 | 2020-12-25 | ||
| CN2020115564248 | 2020-12-25 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN112979482A CN112979482A (en) | 2021-06-18 |
| CN112979482B true CN112979482B (en) | 2024-02-02 |
Family
ID=76335352
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110276027.3A Active CN112979482B (en) | 2020-12-25 | 2021-03-15 | High-purity L-valine as well as preparation method and application thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN112979482B (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114014771B (en) * | 2021-06-30 | 2023-12-12 | 安徽华恒生物科技股份有限公司 | Ultra-high purity amino acid, preparation method and application thereof |
| CN114044797A (en) * | 2021-09-30 | 2022-02-15 | 安徽华恒生物科技股份有限公司 | Extraction method and application of alpha-arbutin |
| CN115721020A (en) * | 2022-12-16 | 2023-03-03 | 山东省鲁洲食品集团有限公司 | Preparation method of instant branched chain amino acid |
Citations (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62255453A (en) * | 1986-04-28 | 1987-11-07 | Ajinomoto Co Inc | Method for separating and purifying valine |
| CN102432479A (en) * | 2011-12-30 | 2012-05-02 | 梅花生物科技集团股份有限公司 | Method for extracting L-valine from L-valine fermentation liquid |
| CN103508933A (en) * | 2013-08-26 | 2014-01-15 | 三达膜科技（厦门）有限公司 | Separating and purifying method for L-tryptophan |
| CN103695488A (en) * | 2013-12-24 | 2014-04-02 | 山东民强生物科技股份有限公司 | Arginine preparation method |
| CN103695489A (en) * | 2013-12-24 | 2014-04-02 | 山东民强生物科技股份有限公司 | Arginine refining technology |
| CN105274182A (en) * | 2015-10-28 | 2016-01-27 | 新疆阜丰生物科技有限公司 | Process for efficiently extracting L-valine from fermentation liquor |
| CN105294467A (en) * | 2015-11-20 | 2016-02-03 | 山东恩贝生物工程有限公司 | Novel process for extracting feed-grade valine from fermentation liquid |
| CN106631852A (en) * | 2016-09-30 | 2017-05-10 | 南京工业大学 | Method for extracting L-ornithine hydrochloride from L-ornithine fermentation broth |
| CN107488129A (en) * | 2016-06-13 | 2017-12-19 | 黄冈威尔曼生物科技有限责任公司 | A kind of method that L valines are purified in the valine compound from L |
| CN108658827A (en) * | 2018-07-02 | 2018-10-16 | 无锡晶海氨基酸股份有限公司 | A kind of preparation method of proline crude product |
| CN109020854A (en) * | 2018-10-17 | 2018-12-18 | 浙江工业大学 | A method of extracting L-Methionine from fermentation liquid |
| CN109678743A (en) * | 2019-02-24 | 2019-04-26 | 内蒙古拜克生物有限公司 | A kind of isolation and purification method of Valine |
| CN109761833A (en) * | 2019-02-24 | 2019-05-17 | 内蒙古拜克生物有限公司 | A kind of isolation and purification method of L-Leu |
-
2021
- 2021-03-15 CN CN202110276027.3A patent/CN112979482B/en active Active
Patent Citations (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS62255453A (en) * | 1986-04-28 | 1987-11-07 | Ajinomoto Co Inc | Method for separating and purifying valine |
| CN102432479A (en) * | 2011-12-30 | 2012-05-02 | 梅花生物科技集团股份有限公司 | Method for extracting L-valine from L-valine fermentation liquid |
| CN103508933A (en) * | 2013-08-26 | 2014-01-15 | 三达膜科技（厦门）有限公司 | Separating and purifying method for L-tryptophan |
| CN103695488A (en) * | 2013-12-24 | 2014-04-02 | 山东民强生物科技股份有限公司 | Arginine preparation method |
| CN103695489A (en) * | 2013-12-24 | 2014-04-02 | 山东民强生物科技股份有限公司 | Arginine refining technology |
| CN105274182A (en) * | 2015-10-28 | 2016-01-27 | 新疆阜丰生物科技有限公司 | Process for efficiently extracting L-valine from fermentation liquor |
| CN105294467A (en) * | 2015-11-20 | 2016-02-03 | 山东恩贝生物工程有限公司 | Novel process for extracting feed-grade valine from fermentation liquid |
| CN107488129A (en) * | 2016-06-13 | 2017-12-19 | 黄冈威尔曼生物科技有限责任公司 | A kind of method that L valines are purified in the valine compound from L |
| CN106631852A (en) * | 2016-09-30 | 2017-05-10 | 南京工业大学 | Method for extracting L-ornithine hydrochloride from L-ornithine fermentation broth |
| CN108658827A (en) * | 2018-07-02 | 2018-10-16 | 无锡晶海氨基酸股份有限公司 | A kind of preparation method of proline crude product |
| CN109020854A (en) * | 2018-10-17 | 2018-12-18 | 浙江工业大学 | A method of extracting L-Methionine from fermentation liquid |
| CN109678743A (en) * | 2019-02-24 | 2019-04-26 | 内蒙古拜克生物有限公司 | A kind of isolation and purification method of Valine |
| CN109761833A (en) * | 2019-02-24 | 2019-05-17 | 内蒙古拜克生物有限公司 | A kind of isolation and purification method of L-Leu |
Non-Patent Citations (1)
| Title |
|---|
| 陈建军等."离子交换分离 L-缬氨酸的传质动力学及动态穿透特征".《过程工程学报》.第47-56页. * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN112979482A (en) | 2021-06-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112979482B (en) | High-purity L-valine as well as preparation method and application thereof | |
| CN101812009B (en) | Novel technique for extracting L-tryptophan from fermentation broth | |
| CN104529755B (en) | A kind of method being separated α-ketoglutaric acid from conversion fluid | |
| CN109265498B (en) | Method for preparing N-acetylneuraminic acid by integrated separation and purification of polysialic acid | |
| CN105566136A (en) | Method for separating and extracting 4-hydroxyisoleucine from fermentation liquor | |
| CN106565425B (en) | Method for recovering catechol and levodopa from levodopa mother liquor | |
| CN112266362B (en) | Method for extracting tetrahydropyrimidine by combining aqueous two-phase extraction with ion exchange chromatography | |
| CN111171097B (en) | Separation and purification method for producing adenosine by fermentation | |
| CN101709037A (en) | Method for preparing high-purity D-amino acid | |
| CN110698472B (en) | Purification method of pyrroloquinoline quinone | |
| CN115073539B (en) | Method for separating and purifying 2' -fucosyllactose | |
| CN116283553A (en) | Method for extracting 3, 4-dihydroxybenzoic acid from fermentation broth | |
| CN115772549A (en) | Preparation method for extracting nicotinamide containing trace nicotinic acid from fermentation liquor | |
| CN116836143A (en) | Production method of high-content baicalein | |
| CN100509757C (en) | Purification method of *N-L-arginine | |
| CN110606863B (en) | Preparation method of N-acetylneuraminic acid dihydrate | |
| CN117050021B (en) | Method for separating and extracting tetrahydropyrimidine from fermentation liquor | |
| CN112939795B (en) | High-purity granular L-valine crystal, and preparation method and application thereof | |
| CN106496020B (en) | A method of extracting α-ketoglutaric acid from microbial fermentation solution or enzymatic conversion liquid | |
| CN106381316B (en) | A kind of preparation method and method of purification of sodium alpha-ketoglutarate | |
| CN110903165A (en) | High-yield preparation method of erythritol | |
| CN113773215B (en) | L-valine with high bulk density and preparation method and application thereof | |
| CN114702487B (en) | Purification method of lysergic acid | |
| CN111909224B (en) | Method for separating and purifying trehalose from mixture containing trehalose and maltose | |
| CN114213241B (en) | Method for extracting shikimic acid from shikimic acid fermentation liquor |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |