CN117510361A - Process for preparing high purity D-calcium pantothenate - Google Patents
Process for preparing high purity D-calcium pantothenate Download PDFInfo
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- CN117510361A CN117510361A CN202311439338.2A CN202311439338A CN117510361A CN 117510361 A CN117510361 A CN 117510361A CN 202311439338 A CN202311439338 A CN 202311439338A CN 117510361 A CN117510361 A CN 117510361A
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- calcium
- pantothenate
- exchange resin
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- pantothenic acid
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- FAPWYRCQGJNNSJ-UBKPKTQASA-L calcium D-pantothenic acid Chemical compound [Ca+2].OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O.OCC(C)(C)[C@@H](O)C(=O)NCCC([O-])=O FAPWYRCQGJNNSJ-UBKPKTQASA-L 0.000 title claims abstract description 159
- 238000004519 manufacturing process Methods 0.000 title claims description 9
- GHOKWGTUZJEAQD-UHFFFAOYSA-N pantothenic acid Chemical compound OCC(C)(C)C(O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-UHFFFAOYSA-N 0.000 claims abstract description 151
- 239000003729 cation exchange resin Substances 0.000 claims abstract description 83
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 claims abstract description 75
- 229920005989 resin Polymers 0.000 claims abstract description 66
- 239000011347 resin Substances 0.000 claims abstract description 65
- 238000000855 fermentation Methods 0.000 claims abstract description 58
- 230000004151 fermentation Effects 0.000 claims abstract description 58
- 239000003957 anion exchange resin Substances 0.000 claims abstract description 45
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims abstract description 25
- 229910001424 calcium ion Inorganic materials 0.000 claims abstract description 25
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical group [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 20
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 20
- 239000001257 hydrogen Substances 0.000 claims abstract description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical group [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 claims abstract description 18
- 239000003463 adsorbent Substances 0.000 claims abstract description 15
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims abstract description 14
- GHOKWGTUZJEAQD-ZETCQYMHSA-N (D)-(+)-Pantothenic acid Chemical compound OCC(C)(C)[C@@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-ZETCQYMHSA-N 0.000 claims abstract description 13
- 230000009466 transformation Effects 0.000 claims abstract description 13
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 11
- 238000002360 preparation method Methods 0.000 claims abstract description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 48
- 239000007788 liquid Substances 0.000 claims description 39
- 238000000034 method Methods 0.000 claims description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 27
- 238000001914 filtration Methods 0.000 claims description 19
- 238000001179 sorption measurement Methods 0.000 claims description 19
- 239000000047 product Substances 0.000 claims description 17
- 239000008213 purified water Substances 0.000 claims description 17
- 230000004913 activation Effects 0.000 claims description 15
- 230000008569 process Effects 0.000 claims description 13
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 12
- 239000002253 acid Substances 0.000 claims description 12
- 238000004458 analytical method Methods 0.000 claims description 12
- 239000007791 liquid phase Substances 0.000 claims description 12
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 claims description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 9
- 239000012528 membrane Substances 0.000 claims description 9
- 230000007935 neutral effect Effects 0.000 claims description 9
- 238000000746 purification Methods 0.000 claims description 8
- GPRLSGONYQIRFK-UHFFFAOYSA-N hydron Chemical group [H+] GPRLSGONYQIRFK-UHFFFAOYSA-N 0.000 claims description 7
- 102000004169 proteins and genes Human genes 0.000 claims description 6
- 108090000623 proteins and genes Proteins 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 6
- 239000003513 alkali Substances 0.000 claims description 5
- 238000005341 cation exchange Methods 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 238000002834 transmittance Methods 0.000 claims description 5
- PPBRXRYQALVLMV-UHFFFAOYSA-N Styrene Chemical compound C=CC1=CC=CC=C1 PPBRXRYQALVLMV-UHFFFAOYSA-N 0.000 claims description 4
- 239000000919 ceramic Substances 0.000 claims description 4
- 239000000706 filtrate Substances 0.000 claims description 4
- 239000000049 pigment Substances 0.000 claims description 4
- 239000006228 supernatant Substances 0.000 claims description 4
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 3
- 239000011575 calcium Substances 0.000 claims description 3
- 229910052791 calcium Inorganic materials 0.000 claims description 3
- 239000001110 calcium chloride Substances 0.000 claims description 3
- 229910001628 calcium chloride Inorganic materials 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- 244000005700 microbiome Species 0.000 claims description 3
- 239000000203 mixture Substances 0.000 claims description 3
- 239000002245 particle Substances 0.000 claims description 2
- 230000002378 acidificating effect Effects 0.000 claims 2
- 239000003456 ion exchange resin Substances 0.000 claims 1
- 229920003303 ion-exchange polymer Polymers 0.000 claims 1
- 239000011148 porous material Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 230000036541 health Effects 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 abstract description 2
- 239000000243 solution Substances 0.000 description 55
- 238000012856 packing Methods 0.000 description 11
- 238000011049 filling Methods 0.000 description 8
- 108010089977 LXT-101 Proteins 0.000 description 6
- 239000011550 stock solution Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- 238000000108 ultra-filtration Methods 0.000 description 6
- 238000005516 engineering process Methods 0.000 description 5
- 229940055726 pantothenic acid Drugs 0.000 description 5
- 235000019161 pantothenic acid Nutrition 0.000 description 5
- 239000011713 pantothenic acid Substances 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 230000000813 microbial effect Effects 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 230000003287 optical effect Effects 0.000 description 3
- GHOKWGTUZJEAQD-SSDOTTSWSA-N 3-[[(2s)-2,4-dihydroxy-3,3-dimethylbutanoyl]amino]propanoic acid Chemical compound OCC(C)(C)[C@H](O)C(=O)NCCC(O)=O GHOKWGTUZJEAQD-SSDOTTSWSA-N 0.000 description 2
- UAOZQUWDRJVBFG-UHFFFAOYSA-N 3-aminopropanoic acid;calcium Chemical compound [Ca].NCCC(O)=O UAOZQUWDRJVBFG-UHFFFAOYSA-N 0.000 description 2
- 241001465754 Metazoa Species 0.000 description 2
- 230000003213 activating effect Effects 0.000 description 2
- 230000002862 amidating effect Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229960002079 calcium pantothenate Drugs 0.000 description 2
- 150000001720 carbohydrates Chemical class 0.000 description 2
- 229940023913 cation exchange resins Drugs 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- RSWGJHLUYNHPMX-UHFFFAOYSA-N 1,4a-dimethyl-7-propan-2-yl-2,3,4,4b,5,6,10,10a-octahydrophenanthrene-1-carboxylic acid Chemical compound C12CCC(C(C)C)=CC2=CCC2C1(C)CCCC2(C)C(O)=O RSWGJHLUYNHPMX-UHFFFAOYSA-N 0.000 description 1
- FAPWYRCQGJNNSJ-UHFFFAOYSA-L Calcium DL-pantothenate Chemical compound [Ca+2].OCC(C)(C)C(O)C(=O)NCCC([O-])=O.OCC(C)(C)C(O)C(=O)NCCC([O-])=O FAPWYRCQGJNNSJ-UHFFFAOYSA-L 0.000 description 1
- RGJOEKWQDUBAIZ-IBOSZNHHSA-N CoASH Chemical compound O[C@@H]1[C@H](OP(O)(O)=O)[C@@H](COP(O)(=O)OP(O)(=O)OCC(C)(C)[C@@H](O)C(=O)NCCC(=O)NCCS)O[C@H]1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-IBOSZNHHSA-N 0.000 description 1
- 239000003674 animal food additive Substances 0.000 description 1
- 150000001449 anionic compounds Chemical class 0.000 description 1
- 159000000007 calcium salts Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 150000001767 cationic compounds Chemical class 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- RGJOEKWQDUBAIZ-UHFFFAOYSA-N coenzime A Natural products OC1C(OP(O)(O)=O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 RGJOEKWQDUBAIZ-UHFFFAOYSA-N 0.000 description 1
- 239000005516 coenzyme A Substances 0.000 description 1
- 229940093530 coenzyme a Drugs 0.000 description 1
- -1 compound D-calcium pantothenate Chemical class 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 238000011109 contamination Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000004042 decolorization Methods 0.000 description 1
- KDTSHFARGAKYJN-UHFFFAOYSA-N dephosphocoenzyme A Natural products OC1C(O)C(COP(O)(=O)OP(O)(=O)OCC(C)(C)C(O)C(=O)NCCC(=O)NCCS)OC1N1C2=NC=NC(N)=C2N=C1 KDTSHFARGAKYJN-UHFFFAOYSA-N 0.000 description 1
- 238000011033 desalting Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000003925 fat Substances 0.000 description 1
- 239000006052 feed supplement Substances 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 229910001412 inorganic anion Inorganic materials 0.000 description 1
- 229910001411 inorganic cation Inorganic materials 0.000 description 1
- 229910017053 inorganic salt Inorganic materials 0.000 description 1
- 235000015073 liquid stocks Nutrition 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 235000015097 nutrients Nutrition 0.000 description 1
- 230000035790 physiological processes and functions Effects 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 235000019156 vitamin B Nutrition 0.000 description 1
- 239000011720 vitamin B Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/22—Separation; Purification; Stabilisation; Use of additives
- C07C231/24—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P10/00—Technologies related to metal processing
- Y02P10/20—Recycling
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
The invention belongs to the technical field of preparation of pharmaceutical compounds, and relates to a preparation method of high-purity D-calcium pantothenate. The technical scheme adopted by the invention is as follows: treating the biological fermentation broth of calcium D-pantothenate with a combination of anion exchange resin (transformation to hydroxide form), cation exchange resin (transformation to hydrogen form) and weakly polar macroporous adsorbent resin to obtain purified D-pantothenate solution; the D-pantothenic acid solution is converted into a D-calcium pantothenate solution through cation exchange resin (converted into calcium ions), and the D-calcium pantothenate solution is decolorized by active carbon and evaporated and concentrated to obtain high-purity D-calcium pantothenate. The preparation method of the invention has simple operation, high yield and good product quality, and is suitable for industrialization, and the prepared D-calcium pantothenate is suitable for further preparing medicines and health products.
Description
Technical Field
The invention belongs to the technical field of preparation of pharmaceutical compounds, and particularly relates to a preparation method of a chiral compound D-calcium pantothenate with high purity.
Background
The D-calcium pantothenate is used as B vitamins, is one of nutrient substances necessary for the normal growth of organisms, and is widely applied to the field of medical health care. The D-calcium pantothenate is also used as a constituent substance of coenzyme A and is involved in the metabolism of carbohydrates, fats and proteins, and is an essential trace substance for maintaining normal physiological functions of human bodies and animals.
Calcium pantothenate is known as calcium N- (2, 4-dihydroxy-3, 3-dimethylbutyryl) -beta-aminopropionate, also known as calcium present-polysaccharide, and has the following chemical formula in the form of white or yellowish needle crystals or powder:
calcium pantothenate exists in three forms due to the chiral carbon atom: DL-forms (racemates), D-forms (dextroisomers) and L-forms (levorotatory forms), only calcium D-pantothenate being biologically active.
Many documents report chemical synthesis methods of D-calcium pantothenate, for example, the article "technology and application of D-calcium pantothenate" (Li Lichang, hubei chemical, 2 nd, pages 30 to 31 of 2002), the article "technology and progress of D-calcium pantothenate synthesis" (Yang Yihong et al, 25 th, 6 th, 8 to 11 of 2004), and the patent document CN1319937C relates to a method for synthesizing D-calcium pantothenate. As an example, the synthesis of calcium D-pantothenate is relatively complex, comprising the steps of: the D-calcium pantothenate is obtained by amidating the mixture of the D-butyrolactone and the beta-alanine calcium after resolution, or the D-calcium pantothenate is obtained by amidating the mixture of the D-butyrolactone and the beta-alanine calcium without resolution and then resolution. It can be seen that the chemical synthesis of calcium D-pantothenate, which uses a large variety of chemical reagents and involves a large number of steps, involves resolution and is disadvantageous in terms of toxicity and contamination.
With the continuous development of biotechnology, the method for producing the D-calcium pantothenate by utilizing a microbial fermentation method has the advantages of low cost, mild reaction conditions and small environmental pollution. Chinese patent document CN1946851B discloses a process for preparing calcium D-pantothenate, which comprises isolating and purifying calcium D-pantothenate from a fermentation broth of a pantothenic-acid-producing microorganism, which process is characterized by the following steps: (a) Eluting D-pantothenic acid from the strongly basic anion exchange resin with 10-20% w/w aqueous acetic acid; (b) Neutralizing the eluate by adding an alkaline calcium salt, and (c) converting the solution into a free-flowing product that can be used as an animal feed supplement.
Early-stage calcium D-pantothenate is mainly applied to feed additives, and as the calcium D-pantothenate is applied to human health products and medicines, high-purity and good-quality calcium D-pantothenate is required. The microbial fermentation process is utilized to produce D-calcium pantothenate, and the biological fermentation liquid contains insoluble matters such as microbial cells, saccharides, proteins, inorganic salts, various unknown impurities and the like, and CN1946851B provides a feed-grade D-calcium pantothenate raw material.
Accordingly, there is a need for continuous research and improvement in the production of calcium D-pantothenate to provide different qualities of calcium D-pantothenate to meet the various quality demands of the market.
Disclosure of Invention
Technical problem
Accordingly, the present invention has been made to solve the above-mentioned problems occurring in the prior art. The invention aims to provide a preparation method of high-purity D-calcium pantothenate, which is simple and convenient to operate, high in yield, good in product quality and suitable for industrialization, and the prepared D-calcium pantothenate is suitable for further preparing medicines and health-care products.
Technical proposal
In order to achieve the above purpose of the present invention, the present invention adopts the following technical scheme: treating the biological fermentation broth of calcium D-pantothenate with a combination of anion exchange resin (transformation to hydroxide form), cation exchange resin (transformation to hydrogen form) and weakly polar macroporous adsorbent resin to obtain purified D-pantothenate solution; the D-pantothenic acid solution is converted into a D-calcium pantothenate solution through cation exchange resin (converted into calcium ions), and the D-calcium pantothenate solution is decolorized by active carbon and evaporated and concentrated to obtain high-purity D-calcium pantothenate.
According to the present invention, there is provided a process for producing high-purity calcium D-pantothenate, comprising the steps of:
(1) Purification treatment
Passing the filtered biological fermentation liquor of the D-calcium pantothenate through hydroxide anion exchange resin to obtain decolored and desalted fermentation liquor; the decolorized and desalted fermentation liquor is subjected to cation exchange through hydrogen type cation exchange resin and is converted into D-pantothenic acid solution; d-pantothenic acid solution passes through weak-polarity macroporous adsorption resin, D-pantothenic acid is adsorbed on the weak-polarity macroporous adsorption resin, and then the D-pantothenic acid adsorbed on the resin is resolved by using a resolving agent to obtain D-pantothenic acid resolving liquid;
wherein the hydroxide anion exchange resin is converted into hydroxide anion exchange resin through alkali activation treatment, and the hydrogen cation exchange resin is converted into hydrogen cation exchange resin through acid activation treatment;
(2) Preparation of D-calcium pantothenate
The D-pantothenic acid analysis solution obtained above is converted into a D-calcium pantothenate solution through a calcium ion type cation exchange resin, and the D-calcium pantothenate solution is decolorized and evaporated by active carbon to obtain solid D-calcium pantothenate, wherein the calcium ion type cation exchange resin is converted into the calcium ion type cation exchange resin through acid activation and calcium chloride solution treatment.
Advantageous effects
The invention has the advantages that: in the invention, the anion exchange resin (transformed into oxyhydrogen type), the cation exchange resin (transformed into hydrogen type) and the weak-polarity macroporous adsorption resin are sequentially combined and applied, so that the biological fermentation liquor of the filtered D-calcium pantothenate has good purification effect, and the impurities such as salt (including inorganic anions and inorganic cations), pigment, nonpolar substances and the like in the biological fermentation liquor are removed, thereby obtaining purified D-pantothenic acid solution; the D-pantothenic acid solution is converted into purified D-calcium pantothenate solution by cation exchange resin (converted into calcium ion type), thereby obtaining high-purity D-calcium pantothenate. In addition, the preparation method is simple and convenient to operate, high in yield and good in product quality, and is suitable for industrialization.
Detailed Description
Hereinafter, the method for producing high-purity calcium D-pantothenate of the present invention will be described in more detail to aid in understanding the present invention.
According to one embodiment of the present invention, in the process for producing high-purity calcium D-pantothenate of the present invention, a biological fermentation broth of calcium D-pantothenate is treated with a combination of anion-exchange resin (transformation to hydroxide form), cation-exchange resin (transformation to hydrogen form) and weakly polar macroporous adsorption resin in order to obtain a purified D-pantothenic acid solution, namely: in the purification treatment step, the biological fermentation liquid of the filtered D-calcium pantothenate is passed through hydroxide-type anion exchange resin to obtain decolored and desalted fermentation liquid; the decolorized and desalted fermentation liquor is subjected to cation exchange through hydrogen type cation exchange resin and is converted into D-pantothenic acid solution; d-pantothenic acid solution passes through weak-polarity macroporous adsorption resin, D-pantothenic acid is adsorbed on the weak-polarity macroporous adsorption resin, and then the D-pantothenic acid adsorbed on the resin is resolved by using a resolving agent to obtain D-pantothenic acid resolving liquid; wherein the hydroxide anion exchange resin is converted into hydroxide anion exchange resin through alkali activation treatment, and the hydrogen cation exchange resin is converted into hydrogen cation exchange resin through acid activation treatment.
Wherein the filtered biological fermentation liquid of the D-calcium pantothenate refers to fermentation liquid clear liquid obtained by filtering a biological fermentation liquid stock solution of the D-calcium pantothenate obtained by microbial fermentation. Wherein the stock solution of the biological fermentation liquid of the D-calcium pantothenate is fermentation liquid obtained by utilizing microorganism fermentation, the pH value of the fermentation liquid is generally 6.5-7.5, the concentration of the D-calcium pantothenate is 60-85 g/L measured by centrifuging supernatant, the liquid phase purity of the D-calcium pantothenate is 50-60%, the conductivity is 15-30 ms/cm, and the fermentation liquid further contains sugar, protein, inorganic salt and various unknown impurities. Here, the liquid phase purity of D-calcium pantothenate means the percentage of the peak area of D-calcium pantothenate in a chromatogram obtained by HPLC analysis.
Specifically, in the filtration treatment, a ceramic membrane is adopted to carry out filtration pretreatment on the biological fermentation liquor stock solution of the D-calcium pantothenate so as to remove mycelium and solid matters in the fermentation liquor and obtain the D-calcium pantothenate Tao Lvye; and then ultra-filtering the D-calcium pantothenate Tao Lvye by using an ultra-filtering membrane to remove pigments and soluble proteins in the D-calcium pantothenate to obtain the D-calcium pantothenate ultra-filtrate.
More specifically, firstly, a ceramic membrane with the filtering precision of 50nm is adopted to filter and pretreat the biological fermentation liquor stock solution of the D-calcium pantothenate at the temperature of 20-40 ℃ so as to remove mycelium and solids in the fermentation liquor, and when the concentration multiple of the fermentation liquor reaches 3-5 times, purified water with the volume of 3-4 times of the concentration liquor is continuously added into the concentration liquor for washing filtration, and the water inflow and the filtrate output are controlled to be balanced, so that the obtained filtrate is the D-calcium pantothenate Tao Lvye. In the obtained calcium D-pantothenate Tao Lvye, the concentration of the calcium D-pantothenate is generally 35 to 60g/L.
Then, under the condition of 20-40 ℃, an ultrafiltration membrane with the molecular weight cut-off of 1000-5000 daltons, more preferably an ultrafiltration membrane with the molecular weight cut-off of 2000-3000 daltons is adopted to carry out ultrafiltration treatment on the D-calcium pantothenate Tao Lvye, and pigments and soluble proteins in the D-calcium pantothenate ultrafiltrate are removed to obtain the D-calcium pantothenate ultrafiltrate. In the ultrafiltration process, the concentrate may be appropriately washed with purified water to increase the yield, as required. In the obtained ultrafiltrate of D-calcium pantothenate, the concentration of D-calcium pantothenate is generally 30 to 55g/L.
In the present invention, the filtered biological fermentation broth of calcium D-pantothenate is first treated with a hydroxide-type anion-exchange resin, i.e., the ultrafiltrate of calcium D-pantothenate obtained as described above is first treated with a hydroxide-type anion-exchange resin. Specifically, the obtained D-calcium pantothenate ultrafiltrate is decolorized and desalted by hydroxide-type anion exchange resin at a certain flow rate, and the effluent liquid at the column outlet with the light transmittance of more than 90% (420 nm) is collected to obtain decolorized and desalted fermentation liquor.
The hydroxide anion exchange resin is changed into hydroxide anion exchange resin through alkali activation treatment, and the adopted anion exchange resin is alkalescent anion exchange resin, and can be obtained from the market, for example, FPA-53 type anion exchange resin produced by Roman Hasi, or any one of LXT-267 and LXT-281 type anion exchange resin produced by Siemens blue and technology new materials Co. Specifically, the hydroxide anion exchange resin is obtained by treating anion exchange resin transformation according to the following method: the anion exchange resin is activated with sodium hydroxide solution and then rinsed with purified water until the eluate is neutral and has a conductivity below 50 mus/cm. The hydroxide anion exchange resin is applied in the form of a circular resin bed by wet column packing, and the obtained D-calcium pantothenate ultrafiltrate is passed through the hydroxide anion exchange resin bed at a certain flow rate, for example, at a flow rate of 1-3 times of the total volume of the resin per hour. In the collected decolored and desalted fermentation liquor, the concentration of the general D-calcium pantothenate is 25-50 g/L, and the purity of the D-calcium pantothenate liquid phase is 80-85%.
Alternatively, in this step, an anion exchange resin may be packed into a resin bed, then converted into an hydroxide-type anion exchange resin by alkali activation treatment, and the obtained ultrafiltration liquid of calcium D-pantothenate may be passed through the resin bed to obtain a decolorized and desalted fermentation liquid.
Then, the decolorized and desalted fermentation broth is subjected to cation exchange by a hydrogen cation exchange resin to be converted into D-pantothenic acid solution. Specifically, the decolorized and desalted fermentation liquor passes through hydrogen type cation exchange resin at a certain flow rate to carry out cation exchange, so that the further decolorization and the desalting are achieved, and the effluent liquid at the column outlet with the pH less than 2.0 is collected, namely the converted D-pantothenic acid solution.
The hydrogen type cation exchange resin is a hydrogen type cation exchange resin which is converted into the hydrogen type cation exchange resin through acid activation treatment, and the adopted cation exchange resin is a strong acid cation exchange resin which can be purchased from the market, for example, any one of LXT-101 and LXT-105 type cation exchange resins manufactured by SiAN blue and technology new materials Co., ltd. Specifically, the hydrogen-type cation exchange resin is obtained by treating the transformation of the cation exchange resin according to the following method: the cation exchange resin was activated with hydrochloric acid solution and then rinsed with purified water until the eluate was neutral and had a conductivity below 50 mus/cm. The hydrogen type cation exchange resin is applied in the form of a circular resin bed by wet column packing, and the decolorized and desalted fermentation liquid obtained above passes through the hydrogen type cation exchange resin bed at a certain flow rate, for example, at a flow rate of 1-3 times of the total volume of the resin per hour. In the collected D-pantothenic acid solution, the D-pantothenic acid concentration (based on the calcium D-pantothenate) is generally from 23 to 46g/L, and the purity of the pantothenic acid liquid phase is from 86% to 92%. Alternatively, in this step, the cation exchange resin may be packed into a resin bed, then converted into a hydrogen type cation exchange resin by acid activation treatment, and the decolorized and desalted fermentation liquid obtained as described above may be passed through the resin bed to obtain a D-pantothenic acid solution.
Then, the D-pantothenic acid solution is passed through a weakly polar macroporous adsorbent resin, and D-pantothenic acid is adsorbed on the weakly polar macroporous adsorbent resin. The macroporous adsorption resin with weak polarity can be prepared from macroporous adsorption resin with aperture of 10-30 nm, particle size of 300-500 μm and specific surface area of 450-800 m 2 And/g of a styrene-based skeleton structure of weak-polarity macroporous adsorption resin. For example, a weak polar macroporous adsorbent resin of any of the model DM130, SD-8 and CAD45 manufactured by Ningbo light-striving resin Co., ltd. The weak-polarity macroporous adsorption resin is applied in the form of a circular resin bed by wet column packing, the ratio of the height to the diameter (namely the ratio of the height to the diameter) of the circular resin bed is more than or equal to 4, and the obtained D-pantothenic acid solution passes through the weak-polarity macroporous adsorption resin at a certain flow rate, for example, the weak-polarity macroporous adsorption resin can pass through the resin bed at a flow rate of 0.5-2 times of the total volume of the resin per hour, and preferably passes through the resin bed at a flow rate of 0.5-1 times of the total volume of the resin per hour. In actual operation, D-pantothenic acid at the outlet of the lower end of the column bed is used as the basis, and the column feeding is stopped during the detection.
D-pantothenic acid is adsorbed on a weak-polarity macroporous adsorption resin, and then the D-pantothenic acid adsorbed on the resin is resolved by using a resolving agent to obtain D-pantothenic acid resolving liquid. The adopted resolving agent is methanol and water according to the volume ratio of 60-100: 40 to 0, and preferably 80 to 100:20 to 0, and the flow rate of the resolving agent is 0.5 to 1 times of the total volume of the resin per hour. The effluent is collected after the analysis is started, and when the D-pantothenic acid concentration in the effluent is collected to be lower than 0.5g/L (calculated by D-calcium pantothenate), the collection is stopped, and the part of the collected liquid is the D-pantothenic acid analysis liquid, wherein the D-pantothenic acid concentration (calculated by D-calcium pantothenate) is 73-95 g/L, and the D-pantothenic acid liquid phase purity is more than or equal to 98%.
According to one embodiment of the present invention, in the preparation of D-calcium pantothenate in step (2), the above-obtained D-pantothenic acid analysis solution is converted into a D-calcium pantothenate solution by a calcium ion type cation exchange resin, and the D-calcium pantothenate solution is decolorized by activated carbon and concentrated by evaporation to obtain solid D-calcium pantothenate, wherein the calcium ion type cation exchange resin is a cation exchange resin converted into a calcium ion type cation exchange resin by acid activation and calcium chloride solution treatment.
The calcium ion type cation exchange resin is converted into calcium ion type cation exchange resin through acid activation and calcium chloride solution treatment, the adopted cation exchange resin is strong acid cation exchange resin, and the cation exchange resin can be obtained in the market, for example, any one of LXT-101 and LXT-105 type cation exchange resins produced by XAn blue Xiao technology and New Material Co., ltd, which are used in the step (1) can be selected. Specifically, the calcium ion type cation exchange resin is obtained by treating the transformation of the cation exchange resin according to the following method: adopting hydrochloric acid solution to activate and treat cation exchange resin to convert into hydrogen form, and then using purified water to wash until the eluate is neutral; the resin was then converted to calcium ions by treatment with a calcium chloride solution followed by rinsing with purified water until the eluate was free of calcium chloride and had a conductivity below 50 mus/cm. The calcium ion type cation exchange resin is applied in the form of a circular resin column bed through wet column packing, the obtained D-pantothenic acid analysis liquid passes through the calcium ion type cation exchange resin column bed at a certain flow rate, for example, the flow rate of 0.5-1 times of the total volume of the resin per hour, and column outlet effluent with the pH value of more than 6.0 is collected, so that the converted D-pantothenic acid calcium solution is obtained. In the collected D-calcium pantothenate solution, the concentration of the D-calcium pantothenate is generally 70-90 g/L, and the purity of the liquid phase of the D-calcium pantothenate is more than or equal to 99%.
Alternatively, in this step, a cation exchange resin may be packed into a resin bed, then acid-activated, and the calcium chloride solution is treated to convert it into a calcium ion type cation exchange resin, and then the D-pantothenic acid analysis solution obtained as described above is passed through the resin bed to obtain a D-calcium pantothenate solution.
Adding active carbon into the D-calcium pantothenate solution, wherein the dosage of the active carbon is 0.2-0.5 g of active carbon per 100 ml of the D-calcium pantothenate solution, stirring and decoloring for 30-60 minutes, and filtering to obtain decolored D-calcium pantothenate solution; then removing methanol and water in the D-calcium pantothenate solution by adopting a vacuum concentration mode at 60-80 ℃ to obtain the D-calcium pantothenate product with the quality meeting the standard. For example, methanol can be recovered by distillation and then spray-dried to directly obtain the calcium D-pantothenate product.
The method for producing high-purity calcium D-pantothenate of the present invention will be described more specifically by way of examples, but the scope of the present invention is not limited to these examples.
Filtration treatment of biological fermentation liquor stock solution of D-calcium pantothenate
150L of a stock solution of the biological fermentation broth of the calcium D-pantothenate was taken, the pH thereof was 7.2, the concentration of the calcium D-pantothenate was 75g/L as measured by centrifuging the supernatant, the purity of the liquid phase was 53%, and the conductivity was 25ms/cm. Filtering and pre-treating the fermentation liquor by adopting a ceramic membrane with the filtering precision of 50nm at the temperature of 23 ℃, continuously washing and filtering the concentrated liquor by using 90L of purified water after the volume is concentrated to 30L, and finally obtaining Tao Lvye L, wherein the concentration of the D-calcium pantothenate is 46g/L; the concentrate was then subjected to an ultrafiltration membrane treatment Tao Lvye having a molecular weight cut-off of 2500 daltons, and suitably washed with purified water to give an ultrafiltrate 240L, in which the concentration of calcium D-pantothenate was 39g/L.
Treatment of resin
The hydroxide anion exchange resin is obtained by treating anion exchange resin transformation according to the following method: activating the anion exchange resin with 4-5% (w/v) sodium hydroxide solution, and then washing with purified water until the eluate is neutral and the conductivity is below 50 μs/cm;
the hydrogen type cation exchange resin is obtained by treating the transformation of the cation exchange resin according to the following method: activating the cation exchange resin with 4-5% (w/v) hydrochloric acid solution, and then washing with purified water until the eluate is neutral and the conductivity is below 50 μs/cm;
pretreatment of weak-polarity macroporous adsorption resin: activation with methanol followed by rinsing the resin with purified water until no methanol odor;
the calcium ion type cation exchange resin is obtained by treating the transformation of the cation exchange resin according to the following method: adopting 4-5% (w/v) hydrochloric acid solution to activate and treat cation exchange resin to convert into hydrogen form, and then using purified water to wash until the eluate is neutral; the resin was then converted to calcium ions using a 0.5mol/L calcium chloride solution followed by washing with purified water until the eluate was free of calcium chloride and had a conductivity below 50. Mu.s/cm.
Example 1
Passing the obtained D-calcium pantothenate ultrafiltrate 97L through hydroxide-type anion exchange resin (model of anion exchange resin is LXT-281, wet packing is carried out, packing amount is 10L, height-diameter ratio is 4) at a flow rate of 10L per hour, and collecting column outlet effluent with light transmittance of more than 90% (420 nm), namely decolorized and desalted fermentation liquor; then, the decolorized and desalted fermentation liquid passes through hydrogen type cation exchange resin (the type of the cation exchange resin is LXT-101, the wet method is used for filling the column, the filling amount is 10L, the height-diameter ratio is 4) at the flow rate of 10L per hour, and the effluent liquid at the outlet of the column with the pH less than 2.0 is collected, namely the converted D-pantothenic acid solution; the D-pantothenic acid solution was passed through a weakly polar macroporous adsorbent resin (model DM130, wet packed column, packed amount 20L, aspect ratio 4) at a flow rate of 10L per hour, D-pantothenic acid was adsorbed on the weakly polar macroporous adsorbent resin, and the column was stopped when D-pantothenic acid was detected as a basis at the outlet at the lower end of the bed.
Then, the D-pantothenic acid adsorbed on the weak polar macroporous adsorbent resin is resolved by using methanol as a resolving agent, the methanol is passed through the resin bed at a flow rate of 20L per hour, and the effluent is discharged from the outlet at the lower end of the columnWhen the D-pantothenic acid concentration was less than 0.5g/L, the collection was stopped, and 40L of D-pantothenic acid-containing analytical solution was obtained, wherein the pantothenic acid concentration was 88g/L (based on calcium D-pantothenate) and the purity of the liquid phase was 98.4%. Then, the D-pantothenic acid analysis solution passes through calcium ion type cation exchange resin (the model of the cation exchange resin is LXT-101, the wet method is used for filling the column, the filling amount is 10L, the height-diameter ratio is 4) at the flow rate of 10L per hour, and the effluent liquid at the outlet of the column with the pH value of more than 6.0 is collected, namely the D-calcium pantothenate solution; then adding 200g of active carbon, stirring and decoloring for 30 minutes, and filtering to obtain decolored D-calcium pantothenate solution; then removing methanol and water by vacuum concentration at 70-80 ℃ to obtain 3485 g of D-calcium pantothenate product. The yield from ultrafiltrate to product was 92.1%, the appearance of the D-calcium pantothenate product was white powder, the content was 99.6%, and the specific optical rotation [ alpha ]]20/D＝27.5(C＝5％in H 2 O)。
Example 2
Passing 95L of the obtained D-calcium pantothenate ultrafiltrate through hydroxide-type anion exchange resin (model of anion exchange resin is LXT-281, wet packing is carried out, packing amount is 10L, height-diameter ratio is 4) at a flow rate of 10L per hour, and collecting effluent liquid at a column outlet with light transmittance of more than 90% (420 nm), namely decolorized and desalted fermentation liquor; then, the decolorized and desalted fermentation liquid passes through hydrogen type cation exchange resin (the type of the cation exchange resin is LXT-101, the wet method is used for filling the column, the filling amount is 10L, the height-diameter ratio is 4) at the flow rate of 10L per hour, and the effluent liquid at the outlet of the column with the pH less than 2.0 is collected, namely the converted D-pantothenic acid solution; the D-pantothenic acid solution was passed through a weakly polar macroporous adsorbent resin (model CAD45, wet packed column, packed amount 20L, aspect ratio 4) at a flow rate of 10L per hour, D-pantothenic acid was adsorbed on the weakly polar macroporous adsorbent resin, and the column was stopped when D-pantothenic acid was detected as a basis at the outlet at the lower end of the bed.
Then, D-pantothenic acid adsorbed on the weakly polar macroporous adsorbent resin was analyzed by using methanol/water (volume ratio 90:10) as an resolving agent, the methanol/water was passed through the resin bed at a flow rate of 10L per hour, and the collection was stopped when the D-pantothenic acid concentration in the effluent at the outlet of the lower end of the column was lower than 0.5g/L, and D-pantothenic acid resolving liquid 40L was obtained by collecting the D-pantothenic acid resolving liquid, wherein the pantothenic acid concentration was 85g/L (calculated as calcium D-pantothenate) and the purity of the liquid phase was 98.2%. Then, the D-pantothenic acid analysis solution passes through calcium ion type cation exchange resin (the model of the cation exchange resin is LXT-101, the wet method is used for filling the column, the filling amount is 10L, the height-diameter ratio is 4) at the flow rate of 10L per hour, and the effluent liquid at the outlet of the column with the pH value of more than 6.0 is collected, namely the D-calcium pantothenate solution; then adding 200g of active carbon, stirring and decoloring for 30 minutes, and filtering to obtain decolored D-calcium pantothenate solution; then under the condition of 70-80 ℃, adopting a vacuum concentration mode to remove methanol and water, and obtaining 3298 g of D-calcium pantothenate product. The yield from ultrafiltrate to product was 89.0%, the appearance of the D-calcium pantothenate product was white powder, the content was 99.5%, and the specific optical rotation [ alpha ]]20/D＝27.4(C＝5％in H 2 O)。
Example 3
Passing 100L of the obtained D-calcium pantothenate ultrafiltrate through hydroxide-type anion exchange resin (model of anion exchange resin is LXT-281, wet packing is carried out, packing amount is 10L, height-diameter ratio is 4) at a flow rate of 10L per hour, and collecting effluent from a column outlet with light transmittance of more than 90% (420 nm), namely decolorized and desalted fermentation liquor; then, the decolorized and desalted fermentation liquid passes through hydrogen type cation exchange resin (the type of the cation exchange resin is LXT-105, the wet method is packed into columns, the packing amount is 10L, the height-diameter ratio is 4) at the flow rate of 10L per hour, and column outlet effluent with the pH less than 2.0 is collected, namely the converted D-pantothenic acid solution; the D-pantothenic acid solution was passed through a weakly polar macroporous adsorbent resin (model CAD45, wet packed column, packed amount 20L, aspect ratio 4) at a flow rate of 10L per hour, D-pantothenic acid was adsorbed on the weakly polar macroporous adsorbent resin, and the column was stopped when D-pantothenic acid was detected as a basis at the outlet at the lower end of the bed.
Then, D-pantothenic acid adsorbed on the weakly polar macroporous adsorbent resin was analyzed using methanol as an analytical agent, the methanol was passed through the resin bed at a flow rate of 10L per hour, and the collection was stopped when the D-pantothenic acid concentration in the effluent at the outlet of the lower end of the column was lower than 0.5g/L, and D-pantothenic acid analytical liquid 40L was obtained by collecting, wherein the pantothenic acid concentration was 93g/L (based on D-calcium pantothenate) and the purity of the liquid phase was 98.6%. Then, the D-pantothenic acid analysis solution was passed through a calcium ion type cation exchange resin (model of cation exchange resin is LXT-105, wet packed column, packed amount is 10L, aspect ratio is 4) at a flow rate of 10L per hour,collecting effluent liquid at the outlet of the column with pH greater than 6.0 to obtain D-calcium pantothenate solution; then adding 200g of active carbon, stirring and decoloring for 30 minutes, and filtering to obtain decolored D-calcium pantothenate solution; then under the condition of 70-80 ℃ and adopting a vacuum concentration mode to remove methanol and water, 3646 g of D-calcium pantothenate product is obtained. The yield from ultrafiltrate to product was 93.5%, the appearance of the D-calcium pantothenate product was white powder, the content was 99.5%, and the specific optical rotation [ alpha ]]20/D＝27.6(C＝5％in H 2 O)。
Claims (10)
1. A process for the preparation of high purity calcium D-pantothenate, comprising the steps of:
(1) Purification treatment
Passing the filtered biological fermentation liquor of the D-calcium pantothenate through hydroxide anion exchange resin to obtain decolored and desalted fermentation liquor; the decolorized and desalted fermentation liquor is subjected to cation exchange through hydrogen type cation exchange resin and is converted into D-pantothenic acid solution; d-pantothenic acid solution passes through weak-polarity macroporous adsorption resin, D-pantothenic acid is adsorbed on the weak-polarity macroporous adsorption resin, and then the D-pantothenic acid adsorbed on the resin is resolved by using a resolving agent to obtain D-pantothenic acid resolving liquid;
wherein the hydroxide anion exchange resin is converted into hydroxide anion exchange resin through alkali activation treatment, and the hydrogen cation exchange resin is converted into hydrogen cation exchange resin through acid activation treatment;
(2) Preparation of D-calcium pantothenate
The D-pantothenic acid analysis solution obtained above is converted into a D-calcium pantothenate solution through a calcium ion type cation exchange resin, and the D-calcium pantothenate solution is decolorized and evaporated by active carbon to obtain solid D-calcium pantothenate, wherein the calcium ion type cation exchange resin is converted into the calcium ion type cation exchange resin through acid activation and calcium chloride solution treatment.
2. The process for producing high-purity calcium D-pantothenate according to claim 1, wherein in the purification treatment step, the anion-exchange resin used is a weakly basic anion-exchange resin; the hydroxide anion exchange resin is obtained by converting the anion exchange resin according to the following method: the anion exchange resin is activated with sodium hydroxide solution and then rinsed with purified water until the eluate is neutral and has a conductivity below 50 mus/cm.
3. The process for producing high-purity calcium D-pantothenate according to claim 1, wherein in the purification treatment step, the cation-exchange resin used is a strongly acidic cation-exchange resin; the hydrogen type cation exchange resin is obtained by treating the transformation of the cation exchange resin according to the following method: the cation exchange resin was activated with hydrochloric acid solution and then rinsed with purified water until the eluate was neutral and had a conductivity below 50 mus/cm.
4. The process for preparing high-purity calcium D-pantothenate according to claim 1, wherein in the purification step, the weakly polar macroporous adsorbent resin has a pore diameter of 10 to 30 nm, a particle diameter of 300 to 500. Mu.m, and a specific surface area of 450 to 800m 2 And/g of a styrene-based skeleton structure of weak-polarity macroporous adsorption resin.
5. The process for producing high-purity calcium D-pantothenate according to claim 1, wherein in the step (2) of producing calcium D-pantothenate, the cation-exchange resin used is a strongly acidic cation-exchange resin, and the calcium ion-exchange resin is obtained by converting a cation-exchange resin according to the following method: adopting hydrochloric acid solution to activate and treat cation exchange resin to convert into hydrogen form, and then using purified water to wash until the eluate is neutral; the resin was then converted to calcium ions by treatment with a calcium chloride solution followed by rinsing with purified water until the eluate was free of calcium chloride and had a conductivity below 50 mus/cm.
6. The process for producing high-purity D-calcium pantothenate according to any one of claims 1 to 5, wherein the filtered biological fermentation broth of D-calcium pantothenate is a fermentation broth supernatant obtained by filtering a biological fermentation broth stock of D-calcium pantothenate obtained by fermentation with a microorganism, wherein the pH of the biological fermentation broth stock of D-calcium pantothenate is 6.5 to 7.5, the concentration of D-calcium pantothenate is 60 to 85g/L, the liquid phase purity of D-calcium pantothenate is 50 to 60%, and the conductivity is 15 to 30ms/cm as measured by centrifuging the supernatant.
7. The process for producing high-purity calcium D-pantothenate according to claim 6, wherein the process comprises the steps of filtering a raw liquid of a biological fermentation liquid of calcium D-pantothenate with a ceramic membrane to remove mycelia and solids in the fermentation liquid and obtain calcium D-pantothenate Tao Lvye; and then ultra-filtering the D-calcium pantothenate Tao Lvye by using an ultra-filtering membrane to remove pigments and soluble proteins in the D-calcium pantothenate to obtain the D-calcium pantothenate ultra-filtrate.
8. The process for producing high-purity calcium D-pantothenate according to claim 7, wherein, in the purification treatment step,
passing the obtained D-calcium pantothenate ultrafiltrate through an oxyhydrogen anion exchange resin column bed, and collecting column outlet effluent with light transmittance of more than 90% at 420nm, namely decolorized and desalted fermentation liquor, wherein the concentration of the D-calcium pantothenate is 25-50 g/L;
passing the decolorized and desalted fermentation liquor through a hydrogen type cation exchange resin column bed, and collecting column outlet effluent with the pH less than 2.0 to obtain a converted D-pantothenic acid solution, wherein the D-pantothenic acid concentration is 23-46 g/L, calculated by D-calcium pantothenate;
passing the D-pantothenic acid solution through a weak-polarity macroporous adsorption resin bed, adsorbing the D-pantothenic acid on weak-polarity macroporous adsorption resin, and then using methanol and water according to the volume ratio of 60-100: 40-0 to obtain D-pantothenic acid analysis liquid, wherein the D-pantothenic acid concentration is 73-95 g/L, calculated by D-calcium pantothenate.
9. The process for producing high-purity calcium D-pantothenate according to claim 7, wherein in the step (2) of producing calcium D-pantothenate, the obtained D-pantothenate analysis solution is passed through a bed of a calcium ion-type cation-exchange resin, and the effluent from the column outlet having a pH of more than 6.0 is collected to obtain a converted calcium D-pantothenate solution having a concentration of 70 to 90g/L of calcium D-pantothenate and a purity of 99% or more in the liquid phase of calcium D-pantothenate.
10. The process for producing high-purity calcium D-pantothenate according to claim 9, wherein in the production of calcium D-pantothenate in the step (2), 0.2 to 0.5g of activated carbon is added per 100 ml of the calcium D-pantothenate solution, and the mixture is decolorized by stirring for 30 to 60 minutes and then filtered to obtain a decolorized calcium D-pantothenate solution; then removing methanol and water in the D-calcium pantothenate solution by adopting a vacuum concentration mode at 60-80 ℃ to obtain the D-calcium pantothenate product with the quality meeting the standard.
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