CN101659641A - Preparation method of L-carnosine zinc - Google Patents
Preparation method of L-carnosine zinc Download PDFInfo
- Publication number
- CN101659641A CN101659641A CN200910182738A CN200910182738A CN101659641A CN 101659641 A CN101659641 A CN 101659641A CN 200910182738 A CN200910182738 A CN 200910182738A CN 200910182738 A CN200910182738 A CN 200910182738A CN 101659641 A CN101659641 A CN 101659641A
- Authority
- CN
- China
- Prior art keywords
- carnosine
- zinc
- preparation
- exchange resin
- aqueous solution
- 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.)
- Granted
Links
- MORUQNQGRSLTCD-FJXQXJEOSA-N (2s)-2-(3-aminopropanoylamino)-3-(1h-imidazol-5-yl)propanoic acid;zinc Chemical compound [Zn].NCCC(=O)N[C@H](C(O)=O)CC1=CNC=N1 MORUQNQGRSLTCD-FJXQXJEOSA-N 0.000 title claims abstract description 67
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- CQOVPNPJLQNMDC-ZETCQYMHSA-N carnosine Chemical compound [NH3+]CCC(=O)N[C@H](C([O-])=O)CC1=CNC=N1 CQOVPNPJLQNMDC-ZETCQYMHSA-N 0.000 claims abstract description 69
- 108010087806 Carnosine Proteins 0.000 claims abstract description 67
- CQOVPNPJLQNMDC-UHFFFAOYSA-N N-beta-alanyl-L-histidine Natural products NCCC(=O)NC(C(O)=O)CC1=CN=CN1 CQOVPNPJLQNMDC-UHFFFAOYSA-N 0.000 claims abstract description 67
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 28
- 230000004913 activation Effects 0.000 claims abstract description 21
- 239000011701 zinc Substances 0.000 claims abstract description 21
- 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 19
- 239000003456 ion exchange resin Substances 0.000 claims abstract description 19
- 229920003303 ion-exchange polymer Polymers 0.000 claims abstract description 19
- 239000007788 liquid Substances 0.000 claims abstract description 15
- 238000000926 separation method Methods 0.000 claims abstract description 15
- 239000011347 resin Substances 0.000 claims abstract description 10
- 229920005989 resin Polymers 0.000 claims abstract description 10
- 150000003751 zinc Chemical class 0.000 claims abstract description 10
- 229910052725 zinc Inorganic materials 0.000 claims abstract description 4
- 239000007864 aqueous solution Substances 0.000 claims description 38
- 239000003957 anion exchange resin Substances 0.000 claims description 26
- 150000002500 ions Chemical class 0.000 claims description 12
- 230000000694 effects Effects 0.000 claims description 7
- ZOIORXHNWRGPMV-UHFFFAOYSA-N acetic acid;zinc Chemical compound [Zn].CC(O)=O.CC(O)=O ZOIORXHNWRGPMV-UHFFFAOYSA-N 0.000 claims description 6
- 235000013904 zinc acetate Nutrition 0.000 claims description 6
- 239000004246 zinc acetate Substances 0.000 claims description 6
- 230000003068 static effect Effects 0.000 claims description 5
- ONDPHDOFVYQSGI-UHFFFAOYSA-N zinc nitrate Chemical compound [Zn+2].[O-][N+]([O-])=O.[O-][N+]([O-])=O ONDPHDOFVYQSGI-UHFFFAOYSA-N 0.000 claims description 4
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 2
- -1 zinc halide Chemical class 0.000 claims description 2
- 229960001763 zinc sulfate Drugs 0.000 claims description 2
- 229910000368 zinc sulfate Inorganic materials 0.000 claims description 2
- BEAZKUGSCHFXIQ-UHFFFAOYSA-L zinc;diacetate;dihydrate Chemical compound O.O.[Zn+2].CC([O-])=O.CC([O-])=O BEAZKUGSCHFXIQ-UHFFFAOYSA-L 0.000 claims description 2
- RXBXBWBHKPGHIB-UHFFFAOYSA-L zinc;diperchlorate Chemical compound [Zn+2].[O-]Cl(=O)(=O)=O.[O-]Cl(=O)(=O)=O RXBXBWBHKPGHIB-UHFFFAOYSA-L 0.000 claims description 2
- 230000003287 optical effect Effects 0.000 abstract description 12
- 239000002994 raw material Substances 0.000 abstract description 6
- 239000003960 organic solvent Substances 0.000 abstract description 4
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 abstract description 2
- 239000003480 eluent Substances 0.000 abstract 2
- PTFCDOFLOPIGGS-UHFFFAOYSA-N Zinc dication Chemical compound [Zn+2] PTFCDOFLOPIGGS-UHFFFAOYSA-N 0.000 abstract 1
- 238000009776 industrial production Methods 0.000 abstract 1
- 239000012450 pharmaceutical intermediate Substances 0.000 abstract 1
- 230000001376 precipitating effect Effects 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 21
- 238000001179 sorption measurement Methods 0.000 description 21
- QRYRORQUOLYVBU-VBKZILBWSA-N Carnosic acid Natural products CC([C@@H]1CC2)(C)CCC[C@]1(C(O)=O)C1=C2C=C(C(C)C)C(O)=C1O QRYRORQUOLYVBU-VBKZILBWSA-N 0.000 description 18
- 229940044199 carnosine Drugs 0.000 description 18
- 238000000034 method Methods 0.000 description 14
- 239000000126 substance Substances 0.000 description 14
- 238000010828 elution Methods 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- 238000005342 ion exchange Methods 0.000 description 10
- 239000003814 drug Substances 0.000 description 5
- 108700035912 polaprezinc Proteins 0.000 description 4
- 238000010521 absorption reaction Methods 0.000 description 3
- 238000004519 manufacturing process Methods 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- NTYJJOPFIAHURM-UHFFFAOYSA-N Histamine Chemical compound NCCC1=CN=CN1 NTYJJOPFIAHURM-UHFFFAOYSA-N 0.000 description 2
- 208000008469 Peptic Ulcer Diseases 0.000 description 2
- 208000019425 cirrhosis of liver Diseases 0.000 description 2
- 208000011906 peptic ulcer disease Diseases 0.000 description 2
- 239000002594 sorbent Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- IUWLTSZHVYHOHY-FJXQXJEOSA-L zinc;(2s)-2-(3-azanidylpropanoylazanidyl)-3-(1h-imidazol-5-yl)propanoate Chemical compound [Zn+2].[NH-]CCC(=O)[N-][C@H](C([O-])=O)CC1=CN=CN1 IUWLTSZHVYHOHY-FJXQXJEOSA-L 0.000 description 2
- NSVFSAJIGAJDMR-UHFFFAOYSA-N 2-[benzyl(phenyl)amino]ethyl 5-(5,5-dimethyl-2-oxido-1,3,2-dioxaphosphinan-2-yl)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3-carboxylate Chemical compound CC=1NC(C)=C(C(=O)OCCN(CC=2C=CC=CC=2)C=2C=CC=CC=2)C(C=2C=C(C=CC=2)[N+]([O-])=O)C=1P1(=O)OCC(C)(C)CO1 NSVFSAJIGAJDMR-UHFFFAOYSA-N 0.000 description 1
- IVVHAAOJLULJLK-YDXSIYMFSA-E Aceglutamide aluminum Chemical compound [OH-].[OH-].[OH-].[OH-].[Al+3].[Al+3].[Al+3].CC(=O)N[C@H](C([O-])=O)CCC(N)=O.CC(=O)N[C@H](C([O-])=O)CCC(N)=O.CC(=O)N[C@H](C([O-])=O)CCC(N)=O.CC(=O)N[C@H](C([O-])=O)CCC(N)=O.CC(=O)N[C@H](C([O-])=O)CCC(N)=O IVVHAAOJLULJLK-YDXSIYMFSA-E 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 229960002627 aceglutamide aluminum Drugs 0.000 description 1
- 230000002467 anti-pepsin effect Effects 0.000 description 1
- 239000003699 antiulcer agent Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 230000007882 cirrhosis Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000006378 damage Effects 0.000 description 1
- 230000002950 deficient Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 229950003102 efonidipine Drugs 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 201000005917 gastric ulcer Diseases 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 229960001340 histamine Drugs 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229950004693 polaprezinc Drugs 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 235000014347 soups Nutrition 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a preparation method of L-carnosine zinc, which belongs to the technical field of preparation of pharmaceutical intermediates. The preparation method comprises the steps of dissolving L-carnosine in water for forming water solution of the L-carnosine, leading the water solution of the L-carnosine to be reacted with ion exchange resin for absorbing the L-carnosine on the resin for activation, adopting the water solution of zinc salt for eluting the resin absorbed with the L-carnosine, combining zinc ions in eluent with the activated L-carnosine molecules for forming L-carnosine zinc, precipitating from the water and carrying out solid-liquid separation on the eluent, thereby obtaining the L-carnosine zinc. The preparation method has the advantages that the technicalscheme for preparing the L-carnosine zinc has good yield, the zinc content in a product is not less than 22.0%, the optical rotation is not less than plus 8.0 degrees, and the quality is stable; andthe technical scheme does not use an organic solvent, the used ion exchange resin is recycled, and the main raw material of the L-carnosine is completely reacted, thereby improving the utilization rate of raw materials, reducing the preparation cost and meeting the industrial production requirements.
Description
Technical field
The invention belongs to the preparing technical field of medicine intermediate, be specifically related to a kind of preparation method of L-carnosine zinc, a kind of mode by ion-exchange of more specifically saying so prepares the method for L-carnosine zinc.
Background technology
The proterties of L-carnosine zinc is white powder, and is water insoluble, is insoluble in organic solvent; Molecular formula is C
9H
12N
4O
3Zn; The English chemical name of L-carnosine zinc is: Zinc N-(3-aminopropionyl) histidine, and structural formula is as follows:
L-carnosine zinc (L-carnosine zincate) has another name called zinc L-carnosine (polaprezinc), is the antiulcer agent new drug that Japanese Hamari chemistry limited-liability company and Zeria drugmaker develop jointly.Studies show that by animal experimental model the L-carnosine zinc can quicken the healing of chronic gastric ulcer, and can stimulate epithelium layer propagation.Oral in advance L-carnosine zinc soup can prevent the development by water logging, histamine, hydrochloric acid-acetylsalicylic acid-caused rat stomach injury of ethanol.The relieving haperacidity effect of L-carnosine zinc is better than sodium bicarbonate, and the effect of its anti-peptic ulcer is higher than aceglutamide aluminum.Therefore the L-carnosine zinc is a kind of mucosa protective agent with antioxygenation, and is the effective drug for peptic ulcer thing (1984-88270 communiques of Japanese Patent) that is widely used already.Simultaneously diseases such as hepatitis and liver cirrhosis there is good curative effect, asks for an interview Chinese invention patent Granted publication CN100349609C (cirrhosis treating medicine).This medicine was submitted application for registration in Japan in 1993, and 1994 at Japanese Initial Public Offering, trade(brand)name Promac.Bamarl company in 1989 in European application the compound of zinc L-carnosine (crystallization) patent.Do not look into and see that the related manufacturing processes of this medicine patent is arranged in China.
Find by retrieval: with EP0203320A2, JP2007246401, JP59033270, JP64042471 etc. is that the method for preparing the L-carnosine zinc of representative is: the L-carnosine is dissolved in the anhydrous of alkalescence or the polar organic solvent that water content is low, then above-mentioned drips of solution is added in the organic solvent that is dissolved with zinc salt, product is separated out in the dropping process, last solid-liquid separation obtains thick product, thick product through water washing desalt the finished product.Chemical equation is as follows:
L-carnosine (L-Car) L-carnosine zinc (L-Car-Zn)
But it is big that above-mentioned technology exists solvent-oil ratio, and raw material availability is low, defective such as residual salt height in the product.
Summary of the invention
Task of the present invention is to provide a kind of and need not to use solvent, raw material availability height and yield good and use the preparation method who reduces preparation cost and satisfy the L-carnosine zinc that suitability for industrialized production requires.
Task of the present invention is finished like this, a kind of preparation method of L-carnosine zinc, it is the L-carnosine to be dissolved in the water form the L-carnosine aqueous solution, the L-carnosine aqueous solution and ion exchange resin effect, the L-carnosine is adsorbed on the resin activates, adopt the above-mentioned resin that is adsorbed with the L-carnosine of aqueous solution wash-out of zinc salt, the zine ion in the elutriant combines formation L-carnosine zinc and separates out from water with activatory L-carnosine molecule, to the elute soln solid-liquid separation, obtain the L-carnosine zinc.
In a specific embodiment of the present invention, described L-carnosine is dissolved in the water and is dissolved in the pure water for the L-carnosine.
In another specific embodiment of the present invention, the mass percent concentration of the described L-carnosine aqueous solution is 0.5-2.5%.
In another specific embodiment of the present invention, described ion exchange resin is macroporous anion exchange resin.
In another specific embodiment of the present invention, described macroporous anion exchange resin is the macropore basic anion exchange resin.
Also have in the specific embodiment of the present invention, the mode of action of the described L-carnosine aqueous solution and ion exchange resin effect be static state or dynamic in any one mode of action.
More of the present invention and in specific embodiment, described L-carnosine is adsorbed in that the activatory activation temperature is 0-10 ℃ on the resin.
In of the present invention and then specific embodiment, described zinc salt is zinc halide, zinc sulfate, zinc nitrate, zinc acetate, Zinc diacetate dihydrate or zinc perchlorate.
Of the present invention again more and in specific embodiment, the eluting temperature of described wash-out is 15-30 ℃.
In again of the present invention and then specific embodiment, the flow velocity of the aqueous solution of the zinc salt the during aqueous solution wash-out of described employing zinc salt is 5.0-10.0vvh
-1
It is good to adopt technique scheme to prepare L-carnosine zinc yield, zinc content 〉=22.0% in the product, specific rotation 〉=+8.0 °, steady quality; And not with an organic solvent, employed ion exchange resin is able to cyclically utilizing in the technique scheme, and main raw material L-carnosine reacts completely, thereby can improve raw material availability, reduces preparation cost, satisfies the suitability for industrialized production requirement.
Embodiment:
Embodiment 1:
Get the L-carnosine 2.5g of optical purity more than 99.5%, dissolve with the 500g pure water, get preprepared preferred but not marque that produced by Chinese Hebei province Langfang New Times chemical industry company limited is that macropore basic anion exchange resin 100g drops into the above-mentioned L-carnosine aqueous solution for the D201 macroporous anion exchange resin with being limited to, stir 2.0h (Static Adsorption), temperature is controlled in 5-10 ℃, the resin that absorption is good is adorned post, is 2% ZnCl with mass percent concentration
2The reverse wash-out of the aqueous solution, temperature is controlled in 15-20 ℃ during wash-out, and elution speed is controlled in 5.0-6.0vvh
-1Along with the carrying out of wash-out, the L-carnosine zinc of generation is separated out from the aqueous solution, when no solid washes out in the elutriant, merges and contains L-carnosine zinc elutriant, and 80 ℃ of oven dry after the solid-liquid separation get L-carnosine zinc product 3g.Mass yield: 120%; Product Zn%:22.1%; Specific rotation :+8.0 °.The chemical equation of said process is as follows:
ROH
-+L-Car→RCar
-+OH
-
RCar
-+ZnCl
2→RCl
-+L-Car-Zn
R------ion exchange resin skeleton;
The L-car-----L-carnosine is called for short.
Embodiment 2:
Get the L-carnosine 5.0g of optical purity more than 99.5%, dissolve with the 500g pure water, get the same embodiment 1 described ion exchange resin 100g that anticipates and drop into the above-mentioned L-carnosine aqueous solution, (Static Adsorption: the sorbent material of Static Adsorption specified amount reaches balance with quantitative solution through fully contacting for a long time to stir 2.0h.), temperature is controlled in 5-10 ℃, and the resin dress post that absorption is good is with the ZnCl of zine ion mass concentration 2%
2The reverse wash-out of the aqueous solution, temperature is controlled in 20-30 ℃ during wash-out, and elution speed is controlled in 5.0-6.0vvh
-1Along with the carrying out of wash-out, the L-carnosine zinc of generation is separated out from the aqueous solution, when no solid washes out in the elutriant, merge and to contain L-carnosine zinc elutriant, after the solid-liquid separation 80 ℃ dry L-carnosine zinc product 6.2g.Mass yield: 124%; Product Zn%:22.0%; Specific rotation :+8.0 °.The chemical equation of said process such as embodiment 1.
Embodiment 3:
Get the L-carnosine 20g of optical purity more than 99.5%, dissolve with the 1000g pure water, get D201 (marque, macroporous anion exchange resin are the macropore basic anion exchange resin) the ion exchange resin 200g that anticipates and adorn post, with the ion exchange column of above-mentioned carnosine solution by installing, adsorption activation (dynamic adsorption), temperature is controlled in 0-5 ℃, and flow rate control is 1.0vvh
-1, after the carnosine solution upper prop activation, be 2% ZnCl with the zine ion mass concentration
2The reverse wash-out of the aqueous solution, temperature is controlled in 20-30 ℃ during wash-out, and elution speed is controlled in 5.0-6.0vvh
-1Along with the carrying out of wash-out, the L-carnosine zinc of generation is separated out from the aqueous solution, when no solid washes out in the elutriant, merge and to contain L-carnosine zinc elutriant, after the solid-liquid separation 80 ℃ dry L-carnosine zinc product 25.3g.Mass yield: 126.5%; Product Zn%:22.2%; Specific rotation :+8.0 °.The chemical equation of said process such as embodiment 1.
Embodiment 4:
Get the L-carnosine 22.6g of optical purity more than 99.5%, dissolve with the 1000g pure water, get D293 (marque, macroporous anion exchange resin are the macropore basic anion exchange resin) the ion exchange resin 250g that anticipates and adorn post, with the ion exchange column of above-mentioned carnosine solution by installing, adsorption activation (dynamic adsorption), temperature is controlled in 0-5 ℃, and flow rate control is 1.0vvh
-1, after the carnosine solution upper prop activation, be 2% ZnCl with the zine ion mass concentration
2The reverse wash-out of the aqueous solution, temperature is controlled in 20-30 ℃ during wash-out, and elution speed is controlled in 5.0-6.0vvh
-1Along with the carrying out of wash-out, the L-carnosine zinc of generation is separated out from the aqueous solution, when no solid washes out in the elutriant, merge and to contain L-carnosine zinc elutriant, solid-liquid separation, 80 ℃ dry L-carnosine zinc product 28.7g.Mass yield: 127.0%; Product Zn%:22.4%; Specific rotation :+8.3 °.The chemical equation of said process such as embodiment 1.
Embodiment 5:
Get the L-carnosine 16.6g of optical purity more than 99.5%, dissolve with the 1000g pure water, get D202 (marque, macroporous anion exchange resin are the macropore basic anion exchange resin) the ion exchange resin 200g that anticipates and adorn post, with the ion exchange column of above-mentioned carnosine solution by installing, adsorption activation (dynamic adsorption), temperature is controlled in 0-5 ℃, and flow rate control is 1.0vvh
-1, after the carnosine solution upper prop activation, be 2% ZnCl with the zine ion mass concentration
2The reverse wash-out of the aqueous solution, temperature is controlled in 20-30 ℃ during wash-out, and elution speed is controlled in 5.0-6.0vvh
-1Along with the carrying out of wash-out, the L-carnosine zinc of generation is separated out from the aqueous solution, when no solid washes out in the elutriant, merge and to contain L-carnosine zinc elutriant, solid-liquid separation, 80 ℃ dry L-carnosine zinc product 21g.Mass yield: 126.5%; Product Zn%:22.2%; Specific rotation :+8.2 °.The chemical equation of said process such as embodiment 1.
Embodiment 6:
Get the L-carnosine 22.6g of optical purity more than 99.5%, dissolve with the 1000g pure water, get D293 (marque, macroporous anion exchange resin are the macropore basic anion exchange resin) the ion exchange resin 200g that anticipates and adorn post, with the ion exchange column of above-mentioned carnosine solution by installing, adsorption activation (dynamic adsorption), temperature is controlled in 0-5 ℃, and flow rate control is 1.0vvh
-1, after the carnosine solution upper prop activation, be 2% ZnCl with the zine ion mass concentration
2The reverse wash-out of the aqueous solution, temperature is controlled in 20-30 ℃ during wash-out, and elution speed is controlled in 6.0-8.0vvh
-1Along with the carrying out of wash-out, the L-carnosine zinc of generation is separated out from the aqueous solution, when no solid washes out in the elutriant, merge and to contain L-carnosine zinc elutriant, solid-liquid separation, 80 ℃ dry L-carnosine zinc product 28.7g.Mass yield: 127.2%; Product Zn%:22.3%; Specific rotation :+8.4 °.The chemical equation of said process such as embodiment 1.
Embodiment 7:
Get the L-carnosine 22.6g of optical purity more than 99.5%, dissolve with the 1000g pure water, get D293 (marque, macroporous anion exchange resin are the macropore basic anion exchange resin) the ion exchange resin 200g that anticipates and adorn post, with the ion exchange column of above-mentioned carnosine solution by installing, adsorption activation (dynamic adsorption: the circulation absorption of promptly adopting usually, the sorbent material of certainweight is filled in the adsorption column, makes the certain solution of concentration flow through with certain flow velocity.), temperature is controlled in 0-5 ℃, and flow rate control is 1.0vvh
-1, after the carnosine solution upper prop activation, be 2% ZnS0 with the zine ion mass concentration
4The reverse wash-out of the aqueous solution, temperature is controlled in 20-30 ℃ during wash-out, and elution speed is controlled in 5.0-6.0vvh
-1Along with the carrying out of wash-out, the L-carnosine zinc of generation is separated out from the aqueous solution, when no solid washes out in the elutriant, merge and to contain L-carnosine zinc elutriant, solid-liquid separation, 80 ℃ dry L-carnosine zinc product 28.4g.Mass yield: 125.7%; Product Zn%:22.0%; Specific rotation :+8.0 °.The chemical equation of present embodiment is as follows:
ROH
-+L-Car→RCar
-+OH
-
RCar
-+ZnSO
4→RSO
4 2-+L-Car-Zn
R------ion exchange resin skeleton,
The L-car-----L-carnosine is called for short.
Embodiment 8:
Get the L-carnosine 20g of optical purity more than 99.5%, dissolve with the 1000g pure water, get D293 (marque, macroporous anion exchange resin are the macropore basic anion exchange resin) the ion exchange resin 200g that anticipates and adorn post, with the ion exchange column of above-mentioned carnosine solution by installing, adsorption activation (dynamic adsorption), temperature is controlled in 0-5 ℃, and flow rate control is 1.0vvh
-1, after the carnosine solution upper prop activation, be 2% the reverse wash-out of zinc acetate aqueous solution with the zine ion mass concentration, temperature is controlled in 20-25 ℃ during wash-out, and elution speed is controlled in 5.0-6.0vvh
-1Along with the carrying out of wash-out, the L-carnosine zinc of generation is separated out from the aqueous solution, when no solid washes out in the elutriant, merge and to contain L-carnosine zinc elutriant, solid-liquid separation, 80 ℃ dry L-carnosine zinc product 25.2g.Yield: 126%; Product Zn%:22.2%; Specific rotation :+8.3 °.The chemical equation of present embodiment is as follows:
ROH
-+L-Car→RCar
-+OH
-
RCar
-+Zn(CH3COO
-)
2→RCH
3COO
-+L-Car-Zn
R------ion exchange resin skeleton,
The L-car-----L-carnosine is called for short.
Embodiment 9:
Get the L-carnosine 22.6g of optical purity more than 99.5%, dissolve with the 1000g pure water, get D202 (marque, macroporous anion exchange resin are the macropore basic anion exchange resin) the ion exchange resin 250g that anticipates and adorn post, with the ion exchange column of above-mentioned carnosine solution by installing, adsorption activation, temperature is controlled in 0-5 ℃, and flow rate control is 1.0vvh
-1, after the carnosine solution upper prop activation, be 2.5% the reverse wash-out of zinc acetate aqueous solution with the zine ion mass concentration, temperature is controlled in 20-25 ℃ during wash-out, and elution speed is controlled in 8.0-10.0vvh
-1Along with the carrying out of wash-out, the L-carnosine zinc of generation is separated out from the aqueous solution, when no solid washes out in the elutriant, merge and to contain L-carnosine zinc elutriant, solid-liquid separation, 80 ℃ dry L-carnosine zinc product 28.3g.Mass yield: 125.2%; Product Zn%; 22.5%, specific rotation :+8.4 °.The chemical equation of said process such as embodiment 8.
Embodiment 10:
Get the L-carnosine 22.6g of optical purity more than 99.5%, dissolve with the 1000g pure water, get D201 (marque, macroporous anion exchange resin are the macropore basic anion exchange resin) the ion exchange resin 200g that anticipates and adorn post, with the ion exchange column of above-mentioned carnosine solution by installing, adsorption activation (dynamic adsorption), temperature is controlled in 0-5 ℃, and flow rate control is 1.0vvh
-1, after the carnosine solution upper prop activation, be 2% the reverse wash-out of zinc acetate aqueous solution with the zine ion mass concentration, temperature is controlled in 20-30 ℃ during wash-out, and elution speed is controlled in 6.0-8.0vvh
-1Along with the carrying out of wash-out, the L-carnosine zinc of generation is separated out from the aqueous solution, when no solid washes out in the elutriant, merge and to contain L-carnosine zinc elutriant, solid-liquid separation, 80 ℃ dry L-carnosine zinc product 28.5g.Yield: 126.1%; Product Zn%:22.2%; Specific rotation :+8.2 °.The chemical equation of said process such as embodiment 8
Embodiment 11:
Get the L-carnosine 16.6g of optical purity more than 99.5%, dissolve with the 1000g pure water, get D201 (marque, macroporous anion exchange resin are the macropore basic anion exchange resin) the ion exchange resin 200g that anticipates and adorn post, with the ion exchange column of above-mentioned carnosine solution by installing, adsorption activation (dynamic adsorption), temperature is controlled in 0-5 ℃, and flow rate control is 1.0vvh
-1, after the carnosine solution upper prop activation, be 2% the reverse wash-out of zinc acetate aqueous solution with the zine ion mass concentration, temperature is controlled in 20-30 ℃ during wash-out, and elution speed is controlled in 8.0-10.0vvh
-1Along with the carrying out of wash-out, the L-carnosine zinc of generation is separated out from the aqueous solution, when no solid washes out in the elutriant, merge and to contain L-carnosine zinc elutriant, solid-liquid separation, 80 ℃ dry L-carnosine zinc product 21.1g.Mass yield: 127.1%; Product Zn%:22.0%; Specific rotation :+8.2 °.The chemical equation of said process such as embodiment 8.
Claims (10)
1, a kind of preparation method of L-carnosine zinc, it is characterized in that it is the L-carnosine to be dissolved in the water form the L-carnosine aqueous solution, the L-carnosine aqueous solution and ion exchange resin effect, the L-carnosine is adsorbed on the resin to be activated, adopt the above-mentioned resin that is adsorbed with the L-carnosine of aqueous solution wash-out of zinc salt, zine ion in the elutriant combines formation L-carnosine zinc and separates out from water with activatory L-carnosine molecule, to the elute soln solid-liquid separation, obtain the L-carnosine zinc.
2, the preparation method of L-carnosine zinc according to claim 1 is characterized in that described L-carnosine is dissolved in the water to be dissolved in the pure water for the L-carnosine.
3, the preparation method of L-carnosine zinc according to claim 1, the mass percent concentration that it is characterized in that the described L-carnosine aqueous solution is 0.5-2.5%.
4, the preparation method of L-carnosine zinc according to claim 1 is characterized in that described ion exchange resin is macroporous anion exchange resin.
5, the preparation method of L-carnosine zinc according to claim 4 is characterized in that described macroporous anion exchange resin is the macropore basic anion exchange resin.
6, the preparation method of L-carnosine zinc according to claim 1, the mode of action that it is characterized in that the described L-carnosine aqueous solution and ion exchange resin effect for static or dynamically in any one mode of action.
7, the preparation method of L-carnosine zinc according to claim 1 is characterized in that described L-carnosine is adsorbed in that the activatory activation temperature is 0-10 ℃ on the resin.
8, the preparation method of L-carnosine zinc according to claim 1 is characterized in that described zinc salt is zinc halide, zinc sulfate, zinc nitrate, zinc acetate, Zinc diacetate dihydrate or zinc perchlorate.
9, the preparation method of L-carnosine zinc according to claim 1, the eluting temperature that it is characterized in that described wash-out is 15-30 ℃.
10, the preparation method of L-carnosine zinc according to claim 1, the flow velocity of the aqueous solution of the zinc salt when it is characterized in that the aqueous solution wash-out of described employing zinc salt is 5.0-10.0vvh
-1
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101827383A CN101659641B (en) | 2009-09-04 | 2009-09-04 | Preparation method of L-carnosine zinc |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2009101827383A CN101659641B (en) | 2009-09-04 | 2009-09-04 | Preparation method of L-carnosine zinc |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101659641A true CN101659641A (en) | 2010-03-03 |
| CN101659641B CN101659641B (en) | 2011-02-16 |
Family
ID=41787917
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2009101827383A Active CN101659641B (en) | 2009-09-04 | 2009-09-04 | Preparation method of L-carnosine zinc |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101659641B (en) |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103120646A (en) * | 2011-11-21 | 2013-05-29 | 四川海思科制药有限公司 | Polaprezinc granules and preparation method thereof |
| CN107865827A (en) * | 2016-09-28 | 2018-04-03 | 四川海思科制药有限公司 | A kind of Polaprezinc Orally disintegrating tablet medicament composition and preparation method thereof |
| CN111196837A (en) * | 2018-11-20 | 2020-05-26 | 皕达生物科技(上海)有限公司 | Preparation method of polaprezinc and polaprezinc preparation |
| CN111317812A (en) * | 2020-03-18 | 2020-06-23 | 西北工业大学 | Self-assembled carnosine fluorescent nanoparticles, preparation method and application |
| KR20200143805A (en) * | 2019-06-17 | 2020-12-28 | 주식회사 한서켐 | Preparing method of crystalline polaprezinc using aqueous solution |
-
2009
- 2009-09-04 CN CN2009101827383A patent/CN101659641B/en active Active
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103120646A (en) * | 2011-11-21 | 2013-05-29 | 四川海思科制药有限公司 | Polaprezinc granules and preparation method thereof |
| CN103120646B (en) * | 2011-11-21 | 2015-05-20 | 四川海思科制药有限公司 | Polaprezinc granules and preparation method thereof |
| CN107865827A (en) * | 2016-09-28 | 2018-04-03 | 四川海思科制药有限公司 | A kind of Polaprezinc Orally disintegrating tablet medicament composition and preparation method thereof |
| CN107865827B (en) * | 2016-09-28 | 2022-04-05 | 四川海思科制药有限公司 | Pharmaceutical composition of polaprezinc orally disintegrating tablets and preparation method thereof |
| CN111196837A (en) * | 2018-11-20 | 2020-05-26 | 皕达生物科技(上海)有限公司 | Preparation method of polaprezinc and polaprezinc preparation |
| CN111196837B (en) * | 2018-11-20 | 2023-07-28 | 皕达生物科技(上海)有限公司 | Preparation method of polyprenone and polyprenone preparation |
| KR20200143805A (en) * | 2019-06-17 | 2020-12-28 | 주식회사 한서켐 | Preparing method of crystalline polaprezinc using aqueous solution |
| KR102212260B1 (en) * | 2019-06-17 | 2021-02-04 | 주식회사 한서켐 | Preparing method of crystalline polaprezinc using aqueous solution |
| CN111317812A (en) * | 2020-03-18 | 2020-06-23 | 西北工业大学 | Self-assembled carnosine fluorescent nanoparticles, preparation method and application |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101659641B (en) | 2011-02-16 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101659641B (en) | Preparation method of L-carnosine zinc | |
| WO2018024083A1 (en) | Method using highly concentrated vanadium solution for manufacturing ammonium polyvanadate | |
| CN107311875A (en) | The synthetic method of aramine | |
| CN104860939A (en) | Cinchona alkaloids compound and preparation method thereof | |
| CN104072390A (en) | Escitalopram compound and preparation method thereof | |
| CN104402838B (en) | The process for purification of valsartan | |
| CN106478600B (en) | A kind of refining methd of Lansoprazole | |
| CN101973864A (en) | Method for extracting shikonin from lithospermum | |
| CN107056859A (en) | A kind of preparation method of high-purity P1, P4-di(uridine-5'-tetraphosphate) salt | |
| CN108794473B (en) | A kind of peryleneimide-nojiri toxin derivative and its preparation method and application | |
| CN102093383A (en) | Potassium cantharidate and preparation method thereof | |
| CN107540604A (en) | A kind of preparation method of the bromopyridine of 2 amino 5 | |
| CN103936809B (en) | A kind of dexamethasone sodium phosphate intermediate preparation method of improvement | |
| CN1587240A (en) | New method for preparing and separating integrately antibiotic medicine in ionic liquid double water phase | |
| CN103193800B (en) | A kind of method of each component of separation and purification from cefaclor enzymatic reaction liquid | |
| WO2021052002A1 (en) | Method for preparing copper sulfide collecting agent | |
| CN109694399A (en) | A kind of preparation method of Glycyl-L-tyrosine zinc | |
| CN109776346A (en) | A kind of preparation method of tyrosine zinc | |
| CN107573385B (en) | Oxaliplatin impurity C and preparation method and application thereof | |
| CN109694329A (en) | A method of preparing serinol zinc by way of ion exchange | |
| CN109776309A (en) | Synthetic method of the medicine intermediate to benzene butoxybenzoic acid sodium | |
| CN100348751C (en) | Treatment method of high alkali concentration sodium tungstate solution | |
| CN102311356A (en) | Synthetic method of ethyl p-aminobenzoate | |
| CN110423257A (en) | A kind of Suo Feibuwei synthesis technology | |
| CN106519071A (en) | Synthetic method of antitumor drug 6-hydroxy seleninic acid esterification chitosan copper |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C56 | Change in the name or address of the patentee |
Owner name: SUZHOU FUSHILAI PHARMACEUTICAL CO., LTD. Free format text: FORMER NAME: CHANGSHU FUSHILAI MEDICINE CHEMICAL CO., LTD. |
|
| CP03 | Change of name, title or address |
Address after: 215522 Jiangsu province Changshu New Material Industrial Park Haiwang Road No. 16 Patentee after: SUZHOU FUSHILAI PHARMACEUTICAL CO., LTD. Address before: 215558 former port road, Southeast Development Zone, Jiangsu, Changshou City Patentee before: Changshu Fushilai Medicine Chemical Co., Ltd. |