CN102504047A - Ultrafiltration method of sodium hyaluronate fermentation liquid - Google Patents
Ultrafiltration method of sodium hyaluronate fermentation liquid Download PDFInfo
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- CN102504047A CN102504047A CN2011103896192A CN201110389619A CN102504047A CN 102504047 A CN102504047 A CN 102504047A CN 2011103896192 A CN2011103896192 A CN 2011103896192A CN 201110389619 A CN201110389619 A CN 201110389619A CN 102504047 A CN102504047 A CN 102504047A
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- hyaluronic acid
- acid sodium
- purified water
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- fermented liquid
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Abstract
The invention relates to an ultrafiltration method of a sodium hyaluronate fermentation liquid. The method comprises the following steps: firstly adding purified water into the sodium hyaluronate fermentation liquid for dilution, filtering and sterilizing; then concentrating the obtained material liquid; and finally keeping the volume of the material liquid unchanged, adding the purified water to perform filter washing on the material liquid, and further adding a sodium chloride solution to perform the filter washing on the material liquid after the filter washing through the purified water is completed. The sodium hyaluronate fermentation liquid prepared by the method is safe, effective, low in cost and low in risk; and the method can be used for basically removing ingredients of a culture medium in the fermentation liquid and greatly reducing the contents of nucleic acid, proteins and the like, and is especially suitable for industrial production of medical-grade sodium hyaluronate.
Description
Technical field:
The present invention relates to a kind of treatment process of hyaluronic acid sodium fermented liquid, particularly a kind of hyperfiltration process of hyaluronic acid sodium fermented liquid.
Background technology:
Glass acid (Hyaluronic acid is called for short HA), by the straight chain saccharan that (1 → 3)-2-acetylaminohydroxyphenylarsonic acid 2-deoxidation-β-D-glucose-(1 → 4)-O-β-D-glucuronic acid disaccharide repeating unit is formed, molecular formula is (C
14H
21NO
11)
n, according to tissue-derived difference, the molecular weight variation range is 2 * 10
5～7 * 10
6, the disaccharide units is 300～11000 pairs.The glass acid structure of different sources is consistent, and only there is the difference of relative molecular weight in no species variation.
The acid of commodity glass is generally sodium-salt form, is white fiber shape or pulverulent solids, and stronger water absorbability is arranged, and is water-soluble, is insoluble to organic solvent.The macromolecular network structure of hyaluronic acid sodium through with H
2The a large amount of water of O formation hydrogen bonded has the multiple matrix of formation in vivo, regulates osmotic pressure, regulates and control the transhipment of macromolecular substance, forms effects such as physical barriers and adjusting cell function at cell peripheral.Hyaluronic acid sodium can be used as the assisting therapy of ophthalmologic operation adjuvant drug and deformability gonarthrosis and scapulohumeral periarthritis, is also organizing generation, wound healing, tumour invasion and adjusting cell function aspects to have the important physical function.
Domestic medical grade hyaluronic acid sodium production at present is the production technique that animal tissues extracts mostly, and raw materials cost is higher, and it is limited to originate, and has animal derived risk.And the fermentative Production hyaluronic acid sodium through gene engineering, can filter out the dissociant that does not contain intracellular toxin and extracellular toxin and high yield HA, and is safer than tissue extraction; Fermented liquid and animal tissues compare, and moity is simple, more helps extraction and purification, preparation high purity HA; Can guarantee that raw material sources is unrestricted, and raw materials cost is cheaper.
In disclosed document in the past, the processing mode of hyaluronic acid sodium fermented liquid is normally directly used organic solvent deposit, and then with resolution of precipitate, carries out further purifying such as complexing.With an organic solvent sedimentary method, the organic solvent usage quantity is big, and cost is high, and the use of organic solvent, stores and all have security risk, the discharging of organic solvent and handle and have the risk of polluting.Therefore this method exists not enough in suitability for industrialized production.
Summary of the invention:
The hyperfiltration process that the purpose of this invention is to provide a kind of hyaluronic acid sodium fermented liquid is to overcome the deficiency of above-mentioned hyaluronic acid sodium fermentation liquor treatment method.
For realizing the object of the invention, the technical scheme that the present invention adopted is:
A kind of hyperfiltration process of hyaluronic acid sodium fermented liquid is characterized in that, may further comprise the steps:
(1) the hyaluronic acid sodium fermented liquid is added purified water dilution, filtration sterilization;
(2) feed liquid with step (1) gained concentrates;
(3) keep the material liquid volume of step (2) gained constant, stream adds purified water feed liquid is carried out filter wash, and the purified water filter wash stream that finishes again adds the chlorination sodium solution feed liquid is carried out filter wash.
In a preferred embodiment of the present invention, the middle fermented liquid of step (1) is diluted to 2-4 times of its volume.
In a more preferred embodiment of the present invention, the middle fermented liquid of step (1) is diluted to 3 times of its volume.
In a preferred embodiment of the present invention, fermented liquid concentrates 1～3 times in the step (2).
In a preferred embodiment of the present invention, the consumption of the middle purified water of said step (3) is 1～6 times of material liquid volume.
In a preferred embodiment of the present invention, the concentration of sodium chloride solution is 0.005-0.1mol/L in the said step (3), and consumption is 1～6 times of material liquid volume.
Hyaluronic acid sodium fermented liquid of the present invention is handled with hyperfiltration process; This method prepares the hyaluronic acid sodium fermented liquid safety of gained, effective, low-cost, low risk; Can remove the substratum composition in the fermented liquid basically; Significantly reduce the content of nucleic acid and albumen etc., be particularly suitable for the suitability for industrialized production of medical grade hyaluronic acid sodium.
Embodiment:
Can further be well understood to the present invention through specific embodiment of the present invention given below, but they not to qualification of the present invention.
Embodiment 1:
Get hyaluronic acid sodium fermented liquid 4L, add the dilution of 8L purified water, carry out ultrafiltration after the filtration sterilization, ultra-filtration process is divided into two steps: at first feed liquid is concentrated 1 times, to 6L; Keep material liquid volume constant then, stream adds the 12L purified water, and promptly 2 times of material liquid volumes carry out filter wash to feed liquid, and the purified water filter wash finishes again, and to add 12L concentration be the 0.05mol/L sodium chloride solution to stream, and promptly 2 times of material liquid volumes continue feed liquid is carried out filter wash.The hyaluronic acid sodium solution that complex-precipitation can be directly carried out in final acquisition.Ultrafiltration each association that records that finishes is following: average flux 27.8L/m
2H; Albumen clearance 93.2%; Hyaluronic acid sodium yield 87.1%.
Embodiment 2:
Get hyaluronic acid sodium fermented liquid 5L, add the dilution of 10L purified water, carry out ultrafiltration after the filtration sterilization, ultra-filtration process is divided into two steps: at first feed liquid is concentrated 2 times, to 5L; Keep material liquid volume constant then, stream adds the 10L purified water, and promptly 2 times of material liquid volumes carry out filter wash to feed liquid, and the purified water filter wash finishes again, and to add 20L concentration be the 0.07mol/L sodium chloride solution to stream, and promptly 4 times of material liquid volumes continue feed liquid is carried out filter wash.The hyaluronic acid sodium solution that complex-precipitation can be directly carried out in final acquisition.Ultrafiltration each association that records that finishes is following: average flux 31.3L/m
2H; Albumen clearance 94.0%; Hyaluronic acid sodium yield 83.1%.
Embodiment 3:
Get hyaluronic acid sodium fermented liquid 5L, add the dilution of 10L purified water, carry out ultrafiltration after the filtration sterilization, ultra-filtration process is divided into two steps: at first feed liquid is concentrated 2 times, to 5L; Keep material liquid volume constant then, stream adds the 20L purified water, and promptly 4 times of material liquid volumes carry out filter wash to feed liquid, and the purified water filter wash finishes again, and to add 10L concentration be the 0.1mol/L sodium chloride solution to stream, and promptly 2 times of material liquid volumes continue feed liquid is carried out filter wash.The hyaluronic acid sodium solution that complex-precipitation can be directly carried out in final acquisition.Ultrafiltration each association that records that finishes is following: average flux 20.1L/m
2H; Albumen clearance 96.8%; Hyaluronic acid sodium yield 87.9%.
Embodiment 4:
Get hyaluronic acid sodium fermented liquid 4L, add the dilution of 8L purified water, carry out ultrafiltration after the filtration sterilization, ultra-filtration process is divided into two steps: at first feed liquid is concentrated 1 times, to 6L; Keep material liquid volume constant then, stream adds the 12L purified water, and promptly 2 times of material liquid volumes carry out filter wash to feed liquid, and the purified water filter wash finishes again, and to add 24L concentration be the 0.06mol/L sodium chloride solution to stream, and promptly 4 times of material liquid volumes continue feed liquid is carried out filter wash.The hyaluronic acid sodium solution that complex-precipitation can be directly carried out in final acquisition.Ultrafiltration each association that records that finishes is following: average flux 30.4L/m
2H; Albumen clearance 94.0%; Hyaluronic acid sodium yield 79.8%.
Although the present invention has been done detailed explanation and has quoted some specific embodiments as proof, to those skilled in the art, only otherwise leave that the spirit and scope of the present invention can be done various variations and correction is obvious.
Claims (6)
1. the hyperfiltration process of a hyaluronic acid sodium fermented liquid is characterized in that, may further comprise the steps:
(1) the hyaluronic acid sodium fermented liquid is added purified water dilution, filtration sterilization;
(2) feed liquid with step (1) gained concentrates;
(3) keep the material liquid volume of step (2) gained constant, stream adds purified water feed liquid is carried out filter wash, and the purified water filter wash stream that finishes again adds the chlorination sodium solution feed liquid is carried out filter wash.
2. the hyperfiltration process of hyaluronic acid sodium fermented liquid according to claim 1 is characterized in that, the middle fermented liquid of step (1) is diluted to 2-4 times of its volume.
3. the hyperfiltration process of hyaluronic acid sodium fermented liquid according to claim 2 is characterized in that, the middle fermented liquid of step (1) is diluted to 3 times of its volume.
4. the hyperfiltration process of hyaluronic acid sodium fermented liquid according to claim 1 is characterized in that, fermented liquid concentrates 1～3 times in the step (2).
5. the hyperfiltration process of hyaluronic acid sodium fermented liquid according to claim 1 is characterized in that, the consumption of the middle purified water of said step (3) is 1～6 times of material liquid volume.
6. the hyperfiltration process of hyaluronic acid sodium fermented liquid according to claim 1 is characterized in that, the concentration of sodium chloride solution is 0.005-0.1mol/L in the said step (3), and consumption is 1～6 times of material liquid volume.
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|---|---|---|---|
| CN2011103896192A CN102504047A (en) | 2011-11-30 | 2011-11-30 | Ultrafiltration method of sodium hyaluronate fermentation liquid |
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| CN2011103896192A CN102504047A (en) | 2011-11-30 | 2011-11-30 | Ultrafiltration method of sodium hyaluronate fermentation liquid |
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5563051A (en) * | 1990-11-07 | 1996-10-08 | Fermentech Medical Limited | Production of hyaluronic acid |
| US6489467B1 (en) * | 1999-01-28 | 2002-12-03 | Chemedica S.A. | Process for purifying high molecular weight hyaluronic acid |
| CN101512006A (en) * | 2006-07-06 | 2009-08-19 | 利莱恩斯生命科学有限公司 | Efficient process for purification of high molecular weight hyaluronic acid |
| CN101914169A (en) * | 2008-12-01 | 2010-12-15 | 思德生物科技股份有限公司 | Process for purifying hyaluronic acid |
-
2011
- 2011-11-30 CN CN2011103896192A patent/CN102504047A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5563051A (en) * | 1990-11-07 | 1996-10-08 | Fermentech Medical Limited | Production of hyaluronic acid |
| US6489467B1 (en) * | 1999-01-28 | 2002-12-03 | Chemedica S.A. | Process for purifying high molecular weight hyaluronic acid |
| CN101512006A (en) * | 2006-07-06 | 2009-08-19 | 利莱恩斯生命科学有限公司 | Efficient process for purification of high molecular weight hyaluronic acid |
| CN101914169A (en) * | 2008-12-01 | 2010-12-15 | 思德生物科技股份有限公司 | Process for purifying hyaluronic acid |
Non-Patent Citations (1)
| Title |
|---|
| 张延良等: "超滤技术应用于透明质酸发酵液初提工艺的研究", 《医学信息》 * |
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Application publication date: 20120620 |