CN102516411A - Method for pre-treating sodium hyaluronate fermentation broth - Google Patents
Method for pre-treating sodium hyaluronate fermentation broth Download PDFInfo
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- CN102516411A CN102516411A CN2011103896188A CN201110389618A CN102516411A CN 102516411 A CN102516411 A CN 102516411A CN 2011103896188 A CN2011103896188 A CN 2011103896188A CN 201110389618 A CN201110389618 A CN 201110389618A CN 102516411 A CN102516411 A CN 102516411A
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- hyaluronic acid
- acid sodium
- fermented liquid
- fermentation broth
- sodium hyaluronate
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Abstract
The invention relates to a method for pre-treating sodium hyaluronate fermentation broth, which comprises the steps of firstly adding water to dilute the sodium hyaluronate fermentation broth to enable the volume to be 1-5 times of the original volume of the sodium hyaluronate fermentation broth, then adding diatomite under the stirring condition to perform even stirring and circulating the step through a plate-and-frame filter until the fermentation broth is clear, and finally using a filter element to perform microfihration. The method is low in cost, safe and effective. By means of the method for pre-treating the sodium hyaluronate fermentation broth, thalluses in the fermentation broth can removed basically, impurities including nucleic acid, protein and the like are decreased effectively, and the method is specially suitable for industrialization production of pharmaceutical 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 pre-treating 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 * 105～7 * 106, the disaccharide units is 300～11000 pairs.The structure of the glass acid of different sources is consistent, and only there is the difference of relative molecular weight in no species variation, and its structural formula is:
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.
The production of at present domestic medical grade hyaluronic acid sodium 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 with organic solvent deposit or overlaying flocculating aids filters.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; Carry out filtering method with overlaying flocculating aids, it is relatively poor to overlay effect, and flocculating aids overlays inhomogeneous, can cause filtration time long, and stops up easily when filtering, so above two kinds of methods all have deficiency in suitability for industrialized production.
Summary of the invention:
The object of the present invention is to provide a kind of pre-treating process of hyaluronic acid sodium fermented liquid, to overcome the deficiency of above-mentioned hyaluronic acid sodium fermentation liquor treatment method, this method cost is low, safe, effective.
For realizing the object of the invention, the technical scheme that the present invention adopted is:
A kind of pre-treating process of hyaluronic acid sodium fermented liquid is characterized in that, may further comprise the steps:
(1) 2～5 times with hyaluronic acid sodium fermented liquid thin up to its volume make suspension liquid;
(2) with the suspension liquid of step (1) gained, under agitation condition, add zeyssatite, after stirring, through flame filter press, this step to the fermented liquid that circulates is clarified;
(3) with the filtrating of step (2) gained with the clarifying hyaluronic acid sodium fermented liquid of filter core micro-filtration degerming.
In a preferred embodiment of the present invention, it is 1～10kg that every 100L suspension liquid adds diatomaceous amount.
In a preferred embodiment of the present invention, said filter core is 0.22um.
In a preferred embodiment of the present invention, the amount of zeyssatite filter cake is 0.4～2.0kg/m in the sheet frame
2
In the pre-treating process of hyaluronic acid sodium fermented liquid of the present invention, behind the diatomite adsorption, the degerming purpose that filtration and the micro-filtration through physical method reaches the hyaluronic acid sodium fermented liquid, its cost is low, safe, effectively; The hyaluronic acid sodium fermented liquid that utilizes present method to handle; Can remove thalline in the fermented liquid basically; Effectively reduced the content of impurity such as nucleic acid and albumen, be particularly suitable for the suitability for industrialized production of pharmaceutical grade hyaluronic acid sodium, and the transmittance of the hyaluronic acid sodium fermented liquid of being handled by this method is than higher.
Embodiment:
Further specify the present invention through following specific embodiment, but they not to qualification of the present invention.
Embodiment 1:
Get hyaluronic acid sodium fermented liquid 20L; Add purified water 20L dilute hyaluronic acid sodium fermented liquid suspension liquid; Under agitation condition, in hyaluronic acid sodium fermented liquid suspension liquid, add zeyssatite; Diatomaceous add-on is that every 100L hyaluronic acid sodium fermented liquid suspension liquid adds zeyssatite 5g, after stirring, is 2m through filtration area
2Flame filter press, make that the amount of zeyssatite filter cake is 1.0kg/m in the sheet frame
2, circulation adds diatomite adsorption and is filtered to the fermented liquid clarification through flame filter press, again through 0.22um filter core micro-filtration, obtains the clarifying hyaluronic acid sodium fermented liquid of degerming.The mean flow rate that records when filtering is 5.4L/min, and the transmittance that filters secondary fermentation liquid is 91.4%.
Embodiment 2:
Get hyaluronic acid sodium fermented liquid 20L; Add purified water 20L dilute hyaluronic acid sodium fermented liquid suspension liquid; Under agitation condition, in hyaluronic acid sodium fermented liquid suspension liquid, add zeyssatite; Diatomaceous add-on is that every 100L hyaluronic acid sodium fermented liquid suspension liquid adds zeyssatite 2g, after stirring, is 2m through filtration area
2Flame filter press, make that the amount of zeyssatite filter cake is 0.4kg/m in the sheet frame
2, circulation adds diatomite adsorption and is filtered to after the fermented liquid clarification again through 0.22um filter core micro-filtration through flame filter press, obtains the clarifying hyaluronic acid sodium fermented liquid of degerming.The mean flow rate that records when filtering is 7.1L/min, and the transmittance that filters secondary fermentation liquid is 86.4%.
Embodiment 3:
Get hyaluronic acid sodium fermented liquid 20L; Add purified water 40L dilute hyaluronic acid sodium fermented liquid suspension liquid; Under agitation condition, in hyaluronic acid sodium fermented liquid suspension liquid, add zeyssatite; Diatomaceous add-on is that every 100L hyaluronic acid sodium fermented liquid suspension liquid adds zeyssatite 2g, after stirring, is 2m through filtration area
2Flame filter press, make that the amount of zeyssatite filter cake is 1.0kg/m in the sheet frame
2, circulation adds diatomite adsorption and is filtered to after the fermented liquid clarification again through 0.22um filter core micro-filtration through flame filter press, obtains the clarifying hyaluronic acid sodium fermented liquid of degerming.The mean flow rate that records when filtering is 14.8L/min, and the transmittance that filters secondary fermentation liquid is 96.6%.
Embodiment 4:
Get hyaluronic acid sodium fermented liquid 20L; Add purified water 40L dilute hyaluronic acid sodium fermented liquid suspension liquid; Under agitation condition, in hyaluronic acid sodium fermented liquid suspension liquid, add zeyssatite; Diatomaceous add-on is that every 100L hyaluronic acid sodium fermented liquid suspension liquid adds zeyssatite 5g, after stirring, is 2m through filtration area
2Flame filter press, make that the amount of zeyssatite filter cake is 1.5kg/m in the sheet frame
2, circulation adds diatomite adsorption and is filtered to after the fermented liquid clarification again through 0.22um filter core micro-filtration through flame filter press, obtains the clarifying hyaluronic acid sodium fermented liquid of degerming.The mean flow rate that records when filtering is 12.8L/min, and the transmittance that filters secondary fermentation liquid is 96.0%.
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 leaving the spirit and scope of the present invention can be obvious as various changes and modifications.
Claims (4)
1. the pre-treating process of a hyaluronic acid sodium fermented liquid is characterized in that, may further comprise the steps:
(1) 2～5 times with hyaluronic acid sodium fermented liquid thin up to its volume make suspension liquid;
(2) with the suspension liquid of step (1) gained, under agitation condition, add zeyssatite, after stirring, through flame filter press, this step to the fermented liquid that circulates is clarified;
(3) with the filtrating of step (2) gained with the clarifying hyaluronic acid sodium fermented liquid of filter core micro-filtration degerming.
2. the pre-treating process of hyaluronic acid sodium fermented liquid according to claim 1 is characterized in that, it is 1～10kg that every 100L suspension liquid adds diatomaceous amount.
3. the pre-treating process of hyaluronic acid sodium fermented liquid according to claim 1 is characterized in that, said filter core is 0.22um.
4. the pre-treating process of hyaluronic acid sodium fermented liquid according to claim 1 is characterized in that, the amount of zeyssatite filter cake is 0.4～2.0kg/m in the sheet frame
2
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| Application Number | Priority Date | Filing Date | Title |
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| CN2011103896188A CN102516411A (en) | 2011-11-30 | 2011-11-30 | Method for pre-treating sodium hyaluronate fermentation broth |
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| CN2011103896188A CN102516411A (en) | 2011-11-30 | 2011-11-30 | Method for pre-treating sodium hyaluronate fermentation broth |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110680932A (en) * | 2019-11-10 | 2020-01-14 | 云南自由贸易试验区吉美生物科技有限公司 | Non-destructive degerming process for hyaluronic acid aqueous solution |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101935362A (en) * | 2009-06-30 | 2011-01-05 | 上海佰加壹医药有限公司 | Method for purifying hyaluronic acid by pre-laying filter aid |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101935362A (en) * | 2009-06-30 | 2011-01-05 | 上海佰加壹医药有限公司 | Method for purifying hyaluronic acid by pre-laying filter aid |
Non-Patent Citations (2)
| Title |
|---|
| 张延良: "发酵法生产医用级透明质酸的工艺研究", 《中国优秀硕士学位论文全文数据库工程科技Ⅰ辑》, no. 10, 15 October 2010 (2010-10-15), pages 30 - 32 * |
| 张延良等: "超滤技术应用与透明质酸发酵液初提工艺的研究", 《医学信息》, no. 6, 31 December 2010 (2010-12-31) * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110680932A (en) * | 2019-11-10 | 2020-01-14 | 云南自由贸易试验区吉美生物科技有限公司 | Non-destructive degerming process for hyaluronic acid aqueous solution |
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Application publication date: 20120627 |