CN103992364A - Separation extraction method of fondaparinux sodium - Google Patents
Separation extraction method of fondaparinux sodium Download PDFInfo
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- CN103992364A CN103992364A CN201410111617.0A CN201410111617A CN103992364A CN 103992364 A CN103992364 A CN 103992364A CN 201410111617 A CN201410111617 A CN 201410111617A CN 103992364 A CN103992364 A CN 103992364A
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- fondaparinux sodium
- solution
- salt
- exchange resin
- ion exchange
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Abstract
The invention discloses a separation extraction method of fondaparinux sodium. The method includes the following steps: adsorbing a dilute salt solution of a fondaparinux sodium compound by ion exchange resin, then eluting with concentrated brine solution to achieve the purpose of salt removal and concentration, so as to obtain concentrated liquid of fondaparinux sodium. The invention uses ion exchange resin before fondaparinux sodium adsorption, to separate most of the salt and water, and then a small amount of concentrated brine solution is employed to elute the product, and the subsequent precipitation is carried out directly to obtain the product. The method is simple and practical in operation and low in cost and can control processing batch arbitrarily, so as to greatly facilitate the posttreatment process of the fondaparinux sodium product.
Description
Technical field
The present invention relates to a kind of separating and extracting method of Fondaparinux sodium.
Background technology
D254 is a kind of macroporous strong basic quaternary ammonium salt cationic exchange resin.Before this, be widely used separated, easy to operate with heparin sodium and the magazines such as protein of D254, the heparin sodium rate of recovery is high, and the renewable recycle of resin.
Fondaparinux sodium is the highly selective Xa factor inhibitor of France match Norfin, Inc exploitation, and 2008 in Discussion on Chinese Listed, trade(brand)name " Android ".With respect to Low molecular heparin, it is the definite single compound of structure, has lower molecular weight.Compare with enoxaparin, curative effect is all not less than enoxaparin, and hemorrhage relative risk reduces by 50%.
Although Fondaparinux sodium clinical manifestation is fine, due to its complicated structure and purifying and the suitable complexity of last handling process, limited applying of it.
Sulphur reaches last purifying to be completed by preparative chromatography, and moving phase is NaCl solution, and this has just determined that having quite a large amount of sulphur reaches salts solution generation.If fast and effectively sulphur is reached to product separation and Extraction from preparing liquid, out, the production capacity of this medicine will be determined to a great extent.Usual method is that direct vacuum concentration dewaters and the nanofiltration method desalination that dewaters.The method that vacuum concentration dewaters expends a large amount of electric power energies, inefficiency, and be concentrated to and have a large amount of salt after finite concentration and separate out prior to product, unfavorable to further purification; And the method apparatus expensive of nanofiltration, maintenance of the equipment is loaded down with trivial details.
summary of the invention
For overcoming deficiency of the prior art, the invention provides a kind of separating and extracting method of Fondaparinux sodium, the method energy consumption is little, time-consuming few, the requirement that the renewable cycle applications of medium and being suitable for is produced in enormous quantities.
For realizing above-mentioned technical purpose, reach above-mentioned technique effect, the present invention is achieved through the following technical solutions:
A kind of separating and extracting method of Fondaparinux sodium, comprise following content: rare salt brine solution of Fondaparinux sodium compound is adsorbed, uses dense salt brine solution wash-out by ion exchange resin, reach desalination and concentrated object, thereby obtain the concentrated solution of Fondaparinux sodium.
Further, described ion exchange resin preferred cationic type, more preferably quaternary ammonium salt cationic resin, most preferably D254 type.
Further, the aqueous solution of the preferred inorganic salt of described salt brine solution, the more preferably muriatic aqueous solution, most preferably NaCl solution.
Further, the molecular formula of described Fondaparinux sodium compound is
.
Beneficial effect of the present invention:
The present invention utilizes ion exchange resin to reach absorption prior to sulphur, separate most salt and water, again with a small amount of product being eluted compared with strong brine, directly carry out follow-up precipitation product, operation is simple, cost is low, processes in batches and can control arbitrarily, greatly facilitates the last handling process that sulphur reaches product.
Above-mentioned explanation is only the general introduction of technical solution of the present invention, in order to better understand technique means of the present invention, and can be implemented according to the content of specification sheets, below with preferred embodiment of the present invention, is described in detail as follows.The specific embodiment of the present invention is provided in detail by following examples.
Embodiment
Below in conjunction with embodiment, describe the present invention in detail.
A kind of separating and extracting method of Fondaparinux sodium, comprise following content: rare salt brine solution of Fondaparinux sodium compound is adsorbed, uses dense salt brine solution wash-out by ion exchange resin, reach desalination and concentrated object, thereby obtain the concentrated solution of Fondaparinux sodium.
Further, described ion exchange resin preferred cationic type, more preferably quaternary ammonium salt cationic resin, most preferably D254 type.
Further, the aqueous solution of the preferred inorganic salt of described salt brine solution, the more preferably muriatic aqueous solution, most preferably NaCl solution.
Further, the molecular formula of described Fondaparinux sodium compound is
.
Embodiment 1:
1,10 g Fondaparinux sodium crude products (content 35%) are dissolved in 100 mL pure water, be diluted with water to specific conductivity 40 us, then this solution is pumped into 400 mL D254 resin absorption, upon adsorption completely after, with 400 mL 20 % NaCl solution circulated wash-out 1 h, then collect elutriant, after precipitation process, obtain sulphur and reach product 3.32 g, the rate of recovery 94.8%.
2,50 L sulphurs are reached and prepare liquid (specific conductivity 90us) and be diluted with water to specific conductivity 40-45us, then this solution is pumped into 4 L D254 resin absorption, upon adsorption completely after, with 2*3 L 20 % NaCl solution circulated wash-out 1 h, then merge elutriant, after precipitation process, obtain sulphur and reach product 30 g, used times 18 h.
The foregoing is only the preferred embodiments of the present invention, be not limited to the present invention, for a person skilled in the art, the present invention can have various modifications and variations.Within the spirit and principles in the present invention all, any modification of doing, be equal to replacement, improvement etc., within all should being included in protection scope of the present invention.
Claims (4)
1. the separating and extracting method of a Fondaparinux sodium, it is characterized in that, comprise following content: rare salt brine solution of Fondaparinux sodium compound is adsorbed, uses dense salt brine solution wash-out by ion exchange resin, reach desalination and concentrated object, thereby obtain the concentrated solution of Fondaparinux sodium.
2. the separating and extracting method of Fondaparinux sodium according to claim 1, is characterized in that, described ion exchange resin preferred cationic type, more preferably quaternary ammonium salt cationic resin, most preferably D254 type.
3. the separating and extracting method of Fondaparinux sodium according to claim 1, is characterized in that, the aqueous solution of the preferred inorganic salt of described salt brine solution, the more preferably muriatic aqueous solution, most preferably NaCl solution.
4. the separating and extracting method of Fondaparinux sodium according to claim 1, is characterized in that, the molecular formula of described Fondaparinux sodium compound is
.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201410111617.0A CN103992364B (en) | 2014-03-25 | 2014-03-25 | A kind of separating and extracting process of Fondaparinux sodium |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201410111617.0A CN103992364B (en) | 2014-03-25 | 2014-03-25 | A kind of separating and extracting process of Fondaparinux sodium |
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| CN103992364A true CN103992364A (en) | 2014-08-20 |
| CN103992364B CN103992364B (en) | 2016-08-10 |
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| CN201410111617.0A Active CN103992364B (en) | 2014-03-25 | 2014-03-25 | A kind of separating and extracting process of Fondaparinux sodium |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105037452A (en) * | 2015-06-19 | 2015-11-11 | 天津红日药业股份有限公司 | Refining method for preparing high-purity fondaparinux sodium |
| CN107636002A (en) * | 2014-10-03 | 2018-01-26 | 美药星（南京）制药有限公司 | The purification process of idraparinux sodium |
| CN113461744A (en) * | 2020-03-30 | 2021-10-01 | 鲁南制药集团股份有限公司 | Purification method of fondaparinux sodium intermediate |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050020536A1 (en) * | 2003-02-27 | 2005-01-27 | Jean-Francois Branellec | Highly pure fondaparinux sodium composition, process for preparing said composition and pharmaceutical compositions containing it as active principle |
| CN103360439A (en) * | 2012-04-02 | 2013-10-23 | 浙江海正药业股份有限公司 | New intermediate for preparing heparin pentasaccharide and preparation method thereof |
| CN103570774A (en) * | 2012-08-07 | 2014-02-12 | 博瑞生物医药技术(苏州)有限公司 | Method for purifying pentose compounds |
-
2014
- 2014-03-25 CN CN201410111617.0A patent/CN103992364B/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050020536A1 (en) * | 2003-02-27 | 2005-01-27 | Jean-Francois Branellec | Highly pure fondaparinux sodium composition, process for preparing said composition and pharmaceutical compositions containing it as active principle |
| CN103360439A (en) * | 2012-04-02 | 2013-10-23 | 浙江海正药业股份有限公司 | New intermediate for preparing heparin pentasaccharide and preparation method thereof |
| CN103570774A (en) * | 2012-08-07 | 2014-02-12 | 博瑞生物医药技术(苏州)有限公司 | Method for purifying pentose compounds |
Non-Patent Citations (2)
| Title |
|---|
| 吴梧桐: "《生物制药工艺学》", 30 April 2013, 中国医药科技出版社 * |
| 邵雪玲，等: "《生物化学与分子生物学实验指导》", 31 October 2003, 武汉大学出版社 * |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN107636002A (en) * | 2014-10-03 | 2018-01-26 | 美药星（南京）制药有限公司 | The purification process of idraparinux sodium |
| CN107636002B (en) * | 2014-10-03 | 2021-11-02 | 美药星（南京）制药有限公司 | Purification method of edaliver sodium |
| CN105037452A (en) * | 2015-06-19 | 2015-11-11 | 天津红日药业股份有限公司 | Refining method for preparing high-purity fondaparinux sodium |
| CN113461744A (en) * | 2020-03-30 | 2021-10-01 | 鲁南制药集团股份有限公司 | Purification method of fondaparinux sodium intermediate |
| CN113461744B (en) * | 2020-03-30 | 2024-03-15 | 鲁南制药集团股份有限公司 | Purification method of fondaparinux sodium intermediate |
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|---|---|
| CN103992364B (en) | 2016-08-10 |
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