CN1047342A - The production of Factor IX and virus inactivating method thereof - Google Patents
The production of Factor IX and virus inactivating method thereof Download PDFInfo
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- CN1047342A CN1047342A CN 89103261 CN89103261A CN1047342A CN 1047342 A CN1047342 A CN 1047342A CN 89103261 CN89103261 CN 89103261 CN 89103261 A CN89103261 A CN 89103261A CN 1047342 A CN1047342 A CN 1047342A
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- factor viii
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- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention provides a kind of production and virus inactivating method thereof of Factor IX.-20～-40 ℃ packed fresh frozen plasma inserted in 2～6 ℃ the circulator bath and melt siphon, the Factor IX ice-nucleus in every bag is melted merge again, and, repeat aforesaid operations, make work in-process Factor IX solution through-20～-40 ℃ of quick-frozens.Add protective material sucrose and glycine again.Then Factor IX solution is inserted 60 ℃ of water-baths, the 10 hours inactivation of virus of heating.The present invention adopts pure physical method to produce Factor IX, keeps the native state of Factor IX, and production process equipment is simple, Factor IX recovery rate height, and inactivation of virus is thorough, is easy to apply.
Description
The present invention relates to a kind of production and virus inactivating method thereof of factor VIII.Factor VIII is a hematostatic specifics when being used for the hemophilia A patient's bleeding.
The 68th volume (Journal of American Chemical Society vol68) the 459th～475 page discloses the method that a kind of employing albumen sepn method (being the pure method of low temperature) prepares factor VIII in U.S. chemical institute magazine.It is low temperature alcohol, different ionic strength and the different pH value that utilizes different concns, and plasma proteins is divided into different components, and wherein the component I is a factor VIII etc.Its weak point is, complex process, and the factor VIII purity of producing is low, and extensive pooled plasma fast spreading disease.
The 273rd volume (New England Journal of Medicine vol273) the 1443rd page discloses a kind of method for preparing factor VIII at New England Journal of Medicine, its step is that the freezed fresh plasma below-20 ℃ was placed 4 ℃ of cold houses 14～18 hours, again through centrifugal treating, remove supernatant blood plasma, remaining white cold insoluble throw out is low pure factors VIII.Its weak point is that factor VIII purity is low, contains certain Fibrinogen, needs the input of match type, clinical application inconvenience, and easy transmitted virus.
A kind of method for preparing factor VIII is disclosed in lancet magazine II volume (The Lancet vol II) the 17th page, it is that the fresh frozen plasma below-20 ℃ is not melted siphon in the circulator bath at 4 ℃, low pure factors VIII remaining after the siphon, without mixing, store in quick-frozen below-20 ℃ for single bag.Its weak point is, water-bath does not circulate, and the thawing time is long, and single bag of storage of factor VIII, needs the input of match type, clinical use inconvenience.
The sound (vox Sanguinis) the 54th of the blood of publishing in Switzerland is rolled up the 4th phase the 199th page of virus that discloses in a kind of dry heating method inactivated factor VIII, it is in factor VIII freeze-drying process or the freeze-drying of factor VIII is placed in the hot cell, the 10 hours inactivation of virus of heating.Its weak point is, thermal conduction is slow, and the inactivation of virus inequality is not thorough, easy transmitted virus in the application.
The objective of the invention is to avoid above-mentioned weak point of the prior art, and provide a kind of production technique and equipment simple; Factor VIII recovery rate height, clinical application is convenient, and factor VIII is produced and virus inactivating method safely and effectively.
Purpose of the present invention can reach by following technical proposal.The present invention inserts-20 ℃～-40 ℃ fresh frozen plasma in 2～6 ℃ the circulator bath to melt siphon, merge respectively after factor VIII ice-nucleus left in the plasma bags melted in 35～40 ℃ water-bath, after-20～40 ℃ of quick-frozens, repeat aforesaid operations again, make work in-process factor VIII.In work in-process factor VIII solution, add protective material sucrose and glycine, carry out the damp-heat virus inactivation treatment then, promptly factor VIII solution is placed 60 ℃ of water-baths, the 10 hours inactivation of virus of heating.Adding protectant purpose, is in inactivation of viruses, makes factor VIII keep biological activity, and improves its purity.The add-on of sucrose and glycine is respectively 11: 0.6～1.4 and 1: 0.1～0.2, and (all with respect to work in-process factor VIII solution weight), making the sucrose concentration in the work in-process factor VIII solution is 40～70%, glycine concentration is 1～2M.At last the factor VIII solution centrifugal behind the inactivation of virus is handled, discarded throw out, the supernatant liquor splitting is revolved freeze and freeze-drying.
Details are as follows by embodiment in the present invention :-20 ℃ packed fresh frozen plasma, insert and melt in the siphon groove, the plasma bags mouth of pipe is passed from the siphon groove bottom, feed in the container, the cold water that is chilled to 4 ℃ is in advance pumped in the thawing siphon groove, regulate quantity of circulating water, make it to move in circles, refrigerated plasma begins to melt and flows in the container at siphon groove place, remain at last in bag for cold insolubles-factor VIII ice-nucleus.Factor VIII ice-nucleus in every bag is melted in 38 ℃ of water-baths, and they are incorporated in the plasma bags, after quick-frozen below-20 ℃, repeat aforesaid operations, make factor VIII solution reach the purity requirement of middle pure factors VIII, make work in-process factor VIII solution.In work in-process factor VIII solution, add the sucrose of 1: 0.8 weight and the glycine of 1: 0.1 weight again.Carry out viral inactivation treatment then.Factor VIII solution is placed 60 ℃ of water-baths, the 10 hours inactivation of viruses of heating.Again the factor VIII solution centrifugal behind the inactivation of virus is handled, is discarded throw out, be filled to the supernatant liquor branch in the plasma bottle and immediately revolve freeze the freeze-drying of machine inward turning after low tempertaure storage standby.
Compared with prior art, the present invention has the following advantages:
1, the present invention adopts pure physical method to produce I2GdBN, does not contain any other chemical substance, keeps the native state of I2GdBN, and is harmless.
2, production process equipment of the present invention is simple, and factor VIII recovery rate height is easy to general blood station and applies.Improved the comprehensive utilization of blood.
3, the present invention adopts damp heat inactivating virus, and the inactivation of virus uniform and complete prevents and reduced the propagation of viruses such as hepatitis and AIDS effectively.
Claims (3)
1; a kind of production of factor VIII and virus inactivating method thereof; it is that packed fresh frozen plasma is placed not circulator bath; by melting the factor VIII in the siphon extraction blood plasma; and carry out inactivation of virus with dry heating method; it is characterized in that the fresh frozen plasma-20～-40 ℃ places 2～6 ℃ circulator bath to melt siphon; the factor VIII ice-nucleus in after the siphon every bag in 35～40 ℃ of water-baths, melt close after; through-20～-40 ℃ of quick-frozens; repeat aforesaid operations; make work in-process factor VIII solution; add protective material sucrose and glycine again, adopt wet-heating to carry out the viral inactivation treatment of factor VIII solution then.
2, method according to claim 1, the amount that it is characterized in that in work in-process factor VIII solution adding protective material sucrose and glycine be respectively 1: 0.6～1.4 and 11: 0.1～0.2(all with respect to above-mentioned solution weight).
3, the method according to claim 1 is characterized in that the wet-heating inactivation of virus, promptly is factor VIII solution to be contained in container be built in 60 ℃ of water-baths, heats 10 hours inactivation of viruses.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 89103261 CN1047342A (en) | 1989-05-13 | 1989-05-13 | The production of Factor IX and virus inactivating method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 89103261 CN1047342A (en) | 1989-05-13 | 1989-05-13 | The production of Factor IX and virus inactivating method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1047342A true CN1047342A (en) | 1990-11-28 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 89103261 Pending CN1047342A (en) | 1989-05-13 | 1989-05-13 | The production of Factor IX and virus inactivating method thereof |
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| CN (1) | CN1047342A (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100360184C (en) * | 1995-07-27 | 2008-01-09 | 基因技术股份有限公司 | Stable isotonic lyophilized protein formulation |
| US8372800B2 (en) | 1999-02-22 | 2013-02-12 | Baxter International Inc. | Albumin-free factor VIII formulations |
| US10512674B2 (en) | 2008-11-07 | 2019-12-24 | Baxalta Incorporated | Factor VIII formulations |
-
1989
- 1989-05-13 CN CN 89103261 patent/CN1047342A/en active Pending
Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100360184C (en) * | 1995-07-27 | 2008-01-09 | 基因技术股份有限公司 | Stable isotonic lyophilized protein formulation |
| US8372800B2 (en) | 1999-02-22 | 2013-02-12 | Baxter International Inc. | Albumin-free factor VIII formulations |
| US8765665B2 (en) | 1999-02-22 | 2014-07-01 | Baxter International Inc. | Albumin-free factor VIII formulations |
| US9352027B2 (en) | 1999-02-22 | 2016-05-31 | Baxalta Incorporated | Albumin-free factor VIII formulations |
| US10512674B2 (en) | 2008-11-07 | 2019-12-24 | Baxalta Incorporated | Factor VIII formulations |
| US11020459B2 (en) | 2008-11-07 | 2021-06-01 | Baxalta Incorporated | Factor VIII formulations |
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