CN1207064C - Process for producing freeze-dried human fibrin glue - Google Patents
Process for producing freeze-dried human fibrin glue Download PDFInfo
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- CN1207064C CN1207064C CN 02103825 CN02103825A CN1207064C CN 1207064 C CN1207064 C CN 1207064C CN 02103825 CN02103825 CN 02103825 CN 02103825 A CN02103825 A CN 02103825A CN 1207064 C CN1207064 C CN 1207064C
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Abstract
The present invention discloses freeze drying human fibrin glue. The production process of fibrinogen comprises the following steps: the production process of fibrinogen comprises the following steps: using component I sediment obtained by a human blood plasma low temperature alcohol multiplestep separation method as raw material; carrying out S/D inactivation of viruses, filtration sterilization subpackage and freeze drying. The present invention is characterized in that the separately loaded cold fibrin is maintained in boiling water bath for 98 to 100 DEG C to be inactivated in a dry heat mode; the production process of the thrombin comprises the following steps: using component III sediment obtained by a human blood plasma low temperature alcohol multistep separation method as raw material; carrying out dissolution, S/D virus inactivation, ultrafiltration concentration, activation, purification by cation exchange chromatography, ultrafiltration degerming separated loading and freeze drying. The present invention is characterized in that an activating agent is CaCl2. The fibrin glue prepared by the present invention passes through double virus inactivation; use is safer, and dissolving temperature is normal temperature; use is convenient, and particularly, the present invention provides a convenient condition for application in the open air.
Description
One, technical field: the present invention relates to a kind of medical material production method, particularly a kind of surgery is gone into the production technology of Fibrin Glue with lyophilizing.
Two, background technology: surgery has been widely used in the surgical operation with freeze-dried human fibrin glue abroad, its English be abbreviated as FS, this freeze-dried human fibrin glue is made up of human fibrinogen and thrombin, its blood clotting mechanism is: the final stage of Fibrin Glue simulation body blood coagulation, finally make Fibrinogen change fibrin net performance hemostasia effect into, be a kind of physiological biological hemostatic material of nature that meets, its hemostasis is fast, only needs 3-5 second.When doing blood vessel and neural micro anastomosis operation, use the FS hemostasis, can reduce even need not sew up fully, operating time is shortened, and safer, be a kind of optimal hemostatic material.Only adopted S/D inactivation of virus technology in the production technology of external freeze-dried human fibrin glue, inactivating efficacy to tiny cell virus is relatively poor, need be in 37 ℃ water-bath when the Fibrinogen component in secondly existing freeze-dried human fibrin glue uses dissolved condition, can not satisfy in the open air and use fast under the condition.
Three, summary of the invention: technical problem to be solved by this invention is that the virus safe of the freeze-dried human fibrin glue produced is stronger, and has dissolved lyophilized human fibrinogen under normal temperature condition.Technical solution of the present invention is such, it comprises fibrin original production process and thrombin production technology, fibrinogenic production technology may further comprise the steps: dividing the component I precipitate of step separation with the human plasma cold ethanol is that raw material is through S/O inactivation of viruses, filtration sterilization packing, lyophilization, it is characterized in that: after carry out the packing lyophilizing after the cold ethanol separation and purification, the Fibrinogen after the lyophilizing is kept carrying out in 30 minutes xeothermic deactivation in 98-100 ℃ boiling water bath at the S/D inactivation of virus; The production technology of thrombin may further comprise the steps: dividing the component III of step separation with the human plasma cold ethanol is that material dissolution, S/O inactivation of virus, ultrafiltration and concentration, activation, cation-exchange chromatography carry out purification, ultrafiltration, degerming packing, lyophilizing, and it is characterized in that: activator is CaCl
2In the technology of the present invention owing to increased xeothermic virus inactivation technology, when producing Fibrinogen, choose reasonable to TWeen-80 and Nacl content, thereby the present invention compared with the prior art, the use of prepared freeze-dried human fibrin glue is safer, and has soluble remarkable advantage under the room temperature.
Four, the specific embodiment: the fibrin original production process in the freeze-dried human fibrin glue includes following steps: dividing the component I precipitate of step separation with the human plasma cold ethanol is raw material, (1) gets its 2 kilograms, dissolve with the 20L lysate, (2) add S/O mother solution 2.1L, carried out deactivation in 6 hours 25 ℃ of slow down stirrings, get volume 23L, (3) add 4.3L ethanol conciliation pH value to 7.0 and be cooled to-1.5 ℃, carry out centrifugalize, get 5 kilograms of precipitate, dissolve with the 15L lysate (4), add ethanol 3.1L and transfer pH value 7.0, be cooled to-1.5 ℃, 1.2 kilograms of precipitate are received in centrifugalize, and (5) add lysate 4.8L dissolving centrifugation, (6) ultrafiltration sterilization packing, (7) lyophilizing, (8) place temperature 98-100 ℃ boiling water bath to carry out the xeothermic poison processing of going out in 30 minutes the Fibrinogen of lyophilizing packing, get finished product.The production craft step of thrombin has: (1) gets 3 kilograms of component III is raw material, with the dissolving of 12L lysate, solution temperature is 25 ℃, and (2) add 2.14LPEG and 600mlNaHCO3 adjusts PH to 6.8, be cooled to 5 ℃, (3) add S/O mother solution 1.55L after the centrifugal filtration, under 25 ℃ of conditions, slowly stirred 6 hours inactivation of virus, (4) carry out gel detergent and eluting with cleaning mixture and eluent, and ultrafiltration and concentration, getting volume is 0.5L, (5) add CaCl
23.5mL activate, the SP-Sepharoseff chromatography glue that (6) add 30mL carries out chromatography, gets volume 100mL, its about 700IU/mL that tires, (7) be that the film of 0.2um carries out degerming with the aperture, packing, lyophilizing (B) keep carrying out in 30 minutes xeothermic deactivation in 98-100 ℃ boiling water bath.
The using method of freeze-dried human fibrin glue: when needing to implement hemostasis in the operation, at first aspirate Fibrinogen diluent and thrombin lysate respectively with two syringes, inject in lyophilized human fibrinogen's bottle respectively and the freeze dried human zymoplasm bottle in, after aspirating fibrinogen solution and thrombin solution respectively with two other syringes then, blocking the people respectively pushes away on the liquid frame, two syringe coneheads are connected on the connection needle stand securely, again entry needle needle stand or nozzle are installed on the conehead that connects needle stand, this moment pushing syringe, make mixed liquor point cloth to organizing on the wound surface that needs are handled, promptly finished the hemostasis of freeze-dried human fibrin glue.Should be noted in the discussion above that the liquid in two syringes must equivalent.
Claims (1)
1, a kind of production technology of freeze-dried human fibrin glue, it comprises fibrin original production process and thrombin production technology, fibrinogenic production technology may further comprise the steps: dividing the component I precipitate of step separation with the human plasma cold ethanol is that raw material is through S/O inactivation of viruses, filtration sterilization packing, lyophilization, it is characterized in that: after carry out the packing lyophilizing after the cold ethanol separation and purification, the Fibrinogen after the packing lyophilizing is kept carrying out in 30 minutes xeothermic deactivation in 98-100 ℃ boiling water bath at the S/D inactivation of virus; The production technology of thrombin may further comprise the steps: dividing the component III of step separation with the human plasma cold ethanol is that material dissolution, S/O inactivation of virus, ultrafiltration and concentration, activation, cation-exchange chromatography carry out purification, heat sterilization packing, lyophilizing, and it is characterized in that: activator is CaCl
2
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02103825 CN1207064C (en) | 2002-03-29 | 2002-03-29 | Process for producing freeze-dried human fibrin glue |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02103825 CN1207064C (en) | 2002-03-29 | 2002-03-29 | Process for producing freeze-dried human fibrin glue |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1408441A CN1408441A (en) | 2003-04-09 |
| CN1207064C true CN1207064C (en) | 2005-06-22 |
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| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 02103825 Expired - Lifetime CN1207064C (en) | 2002-03-29 | 2002-03-29 | Process for producing freeze-dried human fibrin glue |
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| CN (1) | CN1207064C (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9932388B2 (en) | 2014-11-13 | 2018-04-03 | Hemarus Therapeutics Limited | Chromatographic process for producing high purity fibrinogen and thrombin |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100345591C (en) * | 2003-08-01 | 2007-10-31 | 上海新兴医药股份有限公司 | Instant freeze-dried fibriogen preparation with anti dry heat treatment |
| US9624260B2 (en) * | 2004-06-07 | 2017-04-18 | Therapure Biopharma Inc. | Process for isolation of plasma or serum proteins |
| CN102286095B (en) * | 2011-07-06 | 2013-08-21 | 大田华灿生物科技有限公司 | Preparation method for fibrinogen |
| CN107827974B (en) * | 2017-11-10 | 2021-01-01 | 中国科学院过程工程研究所 | Preparation method of human fibrinogen |
| CN111657269B (en) * | 2020-06-22 | 2022-02-08 | 镇江雷音再生医学科技有限公司 | Method for protecting and treating fibrin glue before preservation of SMILE-derived human corneal lens |
-
2002
- 2002-03-29 CN CN 02103825 patent/CN1207064C/en not_active Expired - Lifetime
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US9932388B2 (en) | 2014-11-13 | 2018-04-03 | Hemarus Therapeutics Limited | Chromatographic process for producing high purity fibrinogen and thrombin |
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| Publication number | Publication date |
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| CN1408441A (en) | 2003-04-09 |
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