CN1376520A - Process for deactivating freeze dried human plasma virus - Google Patents
Process for deactivating freeze dried human plasma virus Download PDFInfo
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- CN1376520A CN1376520A CN 02103960 CN02103960A CN1376520A CN 1376520 A CN1376520 A CN 1376520A CN 02103960 CN02103960 CN 02103960 CN 02103960 A CN02103960 A CN 02103960A CN 1376520 A CN1376520 A CN 1376520A
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Abstract
A process for deactivating freeze-dried human plasmka virus includes such steps as freezing plasma, thawing, S/D deactivating to virus, plant extracting of deactivator, adsorbing deactivator by C18 chromatographic column, ultrafiltrating, concentrating, removing bacteria by filter membrane, loading in containers, low-temp vacuum sublimation drying, sealing, and thermal deactivating in boiling water bath. Its advantages are thorough deactivating to virus and high safety.
Description
One, technical field: the present invention relates to the medical material sterilization method, particularly a kind of process for deactivating freeze dried human plasma virus.
Two, background technology: component blood transfusion for a long time becomes important means medically in healing the wounded and rescue the dying.Yet after nineteen sixties, hepatitis virus is by the blood transfusion infectious matters of aggravation that starts an inflammation of the liver, and people have had new concern to the virus safe of blood plasma.The eighties mid-term, the appearance of acquired immune deficiency syndrome (AIDS) and HIV (human immunodeficiency virus) cause infectious incident by the injecting blood goods, have caused the great attention of countries in the world.European and American countries requires to use the whole plasm through inactivation of virus clinically.The Chinese government bans use of the lyophilizing people whole plasm without inactivation of virus nineteen ninety-five, and the producer that produces the human plasma,freeze-dried has all stopped producing.But the fresh frozen plasma that the blood station, center of present domestic various places provides is not used the technical measures of inactivation of virus yet, and therefore, the existing use fresh frozen plasma of China should be thought a kind of blood products of high-risk degree.The inactivation of virus technology of whole plasm becomes the problem that China blood transfusion circle urgently need solve.
At present, abroad when preparation inactivation of virus blood plasma or blood products, used S/D, low PH to incubate to put with Pasteur's deactivation method etc., wherein S/D inactivation of virus technology has obtained the approval of U.S. sanitary department, its use has the history in 15 years, and its inactivation of virus effect is sure.The method of S/D inactivation of viruses is that the TNBP (tributyl phosphate) of adding 1% and 1% Tritonx-100 (TritonX 1) are heated to 30 ± 1 ℃ in blood plasma, stir 4 hours, get final product inactivation of viruses.Although S/D, low PH are incubated to put with Pasteur's deactivation method the probability of original blood products virus disseminating is greatly reduced and since above-mentioned inactivation of viruses method can not guarantee the diversity of inactivation of virus mechanism the receptor in a large number, these goods of infusion and not infected by it repeatedly.Known S/D method only can the deactivation lipid-coated virus, and can not deactivation to parvovirus, and external inactivation of virus blood plasma only adopts one-step method to carry out inactivation of virus at present, therefore, the inactivation of virus blood plasma of this one-step method preparation still has the danger of viral infection, and simultaneously, S/D inactivation of viruses blood plasma is freezing dosage form, it stores and the condition of movement requirement-30 ℃, for storing and transportation causes big difficult.
Three, summary of the invention: technical problem to be solved by this invention is to adopt the Geminivirus ablation method to make the inactivation of virus in the blood plasma more thorough, and be convenient to store and transportation.Technical scheme of the present invention is such, this method includes following steps, (1) refrigerated plasma is placed melt the slurry jar, melt pulp-water temperature≤30 ℃, make slurry temperature rise to 20-25 ℃, (2) the above-mentioned slurry that melts places the inactivation of viruses jar, add the tributyl phosphate of weight ratio 1% and 1% TritonX-100 in the blood plasma and stir and heat up, when blood plasma is warming up to 30 ± 1 ℃, kept 4 hours, stir therebetween and do not stop, (3) blood plasma with inactivation of viruses moves in the cup type centrifuge from the inactivation of viruses jar, and the vegetable oil of adding volume ratio 5%, carried out centrifugalize 20 minutes, it is standby to abandon oil phase reservation water blood plasma, (4) the water blood plasma after will separating flows out through containing C18 resin chromatographic column, make the not blood plasma of phosphoric acid tributyl and TritonX-100, (5) above-mentioned blood plasma is concentrated through ultrafilter membrane, (6) be to carry out packing after 0.2 micron the membrane filtration degerming with spissated blood plasma via hole diameter, it is characterized in that: also have following steps, (7) with plasma bottle pre-freeze in 0-4 ℃ of environment of packing, and freeze with backspin in-40 ℃, place in the freezer dryer then and be refrigerated to below-40 ℃, and carry out evacuation, vacuum is below the 10pa, distils 40～45 hours, slowly be warming up to then less than 35 ℃, whole process is 100～120 hours, and blood plasma is Powdered in the bottle, and bottleneck is carried out vacuum seal, (8) the bottled blood plasma after the lyophilization is placed boiling water bathe and heated 30 minutes, boiled water temperature is 98-100 ℃.The present invention is owing to the blood plasma of producing at existing S/D virus inactivation technology is further implemented xeothermic inactivation technology, and Freeze Drying Technique, and the dosage form of blood plasma is Powdered, therefore, it is safer that the blood plasma that the present invention produced has infusion, and storing temperature is 2-8 ℃, 3 years, be convenient to storage and transportation.
Four, the specific embodiment: the blood plasma 20l that gets lower A type of AB type or isoagglutination cellulose content or Type B places: (1) is melted the slurry jar and is melted slurry, melts 20-30 ℃ of pulp-water temperature, ceaselessly stirs, when slurry temperature rises to till 23 ℃; (2) the above-mentioned slurry that melts is placed the inactivation of viruses jar, outside jar, join the 2LS/D dope earlier, promptly get tributyl phosphate 224.4Ml (11%, W/V) and TritonX-100 be 220 the gram (11%, W/V) add water for injection and stir evenly the back to 2L and join in the blood plasma in the inactivation of viruses jar with 500ml/ minute speed, this moment, the volume of blood plasma was 22L, stir and be warming up to 30 ± 1 ℃ after, continue to stir 4 hours, realize inactivation of viruses; (3) blood plasma with inactivation of viruses places cup type centrifuge, get the 1.1L Oleum Ricini join in the blood plasma stir extracted in 30 minutes after, start centrifuge, its rotating speed is 2500 rev/mins, keep 20 ± 1 ℃ of temperature, separated 20 minutes, extract the about 1.3L of upper strata oil reservoir garbage out with pump, most inactivator tributyl phosphate and TritonX-100 take out from blood plasma, get the about 21.6L of water blood plasma; (4) above-mentioned water blood plasma is injected the outflow of resin C18 chromatographic column and carry out chromatography, the remaining inactivator in the blood plasma is adsorbed in the C18 resin.The plasma volume that requires each process C18 resin is 6 times a amount of resin, and flow velocity is 60cm/ hour, gets the about 25L of chromatographic column effluent, because water for injection washes resin column, can increase so flow out liquid measure; (5) above-mentioned chromatographic column effluent is concentrated in molecular weight is the ultrafilter membrane of 10K, the about 18-19L of concentrated solution, its concentration is about 5-5.5%; (6) the concentrated solution via hole diameter is that 0.2 micron membrane filtration carries out using the vial packing after the degerming, and the sub-bottling specification can have 100 milliliters, 50 milliliters and 25 milliliters/bottle, and bottle stopper partly is pressed in the bottleneck; (7) blood plasma in the sub-bottling is carried out lyophilization, at first sub-bottling is carried out 4 ℃ pre-freeze, then sub-bottling is placed in the freeze dryer, the freeze dryer temperature is below-40 ℃, simultaneously evacuation, vacuum is after distilling below the 10pa 40-45 hour, little by little slowly be warmed up to≤35 ℃, all processes is 100-120 hour, gets powder blood plasma, moisture content in the blood plasma carries out vacuum seal less than 1% to sub-bottling; (8) powder blood plasma in the bottle of sealing is carried out xeothermic inactivation of viruses and handle, sub-bottling is placed boiling water bath heating 30 minutes, boiled water temperature is 98-100 ℃, obtains the frozen dry blood plasma finished product of secondary inactivation of viruses.
The indication of frozen dry blood plasma and using method, this product are mainly used in and prevent to perform the operation, burn, lose blood, traumatic shock and the treatment hypoproteinemia, the low person of thrombin level.Should use 30-37 ℃ 0.1% citric acid soln dissolving when using this product earlier, and carry out venoclysis with the blood exchange transfusion set who has filter screen, infusion dosage is generally 12-15 milliliter/kg body weight.
Goods of the present invention are in January, 2002 Nat'l Pharmaceutical ﹠ Biological Products Control Institute's detection, and every index all meets the requirements.
Claims (2)
1, a kind of process for deactivating freeze dried human plasma virus, this method includes following steps, (1) refrigerated plasma is placed melt the slurry jar, melt pulp-water temperature≤30 ℃, make slurry temperature rise to 20-25 ℃, (2) the above-mentioned slurry that melts places the inactivation of viruses jar, add the tributyl phosphate of weight ratio 1% and 1% TritonX-100 in the blood plasma and stir and heat up, when blood plasma is warming up to 30 ± 1 ℃, kept 4 hours, stir therebetween and do not stop, (3) blood plasma with inactivation of viruses moves in the cup type centrifuge from the inactivation of viruses jar, and the vegetable oil of adding volume ratio 5%, carried out centrifugalize 20 minutes, it is standby to abandon oil phase reservation water blood plasma, (4) the water blood plasma after will separating flows out through containing C18 resin chromatographic column, make the not blood plasma of phosphoric acid tributyl and TritonX-100, (5) above-mentioned blood plasma is concentrated through ultrafilter membrane, (6) be to carry out packing after 0.2 micron the membrane filtration degerming with spissated blood plasma via hole diameter, it is characterized in that: also have following steps, (7) with plasma bottle pre-freeze in 0-4 ℃ of cryostat of packing, and freeze in-40 ℃ of backspins, place in the freezer dryer then and be refrigerated to below-40 ℃, and carry out evacuation, vacuum is below the 10pa, distils 40～45 hours, slowly is warming up to then less than 35 ℃, whole process is 100～120 hours, blood plasma is Powdered in the bottle, and bottleneck is carried out vacuum seal, and (8) place boiling water bath to heat 30 minutes the bottled blood plasma after the lyophilization.
2, a kind of process for deactivating freeze dried human plasma virus according to claim 1 is characterized in that: the described boiled water temperature of step (8) is 98-100 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02103960 CN1376520A (en) | 2002-02-28 | 2002-02-28 | Process for deactivating freeze dried human plasma virus |
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| Application Number | Priority Date | Filing Date | Title |
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| CN 02103960 CN1376520A (en) | 2002-02-28 | 2002-02-28 | Process for deactivating freeze dried human plasma virus |
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| CN1376520A true CN1376520A (en) | 2002-10-30 |
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1953728A (en) * | 2005-02-01 | 2007-04-25 | 诊断研究基金会 | Set of disposable bags for viral inactivation of biological fluids |
| CN100417722C (en) * | 2006-10-25 | 2008-09-10 | 中国辐射防护研究院 | Method for inactivating virus in blood product |
| CN104524603A (en) * | 2014-12-30 | 2015-04-22 | 广州市拜特凇医药科技有限公司 | Virus removal/inactivation method for hemostasis biological product/biological material capable of being absorbed by living organism |
| CN106008706A (en) * | 2016-07-28 | 2016-10-12 | 武汉生物制品研究所有限责任公司 | Virus inactivation method for human alpha1-antitrypsin product |
| US11604026B2 (en) | 2019-03-14 | 2023-03-14 | Terumo Bct Biotechnologies, Llc | Lyophilization loading tray assembly and system |
| US11634257B2 (en) | 2017-10-09 | 2023-04-25 | Terumo Bct Biotechnologies, Llc | Lyophilization container and method of using same |
-
2002
- 2002-02-28 CN CN 02103960 patent/CN1376520A/en active Pending
Cited By (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1953728A (en) * | 2005-02-01 | 2007-04-25 | 诊断研究基金会 | Set of disposable bags for viral inactivation of biological fluids |
| CN100417722C (en) * | 2006-10-25 | 2008-09-10 | 中国辐射防护研究院 | Method for inactivating virus in blood product |
| CN104524603A (en) * | 2014-12-30 | 2015-04-22 | 广州市拜特凇医药科技有限公司 | Virus removal/inactivation method for hemostasis biological product/biological material capable of being absorbed by living organism |
| CN106008706A (en) * | 2016-07-28 | 2016-10-12 | 武汉生物制品研究所有限责任公司 | Virus inactivation method for human alpha1-antitrypsin product |
| US11634257B2 (en) | 2017-10-09 | 2023-04-25 | Terumo Bct Biotechnologies, Llc | Lyophilization container and method of using same |
| US11604026B2 (en) | 2019-03-14 | 2023-03-14 | Terumo Bct Biotechnologies, Llc | Lyophilization loading tray assembly and system |
| US11609042B2 (en) | 2019-03-14 | 2023-03-21 | Terumo Bct Biotechnologies, Llc | Multi-part lyophilization container and method of use |
| US11609043B2 (en) | 2019-03-14 | 2023-03-21 | Terumo Bct Biotechnologies, Llc | Lyophilization container fill fixture, system and method of use |
| US11740019B2 (en) | 2019-03-14 | 2023-08-29 | Terumo Bct Biotechnologies, Llc | Lyophilization loading tray assembly and system |
| US11747082B2 (en) | 2019-03-14 | 2023-09-05 | Terumo Bct Biotechnologies, Llc | Multi-part lyophilization container and method of use |
| US11815311B2 (en) | 2019-03-14 | 2023-11-14 | Terumo Bct Biotechnologies, Llc | Lyophilization container fill fixture, system and method of use |
| US11994343B2 (en) | 2019-03-14 | 2024-05-28 | Terumo Bct Biotechnologies, Llc | Multi-part lyophilization container and method of use |
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