CN100417722C - Method for inactivating virus in blood product - Google Patents
Method for inactivating virus in blood product Download PDFInfo
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- CN100417722C CN100417722C CNB2006101507540A CN200610150754A CN100417722C CN 100417722 C CN100417722 C CN 100417722C CN B2006101507540 A CNB2006101507540 A CN B2006101507540A CN 200610150754 A CN200610150754 A CN 200610150754A CN 100417722 C CN100417722 C CN 100417722C
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- virus
- blood products
- value
- blood
- inactivation
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- 241000700605 Viruses Species 0.000 title claims abstract description 25
- 238000000034 method Methods 0.000 title claims abstract description 22
- 239000010836 blood and blood product Substances 0.000 title claims abstract description 17
- 229940125691 blood product Drugs 0.000 title claims abstract description 17
- 230000000415 inactivating effect Effects 0.000 title description 5
- 239000008280 blood Substances 0.000 claims abstract description 3
- 210000004369 blood Anatomy 0.000 claims abstract description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 11
- 239000002504 physiological saline solution Substances 0.000 claims description 6
- 238000002679 ablation Methods 0.000 claims description 5
- 238000003756 stirring Methods 0.000 claims description 5
- 238000009413 insulation Methods 0.000 claims description 4
- 230000002779 inactivation Effects 0.000 abstract description 10
- 239000012530 fluid Substances 0.000 abstract description 3
- 239000002253 acid Substances 0.000 abstract description 2
- 230000007935 neutral effect Effects 0.000 abstract description 2
- 239000003513 alkali Substances 0.000 abstract 1
- 230000009849 deactivation Effects 0.000 description 5
- 241000710960 Sindbis virus Species 0.000 description 3
- 239000013543 active substance Substances 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000012528 membrane Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 241000725303 Human immunodeficiency virus Species 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- 244000000010 microbial pathogen Species 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 238000009928 pasteurization Methods 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 239000006228 supernatant Substances 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 230000001256 tonic effect Effects 0.000 description 1
- 238000000108 ultra-filtration Methods 0.000 description 1
- 230000003612 virological effect Effects 0.000 description 1
Landscapes
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
Abstract
The invention relates to a virus inactivation method for blood products, belonging to the field of virus inactivation. Homogenizing a blood sample to be treated to prepare a uniform fluid, adjusting the pH value of the fluid to 3.5 by using acid, uniformly mixing, preserving the temperature at 37 ℃ for 1 hour, and adjusting the pH value to be neutral by using alkali. The invention has simple operation, short time and complete inactivation, and can be widely used for virus inactivation of blood products.
Description
Technical field
The invention belongs to biological products (comprising blood products) inactivation of virus field, be specifically related to a kind of ablation method that is used for blood products production to the residual virus of possibility.
Background technology
In the biological products in the market to the deactivation that may residual virus and the main SD method of removal, heating method and the membrane filter method etc. of pathogenic micro-organism.The SD method need add tensio-active agent, therefore needs to increase removal tensio-active agent technology; Heating method mainly is a pasteurization, and mainly the method by adding thermal material is to inactivation of virus, the long need more than 10 hours of technological operation time, and have the risk that makes the active substance inactivation; Membrane filter method mainly adopts millipore filtration or ultra-filtration membrane etc. that virus etc. is dammed, and processing mode is gentle relatively, but might deactivation not thorough, have the residual risk of virus, and the method for membrane filtration can not be applicable to the inactivation of virus of sticky material.
Summary of the invention
The object of the present invention is to provide short, a kind of completely virus inactivating method of deactivation of a kind of that carry out at a lower temperature, time spent, and be applicable to the virus inactivating method of sticky material.
Technical scheme of the present invention is: earlier with pending blood sample homogenate and stir, in blood products, add physiological saline again, and stir, to be adjusted to 3.0～4.0 with the pH value of physiological saline mixing gained blood products with hydrochloric acid then, at last, 35～39 ℃ of insulations at least 1 hour, again pH value is adjusted to neutrality with sodium hydroxide.
The present invention is simple to operate, just can carry out at a lower temperature, and operating time minimum usefulness 1 hour, and, through multiple batches of detection, find that deactivation is thorough.
Below by embodiment the present invention is done more detailed introduction.
Embodiment
A kind of method that is used for the blood products inactivation of virus comprises the steps:
1. pending blood products raw material or work in-process are handled with homogenizer,, made the fluid of easy stirring by adding a certain amount of physiological saline, and uniform mixing;
2. with 2N hydrochloric acid the pH value of blood products is adjusted to 3.5;
3. 37 ℃ of insulations 1 hour;
4. the pH value being adjusted to pH value with 2N sodium hydroxide is 7.0.
In the aforesaid method, the sodium hydroxide that the hydrochloric acid that step (3) is used uses in 2N～4N, step (4) all can be implemented at 2～4N, as long as can satisfy the requirement that relevant PH regulates.And, the consideration of control easily when the qualification of above-mentioned scope also mainly is based on operation, because if concentration is excessive, then often make the difficulty of the accurate control change of pH value easily, if and salt and acid concentration are too hour, then often need to add the solution of volume (volume) again, make pending article concentration rare excessively.And the pH value in the step (4) so long as neutral range in get final product, just be 7.0 o'clock, effect is better.
Be to utilize method of the present invention to carry out inactivation of virus and to the example of the detection of inactivating efficacy below, the detection of inactivating efficacy is according to for defending No. 433 literary composition of medicine hair tonic [1997].
1, get three batch samples respectively in the 144ml Boiling tube, each pipe adds 16ml respectively, and (titre is: 7.51logPFU/ml) Sindbis virus liquid is as indicator virus;
2, transferring PH with HCl is 3.5, and the hydrolysis insulation is 1 hour in 37 ℃ of water-baths, and NaOH transfers PH to 7.0;
3, with 5000 rev/mins speed centrifugation 30 minutes, get supernatant, filter with 0.8 μ m strainer, filter mainly again with 0.22 μ m filter, packing is put-70 ℃ of refrigerators and is equipped with survey;
4, retaining part virus simultaneously compares;
5, virus detects:
Adopt BHK-21 cell plaques method.Violet staining, record plaque number calculates viral remaining titre.
Titration of virus and blind passage three generations the results are shown in Table 1
Table 1 acidization deactivation sindbis virus result
Annotate: titre measure unit: logPFU/ml, ND: expression does not detect virus ,-: expression is negative
Except that above-mentioned Sindbis virus, indicator virus also can be selected VSV virus, HIV virus for use, and its result is similar.
Claims (3)
1. the ablation method of virus in the blood products comprises the steps:
(1) with pending blood sample homogenate and stir;
(2) in blood products, add physiological saline, and stir;
(3) will be adjusted to 3.0～4.0 with the pH value of physiological saline mixing gained blood products with hydrochloric acid;
(4) 35～39 ℃ of insulations at least 1 hour, again the pH value is adjusted to neutrality with sodium hydroxide.
2. the ablation method of virus in the blood products as claimed in claim 1 is characterized in that: will transfer to 3.5 with the hydrochloric acid of 2～4N with the pH value of physiological saline mixing gained blood products in step (3).
3. the ablation method of virus in the blood products as claimed in claim 1 or 2, it is characterized in that: holding temperature is 37 ℃ in step (4), and the sodium hydroxide that uses is 2～4N.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006101507540A CN100417722C (en) | 2006-10-25 | 2006-10-25 | Method for inactivating virus in blood product |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006101507540A CN100417722C (en) | 2006-10-25 | 2006-10-25 | Method for inactivating virus in blood product |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1944638A CN1944638A (en) | 2007-04-11 |
| CN100417722C true CN100417722C (en) | 2008-09-10 |
Family
ID=38044293
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2006101507540A Active CN100417722C (en) | 2006-10-25 | 2006-10-25 | Method for inactivating virus in blood product |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100417722C (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1249952A (en) * | 1998-10-07 | 2000-04-12 | 上海市血液中心 | Blood plasma virus deactivating method and apparatus |
| CN1376520A (en) * | 2002-02-28 | 2002-10-30 | 华兰生物工程股份有限公司 | Process for deactivating freeze dried human plasma virus |
| WO2006091038A1 (en) * | 2005-02-25 | 2006-08-31 | Medigenes Co., Ltd. | Pharmaceutical composition for treating avellino cornea dystrophy comprising blood plasma or serum |
-
2006
- 2006-10-25 CN CNB2006101507540A patent/CN100417722C/en active Active
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1249952A (en) * | 1998-10-07 | 2000-04-12 | 上海市血液中心 | Blood plasma virus deactivating method and apparatus |
| CN1376520A (en) * | 2002-02-28 | 2002-10-30 | 华兰生物工程股份有限公司 | Process for deactivating freeze dried human plasma virus |
| WO2006091038A1 (en) * | 2005-02-25 | 2006-08-31 | Medigenes Co., Ltd. | Pharmaceutical composition for treating avellino cornea dystrophy comprising blood plasma or serum |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1944638A (en) | 2007-04-11 |
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| C14 | Grant of patent or utility model | ||
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| EE01 | Entry into force of recordation of patent licensing contract |
Assignee: Tonrol Bio-Pharmaceutical Co., Ltd. Assignor: China Radiation Protection Research Inst. Contract fulfillment period: 2009.4.15 to 2015.4.14 contract change Contract record no.: 2009340000030 Denomination of invention: Inactivating method for virus in blood products Granted publication date: 20080910 License type: Exclusive license Record date: 2009.4.15 |
|
| LIC | Patent licence contract for exploitation submitted for record |
Free format text: EXCLUSIVE LICENSE; TIME LIMIT OF IMPLEMENTING CONTACT: 2009.4.15 TO 2015.4.14; CHANGE OF CONTRACT Name of requester: TONGLU BIOLOGY PHARMACY CO., LTD. Effective date: 20090415 |