CN102363041A - Method for preparing preservative-free vaccine - Google Patents
Method for preparing preservative-free vaccine Download PDFInfo
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- CN102363041A CN102363041A CN2011103656555A CN201110365655A CN102363041A CN 102363041 A CN102363041 A CN 102363041A CN 2011103656555 A CN2011103656555 A CN 2011103656555A CN 201110365655 A CN201110365655 A CN 201110365655A CN 102363041 A CN102363041 A CN 102363041A
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Abstract
The invention discloses a process for preparing a preservative-free vaccine. The process comprises the following steps of: (1) refining, namely removing thallus, concentrating, salting out and collecting precipitates, dissolving precipitates and then performing ultrafiltration desalting; (2) performing detoxification, adding a 0.1 to 0.3 percent formaldehyde solution, and performing detoxification at the temperature of between 36 and 40 DEG C for 30 to 50 days; (3) performing detoxification inspection, namely sampling and performing detoxification inspection; (4) degerming and filtering, namely degerming and filtering a qualified stock solution which is obtained after detoxification inspection to prepare the stock solution of the preservative-free vaccine; and (5) preparing, namely preparing a semi-finished product by using a 7 to 9Lf/ml stock solution of preservative-free vaccine, 1.0 to 3.0g/L adsorbent, 0.05 to 0.07g/L Na2HPO4, 0.005 to 0.015g/L KH2PO4, and 7 to 9g/L NaCl; and (6) performing split charging. The vaccine does not contain the preservative, and the process is suitable for various vaccines, and has the advantages of sterility during preparation, storing and transportation, using and the like.
Description
Technical field
The present invention relates to a kind of processing technology that does not contain the antiseptic vaccine.
Background technology
Mostly the inoculation of vaccine is that groupment queuing carries out in turn, has a group of people crowd's inoculation to finish often, waits for the neutral gear gap of a group of people crowd's inoculation down; When the vaccine than big specification packing finishes from the inoculation that breaks a seal, have the time of staying of one section ingress of air, and the storage and transportation process of vaccine product after production touches germ contamination easily; Therefore, just have the requirement for anticorrosion to vaccine, a lot of vaccine products prepare at finished product and add the antiseptic thimerosal in the process with bacteria growing inhibiting; But be to use thimerosal to cause potential safety hazard to human body, can produce intensive local pain sense behind the human vaccination, have document to point out: high-load hydrargyrum is a kind of never poison in the period of development of key; And research shows that the vaccine that contains thimerosal can make the intravital mercury content of neonate increase (referring to " biological product news flash "; 2000 the 3rd phases, select from Vaccine Weekly, 2000; May 24, p10); Also have document to point out: heavy dose of thimerosal can cause nerve and Toxicity of Kidney; The level of security that EPA (U.S. environment protection management board) and WHO (World Health Organization (WHO)) make respectively about hydrargyrum was defined as for 0.7 μ g/ kg body weight/week and 3.3 μ g/kg body weight/weeks, according to statistics, and in the U.S.; The broken vaccine (being equivalent to contain 75 μ g ethyl mercuries) of 3 doses of one hundred days of baby due 14 week inoculation, Hepatitis B virus vaccine (being equivalent to contain 37.5 μ g ethyl mercuries), Hib (Type B haemophilus) vaccine (being equivalent to contain 75 μ g ethyl mercuries); The ethyl mercury total content has surpassed the high limit that each mechanism defines (referring to " foreign medical science, the biological product fascicle is used in prevention, diagnosis, treatment " up to 187.5 μ g; 2000; 23 (3), pp105-107 is translated from Wkly Epidem Rec 2000; 75 (2): 12-16), the meeting of the relevant thimerosal of international vaccine consultative committee tissue in 1999 thinks that the baby lacks the ability of removing hydrargyrum, and 2002 the 3rd phase 128-130 pages or leaves are translated from Wkly Epidem Rec 2002; 77 (47): 389-394).
At present, vaccine commonly used contains antiseptic mostly, and is bigger to the human injury; In the preparation process, cause germ contamination easily, vaccine finished product accumulating and preservation process in its effect duration can not be guaranteed aseptic, and vaccine safety is lower; Adopt many person-times with the packing of dosage specification; Storage and use are inconvenient, and the seeded process potential safety hazard is more, causes ill symptomses such as cross infection easily.
Summary of the invention
The object of the invention promptly is to overcome the deficiency of prior art, and a kind of employing Strict aseptic technology is provided, and makes the vaccine finished product in its effect duration, keep aseptic condition; Guarantee vaccine safety; Solved the problem that the traditional vaccine goods contain antiseptic, be applicable to the various bacteria toxoid, the scope of application is wider; Guarantee each person-time use one vaccinating agent, guarantee the processing technology that does not contain the antiseptic vaccine of use safety, health.
The objective of the invention is to realize through following technical scheme: do not contain the processing technology of antiseptic vaccine, it may further comprise the steps:
(1) refining: as to adopt the plate and frame filter press technique to remove thalline; Collect filtrating; Is that the ultrafiltration system of 28～32KD concentrates with the filtrating of collecting with molecular weight; Adding ammonium sulfate is saltoutd after concentrating completion; Centrifugal collecting precipitation after saltouing; Treat to carry out the ultrafiltration desalination after the precipitation dissolving, obtain refining toxoid;
(2) detoxification: add formalin by 0.1～0.3% of refining toxoid solution, 36～40 ℃ of following detoxifications 30～50 days;
(3) detoxification inspection: detoxification is taken a sample to every bottle of refining toxoid after accomplishing, and chooses body weight and be at least 2 of the Cavia porcelluss of 300～400g; Every subcutaneous injection 400～600 Lf are diluted to 90～110Lf/ml with 0.8～1.0% aseptic sodium chloride solution, every subcutaneous injection 4～6ml with every bottle of refining toxoid detoxification sample; Observed in the 5th～9 day, the 12nd～16 day, the 19th～23 day in the injection back; Animal does not have bad symptom, and body weight does not have before the injection and do not alleviate, and strong deposit the used toxoid of animal be qualified; The person of losing weight should increase injection volume and carry out the retrial judgement, continues detoxification with the used toxoid of ill symptoms animal takes place;
(4) aseptic filtration: the stock solution of detoxification passed examination is carried out aseptic filtration, make and do not contain the antiseptic vaccinogen liquid;
(5) preparation: prepare by following component and weight: do not contain antiseptic vaccinogen liquid 7～9Lf/L, adsorbent 1.0 ~ 3.0g/L, Na
2HPO
40.05 ~ 0.07g/L, KH
2PO
40.005 ~ 0.015g/L, NaCl 7 ~ 9g/L makes after preparation is accomplished and does not contain antiseptic vaccine semi-finished product;
(6) packing: will not contain antiseptic vaccine semi-finished product by human dosage specification packing each time, and preserve in 2～8 ℃ of shadings.
The described antiseptic vaccine that do not contain comprises bacillary toxoid vaccine; Described bacillary toxoid vaccine comprises tetanus vaccine, diphtheria vaccine, pertussis vaccine at least; Described adsorbent is Al (OH)
3
The invention has the beneficial effects as follows: the present invention provides a kind of processing technology that does not contain the antiseptic vaccine, adopt unique sterile production equipment and technology and pharmaceutical formulation, has the problem that the traditional vaccine goods contain antiseptic that solved; Aseptic in the vaccine production overall process, vaccine finished product accumulating and preservation process in its effect duration is aseptic, improves vaccine safety; Adopt each time human dosage specification to carry out packing, each person-time use potion is guaranteed in storage and easy to use; Pollution when having avoided many person-times of uses in the wait process with potion; Guarantee use health, safety, be applicable to the various bacteria toxoid, advantage such as the scope of application is wider.
The specific embodiment
Below in conjunction with embodiment the present invention is done further description, but protection scope of the present invention is not limited to the following stated.
Embodiment 1:
Do not contain the processing technology of antiseptic vaccine, it may further comprise the steps:
(1) refining: as to adopt the plate and frame filter press technique to remove thalline; Collect filtrating; Is that the ultrafiltration system of 28KD concentrates with the filtrating of collecting with molecular weight; Adding ammonium sulfate is saltoutd after concentrating completion; Centrifugal collecting precipitation after saltouing; Treat to carry out the ultrafiltration desalination after the precipitation dissolving, obtain refining toxoid;
(2) detoxification: add formalin by 0.1% of refining toxoid solution, 36 ℃ of following detoxifications 30 days;
(3) detoxification inspection: after detoxification is accomplished; Every bottle of refining toxoid is taken a sample; Choose body weight and be at least 2 of the cavys of 400g; Every hypodermic injection 600Lf; Every bottle of refining toxoid detoxification sample is diluted to 90Lf/ml with 1.0% aseptic sodium chloride solution; Every hypodermic injection 6.67ml; In injecting the back the 9th day; The 16th day; Observed in the 23rd day; Animal does not have bad symptom; The body weight preceding nothing of injection alleviates; And the strong used toxoid of animal of depositing is qualified, and the person of losing weight should increase injection volume and carry out retrial and judge, continues detoxification with the used toxoid of ill symptoms animal takes place;
(4) aseptic filtration: the stock solution of detoxification passed examination is carried out aseptic filtration, make and do not contain the antiseptic vaccinogen liquid;
(5) preparation: prepare by following component and weight: do not contain antiseptic vaccinogen liquid 7Lf/ml, Al (OH)
31.0g/L, Na
2HPO
40.07g/L, KH
2PO
40.005g/L NaCl 9g/L makes after preparation is accomplished and does not contain antiseptic vaccine semi-finished product;
(6) packing: will not contain antiseptic vaccine semi-finished product by human dosage specification packing each time, and preserve in 8 ℃ of shadings.
The described antiseptic vaccine that do not contain comprises bacillary toxoid vaccine; Described bacillary toxoid vaccine comprises tetanus vaccine, diphtheria vaccine, pertussis vaccine at least.
Embodiment 2:
Do not contain the processing technology of antiseptic vaccine, it may further comprise the steps:
(1) refining: as to adopt the plate and frame filter press technique to remove thalline; Collect filtrating; Is that the ultrafiltration system of 32KD concentrates with the filtrating of collecting with molecular weight; Adding ammonium sulfate is saltoutd after concentrating completion; Centrifugal collecting precipitation after saltouing; Treat to carry out the ultrafiltration desalination after the precipitation dissolving, obtain refining toxoid;
(2) detoxification: add formalin by 0.3% of refining toxoid solution, 40 ℃ of following detoxifications 50 days;
(3) detoxification inspection: after detoxification is accomplished; Every bottle of refining toxoid is taken a sample; Choose body weight and be at least 2 of the cavys of 300g; Every hypodermic injection 400Lf; Every bottle of refining toxoid detoxification sample is diluted to 110Lf/ml with 0.8% aseptic sodium chloride solution; Every hypodermic injection 3.64ml; In injecting the back the 5th day; The 12nd day; Observed in the 19th day; Animal does not have bad symptom; The body weight preceding nothing of injection alleviates; And the strong used toxoid of animal of depositing is qualified, and the person of losing weight should increase injection volume and carry out retrial and judge, continues detoxification with the used toxoid of ill symptoms animal takes place;
(4) aseptic filtration: the stock solution of detoxification passed examination is carried out aseptic filtration, make and do not contain the antiseptic vaccinogen liquid;
(5) preparation: prepare by following component and weight: do not contain antiseptic vaccinogen liquid 9Lf/ml, Al (OH)
33.0g/L, Na
2HPO
40.05g/L, KH
2PO
40.015g/L NaCl 7g/L makes after preparation is accomplished and does not contain antiseptic vaccine semi-finished product;
(6) packing: will not contain antiseptic vaccine semi-finished product by human dosage specification packing each time, and preserve in 2 ℃ of shadings.
The described antiseptic vaccine that do not contain comprises bacillary toxoid vaccine; Described bacillary toxoid vaccine comprises tetanus vaccine, diphtheria vaccine, pertussis vaccine at least.
Embodiment 3:
Do not contain the processing technology of antiseptic vaccine, it may further comprise the steps:
(1) refining: as to adopt the plate and frame filter press technique to remove thalline; Collect filtrating; Is that the ultrafiltration system of 30KD concentrates with the filtrating of collecting with molecular weight; Adding ammonium sulfate is saltoutd after concentrating completion; Centrifugal collecting precipitation after saltouing; Treat to carry out the ultrafiltration desalination after the precipitation dissolving, obtain refining toxoid;
(2) detoxification: add formalin by 0.2% of refining toxoid solution, 38 ℃ of following detoxifications 40 days;
(3) detoxification inspection: after detoxification is accomplished; Every bottle of refining toxoid is taken a sample; Choose body weight and be at least 2 of the cavys of 350g; Every hypodermic injection 500Lf; Every bottle of refining toxoid detoxification sample is diluted to 100Lf/ml with 0.9% aseptic sodium chloride solution; Every hypodermic injection 5ml; In injecting the back the 7th day; The 14th day; Observed in the 21st day; Animal does not have bad symptom; The body weight preceding nothing of injection alleviates; And the strong used toxoid of animal of depositing is qualified, and the person of losing weight should increase injection volume and carry out retrial and judge, continues detoxification with the used toxoid of ill symptoms animal takes place;
(4) aseptic filtration: the stock solution of detoxification passed examination is carried out aseptic filtration, make and do not contain the antiseptic vaccinogen liquid;
(5) preparation: prepare by following component and weight: do not contain antiseptic vaccinogen liquid 8Lf/ml, Al (OH)
32.0g/L, Na
2HPO
40.06g/L, KH
2PO
40.01g/L NaCl 8g/L makes after preparation is accomplished and does not contain antiseptic vaccine semi-finished product;
(6) packing: will not contain antiseptic vaccine semi-finished product by human dosage specification packing each time, and preserve in 5 ℃ of shadings.
The described antiseptic vaccine that do not contain comprises bacillary toxoid vaccine; Described bacillary toxoid vaccine comprises tetanus vaccine, diphtheria vaccine, pertussis vaccine at least.
Claims (4)
1. do not contain the processing technology of antiseptic vaccine, it is characterized in that: it may further comprise the steps:
(1) refining: as to adopt the plate and frame filter press technique to remove thalline; Collect filtrating; Is that the ultrafiltration system of 28～32KD concentrates with the filtrating of collecting with molecular weight; Adding ammonium sulfate is saltoutd after concentrating completion; Centrifugal collecting precipitation after saltouing; Treat to carry out the ultrafiltration desalination after the precipitation dissolving, obtain refining toxoid;
(2) detoxification: add formalin by 0.1～0.3% of refining toxoid solution, 36～40 ℃ of following detoxifications 30～50 days;
(3) detoxification inspection: detoxification is taken a sample to every bottle of refining toxoid after accomplishing, and chooses body weight and be at least 2 of the Cavia porcelluss of 300～400g; Every subcutaneous injection 400～600 Lf are diluted to 90～110Lf/ml with 0.8～1.0% aseptic sodium chloride solution, every subcutaneous injection 4～6ml with every bottle of refining toxoid detoxification sample; Observed in the 5th～9 day, the 12nd～16 day, the 19th～23 day in the injection back; Animal does not have bad symptom, and body weight does not have before the injection and do not alleviate, and strongly deposits the used toxoid of animal and be qualified stock solution; The person of losing weight should increase injection volume and carry out the retrial judgement, continues detoxification with the used toxoid of ill symptoms animal takes place;
(4) aseptic filtration: the stock solution of detoxification passed examination is carried out aseptic filtration, make and do not contain the antiseptic vaccinogen liquid;
(5) preparation: prepare by following component and weight: do not contain antiseptic vaccinogen liquid 7～9Lf/ml, adsorbent 1.0 ~ 3.0g/L, Na
2HPO
40.05 ~ 0.07g/L, KH
2PO
40.005 ~ 0.015g/L, NaCl 7 ~ 9g/L makes after preparation is accomplished and does not contain antiseptic vaccine semi-finished product;
(6) packing: will not contain antiseptic vaccine semi-finished product by human dosage specification packing each time, and preserve in 2～8 ℃ of shadings.
2. the processing technology that does not contain the antiseptic vaccine according to claim 1 is characterized in that: the described antiseptic vaccine that do not contain comprises bacillary toxoid vaccine.
3. the processing technology that does not contain the antiseptic vaccine according to claim 2 is characterized in that: described bacillary toxoid vaccine comprises tetanus vaccine, diphtheria vaccine, pertussis vaccine at least.
4. the processing technology that does not contain the antiseptic vaccine according to claim 1 is characterized in that: described adsorbent is Al (OH)
3
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN2011103656555A CN102363041A (en) | 2011-11-17 | 2011-11-17 | Method for preparing preservative-free vaccine |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2011103656555A CN102363041A (en) | 2011-11-17 | 2011-11-17 | Method for preparing preservative-free vaccine |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102961741A (en) * | 2012-12-10 | 2013-03-13 | 武汉生物制品研究所有限责任公司 | Method for preparing tetanus toxoid vaccine |
| CN106039308A (en) * | 2016-06-29 | 2016-10-26 | 玉溪九洲生物技术有限责任公司 | Preservative-free horse tetanus immune globulin preparation for injection and preparation method thereof |
| CN106046127A (en) * | 2016-08-10 | 2016-10-26 | 成都生物制品研究所有限责任公司 | Preparation method of diphtheria toxoid |
| CN106167519A (en) * | 2016-08-10 | 2016-11-30 | 成都生物制品研究所有限责任公司 | A kind of preparation method of tetanus toxoid |
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| WO1998019702A1 (en) * | 1996-11-07 | 1998-05-14 | Smithkline Beecham Biologicals S.A. | Acellular pertussis vaccine with diphthriae- and tetanus-toxoids |
| WO2002055105A1 (en) * | 2001-01-10 | 2002-07-18 | Lg Life Sciences Ltd. | Manufacturing method of combined vaccine |
| CN101380471A (en) * | 2008-10-15 | 2009-03-11 | 浙江卫信生物药业有限公司 | Preparation method of absorption diphtheria tetanus combined vaccine without formaldehyde and merthiolate |
| CN101385853A (en) * | 2008-10-24 | 2009-03-18 | 浙江卫信生物药业有限公司 | Preparation of domestic adsorhed diphtheria tetanus and acellular pertussis combined vaccine without formaldehyde and merthiolate |
-
2011
- 2011-11-17 CN CN2011103656555A patent/CN102363041A/en active Pending
Patent Citations (4)
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| WO1998019702A1 (en) * | 1996-11-07 | 1998-05-14 | Smithkline Beecham Biologicals S.A. | Acellular pertussis vaccine with diphthriae- and tetanus-toxoids |
| WO2002055105A1 (en) * | 2001-01-10 | 2002-07-18 | Lg Life Sciences Ltd. | Manufacturing method of combined vaccine |
| CN101380471A (en) * | 2008-10-15 | 2009-03-11 | 浙江卫信生物药业有限公司 | Preparation method of absorption diphtheria tetanus combined vaccine without formaldehyde and merthiolate |
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102961741A (en) * | 2012-12-10 | 2013-03-13 | 武汉生物制品研究所有限责任公司 | Method for preparing tetanus toxoid vaccine |
| CN102961741B (en) * | 2012-12-10 | 2014-12-03 | 武汉生物制品研究所有限责任公司 | Method for preparing tetanus toxoid vaccine |
| CN106039308A (en) * | 2016-06-29 | 2016-10-26 | 玉溪九洲生物技术有限责任公司 | Preservative-free horse tetanus immune globulin preparation for injection and preparation method thereof |
| CN106046127A (en) * | 2016-08-10 | 2016-10-26 | 成都生物制品研究所有限责任公司 | Preparation method of diphtheria toxoid |
| CN106167519A (en) * | 2016-08-10 | 2016-11-30 | 成都生物制品研究所有限责任公司 | A kind of preparation method of tetanus toxoid |
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Application publication date: 20120229 |