CN1284601C - Vaccine composition stable at normal temperature and its prepn - Google Patents
Vaccine composition stable at normal temperature and its prepn Download PDFInfo
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- CN1284601C CN1284601C CNB031285864A CN03128586A CN1284601C CN 1284601 C CN1284601 C CN 1284601C CN B031285864 A CNB031285864 A CN B031285864A CN 03128586 A CN03128586 A CN 03128586A CN 1284601 C CN1284601 C CN 1284601C
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Abstract
The present invention relates to a vaccine composition stable at normal temperature and a preparation method for the vaccine composition. The vaccine composition of the present invention is characterized in that the mixture of vaccines and other auxiliary materials except core auxiliary materials is fixed to the core auxiliary materials in a microencapsulation mode through airflow spray drying. The vaccine composition of the present invention is preserved for more than one year under the condition of the temperature of 25 DEG C, and the normal antigen potency cab be maintained. The present invention is a group of vaccine compositions stable at normal temperature. The vaccine composition stable at normal temperature of the present invention has the advantages of easy use and no adverse reaction, and simultaneously, the production cost, the transportation cost and the storage cost are saved. The vaccine composition has an obvious economic meaning.
Description
The present invention relates to field of pharmaceutical preparations, particularly, the present invention relates to one group and can under 25 ℃ of conditions Celsius, preserve more than 1 year and to also have vaccine combination that normal antigen tires and preparation method thereof.
Vaccine is the main means that keep off infection, and microbial numbers and viability have direct relation in the effectiveness of live vaccine and the vaccine.The current freeze drying process that generally adopts is preserved microbial numbers and vigor in the vaccine, and its principle is that the metabolic activity of microorganism reduces in the live vaccine, is in resting state, thereby can survives for a long time through behind the freeze-dry process.But the freeze-dry process complexity, the influence factor is many, as the kind of microorganism, protectant composition, freeze drying process, storage temperature etc., the cost height, transportation needs cold preservation with storage process.Inactivated vaccine does not need freeze-dry process, but wants low temperature storage yet, has the problem of ambient stable yet.What address this problem is to develop a kind of bacterin preparation that has versatility, can substitute the ambient stable of freeze-dry process product at all, and the present invention finishes in order to address this problem just.
Therefore, the vaccine combination that the purpose of this invention is to provide a kind of ambient stable;
Another object of the present invention provides the preparation method of the vaccine combination of ambient stable.
The present invention adopts pneumatic spray drying equipment, can rapidly biological raw material in the mixing material prescription such as vaccine be fixed on the microgranule core of fluidizing core adjuvant, realizes micro encapsulation, and the bacterin preparation of making can be deposited more than 1 year under 25 ℃ of conditions.The expensive expense of freeze-dry process has been exempted in the application of pneumatic spray drying equipment, increases work efficiency; Also can solve the inactivation problem of vaccine in freeze-dry process, improve the quality and the effect of vaccine; Vaccine does not need stored refrigerated simultaneously.So both can reduce the production cost of vaccine, make things convenient for transportation, storage and the use of bacterin preparation again.
Ambient stable vaccine combination of the present invention can be mixed with various biologic activity units, it generally is every gram vaccine combination 1-1000 person-portion or plumage part or head part, every in other words gram vaccine combination can for 1-1000 people or 1-1000 fowl or the 1-1000 head is beastly uses, and reaches prophylactic purpose.
The adjuvant of ambient stable vaccine combination of the present invention is the conventional adjuvant of medicine, can be selected from and comprise mannitol, gelatin, propylene glycol, trehalose, glucosan, sodium hydrogen phosphate, sodium dihydrogen phosphate, glycine, ovalbumin, sodium chloride, tetraacethyl diethylamine disodium or their mixture, in addition, the adjuvant of the vaccine combination of ambient stable of the present invention can also be selected from and comprise sucrose, lactose, potassium dihydrogen phosphate, tryptone, polyvinylpyrrolidone, bovine serum albumin, sodium glutamate, vitamin C or their mixture.Wherein the core adjuvant is selected from mannitol.
Mannitol in the above-mentioned adjuvant is the core adjuvant and the filler of vaccine combination; the glucosan of above-mentioned adjuvant is a filler, and the trehalose of above-mentioned adjuvant is a protective agent, and the gelatin of above-mentioned adjuvant is a bonding agent; the gelatin of above-mentioned adjuvant is the coating composition, and the propylene glycol of above-mentioned adjuvant is a wetting agent.
Calculate with adjuvant weight, the weight ratio of adjuvant is: mannitol 40-70%, gelatin 15-35%, propylene glycol 1-10%, trehalose 1-10%, glucosan 1-10%, ovalbumin 0.1-5%, glycine 0.1-5%, sodium hydrogen phosphate 0.1-5%, sodium dihydrogen phosphate 0.1-5%, sodium chloride 0.1-5%, tetraacethyl diethylamine disodium 0.1-5%, if necessary, can also include sucrose 7-20% in the adjuvant, lactose 5-20%, potassium dihydrogen phosphate 2-5%, tryptone 1-5%, polyvinylpyrrolidone 1-5%, bovine serum albumin 3-10%, sodium glutamate 3-5%, vitamin C 2-5%.
The preparation method of ambient stable vaccine combination of the present invention may further comprise the steps:
1. be mixed in proportion other the various adjuvants except that core adjuvant mannitol, add the abundant mix homogeneously of suitable quantity of water, make coating solution;
2. according to the units activity requirement of the specific activity and the finished product of vaccinogen liquid, add an amount of vaccinogen liquid in coating solution, fully mix homogeneously;
3. at 40-90 ℃, core adjuvant mannitol is in fluidized state by using the air-stream spraying drying equipment;
4. with 100-240m
3/ hour spraying rate the mixed liquor of coating solution and vaccine evenly is ejected into the surface of the core adjuvant mannitol of fluidized state;
5. at 25-50 ℃, preferred 30-40 ℃ dried 5-80 minute, make the vaccine microparticle.
Vaccine combination manufacture method of the present invention adopts the air-stream spraying seasoning, and (its operational approach and equipment thereof are seen " spray drying technology complete works ", Liu Guangwen writes, China Light Industry Press, October calendar year 2001 front page), use the air-stream spraying drying equipment to be in fluidized state as the mannitol of core adjuvant, then the mixed liquor of coating solution and vaccine evenly is ejected into the surface of core adjuvant such as mannitol, be fixed on the fluidizing microgranule core mannitol, realize micro encapsulation, make bacterin preparation after the drying.
Vaccine combination of the present invention can transform to make in case of necessity becomes various dosage forms, can be capsule, tablet, pill, granule, powder, paste, syrup, injection, spray, drop or suppository.
Description of drawings
Accompanying drawing 1 is that the room temperature of newcastle disease (ND, Lasota strain) vaccine combination is preserved the testing result of tiring;
Accompanying drawing 2 is newcastle disease ND antibody its growth figure.
Compared with prior art, vaccine combination of the present invention has following remarkable advantage and positive effect:
1. ambient stable vaccine combination of the present invention adopts the air-stream spraying granulation, replace freeze-dry process fully, techniques such as mixing, granulate, be dry can be finished in the short time simultaneously at the utmost point, greatly save operation and time, production efficiency is high, low cost of manufacture is finished under 30-40 ℃ of condition, the almost free of losses of the activity of vaccine;
2. after ambient stable vaccine combination of the present invention adopts air-stream spraying drying and granulating method to process, microencapsulation, can under 25 ℃ of conditions Celsius, preserve and also have normal antigen to tire more than 1 year, transportation and storage process do not need refrigeration, easy to use, reduce cost, do not react simultaneously.
The present invention is further illustrated with embodiment below.It should be understood that embodiments of the invention are only used for illustrating the present invention, rather than limitation of the present invention, the simple modifications of under design prerequisite of the present invention the present invention being carried out all belongs to the scope of protection of present invention.Except as otherwise noted, the percent among the present invention all is percetage by weight.
Embodiment 1: infectious bronchitis of chicken (IB, H120) live vaccine compositions
Its material formula is:
Mannitol 46% (core adjuvant)
Gelatin 29%
Propylene glycol 2%
Trehalose 5%
Ovalbumin 2%
Sodium hydrogen phosphate 1.5%
Sodium dihydrogen phosphate 0.5%.
Sodium chloride 0.5%
Tetraacethyl diethylamine disodium 0.5%
Every gram compositions contains chicken H120 vaccine 100 plumage parts, accounts for 2% of composition weight, and the weight ratio of moisture is 2%.
Preparation method:
(1) takes by weighing in proportion and mix above-mentioned each adjuvant except that core material mannitol, add the abundant mix homogeneously of suitable quantity of water, make coating solution;
(2) according to the units activity requirement of the specific activity and the finished product of vaccinogen liquid, add account for composition weight 2% above-mentioned vaccinogen liquid in coating solution, abundant mix homogeneously;
(3) will be in fluidized state at 80 ℃ as the mannitol of core material by use air-stream spraying drying equipment;
(4) with 100m
3/ hour spraying rate the mixed liquor of coating solution and vaccine evenly is ejected into the mannitol surface of fluidized state;
(5) 33 ℃ of dried 60 minutes, make the vaccine microparticle.
Embodiment 2: infectious bursal disease (IBD NF8 strain) live vaccine compositions
Its material formula is:
Mannitol 53% (core adjuvant)
Gelatin 20%
Bovine serum albumin 2%
Tryptone 1%
Catergen %
Trehalose 3%
Glucosan 6%
Ovalbumin 2%
Sodium dihydrogen phosphate 1%
Sodium hydrogen phosphate 1%
Potassium dihydrogen phosphate 1%
Every gram compositions contains chicken bursa vaccine 500 plumage parts, accounts for 4% of composition weight, and moisture proportion is 1%
Preparation method:
(1) takes by weighing in proportion and mix above-mentioned each adjuvant except that core material mannitol, add the abundant mix homogeneously of suitable quantity of water, make coating solution;
(2) according to the units activity requirement of the specific activity and the finished product of vaccinogen liquid, add account for composition weight 4% above-mentioned vaccinogen liquid in coating solution, abundant mix homogeneously;
(3) will be in fluidized state at 50 ℃ as the mannitol of core material by use air-stream spraying drying equipment;
(4) with 200m
3/ hour spraying rate the mixed liquor of coating solution and vaccine evenly is ejected into the mannitol surface of fluidized state;
(5) 40 ℃ of dried 25 minutes, make the vaccine microparticle.
Embodiment 3: newcastle disease (ND, Lasota strain) live vaccine compositions
Its material formula is:
Mannitol 50% (core adjuvant)
Gelatin 19%
Trehalose 7%
Dextran 8 %
Glycine 2%
Sodium dihydrogen phosphate 0.5%.
Ovalbumin 1.5%
Sodium chloride 0.5%
Tetraacethyl diethylamine disodium 0.5%
Every gram compositions contains newcastle disease (ND, Lasota strain) vaccine 100 plumage parts, accounts for 0.5% of composition weight percentage ratio, and the weight ratio of moisture is 2.5%.
Preparation method:
(1) takes by weighing in proportion and mix above-mentioned each adjuvant except that core material mannitol, add the abundant mix homogeneously of suitable quantity of water, make coating solution;
(2) according to the units activity requirement of the specific activity and the finished product of vaccinogen liquid, add account for composition weight 0.5% above-mentioned vaccinogen liquid in coating solution, abundant mix homogeneously;
(3) will be in fluidized state at 80 ℃ as the mannitol of core material by use air-stream spraying drying equipment;
(4) with 16m
3/ hour spraying rate the mixed liquor of coating solution and vaccine evenly is ejected into the mannitol surface of fluidized state;
(5) 35 ℃ of dried 10 minutes, make the vaccine microparticle.
Embodiment 4: live virus content (the malicious valency EID of newcastle disease (ND, Lasota strain) the live vaccine compositions of the embodiment of the invention 3 preparations
50/ 2g) measure and results of stability
Newcastle disease (ND, Lasota strain) the vaccine combination laboratory sample of the embodiment of the invention 3 preparations quantitatively is sub-packed in the aseptic vial, places respectively under 4 ℃, 25 ℃, 35 ℃ and deposit, and measure different each batch sample live virus content (EID of holding time
50/ 2g).Sample detection is carried out in strict accordance with " veterinary biologics rules) " (version in 2000).Result's following (see Table 1 and accompanying drawing 1):
The live virus assay result of the newcastle disease of table 1: embodiment 3 (ND, Lasota strain) live vaccine compositions
| Group | Initially tire | 35 C 7 days | 35 mouthfuls of C 14 days | 35 mouthfuls of C 30 days | 25 mouthfuls of C 30 days | |
| (EID 50/2g) | ||||||
| Experimental group | 7.38 | 5.5 | 6.5 | |||
| Lyophilized control | 8.11 | 6.5 | 4.83 | 3.69 | 6.5 | |
The result shows microcapsule process of the present invention to the basic not damaged of vaccine antigen, and sample is initially tired and tired near vaccine antigen stock solution.Test specimen is stable, and the test group sample is deposited a week and 25 ℃ and deposited a month EID under 35 ℃
50The decline titre is all less than the lyophilized control product.
Antibody test experiment after the newcastle disease of the embodiment 5 animal inoculation embodiment of the invention 3 (ND, Lasota strain) the live vaccine compositions
4 30 of age in days SPF chickling are divided into three groups, 10 every group, the newcastle disease of the first winding kind embodiment of the invention 3 (ND Lasota strain) vaccine combination; The second winding kind freeze dried vaccine (the finished product 809-2 of Zhongmu Stocks Trading Co. Nanjing medical instruments factory criticizes) is made blank for the 3rd group.Test group is different with the antigen amount of matched group inoculation, and antigenic content is every plumage part 10 in the freeze dried vaccine 0.1ml vaccine
6.0EID
50, and antigenic content is 0.1 plumage part (10 in the 0.1ml vaccine of test group vaccine dissolving back
5.0EID
50), only be 1/10 of freeze-dried vaccine.
Test with under equal conditions isolated rearing of chicken, observation for three groups, and respectively at inoculation back 7 days, 14 days, 21 days, 28 days and blood sampling in 35 days, separation of serum is surveyed HI antibody with fixed virus dilute serum method.(see Table 2 and accompanying drawing 2)
HI TPPA behind the table 2 laboratory sample inoculation chicken
| Group | The chicken number | The HI antibody nlog2 that on average tires, x | ||||
| 7 days | 14 days | 21 days | 28 days | 35 days | ||
| Test specimen | 10 | 1.25 | 2.8 | 3.5 | 4.17 | 4 |
| The lyophilizing sample | 10 | 1.83 | 3.8 | 4.6 | 4.83 | 4.6 |
| Blank | 10 | 0.5 | ||||
The result shows, only is under 1/10 the situation of matched group at the test group dosage of inoculation, can measure antibody in back 7 days in inoculation, and compare no significant difference with the lyophilized control group, its antibody growth and decline trend and lyophilized control group basically identical.The inoculation chicken is normal, does not have any untoward reaction.
Claims (6)
1, a kind of vaccine combination of ambient stable, form by vaccine and adjuvant, it is characterized in that vaccine is infectious bronchitis of chicken live vaccine or infectious bursal disease live vaccine or chicken Newcastle disease live vaccine, in vaccine and the mannitol that is ejected into fluidized state after the coating solution of adjuvant system mixes fixing in its surface, adjuvant is the mixture of gelatin, propylene glycol, trehalose, glucosan, sodium hydrogen phosphate, sodium dihydrogen phosphate, glycine, ovalbumin, sodium chloride, tetraacethyl diethylamine disodium.
2,, it is characterized in that adjuvant can also be selected from sucrose, lactose, potassium dihydrogen phosphate, tryptone, polyvinylpyrrolidone, bovine serum albumin, vitamin C, sodium glutamate or their mixture according to the vaccine combination of claim 1.
3, according to the vaccine combination of claim 1, the biologic activity unit that it is characterized in that vaccine in every gram vaccine combination is 1-1000 person-portion or plumage part or head part.
4,, it is characterized in that adjuvant contains mannitol 40-70%, gelatin 15-35%, propylene glycol 1-10%, trehalose 1-10%, glucosan 1-10%, ovalbumin 0.1-5%, glycine 0.1-5%, sodium hydrogen phosphate 0.1-5%, sodium dihydrogen phosphate 0.1-5%, sodium chloride 0.1-5%, tetraacethyl diethylamine disodium 0.1-5% by weight according to the vaccine combination of claim 1.
5, according to the vaccine combination of claim 4, it is characterized in that adjuvant can also contain lactose 5-20% by weight,, sucrose 7-20%, bovine serum albumin 3-10%, potassium dihydrogen phosphate 2-5%, tryptone 1-5%, polyvinylpyrrolidone 1-5%, sodium glutamate 3-5%, Catergen-5%.
6, a kind of method for preparing the vaccine combination of one of claim 1～5 comprises the steps:
(1) is mixed in proportion other various adjuvants except that mannitol, adds the abundant mix homogeneously of suitable quantity of water, make coating solution;
(2) according to the units activity requirement of the specific activity and the finished product of vaccinogen liquid, add an amount of vaccinogen liquid in coating solution, fully mix homogeneously;
(3) under 40～90 ℃, mannitol is in fluidized state by use air-stream spraying drying equipment;
(4) with 100～240m
3/ hour spraying rate the mixed liquor of coating solution and vaccine evenly is ejected into the mannitol surface of fluidized state;
(5) 25-50 ℃ dried 5-80 minute, make the vaccine microparticle.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031285864A CN1284601C (en) | 2003-05-22 | 2003-05-22 | Vaccine composition stable at normal temperature and its prepn |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031285864A CN1284601C (en) | 2003-05-22 | 2003-05-22 | Vaccine composition stable at normal temperature and its prepn |
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| Publication Number | Publication Date |
|---|---|
| CN1548155A CN1548155A (en) | 2004-11-24 |
| CN1284601C true CN1284601C (en) | 2006-11-15 |
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|---|---|---|---|
| CNB031285864A Expired - Fee Related CN1284601C (en) | 2003-05-22 | 2003-05-22 | Vaccine composition stable at normal temperature and its prepn |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI745278B (en) * | 2014-10-10 | 2021-11-11 | 以色列商艾畢克生物實驗有限公司 | Reduced foaming vaccine compositions |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102228687B (en) * | 2011-06-24 | 2012-10-10 | 浙江普康生物技术股份有限公司 | Freeze-dried live attenuated hepatitis A vaccine not containing gelatin or human albumin protective agent and preparation method for freeze-dried live attenuated hepatitis A vaccine |
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2003
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TWI745278B (en) * | 2014-10-10 | 2021-11-11 | 以色列商艾畢克生物實驗有限公司 | Reduced foaming vaccine compositions |
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| CN1548155A (en) | 2004-11-24 |
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Address after: 611930 Pengzhou Province, Chengdu City, the town of days Peng Road, No. 252 culture Patentee after: Weiao Pharmaceutical Co., Ltd., Sichuan Address before: 610041, No. 778, south section of Feng Xi Road, Wenjiang District, Sichuan, Chengdu Patentee before: Weiao Pharmaceutical Co., Ltd., Sichuan |
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