CN1548155A - 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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- CN1548155A CN1548155A CNA031285864A CN03128586A CN1548155A CN 1548155 A CN1548155 A CN 1548155A CN A031285864 A CNA031285864 A CN A031285864A CN 03128586 A CN03128586 A CN 03128586A CN 1548155 A CN1548155 A CN 1548155A
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- vaccine
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- mannitol
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Links
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- 239000000203 mixture Substances 0.000 title claims abstract description 39
- 239000007921 spray Substances 0.000 claims abstract description 3
- 239000002671 adjuvant Substances 0.000 claims description 41
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- 239000000594 mannitol Substances 0.000 claims description 25
- 235000010355 mannitol Nutrition 0.000 claims description 25
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 24
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- 238000000034 method Methods 0.000 claims description 14
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 12
- 230000000694 effects Effects 0.000 claims description 12
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- 229910000397 disodium phosphate Inorganic materials 0.000 claims description 7
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- TWNIBLMWSKIRAT-VFUOTHLCSA-N levoglucosan Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@H]2CO[C@@H]1O2 TWNIBLMWSKIRAT-VFUOTHLCSA-N 0.000 claims description 7
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 7
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 7
- 229940092253 ovalbumin Drugs 0.000 claims description 7
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 7
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 6
- 239000004471 Glycine Substances 0.000 claims description 6
- BPTQPROSVJPWNL-UHFFFAOYSA-N [Na].[Na].C(C)NCC Chemical compound [Na].[Na].C(C)NCC BPTQPROSVJPWNL-UHFFFAOYSA-N 0.000 claims description 6
- 108091003079 Bovine Serum Albumin Proteins 0.000 claims description 5
- 229940098773 bovine serum albumin Drugs 0.000 claims description 5
- 238000005538 encapsulation Methods 0.000 claims description 5
- 239000011859 microparticle Substances 0.000 claims description 5
- 229910000402 monopotassium phosphate Inorganic materials 0.000 claims description 5
- 235000019796 monopotassium phosphate Nutrition 0.000 claims description 5
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 claims description 5
- 239000011780 sodium chloride Substances 0.000 claims description 5
- 239000012137 tryptone Substances 0.000 claims description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 5
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 4
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 4
- 229930006000 Sucrose Natural products 0.000 claims description 4
- PXEDJBXQKAGXNJ-QTNFYWBSSA-L disodium L-glutamate Chemical compound [Na+].[Na+].[O-]C(=O)[C@@H](N)CCC([O-])=O PXEDJBXQKAGXNJ-QTNFYWBSSA-L 0.000 claims description 4
- 239000008101 lactose Substances 0.000 claims description 4
- 235000013923 monosodium glutamate Nutrition 0.000 claims description 4
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 4
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 4
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 4
- 229940073490 sodium glutamate Drugs 0.000 claims description 4
- 239000005720 sucrose Substances 0.000 claims description 4
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 claims description 3
- 229930003268 Vitamin C Natural products 0.000 claims description 3
- 230000004071 biological effect Effects 0.000 claims description 3
- 239000008187 granular material Substances 0.000 claims description 3
- 235000019154 vitamin C Nutrition 0.000 claims description 3
- 239000011718 vitamin C Substances 0.000 claims description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 claims description 2
- 239000002775 capsule Substances 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 239000006196 drop Substances 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000006072 paste Substances 0.000 claims description 2
- 239000006187 pill Substances 0.000 claims description 2
- 239000000843 powder Substances 0.000 claims description 2
- 239000000829 suppository Substances 0.000 claims description 2
- 239000006188 syrup Substances 0.000 claims description 2
- 235000020357 syrup Nutrition 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 239000000427 antigen Substances 0.000 abstract description 6
- 102000036639 antigens Human genes 0.000 abstract description 6
- 108091007433 antigens Proteins 0.000 abstract description 6
- 239000003094 microcapsule Substances 0.000 abstract description 3
- 239000011162 core material Substances 0.000 description 19
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- 208000010359 Newcastle Disease Diseases 0.000 description 9
- 238000012360 testing method Methods 0.000 description 9
- 241000287828 Gallus gallus Species 0.000 description 7
- 238000011081 inoculation Methods 0.000 description 7
- 239000000523 sample Substances 0.000 description 5
- 238000003860 storage Methods 0.000 description 5
- 241000700605 Viruses Species 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
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- 208000015181 infectious disease Diseases 0.000 description 3
- 238000001694 spray drying Methods 0.000 description 3
- 238000005303 weighing Methods 0.000 description 3
- 230000000890 antigenic effect Effects 0.000 description 2
- 230000007423 decrease Effects 0.000 description 2
- 239000000945 filler Substances 0.000 description 2
- 238000004108 freeze drying Methods 0.000 description 2
- 230000002458 infectious effect Effects 0.000 description 2
- 239000006101 laboratory sample Substances 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000004531 microgranule Substances 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 210000002966 serum Anatomy 0.000 description 2
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- PFTAWBLQPZVEMU-DZGCQCFKSA-N (+)-catechin Chemical compound C1([C@H]2OC3=CC(O)=CC(O)=C3C[C@@H]2O)=CC=C(O)C(O)=C1 PFTAWBLQPZVEMU-DZGCQCFKSA-N 0.000 description 1
- 101100046775 Arabidopsis thaliana TPPA gene Proteins 0.000 description 1
- 241001260012 Bursa Species 0.000 description 1
- 208000027312 Bursal disease Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 229960000074 biopharmaceutical Drugs 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 239000007767 bonding agent Substances 0.000 description 1
- 206010006451 bronchitis Diseases 0.000 description 1
- 239000008199 coating composition Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
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- 235000011194 food seasoning agent Nutrition 0.000 description 1
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- 229940031551 inactivated vaccine Drugs 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 235000013772 propylene glycol Nutrition 0.000 description 1
- 239000003223 protective agent Substances 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 230000000384 rearing effect Effects 0.000 description 1
- 238000005057 refrigeration Methods 0.000 description 1
- 230000000284 resting effect Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- 239000011550 stock solution Substances 0.000 description 1
- XZZNDPSIHUTMOC-UHFFFAOYSA-N triphenyl phosphate Chemical compound C=1C=CC=CC=1OP(OC=1C=CC=CC=1)(=O)OC1=CC=CC=C1 XZZNDPSIHUTMOC-UHFFFAOYSA-N 0.000 description 1
- 230000035899 viability Effects 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Images
Abstract
The present invention features that the mixture of vaccine and some supplementary material is airflow spray dried into microcapsule and fixed to kernel supplementary material to form the vaccine composition. The vaccine composition of the present invention may be maintained at 25 deg.c for over one year to keep its normal antigen potency. The vaccine composition is convenient in use, and has low cost and no bad reaction.
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%, Catergen-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, the present invention's vaccine combination has following remarkable advantage and positive effect:
1. the present invention's ambient stable vaccine combination adopts air-stream spraying granulation method, 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, and the activity of vaccine is almost without loss;
2. after the present invention's ambient stable vaccine combination adopts air-stream spraying drying and granulating method to process, microcapsules, 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 have simultaneously bad reaction.
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%
Glucosan 5%
Ovalbumin 2%
Glycine 4%
Sodium hydrogen phosphate 1.5%
Sodium dihydrogen phosphate 0.5%.
Sodium oxide 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 %
Propylene glycol 3%
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%
Propylene glycol 5%
Dextran 8 %
Glycine 2%
Sodium hydrogen phosphate 3%
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 160m
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 C7 days | 35 C14 days | 35 C30 days | 25 C30 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 (13)
1. the vaccine combination of an ambient stable is made up of vaccine and adjuvant, it is characterized in that vaccine is fixed on the core adjuvant by micro encapsulation.
2. according to the vaccine combination of claim 1, it is characterized in that vaccine is fixed on the core adjuvant by micro encapsulation by the air-stream spraying drying.
3. according to the vaccine combination of claim 2, it is characterized in that the mixture of vaccine and other adjuvants except that the core adjuvant is fixed on the core adjuvant by micro encapsulation by the air-stream spraying drying.
4. according to the vaccine combination of claim 3, it is characterized in that the core adjuvant is selected from mannitol, other adjuvants are selected from gelatin, propylene glycol, trehalose, glucosan, sodium hydrogen phosphate, sodium dihydrogen phosphate, glycine, ovalbumin, sodium chloride, tetraacethyl diethylamine disodium or their mixture.
5. according to the vaccine combination of claim 4, wherein other adjuvants can also be selected from sucrose, lactose, potassium dihydrogen phosphate, tryptone, polyvinylpyrrolidone, bovine serum albumin, vitamin C, sodium glutamate or their mixture.
6. according to the vaccine combination of one of claim 1-5, it is characterized in that every gram vaccine combination can be mixed with contains various biologic activity unit content vaccines.
7. according to the vaccine combination of claim 6, the biologic activity of vaccine is 1-1000 person-portion or plumage part or head part in wherein every gram vaccine combination.
8. according to the vaccine combination of claim 7, it 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.
9. vaccine combination according to Claim 8, it can also contain lactose 5-20%, sucrose 7-20%, bovine serum albumin 3-10%, potassium dihydrogen phosphate 2-5%, tryptone 1-5%, polyvinylpyrrolidone 1-5%, sodium glutamate 3-5%, vitamin C 2-5% by weight.
10. a method for preparing the vaccine combination of one of claim 1-9 comprises the steps:
(1). be mixed in proportion other the various adjuvants except that the core adjuvant, add the abundant mix homogeneously of suitable quantity of water, make coating solution;
(2). the units activity requirement according to the specific activity and the finished product of vaccinogen liquid adds an amount of vaccinogen liquid in coating solution, fully mix homogeneously;
(3). under 40-90 ℃, the core adjuvant 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 core adjuvant surface of fluidized state;
(5) .25-50 ℃ dried 5-80 minute, make the vaccine microparticle.
11. the method for preparing vaccine combination according to claim 10 is characterized in that described core adjuvant is a mannitol.
12. the method for preparing vaccine combination according to claim 11 is characterized in that step (5) carries out under 30-40 ℃.
13., it is characterized in that to be converted into various dosage forms in case of necessity, can be capsule, tablet, pill, granule, powder, paste, syrup, injection, spray, drop or suppository according to the vaccine combination of one of claim 1-9.
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| CNB031285864A CN1284601C (en) | 2003-05-22 | 2003-05-22 | Vaccine composition stable at normal temperature and its prepn |
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| CNB031285864A CN1284601C (en) | 2003-05-22 | 2003-05-22 | Vaccine composition stable at normal temperature and its prepn |
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| CN1548155A true CN1548155A (en) | 2004-11-24 |
| CN1284601C CN1284601C (en) | 2006-11-15 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102228687A (en) * | 2011-06-24 | 2011-11-02 | 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 |
Families Citing this family (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 |
-
2003
- 2003-05-22 CN CNB031285864A patent/CN1284601C/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102228687A (en) * | 2011-06-24 | 2011-11-02 | 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 |
| 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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| CN1284601C (en) | 2006-11-15 |
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