CN103610641A - Two-phase oil emulsion adjuvant for veterinary vaccines, and production method thereof - Google Patents
Two-phase oil emulsion adjuvant for veterinary vaccines, and production method thereof Download PDFInfo
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- CN103610641A CN103610641A CN201310619292.2A CN201310619292A CN103610641A CN 103610641 A CN103610641 A CN 103610641A CN 201310619292 A CN201310619292 A CN 201310619292A CN 103610641 A CN103610641 A CN 103610641A
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- 229960005486 vaccine Drugs 0.000 title claims abstract description 65
- 239000002671 adjuvant Substances 0.000 title claims abstract description 50
- 239000000839 emulsion Substances 0.000 title claims abstract description 40
- 238000004519 manufacturing process Methods 0.000 title claims abstract description 8
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims abstract description 81
- 239000003921 oil Substances 0.000 claims abstract description 46
- 239000002480 mineral oil Substances 0.000 claims abstract description 38
- 235000010446 mineral oil Nutrition 0.000 claims abstract description 38
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 claims abstract description 22
- 229920000053 polysorbate 80 Polymers 0.000 claims abstract description 22
- 238000003756 stirring Methods 0.000 claims description 48
- 239000000263 2,3-dihydroxypropyl (Z)-octadec-9-enoate Substances 0.000 claims description 26
- RZRNAYUHWVFMIP-GDCKJWNLSA-N 3-oleoyl-sn-glycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-GDCKJWNLSA-N 0.000 claims description 26
- 239000004698 Polyethylene Substances 0.000 claims description 26
- 239000002253 acid Substances 0.000 claims description 26
- RZRNAYUHWVFMIP-UHFFFAOYSA-N monoelaidin Natural products CCCCCCCCC=CCCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-UHFFFAOYSA-N 0.000 claims description 26
- -1 polyethylene Polymers 0.000 claims description 26
- 229920000573 polyethylene Polymers 0.000 claims description 26
- NWGKJDSIEKMTRX-MDZDMXLPSA-N Sorbitan oleate Chemical compound CCCCCCCC\C=C\CCCCCCCC(=O)OCC(O)C1OCC(O)C1O NWGKJDSIEKMTRX-MDZDMXLPSA-N 0.000 claims description 21
- 238000005303 weighing Methods 0.000 claims description 15
- 239000000463 material Substances 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 11
- 239000000428 dust Substances 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 238000004140 cleaning Methods 0.000 claims description 5
- 238000005374 membrane filtration Methods 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- 229920000136 polysorbate Polymers 0.000 claims description 5
- 239000002994 raw material Substances 0.000 claims description 5
- 238000005516 engineering process Methods 0.000 abstract description 6
- 230000000694 effects Effects 0.000 abstract description 2
- 238000004945 emulsification Methods 0.000 abstract description 2
- RZRNAYUHWVFMIP-KTKRTIGZSA-N 1-oleoylglycerol Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC(O)CO RZRNAYUHWVFMIP-KTKRTIGZSA-N 0.000 abstract 1
- 239000004372 Polyvinyl alcohol Substances 0.000 abstract 1
- NWGKJDSIEKMTRX-AAZCQSIUSA-N Sorbitan monooleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O NWGKJDSIEKMTRX-AAZCQSIUSA-N 0.000 abstract 1
- RZRNAYUHWVFMIP-HXUWFJFHSA-N glycerol monolinoleate Natural products CCCCCCCCC=CCCCCCCCC(=O)OC[C@H](O)CO RZRNAYUHWVFMIP-HXUWFJFHSA-N 0.000 abstract 1
- 239000000203 mixture Substances 0.000 abstract 1
- 229940074096 monoolein Drugs 0.000 abstract 1
- 229920002451 polyvinyl alcohol Polymers 0.000 abstract 1
- 238000012360 testing method Methods 0.000 description 16
- 241000282898 Sus scrofa Species 0.000 description 10
- 208000007212 Foot-and-Mouth Disease Diseases 0.000 description 8
- 241000710198 Foot-and-mouth disease virus Species 0.000 description 8
- 238000002965 ELISA Methods 0.000 description 5
- 241001465754 Metazoa Species 0.000 description 3
- 241000282887 Suidae Species 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 230000036039 immunity Effects 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 208000024891 symptom Diseases 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 2
- 239000000427 antigen Substances 0.000 description 2
- 102000036639 antigens Human genes 0.000 description 2
- 108091007433 antigens Proteins 0.000 description 2
- 238000010241 blood sampling Methods 0.000 description 2
- 230000005847 immunogenicity Effects 0.000 description 2
- 229940031551 inactivated vaccine Drugs 0.000 description 2
- 238000010255 intramuscular injection Methods 0.000 description 2
- 239000007927 intramuscular injection Substances 0.000 description 2
- 239000003128 rodenticide Substances 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 238000012795 verification Methods 0.000 description 2
- 206010022085 Injection site oedema Diseases 0.000 description 1
- 206010028851 Necrosis Diseases 0.000 description 1
- 231100000645 Reed–Muench method Toxicity 0.000 description 1
- 208000025865 Ulcer Diseases 0.000 description 1
- 238000010171 animal model Methods 0.000 description 1
- 230000000890 antigenic effect Effects 0.000 description 1
- 238000003149 assay kit Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 230000037396 body weight Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003995 emulsifying agent Substances 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 210000000003 hoof Anatomy 0.000 description 1
- 229960001438 immunostimulant agent Drugs 0.000 description 1
- 239000003022 immunostimulating agent Substances 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 239000003446 ligand Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000017074 necrotic cell death Effects 0.000 description 1
- 231100000614 poison Toxicity 0.000 description 1
- 238000004321 preservation Methods 0.000 description 1
- 208000009146 rhinoscleroma Diseases 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- UAJTZZNRJCKXJN-UHFFFAOYSA-M sodium;2-dodecoxy-2-oxoethanesulfonate Chemical compound [Na+].CCCCCCCCCCCCOC(=O)CS([O-])(=O)=O UAJTZZNRJCKXJN-UHFFFAOYSA-M 0.000 description 1
- 239000003440 toxic substance Substances 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
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- Medicinal Preparation (AREA)
Abstract
The invention discloses a two-phase oil emulsion adjuvant for veterinary vaccines. The two-phase oil emulsion adjuvant for veterinary vaccines comprises the following compositions in percentage by weight: 84.5%-88.5% of mineral oil, 2.5%-3.5% of tween 80, 2.5%-3.5% of span 80, 2.5%-3.5% of propylene glycol, 2%-2.5% of polyvinyl alcohol, and 2%-2.5% of monoolein. The invention further discloses a production method for the two-phase oil emulsion adjuvant for veterinary vaccines. The two-phase oil emulsion adjuvant for veterinary vaccines is good in stability and less in side effect, can provide long and stable immune protection, vaccines can be prepared through the adjuvant by adopting one-step emulsion process, and the technology is simplified, and suitable for market promotion and application.
Description
Technical field
The present invention relates to two-phase oil emulsion adjuvant and preparation method thereof for a kind of live vaccine
.
Background technology
Live vaccine oil emulsion adjuvant, be a kind of prior to or use with antigen simultaneously, can the non-specific immunity of enhancing body and the immunogenicity of antigen, and self does not possess the material of antigenic characteristic.Oil emulsion adjuvant vaccine be use mineral oil and emulsifying agent as immunostimulant vaccine, be one of type that at present domestic and international vaccine market, product is maximum, oil emulsion adjuvant vaccine can be divided into three kinds of dosage forms: Water-In-Oil (W/O) type, oil-in-water (O/W) type and W/O/W (W/O/W) type.
Water-In-Oil (W/O) type vaccine can obtain the immunne response of higher level; and immune period is longer; but the larger defect also existing: viscosity is large; be unfavorable for injection; and usually cause serious animal side reaction; for example immune animal body temperature height, does not take food, injection site edema, scleroma, necrosis etc.Oil-in-water (O/W) type vaccine viscosity is low, easily injection, but be difficult to obtain satisfied immunne response level, on vaccine market, use less.
W/O/W (W/O/W) dosage form vaccine has advantages of W/O type and O/W type simultaneously, and conventional way is first to prepare w/o type vaccine, then through being distributed in water and being prepared from for the second time.Object is to reduce viscosity, is not only convenient to injection but also has good immunogenicity.But difficulty is larger in technology of preparing, vaccine stability is poor.
Summary of the invention
Based on this, for the problems referred to above, be necessary to propose that a kind of preparation technology is simple, viscosity is low, good stability, the little live vaccine of side effect two-phase oil emulsion adjuvant.
For solving the problems of the technologies described above, the invention provides a kind of live vaccine two-phase oil emulsion adjuvant, comprise mineral oil, Tween 80, sorbester p17, propylene glycol, acid polyethylene and glyceryl monooleate, the percentage by weight of each material is respectively: mineral oil is 84.5%-88.5%, Tween 80 is 2.5%-3.5%, sorbester p17 is 2.5%-3.5%, propylene glycol is 2.5%-3.5%, acid polyethylene is 2%-2.5%, glyceryl monooleate is 2%-2.5%.
In a preferred embodiment, described mineral oil is the white oil of food or pharmaceutical grade.
In a preferred embodiment, the percentage by weight of described mineral oil, Tween 80, sorbester p17, propylene glycol, acid polyethylene and glyceryl monooleate is followed successively by 88.5%, 2.5%, 2.5%, 2.5%, 2%, 2%.
In a preferred embodiment, the percentage by weight of described mineral oil, Tween 80, sorbester p17, propylene glycol, acid polyethylene and glyceryl monooleate is followed successively by 84.5%, 3.5%, 3.5%, 3.5%, 2.5%, 2.5%.
In a preferred embodiment, the percentage by weight of described mineral oil, Tween 80, sorbester p17, propylene glycol, acid polyethylene and glyceryl monooleate is followed successively by 86.5%, 3.1%, 3.1%, 3.1%, 2.1%, 2.1%.
For solving the problems of the technologies described above, the present invention also proposes the manufacture method of two-phase oil emulsion adjuvant for a kind of live vaccine, comprises the following steps:
Getting percentage by weight is 84.5%-88.5% mineral oil, 2.5%-3.5% Tween 80,2.5%-3.5% sorbester p17,2.5%-3.5% propylene glycol, 2%-2.5% acid polyethylene, 2%-2.5% glyceryl monooleate, standby after weighing;
Mineral oil is added in retort and stirred, and the rotating speed of stirring is controlled and is 86-96 revs/min, stirs after 28-40 minutes, and mineral oil is warmed up to 35 ℃-40 ℃;
In retort, add successively weighing standby sorbester p17, acid polyethylene and glyceryl monooleate, continue to stir, the rotating speed of stirring is controlled and is 86-96 revs/min, stirs after 28-40 minutes, will in retort, be cooled to room temperature;
In retort, add successively weighing standby Tween 80 and propylene glycol, continue stirring standing after 28-40 minutes, the rotating speed of stirring is controlled and is 86-96 revs/min;
Mixing material in standing rear retort is adopted to 0.45 micron of membrane filtration, can produce live vaccine two-phase oil emulsion adjuvant.
In a preferred embodiment, the time of stirring is 30 minutes, and the rotating speed of stirring is 88 revs/min.
In a preferred embodiment, retort and other raw materials are all placed in the environment without dust, no-sundries.
In a preferred embodiment, further comprising the steps of: cleaning reaction tank, will clean to the environment without dust, no-sundries in retort.
The invention has the beneficial effects as follows:
(1) the live vaccine two-phase oil emulsion adjuvant that the technical program proposes, dosage form is W/O/W, its performance is slightly better than monopolization product 206 adjuvants of France match BIC Corp, be at present unique one can replace imported two-phase oil emulsion adjuvant domestic adjuvant, adopts two-phase oil emulsion adjuvant of the present invention can in the quality of raising vaccine, reduce the production cost of live vaccine producer;
(2) vaccine stability that this adjuvant and psma ligand are made is good, and side reaction is little, and permanent stable immunoprotection can be provided, and adjuvant of the present invention adopts a step emulsion process to prepare vaccine, and work simplification is applicable to marketing and uses very much;
(3) advantage of this adjuvant in performance is mainly manifested in aspect following two:
A. stability is better than similar products at home and abroad; can stablize preservation at least 30 days for 37 ℃; compare 37 ℃ of stability of 15 days of France's match BIC Corp's 206 adjuvant, two-phase oil emulsion adjuvant of the present invention can further improve the stability of vaccine product, is more conducive to vaccine and provides long-term protection to immune animal;
B. foot-and-mouth disease vaccine is the first seedlings of live vaccine, and the foot-and-mouth disease vaccine immune swine antibody of two-phase oil emulsion adjuvant configuration of the present invention is a little more than the foot-and-mouth disease vaccine of France's match Bick 206 adjuvant configurations.
The specific embodiment
Below embodiments of the invention are elaborated.
Embodiment 1:
A kind of live vaccine two-phase oil emulsion adjuvant, comprise mineral oil, Tween 80, sorbester p17, propylene glycol, acid polyethylene and glyceryl monooleate, the percentage by weight of each material is respectively: mineral oil is 88.5%, Tween 80 is 2.5%, sorbester p17 is 2.5%, propylene glycol is 2.5%, acid polyethylene is 2%, glyceryl monooleate is 2%.Described mineral oil is the white oil of food or pharmaceutical grade.
The manufacture method of two-phase oil emulsion adjuvant for live vaccine described in the present embodiment 1, comprises the following steps:
Step 1, getting percentage by weight is 88.5% mineral oil, 2.5% Tween 80,2.5% sorbester p17,2.5% propylene glycol, 2% acid polyethylene, 2% glyceryl monooleate, standby after weighing;
Step 2, adds mineral oil in retort and stirs, and the rotating speed of stirring is controlled and is 86-96 revs/min, stirs after 28-40 minutes, and mineral oil is warmed up to 35 ℃-40 ℃;
Step 3 adds successively weighing standby sorbester p17, acid polyethylene and glyceryl monooleate in retort, continues to stir, and the rotating speed of stirring is controlled and is 86-96 revs/min, stirs after 28-40 minutes, will in retort, be cooled to room temperature;
Step 4 adds successively weighing standby Tween 80 and propylene glycol in retort, continues stirring standing after 28-40 minutes, and the rotating speed of stirring is controlled and is 86-96 revs/min;
Step 5, adopts 0.45 micron of membrane filtration by mixing material in standing rear retort, can produce the live vaccine two-phase oil emulsion adjuvant described in the present embodiment 1.
In above-mentioned steps, it is 30 minutes that the time of stirring is preferably all controlled, and it is 88 revs/min that the rotating speed of stirring is preferably all controlled.Retort and other raw materials are preferably all placed in the environment without dust, no-sundries.Before using retort, preferably first cleaning reaction tank, will clean to the environment without dust, no-sundries in retort.
Embodiment 2:
A kind of live vaccine two-phase oil emulsion adjuvant, comprise mineral oil, Tween 80, sorbester p17, propylene glycol, acid polyethylene and glyceryl monooleate, the percentage by weight of each material is respectively: mineral oil is 84.5%, Tween 80 is 3.5%, sorbester p17 is 3.5%, propylene glycol is 3.5%, acid polyethylene is 2.5%, glyceryl monooleate is 2.5%.Described mineral oil is the white oil of food or pharmaceutical grade.
The manufacture method of two-phase oil emulsion adjuvant for live vaccine described in the present embodiment 2, comprises the following steps:
Step 1, getting percentage by weight is 84.5% mineral oil, 3.5% Tween 80,3.5% sorbester p17,3.5% propylene glycol, 2.5% acid polyethylene, 2.5% glyceryl monooleate, standby after weighing;
Step 2, adds mineral oil in retort and stirs, and the rotating speed of stirring is controlled and is 86-96 revs/min, stirs after 28-40 minutes, and mineral oil is warmed up to 35 ℃-40 ℃;
Step 3 adds successively weighing standby sorbester p17, acid polyethylene and glyceryl monooleate in retort, continues to stir, and the rotating speed of stirring is controlled and is 86-96 revs/min, stirs after 28-40 minutes, will in retort, be cooled to room temperature;
Step 4 adds successively weighing standby Tween 80 and propylene glycol in retort, continues stirring standing after 28-40 minutes, and the rotating speed of stirring is controlled and is 86-96 revs/min;
Step 5, adopts 0.45 micron of membrane filtration by mixing material in standing rear retort, can produce the live vaccine two-phase oil emulsion adjuvant described in the present embodiment 2.
In above-mentioned steps, it is 30 minutes that the time of stirring is preferably all controlled, and it is 88 revs/min that the rotating speed of stirring is preferably all controlled.Retort and other raw materials are preferably all placed in the environment without dust, no-sundries.Before using retort, preferably first cleaning reaction tank, will clean to the environment without dust, no-sundries in retort.
Embodiment 3:
A live vaccine two-phase oil emulsion adjuvant, comprises mineral oil, Tween 80, sorbester p17, propylene glycol, acid polyethylene and glyceryl monooleate.The percentage by weight of each material is respectively: mineral oil is 86.5%, Tween 80 is 3.1%, sorbester p17 is 3.1%, propylene glycol is 3.1%, acid polyethylene is 2.1%, glyceryl monooleate is 2.1%.Described mineral oil is the white oil of food or pharmaceutical grade.
The manufacture method of two-phase oil emulsion adjuvant for live vaccine described in the present embodiment 3, comprises the following steps:
Step 1, getting percentage by weight is 86.5% mineral oil, 3.1% Tween 80,3.1% sorbester p17,3.1% propylene glycol, 2.1% acid polyethylene, 2.1% glyceryl monooleate, standby after weighing;
Step 2, adds mineral oil in retort and stirs, and the rotating speed of stirring is controlled and is 86-96 revs/min, stirs after 28-40 minutes, and mineral oil is warmed up to 35 ℃-40 ℃;
Step 3 adds successively weighing standby sorbester p17, acid polyethylene and glyceryl monooleate in retort, continues to stir, and the rotating speed of stirring is controlled and is 86-96 revs/min, stirs after 28-40 minutes, will in retort, be cooled to room temperature;
Step 4 adds successively weighing standby Tween 80 and propylene glycol in retort, continues stirring standing after 28-40 minutes, and the rotating speed of stirring is controlled and is 86-96 revs/min;
Step 5, adopts 0.45 micron of membrane filtration by mixing material in standing rear retort, can produce the live vaccine two-phase oil emulsion adjuvant described in the present embodiment 3.
In above-mentioned steps, it is 30 minutes that the time of stirring is preferably all controlled, and it is 88 revs/min that the rotating speed of stirring is preferably all controlled.Retort and other raw materials are preferably all placed in the environment without dust, no-sundries.Before using retort, preferably first cleaning reaction tank, will clean to the environment without dust, no-sundries in retort.
Inventor has carried out following contrast test to two-way oil emulsion adjuvant of the present invention and 206 adjuvants that use on the market.
1, materials and methods
1.1 vaccines: Schweineseuche O-shaped inactivated vaccine (O/GX/09-7 strain+O/XJ/10-11 strain) (206 adjuvant), Schweineseuche O-shaped inactivated vaccine (O/GX/09-7 strain+O/XJ/10-11 strain) (live vaccine of the present invention two-phase oil emulsion adjuvant).
1.2 counteracting toxic substances strains: O/GX/09-7 strain neonatal rat poison (10
5.25iD
50/ 0.2ml).
1.3 experimental animals: purchased from the pig without foot and mouth disease Prevalent district, more than 35kg, blood sampling before test, selects the negative healthy susceptible pig of neonatal rat NAT≤1:4 or cell NAT≤1:8 or LPB-ELISA antibody titer≤1:8 and 3ABC antibody test for test.
1.4 antibody assay kits: the foot and mouth disease LPB-ELISA test kit that Lanzhou veterinary institute is produced.
1.5 method
1.5.1 safety verification: with healthy susceptible piglet (neonatal rat NAT≤1:4 or cell NAT≤1:8 or LPB-ELISA antibody titer≤1:8 and 3ABC antibody test are negative) 2 of 30-40 age in days, muscle branch vaccinate 4ml(2 head part after each two Herba Houttuyniae), every side 2ml, day by day observe 14, all must not occur foot and mouth disease symptom or the abnormal response being caused by vaccine.
1.5.2 antibody test: 7 days, 14 days, 21 days and blood sampling respectively in 28 days after vaccine immunity, distinguish serum, by LPB-ELISA method, detect antibody.
1.5.3 efficacy test: two kinds of vaccines each with 15 of the healthy susceptible pigs (neonatal rat NAT≤1:4 or cell NAT≤1:8 or LPB-ELISA antibody titer≤1:8 and 3ABC antibody test are negative) of body weight 40kg left and right.Be divided into 3 groups, 5 every group.Vaccine to be checked is divided into 1 part (2ml), 1/3 part (0.67ml), 3 dosage groups of 1/9 part (0.22ml), each dosage group respectively at the basal part of the ear after 5 pigs of intramuscular injection.Inoculate latter 28 days, together with 2 of the identical contrast pigs of condition, after every pig basal part of the ear, intramuscular injection O/GX/09-7 neonatal rat poison 2ml(is containing 10
3iD
50).Continuous Observation 10 days.Contrast pig all should have at least 1 hoof to occur that blister can ulcer.Immune swine occurs that any foot and mouth disease symptom is judged to and does not protect.Occur will isolating in time after morbidity pig.According to the protection number of immune swine, by Reed-Muench method, calculate the PD of tested vaccine
50.
2, experimental result
2.1 safety verification results: do not occur foot and mouth disease symptom or the abnormal response being caused by vaccine.
2.2 antibody test results and efficacy test the results are shown in following table
Table 1: two-way oil emulsion adjuvant vaccine antibody testing result of the present invention and efficacy test result
Table 2:206 Adjuvanted vaccines antibody test result and efficacy test result
3, conclusion
Two-phase oil emulsion adjuvant and 206 Adjuvanted vaccines PD for live vaccine of the present invention
5Otesting result is 15.59PD
50/ head part, live vaccine of the present invention uses two-phase oil emulsion adjuvant vaccine immunity pig antibody higher than 206 Adjuvanted vaccines immune swine antibody.
The above embodiment has only expressed the specific embodiment of the present invention, and it describes comparatively concrete and detailed, but can not therefore be interpreted as the restriction to the scope of the claims of the present invention.It should be pointed out that for the person of ordinary skill of the art, without departing from the inventive concept of the premise, can also make some distortion and improvement, these all belong to protection scope of the present invention.
Claims (9)
1. a live vaccine two-phase oil emulsion adjuvant, it is characterized in that, comprise mineral oil, Tween 80, sorbester p17, propylene glycol, acid polyethylene and glyceryl monooleate, the percentage by weight of each material is respectively: mineral oil is 84.5%-88.5%, Tween 80 is 2.5%-3.5%, sorbester p17 is 2.5%-3.5%, propylene glycol is 2.5%-3.5%, acid polyethylene is 2%-2.5%, glyceryl monooleate is 2%-2.5%.
2. live vaccine according to claim 1 two-phase oil emulsion adjuvant, is characterized in that, described mineral oil is the white oil of food or pharmaceutical grade.
3. live vaccine according to claim 1 and 2 two-phase oil emulsion adjuvant, it is characterized in that, the percentage by weight of described mineral oil, Tween 80, sorbester p17, propylene glycol, acid polyethylene and glyceryl monooleate is followed successively by 88.5%, 2.5%, 2.5%, 2.5%, 2%, 2%.
4. live vaccine according to claim 1 and 2 two-phase oil emulsion adjuvant, it is characterized in that, the percentage by weight of described mineral oil, Tween 80, sorbester p17, propylene glycol, acid polyethylene and glyceryl monooleate is followed successively by 84.5%, 3.5%, 3.5%, 3.5%, 2.5%, 2.5%.
5. live vaccine according to claim 1 and 2 two-phase oil emulsion adjuvant, it is characterized in that, the percentage by weight of described mineral oil, Tween 80, sorbester p17, propylene glycol, acid polyethylene and glyceryl monooleate is followed successively by 86.5%, 3.1%, 3.1%, 3.1%, 2.1%, 2.1%.
6. a manufacture method for two-phase oil emulsion adjuvant for live vaccine as claimed in claim 1 or 2, is characterized in that, comprises the following steps:
Getting percentage by weight is 84.5%-88.5% mineral oil, 2.5%-3.5% Tween 80,2.5%-3.5% sorbester p17,2.5%-3.5% propylene glycol, 2%-2.5% acid polyethylene, 2%-2.5% glyceryl monooleate, standby after weighing;
Mineral oil is added in retort and stirred, and the rotating speed of stirring is controlled and is 86-96 revs/min, stirs after 28-40 minutes, and mineral oil is warmed up to 35 ℃-40 ℃;
In retort, add successively weighing standby sorbester p17, acid polyethylene and glyceryl monooleate, continue to stir, the rotating speed of stirring is controlled and is 86-96 revs/min, stirs after 28-40 minutes, will in retort, be cooled to room temperature;
In retort, add successively weighing standby Tween 80 and propylene glycol, continue stirring standing after 28-40 minutes, the rotating speed of stirring is controlled and is 86-96 revs/min;
Mixing material in standing rear retort is adopted to 0.45 micron of membrane filtration, can produce live vaccine two-phase oil emulsion adjuvant.
7. method according to claim 6, is characterized in that, the time of stirring is 30 minutes, and the rotating speed of stirring is 88 revs/min.
8. method according to claim 6, is characterized in that, retort and other raw materials are all placed in the environment without dust, no-sundries.
9. method according to claim 6, is characterized in that, further comprising the steps of:
Cleaning reaction tank, will clean to the environment without dust, no-sundries in retort.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105854013A (en) * | 2015-01-22 | 2016-08-17 | 中牧实业股份有限公司 | Animal vaccine adjuvant and animal vaccine thereof |
| CN106267184A (en) * | 2016-03-03 | 2017-01-04 | 呼和浩特市佐瑞特生物科技有限责任公司 | A kind of water-in-oil-in water emulsifying agent and application thereof and using method |
| CN106692966A (en) * | 2015-07-29 | 2017-05-24 | 刘卓灵 | Adjuvant for animal vaccines, and preparation method and application thereof |
| CN108014332A (en) * | 2016-10-28 | 2018-05-11 | 哈尔滨润科旺生物技术开发有限公司 | A kind of live vaccine adjuvant |
| CN108159414A (en) * | 2018-01-15 | 2018-06-15 | 四川诺顺科技有限公司 | Animal vaccine water-in-oil adjuvant and its preparation method and application |
| CN111110840A (en) * | 2020-01-17 | 2020-05-08 | 四川诺顺科技有限公司 | Oil-in-water adjuvant for animal vaccine and preparation method thereof |
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| CN105854013A (en) * | 2015-01-22 | 2016-08-17 | 中牧实业股份有限公司 | Animal vaccine adjuvant and animal vaccine thereof |
| CN105854013B (en) * | 2015-01-22 | 2019-06-07 | 中牧实业股份有限公司 | A kind of animal vaccine oil adjuvant and its animal vaccine |
| CN106692966A (en) * | 2015-07-29 | 2017-05-24 | 刘卓灵 | Adjuvant for animal vaccines, and preparation method and application thereof |
| CN106267184A (en) * | 2016-03-03 | 2017-01-04 | 呼和浩特市佐瑞特生物科技有限责任公司 | A kind of water-in-oil-in water emulsifying agent and application thereof and using method |
| CN106267184B (en) * | 2016-03-03 | 2020-01-21 | 彭建彪 | Water-in-oil-in-water emulsifier and application and using method thereof |
| CN108014332A (en) * | 2016-10-28 | 2018-05-11 | 哈尔滨润科旺生物技术开发有限公司 | A kind of live vaccine adjuvant |
| CN108159414A (en) * | 2018-01-15 | 2018-06-15 | 四川诺顺科技有限公司 | Animal vaccine water-in-oil adjuvant and its preparation method and application |
| CN108159414B (en) * | 2018-01-15 | 2021-07-27 | 四川诺顺科技有限公司 | Water-in-oil adjuvant for animal vaccine and preparation method and application thereof |
| CN111110840A (en) * | 2020-01-17 | 2020-05-08 | 四川诺顺科技有限公司 | Oil-in-water adjuvant for animal vaccine and preparation method thereof |
| CN111110840B (en) * | 2020-01-17 | 2024-02-06 | 四川百诺吉科技有限公司 | Oil-in-water adjuvant for animal vaccine and preparation method thereof |
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