CN107261134A - A kind of atrophic rhinitis inactivated vaccine immunopotentiator and preparation method thereof - Google Patents

A kind of atrophic rhinitis inactivated vaccine immunopotentiator and preparation method thereof Download PDF

Info

Publication number
CN107261134A
CN107261134A CN201710476126.XA CN201710476126A CN107261134A CN 107261134 A CN107261134 A CN 107261134A CN 201710476126 A CN201710476126 A CN 201710476126A CN 107261134 A CN107261134 A CN 107261134A
Authority
CN
China
Prior art keywords
liquid
atrophic rhinitis
immunopotentiator
dry powder
inactivated vaccine
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
CN201710476126.XA
Other languages
Chinese (zh)
Other versions
CN107261134B (en
Inventor
马晶晶
赖�志
吴碧清
高俊锋
韩相敏
张秉金
沈明志
张瑜
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Biotechnology Co Ltd Shanghai Chuanghong
Original Assignee
Biotechnology Co Ltd Shanghai Chuanghong
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Biotechnology Co Ltd Shanghai Chuanghong filed Critical Biotechnology Co Ltd Shanghai Chuanghong
Priority to CN201710476126.XA priority Critical patent/CN107261134B/en
Publication of CN107261134A publication Critical patent/CN107261134A/en
Application granted granted Critical
Publication of CN107261134B publication Critical patent/CN107261134B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/39Medicinal preparations containing antigens or antibodies characterised by the immunostimulating additives, e.g. chemical adjuvants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/02Bacterial antigens
    • A61K39/0208Specific bacteria not otherwise provided for
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K39/02Bacterial antigens
    • A61K39/102Pasteurellales, e.g. Actinobacillus, Pasteurella; Haemophilus
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/51Medicinal preparations containing antigens or antibodies comprising whole cells, viruses or DNA/RNA
    • A61K2039/52Bacterial cells; Fungal cells; Protozoal cells
    • A61K2039/521Bacterial cells; Fungal cells; Protozoal cells inactivated (killed)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/55Medicinal preparations containing antigens or antibodies characterised by the host/recipient, e.g. newborn with maternal antibodies
    • A61K2039/552Veterinary vaccine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/555Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55505Inorganic adjuvants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/555Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511Organic adjuvants
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/555Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511Organic adjuvants
    • A61K2039/55577Saponins; Quil A; QS21; ISCOMS
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/555Medicinal preparations containing antigens or antibodies characterised by a specific combination antigen/adjuvant
    • A61K2039/55511Organic adjuvants
    • A61K2039/55583Polysaccharides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/57Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00Medicinal preparations containing antigens or antibodies
    • A61K2039/57Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2
    • A61K2039/575Medicinal preparations containing antigens or antibodies characterised by the type of response, e.g. Th1, Th2 humoral response

Abstract

The invention discloses a kind of atrophic rhinitis inactivated vaccine immunopotentiator, liquid and solvent including the immunity particle containing dry powder, the sub- liquid that grain is immunized containing dry powder are mainly made up of the aluminium hydroxide aqueous solution, ginsenoside, cholesterol, vitamin C, DEAE-dextran, KI and polyethylene glycol by proper ratio compatibility.Compared with prior art, the atrophic rhinitis inactivated vaccine immunopotentiator that the present invention is prepared, the effective foundation for suppressing bordetella branchiseptica and pasteurella multocida latent infection is with reactivating, the window phase of antibody generation can be shortened, improve the immune effect of atrophic rhinitis vaccine, immune duration extends, it efficiently avoid the latent infection of atrophic rhinitis, guarantee is provided for the prevention and elimination of atrophic rhinitis disease, it can be widely used in the preventing and treating that pig farm carries out atrophic rhinitis, improve the economic benefit on pig farm.

Description

A kind of atrophic rhinitis inactivated vaccine immunopotentiator and preparation method thereof
Technical field
The invention belongs to veterinary biologicses technical field, and in particular to a kind of atrophic rhinitis inactivated vaccine is used immune Reinforcing agent and preparation method thereof.
Background technology
Atrophic rhinitis is mainly as caused by bordetella branchiseptica and Toxigenic Pasteurella multocida It is a kind of chronic and with communicable breathing problem.The World Health Organization is defined as B class diseases, and ill pig goes out Now sneeze, the deformation of nose is bleeding, face, nose is crooked and the adverse reaction such as growthing lag, causing the feed conversion rate of pig reduces, Production performance is low, and huge economic loss is caused to intensive industrialized piggery.Simultaneously as after pathogen infection pig, infringement is exhaled The normal configuration and function in road are inhaled, makes the reduction of pig body resistance, easily infects other cause of diseases, cause respiratory system syndrome, increase Plus the death and culling rate of pig.This disease often betides the pig at 2~5 monthly ages, now the almost flourishing area of pig industry all over the world, and China is permitted Also there is this disease in many areas.
Specifically, atrophic rhinitis is pig caused branch when being infected by environmental stimulus or other pathogens Tracheae sepsis bordetella bacilli is adsorbed onto the epithelial cell of schneiderian membrane, destruction cilium and schneiderian membrane, bordetella bacilli release by flagellum Dermotoxin pass through turbinate, destroy Gegenbaur's cell, interference calcium uptake and ostosis;Pasteurella multocida resides in Dermotoxin is discharged on the schneiderian membrance destroyed by bordetella bacilli, osteoclast activity is strengthened, and causes bone to decompose.Typically In the case of Pasteurella be difficult on the schneiderian membrance of health pig breed, only by Bordetella bordetella bacilli or other Factor invasion and attack, mucous membrane are possible to cause to propagate in pig farm when suffering damage, therefore prevent bordetella bacilli from being adsorbed in schneiderian membrance The problem of being primary solve.
To avoid propagation of the atrophic rhinitis in swinery, pig farm would generally inject atrophic rhinitis epidemic disease to pig Seedling, however be used alone vaccine immune effect it is not good, generally require with the use of can strengthen vaccine immunity stress, excite and exempt from The adjuvant of epidemic disease response strengthens the immune effect of vaccine, and that one kind can strengthen the preferential definite value of atrophic rhinitis vaccine antigen is glutinous in nose The immunopotentiator of film is very in short supply.Adjuvant does not provide immune in itself, it only when constituting a kind of preparation with immunizing antigen, The range and effect by the immune response of vaccine-induced generation can be improved.The atrophic rhinitis applied in the market is gone out Live vaccine adjuvant includes alocol, lipoid adjuvant and propolis adjuvant;Aluminium hydroxide gel adjuvanted immunogenic is good, side effect It is small, but it is unable to inducing cellular immune;Lipoid adjuvant and propolis adjuvant immunogenicity are good, can induce humoral immunity and cell is exempted from Epidemic disease, the immune duration is long, but the prices of raw materials are expensive, and cost is too high.Therefore in recent years, researcher application in various countries' is different Raw material and use distinct methods have developed a series of new adjuvant, but because effect difference or toxicity are big, be expired without one kind Meaning effect.Therefore, the stimulation of atrophic rhinitis vaccine immunity can be strengthened by needing research one kind badly, excite immune response, realization has Effect prevents and treats the immunopotentiator of atrophic rhinitis.
The content of the invention
Strong Th1, Th2 reaction is induced it is an object of the invention to provide a kind of, is drenched while inducing and producing cytotoxic T Bar cell and bone-marrow-derived lymphocyte, the pig for making antigen preferentially be colonized in schneiderian membrance with enhancing cellular immunity and humoral immune function wither Contracting rhinitis inactivated vaccine immunopotentiator.
The object of the present invention is achieved like this, and the atrophic rhinitis inactivated vaccine is included containing dry with immunopotentiator The liquid and solvent of powder immunity particle, the liquid of the immunity particle containing dry powder it is main by the aluminium hydroxide aqueous solution, ginsenoside, Cholesterol, vitamin C, DEAE-dextran, KI and polyethylene glycol are constituted by proper ratio compatibility.
It is preferred that, aluminium hydroxide contains in the liquid of the immunity particle containing dry powder described in the liquid of immunity particle containing dry powder Measure as 75~85wt%, the content of ginsenoside is 0.1~2wt%, and the content of cholesterol is 0.1~2wt%, diethylin second The content of base glucan is 0.1~1wt%.
It is preferred that, the content of vitamin C and KI meets following condition in the liquid of the immunity particle containing dry powder:Dimension Raw element C and KI total mole number/aluminium hydroxide molal quantity >=1, the mass ratio of the aluminium hydroxide and polyethylene glycol is 1:0.1 ~1.
It is preferred that, the solvent is physiological saline or PBS.
Present invention also offers a kind of method for preparing the atrophic rhinitis inactivated vaccine immunopotentiator, including Following steps:
A, it is slowly added to ginsenoside, cholesterol into the aluminium hydroxide aqueous solution, vitamin C, diethylin ethyl Portugal gathers Sugar and KI, continue to add polyethylene glycol after stirring 3~5min, are further continued for obtaining containing for golden yellow after 10~20min of stirring The liquid of dry powder immunity particle, sterile guarantor is in brown receiving flask, being filled with liquid nitrogen by the liquid-packing of the immunity particle containing dry powder Deposit;
B, immunopotentiator preparation:The liquid of the immunity particle containing dry powder of appropriate metrology is taken to be placed in the reaction equipped with solvent In container, the concentration control by the liquid of the immunity particle containing dry powder in reaction vessel is 15wt%, opens agitating device stirring 20 ~40min, is 2~8 DEG C by the temperature control in reaction vessel, stands 10~20h, immunopotentiator is obtained after filtration sterilization.
It is preferred that, the solvent is physiological saline or PBS.
Compared with prior art, the atrophic rhinitis inactivated vaccine immunopotentiator that the present invention is prepared, effectively The foundation for suppressing bordetella branchiseptica and pasteurella multocida latent infection with reactivating, antibody can be shortened The window phase of generation, improves the immune effect of atrophic rhinitis vaccine, and immune duration extension effectively avoids pig atrophy Property rhinitis latent infection, be atrophic rhinitis disease prevention and eradicate provide guarantee, can be widely used in pig farm The preventing and treating of atrophic rhinitis is carried out, the economic benefit on pig farm is improved.
Brief description of the drawings
Fig. 1 takes a blood sample after 42 days for first immunisation and detects obtained average PMT titres schematic diagram;
Fig. 2 takes a blood sample after 42 days for first immunisation and detects obtained ELISA mean antibody levels schematic diagrames;
Fig. 3 turns positive rate schematic diagram for immune rear piglet;
Fig. 4 is immune rear piglet antibody level schematic diagram;
Embodiment
With reference to embodiment, the present invention is further illustrated, but the present invention must not be added in any way To limit, based on present invention teach that any changes and modifications made, belong to protection scope of the present invention.While institute of the present invention It is commercially available prod unless otherwise instructed with test material.
The preparation of atrophic rhinitis inactivated vaccine immunopotentiator
Embodiment 1
It is prepared by a, the liquid of the immunity particle containing dry powder:The aqueous solution that 30ml aluminum hydroxide concentrations are 100ug/ml is taken, slowly The lower ginsenoside for adding 4ug is stirred, 4ug cholesterol, 4ug DEAE-dextran adds after continuing stirring 5min Enter vitamin C and KI total mole number/aluminium hydroxide molal quantity in polyethylene glycol, the liquid of the immunity particle containing dry powder= 4, the mass ratio of the aluminium hydroxide and polyethylene glycol is 1:1, it is further continued for after stirring 20min obtaining the immune containing dry powder of golden yellow The liquid of particle, is observed using atomic force microscope, a diameter of 50nm of obtained dry powder immunity particle, will contain dry powder immunity particle Liquid-packing do Preservation in sterile condition in brown receiving flask, being filled with liquid nitrogen, the shelf-life is 2 years;
B, immunopotentiator preparation:The liquid of the immunity particle containing dry powder of appropriate metrology is taken to be placed in equipped with PBS Reaction vessel in, by reaction vessel the liquid of the immunity particle containing dry powder concentration control be 15wt%, open agitating device 20min is stirred, the rotating speed of agitating device is advisable most very much not to produce bubble, is 2 DEG C by the temperature control in reaction vessel, stands 20h is stayed overnight, and immunopotentiator is obtained after filtration sterilization, in the environment that obtained immunopotentiator is stored in 0 DEG C, controls the PH to be 6.5。
Embodiment 2
It is prepared by a, the liquid of the immunity particle containing dry powder:The aqueous solution that 30ml aluminum hydroxide concentrations are 100ug/ml is taken, slowly The lower ginsenoside for adding 80ug of stirring, 80ug cholesterol, 40ug DEAE-dextran continues to stir after 3min Add vitamin C and KI total mole number/aluminium hydroxide molal quantity in polyethylene glycol, the liquid of the immunity particle containing dry powder =1, the mass ratio of the aluminium hydroxide and polyethylene glycol is 1:0.1, be further continued for stir 10min after obtain golden yellow contain dry powder The liquid of immunity particle, is observed using atomic force microscope, a diameter of 120nm of obtained dry powder immunity particle, will be contained dry powder and be exempted from The liquid-packing of epidemic disease particle does Preservation in sterile condition in brown receiving flask, being filled with liquid nitrogen, and the shelf-life is 2 years;
B, immunopotentiator preparation:The liquid of the immunity particle containing dry powder of appropriate metrology is taken to be placed in equipped with physiological saline In reaction vessel, the concentration control by the liquid of the immunity particle containing dry powder in reaction vessel is 15wt%, opens agitating device and stirs 40min is mixed, the rotating speed of agitating device is advisable most very much not to produce bubble, is 8 DEG C by the temperature control in reaction vessel, stands Immunopotentiator is obtained after 10h, filtration sterilization, in the environment that obtained immunopotentiator is stored in 4 DEG C, it is 7.5 to control PH.
Embodiment 3
It is prepared by a, the liquid of the immunity particle containing dry powder:The aqueous solution that 30ml aluminum hydroxide concentrations are 100ug/ml is taken, slowly The lower ginsenoside for adding 40ug of stirring, 40ug cholesterol 20ug DEAE-dextran continues to stir after 4min Add vitamin C and KI total mole number/aluminium hydroxide molal quantity in polyethylene glycol, the liquid of the immunity particle containing dry powder =2, the mass ratio of the aluminium hydroxide and polyethylene glycol is 1:0.5, be further continued for stir 15min after obtain golden yellow contain dry powder The liquid of immunity particle, is observed using atomic force microscope, a diameter of 100nm of obtained dry powder immunity particle, will be contained dry powder and be exempted from The liquid-packing of epidemic disease particle does Preservation in sterile condition in brown receiving flask, being filled with liquid nitrogen, and the shelf-life is 2 years;
B, immunopotentiator preparation:The liquid of the immunity particle containing dry powder of appropriate metrology is taken to be placed in equipped with physiological saline In reaction vessel, the concentration control by the liquid of the immunity particle containing dry powder in reaction vessel is 15wt%, opens agitating device and stirs 40min is mixed, the rotating speed of agitating device is advisable most very much not to produce bubble, is 8 DEG C by the temperature control in reaction vessel, stands Immunopotentiator is obtained after 10h, filtration sterilization, in the environment that obtained immunopotentiator is stored in 8 DEG C, it is 7.5 to control PH.
Embodiment 4
It is prepared by a, the liquid of the immunity particle containing dry powder:The aqueous solution that 30ml aluminum hydroxide concentrations are 100ug/ml is taken, slowly The lower ginsenoside for adding 60ug of stirring, 60ug cholesterol, 24ug DEAE-dextran continues to stir after 5min Add vitamin C and KI total mole number/aluminium hydroxide molal quantity in polyethylene glycol, the liquid of the immunity particle containing dry powder =1.4, the mass ratio of the aluminium hydroxide and polyethylene glycol is 1:0.8, it is further continued for obtaining doing containing for golden yellow after stirring 20min The liquid of powder immunity particle, is observed using atomic force microscope, a diameter of 100nm of obtained dry powder immunity particle, will contain dry powder The liquid-packing of immunity particle does Preservation in sterile condition in brown receiving flask, being filled with liquid nitrogen, and the shelf-life is 2 years;
B, immunopotentiator preparation:The liquid of the immunity particle containing dry powder of appropriate metrology is taken to be placed in equipped with physiological saline In reaction vessel, the concentration control by the liquid of the immunity particle containing dry powder in reaction vessel is 15wt%, opens agitating device and stirs 40min is mixed, the rotating speed of agitating device is advisable most very much not to produce bubble, is 8 DEG C by the temperature control in reaction vessel, stands Immunopotentiator is obtained after 10h, filtration sterilization, in the environment that obtained immunopotentiator is stored in 35 DEG C, it is 7 to control PH.
The atrophic rhinitis inactivated vaccine that aforementioned four embodiment is successfully prepared is carried out surely with immunopotentiator sample Qualitative test, obtained data such as table 1:
The stability test data of the immunopotentiator of table 1
Above-mentioned result of the test shows, atrophic rhinitis inactivated vaccine prepared by 4 embodiments that the present invention is provided is with exempting from Epidemic disease reinforcing agent sample has good stability.
Effect test of the immunopotentiator to atrophic rhinitis inactivated vaccine immunological enhancement
(1) prepare using the immunopotentiator prepared, after filtration sterilization, withered by 2mg/ parts and the pig containing 5ug/ parts Contracting rhinitis antigen is mixed, and is prepared into vaccine.
(2) 20 double-negative replacement gilts of atrophic rhinitis antigen-antibody are randomly divided into 4 groups by packet, every group 5, in detail Thin experiment packet situation is shown in Table 2.
(3) vaccine that will be prepared is immunized, replacement gilt was immunized respectively at antenatal 6-8 weeks and antenatal 3-4 weeks 1 time.
(4) antibody test blood sampling detection ELISA antibody and neutralizing antibody after first immunisation 42 days, and use single factor test side Difference is analysed and double tail paired t-test statistics group differences.
Table 2 tests grouping sheet one
As Figure 1-Figure 2, A, B group represent addition immunopotentiator group to result of the test in figure, and C, D group represent no added Group, result of the test shows:1st, addition immunopotentiator can significantly improve the neutralizing antibody level and ELISA of atrophic rhinitis Antibody level;2nd, the antibody level that the atrophic rhinitis inactivated vaccine of the antigen containing 5ug is produced after addition immunopotentiator is higher than The atrophic rhinitis inactivated vaccine of the antigen containing 20ug of immunopotentiator is not added, therefore can reduce by 4 times of antigen usage amounts, is saved About cost.
Application test of the immunopotentiator in atrophic rhinitis inactivated vaccine
(1) prepare using the immunopotentiator for preparing, after filtration sterilization, by 2mg/ parts respectively with containing 20ug/ parts Atrophic rhinitis killed vaccine antigen is mixed, and is prepared into vaccine.
(2) the double-negative 12 week old piglet of 20 atrophic rhinitis antigen-antibodies is randomly divided into 4 groups by packet, every group 5, Detailed packet situation is shown in Table 3.
(3) vaccine that will be prepared is immunized piglet is immunized using intramuscular injection by 2ml/ parts.
(4) antibody test before immune and it is immune after 7,14,28,60, blood samplings in 90 and 120 days, ELISA in detection blood Antibody level.
Table 3 tests grouping sheet two
As Figure 3-Figure 4, result of the test shows result of the test, and immunopotentiator can stimulate piglet quickly to produce pig atrophy Property rhinitis antibody, being immunized 7 days can be with 80% turn of sun, hence it is evident that higher than other adjuvant groups, in addition, the antibody level produced is also above it Its adjuvant group.
Safety testing of the immunopotentiator to pig
The immunopotentiator prepared in Example 1, musculi colli injection, note are carried out to swinery by 10ml/ parts 1 after penetrating, observe swinery reaction within 3,7,14 days, result of the test result as shown in table 4 shows that immunopotentiator has good safety Property.
The safety testing result of the large bolus injection immunopotentiator of table 4
The immunopotentiator prepared using embodiment 1 coordinates atrophic rhinitis inactivated vaccine to atrophic rhinitis Negative pig is immunized, 24h body temperature after detection is immune, the result of variations such as table 5 of body temperature after being immunized.
Table 5 carries out the body temperature reaction test result after being immunized after coordinating using different adjuvants and different vaccines to pig
Above-mentioned result of the test shows that the immunopotentiator prepared using the present invention coordinates atrophic rhinitis inactivation epidemic disease When seedling carries out immune to pig, stress reaction is small, does not interfere with the identification of antigen, does not also interfere with immunogenicity and immune lasting Phase, at the same can effectively strengthen vaccine Double immune stimulate, excite immune response, be atrophic rhinitis disease prevention and Eradicate to provide and ensure, can be widely used in the preventing and treating that pig farm carries out atrophic rhinitis, improve the economic effect on pig farm Benefit.
Above is the description to better embodiment of the present invention, and it is not understood to the limitation present invention, those skilled in the art A variety of changes or combination can be made according to the present invention, without departing from the spirit of the present invention, the protection of the present invention all should be belonged to Scope.

Claims (7)

1. a kind of atrophic rhinitis inactivated vaccine immunopotentiator, it is characterised in that:Liquid including the immunity particle containing dry powder Body and solvent, the liquid of the immunity particle containing dry powder are main by the aluminium hydroxide aqueous solution, ginsenoside, cholesterol, vitamin C, DEAE-dextran, KI and polyethylene glycol are constituted by proper ratio compatibility.
2. atrophic rhinitis inactivated vaccine immunopotentiator according to claim 1, it is characterised in that:It is described to contain dry The content of aluminium hydroxide is 75~85wt% in the liquid of powder immunity particle, and the content of ginsenoside is 0.1~2wt%, and courage is solid The content of alcohol is 1~2wt%, and the content of DEAE-dextran is 0.1~1wt%.
3. atrophic rhinitis inactivated vaccine immunopotentiator according to claim 2, it is characterised in that:It is described to contain dry The content of vitamin C and KI meets following condition in the liquid of powder immunity particle:
Vitamin C and KI total mole number/aluminium hydroxide molal quantity >=1, the mass ratio of the aluminium hydroxide and polyethylene glycol For 1:0.1~1.
4. atrophic rhinitis inactivated vaccine immunopotentiator according to claim 1, it is characterised in that:The solvent For physiological saline or PBS.
5. a kind of method of the atrophic rhinitis inactivated vaccine immunopotentiator prepared as described in Claims 1 to 4 is any, It is characterized in that comprising the following steps:
It is prepared by a, the liquid of the immunity particle containing dry powder:Ginsenoside, cholesterol, dimension life are slowly added into the aluminium hydroxide aqueous solution Plain C, DEAE-dextran and KI, continue stir 3~5min after add polyethylene glycol, be further continued for stirring 10~ The liquid of the immunity particle containing dry powder of golden yellow is obtained after 20min, the liquid-packing of the immunity particle containing dry powder is collected in brown In bottle, it is filled with liquid nitrogen and does Preservation in sterile condition;
B, immunopotentiator preparation:The liquid of the immunity particle containing dry powder of appropriate metrology is taken to be placed in the reaction vessel equipped with solvent In, by reaction vessel the liquid of the immunity particle containing dry powder concentration control be 15wt%, open agitating device stirring 20~ 40min, is 2~8 DEG C by the temperature control in reaction vessel, stands 10~20h, immunopotentiator is obtained after filtration sterilization.
6. the method according to claim 5 for preparing atrophic rhinitis inactivated vaccine immunopotentiator, its feature exists In:The solvent is physiological saline or PBS.
7. the method according to claim 5 for preparing atrophic rhinitis inactivated vaccine immunopotentiator, its feature exists In:The storage temperature of the immunopotentiator is 0~35 DEG C, and the shelf-life is 24 months.
CN201710476126.XA 2017-06-21 2017-06-21 Immunopotentiator for porcine atrophic rhinitis inactivated vaccine and preparation method thereof Active CN107261134B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201710476126.XA CN107261134B (en) 2017-06-21 2017-06-21 Immunopotentiator for porcine atrophic rhinitis inactivated vaccine and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201710476126.XA CN107261134B (en) 2017-06-21 2017-06-21 Immunopotentiator for porcine atrophic rhinitis inactivated vaccine and preparation method thereof

Publications (2)

Publication Number Publication Date
CN107261134A true CN107261134A (en) 2017-10-20
CN107261134B CN107261134B (en) 2020-12-01

Family

ID=60068749

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201710476126.XA Active CN107261134B (en) 2017-06-21 2017-06-21 Immunopotentiator for porcine atrophic rhinitis inactivated vaccine and preparation method thereof

Country Status (1)

Country Link
CN (1) CN107261134B (en)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108635578A (en) * 2018-08-14 2018-10-12 上海创宏生物科技有限公司 A kind of live vaccines of hog cholera immunopotentiator and preparation method thereof
CN113967252A (en) * 2020-07-24 2022-01-25 洛阳赛威生物科技有限公司 Immunopotentiator for poultry, vaccine composition containing immunopotentiator and application of vaccine composition
CN116983396A (en) * 2023-08-09 2023-11-03 浙江省农业科学院 Rabbit bronchogenic bordetella inactivated vaccine emulsion, and preparation and application thereof

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102247600A (en) * 2010-05-21 2011-11-23 上海创宏生物科技有限公司 Method for preparing diluent for pseudorabies live vaccine
CN102302771A (en) * 2011-07-13 2012-01-04 普莱柯生物工程股份有限公司 Polyvalent inactivity vaccine for preventing and treating atrophic rhinitis of swine
CN104069480A (en) * 2014-06-11 2014-10-01 广州市华南农大生物药品有限公司 Immunopotentiator and vaccine preparation for emergency vaccination of Newcastle disease
CN106177939A (en) * 2015-06-01 2016-12-07 普莱柯生物工程股份有限公司 A kind of vaccine adjuvant and application thereof

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102247600A (en) * 2010-05-21 2011-11-23 上海创宏生物科技有限公司 Method for preparing diluent for pseudorabies live vaccine
CN102302771A (en) * 2011-07-13 2012-01-04 普莱柯生物工程股份有限公司 Polyvalent inactivity vaccine for preventing and treating atrophic rhinitis of swine
CN104069480A (en) * 2014-06-11 2014-10-01 广州市华南农大生物药品有限公司 Immunopotentiator and vaccine preparation for emergency vaccination of Newcastle disease
CN106177939A (en) * 2015-06-01 2016-12-07 普莱柯生物工程股份有限公司 A kind of vaccine adjuvant and application thereof

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108635578A (en) * 2018-08-14 2018-10-12 上海创宏生物科技有限公司 A kind of live vaccines of hog cholera immunopotentiator and preparation method thereof
CN108635578B (en) * 2018-08-14 2021-01-08 上海创宏生物科技有限公司 Immunopotentiator for swine fever live vaccine and preparation method thereof
CN113967252A (en) * 2020-07-24 2022-01-25 洛阳赛威生物科技有限公司 Immunopotentiator for poultry, vaccine composition containing immunopotentiator and application of vaccine composition
CN113967252B (en) * 2020-07-24 2024-03-26 洛阳赛威生物科技有限公司 Immunopotentiator for poultry, vaccine composition containing immunopotentiator and application of immunopotentiator
CN116983396A (en) * 2023-08-09 2023-11-03 浙江省农业科学院 Rabbit bronchogenic bordetella inactivated vaccine emulsion, and preparation and application thereof

Also Published As

Publication number Publication date
CN107261134B (en) 2020-12-01

Similar Documents

Publication Publication Date Title
CN1056085C (en) Tocols as adjuvant in vaccine
TWI228420B (en) Novel vaccine composition
CN107261134A (en) A kind of atrophic rhinitis inactivated vaccine immunopotentiator and preparation method thereof
CN102933229A (en) Vaccine formulations
CN105688202B (en) A kind of Vaccinum Encephalitis B composition and preparation method thereof
CN103169773B (en) Traditional Chinese medicine compound preparation for enhancing livestock immunity and preparation method
CN111346224B (en) Immunoadjuvant composition, preparation method and application thereof
CN108969492B (en) Oral attenuated freeze-dried vaccine for swine fever and preparation method thereof
EP3076997B1 (en) Swine vaccine against prrs and lawsonia intracellularis
CN104096222B (en) A kind of vaccine combination and its preparation method and application
CN110809477A (en) Novel multivalent polysaccharide-protein conjugate vaccine compositions and formulations thereof
CN109172817B (en) Preparation method and application of chitosan microspheres of attenuated live vaccine of porcine epidemic diarrhea virus
CN104288762B (en) A kind of vaccine combination and its preparation method and application
CN106267183B (en) Live vaccine composition containing adjuvant and preparation method and application thereof
US20150086587A1 (en) Vaccine adjuvant
CN104248759B (en) Vaccine composition, preparation method and application thereof
CN106798920A (en) A kind of compound immunological adjuvant and its preparation method and application
JP3812814B2 (en) Multivalent oil adjuvant vaccine for animals
CN105396131A (en) Adjuvant for reovirus inactivated vaccine and preparing method thereof
EP3392291B1 (en) Vaccine adjuvant composition based on amphiphilic polyamino acid polymer, containing squalene
RU2259214C1 (en) Method for preparing inactivated dry smallpox vaccine "ospavir"
Kusov et al. Immunogenicity trial of inactivated hepatitis A virus vaccine in human volunteers
BR112019010394A2 (en) swine vaccine
CN108704131B (en) Vaccine diluent for swine fever oral attenuated freeze-dried vaccine and application thereof
CN106466478A (en) A kind of immune composition, contain said composition vaccine and its application

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant
EE01 Entry into force of recordation of patent licensing contract

Application publication date: 20171020

Assignee: LONGKUO (SUZHOU) BIOLOGICAL ENGINEERING Co.,Ltd.

Assignor: SHANGHAI CHUANG HONG BIOTECHNOLOGY Co.,Ltd.

Contract record no.: X2021980008325

Denomination of invention: The invention relates to an immune enhancer for porcine atrophic rhinitis inactivated vaccine and a preparation method thereof

Granted publication date: 20201201

License type: Common License

Record date: 20210825

EE01 Entry into force of recordation of patent licensing contract