CN105288614A - Vaccine composition and its preparation method - Google Patents
Vaccine composition and its preparation method Download PDFInfo
- Publication number
- CN105288614A CN105288614A CN201510065536.6A CN201510065536A CN105288614A CN 105288614 A CN105288614 A CN 105288614A CN 201510065536 A CN201510065536 A CN 201510065536A CN 105288614 A CN105288614 A CN 105288614A
- Authority
- CN
- China
- Prior art keywords
- vaccine
- adjuvant
- emulsion
- nano
- phase
- 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.)
- Pending
Links
Landscapes
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention provides a vaccine composition and its preparation method. The vaccine composition comprises an antigen and a nanoemulsion vaccine adjuvant, wherein the nanoemulsion vaccine adjuvant has an oil phase of squalene and is mixed with two surfactants, a buffer liquid is added as an aqueous phase, in a whole system HLB value is 8-12, a total amount of the surfactants has a range of 8%-12%, and a water-oil ratio is 0.2-0.8; a mixture above is quickly stirred for initial emulsification at a temperature lower than phase inversion temperature; then preheating is carried out at a certain stirring speed to allow further emulsification; the mixture is heated to a temperature higher than the phase inversion temperature prior to being cooled, the aqueous phase fully covers the oil phase, and finally the nano-level vaccine adjuvant having uniform particles is formed. The nanoemulsion vaccine aid in the vaccine composition has uniformly distributed particles, good stability and good immunologic enhancement, so that the vaccine composition has better immune effect than vaccines without an adjuvant or with other common adjuvants.
Description
The divisional application that patent application of the present invention is the applying date is on June 18th, 2014, application number is 201410272698.2, name is called the Chinese patent application of nano-emulsion vaccine adjuvant.
Technical field
The invention belongs to biomedicine field, relate to a kind of vaccine combination, particularly a kind of vaccine combination and preparation method thereof comprising novel nano breast vaccine adjuvant.
Background technology
Vaccine adjuvant is also known as immunological adjuvant (Adjuvant), it is a class general non-immunogenicity when being used alone, but can enhancement antigen material immunogenicity when merging use with antigenic substance, enhancing human body immunity is replied, or changes the material of immune response type.Adjuvant is a class nonspecific immunity strengthening agent in essence, inoculates separately or mix rear Simultaneous vaccination with vaccine before vaccine immunity of being everlasting clinically.After adjuvant is used in secondary immunity, the potentiation of its immunity is more obvious.Facts have proved that the use in conjunction of vaccine and adjuvant not only can significantly improve the immune effect of vaccine, can also lower the immunologic tolerance of animal body.
Present commodity production mainly contains following several adjuvant, aluminum salt, the microbial product of improvement, liposome and Emulsion.Wherein aluminum adjuvant mainly contains aluminium hydroxide, aluminum phosphate etc., is the most widely used adjuvant in the whole world.But this adjuvant has a lot of limitation, as low in adsorption effect, the amount of needs is large.Develop rapidly along with modern biological project is engineered, traditional deactivation or the importance of live vaccine reduce gradually, but the problem such as the modern vaccination ubiquity immunogenicity be made up of genetic engineering recombinant antigen or chemically synthesized polypeptide is weak, therefore there is again strong active adjuvant to strengthen its effect in the urgent need to safety.For a change the backward situation of this immune adjuvant research and development, has started in many developed countries the research carrying out novel adjuvant, has wherein just comprised the research and development of some nano-emulsion adjuvant.Existing emulsion adjuvant is representative with MF59, AS04 etc. on the market, is class Water-In-Oil or an oil-in-water emulsifiers.The research of Emulsion adjuvant is shown that this is a kind of novel adjuvant not second to aluminum adjuvant, its several clinical before exploitation and clinical trial in show even more excellent, hepatitis B, hepatitis C and HIV subunit antigen etc. have also carried out large-scale clinical experiment at application novel adjuvant, such as AS04, as Hepatitis B virus vaccine adjuvant, has achieved listing license in European Union.Particularly based on the influenza vaccines of MF59 Emulsion adjuvant
go on the market 10 years, this is a kind of vaccine adjuvant utilizing hyperpressure homogenization to prepare, but the technique of this high energy has a lot of defect, is mainly manifested in: need special equipment to carry out nanorize as high pressure homogenizer, longer processing operation time, a large amount of energy requirement and high cost.
Summary of the invention
The object of the present invention is to provide a kind of vaccine combination of good immune effect, wherein vaccine adjuvant function admirable used and cost is low, to overcome above-mentioned shortcoming.
The present invention passes through phase transition temperature (phaseinversiontemperature (PIT)) legal system for novel nano breast vaccine adjuvant, key factor needs to determine suitable surfactant and suitable HLB value, such could oil meter face formed supporting structure, wrapped up by aqueous phase, form the water oil particles of uniform nanoscale (130 ~ 165nm scope), and Stability Analysis of Structures; Secondly surfactant total amount needs to control, otherwise can affect the safety of product; Finally must there is the ratio of suitable water and oil, so just can guarantee the parcel of suitable water oil.Find a kind of suitable phase transition temperature surfactant finally by experimental design, determine suitable phase transition temperature method technological process, determine main Quality Control project and the standard of nanometer emulsified vaccine adjuvant.
For achieving the above object, the present invention takes following technical proposals to realize:
A kind of vaccine combination, comprise a kind of nano-emulsion vaccine adjuvant and antigen, wherein said vaccine adjuvant is obtained by following steps: take Squalene as oil phase, mix with two kinds of surfactants, adding buffer is aqueous phase, and in whole system, HLB value is 8-12, the total weight range of surfactant is 8%-20%, and water-oil factor example is 0.2-0.8; By said mixture lower than under phase transition temperature, rapid mixing stir carry out primary emulsifying; Then carry out preheating further emulsifying under certain mixing speed; Lower the temperature after mixture being heated above phase transition temperature, aqueous phase wraps up oil phase completely, a kind of evengranular nanoscale vaccine adjuvant of final formation.
Further, described two kinds of surfactants are respectively tween and span.
Preferably, described two kinds of surfactants are respectively Tween 80 and sorbester p17.
Preferably, described HLB value is 9.5.
Preferably, the scope of described surfactant total amount is 11%
Preferably, described water-oil factor example scope is 0.4.
Preferably, the pH of cushioning fluid of described aqueous phase is neutral.
As one of them embodiment, described antigen is hemorrhagic fever antigen.
Wherein core technology of the present invention is the preparation method of nano-emulsion vaccine adjuvant, specifically comprises:
1, the selection of surfactant
Find that nano-emulsion can use phase transition temperature method to be achieved by pretest, the present invention can use different Tween (20,40,60,65,80and85) with different Span (20,40,60,65,80and85), use different combinations, all can prepare nanometer adjuvant by phase transition temperature method, but Tween80 and Span80 is best as surfactant effect, therefore use Tween80 and Span80 as first-selected surfactant, but be not limited to Tween80 and Span80.
2, the selection of HLB (HydrophileLipophilicBalance, hydrophile-lipophile balance)
After determining a kind of oil phase (as Squalene), the type of Emulsion and stability will depend on surfactant and interaction that is oily and water.Hydrophilic surfactant and aqueous phase interact comparatively strong, tend to form oil-in-water emulsion; Vice versa.When temperature is higher than phase transition temperature, the hydrogen bond rupture of surfactant and water dewaters, and just result in surfactant and becomes more lipophilic, so the phase in version of Emulsion just there occurs.According to structure and the HLB value of Tween and Span family, through design experiment, find an optimum HLB value forming Emulsion.For this oil phase of Squalene, finally determine that 8-12 all can prepare nano-emulsion adjuvant, HLB value obtains greatly the Emulsion of minimum grain size about about 9.5 Shi Ke.
3, the determination of the minimum ratio of surfactant
By design experiment, find the minimum surface activating agent ratio that can form uniform particle size, determine that the minimum surface activating agent ratio forming uniform particle size is 8%.When higher than 8% time, surfactant concentration is higher, and particle diameter is less, is conducive to improving its bioavailability, the uniformity of preparation, dispersibility and absorbability.But Surfactant Ratio is less, safer concerning meaning vaccine adjuvant.Comprehensive consideration finally determines that the total weight range of surfactant is 8-20%.
Successfully to have used PIT legal system standby a kind of take Squalene as the nano-emulsion of oil phase in final the present invention, and in the process of method exploitation, we confirm that the selection of PIT surfactant and cosurfactant is the key of method success or failure.Present invention also defines the optimal performance border of HLB value and oil/water ratio simultaneously.To other parameter, comprise Surfactant Ratio, aqueous phase and cooling means are also optimized.
Concrete, water-oil factor example is 0.2-0.8, and preferably, described water-oil factor example scope is 0.4.
Preferably, the pH of cushioning fluid of described aqueous phase is neutral.
Another goal of the invention of the present invention is to provide a kind of method that simple and fast prepares aforementioned vaccine combination.
For realizing this object, the technical solution used in the present invention is:
A preparation method for aforementioned nano-emulsion vaccine adjuvant, comprises the following steps:
A. thick breast preparation: mixing angle zamene, surfactant and cosurfactant are in buffer, and rapid mixing stirring is carried out primary emulsifying;
B. emulsifying further: the thick breast that step a is obtained heats, with further emulsifying under certain mixing speed;
C. the formation of phase in version and nano-emulsion: the mixture in step b is heated to more than phase transition temperature, then lowers the temperature, forms nanoscale emulsion, obtains nano-emulsion vaccine adjuvant;
D. in antigen, the nano-emulsion vaccine adjuvant that step c is obtained is added, obtained vaccine combination.
Wherein concrete technology parameter and flow process are: take Squalene as oil phase, mix with tween and span two kinds of surfactants, and separately adding pH, to be about neutral buffer agent (PBS, Tris, Citric, or Acetate etc.) be aqueous phase.In whole system, HLB scope is at 8-12, and the total weight range of surfactant is 8-20%, and water-oil factor example scope, at 0.2-0.8, stirs and is heated to 55-70 DEG C in 15-20 minute simultaneously.Temperature is remained on 55-70 DEG C, continues stirring and after 5-10 minute, the Emulsion of heat is transferred to rapidly dilution in a large amount of foregoing buffering agents (5-10 times for initial volume) of 4-8 DEG C, do not stop stirring simultaneously.Continue to stir and obtain nano-emulsion vaccine adjuvant in 10-30 minute.Record the electrical conductivity of electrical conductivity close to WFI of gains at the end of reaction, show that the nano-emulsion aqueous phase obtained wraps up oil phase completely.The nano-emulsion vaccine adjuvant subpackage of acquisition is stored in 2-8 DEG C of freezer.
The nano-emulsion vaccine adjuvant uniform particles that the present invention obtains, excellent in stability, immunopotentiating excellent, can be used for the production of various vaccine, especially the production of vaccine for man.
In a word, beneficial effect of the present invention is:
The present invention develops the technique utilizing phase transition temperature (phaseinversiontemperature (PIT)) legal system for novel nano breast vaccine adjuvant first.Phase transition temperature method set forth in the present invention is the hydrophile-lipophile balance that can change PIT surfactant based on temperature.When temperature is lower than phase transition temperature, surfactant forward is curling, forms oil-in-water emulsion; And when temperature is higher than phase transition temperature, surfactant is then oppositely curling, form water-in-oil emulsion.It is hydrophilic that cooling fast makes surfactant become rapidly, thus make it rapid and spontaneous shifting to aqueous phase from oil phase.This transfer rapidly produces very high internal turbulence energy, so emulsion droplet has just been become Nano grade by this power dissipation.Therefore PIT method is adopted not need to use complicated instrument and equipment, do not need high work input, do not need the surfactant of high concentration, do not need with an organic solvent yet, use the method, nano-emulsion with a heater, can complete preparation in a container, is a kind of advanced technologies method of simple and fast.
The present invention mainly completes the selection of PIT surfactant and cosurfactant, profit is optimized mutually, the ratio of surfactant and the optimization of aqueous phase, a kind of technique preparing nano-emulsion vaccine adjuvant of final formation, new generation vaccine adjuvant particle size distribution prepared by this technique about 140nm (having less distribution of particles) compared with other nanometer adjuvant, distribution of particles evenly, excellent in stability, immunopotentiating excellent.Vaccine combination of the present invention comprises this novel nano breast vaccine adjuvant, and good immune effect, can also lower the immunologic tolerance of animal body, will play important influence and effect to the development of vaccine.
Accompanying drawing explanation
Fig. 1 be the embodiment of the present invention 1 nano-emulsion vaccine adjuvant PIT legal system for middle temperature, the schematic diagram of particle diameter and electrical conductivity.
In Fig. 2 embodiment 3 in immunostimulant test and fluorescence to tire schematic diagram.
Fig. 3 is that the blood clotting of immunostimulant test in embodiment 4 suppresses to tire schematic diagram.
Detailed description of the invention
Describe the present invention below in conjunction with embodiment and accompanying drawing.
Embodiment 1
The preparation of nano-emulsion vaccine adjuvant
1) thick breast preparation: take Squalene as oil phase, mix with Tween 80 and sorbester p17.Separately adding pH, to be about neutral buffer agent PBS be aqueous phase.HLB is 9.5, and the total weight range of surfactant is 11%, and water-oil factor example scope, 0.4, stirs and is heated to 55-70 DEG C in 15-20 minute simultaneously.(2) formation of phase in version and nano-emulsion: temperature is remained on 55-70 DEG C, the Emulsion of heat is transferred to rapidly after 5-10 minute in a large amount of (5 times of initial total amounts) PBS buffer agent of 4-8 DEG C by continuation stirring to be diluted, and does not stop to stir simultaneously.Continue to stir 10-30 minute, obtained nano-emulsion vaccine adjuvant product.Product subpackage is stored in 2-8 DEG C of freezer.
Fig. 1 be the present embodiment nano-emulsion vaccine adjuvant PIT legal system for middle temperature, the schematic diagram of particle diameter and electrical conductivity, as shown in Figure 1, reaction starts rear temperature lower than phase transition temperature, and surfactant forward is curling, forms oil-in-water emulsion, the particle diameter of Emulsion is comparatively large, and uneven; When reaction proceeds, temperature reach or higher than phase transition temperature time, surfactant is then oppositely curling, formed water-in-oil emulsion, particle diameter diminishes, and granule is still uneven; Reaction is last, and it is hydrophilic that cooling fast makes surfactant become rapidly, thus make it rapid and spontaneous shifting to aqueous phase from oil phase; This transfer rapidly produces very high internal turbulence energy, so emulsion droplet has just been become Nano grade by this power dissipation; And even particle distribution.
Prepare six batches of products according to above-mentioned technique, PRELIMINARY RESULTS is as shown in table 1 respectively.Table 1 is nano-emulsion particle size and oarse-grained quantity, and wherein mean particle size is 125-165nm, oarse-grained quantity: the amounts of particles being greater than 1.2 μm is less than 1 × 10
7individual/ml.From above-mentioned experimental data, the nano-emulsion vaccine adjuvant that the present embodiment obtains has less distribution of particles, and distribution of particles evenly.
Table 1 nano-emulsion particle size and oarse-grained quantity
| Batch number | Particle size Mean | Large particle(particles/ml) |
| 2013 1-1 | 135.2 | 8.78E+05 |
| 2013 1-2 | 137.7 | 6.94E+05 |
| 2013 2-1 | 137.6 | 6.08E+05 |
| 2013 2-2 | 137.7 | 9.75E+05 |
| 2013 3-1 | 137.4 | 5.41E+05 |
| 2013 3-2 | 136.6 | 6.95E+05 |
Embodiment 2
Product stability is tested
Stability is an important indicator of vaccine adjuvant, and table 2 is that in embodiment 1, the six batches of nano-emulsion vaccine adjuvant place the stability data of 12 months under 25 DEG C of conditions.As known from Table 2, this nano-emulsion vaccine adjuvant particle diameter (topmost stability indicator) nothing in 12 months significantly changes, constant product quality.
The table 2 nano-emulsion vaccine adjuvant particle diameter of 12 months
| Batch | Initial | 1 | 3 | 6 | 9 | 12 |
[0054]
| number | month | month | month | month | month | |
| 1-1 | 135.2 | 136.1 | 138.3 | 135.3 | 135.8 | 136.5 |
| 1-2 | 137.7 | 138.2 | 141.9 | 141 | 137.5 | 136 |
| 2-1 | 137.6 | 139.6 | 138.5 | 138.5 | 138.1 | 137.8 |
| 2-2 | 137.7 | 136.2 | 138.6 | 140 | 145.1 | 135.4 |
| 3-1 | 137.4 | 136.6 | 139 | 135.7 | 132.1 | 140.1 |
| 3-2 | 136.6 | 138.7 | 138.6 | 160.6 | 140.2 | 138.1 |
Embodiment 3
The preparation of vaccine combination and the enhanced sensitivity of vaccine adjuvant thereof.
The immune effect that vaccine combination of the present invention is compared without vaccine adjuvant interpolation or plain vaccine adjuvant is better to adopt rabbit experiment to verify, the vaccine adjuvant namely in the present invention in vaccine combination has enhanced sensitivity.Wherein matched group is that (I type antigen amount is 1: 32 to the conventional hemorrhagic fever vaccine without adjuvant, II type is 1: 16), experimental group chooses same hemorrhagic fever antigen and vaccine adjuvant obtained in final interpolation embodiment 1, and configuration flow is identical without Adjuvanted vaccines flow process with routine.I type antigen minim degree is 1: 32,1: 16,1: 8, II type antigen minim degree is 1: 16,1: 8.Within after just exempting from the 7th day, strengthen a pin, within after initial immunity 21 days, take a blood sample in carrying out and fluorescence titration.Result as shown in Figure 2, therefrom can find out, the fluorescent antibody level after vaccine (I type and II type HA titre are 1: 8) its immunity of adjuvant of the present invention that with the addition of compares with the vaccine (I type and II type HA titre are respectively 1: 32 and 1: 16) of normal compound, still have higher fluorescence to tire, this adjuvant immune stimulatory response effect is obvious.
Embodiment 4
Vaccine combination of the present invention compares with the immune effect of the vaccine combination adding tradition aluminium salt adjuvant
For comparing vaccine combination of the present invention and the immune effect of the vaccine combination of interpolation tradition aluminium salt adjuvant further, We conducted the experiment of another treated animal.I type hemorrhagic fever stock solution (hemagglutinative titer 1: 64) is formulated as each three groups of vaccines that final concentration is 1: 32,1: 16 and 1: 8 respectively, add the obtained adjuvant of embodiment 1 and tradition aluminium salt adjuvant respectively, within after just exempting from the 7th day, strengthen a pin, after initial immunity, 21 days blood sampling survey blood clottings suppress to tire, result as shown in Figure 3, shows that the immune effect of vaccine combination of the present invention is better than adding the vaccine combination of tradition aluminium salt adjuvant.
Tentatively can judge from the immune result above-described embodiment 3 and 4: the nano-emulsion vaccine adjuvant in vaccine combination provided by the invention not only has obvious effect of enhanced sensitivity, and compares with tradition aluminium salt adjuvant, and effect of enhanced sensitivity has significant advantage.
In sum, the present invention develops the vaccine combination comprising and utilize phase transition temperature legal system for novel nano breast vaccine adjuvant first.This new generation vaccine adjuvant particle size distribution about 140nm (there is less distribution of particles compared with other nanometer adjuvant), distribution of particles evenly, excellent in stability, immunopotentiating excellent; Therefore the vaccine combination utilizing this vaccine adjuvant to prepare has good immune effect, and anaphylaxis reduces, the feature of good stability.
Although the present invention with preferred embodiment openly as above, it is not for limiting the present invention.
Claims (9)
1. a vaccine combination, it is characterized in that, comprise a kind of nano-emulsion vaccine adjuvant and antigen, wherein said vaccine adjuvant is obtained by following steps: take Squalene as oil phase, mix with two kinds of surfactants, adding buffer is aqueous phase, in whole system, HLB value is 8-12, and the total weight range of surfactant is 8%-20%, and water-oil factor example is 0.2-0.8; By said mixture lower than under phase transition temperature, rapid mixing stir carry out primary emulsifying; Then carry out preheating further emulsifying under certain mixing speed; Lower the temperature after mixture being heated above phase transition temperature, aqueous phase wraps up oil phase completely, a kind of evengranular nanoscale vaccine adjuvant of final formation.
2. vaccine combination according to claim 1, is characterized in that, described two kinds of surfactants are respectively tween and span.
3. vaccine combination according to claim 2, is characterized in that, described two kinds of surfactants are respectively Tween 80 and sorbester p17.
4. vaccine combination according to claim 1, is characterized in that, described HLB value is 9.5.
5. vaccine combination according to claim 1, is characterized in that, the scope of described surfactant total amount is 11%.
6. vaccine combination according to claim 1, is characterized in that, described water-oil factor example scope is 0.4.
7. vaccine combination according to claim 1, is characterized in that, the pH of cushioning fluid of described aqueous phase is neutral.
8. vaccine combination according to claim 1, is characterized in that, described antigen is hemorrhagic fever antigen.
9. a preparation method for vaccine combination as claimed in claim 1, is characterized in that, described preparation method comprises the following steps:
A. thick breast preparation: mixing angle zamene, surfactant and cosurfactant are in buffer, and rapid mixing stirring is carried out primary emulsifying;
B. emulsifying further: the thick breast that step a is obtained heats, with further emulsifying under certain mixing speed;
C. the formation of phase in version and nano-emulsion: the mixture in step b is heated to more than phase transition temperature, then lowers the temperature, forms nanoscale emulsion, obtains nano-emulsion vaccine adjuvant;
D. in antigen, the nano-emulsion vaccine adjuvant that step c is obtained is added, obtained vaccine combination.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410272698.2A CN105267962A (en) | 2014-06-18 | 2014-06-18 | Nanoemulsion vaccine adjuvant |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410272698.2A Division CN105267962A (en) | 2014-06-18 | 2014-06-18 | Nanoemulsion vaccine adjuvant |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN105288614A true CN105288614A (en) | 2016-02-03 |
Family
ID=55138351
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510065536.6A Pending CN105288614A (en) | 2014-06-18 | 2014-06-18 | Vaccine composition and its preparation method |
| CN201410272698.2A Pending CN105267962A (en) | 2014-06-18 | 2014-06-18 | Nanoemulsion vaccine adjuvant |
| CN201510065477.2A Pending CN105267963A (en) | 2014-06-18 | 2014-06-18 | Preparation method for nanoemulsion vaccine auxiliary agent |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410272698.2A Pending CN105267962A (en) | 2014-06-18 | 2014-06-18 | Nanoemulsion vaccine adjuvant |
| CN201510065477.2A Pending CN105267963A (en) | 2014-06-18 | 2014-06-18 | Preparation method for nanoemulsion vaccine auxiliary agent |
Country Status (1)
| Country | Link |
|---|---|
| CN (3) | CN105288614A (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106109414B (en) * | 2016-07-28 | 2019-07-16 | 金宇保灵生物药品有限公司 | A kind of aftosa vaccine dilution and the preparation method and application thereof |
| CN113617326B (en) * | 2021-08-13 | 2023-01-31 | 中北大学 | Preparation device and preparation method for high-stability O/W nano emulsion |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0618840A1 (en) * | 1991-12-09 | 1994-10-12 | Henkel Kgaa | Method of producing oil-in-water emulsions. |
| US5952395A (en) * | 1996-06-28 | 1999-09-14 | L 'oreal | Gelled ultrafine oil-in-water emulsion stabilized with a crosslinked poly(2-acrylamido-2-methylpropanesulfonic acid) polymer neutralized to at least 90% process of preparation and applications |
| CN101184501A (en) * | 2005-04-15 | 2008-05-21 | 梅瑞尔有限公司 | Novel vaccine formulations |
| CN101217977A (en) * | 2005-07-07 | 2008-07-09 | 赛诺菲巴斯德有限公司 | Thermoreversible immuno-adjuvant emulsion |
| WO2010103022A2 (en) * | 2009-03-12 | 2010-09-16 | Sanofi Pasteur | Oil-in-water adjuvanted influenza vaccine |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2017507C (en) * | 1989-05-25 | 1996-11-12 | Gary Van Nest | Adjuvant formulation comprising a submicron oil droplet emulsion |
| CN100548285C (en) * | 2006-09-20 | 2009-10-14 | 西北农林科技大学 | A kind of Terbinafine nano milk-like liquid antifungal medicine and preparation method thereof |
| CN103784953B (en) * | 2012-10-26 | 2018-04-10 | 上海医药工业研究院 | Oil-in-water type Submicron Emulsion as vaccine adjuvant and preparation method thereof |
-
2014
- 2014-06-18 CN CN201510065536.6A patent/CN105288614A/en active Pending
- 2014-06-18 CN CN201410272698.2A patent/CN105267962A/en active Pending
- 2014-06-18 CN CN201510065477.2A patent/CN105267963A/en active Pending
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0618840A1 (en) * | 1991-12-09 | 1994-10-12 | Henkel Kgaa | Method of producing oil-in-water emulsions. |
| US5952395A (en) * | 1996-06-28 | 1999-09-14 | L 'oreal | Gelled ultrafine oil-in-water emulsion stabilized with a crosslinked poly(2-acrylamido-2-methylpropanesulfonic acid) polymer neutralized to at least 90% process of preparation and applications |
| CN101184501A (en) * | 2005-04-15 | 2008-05-21 | 梅瑞尔有限公司 | Novel vaccine formulations |
| CN101217977A (en) * | 2005-07-07 | 2008-07-09 | 赛诺菲巴斯德有限公司 | Thermoreversible immuno-adjuvant emulsion |
| WO2010103022A2 (en) * | 2009-03-12 | 2010-09-16 | Sanofi Pasteur | Oil-in-water adjuvanted influenza vaccine |
Non-Patent Citations (1)
| Title |
|---|
| 朱善元: "《兽医生物制品生产与检验》", 30 August 2006 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN105267962A (en) | 2016-01-27 |
| CN105267963A (en) | 2016-01-27 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP5300475B2 (en) | Thermoreversible immune adjuvant emulsion | |
| CN102921013B (en) | Preparation method and application of chitosan nanoparticles with pore structures | |
| CN101574638B (en) | Starch nano-microsphere and preparation method thereof | |
| CN105288614A (en) | Vaccine composition and its preparation method | |
| CN113521004B (en) | Preparation method of high-load cannabidiol oil-in-water macromolecular particle emulsion | |
| Salgado et al. | Single-particle detection of transcription following rotavirus entry | |
| CN107227153A (en) | Polymer carbon point, preparation method and its application in targets neoplastic cells context of detection of a kind of high-fluorescence quantum yield | |
| CN109588721A (en) | One Carotenoids-protein particle and its preparation method and application | |
| CN102988982B (en) | Method for preparing nano aluminum hydroxide gel adjuvant | |
| Jiao et al. | Controllable Synthesis of Upconversion Nanophosphors toward Scale‐Up Productions | |
| Shirshahi et al. | Active targeting of HER2-positive breast cancer cells by Herceptin-functionalized organically modified silica nanoparticles | |
| CN108013475B (en) | Polypeptide-polysaccharide composite emulsion and preparation method thereof | |
| CN105148266B (en) | A kind of w/o type vaccine oil adjuvant preparation and preparation method thereof | |
| CN103128309B (en) | Synthetic method of water-solubility biocompatibility monodisperse spherical gold nanometer crystals | |
| CN115120559B (en) | Method for improving embedding rate of ginsenoside Rg3 and CK and stability of nanoemulsion | |
| CN110664749B (en) | MF 59-based entrapped antigen nanoemulsion and preparation method and application thereof | |
| CN113955762B (en) | Mesoporous silicon nano material and preparation method and application thereof | |
| CN103479997B (en) | Preparation method for avian reovirus virus water-in-oil-in-water type inactivated vaccines | |
| Zou et al. | Green preparation of hydrogel particles‐in‐emulsions for simultaneous enhancement of humoral and cell‐mediated immunity | |
| CN102389394A (en) | Oil-emulsion vaccine for poultry and preparation method thereof | |
| CN102028945B (en) | Spirulina polysaccharide immune adjuvant and influenza vaccine containing the same | |
| CN112300768B (en) | Nanoparticle-reinforced residual oil emulsion profile control and flooding agent and preparation method thereof | |
| CN105994345A (en) | Efficient cyfluthrin nano-emulsion composition and preparation method thereof | |
| CN111494619B (en) | Preparation method of squalene-based cationic nanostructured lipid carrier immunologic adjuvant | |
| CN113730351A (en) | High-stability emulsion with high load of cannabidiol and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20160203 |
|
| RJ01 | Rejection of invention patent application after publication |