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Oil-in-water emulsion free of surfactant and use thereof

An oil-in-water emulsion and surfactant technology, applied in the field of biomedicine, can solve the problems of no vaccine preparation design optimization, no Pickering emulsion, and the emulsion cannot be applied.

Active Publication Date: 2014-09-03
INST OF PROCESS ENG CHINESE ACAD OF SCI
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The oil phase investigated in this document includes dodecane (dodecane), polydimethylsiloxane (polydimethylsiloxane), toluene (toluene), and isopropyl myristate (isopropyl myristate), wherein PLGA nanoparticles can stabilize the oil phase as Oil-in-water (o / w) emulsion of dodecane and polydimethylsiloxane, but the above oil phase cannot be used as a pharmaceutical excipient, so it cannot be used as a vaccine adjuvant
Literature (Zengjiang Wei, Chaoyang Wang, Hao Liu, Shengwen Zou, Zhen Tong, Facile fabrication of biocompatible PLGA drug-carrying microspheres by O / W pickering emulsions, Colloids and Surfaces B: Biointerfaces, 2012, 91:97-105) adopted two Silica nanoparticles are used as solid particles, and dichloromethane containing PLGA is used as the oil phase to prepare PLGA microspheres coated with silica nanoparticles, but the silica and dichloromethane in this system are subject to clinical application. limitations, the Pickering emulsion cannot be directly applied in the field of biomedicine
Moreover, there is no research on Pickering emulsion as a vaccine adjuvant in the currently known literature or patents, and the known Pickering emulsion system has not been designed and optimized according to the requirements of vaccine preparations

Method used

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  • Oil-in-water emulsion free of surfactant and use thereof
  • Oil-in-water emulsion free of surfactant and use thereof
  • Oil-in-water emulsion free of surfactant and use thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0105] Embodiment 1: Adopt polyPLGA particle to prepare oil-in-water emulsion

[0106] Preparation of PLGA particles by nanoprecipitation method:

[0107] Accurately weigh 0.30 g of PLGA (LA:GA is 50:50, molecular weight is 110,000 Daltons) using an electronic balance, dissolve it in 1 mL of acetone, and drop the solution at a rate of 1 drop per second with a No. 9 needle. Add it to 20mL aqueous solution (containing 1wt.% PVA (alcoholysis degree: 99%, viscosity: 5.0mPa·s), magnetic stirring, rotating speed: 500rpm), stir overnight at 25°C, centrifuge at 20000g for 20min, discard the upper Clear, add 5 mL of deionized water to the precipitate, ultrasonically disperse, centrifuge at 20,000 g for 5 min, discard the supernatant, freeze-dry the precipitate to obtain PLGA particles, and store in the refrigerator at 4 °C. The average particle diameter of the prepared PLGA particles is 226nm, and the span is 0.535. The surface of the prepared particles was observed by scanning elect...

Embodiment 2

[0115] Embodiment 2: adopt aluminum hydroxide particle to prepare oil-in-water emulsion

[0116] Prepare aluminum hydroxide particles by microemulsion method:

[0117] Triton X-100, n-butanol and cyclohexane were mixed at a volume ratio of 1:0.5:20 and magnetically stirred (800 rpm, 5 min) to obtain an oil phase. Add 1mol / L AlCl dropwise to the oil phase (20mL) under magnetic stirring (500rpm) at a rate of 2mL / min using a syringe propulsion pump 3 solution (2 mL) to obtain an inverse microemulsion of aluminum chloride. Use a syringe propulsion pump to drip ammonia water into the above-mentioned inverse microemulsion at a rate of 0.5mL / min to keep the pH value of the reaction system higher than 10.0. After reacting for 2h, add 10mL of acetone to break the emulsion, and centrifuge (15000g, 5min ), discard the supernatant, wash repeatedly with absolute ethanol three times, and deionized water once, and finally freeze-dry to obtain aluminum hydroxide particles, which are stored ...

Embodiment 3

[0120] Embodiment 3: adopt calcium phosphate particle to prepare oil-in-water emulsion

[0121] Preparation of hollow calcium phosphate particles by template method:

[0122] After mixing and stirring 3.0g Tween80, 0.25g PEG6000, 3.0mL0.5mol / L Tris-HCl (pH8.0) and 1.5mL deionized water, ultrasonic 20min (10W) to form non-ionic surfactant vesicles, drop into 3.55mLCaCl 2 (0.175mol / L) solution, after stirring for 0.5h, add 3.55mL Na 2 HPO 4 (0.175mol / L) solution can obtain the suspension of sodium phosphate particle, add 0.83mL MgCl 2 solution (0.075mmol / L) to stabilize the newly formed calcium phosphate particles, continue to stir for 2h, centrifuge and wash, and vacuum dry to obtain hollow calcium phosphate particles. The average particle diameter of the particles is 210nm, the thickness of the shell layer is 30-40nm, and the Span of the particles is 0.349. The prepared particles are hollow spheres.

[0123] Preparation of oil-in-water emulsion:

[0124] Accurately weig...

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Abstract

The invention discloses an oil-in-water emulsion free of surfactant. The emulsion comprises a metabolizable oil phase, a water phase and oil-water amphipathic solid particles dispersed in the water phase and having biocompatibility, wherein the oil phase comprises squalene or / and tocol; the water phase is any one or a combination of at least two of purified water, water for injection, aqueous liquid of glycerol, buffered saline liquid and clinically available infusion liquid; and the average grain diameter of the solid particles is at nanometer-to-micron grade. The emulsion can be used as a vaccine adjuvant or a medicine delivery or controlled release carrier; the properties of the emulsion can be controlled and regulated; the obtained emulsion is stable; the use of a surfactant is avoided; and harm to the human body and pollution on the environmental can be reduced.

Description

technical field [0001] The present invention relates to a biological product, in particular to an oil-in-water emulsion that can be used in humans or other animals. It is particularly important that the oil-in-water emulsion of the present invention does not contain surfactants and uses solid particles as the emulsion The stabilizer can be used as a vaccine adjuvant or a drug delivery or a sustained and controlled release carrier, and belongs to the technical field of biomedicine. Background technique [0002] With the rapid development of modern biotechnology and the society's increasing attention to the adverse reactions caused by attenuated vaccines, split vaccines, recombinant subunit vaccines, anti-idiotypic antibody vaccines, nucleic acid vaccines and synthetic peptide vaccines have been developed. These vaccine antigens have high purity, relatively small molecular weight, and low adverse reactions to vaccines. However, the immunogenicity and immunoprotection of these ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K39/39A61K47/44A61K47/14A61K47/22A61K47/06A61K9/107A61P37/02
CPCA61K47/06A61K47/22A61K47/44A61K39/39A61K9/1075A61K9/5031A61K9/146A61K47/02A61K47/34A61K47/36A61K2039/55566A61K2039/55555A61K2039/55505A61K2039/55583A61K39/12C12N2730/10134C12N2760/16134A61K2039/5252C12N2770/32134A61K2039/543A61K9/107A61K47/14A61K39/145A61K2039/525A61K2039/5254A61K2039/53C12N7/00
Inventor 马光辉吴颉杨柳青夏宇飞齐峰范清泽
Owner INST OF PROCESS ENG CHINESE ACAD OF SCI
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