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Microneedle array vaccine adjuvant transmission system built by using lipid modifying carrier

A technology of microneedle array and vaccine adjuvant, which can be used in antibody medical ingredients, medical preparations containing active ingredients, allergic diseases, etc. Efficiency of uptake and utilization, elimination of hindrance, effect of wide application

Inactive Publication Date: 2014-10-08
ANHUI MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

3) RNA / DNA vaccine RNA / DNA vaccine is to clone the expression gene of the protein antigen on the expression vector and inject it into the body so that the antigen is expressed in the body to stimulate the body to produce an immune response. The preparation process is complicated and the safety is low
3) The constantly secreted mucus not only hinders the uptake of Ag by APC, but also flows and updates quickly, which often leads to the loss of a large amount of vaccine before it enters the body

Method used

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  • Microneedle array vaccine adjuvant transmission system built by using lipid modifying carrier

Examples

Experimental program
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Effect test

Embodiment 1

[0034]

[0035] With OVA as antigen, SPC / LA (100:1, mole ratio) as membrane material, total lipid / OVA (20:1, mass ratio), 10% trehalose, 20% PVPk30 (excipient) solution as In the water phase, liposomes were prepared by a film dispersion method to form OVA / Lipid A-liposomes (OVA / LL) with an average particle diameter of 250 nanometers, a zeta potential of 6 mV, and an encapsulation efficiency of 10%. Then mix LL with aluminum phosphate (average particle size 500 nm) (1:5, W / W), and fill it into the pinholes (5×5 holes) of the microneedle array mold prepared by polydimethoxysilane by decompression , then covered with 10% trehalose, 20% PVPk30 (excipient) solution, freeze-dried to remove water, and peeled off to obtain OVA / LL-MAV (6 × 6 microneedles, substrate 0.65 × 0.65cm 2 , fixed on the substrate per microneedle: 250×250×500 μm 3 square cone). After OVA / LL-MAV was stored for 2 weeks, H1sAg-MLL was recovered after hydration, and the above indicators had no significant changes...

Embodiment 2

[0037]

[0038] The surface antigen (hemagglutinin1 antigen, H1sAg) of influenza A (H1N1) virus (influenza A (H1N1) virus) was used as the antigen, and SPC / MPC / MPLA / DOTAP (20:1:0.05:1, mole ratio) was used as the membrane material. Lipid / H1sAg (20:1, mass ratio), using 10% trehalose, 20% PVPk30 (excipient) solution as the water phase, prepared liposomes by reverse evaporation method, forming an average particle size of 320 nanometers, zeta potential MPC / Lipid A double modified liposome (MLL) with 13mV and 59% encapsulation efficiency. Afterwards, the MLL was filled into the pinholes of the microneedle array mold prepared by polydimethoxysilane (6×6 holes) by decompression, and then covered with 10% trehalose, 20% PVPk30 (excipient) solution, and then The mold was placed in an anhydrous calcium chloride drying dish to dry for 8 hours, and peeled off to obtain H1sAg-MLL-MAV (6×6 microneedles, substrate 0.65×0.65cm 2 , fixed on the substrate per microneedle: 100×100×3.14×500 / 3...

Embodiment 3

[0040]

[0041] HBsAg was used as antigen, SPC / GMO / LPS (20:4:0.05, mole ratio) was used as membrane material, total lipid / HBsAg (20:1, mass ratio), 10% sucrose, 30% PVPk17 (excipient ) solution is an aqueous phase, and multivesicular liposomes are prepared by emulsification-evaporation method to form LPS-modified multivesicular liposomes (LML) with an average particle diameter of 520 nanometers, a zeta potential of -12mV, and an encapsulation efficiency of 72%. Afterwards, the MLL is filled into the pinholes of the microneedle array mold prepared by polydimethoxysilane by decompression (6 × 6 holes), and then covered with 10% sucrose, 30% PVPk17 (excipient) solution, and then the mold Place in anhydrous calcium chloride drying dish to dry for 8 hours, and peel off to obtain HBsAg-LML-MAV (8×8 microneedles, substrate 0.75×0.75cm 2 , fixed on the substrate per microneedle: 250×250×500 μm 3 Square column needle body +250×250×50 / 3 micron 3 square cone tip). After HBsAg-LML-MA...

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Abstract

The invention discloses a microneedle array which contains lipid modifying carrier and is used for a vaccine adjuvant transmission system. The microneedle array comprises a substrate and a plurality of microneedles fixed on the substrate, wherein the substrate is composed of saccharides, povidone, cellulose, or starch auxiliary materials; each microneedle comprises lipid A modifying carrier, the auxiliary materials (excipients) and vaccine ingredients; the lipid A modifying carrier can be lipidosome, lipid, micro-capsule or nanoparticle, and the like; the vaccine ingredients mainly refer to causative agent antigen proteins. Compared with the existing vaccine preparations, the lipid A-modified lipidosome microneedle array vaccine adjuvant transmission system can contain different vaccine ingredients to form vaccines aiming to different pathogens and therefore has a wide application scope. Biodegradable materials are selected and therefore the safety is high. The microneedle array vaccine adjuvant transmission system is a solid preparation which is high in stability and convenient to inoculate. Inoculation can be completed by a user self through oral mucosa, the vaccine can be prevented from running away along with saliva, and a body can be induced to establish mucosal immunity.

Description

technical field [0001] The invention relates to the field of vaccine adjuvants for preventing infectious diseases, in particular to a novel vaccine adjuvant delivery system, which essentially uses functional carriers to construct microneedle arrays for use as a vaccine adjuvant delivery system. Background technique [0002] Vaccines are immunogenic substances capable of producing antibodies and are preparations used to prevent infectious diseases. After years of development, the current vaccines mainly include the following types from the sources: 1) Inactivated vaccines are selected from bacteria, viruses, rickettsia, spirochetes, etc. with good immunogenicity, artificially cultivated, and then used physical or chemical methods Kill it to make. 2) Live attenuated vaccines are produced by artificial directed mutagenesis, or live vaccines are made from live microorganisms with attenuated virulence or substantially non-virulence screened from nature. Such as Bacillus Calmett...

Claims

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Application Information

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IPC IPC(8): A61K39/39A61P37/04
Inventor 王汀王宁
Owner ANHUI MEDICAL UNIV
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