Preparation of zinc zoledronate micro-nanoparticle adjuvant and use thereof as vaccine adjuvant

Patent metadata

Field	Value
Publication number	US-12472250-B2
Application number	US-202017602214-A
Country	US
Kind code	B2
Filing date	Apr 10, 2020
Priority date	Apr 11, 2019
Publication date	Nov 18, 2025
Grant date	Nov 18, 2025

Abstract

Disclosed is a zinc zoledronate micro-nanoparticle adjuvant, which contains zinc and zoledronic acid and optionally contains a phosphate and aluminum. The preparation method therefor comprises performing mixed precipitation on a soluble salt solution containing zinc ions, zoledronic acid, and sodium hydroxide. The adjuvant can be used to prepare vaccines, etc.

First claim

What is claimed is:

1 . A vaccination method for treatment or prevention of infection in a mammal, said method comprising administering a vaccine composition intramuscularly to a mammal, wherein said vaccine composition comprises an antigen and an adjuvant, wherein the adjuvant comprises zinc zoledronate micro/nanoparticles, and wherein the zinc zoledronate micro/nanoparticles comprise zinc and zoledronic acid at a molar concentration ratio of zinc:zoledronic acid of 1-8:1.

2 . The vaccination method according to claim 1 , wherein said zinc zoledronate micro/nanoparticles have a molar concentration ratio of zinc:zoledronic acid selected from 1:1, 4:1 and 8:1.

3 . The vaccination method according to claim 1 , characterized in any one of the following:
(1) said zinc zoledronate micro/nanoparticles further comprise a phosphate at a molar concentration ratio of zinc:phosphate of 1-8:1; and (2) said zinc zoledronate micro/nanoparticles further comprise a phosphate at a molar concentration ratio of zinc:phosphate selected from 1.5:1 and 4:1.

4 . The vaccination method according to claim 1 , characterized in any one of the following:
(1) said zinc zoledronate micro/nanoparticles further comprise aluminum at a molar concentration ratio of zinc:aluminum of 0.02-1:1; and (2) said zinc zoledronate micro/nanoparticles further comprise aluminum at a molar concentration ratio of zinc:aluminum selected from 0.375:1, 0.5:1 and 0.8:1.

5 . The vaccination method according to claim 1 , wherein the zinc zoledronate micro/nanoparticles are prepared by a method comprising the following steps:
a) providing a soluble salt solution containing zinc ions; b) evenly mixing the soluble salt solution of step a) with a zoledronic acid and a sodium hydroxide; or evenly mixing the soluble salt solution of step a) with a zoledronic acid, a sodium hydroxide, and a sodium phosphate solution, in a manner of sequential precipitation, separated precipitation followed by mixing, or co-precipitation, to obtain the adjuvant comprising zinc zoledronate micro/nanoparticles.

6 . The vaccination method according to claim 5 , characterized in one or more of the following:
(1) said salt solution comprises a solution of hydrochloric acid; and (2) said method further comprises subjecting the mixture of step b) to sterilization, and storing at 2° C. to 8° C. for later use.

7 . The vaccination method according to claim 6 , characterized in any one of the following:
(1) said sterilization comprises a sterilization using a high temperature and high pressure sterilization technique; and (2) said sterilization comprises a sterilization performed at 121° C. for 30 to 60 minutes.

8 . The vaccination method according to claim 1 , characterized in one or more of the following:
(1) said adjuvant has a pH of 8.0-9.0 before sterilization; (2) said adjuvant has a pH of 6.0-8.0 after sterilization; (3) said zinc zoledronate micro/nanoparticles have a particle size of 1-10 μm; (4) said adjuvant has a particle zero charge point of 4.0-11.4; and (5) said adjuvant has a protein adsorption rate of >80%.

9 . The vaccination method according to claim 8 , wherein said protein comprises bovine serum albumin.

Assignees

• Xiamen Innovax Biotech Co Ltd
• Univ Xiamen

Inventors

• Zhao Qinjian
• Huang Xiaofen
• Chen Siyi
• Li Yike
• Zhang Cai
• Xia Ningshao

Classifications

• A61K2039/55511

  Organic adjuvants · CPC title

• A61K39/292

  Serum hepatitis virus, hepatitis B virus, e.g. Australia antigen · CPC title

• A61K39/25

  Varicella-zoster virus · CPC title

• A61K9/14

  Particulate form, e.g. powders, {Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles (microspheres A61K9/16; microcapsules A61K9/50; nanocapsules, nanoparticles of the matrix type A61K9/51)} · CPC title

• A61P37/04

  Immunostimulants · CPC title