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CN-121971366-A - Soluble microneedle patch for monkey pox vaccine and preparation method thereof

CN121971366ACN 121971366 ACN121971366 ACN 121971366ACN-121971366-A

Abstract

The invention relates to the field of vaccine delivery, and in particular discloses a soluble microneedle patch for a monkey pox vaccine and a preparation method thereof, wherein the microneedle patch comprises a back lining and a needle body, the needle body consists of a monkey pox vaccine, a matrix material and a vaccine stabilizer, the matrix material is dextran 70, the vaccine stabilizer is a mixture of human serum albumin and threonine, and the mass ratio of the monkey pox vaccine to the mixture consisting of the matrix material and the vaccine stabilizer is (2:5) - (1:3). The invention solves the problems of strong dependence of the existing monkey pox/smallpox vaccine on cold chain transportation and professional operation, low patient compliance and easy loss of virus activity in the preparation and storage processes of the soluble microneedle by optimizing the specific formula and the preparation process and preferably controlling the mass ratio of the matrix material, the human serum albumin and the threonine to be 10:1:1. The prepared microneedle patch can be stably stored for a long time at normal temperature, and has good mechanical strength and skin penetration dissolution performance.

Inventors

  • LIU WEI
  • Du Xingyue
  • ZHOU RENHUI
  • XU YAQING
  • QIN RIHUI
  • Zou dayang
  • WANG KEHUI
  • WANG BIN
  • LIU XIONG
  • LI XIANHUANG
  • XU ZHIYAO
  • LIU WEIHUA
  • LI LINHAO

Assignees

  • 中国人民解放军疾病预防控制中心

Dates

Publication Date
20260505
Application Date
20260127

Claims (9)

  1. 1. The soluble microneedle patch for the monkey pox vaccine comprises a back lining and a needle body, and is characterized in that the needle body consists of a monkey pox vaccine, a matrix material and a vaccine stabilizer; wherein the matrix material is dextran 70; the vaccine stabilizer is a mixture of human serum albumin and threonine; the mass ratio of the monkey pox vaccine to the mixture consisting of the matrix material and the vaccine stabilizer is (2:5) - (1:3).
  2. 2. The monkey pox vaccine soluble microneedle patch according to claim 1, wherein the mass ratio of the matrix material, the human serum albumin and the threonine is 10:1:1.
  3. 3. The soluble monkey pox vaccine microneedle patch according to claim 1 or 2, wherein the mass ratio of the needle body to the backing is (3-5): 100.
  4. 4. The soluble monkey pox vaccine microneedle patch according to claim 1, wherein the matrix material of the needle is formed by drying a solution of dextran 70 having a concentration of 20% to 40%; the material of the back lining is formed by drying a polyvinylpyrrolidone solution with the concentration of 20-40%.
  5. 5. The soluble monkey pox vaccine microneedle patch according to claim 1, wherein the height of the needle body is 800-1200 μm, the height of the wedge-shaped base of the needle body is 200-400 μm, the bottom diameter of the tip of the needle body is 200-350 μm, and the array density of the needle body is 100-400 needles/cm 2.
  6. 6. The soluble monkey pox vaccine microneedle patch according to claim 1 or 2, wherein the monkey pox vaccine is an attenuated live vaccine and the single patch of the microneedle patch carries a viral titer of 。
  7. 7. A method for preparing a soluble microneedle patch of a monkey pox vaccine according to any one of claims 1 to 6, comprising the steps of: S1, filling a needle body, namely mixing and dissolving a prescription amount of monkey pox vaccine, a matrix material and a vaccine stabilizer to form uniform needle body fluid, coating the needle body fluid on the surface of a female die, filling the needle body fluid into micropores of the female die under a vacuum condition, removing redundant solution outside a hole, centrifuging, and drying; S2, backing filling, namely dissolving a backing material into backing liquid, coating the backing liquid on the surface of the female die treated in the step S1, leveling the backing liquid under a vacuum condition, covering the needle body base, drying and demolding.
  8. 8. The method according to claim 7, wherein in the step S1, the vacuum condition is-0.07 MPa, the holding time is 2 minutes, and the centrifugation condition is 4000r/min, and the centrifugation time is 5 minutes.
  9. 9. The method according to claim 7, wherein the drying conditions in step S1 and step S2 are 25 ℃.

Description

Soluble microneedle patch for monkey pox vaccine and preparation method thereof Technical Field The invention belongs to the field of vaccine delivery, and particularly relates to a soluble monkey pox vaccine microneedle patch and a preparation method thereof. Background Monkey poxvirus (monkeypox virus, MPXV) belongs to the family poxviridae (Poxviridae) genus orthopoxvirus (Orthopoxvirus). The virus has an envelope structure, the genome is double-stranded DNA, and the region of the genome responsible for coding key enzyme systems and structural proteins is highly similar to the sequence of the smallpox virus. Since 2022 spreading of the monkey pox epidemic, WHO has announced 2 times that it constitutes an international focus of sudden public health event, highlighting worldwide urgent need for prophylactic monkey pox vaccines. Vaccination is one of the most cost-effective interventions to prevent various infectious diseases, but no specific vaccine against MPXV is currently approved worldwide. World Health Organization (WHO) recommended three smallpox vaccines LC16m8 (japan KM biology company), MVA-BN (danish bavaria) and ACAM2000 (emerging biotechnology company in the united states) for the prophylaxis of infection with monkey poxviruses. However, the attenuated live vaccines have the remarkable limitations that the attenuated live vaccines are used as freeze-dried preparations and require strict cold chain transportation conditions, so that not only is the logistics transportation cost high, but also the compliance of patients is influenced by a multi-dose subcutaneous injection scheme, and the LC16m8 and ACAM2000 are operated by a bifurcated needle skin puncturing technology, so that the attenuated live vaccines are highly dependent on professional operators, are high in invasiveness and complex in operation, and are easy to cause uneven dose and infection risk. The soluble microneedles (DMNs) are prepared from soluble materials such as hyaluronic acid, polylactic acid-glycolic acid and the like, can be automatically dissolved after penetrating into human skin, and avoid the problems of broken solid microneedle needles, small drug loading of coated microneedles and the like. Unlike other types of microneedles, such microneedles generally have good biocompatibility, do not produce biological waste, and have good immune effects. For monkey pox vaccines, low temperature storage is required to ensure their immunogenicity, and thus the preparation of microneedles may cause damage to viral titres. To solve the problems of reduced viral titers and reduced immunogenicity, stabilizers and protectants are used in the field of functionalized vaccines. Based on the problems, how to develop a micropin patch of a monkey pox vaccine which has a proper prescription, can effectively puncture skin and dissolve quickly in skin, and simultaneously protect a stabilizer of the monkey pox vaccine, so that the monkey pox vaccine is more stable and safer, and the micropin patch is a technical problem to be solved by the person skilled in the art. Disclosure of Invention In order to solve the technical problems, the invention provides a soluble microneedle patch for a monkey pox vaccine, which aims to solve the problem that the monkey pox vaccine in the prior art lacks a specific delivery system. A soluble microneedle patch for a monkey pox vaccine comprises a back lining and a needle body, wherein the needle body consists of a monkey pox vaccine, a matrix material and a vaccine stabilizer; wherein the matrix material is dextran 70; the vaccine stabilizer is a mixture of human serum albumin and threonine; the mass ratio of the monkey pox vaccine to the mixture consisting of the matrix material and the vaccine stabilizer is (2:5) - (1:3). Preferably, the mass ratio of the matrix material, the human serum albumin and the threonine is 10:1:1. Preferably, the mass ratio of the needle body to the back lining is (3-5): 100. Preferably, the matrix material of the needle body is formed by drying a dextran 70 solution with the concentration of 20-40%; the material of the back lining is formed by drying a polyvinylpyrrolidone solution with the concentration of 20-40%. Preferably, the height of the needle body is 800-1200 mu m, the height of the wedge-shaped base of the needle body is 200-400 mu m, the bottom diameter of the needle tip of the needle body is 200-350 mu m, and the array density of the needle body is 100-400 needles/cm <2 >. Preferably, the monkey pox vaccine is an attenuated live vaccine, and the titer of the virus carried by the single patch of the microneedle patch is that。 The preparation method of the soluble monkey pox vaccine microneedle patch comprises the following steps: S1, filling a needle body, namely mixing and dissolving a prescription amount of monkey pox vaccine, a matrix material and a vaccine stabilizer to form uniform needle body fluid, coating the needle body fluid on the surface of a female die, filling