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US-12616824-B2 - Heat-resistant implantable polymer microneedle and preparation method therefor and application thereof

US12616824B2US 12616824 B2US12616824 B2US 12616824B2US-12616824-B2

Abstract

Disclosed are a heat-resistant implantable polymer microneedle and a preparation method therefor and an application thereof. The microneedle comprises a needle tip, a needle body, and a base, wherein the needle tip comprises a homogeneous system formed by mixing a biodegradable macromolecular material which has a glass transition temperature of 35-65° C. and is difficultly soluble in water and a macromolecular material having a glass transition temperature higher than that of the biodegradable macromolecular material. The microneedle has good heat resistance and puncture property.

Inventors

  • Yunhua Gao
  • Xiaoyu ZHAO
  • Suohui ZHANG

Assignees

  • Technical Institute of Physics and Chemistry of the Chinese Academy of Sciences

Dates

Publication Date
20260505
Application Date
20210604
Priority Date
20200604

Claims (16)

  1. 1 . A heat-resistant implantable polymer microneedle, comprising a needle tip, a needle body, and a base, wherein the needle tip comprises a homogeneous system formed by mixing a biodegradable macromolecular material A which has a glass transition temperature of 35-65° C. and is substantially insoluble in water at 25° C. and a macromolecular material B having a glass transition temperature higher than that of the biodegradable macromolecular material A wherein the glass transition temperature of the macromolecular material B is above 130° C., and wherein, in the needle tip, a mass ratio of the macromolecular material B to the biodegradable macromolecular material A is 0.1:1-0.6:1.
  2. 2 . The microneedle according to claim 1 , wherein the biodegradable macromolecular material A is selected from one or more of PLA, PGA, PLGA, PCL, and derivatives thereof.
  3. 3 . The microneedle according to claim 1 , wherein the macromolecular material B is selected from one or more of polyvinylpyrrolidone and derivatives thereof, and cellulose and derivatives thereof.
  4. 4 . The microneedle according to claim 1 , wherein the needle tip further comprises at least one active component.
  5. 5 . The microneedle according to claim 1 , wherein the needle tip further comprises one or more a pore forming agent and a protective agent.
  6. 6 . The microneedle according to claim 1 , wherein the needle body and the base are independently formed from a matrix comprising a water-soluble macromolecular material.
  7. 7 . A method for preparing a microneedle according to claim 1 , comprising the following steps: 1) mixing the biodegradable macromolecular material A and a portion of an organic solvent, adding the macromolecular material B, and adding a pore forming agent and a protective agent to obtain a needle tip matrix solution; mixing an active component and the remainder of the organic solvent to obtain a drug solution; and mixing the drug solution and the needle tip matrix solution to obtain a needle tip injection molding solution; or Mixing the biodegradable macromolecular material A and an organic solvent, adding the macromolecular material B, optionally adding a pore forming agent and a protective agent, and adding an active component to obtain a needle tip matrix solution after mixing; 2) providing an injection molding solution of a needle body and a base; and 3) adding the needle tip injection molding solution to a microneedle mold so that the solution enters a mold cavity under vacuum, performing heating at 30-80° C., and volatilizing the organic solvent, so as to prepare the needle tip; and adding the injection molding solution of the needle body and the base to the microneedle mold so that the solution enters the mold cavity under vacuum, performing drying at the room temperature, and performing demolding, so as to prepare the heat-resistant implantable polymer microneedle.
  8. 8 . A microneedle patch, comprising a microneedle array composed of microneedles according to claim 1 and a back lining.
  9. 9 . Use of the microneedle patch according to claim 8 in the fields of medicine, health care, and cosmetology.
  10. 10 . The microneedle according to claim 4 , wherein the mass ratio of the sum of the biodegradable macromolecular material A and macromolecular material B to the active component is 0.5:1-1000:1.
  11. 11 . The microneedle according to claim 5 , wherein the amount of the added pore forming agent is 0.1%-20% of the total mass of the needle tip.
  12. 12 . The micro needle according to claim 5 , wherein the amount of the added protective agent is less than 20% of the total mass of the needle tip.
  13. 13 . The microneedle according to claim 11 , wherein the amount of the added protective agent is less than 20% of the total mass of the needle tip.
  14. 14 . The microneedle according to claim 6 , wherein the water-soluble macromolecular material is selected from one or more of carboxymethyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, carboxymethyl chitosan, chitosan and derivatives thereof, polyvinyl alcohol and derivatives thereof, polyvinyl pyrrolidone and derivatives thereof, sodium hyaluronate, chondroitin sulfate, dextran and derivatives thereof, sodium alginate, poly γ-glutamic acid, pullulan, gelatin, polydopamine, or polyacrylamide.
  15. 15 . The microneedle of claim 6 , wherein the molecular weight of the water-soluble macromolecular material is 10-1000 kDa.
  16. 16 . The microneedle of claim 14 , wherein the molecular weight of the water-soluble macromolecular material is 10-1000 kDa.

Description

TECHNICAL FIELD The present application relates to the technical field of medicines, in particular to a heat-resistant implantable polymer microneedle, a preparation method therefor, and an application thereof. BACKGROUND Transdermal drug delivery refers to drug delivery implemented via skin. The capillaries in the skin absorb the drug into the blood circulation system to play a therapeutic role. The transdermal drug delivery can avoid the “first pass effect” to release the drug steadily and slowly, thus improving the bioavailability of the drug. Moreover, patients can take the drug by themselves, achieving good compliance. However, due to the barrier of the stratum corneum, the drug penetration efficiency is not high, and the types of drugs for transdermal drug delivery are very limited. The microneedle is a new type of transdermal drug delivery, and is composed of sharp micro protrusion arrays. The microneedle can puncture the stratum corneum to form a micro drug delivery channel on the skin and release the drug to a target cortex. Therefore, the microneedle can overcome the barrier of the stratum corneum, significantly improving transdermal drug penetration efficiency and enriching the types of drugs for transdermal penetration, and thus is a minimally invasive and painless drug delivery way. Currently, there are many kinds of materials for preparing microneedles, such as silicon, glass, metals, and polymers. However, a microneedle made of silicon or glass is brittle and easy to break under an external force, making it inconvenient to use. A metal microneedle has relatively good mechanical strength but requires a high cost and a complicated preparation process and thus is inapplicable to large-scale production. A polymer microneedle has good mechanical strength and requires a low cost and a simple preparation process and thus is applicable to large-scale production of microneedles. The materials for preparing the polymer microneedle include: water-soluble polymers, swelling polymers, and biodegradable polymers. These polymers all have good biocompatibility and a specific degradation mode or swelling property, and a drug release behavior can be effectively controlled according to the properties of the polymer materials. Polylactic acid macromolecular materials have excellent biocompatibility and biodegradability and good mechanical properties, and are ideal materials for preparing biodegradable polymer microneedles. Drug-loaded polymer microneedles, which are prepared using polylactic acid as sustained-release materials, are widely applied in the field of transdermal drug release. Polylactic acid microneedles are widely applied in transdermal drug sustained-release, and storage conditions thereof are problems frequently considered in the field of preparations, wherein the temperature is an important factor that affects the stability of the microneedles. The glass transition temperature is a temperature for transition of an amorphous polymer from a glassy state to a high elastic state, and is an important index for measuring the heat resistance of the polymer. When the external temperature is close to or higher than the glass transition temperature of the polymer, the polymer microneedle melts and deforms, making the microneedle useless. Document 1 (Plastics Industry. 2012 January; 40(1):68-71.) and Document 2 (J Control Release. 2017 March; 249:11-22.) reported that the glass transition temperatures of polylactic acid (PLA), polyglycolic acid (PGA), and polylactic-glycolic acid (PLGA) are respectively 40-60° C., 35-40° C., and 40-60° C. These macromolecular materials have relatively low glass transition temperatures, resulting in poor heat resistance of the microneedles made therefrom. For example, after a microneedle prepared by using PLGA as a tip material stands at 40° C. for two days, the tip of the microneedle melts into a sphere, as shown in FIG. 1. Accordingly, there are great difficulties in the storage and use of polylactic acid microneedles at high temperatures. Therefore, it is necessary to provide a heat-resistant implantable polylactic acid microneedle to facilitate storage and use in summer or tropical areas. BRIEF SUMMARY In view of the defects in the prior art, the first objective of the present application is to provide a heat-resistant implantable polymer microneedle. The second objective of the present application is to provide a method for preparing a heat-resistant implantable polymer microneedle, the method having a simple process and a low cost. The third objective of the present application is to provide a microneedle patch, the microneedle patch having good heat resistance. The fourth objective of the present application is to provide use of the microneedle patch. In order to achieve the first objective, the present application adopts the following technical solution: A heat-resistant implantable polymer microneedle includes a needle tip, a needle body, and a base. The needle tip