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CN-122005425-A - Epinephrine soluble microneedle, preparation method and application thereof, and transdermal patch

CN122005425ACN 122005425 ACN122005425 ACN 122005425ACN-122005425-A

Abstract

The invention relates to the technical field of soluble microneedles, in particular to an epinephrine soluble microneedle, a preparation method and application thereof, and a transdermal patch. The epinephrine soluble micro-needle comprises a needle tip and a substrate, wherein the preparation raw materials of the needle tip comprise, by weight, 10-25 parts of epinephrine compounds, 1-2 parts of polyvinyl alcohol, 2-3 parts of polyvinylpyrrolidone and 30-50 parts of water, and the preparation raw materials of the substrate comprise, by mass, 10-30% of chondroitin sulfate compounds, 10-30% of dextran and 40-80% of water. The epinephrine soluble microneedle has the advantages of high administration efficiency, good mechanical property and formability, high stability and high drug content.

Inventors

  • CHANG ZHIGANG
  • FENG ZHE
  • LIN XUQI
  • YU SHIXING

Assignees

  • 北京医院

Dates

Publication Date
20260512
Application Date
20260304

Claims (10)

  1. 1. The epinephrine soluble micro needle comprises a needle tip and a substrate, and is characterized in that the preparation raw materials of the needle tip comprise, by weight, 10-25 parts of epinephrine compounds, 1-2 parts of polyvinyl alcohol, 2-3 parts of polyvinylpyrrolidone and 30-50 parts of water; the substrate is prepared from, by mass, 10-30% of chondroitin sulfate compounds, 10-30% of dextran and 40-80% of water.
  2. 2. The epinephrine soluble microneedle according to claim 1, wherein the tip is prepared from a material further comprising at least one of an acid, a buffer system, a preservative and a pigment, preferably comprising an acid and a buffer system, further preferably further comprising at least one of a preservative and a pigment.
  3. 3. The epinephrine soluble microneedle of claim 2, wherein the acid comprises citric acid, the buffer system comprises a citric acid-sodium citrate buffer system, and the preservative comprises sodium metabisulfite.
  4. 4. The epinephrine soluble microneedle of claim 2, wherein the amount of the acid substance is 18-20 parts by weight, the buffer system is 18-20 parts by weight, the preservative is 0.1-0.3 parts by weight, and the pigment is 0.1-0.3 parts by weight.
  5. 5. The epinephrine soluble microneedle according to claim 1, wherein the epinephrine compound comprises at least one of epinephrine and epinephrine hydrochloride, and/or the chondroitin sulfate compound comprises at least one of chondroitin sulfate and sodium chondroitin sulfate, and/or the dextran comprises dextran-40, and/or the substrate is prepared from the following raw materials, by mass, 15-25% of the chondroitin sulfate compound, 15-25% of the dextran and 50-60% of water.
  6. 6. The epinephrine soluble microneedle according to claim 1, wherein the mass ratio of polyvinyl alcohol and polyvinylpyrrolidone is 1:1-3 and/or the volume ratio of the tip to the substrate is 1:3-8.
  7. 7. A method of preparing an epinephrine-soluble microneedle according to any one of claims 1 or 5 to 6, comprising the steps of: (1) Mixing polyvinyl alcohol and water, and sequentially adding an epinephrine compound and polyvinylpyrrolidone after the solution is clarified to obtain a needlepoint solution; (2) Mixing a chondroitin sulfate compound, dextran and water to obtain a base solution; (3) Filling the needle point solution into a microneedle mould, standing, filling the substrate solution, standing, drying and demoulding to obtain the product; preferably, the temperature of the water in step (1) is from 30 to 60 ℃; and/or step (1) further comprises centrifuging the tip solution; And/or step (2) further comprises centrifuging the substrate solution.
  8. 8. A method of preparing an epinephrine-soluble microneedle according to any one of claims 2 to 4, comprising the steps of: (1) Mixing polyvinyl alcohol and water, sequentially adding an epinephrine compound and an acid substance after the solution is clarified, adding a buffer system and polyvinylpyrrolidone after the solution is clarified, and adding or not adding a preservative and a pigment to obtain a needlepoint solution; (2) Mixing a chondroitin sulfate compound, dextran and water to obtain a base solution; (3) Filling the needle point solution into a microneedle mould, standing, filling the substrate solution, standing, drying and demoulding to obtain the product; preferably, the temperature of the water in step (1) is from 30 to 60 ℃; and/or step (1) further comprises centrifuging the tip solution; And/or step (2) further comprises centrifuging the substrate solution.
  9. 9. Use of an epinephrine soluble microneedle according to any one of claims 1 to 6 or prepared by the preparation method of any one of claims 7 to 8 for preparing an epinephrine transdermal patch.
  10. 10. An epinephrine transdermal patch, comprising an epinephrine soluble microneedle and a patch base material, wherein the epinephrine soluble microneedle is prepared by the epinephrine soluble microneedle according to any one of claims 1 to 6 or the preparation method according to any one of claims 7 to 8.

Description

Epinephrine soluble microneedle, preparation method and application thereof, and transdermal patch Technical Field The invention relates to the technical field of soluble microneedles, in particular to an epinephrine soluble microneedle, a preparation method and application thereof, and a transdermal patch. Background The transdermal drug delivery system has the advantages of improving patient compliance, continuously delivering drugs, avoiding gastrointestinal irritation and liver first pass effect, and the like. The skin is used as the largest organ of human body, and plays an important role in keeping moisture of the body and preventing external injury. The outermost layer of the skin is the dense stratum corneum, which has a thickness of about 15-20 μm and is the most important barrier for transdermal drug delivery systems, preventing the effective delivery of drugs and limiting the application of transdermal drug delivery. Micropins refer to needle-like structures with diameters less than a few tens of microns and lengths of 25-2000 μm. Microneedle transdermal delivery is an array of several to hundreds of tiny microneedles that achieve drug delivery by piercing the stratum corneum on the skin to create a micro-channel that allows drug molecules and even drug particles to pass directly into the subcutaneous tissue. The microneedle transdermal administration is different from conventional (intramuscular, subcutaneous and intradermal injection) administration, and because the microneedle administration is not easy to stimulate nerve endings, pain is not or less generated, patient compliance can be improved, the burden of medical staff is lightened, and the safety and effectiveness of administration are improved. Microneedles can be classified into solid microneedles, hollow microneedles, coated microneedles, soluble microneedles (or soluble microneedles), and hydrogel microneedles 5 types according to a drug release mechanism. The soluble micro needle (or soluble micro needle) is prepared from water-soluble material, the medicine is dispersed in the needle body, when in use, the micro needle is used for administration according to the principle of poking and releasing, namely, when in administration, the micro needle is inserted into human skin, and the medicine is dissolved after the needle body is contacted with interstitial fluid of the skin, and is released locally. In general, the matrix material of the soluble microneedle should meet the following requirements that 1) it is biocompatible and nontoxic, and has been clinically applied, 2) the material is stable in properties, does not affect the activity of the drug, 3) it has sufficient mechanical strength to penetrate the skin without breaking, 4) it is widely applied, has strong plasticity, and 5) it can dissolve in the skin and control the release rate of the drug. Matrix materials for preparing the soluble microneedles can be classified into ductile materials and brittle materials according to mechanical properties of the materials. The ductile material has better flexibility and stronger plasticity, is not easy to break and fracture when preparing the microneedle, but the mechanical strength of the microneedle is insufficient, and cannot penetrate into skin for administration, such as polyvinyl alcohol (PVA), sodium carboxymethylcellulose (CMC-Na) and other materials, and the brittle material has good strength when preparing the microneedle, but the microneedle is easy to break due to over-brittleness when administering, such as polyvinylpyrrolidone (PVP), chondroitin Sulfate (CS) and the like. In addition to the mechanical properties of soluble microneedles, drug delivery efficiency, formability, stability, drug content are also indicators that must be addressed during the development of microneedle formulations. There is no prior art currently in the field of research directed to soluble microneedles which contain epinephrine. Therefore, it is necessary to develop an epinephrine-soluble microneedle, a preparation method and application thereof, and a transdermal patch which can solve the above technical problems. Disclosure of Invention The invention aims to overcome the defects of the prior art and provide an epinephrine soluble microneedle with higher administration efficiency, better mechanical property and formability and higher stability and drug content, a preparation method and application thereof and a transdermal patch. The invention is realized by the following technical scheme: The invention provides an epinephrine soluble microneedle, which comprises a needlepoint and a substrate, wherein the preparation raw materials of the needlepoint comprise, by weight, 10-25 parts of epinephrine compounds, 1-5 parts of polyvinyl alcohol (PVA), 1-5 parts of polyvinylpyrrolidone (PVP) and 30-50 parts of water; the substrate is prepared from, by mass, 10-30% of chondroitin sulfate compounds, 10-30% of dextran and 40-80% of water. As one embodime