KR-20260065815-A - Intraoral local application system

Abstract

A means is provided to shorten the onset time of action of local anesthetics, antihistamines, etc., on the oral mucosa. A microprotrusion patch comprising a substrate and microprotrusions standing on said substrate, the microprotrusion patch being made of a water-insoluble thermoplastic polymer material and intended for application to an oral mucosa, and a local application system for shortening the duration of drug action on an oral mucosa, comprising said microprotrusion patch, a topical agent (such as a gel or ointment containing a drug), and an adhesive tape for back reinforcement.

Inventors

• 취안, 잉수
• 다나카, 히로시
• 사이토, 미오
• 하세가와, 준야
• 가미야마, 후미오

Assignees

• 코스메드 파마소티컬 씨오 쩜 엘티디

Dates

Publication Date

20260511

Application Date

20240904

Priority Date

20230904

Claims (20)

1. A micro-protrusion patch comprising a substrate and a micro-protrusion standing on said substrate, A micro-protrusion patch made of a water-insoluble thermoplastic polymer material for application to the oral mucosa.
2. A micro-protrusion patch according to claim 1, wherein the tip diameter of the micro-protrusion is 10 μm to 300 μm, the length of the micro-protrusion is 50 μm to 1500 μm, and the thickness of the substrate is 20 to 1000 μm.
3. A micro-protrusion patch according to claim 1 or 2, wherein the density of micro-protrusions is 10 protrusions/cm2 to 1000 protrusions/cm2.
4. A micro-protrusion patch according to any one of claims 1 to 3, wherein the water-insoluble thermoplastic polymer material is selected from the group consisting of polyolefin, soft silicone, and polyurethane.
5. A micro-protrusion patch according to any one of claims 1 to 3, wherein the water-insoluble thermoplastic polymer material is selected from the group consisting of polyvinyl chloride, polyester, polyacetal, polylactic acid, lactic acid-glycolic acid copolymer (PLGA), and polyglycolic acid.
6. In any one of claims 1 to 5, The substrate has flexibility, and A micro-protrusion patch made of a water-insoluble thermoplastic polymer material having an elastic modulus of 5.0 x 10⁴ kgf/cm² or less.
7. A micro-protrusion patch described in any one of claims 1 to 6, and Equipped with adhesive tape, A micro-protrusion patch with adhesive tape attached, in which the micro-protrusion patch is back-reinforced by adhesive tape.
8. A micro-protrusion patch attached to an adhesive tape according to claim 7, wherein the adhesive constituting the adhesive tape contains a plasticizer.
9. An adhesive tape attachment micro-protrusion patch according to claim 7 or 8, wherein the adhesive constituting the adhesive tape contains a hydrophilic material.
10. A micro-protrusion patch attached to an adhesive tape according to claim 9, wherein the hydrophilic material is at least one selected from the group consisting of polyacrylic acid, hyaluronic acid and its sodium salt, carboxymethylcellulose and its sodium salt, polyvinyl alcohol, polyvinylpyrrolidone, dextrin, sodium chondroitin sulfate, collagen, and crosslinkers thereof.
11. An adhesive tape attachment micro-protrusion patch according to any one of claims 7 to 10, wherein the adhesive substrate constituting the adhesive tape is a foam.
12. An adhesive tape attachment micro-protrusion patch according to any one of claims 7 to 10, wherein the adhesive substrate constituting the adhesive tape is a nonwoven fabric.
13. A micro-protrusion patch described in any one of claims 1 to 6, and A local application system for shortening the duration of drug action on the oral mucosa, consisting of a topical agent.
14. An adhesive tape-attached micro-protrusion patch as described in any one of claims 7 to 12, and A local application system for shortening the duration of drug action on the oral mucosa, consisting of a topical agent.
15. A micro-protrusion patch described in any one of claims 1 to 6, and A local application system for shortening the duration of drug action on the oral mucosa, comprising a topical mixture.
16. An adhesive tape-attached micro-protrusion patch as described in any one of claims 7 to 12, and A local application system for shortening the duration of drug action on the oral mucosa, comprising a topical mixture.
17. A local application system according to claim 15 or 16, wherein the viscosity of the application mixture is 15 mPa·s to 300,000 mPa·s.
18. A local application system according to claim 13 or 14, wherein the drug included in the topical agent is a local anesthetic or an antihistamine, and is intended to achieve pain relief or itching suppression in a short time.
19. A local application system according to claim 16 or 17, wherein the drug included in the application mixture is a local anesthetic or an antihistamine, and is intended to achieve pain relief or itching suppression in a short time.
20. A local application system according to claim 18 or 19, wherein the antihistamine is selected from the group consisting of diphenhydramine and its salts, and chlorpheniramine and its salts.

Description

Intraoral local application system The present invention relates to a patch having micro-protrusions for local application to oral mucosa. Furthermore, the invention relates to a local application system using said patch. Dental local anesthetics are widely used, just like skin local anesthetics. (Gel) ointments using lidocaine or ethyl aminobenzoate are common drugs, but the onset of effect is 10 to 20 minutes, which is shorter than the onset of effect for the skin. However, there is a demand from both doctors and patients for the onset of action to occur in a shorter time. The inventors developed a microneedle array containing a local anesthetic for oral application and succeeded in achieving an anesthetic effect in a short time (Patent Document 1). Patent Documents 1 and 2 describe the invention of a skin microneedle preparation in which a local anesthetic is dissolved within microneedles, or a preparation in which a local anesthetic is applied to microneedles. From the perspective of a doctor, there is a desire for a new administration method that can be appropriately prepared and applied in the medical field, allowing for the self-administration of various familiar (gel) ointments and liquid formulations to achieve an effect in a shorter time. Figure 1 is a schematic diagram showing an adhesive tape-attached micro-protrusion patch manufactured in Example 1. The micro-protrusion patch of the present invention applied to the oral mucosa is water-insoluble. Since being water-insoluble means that the micro-protrusions do not dissolve or swell even when in contact with the oral mucosa for minutes to tens of minutes, being water-insoluble is a necessary condition for the material of the present invention. In addition, in the case of water-soluble micro-protrusions, when applied to the mucosa, the micro-protrusions are prone to swelling or dissolving due to moisture on the surface, and a phenomenon of reverse diffusion to the micro-protrusion area may occur simultaneously with the drug diffusing toward the mucosa. The material of the micro-protrusion patch of the present invention is a water-insoluble thermoplastic polymer material. Specifically, a micro-protrusion patch made of polyolefins such as polyethylene (0.3-1.2), polypropylene (1.1-1.5), and ethylene-propylene rubber (0.9-1.3), soft silicone, polyurethane, etc. is suitable. Here, the value in parentheses is the value of the tensile modulus (unit: 10⁴ kgf/ cm² ). These resins are relatively soft thermoplastic polymer materials and are characterized by being difficult to puncture the mucous membrane even when administered into the oral cavity. These thermoplastic polymer materials are characterized by having an elastic modulus of 1.5 x 10⁴ kgf/ cm² or less. Polyvinyl chloride, polycarbonate, polyester, 6-nylon, polyacetal, PS (polystyrene), PPS (polyphenylene sulfide), PAI (polyamideimide), PEEK (polyetheretherketone), PSU (polysulfone), polylactic acid, lactic acid-glycolic acid copolymer (PLGA), polyglycolic acid, etc. are rigid, and microprotrusions made from these materials are prone to puncturing the skin, but they can be used for this purpose. As a water-insoluble thermoplastic polymer material, it is also preferable to select from the group consisting of polyvinyl chloride, polyester, polyacetal, polylactic acid, lactic acid-glycolic acid copolymer (PLGA), and polyglycolic acid. These thermoplastic resins have an elastic modulus exceeding 1.5 x 10⁴ kgf/ cm² . In particular, polyethylene and polypropylene are more desirable as raw material resins for microneedles that have high biocompatibility, flexibility, and do not puncture the oral cavity. A micro-protrusion patch comprises a substrate and micro-protrusions standing upright on said substrate. More specifically, in the micro-protrusion patch, micro-protrusions are standing upright on a first surface of the substrate. In the micro-protrusion patch, it is preferable that the substrate and the micro-protrusions are integrally molded. That is, in the micro-protrusion patch, it is preferable that the substrate and the micro-protrusions are integrally molded made of a water-insoluble thermoplastic polymer. The thickness of the substrate is 20μm to 1000μm, preferably 20μm to 500μm, and more preferably 50μm to 300μm. If the thickness of the substrate is 20μm or more, it is easy to handle, and if it is 1000μm or less, it is easy to adhere to the oral mucosa with large irregularities. In addition, if the thickness of the substrate is 20μm or more and 500μm or less, it is more preferable because it fits well to the irregularities in the oral cavity due to the flexibility of the sheet. The length of the microprotrusion is preferably 50 μm to 1500 μm, and more preferably 100 μm to 1000 μm. In addition, to prevent deep puncture of the oral mucosa, the length of the microprotrusion is more preferably 500 μm or less. If the length of the microprotrusion is 50 μm or more, it is sufficient as a protrusion heig