JPS6130517A - Application drug for mucosa consisting of multilayer structure - Google Patents

Abstract

PURPOSE:The titled pharmaceutical, having a mucosa adhesive film and an adhesive coated sheet in a laminated structure, capable of controlling the release of a chemical, preventing the swelling of the application drug by water permeated from the outer edge parts, and having improved adhesive property. CONSTITUTION:An application drug obtained by applying an adhesive 3, e.g. rubber based adhesive, acrylic adhesive or silicone based adhesive, containing a chemical or no chemical onto a base material 1, e.g. collagen, paper or PE film, and laminating a filmy mucosa adhesive 4, e.g. carboxymethyl cellulose (CMC), hydroxyethyl cellulose or gelatin, containing the chemical or no chemical, to the formed sheet. The adhesive coated sheet part larger than the mucosa adhesive layer is capable of suppressing the swelling of the outer edge parts in application and improving further the adhesive property. A chemical for treating aphtha in the mouth, inhibitor for toothache, remedy for angina pectoris, etc. is used as the chemical, and mainly applied to the mucosa of the oral cavity, pudendum part, etc.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to therapeutic or analgesic mucosal patches.

Prior Art Conventional oral mucosal patches (e.g., JP-A-58-2137
No. 09), a drug is encapsulated in a mucoadhesive made of a water-soluble or water-swellable polymer, but depending on the properties of the drug, the release from the mucoadhesive may be too fast or slow. There were some points where it was too much and difficult to control. In addition, when the patch is applied to mucous membranes, a large amount of moisture is absorbed from the cross section of the side edges of the patch, which causes the edges to swell into a crown shape and easily peel off from there. Ta.

Purpose of the Invention When a mucosal patch is attached to a mucous membrane, water in secretions such as saliva penetrates into the mucoadhesive film and releases the drug, but depending on the type of drug, it is difficult to control the release. becomes. The purpose of the present invention is to optimize the control of drug release by forming a laminated structure of a mucoadhesive film and an adhesive-coated sheet, that is, to achieve appropriate sustained release of drugs, and at the same time, to prevent swelling due to moisture. The purpose of this invention is to prevent the adhesive-applied sheet portion from concentrating on the end sides of the mucosal patch from blistering in a crown shape and becoming easy to peel off by making the adhesive-applied sheet portion larger than the mucosal adhesive film.

Structure of the Invention The present invention provides: (1) A sheet formed by applying an adhesive selected from the following Group B containing or not containing a drug to a base material consisting of one type selected from the following Group A; Or, a patch for mucous membranes laminated with a film-like mucosal adhesive selected from Group C below.

A: Collagen, paper, nonwoven fabric, cloth, polyethylene film, polypropylene film, polyvinyl chloride film, polyvinylidene chloride film, polyethylene terephthalate film, nylon film, urethane film, laminates and foams of these films B: Rubber adhesive adhesives, acrylic adhesives, silicone adhesives, vinyl ether adhesives and other adhesives C: carboxymethyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, gelatin,
casein, gum arabic, gum karaya, sodium alginate, alginate alkyl ester, polyacrylic acid ester, sodium polyacrylate, polyvinylpyrrolidone,
Polyvinyl alcohol and other water-soluble adhesives.

(2) The patch for mucous membranes according to claim 1, wherein the adhesive coated sheet portion is larger than the mucosal adhesive layer.

(3) A patch for mucous membranes according to claim 1, in which a separator is pasted on an adhesive. □ As mentioned earlier, when a mucosal patch is attached to the mucous membrane,
The swelling effect of water in the secreted fluid makes it difficult to control the release of some drugs. Therefore, in this case, the release of the drug is controlled by holding the drug in a water-insoluble rubber adhesive, acrylic adhesive, etc., which is different from a hydrophilic mucoadhesive film.

The present invention will be explained in more detail (Drug) The drug contained in the adhesive and the drug contained in the film-like mucoadhesive may be the same or different. Medications suitable for various purposes can be used, such as oral aphrodisiac treatment agents, toothache suppressants, and angina treatment agents.

(Separator) As a separator to be used as necessary, silicone-treated films and sheets [polyethylene, laminated paper,
Clay coated paper, polyethylene film, polypropylene film, polyethylene terephthalate film, aluminum laminates thereof, etc.) are used.

If necessary, the patch for mucous membranes of the present invention may be coated with an undercoat before the adhesive is coated on the base.

This preparation is mainly applied to mucous membranes such as the oral cavity and vulva, and in particular, as shown in Figure 2, the adhesive layer exposed around the mucosal adhesive is applied to the outer edge of the mucosa when applied. By suppressing the swelling of the parts, the adhesion can be further improved than in the case shown in FIG. In this case, as shown in FIG. 3 or 4, a separator is pasted on top of the adhesive.

Figure 5 shows an example of storage in an aluminum pack.

(Example) The present invention will be described below with reference to Examples, but the present invention is not limited thereto.

Example 17 Mucosal patch for lid treatment Raw natural rubber 1. Ogt! :n-hexane 72g,
It is put into a mixed solvent consisting of toluene Log and allowed to swell. Furthermore, 1.5 g of polybutene HV, -300 (Nippon Petrochemical) was added to petroleum-based alicyclic resin [Finton 13-17
0 (Nippon Zeon)] as an antiaging agent and 0.1 g of dibutylhydroxytoluene [Swanox BH, T (Seiko Chemical)] as a dispersant. Add a solution of 0.1 g of polyethylene glycol 2000 dissolved in 8 g of toluene by heating and stir well. After dissolving 0.022 g of betamethacin valerate in 4 g of acetone, a solution of 0.022 g of betamethacin valerate dissolved in 4 g of acetone is added and further stirred to form a uniform sticky liquid. The pressure-sensitive adhesive sheet is coated on the top at a rate such that the adhesive thickness after solvent volatilization is 60 g/ra, and the solvent is volatilized to form a pressure-sensitive adhesive sheet.This sheet 1d contains 6 μg of betamethacin valerate.This sheet has a diameter of 1 It was punched into a 13an circular shape.

On the other hand, 10 g of hydroxypropyl cellulose was added to 1 part of distilled water.
Betamethacin valerate is dissolved in 0.00g and 0.01
A solution of 2 g dissolved in 1 g of acetone is added, stirred well, and coated on a glass plate at a rate such that the coating amount after drying is 50 g/m, and dried to form a film. This film was peeled off from the glass plate, punched out into a circular shape with a diameter of 0.95 Cl11, and laminated concentrically onto the above-mentioned pressure-sensitive adhesive sheet punched product to obtain a patch for mucous membranes.

1 sheet of main rules (1d) contains 10g of betamethacin valerate
Contains g.

When this patch was applied to old odor, the outer edge did not swell and did not peel off naturally for 48 hours.
After removal, white anemic spots due to the vasoconstrictive action of corticosteroids were observed at the application site. In addition, when betamethacin valerate was not added to the adhesive layer but was added only to the mucoadhesive film, no anemic spots were observed after 24 hours.

Example 2 Mucosal patch for toothache suppression 2-ethylhexyl acrylate 80g, vinyl acetate 1
0 g, 6 g of methyl acrylate, 4 g of acrylic acid and 200 g of ethyl acetate as a solvent, and 0.2 g of benzoyl peroxide.
Polymerization was carried out at 60° C. for 12 hours in the presence of g. The obtained copolymer was purified, 20 g of the purified copolymer was dissolved in 80 g of ethyl acetate, and 13 g of indomethacin was dissolved in 40 g of acetone.
A solution prepared by heating and dissolving the mixture in g was added and stirred. After evaporation of the solvent, this adhesive liquid was applied to the skin surface of the urethane foam so that the solid content was 50 g/d and dried.

Next, 20 g of sodium alginate and 36 g of n-octadecyl bromide were added to 200 g of toluene at 100° C. under a stream of oxygen.
After reacting for 8 hours, the contents were poured into n-hexane.
Purification gave n-octadecyl alginate (yield: 36
g). 10 g of this n-octadecyl alginate was dissolved in 100 g of distilled water, and this was applied onto a glass plate so that the coating amount after drying was 20 g/m 2 and dried. This film was punched out to a diameter of 1 oc'm, and the above-mentioned pressure-sensitive adhesive sheet was laminated thereon, and the film was laminated concentrically on top of the circular die-cut sheet having a diameter of 1.13 cm.

Motoichi ld contains 3 mg of indomethacin Q. Crystal adheres well to mucous membrane surfaces wet with saliva, such as gums and old odor, and there is no swelling of the surrounding area due to water entering through the cut surface of the mucoadhesive film, and no natural peeling due to this.
It did not peel off naturally for 48 hours after application, and it effectively suppressed toothache after tooth extraction.

Effects of the Invention Since the patch for mucous membranes of the present invention has a multilayer structure by providing an adhesive layer, drug release can be controlled by selecting an adhesive according to the properties of the drug. Swelling due to moisture infiltration from the outer edge was suppressed, and adhesion was improved.

[Brief explanation of drawings]

1 to 5 are cross-sectional views of the patch for mucous membranes of the present invention. In FIGS. 1 to 5, 1 represents a base material, 2 represents an undercoat, 3 represents an adhesive, 4 represents a mucosal adhesive, 5 represents a separator, and 6 represents an aluminum pack. Applicant Nichiban Co., Ltd. (and 1 other person) Agent: Patent Attorney Minoru Isaka Figure 1 Figure 2 Figure 3 Figure 4rjA Figure 5

Claims (3)

[Claims] (1) A sheet formed by applying an adhesive selected from Group B below containing or not containing a drug to a base material consisting of one type selected from Group A below, and a sheet formed by applying an adhesive selected from Group B below containing or not containing a drug to a base material consisting of one type selected from Group A below. A patch for mucous membranes laminated with selected film-like mucoadhesives. A: Collagen, paper, nonwoven fabric, cloth, polyethylene film, polypropylene film, polyvinyl chloride film, polyvinylidene chloride film, polyethylene terephthalate film, nylon film, urethane film, laminates and foams of these films B: Rubber adhesive adhesives, acrylic adhesives, silicone adhesives, vinyl ether adhesives, and other adhesives. C: Carboxymethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, gelatin, casein, gum arabic, gum karaya, sodium alginate, alkyl alginate, polyacrylic ester, sodium polyacrylate, polyvinylpyrrolidone, polyvinyl alcohol, and other water-soluble adhesives. (2) The patch for mucous membranes according to claim 1, wherein the adhesive coated sheet portion is larger than the mucosal adhesive layer. (3) The patch for mucous membranes according to claim 1, wherein a separator is pasted on the adhesive.