JPH01299214A - Plaster - Google Patents

Abstract

PURPOSE:To obtain a plaster free from the evaporation of the drug component or the bleeding of the component to the back-side, without lowering the flexibility and the skin-following performance, by laminating a tacky adhesive layer containing a drug to an ethylene/vinyl acetate copolymer film having at least one saponified surface. CONSTITUTION:A tacky adhesive layer containing 0.001-50wt.%, preferably 0.1-30wt.% of a drug is laminated on an ethylene/vinyl acetate copolymer film having at least one saponified surface [preferably a film of 25-200mum thick having a saponified layer of 25-50mum thick (the saponification degree is >=60mol%, especially 90-100mol%)]. When the tacky adhesive layer is laminated to the non-saponified surface, the drug is partially transferred to the non- saponified layer and the evaporation of the drug and the bleeding of the drug on the back surface can be prevented by the saponified layer. Accordingly, the drug is retained in the non-saponified layer and continuously released over a long period.

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to a patch formed by laminating drug-containing adhesive layers.

<Prior Art> Various forms of adhesive patches, such as bags and plasters, have been developed in which a drug is contained in an adhesive and laminated with various supports. In addition, there are a wide variety of drugs to be included, from anti-inflammatory analgesics expected to have local effects to vasodilators expected to have systemic effects.

Since these patches are applied to the body's skin, flexible plastic films, non-woven fabrics, woven fabrics, etc. are usually used to prevent discomfort when applied.
Particularly, for application to bent parts such as elbow and knee joints, a support that has elasticity as well as flexibility and can conform to the skin is required.

<Problems to be Solved by the Invention> The adhesive layer constituting the above-mentioned patch contains a drug, and the desired pharmacological effect is exerted by releasing the drug onto the skin surface. The drug migrates into the support as well as toward the skin debris side. The drug that has migrated into the support diffuses through the support and sometimes evaporates from the back surface of the support. Therefore, the amount of drug in the adhesive decreases with time during storage, and the amount of drug necessary to exert a pharmacological effect may not be secured in the adhesive.

This tendency is noticeable in films made of ethylene/vinyl acetate copolymer, which are widely used as supports with high flexibility and stretchability, and a large amount of drug migrates, causing volatilization from the back of the support or Crystallization on the back surface is likely to occur.

Attempts to impart barrier properties to supports to which such drugs tend to migrate include laminating films with barrier properties and forming metal layers by vapor deposition, etc., but the flexibility of the supports It was difficult to say that it was a good support because of the lack of interlayers, such as lack of elasticity, inhibition of elasticity, and easy peeling of the laminated interface.

<Means for Solving the Problems> The present inventors have conducted extensive studies to prevent drug migration to the support and volatilization from the back surface of the conventional patch described above, and as a result, we have developed a saponified ethylene adhesive. The present inventors have discovered that by using a vinyl acetate copolymer as a support material, migration and volatilization of drugs can be suppressed without impairing the flexibility of the support, and the present invention has been completed.

That is, the present invention provides a patch comprising an ethylene/vinyl acetate copolymer film that has been saponified on at least one side, and an adhesive layer containing a drug laminated thereon.

Hereinafter, the present invention will be explained using the drawings.

FIG. 1 is an example showing the adhesive patch of the present invention.

The support 1 made of ethylene/vinyl acetate copolymer film is saponified on one side 1b to become a hydrophilic surface, and the saponified support layer 1b has a hydrophilic surface. A drug-containing adhesive layer 2 is laminated.

FIG. 2 shows another example of the adhesive patch of the present invention, in which a drug-containing adhesive layer 2 is laminated on the unsaponified support ff1a side.

The support 1 used in the present invention is made of an ethylene/vinyl acetate copolymer, and at least one side has been subjected to alkali saponification treatment. The saponification treatment is carried out with an alkali, and vinyl acetate resin) is
The surface becomes hydrophilic. From the viewpoint of speed of saponification treatment, it is preferable to use a 7μ solution of sodium alcoholade.

The thickness of the support 1 is 25 to 2 from the viewpoint of flexibility and skin conformability.
The thickness of the saponified layer is preferably 25 to 50 μm from the viewpoint of preventing drug migration, and one side, both sides, or the entire support is saponified. The degree of saponification may be partial or complete saponification, but from the viewpoint of preventing drug migration, it is preferably 607% or more, and practically 90 to 100%.

The drug-containing adhesive layer 2 laminated on the support 1 is not particularly limited as long as it is adhesive at room temperature and has skin adhesion, and may be natural rubber, synthetic rubber, acrylic resin, or vinyl resin. , silicone resin, etc. can be used as the base polymer. Among these, acrylic μ-based polymers are copolymerized with (meth)acrylic acid acrylate as a pace monomer and copolymerizable heptamers such as (meth)acrylic acid, vinyl acetate, vinylpyrrolidone, and (meth)acrylamide. Adhesives are preferred in terms of skin adhesion, drug solubility, drug release properties, and the like.

The above-mentioned adhesive may contain drugs that act locally or systemically, such as anti-inflammatory analgesics, hypnotic sedatives, tranquilizers, antihypertensives, antibiotics, anesthetics, antibacterial agents,
Vitamins, antiepileptics, vasodilators, antihinutamines, and other drugs can be selected at any time depending on the intended therapeutic use. These drugs are usually present in adhesives in amounts ranging from 0.001 to
It is contained in dissolved or dispersed state B (undissolved state) in an amount of 50% by weight, preferably in the range of 0.1 to 30% by weight.

In the patch of the present invention, the support 1 is saponified and made hydrophilic, and the saponified support layer 1b prevents the migration of the drug.
The drug contained in the substrate is completely prevented from migrating to the support 1. Therefore, the adhesive layer 2 contains the drug in the amount that was blended at the time of manufacture.

On the other hand, in the case of a patch structure as shown in FIG. 2, part of the drug in the adhesive layer 2 migrates to the unsaponified support layer 1a. However, volatilization of the drug from the back surface of the support and precipitation on the back surface are suppressed by the saponified support layer 1b. Therefore, the unsaponified support layer 1a serves as a kind of drug storage layer, and when a large amount of drug is contained in the adhesive layer 2, the excess drug is transferred to the unsaponified support layer l&. As a result, sustained release of the drug over a long period of time becomes possible, and a sustained pharmacological effect can be expected.

<Effects of the Invention> Since the adhesive patch of the present invention uses an ethylene/vinyl acetate copolymer film saponified on at least one side as a support as described above, the adhesive layer containing the drug can be transferred from the drug-containing adhesive layer to the support or The migration of the drug to the back side of the support can be suppressed, and in particular,
Loss of the contained drug such as volatilization or precipitation on the back surface can be prevented, and the desired pharmacological effect can be exhibited.

Since the ethylene/vinyl acetate copolymer film is saponified to partially render the support itself hydrophilic, the flexibility and skin conformability of the film are not impaired. Therefore, even when the adhesive patch of the present invention is applied to bent areas such as elbow and knee joints, it does not cause discomfort, and does not peel off during application.

<Example> Examples will be shown below to explain more specifically.

In addition, the following parts or % mean weight conversion values.

Example 1 155 parts of 2-ethylhexyl ester A, 30 parts of 2-methoxy acrylate f/L'Nute/L', 15 parts of vinyl acetate, and 0.3 part of azobisisobutyronitrile were placed in a flask. The polymerization reaction was carried out for about 10 hours by controlling the reaction temperature at 60 to 63°C while adding ethyl acetate dropwise under an inert gas atmosphere, and then aged for 2 hours at a temperature of 75 to 80°C to obtain an adhesive solution. I got it.

Add diclofenac sodium and citric acid to the obtained adhesive solution so that the solid content is 20% and 4%, respectively, mix uniformly, and apply this on a release liner to a thickness of 20 μm after drying. A drug-containing adhesive layer was prepared by coating and drying.

On the other hand, the vinyl acetate content is 18 mo/L'% and the thickness is 70 μm.
An ethylene/vinyl acetate copolymer film was immersed in a methano-μ solution of sodium thiewate for 1 hour at 40°C, and then washed three times with methano-μ and dried to form a support. An ethylene/vinyl acetate copolymer film saponified on both sides was prepared (thickness of saponified layer, 25 μm on one side).

A drug-containing adhesive layer was laminated on the support prepared above to obtain a patch of the present invention.

Example 2 An ethylene/vinyl acetate/L'# polymer film having a vinyl acetate content of 18 mol% and a thickness of 70 μm was immersed on only one side in a methanol solution of sodium methylate at 40° C. for 1 hour. Thereafter, the mixture was washed with methanol three times and dried to prepare an ethylene/vinyl acetate copolymer film saponified on one side as a support. (Thickness of saponified layer: 25 μm) The support prepared above was laminated with the drug-containing adhesive layer prepared in Example 1 to form a patch of the present invention.

Example 3 Fu/L//%/biprofen was added to the adhesive solution obtained in Example 1 to a solid content of 6.5% by weight, mixed uniformly, and placed on a release liner. A drug-containing adhesive layer was formed by coating and drying to a thickness of 40 mm after drying.

The above drug adhesive layer was laminated on the support obtained in Example 1 to prepare a patch of the present invention.

Comparative Example 1 A patch was prepared in the same manner as in Example 1, except that the support was an ethylene/vinyl acetate copolymer film that was not subjected to saponification treatment.

Comparative Example 2 A patch was prepared in the same manner as in Example 3, except that a polyvinyl chloride/I/(thickness: 150 μm) film was used as the support.

Comparative Example 3 Ethylene/vinyl acetate copolymer film without saponification treatment (vinyl acetate content 19 mol%, thickness 58 μm)
), the drug-containing adhesive layer prepared in Example 3 was laminated on the polyethylene side of a support formed by laminating a 7 μm thick polyethylene film to obtain a patch.

Comparative Example 4 Ethylene/vinyl acetate copolymer film without R7 treatment (vinyl acetate content 287μ%, thickness 60μ)
m) K. The drug-containing adhesive layer prepared in Example 3 was laminated on the polyethylene side of a support formed by laminating polyethylene films with a thickness of 10 μm to obtain a patch.

The patches obtained in Example 1.2 and Comparative Example 1 were tested for the stability of the drug over time, the state of crystallization of the drug on the back of the support, and the adhesion properties. Shown in Table 1.

Table 1 The measurement method for each characteristic shown in Table 1 is as follows.

[Durational stability]

Each sample piece cut into 5 pieces vertically and 3 pieces horizontally was cut into 6 pieces at a temperature of 40°C.
After storing for a month, each sample piece was extracted with methanol and quantified using high performance liquid chromatography.

The judgment criteria are as follows.

○...Residual rate 95% or more △...Residual rate 90% or more and less than 95% ×...Residual rate less than 9096 [Crystal precipitation state] Each patch was stored at a temperature of 40°C for 6 months, and crystal precipitation occurred. The condition was visually observed.

The criteria for judgment are as follows.

○...No crystals ×...Crystals [Skin adhesion] Vertical 5011. Each sample piece cut to a width of 3 am was applied to the human skin surface for 25 hours, and then the state of adhesion to the skin was visually observed.

The criteria for judgment are as follows.

○...Adhesive area 90% or more Δ...Adhesive area 50%
96 or more and less than 90% ×... less than 50% adhesive area The patches obtained in Example 1 and Comparative Example 1 were stored at a constant temperature of 40°C, and the transfer rate of the drug from the adhesive layer to the support was measured. Examined. The results are shown in Figure 3.

The drug was quantified by methanol extraction and high performance liquid chromatography.

Furthermore, the transfer rate of the drug to the support was also examined for the patches obtained in Example 3 and Comparative Examples 2 to 4 in the same manner as above, and the results are shown in FIG. 4.

[Brief explanation of the drawing]

Fig. 1 is a sectional view showing one example of the patch of the present invention, Fig. 2 is a sectional view showing another example of the patch of the invention, and Figs. 3 and 4 are example products and comparative example products. 3 is a graph showing the drug transfer rate to a support in FIG.

Claims (1)

[Claims] (1) A patch comprising an ethylene/vinyl acetate copolymer film that has been saponified on at least one side and an adhesive layer containing a drug laminated thereon.