JPH02250824A - Application agent for external use - Google Patents

Abstract

PURPOSE:To obtain an application agent for external use excellent in persistence of drug effects for a long period by containing a percutaneous drug, such as nitroglycerol, in a pressure-sensitive tacky agent, holding the resultant tacky agent in a hardly permeable substrate for application and covering parts other than a part applied to the skin with the substrate. CONSTITUTION:An application agent for external use, obtained by holding a pressure-sensitive tacky agent 1 containing a percutaneous drug and successively releasing the drug in a holding part 3 provided in a substrate 2 hardly permeating the drug for application and then covering parts other than a part where the pressure-sensitive tacky agent is applied to the skin in contact therewith with the substrate 2 and capable of sufficiently holding the tacky agent containing the drug and sustaining the drug effects for a long period. Furthermore, edge parts 5 are preferably provided adjacent to the holding part 3 in the sheet-like substrate 2. A separator 6 (without absorbing the contained drug) may be peelably applied to the part of the pressure-sensitive tacky agent applied to the skin. Alternatively, a detachable cover 8 for covering the substrate 2 from the outside may be provided. Thereby, effects of treatment and prevention are produced by the simple structure.

Description

DETAILED DESCRIPTION OF THE INVENTION [Object of the Invention] The present invention relates to an external patch (2) that is applied to the skin and administers a drug transdermally.

Conventionally, vasodilatory therapy has been known as a treatment for angina pectoris, and nitroglycerin has been used in the form of injections or sublingual tablets, but intravenous injections are not sufficient to treat angina in time. Since the active ingredient in sublingual tablets tends to evaporate, they are packed in small containers or two, but when I have an unsteady attack at hand, I don't like to use these small sublingual tablets, and both of them are difficult to handle during sleep. There is nothing that can be done to prevent attacks from occurring. Therefore, by administering this transdermally, the duration of the effect can be extended,
There are attempts to treat or prevent attacks.

As such a method, the applicants have dispersed and supported nitroglycerin in a pressure-sensitive adhesive, and depending on the composition of the adhesive,
A drug that can be administered transdermally by controlling the action of holding the drug in the adhesive and the action of releasing it, and releasing the drug in an appropriate amount from the pressure-sensitive adhesive. was provided first.

The pressure-sensitive adhesive containing this drug is applied to a sheet-like base material of an appropriate shape that does not allow the drug to pass through, and is applied directly to the skin. a large amount is released over a long period of time,
It is desired that the drug be administered.

In order to prolong the duration of this effect, the applicant first increased the drug content in the adhesive, which resulted in the adhesive carrying the drug while maintaining appropriate drug retention and release properties. There was also a certain limit to the amount that could be done. In addition, it was possible to increase the transdermal dose per unit time by increasing the adhesive area of the adhesive on the skin, but it was found that this is not a very effective method for prolonging the duration of the adhesive.

Therefore, we decided to increase the amount of coating per unit area on the base material, that is, increase the thickness of the adhesive layer.We conducted various tests on this and found that it was possible to release and administer the drug in total and for a long time. It was found that increasing the thickness of the 5-adhesive layer was an effective means because it was possible to increase the length of the adhesive layer. However, when the adhesive layer is gradually thickened,
When applied to the skin, the adhesive protrudes outward from the edge of the base material, and the drug contained therein is released outwards, reducing its efficacy, and the extruded adhesive adheres to underwear, underwear, etc. It is not easy to use, and even when the part to be applied to the skin is covered with a release separator and stored, the adhesive may come out from between the base material and the separator. My clothes also look suspicious.

[Structure of the invention]

In the present invention, a pressure-sensitive adhesive that contains a transdermal drug and releases it sequentially is held in a patch base material that does not easily allow the drug to pass through, and the pressure-sensitive adhesive is applied in contact with the skin. By covering the area other than the area to be applied with the base material, the adhesive containing the drug is sufficiently retained and the medicinal effect is maintained for a long time.

In the following examples, a transdermal drug that penetrates through the skin, such as the above-mentioned nitroglycerin, is contained in a pressure-sensitive adhesive, and this adhesive retains the contained drug, And it can sequentially release it to the outside.

The pressure-sensitive adhesive (1) with this agent has a square, rectangular, round, oval, triangular, diamond, polygonal shape.

Sheet-like base material in heart shape or other appropriate shapes (2)
The holding part (8) provided on the holder (8) carries the ζ2 sufficiently, and the parts other than the part (4) to be adhered to the skin are covered with the above-mentioned base material, and in the case shown in the figure, the base material has an edge (5).・This pressure-sensitive adhesive has a thickness of approximately 30μ in the holding part (=), whereas the thickness of the conventional adhesive layer is approximately 30μ. Grade, special C: preferably about 60-1
The thickness is approximately 0θμ, but depending on the case, the thickness may be greater than the above thickness. Further, the area of the part where this is adhered to the skin is usually about 10 to 100 cd, but it is determined to be an appropriate size depending on the drug used, taking into account the dosage per unit time, etc.

The above-mentioned base material is preferably one that does not easily allow the drug held by the adhesive to pass through and does not act on the drug and adversely affect its release properties, such as polyester, polyvinyl chloride, other plastic films, paper, cloth, etc. , various laminates can be used as appropriate; in the case of nitroglycerin, polypropylene.

A polyolefin film such as polyethylene, aluminum foil, a laminate film of aluminum foil, etc. are suitable (- can be used.) The above-mentioned adhesive can be applied to the base material, applied dropwise to suppress it, or held in any other suitable manner. In some cases, a holding step may be provided in advance on the base material.

The above-mentioned pressure-sensitive adhesive can adjust its affinity for the drug it contains by adjusting the adhesive base, tackifier resin, softener, filler, anti-aging agent, and other components and their blending ratio. A balance can be achieved between drug retention and release. For example, when the drug is nitroglycerin, natural rubber, isoprene rubber, isobutylene rubber, or diene rubber containing styrene as a copolymer component may be used alone or in combination as the adhesive base. When a natural rosin containing abietic acid as a main component or one having a polar group such as hydrogenated U-ginglycerin ester or pentaerythritol ester is added as a tackifying resin to this, the tackifying resin having an ester group as a polar group is added. has an affinity with nitroglycerin, and the rubber component of the base has poor affinity, so its retention and release properties can be adjusted by adjusting the blending ratio of the two.
Usually, the resin is used in an amount of about -200 to 200 parts based on 100 parts of the base. Furthermore, petroleum-based tackifying resins having an alicyclic structure that do not have polar groups have poor affinity with nitroglycerin, so if they are used in combination with those having the above-mentioned polar groups, the release properties of the drug can be controlled. Furthermore, if a softener having a polar group or a softener having no polar group is appropriately used, further fine adjustment can be achieved.

The above transdermal drugs (2) In addition to the above-mentioned nitroglycerin, scoloboramine (analgesic)% clonidine (antihypertensive agent),
Tetranaipurin, penicillin, chloramphenicol and other antibiotics, 3-(-monoaminopropyl)indole acetate and other psychoactive agents, thioprobazate hydrochloride and other nerve stabilizers, phenobelpital.

pentaberbital sodicum, codeine, caripromal and other sedatives and hypnotics, adrenocorticosteroids (cortisone, cortisol, triandinolone)
Other hormones, androgenic steroids (methyltestosterone, etc.), nysterogen steroids (estrone, ethinylestradiol, etc.), progestational steroids (methoxyprogesterone acetate, 79-norprogesterone, norethindrone, etc.),
These include thyroxine, aspirin, salicylamide and other antipyretics, atrobin, methscobol aminobromide and other anticonvulsants, deraminoquinoline, pyrimethamine and other antimalarials. In addition, for drugs that cannot be transdermally administered alone, they should be dissolved in transdermal and pharmaceutically acceptable solvents such as glycerin, hexacal, alcohols, aldehydes/ketones, esters, and other solvents. be able to.

When the crystal is applied to the skin, it adheres firmly to the adhesive (2), and the drug is gradually released from the adhesive and administered through the skin, continuing to release the drug over a long period of time. Because the outside is covered with the base material,
The adhesive is sufficiently retained, the drug content is increased, and even if the adhesive is somewhat soft, it can be sufficiently supported, and the adhesive does not come out due to external force.

In FIG. 2, a removable separator (6) is shown to cover the area where the adhesive is applied to the skin. This separator is preferably one that prevents the chemicals in the adhesive from migrating over time, and is usually made of polyethylene, polypropylene, polyester, other plastic films, aluminum foil bags, laminates, etc., and is treated with a peeling process such as silicone treatment. Those subjected to this can be suitably used. Items with this separator pasted are convenient for storage, and depending on the type of drug, they may also be laminated with aluminum foil,
It is best to enclose it in a bag made of plastic film, etc.

Fig. 3 shows a dome-shaped holding part of the base material, and Fig. 9 shows a grip part (7) on a part of the edge of the base material.
) is shown. This pick piece is convenient for separating it from the separator and peeling it off from the skin after use (=
Can be used.

The one in Figure 5 uses a thin and soft plastic sheet as a sheet-like base material, and then a laminate of aluminum foil or other rigid material is placed on top of it.
By surrounding it with a separator (6), it is possible to prevent the medicine from deforming. Also, if necessary, cover
Preservation can be made even more reliable by attaching a drug-free adhesive between the container and the separator. When using this, remove the cover and separator and apply it to the skin (-).In addition, on each side, an adhesive that does not contain any drug and can be applied to the skin is required at the edge of the base material. Depending on the application, edgeless substrates can also be used.

〔Effect of the invention〕

According to the present invention, as described above, it is possible to sufficiently and reliably hold a pressure-sensitive adhesive containing a transdermal drug, and there is no need for a complicated structure such as a drug release control membrane. Since it is possible to continue releasing an effective and appropriate amount of the drug directly over a long period of time, the effectiveness of treatment and prevention can be increased.

[Brief explanation of drawings]

The drawings show the embodiment of the present invention in an enlarged manner, and FIG. 7 is a sectional view, and FIGS. The figure is a sectional view of another example. (1) Drug-containing adhesive, (2) Base material, (3) Holding part, (
5) Edge, (6) Separator% (8) Cover

Claims (1)

[Scope of Claims] 1. A holding part that contains a transdermal drug and is provided with a pressure-sensitive adhesive that can control the retention and release of the drug on a sheet-like base material that is difficult for the drug to permeate. A patch for external use, wherein the pressure-sensitive adhesive is placed on the skin and covered with the base material except for the part to be applied to the skin. 2. The external patch according to claim 1, wherein an edge portion is formed on the sheet-like base material adjacent to the holding portion. 3. The external patch according to claim 1, wherein the pressure-sensitive adhesive is coated with a separator that does not or does not easily absorb the contained drug and is removably attached to the part of the pressure-sensitive adhesive that is applied to the skin. 4. The sheet-like base material is made of a thin and flexible material, and has shape retention properties that cover the base material from the outside to prevent deformation.
The external patch according to claim 3, further comprising a removable cover. 5. The external patch according to claim 4, wherein a patch not containing a transdermal drug is interposed between the cover and the separator.