Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Web – sheet or filament bases; compositions of bandages; or...
Reexamination Certificate
1999-08-11
2001-07-31
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Web, sheet or filament bases; compositions of bandages; or...
C424S443000, C424S449000
Reexamination Certificate
active
06267983
ABSTRACT:
This application is a 371 of PCT/JP98/04850 Oct. 26, 1998.
TECHNICAL FIELD
The present invention relates to a transdermal or dermatological patch (i.e., the so-called a sticky plaster) where an adhesive layer containing a pharmaceutical agent is formed on a substrate, to a substrate sheet therefor, and to a method for the manufacture of the substrate sheet.
More particularly, the invention relates to a sticky transdermal patch in which transfer of the pharmaceutical agent to the substrate sheet does not occur, adhesion between the adhesive layer and the substrate is strong resulting in no so-called residual paste when applied to and then detached from skin, the constituting films in the substrate sheet consisting of layered film are strongly adhered each other, no stickiness on the surface is noted, and texture, smoothness and fitting to skin are all good and also relates to a substrate sheet therefor as well as to a method for manufacturing the substrate.
BACKGROUND OF THE INVENTION
A sticky transdermal patch in which an adhesive containing a pharmaceutical agent such as skin stimulating agent, anti-inflammatory agent, analgesic, etc. is layered on a substrate sheet has been widely used as a transcutaneous agent in the medical field already. In such a patch, it has been known, as described in JP-A-54-138124, that copolymer of a diene type, particularly, a block copolymer of a diene type is suitable as an adhesive because, when applied the patch for skin, it shows good adhesion and fitness to skin and an appropriate elasticity and, further, it does not irritate the skin upon removal but can be easily detached.
On the other hand, as a substrate sheet for the transdermal patch as mentioned above, a vinyl chloride resin which is soft and flexible fitting the skin is suitable. On the contrary, however, a sheet of the vinyl chloride resin has poor affinity for the block copolymer of a diene type as an adhesive and, particularly in the case of patch, the copolymer of a diene type as an adhesive contains higher fatty acids, liquid paraffin, and the like as plasticizers together with the pharmaceutical agents whereby its affinity for an adhesive is more inferior.
As a result, when an adhesive consisting of a block copolymer of a diene type is directly and just applied to the substrate sheet made of a vinyl chloride resin to prepare a patch, there is a disadvantage that an adhesion of the adhesive to the substrate sheet is inferior.
Moreover, when a transdermal patch has a substrate sheet formed of polyvinyl chloride resin and contains a pharmaceutical agent which has a strong property of diffusion and permeation, the pharmaceutical agent permeates and diffuses into the substrate sheet as well so that the substrate sheet is swollen and deteriorated. In some cases, the desired therapeutic effect is reduced. It is of course possible that an appropriate primer treatment is applied to the sheet of the vinyl chloride resin so that the affinity for the block copolymer of a diene type is improved. However, in that case, the plasticizer contained in the vinyl chloride resin sheet transfers to the adhesive layer so that the property of the adhesive is deteriorated.
Under such circumstances, the present inventors had already found that, when a soft vinyl resin film containing a plasticizer is adhered to a polyethylene terephthalate film to prepare a composite film and an adhesive layer comprising a block copolymer of a diene type containing a pharmaceutical agent is formed on the side of the polyethylene terephthalate film of the composite film, the olyethylene terephthalate functions as a barrier layer for the plasticizer and the pharmaceutical agent. Thus, there is neither transfer of the pharmaceutical agent to the substrate sheet nor transfer of the plasticizer to the adhesive layer.
However, even in such a transdermal patch, the plasticizer contained in the film of the vinyl chloride resin bleeds onto its surface resulting in stickiness of the surface. In addition, when the composite film is wound up in a roll, such a bleeding of the plasticizer onto the surface of the vinyl chloride resin film transfers to the polyethylene terephthalate film so that adhesion of the adhesive containing the pharmaceutical agent to the polyethylene terephthalate film becomes low.
In view of the above and for coping with the above-mentioned problems in the known transdermal patches, the present inventors proposed a transdermal patch in JP-A-5-65486 where polyethylene terephthalate film is adhered and layered to a film formed of a polyvinyl chloride-polyurethane composite (which may contain a polyester plasticizer) to prepare a substrate sheet and an adhesive layer comprising a styrene-diene-styrene block copolymer containing a pharmaceutical agent is formed on the side of the polyethylene terephthalate film of the substrate sheet.
In such a transdermal patch, the polyethylene terephthalate film functions as an effective barrier layer both to the plasticizer and the pharmaceutical agent. Accordingly, neither transfer of the pharmaceutical agent to the substrate sheet nor transfer of the plasticizer to the adhesive layer takes place. In addition, stickiness of the surface by bleeding of the plasticizer onto the film surface does not occur and, texture and fitting to skin are good as well.
However, when the composite film of polyvinyl chloride-polyurethane composite, which is a main constituent of the substrate sheet of the transdermal patch, is manufactured by a calendar process of the polyvinyl chloride-polyurethane composite, the composite has not good calendar processing property, but it forms such a film on the rolls which is often hardly removed from the rolls, whereupon not only the yield is poor but also the resulting film has poor gloss or luster whereby the commercial value is reduced.
Further, when the resulting polyvinyl chloride-polyurethane composite film is stored in a rolled state during the manufacturing steps for the transdermal patch of the invention, the so-called “blocking” where the film sticks each other occurs. Therefore, in the manufacture of a transdermal patch by pulling out (i.e., by rewinding) the polyvinyl chloride-polyurethane composite film from the roll followed by subjecting to various processes thereto, a lot of inconveniences are resulted whereby its smooth manufacture is disturbed.
As a further point, when a polyethylene terephthalate film is adhered to the polyvinyl chloride-polyurethane composite film to prepare a substrate sheet and an adhesive layer containing a pharmaceutical agent is formed on the surface of the substrate sheet to prepare a transdermal patch, adhesion between the polyvinyl chloride-polyurethane composite film and the polyethylene terephthalate film is not sufficient and various inconveniences are unavoidable. For example, when such a patch is applied to and then removed from the skin, the adhesive layer is detached from the polyvinyl chloride-polyurethane composite film together with the polyethylene terephthalate film remaining on the skin whereby the so-called “residual paste” (the first residual paste) is resulted. In addition, interlayer detachment may occur in the substrate sheet during storage whereby the commercial value of the product is significantly deteriorated.
Moreover, adhesion between the adhesive layer and the substrate sheet is weak. Thus, when such a patch is applied to and then removed from the skin, the “residual paste” (the second residual paste) may also take place.
In order to solve the latter one in the above-mentioned problems or in order to improve the adhesion between the adhesive layer and the substrate sheet, it is possible, as described in JP-A-6-35381, that various primers are applied onto the polyethylene terephthalate film so that the substrate and the adhesive are strongly adhered. However, some pharmaceutical agents may result in an undesirable interaction with the primers whereby the primer layer and the adhesive layer turn yellow or other color. That significantly lower the commercial value of the product as well.
Th
Fujii Kimihiro
Ikawa Kazuya
Ikeura Yasuhiro
Tanaka Kazuo
Yamasoto Shinji
Bando Chemical Industries Ltd.
Howard S.
Merchant & Gould P.C.
Page Thurman K.
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