(19) Japanese Patent Office (JP)
`(12) Kokai Unexamined Patent Application Bulletin (A)
`(11) Laid Open Patent Application No.
`
`59-184121
`(43) Publication Date
`
`October 19, 1984
`Number of Claims
`
`1
`
`Number of Pages
`
`3
`
`Examination Request
`
`not yet made
`
`
`(51)
`
`
`Int. Cl.3
` A61K 9/70
`//A61K 31/355
`
`Identification Code
`
`
`
`Internal File No.
`7057-4C
`
`(54) Acrylic Plaster
`
`
`
`
`
`
`
`(21) Application No.:
`
`58-57689
`
`(72)
`
`Inventor:
`
`(22) Application Date: March 31, 1983
`
`(72)
`
`Inventor:
`
`(72)
`
`Inventor:
`
`
`
`SASAKI, Hiroaki
`Nitto Electric Industry Co., Ltd.
`1-1-2 Shimohodumi,
`Ibaraki-shi
`HORIUCHI, Tetsuo
`
`
`SPECIFICATION
`1. Title of the Invention
`Acrylic Plaster
`2. Claims
`(1) An acrylic adhesive plaster characterized
`by blending at least one tocopherol selected from
`tocopherols with a plaster comprising an acrylic
`adhesive substance.
`(2) The plaster recited in claim (1), wherein a
`drug is further blended therewith.
`(3) The plaster recited in claim (1), wherein the
`drug has at least one of a phenolic hydroxyl group
`and an amino group.
`3. Detailed Description of the Invention
`to an
`The present
`invention
`relates
`improvement of a plaster comprising an acrylic
`adhesive substance.
`the
`to
`Conventionally, drugs administered
`epidermis were drugs that were intended to act
`locally on the epidermis or tissues therebelow,
`such as bactericides, disinfectants and skin
`stimulants. Recently, however, attempts have been
`made to administer drugs having systemic effects
`via the epidermis, and there have been proposals
`of, or attempts at, epidermal administration of
`various drugs.
`Epidermal drug administration is, for example,
`performed in the form of an adhesive patch
`
`
`
`
`
`
`
`Nitto Electric Industry Co., Ltd.
`1-1-2 Shimohodumi, Ibaraki-shi
`SAWAGUCHI, Mareyoshi
`Nitto Electric Industry Co., Ltd.
`1-1-2 Shimohodumi, Ibaraki-shi
`Nitto Electric Industry Co., Ltd.
`1-1-2 Shimohodumi, Ibaraki-shi
`Patent Attorney, TAKASHIMA,
`Hajime
`
`(71)
`
`(74)
`
`Applicant:
`
`Agent:
`
`
`
`
`
`
`
`preparation, in which a drug is blended with a
`plaster comprising an adhesive substance; but if a
`preparation in which a drug is blended with a
`plaster comprising an acrylic adhesive substance
`is stored for a long period of time, there is a
`tendency
`for
`the
`therapeutic effect of said
`preparation
`to be greatly
`reduced due
`to
`breakdown and dissipation of the drug and the like.
`Here, it is possible to prevent the dissipation
`and photodecomposition of the drug by way of
`sealing and light shielding with aluminum laminate
`packaging or the like, but with drugs blended with a
`plaster comprising an adhesive substance as
`described above, and especially phenolic hydroxyl
`group-containing compounds, amine compounds
`and the like, breakdown of the drug will still
`proceed, even with aluminum laminate packaging,
`and there are more than a few drugs that cannot
`withstand usage involving storage for two to three
`years. In particular, there is a marked content loss
`over time with compounds having a phenolic
`hydroxyl group or an amino group, such as salicylic
`acid derivatives such as methyl salicylate and
`monoglycol salicylate, which are anti-inflammatory
`analgesic agents, skin stimulants such as
`capsaicin, nonyl vanillylamide
`
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`and chili extract, and ethanolamine based
`antihistamines such as diphenhydramine.
`As a countermeasure, BHA, BHT, gallic acid
`esters and the like are added to such preparations,
`but sufficient stabilizing effects are not produced,
`and usage thereof is being progressively restricted
`in view of safety matters, such as carcinogenicity.
`Accordingly,
`there
`is a demand
`for
`the
`development of a plaster comprising an acrylic
`adhesive substance or an adhesive patch
`preparation, with which, if a drug is blended therein,
`breakdown of said drug will not progress.
`Under such circumstances,
`the present
`inventors undertook various investigations and
`discovered that, if a tocopherol is blended in a
`plaster comprising an acrylic adhesive substance,
`if a drug is blended in said plaster, the drug will be
`stably present without breaking down.
`The present invention was completed on the
`basis of such new knowledge, and relates to an
`acrylic adhesive plaster resulting from blending a
`tocopherol with a plaster
`for adhesive patch
`preparation comprising an acrylic adhesive
`substance, and to a plaster obtained by blending a
`drug
`therewith, namely an adhesive patch
`preparation.
`There are no particular limits on the acrylic
`adhesive substance so long as it is a material
`which has been conventionally used or proposed
`as a plaster for acrylic adhesive patch preparations,
`and examples thereof include acrylic compositions
`such as copolymers of one or two or more
`(meth)acrylic acid esters, such as n-butyl
`(meth)acrylate, hexyl (meth)acrylate, 2-ethylbutyl
`(meth)acrylate,
`isooctyl
`(meth)acrylate,
`2-methoxyethyl
`(meth)acrylate,
`2-ethylhexyl
`(meth)acrylate, decyl
`(meth)acrylate, dodecyl
`(meth)acrylate, and tridecyl (meth)acrylate, and a
`functional monomer that can be copolymerized
`with said ester, such as (meth)acrylic acid, itaconic
`acid, maleic acid, maleic anhydride , hydroxyethyl
`acrylate, hydroxypropyl acrylate, acrylamide,
`dimethyl
`acrylamide,
`methylaminoethyl
`methacrylate and methoxyethyl (meth)acrylate,
`and/or a vinyl monomer such as acrylonitrile, vinyl
`acetate or vinyl propionate.
`The plaster comprising an acrylic adhesive
`substance may be further blended with, as a third
`component, a tackifier such as terpene based
`resins and petroleum based resins, an adhesion or
`holding power modifier such as liquid paraffin,
`animal and plant oils (for example, olive oil,
`soybean oil, beef tallow, or lard) , polybutene,
`lower isoprenes and waxes, a filler such as
`titanium oxide, zinc oxide, aluminum metasilicate,
`calcium sulfate, calcium phosphate, water, an
`emulsifier (for example, sorbitan monooleate or
`sodium
`lauryl
`sulfonate), an emulsification
`
`enhancer (for example, magnesium stearate or
`aluminum stearate) or the like.
`In the present invention, the term, tocopherols,
`[refers
`to]
`the general concept
`indicating
`α-tocopherol,
`β-tocopherol,
`γ-tocopherol,
`δ-tocopherol, and derivatives thereof, where the
`derivative is preferably an organic acid derivative,
`and in particular an organic acid ester.
`These tocopherols may be any of an α-isomer,
`an l-isomer, or a dl-isomer, and a mixture of two or
`more thereof may also be used. Specific examples
`of
`tocopherols
`include
`dl-α-tocopherol,
`dl-β-tocopherol, d-γ-tocopherol, d-γ-tocopherol [sic],
`d-δ-tocopherol, and acetic acid esters and succinic
`acid esters thereof.
`The amount of tocopherol blended is on the
`order of 0.005 to 5 wt%, and preferably on the
`order of 0.05 to 1 wt% relative to the acrylic
`adhesive.
`The plaster of the present invention may be
`further blended with an oxyacid such as citric acid,
`malic acid or maleic acid, or a polyphosphoric acid
`or the like.
`The plaster of the present invention can be
`made into an adhesive patch preparation by
`blending it with a drug that can be used on the
`epidermis. Then, the adhesive patch preparation
`using the plaster according to the present invention
`has an [advantageous] effect wherein the drug
`blended therewith is kept stable without breaking
`down.
`There are no particular limits on the drug which
`is blended in the plaster of the present invention,
`
`
`
`
`
`
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`so long as this is a drug that can be formed into an
`adhesive patch preparation and administered, and
`examples include percutaneous absorption drugs
`(where this may be a drug which is percutaneously
`absorbed with
`the aid of a percutaneous
`absorption enhancer or the like, and may be either
`a local drug or a systemic drug), drugs for
`treatment of skin disease, skin stimulating drugs,
`drugs for treatment of indefinite complaints, and
`the like. In particular, there was a marked loss in
`content of phenolic hydroxyl group-containing
`compounds, amine based compounds and the
`like in conventional plasters comprising an acrylic
`adhesive substance, and thus the plaster of the
`present invention is particularly significant when
`making such drugs into preparations. Examples of
`phenolic hydroxyl group-containing compounds
`include salicylic acid derivatives
`(monoglycol
`salicylate, methyl salicylate and the like), capsaicin
`and the like; furthermore, amine based compounds
`include ethanolamine based antihistamine drugs
`such as diphenhydramine, ethylene diamine based
`antihistamine drugs such as chlorpheniramine, and
`lidocaine and the like. Examples of other medicinal
`components
`include
`cool-sensation
`skin
`stimulating drugs such as l-menthol, dl-camphor,
`thymol
`and
`d-borneol,
`nonsteroidal
`anti-inflammatory drugs such as indomethacin and
`diclofenac sodium, steroidal anti-inflammatory
`drugs
`such
`as
`dexamethasone
`and
`betamethasone, bactericides such as chlorhexidine
`diglyconate and acrinol, warm-sensation skin
`stimulating drugs such as chili extract, nonyl
`vanillylamide, capsaicin, ginger extract, tincture of
`cantharides and cantharidin, and raw drugs such
`as lithospermum root and Japanese angelica root,
`and the like.
`Note that, in preparing the adhesive patch
`preparation of the present invention, needless to
`say, a drug may be first added to the adhesive
`substance, followed by adding a tocopherol.
`Furthermore, the adhesive patch preparation of
`the present invention is normally used by way of
`spreading it onto a support such as cloth or plastic
`film.
`Hereafter, the present invention is described in
`more specific terms by way of setting forth working
`examples and experimental examples, but the
`present invention is not limited to these.
`Example 1
`10 g
`adhesive
`0. 05 g
`d-δ-tocopherol
`0. 2 g
`monoglycol salicylate
`0. 2 g
`diphenhydramine
`0. 2 g
`ethyl aminobenzoate
`0.005 g
`citric acid
`acrylate/2-methoxyethyl
`A
`2-ethylhexyl
`acrylate/vinyl acetate copolymer was used as the
`
`adhesive, and after preparation with ethyl acetate
`as a solvent so that the concentration of the above
`substances was 25 %, the preparation was applied
`to a polyester film at a thickness of 0. 2 mm and
`dried at 80°C to produce a drug blend plaster.
`Example 2
`A drug blend plaster was produced in the same
`manner as in Working Example 1, except for
`eliminating citric acid from the formulation in
`Working Example 1.
`Comparative Example 1
`A drug blend plaster was produced in the same
`manner as in Working Example 1, except for
`eliminating d-δ-tocopherol and citric acid from the
`formulation in Working Example 1.
`Experimental Example
`The drug blend plasters produced in Working
`Examples 1 and 2 and Comparative Example 1
`were each
`sealed
`in aluminum
`laminate
`polyethylene film and stored at 40°C for 3 months,
`the drug breakdown rates were found, and the
`results were set forth in Table 1.
`Table 1 : Dug breakdown rates (%)
`Drug
`Drug breakdown rates (%)
`Working
`Working
`Working
`Example
`Example
`Example
`1
`2
`3
`3.2
`3.9
`16.2
`
`5.6
`2.8
`
`7.9
`2.6
`
`20.1
`8.9
`
`monoglycol
`salicylate
`diphenhydramine
`ethyl
`aminobenzoate
`
`
`
`
`
`
`
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`
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`VERIFICATION AND CERTIFICATION OF TRANSLATION
`
`Document translated:
`
`JP-59—184121-A
`
`This is to certify that the document or portion thereof mentioned above was
`translated into English by Patent Translations Inc., and represents an accurate
`and faithful rendition of the original text to the best of my knowledge and belief.
`
`
`
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`
`President, Patent Translations lnc.
`
`10/2/2013
`
`Noven EX. 1005
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