Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Web – sheet or filament bases; compositions of bandages; or...
Reexamination Certificate
1999-08-10
2001-05-15
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...
C424S448000, C424S449000
Reexamination Certificate
active
06231884
ABSTRACT:
TECHNICAL FIELD
The present invention relates to the plasters for the treatment of the ischemic heart disease, and more specifically, to the plasters containing isosorbide dinitrate as an active ingredient.
BACKGROUND ART
Isosorbide dinitrate is nitrate compound widely used as medicine for the treatment of ischemic heart disease, especially as an antianginal drug. It is also used as raw materials for explosive. The pharmaceutical formulations of isosorbide dinitrate such as sublingual tablet for the internal use, injection or spray formulation have been proposed, and furthermore, various kinds of tapes such as sustained releasing transdermal formulation are also proposed.
Isosorbide dinitrate is the substance which melts at 77° C., and for the safety transportation, it is sold in 40% admixture powdery form with lactose. Therefore, to produce adhesive tapes containing isosorbite dinitrate, it has to be extracted from lactose admixture powdery form using organic solvent such as ethyl acetate, and the resulting organic solvent of isosorbite dinitrate is combined into the adhesive base materials. For the adhesive base material to be used for the tapes, solvent type of acrylic acid adhesive can be used. The solvent used for the acrylic acid adhesive may be the same one used for the extraction of isosorbide dinitrate, such as ethyl acetate.
However, there found to be problems such as crystallization of isosorbide dinitrate in the adhesive layer and the decreasing of adhesion when the ratio of isosorbide dinitrate of the base material is increased to achieve its high pharmaceutically effects. As a result, enough adhesion of the tapes to the skin and stable releasing of the active ingredient from the adhesive layer is not obtained.
Isosorbide dinitrate is a substance with sublimation and hygroscopic properties, and therefore, the conventional backings used for the transdermal formulation such as polyvinyl chloride film, polyester film or polypropylene film can not be used. The laminated backing composed of polyester film and another film were used for the transdermal preparation of isosorbide dinitrate; however, it was difficult to apply to the skin due to the thinness of the laminated backing.
DISCLOSURE OF THE INVENTION
This invention is made to solve the above mentioned problems and the purpose of the present invention is to provide the transdermal formulation containing isosorbide dinitrate as an active ingredient. More specifically, present invention is to provide plasters containing isosorbite dinitrate which possess the sufficient adhesion at the time of applying to the skin, and sustain stable releasing of the active ingredient from the adhesive layer.
The inventors of the present invention made intensive and extensive studies to solve the problems, and succeeded in finding that the adhesive base material with main component of styrene-isoprene-styrene block copolymer possesses excellent adhesion and efficient releasing of the ingredient from the adhesive base material at the same time. Furthermore, the present inventors found that the laminated polyester film with non-woven fabrics can be used as the backings for the adhesive base material containing isosorbide dinitrate of the transdermal formulation to overcome these problems.
Therefore, one aspect of the present invention is to provide the plaster containing isosorbide dinitrate as an active ingredient in the adhesive base material which is composed of styrene-isoprene-styrene block copolymer, rosin resin, liquid rubber, antioxidant and oleic acid.
In a specific embodiment of the present invention, it is provided that the plasters containing isosorbide dinitrate which is comprised by mixing ethyl acetate solution of isosorbide dinitrate with the solvent-type adhesive base material consisting styrene-isoprene-styrene block copolymer, rosin resin, liquid rubber, antioxidant and oleic acid. And the resulting mixture is spread on the silicone treated liner and dried. Then, the obtained liner is laminated with the flexible backing.
In a more specific embodiment, the present invention provides the plasters containing isosorbide dinitrate in the adhesive base material composed of 15-35 w/w % (weight/weight percent: the same as hereinafter) of styrene-isoprene-styrene block copolymer, 35-55 w/w % of rosin resin, 5-20 w/w % of synthetic liquid rubber, 0.1-2 w/w % of antioxidant, and 0.1-5 w/w % of oleic acid.
In a preferred embodiment, the present invention provides the plasters containing isosorbide dinitrate with the amount of 15-25 w/w % in the adhesive base material.
In a more preferred embodiment of the present invention, the each components of adhesive base material may be hydrogenated rosin resin for the rosin resin, polybutene or high cis polyisoprene rubber as the liquid rubber, dibutylhydroxytoluene or pentaerythrityl-tetrakis [3-(3,5-di-t-butyl-4-hydroxyphenyl)] propionate as the antioxadant.
BEST MODE FOR CARRING OUT THE INVENTION
The components composed of the adhesive base material for the plasters of the present invention are described below to disclose the present invention in more detail.
The styrene-isoprene-styrene block copolymer used for the plasters of the present invention may be a synthetic liquid rubber. This synthetic rubber acts as basic framework of adhesive base material, and the one which is preferred for the purpose has ratio of styrene/rubber as 14/86. The amount of this synthetic rubber in the adhesive base material may be 15-35 w/w %, more preferably 20-30 w/w %.
When the amount of the synthetic rubber is less than 15 w/w %, aggregated strength of the adhesive base material can not be achieved and the adhesive base material may be likely to form unevenly. On the contrary, when the amount of the rubber is more than 35 w/w %, the adhesive base material becomes too stiff and the crystallization of the isosorbide dinitrate may occur due to the decrease of the amount of the other components, and therefore it is not preferred.
The rosin resin used for this invention may be hydrogenated rosin resin with light color, and this resin possesses wide range of solubility for another components, and excellent stability for heat and oxidation. The amount of this resin in the base material may be 35-55 w/w %, more preferably 40-50 w/w %.
When the amount of the resin is less than 35 w/w %, the adhesive base material may loose appropriate adhesive strength, and when it is more than 55 w/w %, the adhesive base material may become hard and the adhesive strength may decrease, and therefore it is not preferred.
The liquid rubbers to be used for the present invention may be polybutene or high cis polyisoprene rubber. The amount of this liquid rubber may be 5-20 w/w %, more preferably 7-15 w/w %. The liquid rubber of the present invention is used as a softener for the adhesive base material. When the amount of this rubber in the adhesive base material is less than 5 w/w %, softness of the base material may not be seen and therefore it is not preferred. Furthermore, if it is more than 20 w/w %, bleeding of the components from the adhesive base material may occur and it also is not preferred.
The antioxidant is essential component to stabilize the adhesive base material at the time of production and preservation period, and various kinds of antioxidant may be used. Among them, dibutyl-hydroxytoluene or pentaerythrityl-tetrakis [3-(3,5-di-t-butyl-4-hydroxyphenyl)] propionate is most preferable for the sake of safety standpoints, and the amount of the antioxidant in the adhesive base material may be 0.1-2 w/w %.
For the plasters of the present invention, oleic acid is used as the absorption accelerant and the amount of oleic acid in the adhesive base material may be 0.5-5 w/w %, more preferably 0.5-3 w/w %. When the amount of oleic acid is less than 0.5 w/w %, the expected absorption acceleration effect is not achieved, and with it more than 5 w/w %, aggregated strength of the adhesive base material decreases and no more increase in absorption acceleration effect is achieved. Therefore it is not preferred
Kawaji Toshikuni
Yamaji Masahiro
Evenson, McKeown, Edwards & Lenahan P.L.L.C.
Ghae Isis
Page Thurman K.
Teikoku Seiyaku Co., Ltd.
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