JPH0472805B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a pharmaceutical preparation used for percutaneously absorbing a transdermally absorbable drug through the outer skin or mucosal surface of the body. Conventionally, since the skin surface has a barrier function, it is difficult for drugs to be absorbed through the skin, and for this reason, occlusive therapy has been adopted as an administration method that reduces the barrier function. This method swells and softens the skin surface (stratum corneum) by sealing the skin surface to which the drug has been applied.
By lowering the barrier function, drugs can be absorbed smoothly through the skin. According to such a method, the desired transdermal absorption can be achieved, but there is a problem that the skin surface is sealed and the moisture generated causes it to swell, resulting in a dry skin. It was necessary to administer drugs to cure the disease. The present invention relates to a novel pharmaceutical preparation that solves the drawbacks of the prior art. A pharmaceutical preparation for transdermal absorption of a drug in a sealed state, wherein the adhesive layer has a thickness of 1000μ to exert the desired pharmacological effect.
It contains a systemic main drug in an amount of less than g/cm ² and an anti-inflammatory corticosteroid in an amount of less than 30 μg/cm ² to prevent air contact due to sealed application. The pharmaceutical formulation of the present invention is characterized in that even if the pharmaceutical formulation is applied for a long period of time, for example, for about a week, the skin surface will not feel tactile. The carrier used in carrying out the present invention preferably has a moisture permeability of 50 g/m ² /24 Hrs or less, for example, 100 g/m 2 /24 Hrs or less for the purpose of transdermal absorption of the drug in a sealed state. ^m2 /
Even materials with low moisture permeability of about 24 hours can be used. Such carriers include selected plastic films or sheets, metal foils, or low moisture permeability materials thereof, cloth, nonwoven fabric,
Products laminated with highly moisture permeable materials such as woven and knitted fabrics are used. The drug-containing adhesive layer formed on such a carrier includes a rubber and/or synthetic resin pressure-sensitive adhesive composition that is substantially non-irritating to the skin and exhibits the desired pharmacological effect. It consists of a systemic main drug with a content of 1000 μg/cm ² or less, and an anti-inflammatory corticosteroid with a content of 30 μg/cm ² or less, which prevents air contact due to sealed application. Systemic drugs are used as the main drugs, and these drugs are generally used in doses below 1000 μg/cm ² . The amount of anti-inflammatory corticosteroids to be added is determined by the amount of the active ingredient or the thickness of the adhesive layer, but it is desirable that the amount does not exceed 30 μg/cm ² at most. Commercially available corticosteroids can be selectively used. The fact that the pharmaceutical preparation of the present invention has excellent pharmacological effects and anti-contaminant effects will be specifically explained with reference to the following examples. Example 1 An acrylic pressure-sensitive adhesive composition consisting of a copolymer of 2-ethylhexyl acrylate:alkyl acid (weight ratio 96:4) was added with 400μ of isosorbitol nitrate.
g/cm ² and dexamethasone acetate 0.5 μg/cm ² and coated on one side of a 6 μm thick polyester film to a thickness of 50 μm to obtain a pharmaceutical preparation. Example 2 100 μg/cm ² of clonidine and 10 μg/cm ² of prednisolone acetate were added to a rubber pressure-sensitive adhesive composition consisting of natural rubber: polyterpene resin: polybutene (weight ratio 5:5:1). Then, a pharmaceutical preparation was obtained by applying the coating to a thickness of 80 μm on the vapor-deposited surface of a polyester film having a thickness of 80 μm and having aluminum vapor-deposited on one side. Example 3 Styrene-isoprene-styrene block copolymer: Hydrogenated rosin (softening point 100°C): Polybutene:
A rubber-based pressure-sensitive adhesive composition consisting of liquid paraffin (weight ratio 10:9:2:4) was added with 200 μg/cm ² of scopolamine hydrobromide and 1 μg/cm ² of fluocinolone acetate. The mixture was mixed and coated on one side of a polybutadiene closed cell foam having a thickness of 1 mm to a thickness of 100 μm to obtain a pharmaceutical preparation. Example 4 Isopropyl myristate as a transdermal absorption promoting agent for 100 parts by weight of a copolymer of isooctyl acrylate:acrylamide (weight ratio 95:5)
100 μg/cm ² of indomethacin and 5 μg/cm ² of hydrocortisone acetate were added to an acrylic pressure-sensitive adhesive composition containing 10 parts by weight of ethylene-vinyl acetate copolymer ( A pharmaceutical preparation was obtained by applying the compound to a thickness of 80 μm on one side of a composite sheet (150 μm thick) laminated with vinyl acetate (containing 8% by weight). Table 1 shows the test results of Examples 1 to 4. 1st
Reference Examples 1 to 4 in the table correspond to Examples 1 to 4, respectively, and in each case no anti-inflammatory corticosteroid was added.

[Table] Test method in Table 1 Drug absorption rate: Hair is removed from the back of a rabbit and each sample (5 cm x 10 cm) is pasted, 1 hour, 3 hours, 6 hours, 12 hours and 24 hours later. After a period of time, blood was collected from each patient, the blood concentration was measured, a blood concentration curve was drawn, and the area under the curve was calculated to determine the amount of drug absorbed, which was divided by the initial formulation amount (n = 3). Average value). Positive rate: Paste a sample (circle with a diameter of 15 cm) on the back of a guinea pig that has had its hair removed, and remove it after 48 hours.
After a further 1 hour, the condition was observed and evaluated using a 5-step method. The criteria were as follows and the percentage of + was calculated (average of n=20). : Blister + : Edema ± : Erythema – : Redness – : No change

Claims (1)

[Claims] 1. A pharmaceutical preparation for transdermal absorption of a drug in a sealed state, consisting of a carrier and a drug-containing adhesive layer formed on the carrier, wherein the adhesive layer has an objective pharmacological effect. A pharmaceutical preparation characterized by containing a systemic main drug with a content of 1000 μg/cm ² or less to exert its effect, and an anti-inflammatory corticosteroid with a content of 30 μg/cm ² or less to prevent air contact due to sealed application. .