JPH09291028A - Plaster - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prepare a plaster excellent in percutaneous absorption of a medicine and sticking abilities. SOLUTION: This plaster has a tacky agent layer laminated on one side of a carrier and the tacky agent layer comprises a tacky base material, a medicine and crotamiton and further the tacky base material comprises a rubber- based tacky agent and a liquid paraffin. The content of the liquid paraffin in the tacky base material is 30-65wt.% and the content of the crotamiton in the tacky agent layer is 0.5-5wt.%.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a patch having excellent transdermal absorbability and patchability.

[0002]

2. Description of the Related Art A patch is formed by laminating a support and a pressure-sensitive adhesive layer containing a drug, and is used to absorb the drug contained in the pressure-sensitive adhesive layer into the body through the skin. ing. Such a patch is required to have absorbability such that the drug is efficiently transferred into the body through the skin and a patch that has a good feeling of use because the patch itself is not easily physically peeled from the skin.

Patches are generally made of lipophilic polymers such as natural rubber and synthetic rubber; tackifying resins such as terpene resins, petroleum resins and ester gums, and softening agents such as process oil, polybutene, liquid paraffin and lanolin. The one using the following adhesive base is often used. However, a patch using a rubber-based pressure-sensitive adhesive base has poor solubility in the pressure-sensitive adhesive base and solvent even though the physical mobility of the drug in the pressure-sensitive adhesive layer is increased by a softening agent, resulting in transdermal The absorbency was insufficient.

Japanese Patent Application Laid-Open No. 7-196505 discloses an adhesive patch in which an adhesive base made of natural rubber or synthetic rubber, a tackifying resin, indomethacin, and an adhesive layer made of isopropyl myristate are laminated. It is disclosed that it has excellent absorbency. However, with this patch, the addition of isopropyl myristate shows a drug release-promoting effect, but the cohesive force of the adhesive base is reduced, and adhesive cracking, adhesive residue, etc. due to cohesive failure occur, and the patchability etc. I had a problem with.

[0005]

SUMMARY OF THE INVENTION In view of the above, an object of the present invention is to provide a patch having excellent transdermal absorbability and patchability of a drug.

[0006]

The present invention is a patch in which a pressure-sensitive adhesive layer is laminated on one surface of a support, wherein the pressure-sensitive adhesive layer is composed of a pressure-sensitive adhesive base, a drug and crotamiton, The pressure-sensitive adhesive base is composed of a rubber-based pressure-sensitive adhesive and liquid paraffin, and the content of the liquid paraffin in the pressure-sensitive adhesive base is 30 to 65% by weight, and the content in the pressure-sensitive adhesive layer of the crotamiton is in the range. Content is 0.5-5% by weight
The patch is characterized in that Hereinafter, the present invention will be described in detail.

As the support used in the present invention, any support that is flexible, imparts self-supporting property to the patch, prevents volatilization and migration of the drug, and has conformability to the skin surface It is not particularly limited, and examples thereof include a film, a sheet, a foam, a woven or non-woven fabric made of natural fibers or synthetic fibers, and paper having a drug-impermeable property;

Examples of the material for the support include polyethylene, ethylene-vinyl acetate copolymer, polyurethane, polypropylene, polyvinyl chloride, polyvinylidene chloride, cellulose acetate, ethyl cellulose, polyethylene terephthalate, vinyl acetate-vinyl chloride copolymer. Coalescing,
Nylon, polyester, polyolefin, rayon,
Examples thereof include polyamide, aluminum, cotton, suf, and the like.
Among these, polyethylene terephthalate, polyester, polyolefin, rayon and the like, drug non-migratory,
It has chemical resistance, moisture resistance, dimensional stability, dyeability, etc. as a support, and the price is relatively low.
Particularly preferred.

The support may be subjected to corona treatment, plasma discharge treatment, or the like, and may be coated with an anchor coating agent in order to improve the adhesiveness to the pressure-sensitive adhesive layer.

The thickness of the support is preferably 0.01 to 7 mm. If it is less than 0.01 mm, the self-supporting property of the obtained patch will be insufficient and it will be difficult to handle, and 7 m
If it exceeds m, the resulting patch will lack flexibility and the skin will feel uncomfortable.

The adhesive patch of the present invention is an adhesive patch in which an adhesive layer is laminated on one surface of the support, and the adhesive layer is
It consists of adhesive base, drug and crotamiton. The adhesive base comprises a rubber-based adhesive and liquid paraffin.

The rubber-based pressure-sensitive adhesive comprises at least one of natural rubber and synthetic rubber. The synthetic rubber is not particularly limited, and examples thereof include styrene-isoprene block copolymers, styrene-isoprene-styrene block copolymers and other styrene-isoprene block copolymers; styrene-butadiene block copolymers, styrene- Butadiene-styrene block copolymer, styrene-
Examples thereof include styrene-butadiene block copolymers such as ethylene-butadiene-styrene block copolymers. Of these, a styrene-isoprene-styrene block copolymer is preferable because it has appropriate rubber elasticity.

The styrene-isoprene-styrene block copolymer is not particularly limited, and for example, a commercially available styrene-isoprene-styrene block copolymer such as Califlex TR series manufactured by Shell Chemical Co. can be used. However, a styrene-isoprene block copolymer may be added, or a plurality of them may be mixed depending on the case.

In the present invention, the liquid paraffin is
It functions as a softening agent and at the same time promotes drug release. The content of the liquid paraffin in the adhesive base is
It is 30 to 65% by weight. If it is less than 30% by weight, the drug absorbency will be poor, and if it exceeds 65% by weight, liquid paraffin will bleed out and the sticking property will be poor.
It is limited to the above range. It is preferably 40 to 55% by weight.

The pressure-sensitive adhesive base may further contain additives such as a tackifying resin, a softening agent, an antioxidant and a filler, if necessary. The tackifying resin is not particularly limited, and examples thereof include rosin-based resins, polyterpene resins, coumarone-indene resins, petroleum-based resins, terpene-phenol resins, alicyclic saturated hydrocarbon resins, and the like. Among them, the alicyclic saturated hydrocarbon resin exerts the tackifying effect without excessively reducing the cohesive force of the pressure-sensitive adhesive base, and is therefore preferably used.

The amount of the tackifying resin added is preferably 60 to 400 parts by weight based on 100 parts by weight of the adhesive base. If the amount is less than 60 parts by weight, the cohesive force becomes excessive and the adhesive force becomes insufficient, and the drug releasing property decreases, while if it exceeds 400 parts by weight, the cohesive force and the adhesive force become insufficient and the drug releasing property decreases. It is more preferably 80 to 250 parts by weight, further preferably 100 to 230 parts by weight, and 115 to 13 parts by weight.
More preferably, it is 0 parts by weight.

The softening agent is not particularly limited, and examples thereof include liquid polybutene, mineral oil, lanolin, liquid polyisoprene, liquid polyacrylate, and the like other than liquid paraffin. The antioxidant is not particularly limited, and examples thereof include dibutylhydroxytoluene and the like. The filler is not particularly limited, for example,
Titanium oxide and the like can be mentioned. The amount of the additives other than the tackifying resin is preferably within a range that does not impair the cohesive force and the adhesive force.

The drug used in the present invention is not particularly limited as long as it can penetrate the skin and exhibit a drug effect.
For example, nonsteroidal antipyretic and antiphlogistic analgesics such as ketoprofen, flurbiprofen, piroxicam, salicylic acid, steroidal anti-inflammatory agents such as prednisolone and dexamethasone, vasodilators such as isosorbide nitrate, nitroglycerin, hypertension / arrhythmia agents, blood pressure. Antihypertensive agent, antitussive expectorant, antitumor agent, local anesthetic, hormone agent, asthma / nasal allergy treatment agent, antihistamine, anticoagulant, antispasmodic agent, cerebral circulation / metabolic agent, antidepressant / anxiety agent, vitamin D Formulations, hypoglycemic agents, anti-ulcer agents, hypnotics, antibiotics and the like can be mentioned.

The content of the above-mentioned drug varies depending on the kind of the drug, purpose of use of the preparation, etc., but is 0.1 in the pressure-sensitive adhesive layer.
-30% by weight is preferred. If it is less than 0.1% by weight,
30% by weight due to insufficient therapeutic effect and poor therapeutic effect
When it exceeds, crystals are deposited in the pressure-sensitive adhesive layer and the sticking property is deteriorated.

In the present invention, the crotamiton functions as an absorption enhancer. The content of the crotamiton in the pressure-sensitive adhesive layer is 0.5 to 5% by weight. If it is less than 0.5% by weight, the absorption promoting effect is not sufficient, and if it exceeds 5% by weight, the drug is dissolved in crotamiton, the saturated solubility of the drug in the pressure-sensitive adhesive layer increases, and the release property decreases.
The total absorptivity is reduced, so the range is limited. It is preferably 1 to 3% by weight.

The pressure-sensitive adhesive layer has a thickness of 0.01 to 1 mm.
Is preferred. If it is less than 0.01 mm, the skin absorption and adhesive strength of the drug will be insufficient, and if it exceeds 1 mm, the patch will lack flexibility and the skin will feel uncomfortable.

In order to protect the surface of the pressure-sensitive adhesive layer until the patch of the present invention is used, it is usually preferable that the patch surface has a release paper. As the release paper, for example,
Those obtained by subjecting a film of polyethylene terephthalate to silicon treatment, those obtained by subjecting paper to a polyethylene laminate and then subjecting it to silicon treatment, and the like are preferably used. The thickness of the release paper is 1000 μm or less, preferably 20 to 2
Generally, the diameter is 00 μm.

As a method for producing the patch of the present invention, a usual method for producing an adhesive tape can be applied. For example, typical methods such as a solvent coating method and a hot melt coating method, an emulsion coating method, a method by electron beam cross-linking and the like can be mentioned.

To produce by the above solvent coating method, for example,
The adhesive base, the tackifying resin, the drug, the crotamiton and other various additives are dissolved or dispersed in a suitable solvent, the resulting solution or dispersion is directly applied to the surface of the support, dried to obtain an adhesive Allow the layers to form. This adhesive layer is brought into close contact with a protective release paper to obtain the patch of the present invention. In addition, this solution or dispersion may be applied on a release paper and the adhesive layer obtained after drying may be adhered to a support.

To apply by the hot-melt method, for example, the above-mentioned adhesive base, the above-mentioned tackifying resin, the above-mentioned drug, the above-mentioned crotamiton and various other additives are heated and melted and then mixed, and the resulting melt is obtained. The pressure-sensitive adhesive layer is formed by directly coating on the surface of the support and solidifying by cooling. This adhesive layer is brought into close contact with a protective release paper to obtain the patch of the present invention. Alternatively, the melt may be applied onto release paper and the pressure-sensitive adhesive layer obtained after cooling and solidification may be brought into close contact with the support.

The patch of the present invention has a good transdermal absorbability of a drug due to the absorption promoting effect of liquid paraffin and crotamiton, and has an excellent patch property.

[0027]

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples.

Example 1 20 parts by weight of a styrene-isoprene-styrene (SIS) block copolymer (Califlex 1107P, Shell Chemical Co.) was dissolved in 176 parts by weight of cyclohexane, and 27 parts by weight of an alicyclic saturated hydrocarbon resin. (Alcon P85, manufactured by Arakawa Chemical Co., Ltd.), 47 parts by weight of liquid paraffin (manufactured by Nikko Chemical Co., Ltd.) and 1 part by weight of dibutylhydroxytoluene (BHT) (manufactured by Orient Chemical Co., Ltd.) were added, and the mixture was thoroughly stirred and completely dissolved to give a solid. An adhesive base solution having a concentration of 35% was prepared.

Crotamiton (manufactured by Kongo Chemical Co., Ltd.) and isosorbide dinitrate (manufactured by Chugoku Kayaku Co., Ltd., hereinafter referred to as "ISDN") were added to the adhesive base solution in solid concentration of 2% by weight and 3% by weight, respectively. Thus, a coating solution which is uniform throughout is obtained. This coating solution was applied on a release paper obtained by treating a polyethylene terephthalate (PET) film having a thickness of 38 μm with silicon, and dried in a Kia oven at 60 ° C. for 30 minutes to form an adhesive layer. This is thickness 31
It was stuck to a laminated film of μm PET and an ethylene-vinyl acetate copolymer to obtain a patch.

Example 2 27 parts by weight of SIS block copolymer, cyclohexane 1
An adhesive base solution was prepared using 69 parts by weight, 27 parts by weight of an alicyclic saturated hydrocarbon resin, 36 parts by weight of liquid paraffin, and 1 part by weight of BHT, and crotamiton and ISDN were solidified in the adhesive base solution. Mineral concentration is 4% by weight
And a patch was obtained in the same manner as in Example 1 except that the addition amount was 5% by weight.

Example 3 23 parts by weight of SIS block copolymer, cyclohexane 1
An adhesive base solution was prepared using 76 parts by weight, 29 parts by weight of an alicyclic saturated hydrocarbon resin, 42 parts by weight of liquid paraffin, and 1 part by weight of BHT, and crotamiton and ISDN were solidified in the adhesive base solution. Minor concentration is 2% by weight
And a patch was obtained in the same manner as in Example 1 except that the addition amount was 3% by weight.

Comparative Example 1 A patch was obtained in the same manner as in Example 1 except that crotamiton was not added.

Comparative Example 2 33 parts by weight of SIS block copolymer, cyclohexane 1
An adhesive base solution was prepared using 80 parts by weight, 33 parts by weight of an alicyclic saturated hydrocarbon resin, 30 parts by weight of isopropyl myristate, and 1 part by weight of BHT, and ISDN was added to the adhesive base solution to obtain a solid content. A patch was obtained in the same manner as in Example 1 except that the medium concentration was 3% by weight.

Comparative Example 3 12 parts by weight of SIS block copolymer, 1 of cyclohexane
An adhesive base solution was prepared using 69 parts by weight, 12 parts by weight of an alicyclic saturated hydrocarbon resin, 66 parts by weight of liquid paraffin, and 1 part by weight of BHT, and crotamiton and ISDN were solidified in the adhesive base solution. Mineral concentration is 4% by weight
And a patch was obtained in the same manner as in Example 1 except that the addition amount was 5% by weight.

Comparative Example 4 38 parts by weight of SIS block copolymer, cyclohexane 1
An adhesive base solution was prepared by using 76 parts by weight, 46 parts by weight of an alicyclic saturated hydrocarbon resin, 10 parts by weight of liquid paraffin, and 1 part by weight of BHT, and crotamiton and ISDN were solidified in the adhesive base solution. Minor concentration is 2% by weight
And a patch was obtained in the same manner as in Example 1 except that the addition amount was 3% by weight.

Comparative Example 5 25 parts by weight of SIS block copolymer, cyclohexane 1
An adhesive base solution was prepared by using 62 parts by weight, 26 parts by weight of an alicyclic saturated hydrocarbon resin, 35 parts by weight of liquid paraffin, and 1 part by weight of BHT, and crotamiton and ISDN were solidified in the adhesive base solution. A patch was obtained in the same manner as in Example 1 except that the concentration was adjusted to 10% by weight and 3% by weight, respectively.

Evaluation Method With respect to each patch obtained in Examples 1 to 3 and Comparative Examples 1 to 5, the performance in the following items was evaluated. (1) Skin Permeability of Hairless Mice Male hairless mice were sacrificed by cervical dislocation, and then the skin was immediately peeled off to remove subcutaneous fat and set in Franz cells. A sample obtained by punching out each patch of Examples 1 to 3 and Comparative Examples 1 to 5 to 3.14 cm ² was stuck on the skin excised from a hairless mouse.

Sodium hydrogen phosphate (5 × 10 ^-4 mo
l), disodium hydrogen phosphate (2 × 10 ⁻⁴ mol),
Sodium chloride (1.5 × 10 ^-1 mol) and gentamicin 10 mg were dissolved in distilled water, the pH was adjusted to 7.2 with 0.1N aqueous sodium hydroxide solution, and distilled water was further added to make 1000 ml. A liquid was prepared. The receptor solution was placed in the receptor layer below the Franz cell and placed in a constant temperature bath kept at 37 ° C. from the start of the test. Twenty-four hours after the start of the test, a liquid was collected from the lower receptor layer, and the amount of ISDN in the liquid (skin permeation amount) was measured by high performance liquid chromatography. Test n
= 3 and the average value was taken as the skin permeation amount. The results are shown in Table 1.

(2) Initial Adhesion The sample was cut into a size of 30 mm × 30 mm and attached to the back of a guinea pig that had been shaved with a clipper and a shaver. After 30 minutes from application, the sample was peeled off and the application property was evaluated according to the following criteria. The results are shown in Table 1. (I) Adhesion state of sample +: Completely attached ±: Slightly floating −: Fairly floating (ii) Adhesive residue during peeling ○: No adhesive residue ×: Adhesive residue

[0040]

[Table 1]

As is clear from Table 1, the patches of the Examples are high in the skin permeability of the drug and have less adhesive residue and excellent adhesiveness.

[0042]

EFFECTS OF THE INVENTION Since the patch of the present invention is as described above, it has excellent transdermal absorbability and patching property of a drug due to the absorption promoting effect of liquid paraffin and crotamiton.

Claims (1)

[Claims] 1. A patch having a pressure-sensitive adhesive layer laminated on one side of a support, wherein the pressure-sensitive adhesive layer comprises a pressure-sensitive adhesive base, a drug, and crotamiton, and the pressure-sensitive adhesive base is a rubber-based adhesive. It is composed of an adhesive and liquid paraffin, and the content of the liquid paraffin in the adhesive base is 30 to 6
It is 5% by weight, and the content of the crotamiton in the pressure-sensitive adhesive layer is 0.5 to 5% by weight.