JP4361771B2 - External substrate composition - Google Patents

Description

  The present invention relates to a medical pad containing a (co) polymer, which is a combination of hydroxyethyl (meth) acrylamide alone or in combination with other copolymerizable vinyl monomers, which enhances adhesion to the skin, and a topical skin application The present invention relates to an external substrate composition useful as an agent.

  Conventionally, patches are often used as means for transdermal administration by containing a drug in an adhesive layer on a substrate. Rubber adhesives and acrylic adhesives are known as external base compositions for such patches, but recently, a monomer having a hydroxyl group has been used to improve the adhesion to the skin. For example, in Patent Document 1, a group exhibiting excellent adhesiveness to skin by using a pressure-sensitive adhesive obtained by polymerizing hydroxyethyl methacrylate (HEMA) with an alkyl acrylate or glucosyloxyalkyl acrylate as a monomer having a hydroxyl group. I'm getting an agent. However, these (meth) acrylate monomers having a hydroxyl group have extremely high skin irritation, and the PII value of hydroxyethyl acrylate shows 8 (very strong irritation). In the patch used on the human body, if such a highly irritating monomer remains unreacted, it may cause irritation to the human body, itching, rash, erythema, etc., so the residual monomer is extremely reduced. After completion of the polymerization, complicated purification is carried out by removing the residual monomer by repeating isopropyl alcohol-water washing and vacuum drying three times.

  In order to reduce the residual monomer, generally, a method for increasing the reaction rate by increasing the amount of the polymerization initiator, a method for extending the polymerization reaction time, a method for adding or dividing the polymerization initiator during the reaction, etc. are tried. ing. Furthermore, Patent Document 2 discloses the addition of an antioxidant to trap radicals generated due to the polymerization initiator used excessively to reduce the residual monomer. Is described as requiring high safety for application to the skin.

Accordingly, attempts have been made to use low-irritant monomers, and for example, as shown in Patent Document 3, a method of introducing a long-chain ethylene glycol group such as hydroxy polyethylene glycol acrylate has been proposed. However, such a long-chain compound is also an acrylate, so it cannot be said to be sufficiently hypoallergenic.
As described above, when a monomer having a hydroxyl group is used, adhesion is improved, but acrylates have a problem of high skin irritation and cannot be used at a high concentration.
Japanese Patent Application Laid-Open Nos. 7-33111 and 8-325545. Japanese Patent Laid-Open No. 11-5733 JP-A-7-187999

  The problem to be solved is to provide a base composition for external use that has no skin irritation without complicated addition operations and addition of additives other than a polymerization initiator, and exhibits high adhesiveness similar to an acrylate adhesive. It is to be.

The present inventors have found that such problems can be solved by using hydroxyethyl (meth) acrylamide having no skin irritation, and have reached the present invention.
That is, the present invention
(1) A copolymer of hydroxyethyl (meth) acrylamide, ethyl acrylate, ethylhexyl acrylate, and ethylene glycol dimethacrylate, and among the monomers constituting the copolymer, hydroxyethyl (meth) acrylamide Is an external base material composition for adhesives for patches and for mixing drugs, comprising 10 to 90% by weight of the copolymer, and the copolymer itself contains a copolymer exhibiting adhesiveness to the skin.
(2) A patch using the external base material composition described in (1) above ,
Is to provide.

  The base material composition for external use of the present invention has no skin irritation and exhibits high adhesiveness like the acrylate-based adhesive.

Hereinafter, the present invention will be described in detail.
The base material composition for external use of the present invention contains a (co) polymer used in combination with hydroxyethyl (meth) acrylamide and another copolymerizable vinyl monomer to enhance the adhesion to the skin. .

The hydroxyethyl (meth) acrylamide used in the present invention is N-hydroxyethyl acrylamide (HEAA) or N-hydroxyethyl methacrylamide (HEMAA). These compounds include, for example, (meth) acrylic acid alkyl ester (specifically acrylic) whose double bond is protected with cyclopentadiene, as described in JP-B-55-29976 or JP-A-2002-053537. Methyl acid, methyl methacrylate, ethyl acrylate, butyl acrylate, etc.) can be easily produced by subjecting the resulting norbornene amide to gas phase thermal decomposition after amidation reaction with aminoethanol in the presence of a basic catalyst. Can do.
N-hydroxyethyl acrylamide and N-hydroxyethyl methacrylamide have both PII of 0, boiling points of 130 ° C / 0.1 kPa and 135 ° C / 0.1 kPa, respectively. Is a compound with almost no odor. It is a highly safe compound with oral toxicity> 2000 mg / Kg (rat).

Other monomers used in the present invention are ethyl acrylate, ethyl hexyl acrylate, and ethylene glycol dimethacrylate.

The monomer to be copolymerized is preferably a monomer having a PII (skin irritation) of 4 or less and a boiling point of 150 ° C. or less.

The copolymerization method of hydroxyethyl (meth) acrylamide, ethyl acrylate, ethyl hexyl acrylate, and ethylene glycol dimethacrylate is not particularly limited. For example, solution polymerization in an organic solvent such as alcohol or ethyl acetate, Although reverse phase suspension polymerization, reverse phase emulsion polymerization and the like are possible, solution polymerization of alcohol or the like is preferable. The monomer (monomer) concentration during polymerization is 5 to 85% by weight, preferably 5 to 30% by weight. Applicable polymerization initiators include generally known polymerization initiators such as azo series, organic peroxide series, inorganic peroxide series, and redox series.

The polymer preferably contains 10 to 90 % by weight of hydroxyethyl (meth) acrylamide as a structural unit. If it is less than 10% by weight, the effect of enhancing the adhesive strength and the improvement of other properties are not sufficiently exhibited.

The present invention further provides a patch using the external base material composition of the present invention.
The patch is easily manufactured by dissolving the base material composition for external use of the present invention in a solvent, blending it with a drug and other additives, applying it to one side of the support, and then removing the solvent by drying. it can. The coating method is not limited to the solvent coating method described above, and a hot melt coating method, an electron beam curable emulsion coating method, and the like can also be used. It is sufficient to apply the coating amount so as to have a thickness of 20 to 200 μm after drying.
Examples of the support used include plastic sheets such as polyethylene, polypropylene and nylon, non-woven fabrics such as rayon and polyester, and woven fabrics such as polyester, acrylic and cotton.

The patch of the present invention can also be formed by once forming an adhesive layer on a release paper and then transferring and laminating the adhesive layer on a support. In order to protect the adhesive layer, the release paper may be laminated until it is used.
As the release layer, a known layer is used, and examples thereof include a silicon terephthalate film treated with silicon.

Hereinafter, the present invention will be described in detail with reference to examples.
Example 1
In a separable flask equipped with a reflux condenser, a thermometer, a stirrer, and a nitrogen gas introducing device, 300 parts of ethanol and 0.1 part of azobisisobutyronitrile (AIBN) as a polymerization initiator were added to obtain a uniform solution. Then, each monomer component shown in the following Table 1 was added thereto. After passing nitrogen gas for 30 minutes, the mixture was heated to 60 ° C. and polymerized for 8 hours. The polymer solution cooled to 25 ° C. is coated on a 30 μm thick polyethylene terephthalate film so that the film thickness after drying is 70 μm, and is dried in an oven at 60 ° C. for 30 minutes. Produced.

Examples 2, 3 and Comparative Examples 1-3
A patch was prepared in the same manner as in Example 1 except that the charging components of each monomer were changed as shown in Table 1 below.

About the patch produced in the said Examples 1-3 and Comparative Examples 1-3, the holding power test and the sticking test were done.
[Holding force test] Based on JIS Z 0237 (1980), the time until the weight dropped was measured under the conditions of a measurement temperature of 40 ° C., a load of 1 kg, and an adhesion area of 25 mm × 25 mm. The longer the drop time, the higher the adhesiveness. The results are shown in Table 3.
[Attachment test] A sample of 20 mm x 20 mm was attached to the inner side of the upper arm of 5 boys for 24 hours. After sticking, the sample was peeled off, and adhesive residue on the skin, pain at the time of peeling, and the presence or absence of redness were observed and evaluated according to the criteria in Table 2. The results are shown in Table 3.

As is apparent from Table 3, it was shown that by using hydroxyethyl acrylamide in place of hydroxyethyl methacrylate, the adhesiveness did not change and an external base composition without skin irritation was obtained.

  As described above, according to the present invention, it is possible to obtain a base composition for external use that has no skin irritation and exhibits high adhesiveness similar to an acrylate-based adhesive, and is therefore suitable as a medical pad and a skin external preparation. Can be used for

Claims (2)

A copolymer of hydroxyethyl (meth) acrylamide, ethyl acrylate, ethyl hexyl acrylate, and ethylene glycol dimethacrylate, and among the monomers constituting the copolymer, hydroxyethyl (meth) acrylamide is 10 to 10. An external substrate composition for adhesives for patches and for mixing drugs, comprising 90% by weight and containing a copolymer that exhibits adhesiveness to the skin. A patch using the external base material composition according to claim 1 .