JPH04135924U - Sheet-shaped transdermal preparation - Google Patents

Abstract

(57) [Summary] [Purpose] To obtain a sheet-like transdermal preparation that has optimal transdermal absorption and is itself adhesive by controlling the diffusion of the drug in the paste. That is. [Structure] A sheet-shaped transdermal membrane consisting of a sheet-shaped hydrogel layer mainly composed of a water-soluble polymer with a carboxyl group in its molecular chain and an aluminum compound, and a porous membrane that controls the diffusion of the compounded drug enclosed therein. By forming an administration preparation, an adhesive layer is formed with the same composition as the drug-retaining layer, and no separate adhesive is used, thereby preventing a decrease in transdermal absorption of the drug.

Description

[Detailed explanation of the idea]

0001

[Industrial application field]

The present invention relates to a transdermal administration preparation, and more specifically, in a sheet-like hydrogel layer, Encloses a porous membrane that controls the diffusion of the drug in the gel layer. Concerning transdermal preparations that can control transdermal absorption of drugs by controlling It is something.

0002

[Conventional technology]

When a drug is administered externally, it must have a base It must be released from within and absorbed through the skin. However, the skin is exposed to substances from outside. There is a barrier that prevents entry, and most drugs cannot easily penetrate the skin. do not come. For this reason, various efforts have been made to increase the transdermal absorption of drugs. Contains transdermal absorption enhancers such as AZONE, menthol, and glycerin fatty acid ester. Measures are being taken to match. Methods for administering such compositions to the skin include: Reservoir-type transdermal preparations are commonly used. Reservoir-type transdermal preparation Regarding, there are Japanese Patent Publication No. 59-19926, Japanese Patent Application Publication No. 61-165337, Japanese Patent Application Publication No. 2-1283, etc. , all of which are basically packaging material backing, drug storage layer, diffusion control membrane, adhesive, and peeling. It consists of a sex film.

0003

[Problem that the idea aims to solve]

Compositions in which transdermal absorption of drugs is promoted by absorption enhancers are used as transdermal preparations. When administered, the composition is thought to come into contact with the skin and have the effect of promoting transdermal absorption. . However, many reservoir-type drugs use a release control membrane to control drug release. An adhesive is used to adhere the controlled release membrane to the skin. This is the composition Since the material is not in direct contact with the skin, high transdermal absorption cannot be expected.

0004 In order to maximize the effect of promoting transdermal absorption of drugs with reservoir-type preparations, it is necessary to It is necessary that the adhesive layer is a composition that has good transdermal absorbability.

[0005]

[Means to solve the problem]

The present inventors have developed a transdermal drug formulation that has good transdermal absorption and controlled release. As a result of intensive research, we have developed a composition that has good transdermal absorption of drugs, and a structure that incorporates carboxylic acid into the molecular chain. A water-soluble polymer with xyl groups, a sheet containing mainly aluminum compounds. When a porous membrane is inserted into the water gel layer to control the diffusion of the drug, it is possible to This invention was developed by discovering that it has high skin absorption and can control release. It is configured as follows.

[0006] Mainly composed of water-soluble polymers with carboxyl groups in their molecular chains and aluminum compounds. A porous membrane that controls the diffusion of the compounded drug is enclosed in the sheet-like hydrogel layer. A sheet-shaped transdermal administration preparation.

[0007] To explain further, the water-soluble Polymers include polyacrylic acid, polymethacrylic acid, and carboxyvinyl polymers. Limer, carboxymethyl cellulose sodium or carboxymethyl cellulose by hydrolysis in water. Mention methoxyethylene/maleic anhydride copolymers that generate sil groups, etc. I can do it. These can be used alone or in a mixture of two or more in an amount of 3 to 15% by weight. It is preferable that they match. It also neutralizes acidic water-soluble polymers such as polyacrylic acid. However, organic amines such as triethanolamine and diisopropanolamine are added to It may be blended in an amount of 15% by weight.

[0008] Aluminum compounds include water-soluble aluminum chloride, aluminum sulfate, and vinegar. Salts such as aluminum acid, aluminum alum, and poorly soluble aluminum hydroxide dry aluminum hydroxide gel, magnesium aluminate metasilicate, aluminum Nium glycinate and synthetic hydrotalcite can be mentioned, and the blending amount is 0. It is preferable to mix 0.01 to 1% by weight.

[0009] The membrane for controlling drug release is preferably a porous membrane having holes of 0.01 to 5 μm. , the material is polyethylene, polycarbonate, ethylene-polyvinyl alcohol. copolymer, cellulose acetate, polyamide, polyvinyl chloride, polyolefin , polyacrylonitrile, polysulfone, polyvinyl alcohol, polyimide, Examples include fluororesin.

0010 As a typical means of administering the transdermal absorption composition of the present invention to humans or animals, transdermal absorption Figure 1 shows an example of gelling the composition and forming it into a sheet, and a reservoir-type container. Figure 2 shows an example of molding.

[0011] Figure 1 shows how to prepare a percutaneously absorbable composition with good percutaneous absorbability, which has a carboxyl group in its molecular chain. A transdermal absorption compound that is made into a solid gel by a water-soluble polymer and an aluminum compound. The product is molded into a patch, and (a) is a plan view, and (b) is a cross-sectional view. . In this example, a porous membrane that controls the release of the drug (release control membrane 3) has a transdermal composition. It has a structure in which it is sandwiched between substances, and the upper side is thickened to create a drug storage layer (transdermal absorption composition 2). and set backing 1, which is impermeable to drugs. Make the bottom part thinner so that it touches the skin. It has an adhesive layer (transdermal absorption composition 4) and a removable protective film 5. be.

0012 Figure 2 shows how a transdermal composition with good transdermal absorption can be administered to humans or animals. (a) is a plan view, and (b) is a cross-sectional view. In this example, The transdermal absorption composition 2 is sealed between the backing 1 and the release control membrane 3, and the backing 1 and The release control film 3 is adhesively or heat-sealed. On the 3 side of the release control membrane (porous membrane) In order to apply the preparation to the skin, the transdermal absorption composition 4 is spread thinly, and a peelable protective film is further applied. Film 5 has been set.

[0013] In each figure, the backing 1 that prevents diffusion and transmission is aluminum foil, polyethylene Renterephthalate film, polypropylene film, etc. may be used.

[0014] Drugs that can promote transdermal absorption using this invention include systemic paralytics, hypnotic sedatives, Anti-epileptic drugs, antipyretic, analgesic, anti-inflammatory drugs, muscle relaxants, psychoneurotic drugs, antihistamines, Positive blood pressure agents, diuretics, antihypertensive agents, vasodilators, adrenal hormone agents, antineoplastic agents, Narcotics, synthetic narcotics and other pharmacologically active drugs. The amount of these drugs added is Effective release time, transdermal absorption rate, metabolic rate, and effective blood concentration from transdermal absorption compositions and is set for each drug.

[0015]

[Effect]

According to the present invention, the transdermal absorption of drugs from the transdermal absorption composition is significantly increased. In addition, the diffusion of the drug in the plaster is controlled by a porous membrane sandwiched between the layers. By doing so, the release of the drug can be controlled.

[0016]

【Example】

The present invention will be further explained below according to examples, but the technical scope of the present invention will be explained by the following examples. It is not limited to examples.

[0017] Example 1 Diclofenac sodium 1 part, glycerin monooleate 5 parts, polyac 5 parts sodium lylate, 3 parts sodium carboxymethylcellulose, aluminum Disperse 0.3 parts of umglycinate in 40 parts of glycerin to prepare a glycerin dispersion. make Separately, dissolve 3 parts of gelatin and 0.5 part of tartaric acid in 45.2 parts of warm water at 60°C. , added to the glycerin dispersion and stirred until uniform to obtain a paste of the pharmaceutical composition. The paste was spread on a moisture-impermeable film to form a polycarbonate film with holes of about 5 μm. Attach the porous membrane. Furthermore, a peelable plastic is applied by spreading a thin layer of plaster on the porous membrane side. After laminating Tsukufilm, cut into a predetermined area to make a sheet-shaped transdermal preparation. get.

[0018] Example 2 A polycarbonate porous membrane having holes of about 0.8 μm was added to the porous membrane of Example 1. Prepare in the same manner using

[0019] Control example 1 The paste of Example 1 was spread on a moisture-impermeable film to form a porous film having holes of approximately 5 μm. Attach the membrane. Methyl acrylate/2-ethylhexy acrylate on porous membrane After coating and drying the emulsion latex of the copolymer, a removable plastic film is applied. The membranes are pasted together and cut into a predetermined area to obtain a sheet-like transdermal preparation.

[0020] Control example 2 The paste of Example 1 was spread on an impermeable film to form a releasable plastic film. After pasting together, the sheet is cut into a predetermined area to obtain a sheet-like transdermal preparation. (implementation When the porous membrane of Example 1 is not used)

(Skin permeation test method) The skin excised from the back of a hairless rat was placed in a Franz cell (contact area 3.14 cm ² ) kept at 35° C., the transdermal preparation was applied to the stratum corneum side, and the skin was applied to the dermis side. A phosphate isotonic buffer with a pH of 7.4 was added, and the solution on the dermis side was sampled over time, and the amount of drug permeated was measured using a high-performance liquid chromatograph.

The test results of Examples 1 and 2 and Control Examples 1 and 2 are shown in FIG. When a porous membrane was not used in the transdermal preparation (Control Example 2), a large amount of about 670 μg/cm ² was permeated after 6 hours. When polycarbonate porous membranes of 5 μm (Example 1) and 0.8 μm (Example 2) are used, the permeability decreases to approximately 580 and 150 μg/cm ² , respectively, so the pore size of the membrane is changed. It has been shown that drug permeability can be controlled by this method. In addition, when comparing the case where an adhesive was used instead of a transdermal absorption composition on the surface in contact with the skin (Control Example 1) with Example 1, only about 220 μg/cm ² permeated, indicating that the drug was not permeated through the skin. It was shown that skin absorbability was decreased.

The transdermal preparation according to the present invention can be adhered to the skin without using tape or the like. The method and results of measuring the adhesive force are shown below. Adhesion test A piece of high-quality paper (for thermal recording paper) was attached to the bottom of a cylindrical adapter with a diameter of 2 cm. The sample and adapter were pasted together so that the plaster and high-quality paper were in contact with each other, and after applying a load of 1 kg for 30 seconds, the force required to peel them off was measured using a rheometer. Adhesion test measurement results Sample Results Example 1 194g/cm ² Poultice manufactured by M company 215g/cm ² Since this value is comparable to that of commercially available poultices (100 to 250 g/cm ² ), it is considered that the present transdermal preparation has sufficient adhesion to the skin.

[0024]

[Effect of the idea]

According to the present invention, a porous membrane is sandwiched between the plaster of poultices and patches, and the drug is By controlling the diffusion of the drug in the plaster, the drug release control membrane and skin The same adhesive layer as the drug-retaining layer can be used as the adhesive for adhering the , allows a number of drugs to penetrate the skin for a long period of time in amounts thought to be sufficient to produce their medicinal effects. It is possible to develop transdermal absorption formulations that can further control the amount of permeation. It's now possible. Also, there is no need to provide a separate adhesive layer or use adhesive tape. , transdermal formulations can be adhered to the skin.

[Brief explanation of drawings]

FIG. 1 is a diagram showing an example of a transdermal preparation according to the present invention. FIG. 2 is a diagram showing another example of the transdermal preparation according to the present invention. FIG. 3 is a diagram showing test data for transdermal administration formulations. 1 Backing 2 Transdermal absorption composition 3 Release control membrane 4 Transdermal absorption composition 5 Peelable protective film

Claims (1)

[Scope of utility model registration request] Claim 1: A sheet-shaped sheet consisting of a water-containing gel layer mainly composed of a water-soluble polymer having a carboxyl group in its molecular chain and an aluminum compound, in which a porous membrane for controlling the diffusion of a compounded drug is enclosed. Transdermal formulation.