JPH02221218A - Plaster for external use - Google Patents

Abstract

PURPOSE:To obtain economical plaster for external use, said plaster has improved adhesion to skin and increased breathability by forming an adhesive layer containing medicines on one surface of the support of a laminated film which has a moisture-absorbing layer between an air-permeable synthetic resin film and another synthetic resin film of a specific pore size. CONSTITUTION:A laminated film comprising an air-permeating synthetic resin film, a moisture-absorbing layer and a porous synthetic resin film of less than 30mum maximum pore size is used as a support. The support is coated on the surface of the porous synthetic resin film with an adhesive layer containing medicines. If the oxygen permeability of said support is 2,000 to 200,000, preferably 4,000 to 50,000ml/m<2>/24hr/atm, good effect of occlusive dressing technique manifests without any trouble in cutaneous respiration whereby the active ingredients are effectively absorbed into the living body.

Description

Detailed Description of the Invention (a) Industrial Application Field The present invention is applicable to the treatment of skin diseases, anti-inflammation, analgesia, etc., or it is applied to the skin and the drug is absorbed transdermally to treat the whole body or local area. The present invention relates to a topical patch.

(b) Conventional technology In order to improve the transdermal absorption of drugs and effectively treat systemic or local diseases, increasing the water content of horn 91M is necessary to improve not only the hair 1i sebaceous system but also the stratum corneum layer. It is important to use an absorption path that passes directly through the

For this reason, occlusive bandage therapy (O
DT therapy) is becoming popular. This involves applying an external medicine such as an ointment to the skin and covering it with an impermeable film to increase the water content of the stratum corneum and ensure effective absorption of the medicine. However, this ODT therapy is not only troublesome to attach to the affected area, but also has problems such as being too thick, easy to peel off, and difficult to adhere to the affected area when the area of the affected area is large or the shape of the affected area is complex. There were drawbacks.

In addition, waste products such as sweat that seep out from the skin surface cover the epidermis, resulting in inhibition of skin respiration, inhibition of drug diffusion, and rashes on the skin epidermis.

To overcome these drawbacks, patches are commercially available in which a pressure-sensitive adhesive containing a drug is coated on one side of a synthetic resin film support.

(e) rIAj! which the invention seeks to solve; However, although such patches are generally applied to the skin for 4 to 24 hours, the absorption of the drug is poor (a large amount of the drug remains unabsorbed into the skin even after a long period of time after being applied to the skin). Therefore, the pressure-sensitive adhesive layer must contain a much larger amount of drug than necessary for treatment, which is uneconomical.

In addition, in the above OCT therapy, sweat accumulates between the skin and the drug-containing adhesive layer due to sweating, which deteriorates the ffi adhesion between the drug-containing # adhesive layer and the skin, resulting in poor transdermal absorption of the drug. There are issues such as the condition becoming worse.

Furthermore, when this type of patch is applied to the skin, it becomes difficult for the skin to breathe, and the diffusion of sweat from the skin surface becomes poor, causing problems such as whitening of the patch, as well as itching and rashes. occurs.

The present invention provides a patch of this type that uses a specific support characterized by a water-absorbing layer and partially forms a drug-containing adhesive layer on one side of the support to absorb excess sweat and the like. In addition to ensuring good adhesion between the patch and the skin through effective absorption, and ensuring oxygen permeability of the support to facilitate skin respiration, OCT therapy also improves the ability of the drug to pass from the skin into the body. The purpose of the present invention is to provide an economical patch for external use with significantly improved absorbency.

(d)! ! Means for Solving the Problem I In order to achieve the above object, the external patch of the present invention is a patch having a drug-containing adhesive layer formed on one side of a support, in which the support is made of breathable synthetic resin 11ff. Film and maximum pore diameter is 30JJI
It consists of a laminated film in which a water absorption layer is interposed between porous synthetic resin films of 11 or less, and a drug-containing adhesive layer is partially formed on the exposed surface of the porous synthetic resin film in the support. .

That is, in the topical patch of the present invention, by interposing a water-absorbing layer between the breathable synthetic resin film and the porous synthetic resin film, this water-absorbing layer effectively absorbs excess sweat and the patch is constantly applied. It improves the adhesion between the agent and the skin, and also ensures the oxygen permeability of the support, allowing the skin to breathe smoothly.
In addition, by absorbing unnecessary sweat, etc., it prevents whitening, itching, and rashes at the application site, and controls moisture permeability to exert an ODT effect, thereby preventing the drug from entering the body from the skin. It is designed to improve the absorbency of.

The breathable synthetic resin film used in the present invention is not particularly limited as long as it has breathability and is made of synthetic resin. It is desirable to have one.

In addition, this breathable synthetic resin film does not matter whether it is a single layer film or a composite film with two or more layers, but can control air permeability and moisture permeability by making it a composite film with two or more layers. It is also good.

The thickness of the above-mentioned breathable synthetic lubricant film is not particularly limited, but from the viewpoint of stretchability, air permeability, strength, processability such as heat fusion, and handleability, the thickness is preferably 5 to 50 μm. (This is preferably 20 to 40μ.

Synthetic FA for producing this breathable synthetic resin film
The fat is not particularly limited and includes, for example, polyethylene, polypropylene, polystyrene, cellophane, polyvinyl chloride, polyester, polyamide, polyvinyl alcohol, vinylidene chloride, ethylene-vinyl acetate copolymer, etc. Among these, those made of polyethylene are preferred because a homogeneous breathable synthetic resin film can be obtained by stretching.

By the way, Synthesis 13 (In order to impart air permeability to a fat film, it is sufficient to adopt methods such as stretching the film, eluting the soluble filler after stretching, or perforating the synthetic resin film with a very fine needle. be.

The water-absorbing layer used in the present invention is a water-absorbing layer formed of a water-absorbing polymer alone or a water-absorbing composition consisting of a water-absorbing polymer and an inorganic water-absorbing agent.

If desired, this water-absorbing layer may contain an antibacterial agent, anti-fungal agent, etc. to prevent the propagation of bacteria and the generation of mold.

The thickness of this water-absorbing layer is not particularly limited, but from the viewpoint of water absorption and air permeability, it is preferably 5 to 500 microns, especially 10 to 300 microns.

The above-mentioned water-absorbing polymer is not particularly limited, but it is desirable to have a water-absorbing capacity of 15 times or more, preferably 20 times or more of its own weight.
Starch-polyacrylonitrile copolymer disclosed in Japanese Patent Publication No. 95, crosslinked polyalkylene oxide disclosed in Japanese Patent Publication No. 51-39672, Japanese Patent Publication No. 53-13
Saponified product of vinyl ester-ethylenically unsaturated carboxylic acid conjugate, 1m shown in Publication No. 495, 1973
Self-crosslinking polyacrylate obtained by the reverse phase suspension polymerization method disclosed in Publication No. 30710, JP-A-54
-Reaction product of polyvinyl alcohol polymer and cyclic anhydride disclosed in JP-A No. 20093, JP-A-55
Preferred are crosslinked polyacrylates disclosed in Japanese Patent No. 84305.

This water-absorbing layer absorbs excess sweat when the topical patch is attached to the skin and becomes overhumid due to sweating due to skin breathing, etc., and maintains good adhesion between the topical patch and the skin. In addition, it prevents the skin interface from getting wet due to excessive sweat, etc. On the other hand, when the area to which the topical patch is applied becomes dry, this water-absorbing layer has the ability to absorb water and release the absorbed moisture, making it difficult for external use. By repeatedly absorbing and releasing water within the patch, an excellent ODT effect is developed, which makes it safe and provides excellent transdermal absorption of the drug.

In addition, the above-mentioned inorganic water-absorbing agents include those that improve the water-absorbing ability of the water-absorbing layer to achieve long-lasting percutaneous absorption of the external patch, and specifically, activated carbon, zeolite, zeolite-based porous materials, cristobalite, silica-based porous material,
Examples include calcium silicate. In this case, if desired, the inorganic water-absorbing agent may contain an antibacterial agent, anti-mildew, etc.

Furthermore, in order to improve the adhesion between the above-mentioned breathable synthetic resin film and the porous synthetic resin film described below, a hydrophilic adhesive such as a polyurethane adhesive may be added to the above-mentioned water absorption layer, if desired. In this case, the amount of the adhesive added is preferably 500 parts by weight or less, preferably 250 parts by weight or less, per 100 parts by weight of the water-absorbing polymer.

The porous synthetic 11111T film used in the present invention prevents direct contact between the water-absorbing layer and the living body, and allows sweat to flow between the skin and the water-absorbing layer through this film to perform effective OCT therapy. The maximum pore diameter is 30μ or less, especially 1 to 15μ.

If the maximum pore diameter of this porous synthetic resin film exceeds 30 μ-, the strength of the film will deteriorate and it may be partially torn during handling, or when it is packaged into S1 bags by heat sealing etc.
This is not preferable since the sealing strength may decrease and peeling may occur, and the water-absorbing polymer may ooze out from the surface of the porous synthetic resin film.

In this case, the method for measuring the maximum pore diameter is
- This is based on the bubble point method 1 using a Coulter ψ bolometer manufactured by Electronics.

The thickness of this porous synthetic resin film is not particularly limited, but from the viewpoint of film strength, processability such as heat fusion, and handleability, it should be 200 μm or less, especially 20 to 80 μm. It is preferable that

The synthetic resin used to form this porous synthetic film is one that can be made into a film, and a film with a maximum pore size of 30 μl or less can be obtained by various methods such as stretching, extraction of soluble substances after stretching, and extraction of soluble substances. There is no particular limitation as long as it can be used.

Furthermore, as the synthetic resin, hydrophilic synthetic resins and hydrophilized synthetic resins are particularly desirable because they have good moisture and water vapor permeability.

The method for producing this porous synthetic resin film is as follows:
Although not particularly limited, specific examples include the following.

That is, (a) after melting and stretching the polyolefin resin,
It is heat treated and re-stretched.

(b) After forming a synthetic resin mixed with 11 compounds or solids into a film, the mixed liquids or solids are extracted.

(c) A film is formed from synthetic resin and made porous by perforating it with a needle.

(d) After adding a filler to a synthetic resin and melting it to form a film, it is stretched at least once or a little (both times), and the soluble filler is extracted using water, acid, or alkali. .

In particular, in the case of (d) above, polyolefin resin is preferable as the synthetic resin because of its good productivity (and low cost).

Examples of the polyolefin resin include homopolymers such as polyethylene, polypropylene, and polybutanoene. -0,
Alternatively, copolymers or blend polymers thereof may be mentioned, particularly polypropylene (PP), high density polyethylene (HDPE), linear low density polyethylene (
L-LDPE) is more preferable from the above-mentioned viewpoint.

Inorganic and organic fillers are used as the above fillers, and the inorganic fillers include calcium carbonate, talc, clay kaolin, silica, diatomaceous earth, magnesium carbonate, barium carbonate, magnesium sulfate, barium sulfate, calcium sulfate, and hydroxide. Aluminum, zinc oxide, magnesium hydroxide, calcium oxide, magnesium oxide, titanium oxide, Flumina, mica, asbestos powder, glass powder, Shirasu balloon, zeolite 1, clay silicate, etc. are used, especially calcium carbonate, talc, clay silica, Diatomaceous earth, barium sulfate, etc. are suitable, while organic fillers include wood flour, pulp, melamine powder, silicone! (An example is fat powder.

The average particle size of the above-mentioned photonics is 10μl or less, especially from the viewpoint of miscibility with synthetic resin and homogenization of the film.
It is preferably in the range of 5 to 5 μm, and the amount added is 50 to 500 parts by weight, preferably 100 to 300 parts by weight, per 100 parts by weight of the synthetic resin.

A support is formed of the above-mentioned breathable synthetic resin film and a porous synthetic resin film (a laminated film with a water absorbing layer interposed between the fat films), and the porous synthetic resin film is formed on the support. An adhesive layer is partially formed.

In this way, the drug-containing adhesive layer is partially formed on the exposed surface of the porous synthetic resin film of the support, but by configuring it in this way, the drug-containing adhesive layer is formed in the area where the drug-containing adhesive layer is formed. Transdermal absorption takes place, while skin respiration occurs smoothly in areas where this layer is not formed. In addition, excess sweat is effectively absorbed by the water-absorbing layer, ensuring good adhesion between the patch and the skin, preventing wetting of the skin interface, and as mentioned above, ensuring the oxygen permeability of the support to the skin. In addition to facilitating breathing, ODT therapy significantly improves the acidity of the drug from the skin into the body.

The above-mentioned drugs are not particularly limited as long as they are percutaneously absorbable, but specific examples include drugs for the central nervous system, drugs for peripheral nerve threads, drugs for allergy, drugs for circulatory organs,
Examples include one or more of respiratory drugs, gastrointestinal drugs, hormones, metabolic drugs, anti-malignant tumor agents, antibiotics, chemotherapeutic agents, and narcotics.

The above drug is contained in the pressure sensitive adhesive, and the proportion thereof is
In general, 0.000.00% per 100 parts by weight of solids of the pressure-sensitive 41 adhesive.
It is desirable that the amount is in the range of 1 to 45 parts by weight, particularly 1 to 30 parts by weight.

The above-mentioned pressure-sensitive adhesive is not particularly limited as long as it has good adhesion to the skin, and examples include acrylic adhesives, rubber adhesives such as synthetic rubber and natural rubber, and vinyl adhesives. Adhesives, terpene resins, water-soluble rosins, etc. can be used quickly.

Furthermore, although the above-mentioned drug-containing adhesive layer is partially formed on the exposed surface of the porous synthetic resin 1ff film in the support, this MJ partial formation force method is not particularly limited ( The drug-containing adhesive layer may be interspersed over the entire surface of the porous synthetic resin film, or the drug-containing adhesive layer may be formed in a lattice shape, sea-island shape, diagonal cross shape, m-striped shape, or horizontal striped shape. In short, it is sufficient to form drug-containing adhesive layers mutually over 10 to 80%, particularly 30 to 65%, of the total area, and the point is that they can be formed arbitrarily regardless of the pattern. In this case, the drug-containing adhesive layer can be scattered in any shape such as circular, elliptical, rectangular, or triangular.

If the area of the drug-containing adhesive layer is less than 10%, the area of the drug-containing adhesive layer is too small, which poses a problem in terms of drug absorption, and is also undesirable because there is a risk of spontaneous peeling after application to the skin. On the other hand, if it is less than 80%, it is not preferable because the air permeability may decrease and the skin may not be able to breathe smoothly.

In the external patch of the present invention, the oxygen permeability of the support is 2000-200.000 m1/+m2/24hr/a
By being a T-ring, it does not impede skin breathing, and
Efficient oxygen respiration through the skin (and even better OC)
It exhibits the T effect, which allows the drug to be absorbed into the body. From these viewpoints, the oxygen permeability of the support is 4.000 to 50,000.
It is desirable that the range is @1/Ugly2/24hr/atm.

In this case, this oxygen permeability is generally measured using a mixed gas permeability tester GP manufactured by LYSSY at a temperature of 23°C.
It was measured by gas chromatography type isobaric method using Model M-200.

In the external patch of the present invention, the porous synthetic resin fff
The moisture permeability of jy film is determined by the pore size and the degree of hydrophilicity of the film, but the moisture permeability is 50g/ll12.
/ 241 po or more, the moisture permeability, that is, the permeability of sweat, is good, and the sweat generated by perspiration is reliably absorbed, so there is no chance of condensation forming on the application site of the external patch. As a result, it is desirable to prevent the skin interface from getting wet and to improve the adhesion between the external patch and the skin.

By the way, this moisture permeability is measured according to JIS Z-0208.

In the external patch 1 of the present invention, the porous synthetic mui fat film that has been subjected to hydrophilic treatment with a hydrophilic agent has a significantly high sweat absorption rate and can prevent layer condensation. Therefore, it is preferable because it can be applied to areas where sweating is severe.

The above-mentioned hydrophilicity imparting/shaving is not particularly limited as long as it is provided on the surface of the porous synthetic resin film to improve the hydrophilicity of the film, and ethanol,
Examples include alcohols such as propyl alcohol and butanol, polyhydric alcohols such as glycerin, glycerin, ethylene glycol, and polyethylene glycol, and various surfactants.

The method of hydrophilizing the porous synthetic resin film using the hydrophilicity-imparting agent includes a method of mixing the hydrophilicity-imparting agent into the porous synthetic film;
Methods include applying a hydrophilicity imparting agent to the surface of the porous synthetic 1fl'l film, dipping the film in an aqueous solution of the hydrophilicity imparting agent, and spraying this aqueous solution onto the film.

In the external patch of the present invention, it is preferable to partially include a water-absorbing layer because the amount of water absorbed and the permeability of oxygen, etc. can be adjusted.

That is, a water absorbing layer is provided in some areas, and other areas are heat-sealed with a breathable synthetic resin *film and a porous synthetic 11111T film), or a hot-melt adhesive is interposed in other areas to form a surface. film (breathable synthetic front film) and back film (porous synthetic 1fffi film)
You can also heat-bond (in addition, use a water-absorbing layer that can be done simultaneously when heat-sealing the front and back sides, and use any embossing roll to heat-seal in the desired pattern during heat-sealing. be.

Furthermore, in this case, instead of thermally adhering or heat-sealing the breathable synthetic resin film and the porous synthetic resin film, these films may be adhered to each other using various adhesives.

The adhesive is not particularly limited, and examples include acrylic adhesives, rubber adhesives such as synthetic rubber and natural rubber, vinyl adhesives, terpene resins, and water-soluble rosins. Can be mentioned.

By the way, the preparation of the external patch of the present invention does not require any special technique or equipment and can be obtained by a conventional method.

Specifically, for example, a water-absorbing polymer, or a coating liquid prepared by mixing a water-absorbing agent or an adhesive with the water-absorbing polymer, is applied to the surface of either a breathable synthetic resin film or a porous synthetic resin film. After coating by a gravure method, a roll coating method, or a silk screen method, either the breathable synthetic I&8 (rreI film or the porous synthetic U (oil film), the other film is laminated to form a support. , a drug-containing adhesive coating solution is partially applied to the exposed surface of the porous synthetic layer film in the support by a gravure method, a roll coating method, a silk screen method, etc., and then dried. Methods include:

In this case, from the viewpoints of adhesive strength, water absorption amount, moisture absorption ability, etc. between the breathable synthetic resin film and the porous synthetic film, the water absorption layer may be provided on the entire surface or a portion of the film.

By applying the external patch of the present invention to the skin of a living body, the drug can be absorbed transdermally for a long period of time for reasons described below.

In addition, in order to achieve the above object, in the external patch of the present invention, a pressure-sensitive adhesive layer is formed on the peripheral edge of one side of the support, and the support has a maximum bond with the breathable synthetic resin film. Product r/! with a water absorbing layer interposed between porous synthetic resin films with pore diameters of 30 μm or less! J film, a pressure-sensitive adhesive layer is formed on the periphery of the exposed surface of the porous synthetic WI film in the support, and a drug-containing body is provided in a region surrounded by the pressure-sensitive adhesive layer. It is characterized by:

That is, by using the same support as in the above case, this external patch improves the adhesion between the external patch and the skin, and allows the skin to breathe smoothly, thereby improving the adhesive area. It is extremely safe because it prevents the occurrence of whitening, itching, and rashes, and the support absorbs sweat and other substances and exhibits an excellent ODT effect, which prevents the drug from being absorbed from the skin in the body. It is designed to improve absorption into the skin.

The support used in the present invention is the same as described above, and therefore the breathable synthetic resin film, water absorption layer and porous synthetic resin film are the same as those described above.

Further, a pressure-sensitive adhesive MR is formed on the periphery of the exposed surface of the porous synthetic bookstore film in the support, and a drug-containing body is provided in a region surrounded by the pressure-sensitive adhesive layer.

This pressure-sensitive adhesive layer is a layer formed of a pressure-sensitive adhesive, and it does not matter whether it contains a drug or not.This pressure-sensitive adhesive is the same as the above-mentioned external patch. Further, as the drug contained in this pressure-sensitive adhesive layer, the same drugs as those mentioned above can be mentioned.

In the external patch of the present invention, a drug-containing body is provided in a region surrounded by a pressure-sensitive adhesive layer. ! It consists of a drug retained by methods such as j.

Examples of this drug include those similar to the above-mentioned drugs. In addition, this drug may be impregnated and held in the drug carrier described below as it is, or the drug may be mixed with various base materials,
This may be coated or laminated on the drug carrier described below.
In this case, the mixing ratio of the drug and the base material is generally 10
0.1 to 45 parts by weight per 0 parts by weight, especially 1 to 30 parts by weight 1
It is desirable that the range be within the range of

The drug support is not particularly limited as long as it can stably hold the drug by impregnation or other methods, and specific examples include synthetic resins such as zeolite, polyurethane porous materials, etc. Porous materials made of synthetic fibers, fabrics made of synthetic fibers or natural fibers, non-woven fabrics, etc. are used.

With this configuration, in the external patch,
The pressure-sensitive adhesive layer formed on one side of the support, that is, the pressure-sensitive adhesive layer formed on the periphery of the exposed surface of the porous synthetic resin film in the support 9, attaches the topical patch to the outer skin and attaches the drug. The ffi-seal is carried out with the drug-containing body in close contact with the skin. Therefore, at the site where the drug-containing body is provided, transdermal absorption of the drug occurs and smooth skin respiration occurs. In addition, excess sweat is effectively absorbed by the water-absorbing layer, ensuring good adhesion between the patch and the skin.Moreover, as mentioned above, the oxygen permeability of the support is ensured to facilitate skin breathing, and ODT The therapy significantly improves the absorption of drugs into the body through the skin.

In the external patch of the present invention, the oxygen permeability of the support is 2000-200.000a+1/m2/24! +r/
By being at111, it does not impede skin respiration and allows the skin to respire oxygen efficiently (as well as exhibiting even better OCT effects), which allows the drug to be absorbed into the body. From these points of view, the oxygen permeability of the support is 4.000-50.
, OOOi*1/+a2/24hr/atm.

In this case, this oxygen permeability is generally determined using a mixed gas permeability tester GP manufactured by LYSSY at a temperature of 23°C.
Measurements were made using a chromatographic isobaric method using Model M-200.

In the external patch of the present invention, the moisture permeability of the porous synthetic barrier film is determined by the pore size and the degree of hydrophilicity of the film, and the moisture permeability is 50 g/ar'/
By setting it to 241+r or higher, the moisture permeability, that is, the permeability of sweat, is good, and the sweat generated by perspiration is reliably absorbed, so there is no formation of dew condensation at the application site of the external patch, and as a result, it is possible to use it externally. Patch and skin! This is desirable because the XI property becomes even better.

By the way, this moisture permeability is measured according to JIS Z-0208.

In the external patch of the present invention, the porous synthetic tit oil film is hydrophilic and the one that has been subjected to hydrophilic treatment by scraping has a significantly high sweat absorption rate and can prevent layer condensation. This is preferable because it can be applied to areas with severe sweating.

The above-mentioned hydrophilicity imparting agent is not particularly limited as long as it is a porous synthetic υ (provided on the surface of the fat film to improve the hydrophilicity of the film), ethanol,
Examples include alcohols such as propyl alcohol and butanol, polyhydric alcohols such as glycerin, polyglycerin, ethylene glycol, and polyethylene glycol, and various surfactants.

Methods for hydrophilizing the porous synthetic resin film using the hydrophilicity-imparting agent include a method in which the hydrophilicity-imparting agent is mixed into the porous synthetic resin film, and a method in which the surface of the porous synthetic resin film is made hydrophilic. Examples include a method of coating a hydrophilicity-imparting agent, dipping the film in an aqueous solution of a hydrophilicity-imparting agent, and a method of spraying this aqueous solution onto the film.

In the external patch of the present invention, it is preferable to partially include a water-absorbing layer because the amount of water absorbed and the permeability of oxygen, etc. can be adjusted.

In other words, a water absorbing layer is provided partially and other parts (breathable synthetic resin film and porous synthetic resin IIW film) are heat-sealed, or a hot melt adhesive is interposed in other parts to form a surface layer. The film (breathable synthetic 81 resin film) and the back film (porous synthetic resin film) may be thermally bonded, and a water-absorbing layer that can be used simultaneously when heat-sealing the front and back surfaces is used. At the time of application, it can be heat-sealed in a desired pattern using any embossing roll.

In the second case, a breathable synthetic resin film and a porous synthetic a
Instead of thermally adhering or heat-sealing the T-fat films, various adhesives may be used to adhere these films to each other.

The adhesive is not particularly limited (for example, acrylic adhesive, rubber adhesive such as synthetic rubber or natural rubber, vinyl adhesive, terpene resin, or water-soluble ronone). etc.

By the way, the preparation of the external patch of the present invention does not require any special technique or equipment and can be obtained by a conventional method.

Specifically, for example, a coating liquid prepared by mixing a water-absorbing polymer, or a water-absorbing agent or an adhesive therein, is applied to the surface of either a breathable synthetic resin film or a porous synthetic resin film. After applying by gravure method, roll coating method, or silk screen method,
Either the breathable synthetic 81 resin film or the porous synthetic resin film is pasted together to form a support, and the periphery of the exposed surface of the porous synthetic resin film on the support is screened using a silk screen method. For example, a pressure-sensitive adhesive layer is formed by a method such as the like, and a drug-containing body made of gauze or a polyurethane porous body containing a drug is provided in a region surrounded by the pressure-sensitive adhesive layer.

In this case, from the viewpoints of adhesion between the breathable synthetic resin film and the porous synthetic resin film, water absorption amount, moisture absorption ability, etc., a water absorbing layer may be provided on the entire surface or a portion of the film.

By applying the external patch of the present invention to the skin of a living body, the drug can be absorbed transdermally for a long period of time for reasons described below.

(e) Effect In the external patch of the present invention, a specific support characterized by a water-absorbing layer is used, and a drug-containing adhesive layer is partially formed on one side of the support, so that this water-absorbing layer is It effectively absorbs sweat and always maintains good adhesion between the patch and the skin.For this reason, transdermal absorption of the drug occurs in areas where the drug-containing adhesive layer is formed, while this layer The oxygen permeability of the support is ensured in areas where the skin is not formed, allowing the skin to breathe smoothly, preventing whitening, redness, itching, and rashes at the application site.
The support exhibits an ODT effect, thereby improving the absorption of the drug into the body through the skin.

In addition, in the external patch of the present invention, a specific support characterized by a water-absorbing agent is used, and one side (exposed side) of the support is
By forming a pressure-sensitive adhesive layer on the periphery and providing a drug-containing body in a region surrounded by the abdominal pressure-sensitive adhesive layer,
By improving the adhesion between this topical patch and the skin and making it easier for the skin to breathe, it prevents the appearance of whitening, itching, and rashes at the application site, making it extremely safe. The support exhibits excellent OCT effects,
This has the effect of improving the absorption of drugs into the body through the skin.

(f) Examples Hereinafter, the present invention will be explained in detail based on Examples, but the present invention is not limited thereto.

In the following, (a) breathable synthetic opening 1 resin film, (b
) Water absorption layer material, (c) porous base rIL resin film,
For each, the following were used.

(a) Breathable synthetic tree M film □■-degree 0.927g/c-co, MI=2. 0,
Thickness: 30μ thick polyethylene film (1!!
Excessive 6000 me/m2/24hr/atm)
(b) Starch-polyacrylic acid graft copolymer media (manufactured by Sanyo Kasei Co., Ltd., Sunwet IM=300) as the water-absorbing polymer for the water-absorbing layer
), and as a urethane adhesive, Dainippon Ink (Match)! 12, (EPS-75A) was used.

(c) Porous synthetic resin film linear low-density polyethylene (density 0.927 g/c x3,
MI=2.0) Average particle size 2°5 per part of 1.00 weight
By adding 150 parts by weight of μ-ugly barium sulfate, melting the film, and then stretching it, a film with a thickness of 20μ and a moisture permeability of 2000 g/m'/24hr1 and a maximum pore diameter of 7.5
Next, in order to improve the water absorption rate of this film, a phenolic surfactant (manufactured by Kyubishi Yuka Co., Ltd., MTN-F684) was applied to the film surface.
01! ! ! ! The L% isoflovir alcohol solution was applied by dipping and subjected to hydrophilic treatment.

! ! Example 100 parts of the urethane adhesive described in (b) above and 1001 parts of the water-absorbing polymer are mixed at low speed in a homomixer, and this is mixed to form the polyethylene film (synthetic resin film) described in (a) above. After forming a water-absorbing layer (thickness 10 μl) on the surface by coating with a gravure roll, the porous synthetic lubricant film described in (c) above was laminated on the water-absorbing layer, and this laminated film was coated with [ 40+am,
A support was obtained by cutting into a rectangle with a width of 30 u+m.

The oxygen permeability of this support is 4400 m1/aa2/
It was 24hr/at11.

Example 1 Porous synthesis in the above support 6111! A drug-containing adhesive layer, which will be described later, was formed in horizontal stripes on the exposed surface of the T-film. In this case, the formation area of the drug-containing adhesive layer is 60%, and therefore, the remaining 40% of the porous synthetic resin film on the support is exposed.

100 parts by weight of acrylic acid isobutyl ester, 100 parts of acrylic acid isobutyl ester [1 fi part] and 6011 parts of ethyl acetate! of azoisobutyronitrile as a polymerization initiator.
5 parts by weight was added to start polymerization, ethyl acetate was added dropwise, and the polymerization reaction was carried out for 10 hours while controlling the reaction temperature at 60 to 65°C.The solution viscosity at a solid content concentration of 35% by weight and a temperature of 25°C was A copolymer solution of 425 Boi X was obtained.

5.5 parts by weight of propranolol hydrochloride, a drug for cardiovascular organs, was added and mixed to 100 parts by weight of the solid content of the obtained copolymer solution, and the mixture was poured onto a release liner so that the thickness after drying would be 50 μm. Specifically, in this case, the drug-containing adhesive MM was coated in horizontal stripes and dried to form a drug-containing adhesive MM (60% of the total area), which was transferred to the exposed surface of the porous synthetic resin film on the support.

In this way, an external patch of the present invention was obtained.

Comparative Example 1 A support was made of a polyethylene film (synthetic resin film) with a thickness of 50 μm, one side of which was roughened by corona treatment, and a drug was added to the rough side of the support in the same manner as in Example 1. A material with an adhesive layer formed thereon was used.

Example 2 90 weight 1 g of acrylic acid 2-ethylhexyl ester, acrylic acid ethyl ester 10 weight 1 part, and ethyl acetate 50 weight
Using the mji part, a polymerization reaction was carried out in the same manner as in Example 1,
A copolymer solution with a solid content concentration of 38% by weight, a temperature of 25° C., and a viscosity of 330 voids was obtained.

To 100 parts by weight of the solid content of the obtained copolymer solution, 5.5 parts by weight of noaenehydramine hydrochloride, which is an allele warp, was added and mixed, and the mixture was coated on a release liner to a thickness of 50 μm after drying.
After coating in spots, in this case in a 51-diameter circular pattern, the drug-containing adhesive layer is dried to form a drug-containing adhesive layer (65% of the total area), and this is applied as a porous synthetic material to the support. It was transferred to the exposed surface of the resin film.

In this way, an external patch of the present invention was obtained.

Example 3 90 parts by weight of acrylic acid 2-ethylhexyl ester, 1 part by weight of acrylic acid, 1 part by weight of vinyl acetate: [i and 50 parts by weight of ethyl acetate, 11 parts by weight, were combined and subjected to a polymerization reaction in the same manner as in Example 1. Viscosity 60 at solid concentration 40 wt 1% and temperature 25°C
A copolymer solution with zero voids was obtained.

To 100 parts by weight of the solid content of the obtained copolymer solution, 5.5 parts by weight of methoxy 7-enamine hydrochloride, which is a drug for respiratory organs, was added and mixed, and the mixture was placed on a mold release liner to a thickness of 50 μm after drying. It is coated partially (in this case in vertical stripes) and dried to form a drug-containing adhesive layer (45% of the total area), and then applied to the exposed surface of the porous synthetic resin film on the support.
I arrived at g.

In this way, an external patch of the present invention was obtained.

Example 4 A topical patch was obtained in the same manner as in Example 1, except that the same copolymer solution as that used in Example 1 was used and 5 parts by weight of nicotinic acid, a metabolic drug, was used as the drug. Ta.

Example 5 Acrylic PI12-ethylhexyl ester 75 parts by weight, acrylic acid ethyl ester 10 parts by weight, acrylic acid 2
- 15 parts by weight of ethoxyethyl ester and 5 parts by weight of ethyl acetate
A polymerization reaction was carried out in the same manner as in Example 1 using 0 weight ffi parts to obtain a copolymer solution having a solid content concentration of 38%, a temperature of 25° C., and a viscosity of 630 voids.

5.5 parts of ketopro7ene, an anti-inflammatory and analgesic agent, was added and mixed to 100 parts of the solid content of the obtained copolymer solution, and the mixture was placed on a release liner so that the thickness after drying was 50 μm. It was coated in stripes and dried to form a drug-containing adhesive layer (65% of the total area), which was transferred to the exposed surface of the porous synthetic resin film on the support.

In this way, an external patch of the present invention was obtained.

Example 6 The above support was cut into a rectangle with a length of 40 mm and a width of 30 mm.

On the other hand, the copolymer solution (containing no drug) obtained in Example 2 was placed on the four peripheral edges of a release liner cut to the same size as this support, so that the thickness after drying was 50 μmo and the width was 5 μm. A pressure-sensitive adhesive layer was formed by coating and drying so as to form a solid pattern, and this was transferred to the exposed surface of the porous synthetic resin film on the support.

A drug-containing body was prepared by applying the following anti-inflammatory and analgesic ointment to a dog and keeping it there. The size of this drug-containing body is 3 vertically.
It was formed to have a width of 20 mm.

Then, in the support, the drug-containing body was provided in a region surrounded by the pressure-sensitive adhesive layer to form an external patch of the present invention.

Indomethacin: 1.0% by weight Sorbitol 8. Ofi amount% ethanol 70
% solution 56.0 weight 1% water
Example 7 Anti-inflammatory and analgesic ointment prepared by kelizing a formulation consisting of 33.0% by weight hydroxyethylcellulose and 2.0ffNt% In Example 6, in place of the drug-containing material, a flexible foamed polyurethane porous material (thickness 0, 5 i*l11)
An external patch of the present invention was obtained in the same manner as in Example 6, except that the drug-containing body obtained by forming the anti-inflammatory analgesic ointment on one side of the skin was used.

Comparative example 2 The above anti-inflammatory m1itl soft blue agent was used.

Using each of the above Examples and Comparative Example 1,
It was applied to the inside of the body, and its adhesion to the skin surface was investigated 12 hours after application (a total of 10 panelists, 5 men and 5 women) found that each example In all cases, adhesion was good over the entire surface, but in Comparative Example 1, slight curling was observed at some peripheral edges.

Also, use each Example and each Comparative Example, and paste this on the inside of the upper @ part. For Comparative Example 2, apply 4 to 40 mm
3 hours after pasting,
After 6 hours and 12 hours, 5 ml of blood was collected and plasma was separated, which was concentrated using a conventional method, the drug was extracted, and the concentration was determined using gas chromatography.

As a result, it was found that the drug concentration of Example 1 was about 10% lower after 3 hours than that of Comparative Example 1, but after 6 hours, the drug concentration was opposite to that of Example 1. It was found that the sample of Example 1 was about 13% higher, and furthermore, after the addition of 12 Bi, the sample of Example 1 was about 21% higher.

In addition, in Comparative Example 2, the drug concentration after 3 hours was that of Example 6.
However, after 6 hours, the drug concentration of Examples 6 and 7 was about 28% higher than that of Comparative Example 2, and after 12 hours, the drug concentration was also slightly higher than that of Example 7. The drug concentration in Examples 6 and 7 was more than double that in Comparative Example 2 (in Comparative Example 2, the drug concentration after 12 hours was about 1/3 of the drug concentration after 3 hours). Met.).

From the above results, the drugs of each example promote the OD 'l' effect, so compared to the drug of Comparative Example 1, the drug absorption is extremely high (in addition, the adhesion to the skin is good and it lasts for a long time). Good absorption of the drug over time is observed.

Furthermore, in Comparative Example 1, although the initial absorption of the drug was good, the drug concentration decreased over time, and it was observed that long-term sustainability was lacking. The reason for this is understood to be that the adhesion with the skin gradually deteriorates due to sweating, and the percutaneous absorption of the drug decreases.

Furthermore, in Comparative Example 2 (ointment), the absorption time of the drug is limited, resulting in a lack of long-lasting medicinal efficacy.In addition, this product is sticky, causing discomfort9, and may stain underwear. was recognized.

In the above example, a case was explained in which the pressure-sensitive adhesive layer on the peripheral edge of one side (exposed surface) of the support did not contain a drug, but the drug was not contained in the pressure-sensitive adhesive layer within the range where the adhesive strength of the pressure-sensitive adhesive layer was not significantly reduced. It is also possible to contain a drug.

In this case, the drug may be the same as or different from the drug in the drug-containing body, and by using different drugs, the disease may be effectively treated due to the synergistic effects of the drugs.

(Fl) Effects of the Invention Since the present invention is configured as described above, it achieves the effects described below.

In the external patch according to claim 1, a specific support having a water-absorbing layer is used, and a drug-containing adhesive layer is partially formed on one side of the support, so that this water-absorbing layer can absorb excess water. It effectively absorbs sweat and always maintains good adhesion between the patch and the skin.For this reason, while the drug is absorbed transdermally at the site where the drug-containing adhesive layer is formed,
Sweat, etc. will not condense on the skin surface (in areas where this layer is not formed, oxygen permeability of the support is ensured, so the skin can breathe smoothly, preventing whitening and itchiness at the application site). Furthermore, in addition to preventing the occurrence of rash etc., the support exhibits an OCT effect, which has the effect of improving the absorption of the drug into the body through the skin.

In the external patch according to claim 2, since the oxygen permeability of the support is adjusted to 2000 to 200.000,
Efficient oxygen respiration through the skin and better ODT
Therefore, it has the effect of allowing the drug to be absorbed into the body.

In the external patch of claim 3, the porous synthetic 1f
Moisture permeability is determined by the pore size of the t1t film and the degree of hydrophilicity of the film.
hr or more, the moisture permeability, that is, the permeability of sweat, is good, and the sweat generated by perspiration is reliably absorbed, so that no condensation occurs at the application site of the topical patch, and as a result, the skin This has the effect of preventing the surface from getting wet and further improving the adhesion between the external patch and the skin.

In the external patch of claim 4, the porous synthetic tree 11t
Since the film has been subjected to hydrophilic treatment with a hydrophilicity imparting agent, the water absorption rate of sweat is significantly high, and it is possible to prevent dew condensation. Therefore, it has the effect that it can be applied to areas where perspiration is intense.

In the external patch of claim 5, by partially forming the water absorption layer, it has the effect of adjusting the amount of water absorption and the permeability of a-element etc. to 8:4.

In the external patch according to claim 6, the water absorbing layer is
A specific support having one layer is used, and one side of the support (
A pressure-sensitive adhesive layer is formed on the periphery (exposed surface), and a drug-containing body is provided in the area surrounded by the pressure-sensitive adhesive layer, thereby improving the adhesion between this external patch and the skin. By allowing the skin to breathe smoothly, it is extremely safe as it prevents the appearance of whitening, itching, and rashes at the patch M site.Furthermore, the support exhibits an ODT effect, and as a result, This has the effect of improving the absorption of drugs into the body through the skin.

In the external patch of the in claim, the oxygen permeability of the support is adjusted to 2000 to 200,000, so that the skin can efficiently breathe oxygen and suppress the release of excess sweat, making it even better. It expresses the ODT effect,
This has the effect of allowing the drug to be absorbed into the body.

In the external patch of claim 8, the moisture permeability is determined by the pore diameter of the porous synthetic resin film and the degree of hydrophilicity of the film, and the moisture permeability is 50 g/m2/24.
hr or more, moisture permeability, that is, sweat permeability, is good, and sweat generated by perspiration is reliably absorbed, so that condensation does not occur at the application site of the external patch (as a result, This has the effect of further improving the adhesion between the external patch and the skin.

In the external patch according to claim 9, the porous synthetic tree 1jl
't Because the film has been subjected to hydrophilic treatment using a hydrophilicity imparting agent, the water absorption rate of sweat is extremely high and it is possible to prevent dew condensation. be.

In the external patch according to claim 10, by partially forming the water absorbing layer, the amount of water absorbed and the permeability of oxygen, etc. are reduced to 7f4.
It has a calming effect.

Claims (10)

[Claims] (1) In a patch having a drug-containing adhesive layer formed on one side of a support, the support has a water-absorbing layer interposed between an air-permeable synthetic resin film and a porous synthetic resin film with a maximum pore diameter of 30 μm or less. An external patch consisting of a laminated film, in which a drug-containing adhesive layer is partially formed on the exposed surface of a porous synthetic resin film in the support. (2) Oxygen permeability of the support is 2000 to 200,000
The external patch according to claim 1, which has a dosage of ml/m^2/24hr/atm. (3) The moisture permeability of the porous synthetic resin film is 50g/m^
The external patch according to claim 1 or 2, which has a duration of 2/24 hr or more. (4) The external patch according to any one of claims 1 to 3, wherein the porous synthetic resin film is subjected to hydrophilic treatment with a hydrophilicity imparting agent. (5) The external patch according to any one of claims 1 to 4, wherein the water-absorbing layer is partially interposed. (6) In a patch in which a pressure-sensitive adhesive layer is formed on the peripheral edge of one side of a support, the support has a water-absorbing layer between an air-permeable synthetic resin film and a porous synthetic resin film with a maximum pore diameter of 30 μm or less. Consists of a laminated film with intervening
A patch for external use, characterized in that a pressure-sensitive adhesive layer is formed on the periphery of the exposed surface of the porous synthetic resin film in the support, and a drug-containing body is provided in a region surrounded by the pressure-sensitive adhesive layer. agent. (7) Oxygen permeability of the support is 2000 to 200,000
The external patch according to claim 6, which has a dosage of ml/m^2/24hr/atm. (8) The moisture permeability of the porous synthetic resin film is 50g/m^
The external patch according to claim 6 or 7, which has a duration of 2/24 hr or more. (9) The external patch according to any one of claims 6 to 8, wherein the porous synthetic resin film is subjected to hydrophilic treatment with a hydrophilicity imparting agent. (10) The external patch according to any one of claims 6 to 9, wherein the water-absorbing layer is partially interposed.