JPH1072343A - Persistent/fast-acting ketoprofen patch and its production - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a persistent/fast-acting ketoprofen patch having a composite laminate structure in which a medicine layer and an adhesive layer are perfectly different from each other, itself having a medicine release-controlling function, and capable of persistently and uniformly holding the medicinal effect. SOLUTION: This persistent/fast-acting ketoprofen patch has a complicated laminate structure formed by successively laminating a skin-adhering layer having a medicinal solution release-controlling function, a highly aqueous ketoprofen-containing medicinal layer, a non-aqueous primer layer and a water- permeable backing to mold release paper. The ketoprofen patch is excellent in adhesive force to skin, can be attached to or detached from the skin, if necessary, many times, can tightly be adhered to the skin to sufficiently transmit the medicinal effect of the ketoprofen to the body of a patient through the skin, and can persistently release a constant amount of the medicine or is excellent in the initial release of the medicine. The employment of a non-adhesive polymer as a binder for the medicine layer enables to diversify the binder capable of being used.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a ketoprofen patch, and more particularly to a ketoprofen patch (Ketprofen patch) as a therapeutic agent for arthritis, which is capable of transdermally administering ketoprofen which is effective for treating arthritis and rheumatism.
oprofen Patch).

[0002]

2. Description of the Related Art Ketoprofen plaster (trade name: commercially available in the art as a therapeutic agent for arthritis for percutaneous administration).
Keto Top, manufactured by Taiheiyo Pharmaceutical Co., Ltd.)
Acrylic adhesive and propylene glycol monolaurate as an enhancer (skin penetration enhancer) to help the drug penetrate the skin into the acrylic pressure-sensitive adhesive and the polyisobutylene rubber-based pressure-sensitive adhesive transfer-coated as a (primer) (propylene glycol monola
urylate) is formed by transfer coating. Such ketoprofen plasters
There is no difference from existing pass products.

On the other hand, US Pat. No. 5,505,956 discloses a backing of a support and a liner.
When using a backing that does not allow moisture to pass through, there are 2 to 5 adhesive layers between the backing and the surface layer that comes into contact with the skin, so that each layer from a high moisture content layer becomes a gradually lower layer In contrast, when using a backing that allows moisture to pass through like a non-woven fabric, each layer from the backing to the surface layer that comes into contact with the skin is configured such that the layers from low moisture content gradually increase to higher layers Ketoprofen patches have been disclosed. In this ketoprofen patch, a substance such as polyvinyl alcohol is used in an amount of 0.3 to 30% by weight in order to increase the water content. Ketoprofen (0.1 to 40% by weight) includes an acrylic adhesive or , And a mixture with an enhancer such as propylene monoglycolate.

[0004] However, such a ketoprofen patch is excellent in solubility in ketoprofen due to the presence of the ketoprofen drug mixed with the acrylic adhesive, but is slow in diffusion and has a constant drug release amount. As a result, there is a problem that the dose of the drug over time is not kept constant. In addition, since non-adhesive polymer substances such as powdered drugs such as ketoprofen and polyvinyl alcohol are mixed with acrylic adhesives, their adhesion to the skin is very weak, and they once come off the skin. There is also a disadvantage in that if the product is pasted again, it cannot be reattached.

[0005] In addition, the patch is a drug delivery substance through the skin, and its medicinal effect is proportional to the area in contact with the skin. Therefore, the larger the area peeled off from the skin after the patch is attached, the lower the drug delivery rate becomes. There is an inherent problem that the medicinal effect is significantly inferior in proportion to this. For this reason, in the art, ketoprofen which has good adhesiveness so that the drug effect can be maintained for a long time, and which has a constant drug release amount per unit time and excellent initial drug release performance The development of patches is eager.

[0006]

SUMMARY OF THE INVENTION The present invention has been made to solve the above problems inherent in this technical field, and its first problem is as follows.
An object of the present invention is to provide a sustained / rapid-acting ketoprofen patch which has a function of controlling the amount of drug release itself and has a uniform and persistent drug effect. A second object of the present invention is to provide an adhesive agent that has excellent adhesiveness to the skin, can be attached and detached many times as necessary, adheres to the skin when adhered, and has a long lasting property so that the medicinal effects of ketoprofen can be sufficiently transmitted through the skin. / Providing a fast acting ketoprofen patch.
A third object of the present invention is to provide a sustained / rapid-acting ketoprofen patch in which a drug is continuously released in a fixed amount from the beginning or an initial drug release is excellent. A fourth object of the present invention is to provide a production method suitable for producing these sustained / fast-acting ketoprofen patches.

[0007]

In order to achieve the above object, a sustained / fast-acting ketoprofen patch according to the present invention comprises a backing, a non-water-soluble acrylic / rubber-based primer, and a ketoprofen dissolved in a water-soluble polymer. A highly water-soluble drug layer and a skin adhesive layer having a drug release controlling function are sequentially laminated. In particular, the ketoprofen patch according to the present invention is characterized in that it has a composite laminated structure in which the drug layer and the adhesive layer are completely different.

More specifically, the sustained / fast-acting ketoprofen patch according to the present invention comprises a water-permeable backing,
It has a composite laminated structure in which a non-water-soluble primer, a highly water-soluble ketoprofen-containing drug layer, and a skin adhesive layer having a function of controlling a drug solution release amount are sequentially stacked.

Here, in the present specification, “non-water-soluble”
Means that water hardly penetrates, "high moisture"
Means that water is well penetrated. Such a ketoprofen patch differs only in the substance used between a long-lasting case and a fast-acting case, and its production method is almost the same.

That is, a sustained release ketoprofen patch in which a drug is constantly released over time is as follows: (1) A silicone-coated paper or a polyester film is coated with an ethyl acetate solvent type acrylic adhesive to about 80 ° C. Drying for 1-2 minutes (coating thickness 20-50 μm), and then transfer-coating on a backing to form a primer;

(2) A drug solution prepared by dissolving ketoprofen in a mixture of a polyvinyl alcohol (PVA) aqueous solution and an acrylic emulsion adhesive in a skin penetration enhancer is coated on silicon-coated paper and dried (coating thickness: 30). ５０50 μm), and then transfer-coated on the primer to form a drug layer;

(3) After the emulsifier or organic salt is dissolved in ethyl acetate, an acrylic pressure-sensitive adhesive is mixed, stirred and coated on silicon-coated paper, and dried (coating thickness: 5 to 40 μm, preferably 10 to 20 μm). ), And transfer-coating on the drug layer to form a skin adhesive layer.

On the other hand, a quick-acting ketoprofen patch having excellent initial drug release performance is as follows: (1) A rubber-based pressure-sensitive adhesive is coated on a silicon-coated paper or a polyester film, and is coated at a temperature of about 60 ° C. with a temperature of 1-2.
Minute, dried at about 80 ° C for about 1 minute (coating thickness 20 ~
50 μm, preferably 30-40 μm) and then transfer coating on a moisture permeable backing to form a primer;

(2) Ethylene vinyl acetate copolymer (EV
A) Emulsion and / or synthetic rubber latex (lat)
ex) was mixed with an aqueous polyvinyl alcohol solution, and a drug solution prepared by dissolving ketoprofen powder in a skin penetration enhancer was coated on silicon-coated paper, and dried (coating thickness: 10 to 100 μm, preferably 3 μm).
0 to 40 μm), and then transfer-coated on the primer to form a drug layer;

(3) An emulsifier or an organic salt is dissolved in ethyl acetate, and then an acrylic pressure-sensitive adhesive is mixed, stirred and coated on a silicon-coated paper, and dried (coating thickness: 5 to 40 μm, preferably 10 to 20 μm). And then transfer-coating the drug layer to form a skin adhesive layer.

According to such a rapid-acting ketoprofen patch according to the present invention, the rubber adhesive contained in the primer minimizes the reverse diffusion of the drug and the absorption enhancer to the primer and forms a water-soluble polymer. By adding an EVA emulsion or a synthetic rubber-based latex to increase the hydrophobicity of the drug layer, excellent drug release is smoothly performed.

In addition, in a conventional transdermal absorption preparation, in addition to those having a liquid drug layer such as a reservoir type (Reservoir type) or a hydrogel type (Hydrogel type), a matrix in which the drug layer is a solid as in the present invention is used. When a matrix type is adopted, a binder (a high-molecular substance excluding a drug and a skin promoting agent) is mostly used. However, in the case of adopting a matrix type in an existing percutaneous absorption preparation, this binder had to be a sticky / adhesive polymer, but in the present invention, a binder having no tack / adhesive was used. Since it can be used, it is possible to widen the range of binder selection.

[0018]

Embodiments of the present invention will be described below more specifically with reference to the accompanying drawings. FIG. 1 is a cross-sectional view of a sustained and fast acting ketoprofen patch according to the present invention. As shown in the figure, the ketoprofen patch according to the present invention has a structure in which a primer 20, a drug layer 30, a skin adhesive layer 40, and a release paper 50 are sequentially laminated on a backing 10.

As the backing 10, a nonwoven fabric, a polyester film, a polyurethane film or the like can be used. Various materials can be used for the backing 10 irrespective of whether or not moisture is allowed to pass, but it is most preferable to use a moisture-permeable nonwoven fabric.

The primer 20 is for preventing the drug and the skin permeation enhancer in the drug layer 30 from flowing to the backing or the primer or leaking out of the backing, and to provide a sustained drug release property. Ethyl acetate solvent type acrylic adhesive (acrylic adhesive dissolved in ethyl acetate) is used. In such a case, it is possible to control the concentration and diffusion rate of the drug in the matrix by giving the drug back diffusion, thereby controlling the release of the drug. On the other hand, in order to improve the initial drug release characteristics, it is desirable to use a rubber-based pressure-sensitive adhesive. The rubber pressure-sensitive adhesive is a compound formed by adding an antioxidant of a terpene-based tackifier to rubber. In such a case, reverse diffusion of the drug can be minimized. In practicing the present invention, such an adhesive is coated on a silicon-coated paper or polyester film and dried to form a coating. The coating thickness after drying is suitably 20 to 50 μm.

The drug layer 30 preferably uses a non-adhesive mixed matrix of a water-swellable or water-soluble polymer and a hydrophobic polymer in order to maximize the content and release of the drug. In addition, it is preferable to use an absorption enhancer capable of dissolving an oil-soluble and poorly water-soluble ketoprofen drug. Fatty alcohol,
There are sorbitan monooleate, polyethylene glycol, glycerin, pyrrolidone, NMP (N-methylpyrrolidone), DMF (dimethylformamide), DMSO (dimethylsulfoxide) or DETA (diethyltriamide), and a skin penetration enhancer for 1 g of ketoprofen drug Even if only 1 g is used, the ketoprofen powder can be effectively dissolved within 15 minutes. Here, the fatty acid alcohol is selected from oleyl alcohol and its derivatives. When a mixture of oleyl alcohol and sorbitan monooleate is used as a skin penetration enhancer, the mixing ratio is 10:90 to 90:10 parts by weight, preferably 30:70 to 70:30 parts by weight,
Ketoprofen is preferably contained at 1 to 90% by weight, preferably 10 to 20% by weight of the drug solution.

The water-soluble polymer in the polymer material of the matrix includes PVA, polyacrylic acid, polyacrylamide, poly N-vinylpyrrolidone, chitin, chitosan,
One or more of cellulose or salts thereof can be used, but PVA is most preferably used. on the other hand,
An acrylic pressure-sensitive adhesive, EVA, or synthetic rubber latex can be used as the water-insoluble polymer.

The water-soluble polymer and the water-insoluble polymer are used by being mixed with each other. Specifically, a mixture of an aqueous PVA solution and an acrylic pressure-sensitive adhesive, or an EVA emulsion and a PVA aqueous solution are used. What mixed the synthetic rubber latex can be used.

When an acrylic pressure-sensitive adhesive is used, it is mixed with a PVA aqueous solution at a ratio of 10:90 to 90:10 parts by weight, preferably 50:50 to 75:25 parts by weight based on the solid powder content. Good. At this time, the amount of the mixture of the PVA aqueous solution and the acrylic pressure-sensitive adhesive is 5 to 95% by weight based on the total weight of the drug layer. When using an EVA emulsion, 10: 90-90:
What is mixed with a PVA aqueous solution at a ratio of 10 parts by weight, preferably 30:70 to 70:30 parts by weight is good. At this time, P
The amount of the mixture of the VA aqueous solution and the EVA emulsion is 10 to 80% by weight based on the total weight of the drug solution. When a synthetic rubber latex is used, it is preferably mixed with a PVA aqueous solution at a ratio of 10:90 to 90:10 parts by weight, preferably 25:75 to 70:20 parts by weight based on the solid powder content. At this time, the PVA aqueous solution and the synthetic rubber latex mixed matrix occupy 10 to 80% by weight based on the total weight of the drug solution.

An EVA emulsion and a synthetic rubber latex can be mixed in the PVA aqueous solution. At this time, the PVA aqueous solution: EVA emulsion: synthetic rubber is 10 to 90:10 to 90: 1 to 50 based on the solid powder. % By weight. The mixture of the PVA aqueous solution, the EVA emulsion and the synthetic rubber latex accounts for 10 to 80% by weight based on the total weight of the drug layer. Here, the synthetic rubber latex is preferably SBR (Stylene-butadiene rubber) latex. The EVA emulsion has an ethylene content of 1 to 99% by weight, preferably 10 to 50% by weight, and the solution in which the drug is dissolved is 10 to 90% by weight, preferably 50 to 90% by weight based on the whole drug layer. It is used by adjusting to be 70% by weight.

In practicing the present invention, such a mixed matrix of a water-soluble polymer and a water-insoluble polymer and a drug solution obtained by dissolving ketoprofen in a skin penetration enhancer are added to a silicon-coated paper. Alternatively, it is coated on a polyester film, in which case the skin penetration enhancer and ketoprofen are 100: 1 to 50
Mix and use in parts by weight. In this case,
The thickness after drying is preferably 30 to 50 μm.

If the skin adhesive layer 40 is coated with a thick adhesive to simply increase the adhesive strength only to the skin, the delay time for drug release becomes longer. That is, if the thickness is 40 μm or more in order to increase the adhesive maintenance force, the drug release effect is not successful, and if the thickness is 10 μm or less, the adhesive maintenance force on the skin is reduced, so even if the initial adhesion is good. It will come off easily during the activity.
Accordingly, the skin adhesive layer 40 has a strength of 5 to 40 to maintain a strong adhesive force to the skin and to release the drug at a constant rate.
It is good to form it with a thickness of μm, preferably 10 to 20 μm.

The skin pressure-sensitive adhesive layer 40 is prepared by adding an emulsifier or an organic salt-based skin penetration enhancer to the acrylic pressure-sensitive adhesive in an amount of 0.005 to 50% by weight based on the weight of the drug layer 30. By using 0.05-0.5% by weight, water passing through the skin dissolves the salt and does not lose the adhesiveness to the skin, but creates certain fine channels in the polymer structure of the skin adhesive layer. As a result, an effect is obtained in which the medicine is released only in a certain amount within a certain time. Emulsifiers include oleyl alcohol or sorbitan monooleate, poly (acrylic acid), polyacrylamide (poly (acryl amide)), poly N-vinyl pyrrolidone (poly (N-vinyl pyrolidone)), chitin (Chit
in), chitosan, cellulose (Cellulose) and their salts can be used.
When used in the range of 5 to 10% by weight with respect to 0, the effect of increasing the solubility of the drug and releasing the drug constantly within a certain time without losing the adhesive strength can be obtained. In addition, as a salt, a veil salt can be used.

Hereinafter, the present invention will be described in more detail with reference to examples. However, such an embodiment does not limit the scope of the present invention indicated by the claims.

[0030]

Embodiment 1

【Example】

<Production 1 of persistent ketoprofen patch> [A. Formation of Primer] (1) Ethyl acetate solvent-type acrylic pressure-sensitive adhesive (trade name: ST-96, manufactured by Ruitsu Co., Ltd.) having a solid powder content of 55% is coated on a silicon-coated paper, and heated at 800 ° C. for 9 hours.
Dry for 0 seconds. At this time, the coating thickness after drying was 40 μm.

(2) A primer was formed by transfer-coating the treated product of the above (1) on a stretchable nonwoven fabric through which moisture was permeable using a pressure roll.

[B. Formation of Ketoprofen-Containing Drug Layer] (1) 1 g of PVA having a polymerization degree of 500 was mixed with 41 g of water, and the mixture was gradually stirred to form a 20% by weight aqueous PVA solution. % Aqueous solution) and 1.57 g of an acrylic emulsion adhesive having a solid powder content of 55% (trade name: ST-96-E, manufactured by Ruitsu Co., Ltd.) is uniformly added to 4.71 g of the PVA aqueous solution. Was mixed.

(2) 0.5 g of ketoprofen powder as a drug
Was mixed with 0.45 g of oleyl alcohol and stirred to dissolve.

(3) The treated product of (1) and (2) and 1.65 g of sorbitan monooleate are mixed and stirred for 10 minutes to prepare a drug solution, which is then coated on silicon-coated paper and dried. After the thickness was adjusted to 50 μm, the drug layer was formed by transfer coating on the primer A using a pressure roll.

[C. Formation of Skin Adhesive Layer] (1) After dissolving 0.9 g of Vail Salt in 7.5 g of ethyl acetate, 30 g of an acrylic adhesive (trade name: ST-96, manufactured by Ruitsu Co., Ltd.) was mixed and stirred. After that, it was coated on a silicon-coated paper so that the thickness after drying was 30 μm.

(2) The treated product of the above (1) was transfer-coated on the drug layer of the above B (3) using a pressure roll to form a skin adhesive layer.

[0037]

Example 2 <Production 2 of sustained-release ketoprofen patch>

A primer and a drug layer were formed by the same composition and method as in Example 1, and a skin adhesive layer was manufactured by the following method, and then transferred and coated on the drug layer to manufacture a ketoprofen patch.

Production of a skin adhesive layer: 0.18 g of sorbitan monooleate and 7.5 g of ethyl acetate were dissolved in 0.72 g of oleyl alcohol, and then dissolved in an acrylic adhesive (trade name: ST-96, Ruitsu Co., Ltd.) After mixing and stirring with 30 g, the mixture was coated on silicon-coated paper and dried at 60 ° C. for 1 minute and at 120 ° C. for 5 minutes. The coating thickness after drying was 10 μm.

[0040]

Example 3 <Manufacture of Rapid-acting Ketoprofen Patch>

[A. Formation of Primer] (1) 100 g of natural rubber, 120 g of a terpene-based tackifier and 1 g of a conventional rubber antioxidant (BHT; 2,6-di-t-butyl-p-cresol) The mixture was stirred and dissolved in toluene so that the total solid content was 30%, then coated on a silicon-coated paper, and dried at 60 ° C. for 1 minute and at 80 ° C. for 1 minute. The coating thickness after drying was 40 μm.

(2) The treated product of the above (1) was transfer-coated on a nonwoven fabric using a pressure roll to form a primer.

[B. Formation of Ketoprofen-Containing Drug Layer] (1) 1.5 g of PVA having a polymerization degree of 500 and 6 g of water are mixed and gradually stirred to form a 20% aqueous PVA solution.
2.2 g of an EVA emulsion (trade name: 201, manufactured by Ruitsu Co., Ltd.) having a solid powder content of 55% was uniformly mixed with 6.6 g of the aqueous solution A.

(2) Ketoprofen powder 0.81 g, oleyl alcohol 1 g and sorbitan monooleate 2 g
Were mixed and dissolved.

(3) After mixing the treated products (1) and (2), the mixture was stirred for 10 minutes to prepare a drug solution. Then, this is coated on a silicon-coated paper and then dried at 70 ° C. for 6 minutes so that the coating thickness after drying becomes 36 μm. Then, transfer coating is performed on the primer by using a pressure roll to form a drug layer. Formed.

[C. Formation of Skin Adhesive Layer] (1) 0.18 g of sorbitan monooleate and 7.5 g of ethyl acetate were added to 0.72 g of oleyl alcohol and dissolved, and then an acrylic adhesive (trade name: ST-96, manufactured by Ruitsu Co., Ltd.) ) After mixing and stirring with 30 g, coating on silicon coated paper,
The coating thickness after drying was 10 μm by drying at 120 ° C. for 5 minutes.

(2) The above-mentioned (3) of B, using a pressure roll.
The treated product of the above (1) was transfer-coated on the drug layer of No. 1 to form a skin adhesive layer.

[0048]

Example 4 <Production 2 of immediate-acting ketoprofen patch>

A primer and a drug layer were manufactured in the same composition and method as in Example 3, a skin adhesive layer was manufactured by the following method, and transfer coating was performed on the drug layer using a pressure roll to obtain ketoprofen. Patches were manufactured.

Production of skin adhesive layer: 0.9 g of Vail Salt
Was dissolved in 7.5 g of ethyl acetate, mixed with 30 g of an acrylic pressure-sensitive adhesive (trade name: ST-96, manufactured by Ruitsu Co., Ltd.), stirred, coated on silicon-coated paper, and heated at 60 ° C. for 1 minute and at 120 ° C. By drying for 5 minutes, the coating thickness after drying was adjusted to 10 μm.

[0051]

Example 5 <Production 3 of immediate-acting ketoprofen patch>

(1) 4 g of water is added to 1 g of PVA having a polymerization degree of 500
And slowly agitate to make a 20% PVA aqueous solution,
EVA having a solid powder content of 55% was added to 2.2 g of the PVA aqueous solution.
6.6 g of the emulsion was mixed well.

(2) 0.81 g of ketoprofen powder was mixed with 1 g of oleyl alcohol and 2 g of sorbitan monooleate and dissolved by stirring.

(3) After mixing the treated products of (1) and (2) with each other and stirring for 10 minutes to produce a drug solution, coating was performed on silicon-coated paper so that the thickness after drying was 36 μm. And dried at 70 ° C. for 6 minutes, and then transfer-coated on the primer of A in Example 3 using a pressure roll to form a drug layer.

(4) The treated product of (1) in Example 3C was transfer-coated on the next drug layer to form a skin adhesive layer.

[0056]

Example 6 <Preparation 4 of immediate-release ketoprofen patch>

(1) 100 g of synthetic rubber, 120 g of a terpene-based tackifier and 1 g of BHT are dissolved so that the total solid powder content becomes 30%. By drying at 80 ° C. for 1 minute, the coating thickness after drying was adjusted to 40 μm.

(2) The treated product of (1) was transfer-coated on a nonwoven fabric using a pressure roll to form a primer.

(3) The treated product of (4) in Example 3B was transfer-coated on the primer to form a drug layer.

(4) The treated product of (1) in Example 3C was transfer-coated on the drug layer to form a skin adhesive layer.

[0061]

Example 7 <Production 5 of rapid-acting ketoprofen patch>

(1) 1 g of PVA having a polymerization degree of 500 and 4 g of water
Is mixed and slowly stirred to form a 20% PVA aqueous solution, and 2.8 g of this PVA aqueous solution (2.8 g) is an EVA emulsion (trade name: ST-96-E, manufactured by Ruitsu Co., Ltd.) having a 55% solid powder content. And SBR with 48% solid powder (Style
ne-butadiene rubber) and 0.93 g of latex were mixed well.

(2) 0.81 g of ketoprofen powder was
1 g of oleyl alcohol and sorbitan monooleate 2
g and stirred to dissolve.

(3) After mixing the processed products of (1) and (2) and stirring for 10 minutes to prepare a drug solution, this is coated on a silicon-coated paper so that the thickness after drying becomes 36 μm. And dried at 80 ° C for 6 minutes,
The drug layer was formed on the primer A of Example 3 by transfer coating using a pressure roll.

(4) The treatment product of (1) in Example 3C was transfer-coated on the drug layer to form a skin adhesive layer.

[0066]

Example 8 <Production 6 of immediate-acting ketoprofen patch>

(1) 8 g of water is added to 2 g of PVA having a polymerization degree of 500.
And slowly agitate to make a 20% PVA aqueous solution,
7.9 g of this PVA aqueous solution has a solid powder content of 48% SBR.
2 g of latex was mixed well.

(2) 0.1 g of ketoprofen powder was mixed with 1 g of oleyl alcohol and 2 g of sorbitan monooleate and dissolved by stirring.

(3) The treated products of (1) and (2) are mixed and stirred for 10 minutes to produce a drug solution, and the drug solution is dried on silicon-coated paper so that the thickness after drying becomes 36 μm. Coated and dried at 70 ° C. for 6 minutes.

(4) The treatment product of (3) was transfer-coated on the primer A in Example 1 using a pressure roll to form a drug layer.

(5) The treatment product of (1) in Example 1C was transfer-coated on the drug layer to form a skin adhesive layer.

[0072]

[Comparative Example] Ketoprofen plaster distributed in the technical field (trade name: Keto Top, manufactured by Taiheiyo Pharmaceutical Co., Ltd.)
It was used.

For the ketoprofen patch according to the embodiment of the present invention described above and the ketoprofen plaster commercially available in Korea, the drug loading amount per unit area and the respective drug release using a hairless mouse The physical properties of the amount, the drug release rate per unit time, and the adhesion to stainless steel were tested, and the results were shown in Tables 1, 2, 3 and 2,
As shown in FIG.

[0074]

Table 1 [Comparison Table of Drug Loading Amount and Adhesive Force ] Drug Loading Amount Adhesive force (mg / 1.8361 cm ² ) (g / cm) Example 1 0.75 196 Example 2 0.75 195 Example 3 0.77 210 Example 4 0.77 193 Example 5 0.84 157 Example 6 0.77 204 Example 7 0.73 215 Example 8 0.71 230 Comparative example 0.77 170

[0075]

[Table 2] [Drug release amount using hairless mouse] Time / Example 1 2 3 4 5 6 7 8 Comparative example 0 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 0.00 1 0.32 0.40 1.10 0.88 1.43 1.34 0.96 0.91 0.80 2 1.08 0.68 3.69 3.06 5.28 3.79 3.83 3.89 3.29 3 8.01 5.96 7.10 6.39 9.02 8.56 9.52 10.32 5.31 5 11.16 18.68 19.04 15.80 24.75 22.19 37.71 43.93 13.38 7 18.12 23.49 30.61 22.96 41.02 40.64 61.10 71.25 18.95 9 25.73 42.78 38.84 27.63 38.63 25.63 38.38 12 28.82 67.94 61.06 42.74 101.98 80.61 82.09 89.10 38.56 15 80.68 57.28 129.09 100.88 88.12 78.62 47.53 20 103.80 71.62 114.18 127.33 82.62 75.55 71.96 21 66.25 50.35 81.49 69.15 46.81 40.33 55.67

As is clear from the results of the physical property tests, Tables 1 and 2 show that the ketoprofen patch manufactured according to the example of the present invention is loaded with a similar drug as compared with the conventional product (ketoprofen plaster: control group). If the drug release per hour is excellent,
It can be seen that the adhesive strength to the skin is excellent, and the drug effect can be maintained for a long time.

In particular, the amount of drug released using a hairless mouse is shown graphically in FIGS. 2, 3 and 4 so that the effect according to the invention can be easily ascertained visually. Figures 2, 3,
In FIG. 4, all the drug release amounts of the control group are indicated by open triangles. On the other hand, a black circle and a black triangle in FIG.
3 shows the amount of drug release over time of the sustained-release ketoprofen patches prepared in Examples 2 and 3, and the closed circles, triangles, and squares in FIG. It shows the amount of release. Further, black circles, black triangles, and black squares in FIG.
3 shows the amount of drug released from the rapid-acting ketoprofen patch manufactured by the method described in Example 1.

According to Table 1, the drug loading per area of the ketoprofen patch produced in each example and the control group (comparative example) was 0.71 to 0.84 mg / 1.836.
1 cm ² , which is almost the same. However, the ketoprofen patch produced in Example 5 (adhesive strength: 15
The ketoprofen patches according to the examples other than 7 g / cm) have remarkably superior adhesive strength as compared with the control group.

Further, as shown in Table 2 and FIGS. 2, 3, and 4, the sustained release ketoprofen patch of the present invention has the same release amount of the drug over time as compared with the control group. However, when the skin adhesive layer was formed thinly (about 10 μm inside and outside; Example 2), the sustained release of the drug and the amount of drug release depending on the time were excellent, and even in the case of the fast-acting ketoprofen patch, it was better than the control group. Thus, the initial drug release amount is large, and the drug release amount after 3 hours from application of the patch is particularly excellent.

[0080]

As described above, the ketoprofen patch according to the present invention has a function of controlling the amount of drug release itself, so that the drug effect can be maintained continuously and uniformly.
It has excellent adhesion to the skin and can be attached and removed as many times as necessary. At the same time, it adheres to the skin at the time of adhesion and can sufficiently transmit the drug effect through the skin, so that the drug is continuously released in a constant amount, or the initial release of the drug is excellent. Also have.

The present invention relates to a binder for a drug layer.
er: It is possible to diversify the binders that can be used by using non-adhesive polymers as drugs (excluding drugs and low molecular substances such as skin penetration enhancers).

[Brief description of the drawings]

FIG. 1 is a cross-sectional view of a sustained / rapid acting ketoprofen patch according to the present invention.

FIG. 2 is a graph showing a time-dependent drug release amount of a sustained release ketoprofen patch according to Examples 1 and 2 of the present invention.

FIG. 3 is a graph showing a time-dependent drug release amount in the fast-acting ketoprofen patch according to Examples 3 to 5 of the present invention.

FIG. 4 is a graph showing a time-dependent drug release amount of a rapid-acting ketoprofen patch according to Examples 6 to 8 of the present invention.

[Explanation of symbols]

 Reference Signs List 10 backing 20 primer 30 drug layer 40 skin adhesive layer 50 release paper

Continuing on the front page (72) Inventor Choe Jae-Keung Korea South Korea Gangnan-Qu Il-Won-Don Sseota Exzigae Balzig 12 blocks Hyundai Semta Maurua Part 109-902 (72) Inventor I Kwan-Ho South Korea Seoul Yeongdeungpok Murae-dong 3ga 32 (72) Inventor Hyun Byung-Chul South Korea Seoul Dongjak-Sand 1 Dong 488-3 Usun Art Villa 202 (72) Inventor Hi-Dan South Korea Seoul Kwannak-Skull 4 don 482-14

Claims (20)

[Claims] 1. A composite laminated structure in which a water-permeable backing, a non-water-soluble primer, a drug layer containing a highly water-soluble ketoprofen, and a skin adhesive layer having a function of controlling a drug solution release amount are sequentially laminated. Sustained / fast-acting ketoprofen patch. 2. The sustained / fast-acting ketoprofen patch according to claim 1, wherein the primer is a mixture of ethyl acetate and an acrylic adhesive dissolved in a silicone-coated paper. 3. The primer according to claim 1, wherein a mixture of rubber and a terpene-based tackifier and an antioxidant is coated on a silicon-coated paper. Sustained / fast-acting ketoprofen patch according to any one of the preceding claims. 4. The drug layer is a matrix comprising a mixture of an aqueous solution of polyvinyl alcohol (PVA) and an acrylic pressure-sensitive adhesive in an amount of 5 to 95% by weight based on the total weight of the drug solution. 2. The sustained / immediate-release ketoprofen patch of claim 1. 5. Polyacrylic acid, polyacrylamide, poly N-vinylpyrrolidone, chitin, instead of PVA.
The sustained / fast-acting ketoprofen patch according to claim 4, wherein one or more selected from the group consisting of chitosan, cellulose and their salts are used. 6. The mixture of the PVA aqueous solution and the acrylic pressure-sensitive adhesive, based on a solid powder, comprises 50:50 to 75:
The sustained / rapid acting ketoprofen patch according to claim 4, wherein the patch is mixed in a ratio of 25 parts by weight. 7. The drug layer may be a mixture of a PVA aqueous solution and an ethylene-vinyl acetate copolymer (EVA) emulsion in an amount of 10 to 80% by weight based on the total weight of the drug solution.
2. The sustained / rapid acting ketoprofen patch of claim 1, wherein the patch is an included matrix. 8. The mixture of the PVA aqueous solution and the EVA emulsion may have a ratio of 30:70 to 7 based on solid powder.
8. A sustained / rapid acting ketoprofen patch according to claim 7, which is mixed in a ratio of 0:30 parts by weight. 9. The drug layer according to claim 1, wherein the drug layer is a matrix containing a mixture of a PVA aqueous solution and a synthetic rubber latex in an amount of 10 to 80% by weight based on the total weight of the drug solution. A long-lasting / fast-acting ketoprofen patch. 10. The mixture of the PVA aqueous solution and the synthetic rubber latex has a ratio of 10:90 based on solid powder.
The sustained / rapid acting ketoprofen patch according to claim 9, characterized in that it is mixed in a proportion of 90:10 parts by weight. 11. The drug layer may be a PVA aqueous solution, EVA
The sustained / rapid-acting ketoprofen patch according to claim 1, wherein the mixture comprising the emulsion and the synthetic rubber latex is a matrix containing 10 to 80% by weight based on the total weight of the drug solution. 12. The mixture of the PVA aqueous solution, the EVA emulsion and the synthetic rubber latex, wherein they are mixed at a ratio of 10 to 90:10 to 90: 1 to 50 parts by weight on a solid powder basis. Claim 11
Sustained / fast-acting ketoprofen patch according to any one of the preceding claims. 13. The drug layer comprises fatty acid alcohol, sorbitan monooleate, polyethylene glycol, glycerin, pyrrolidone, NMP (N-methylpyrrolidone), DMF (dimethylformamide), DMSO (dimethyl Sulfoxide)
13. A sustained / fast-acting ketoprofen patch according to any of claims 4 to 12, comprising one or more selected from the group consisting of and DETA (diethyltriamide). 14. The patch of claim 13, wherein the fatty acid alcohol is at least one selected from the group consisting of oleyl alcohol and derivatives thereof. 15. The long-acting / rapid-acting ketoprofen patch according to claim 13, wherein the drug layer comprises a skin penetration enhancer and ketoprofen in a ratio of 100: 1 to 100 parts by weight. 16. The skin adhesive layer according to claim 1, wherein said skin adhesive layer is a Vail Salt (b)
ile salt), oleyl alcohol, sorbitan monooleate
e), polyethylene glycol, glycerin, pyrrolidone, NMP (N-methylpyrrolidone), DMF (dimethylformamide), DMSO (dimethylsulfoxide)
2. The sustained / rapid-acting ketoprofen patch according to claim 1, wherein one or more selected from the group consisting of DETA and diethyl triamide are contained in an amount of 0.005 to 50% by weight. . 17. The primer, the drug layer, and the skin adhesive layer each have a thickness of 20 to 50 μm and 10 to 1 μm.
2. A sustained / rapid acting ketoprofen patch according to claim 1, wherein the patch is in the range of 00 pm and 5-40 [mu] m. 18. The sustained / immediate release ketoprofen patch of claim 17, wherein the skin adhesive layer does not contain a drug when the drug layer is of a solid matrix type. 19. A ketoprofen patch, which is a matrix-type transdermal absorption preparation in a solid state, wherein a macromolecular substance having no tackiness and adhesion is used as a binder for a drug layer after coating and drying. 20. A silicone-coated paper or a polyester film is coated with an adhesive selected from rubber or acrylic containing solid powder, dried, and then transfer-coated on a backing to form a primer. A first step of mixing, and mixing, in an aqueous solution of polyvinyl alcohol, at least one selected from the group consisting of an acrylic pressure-sensitive adhesive, an ethylene-vinyl acetate copolymer, and a synthetic rubber latex; A second step of forming a drug layer by coating a drug solution prepared by dissolving the above on a silicon-coated paper and drying the coating, and then transfer-coating the primer on the first-stage processed product to form a drug layer; After dissolving emulsifier or organic salt in ethyl acetate, mix with acrylic adhesive and stir A third step of coating and drying on a recon-coated paper and then transfer-coating the drug layer of the second-step processed product to form a skin adhesive layer. A method for producing a ketoprofen patch.