KR100194968B1 - Ketoprofen Patch - Google Patents

Abstract

The ketoprofen patch according to the present invention has a composite laminate structure in which the drug layer and the adhesive layer are completely separated from each other, a stretchable nonwoven fabric capable of passing moisture, a non-water-sensitive adhesive layer, a highly water-soluble ketoprofen-containing drug layer, and a drug control structure. It consists of a skin adhesive and drug control layer having.

Such ketoprofen patch is (1) water permeable stretchable nonwoven fabric, which is coated with an ethyl acetate solvent-type acrylic adhesive containing no solids and a solid component on a silicone coated paper, and then dried at 80 ° C. for 1 to 2 minutes. To a coating thickness of 30-50 microns, followed by transfer coating onto the nonwoven fabric using a pressing roll, (2) a mixture of polyvinyl alcohol and water-soluble acrylic emulsion, ketoprofen and emulsifier dissolved in oleyl alcohol. Coating the drug layer composition on the silicon-coated paper to have a thickness of 30-50 microns after drying, and then transfer-coating the non-woven fabric coated with the adhesive using a pressing roll, and (3) dissolving it in ethyl acetate. The prepared salt or cholic acid was stirred with an acrylic adhesive and coated on a silicon-coated paper to give a rough thickness of 5-30 microns. It is prepared by an adhesive and a drug controlling layer in the ketoprofen patch production method using the press roll over a layer of the drug (2) comprising the step of coating transferred.

Description

Ketoprofen Patch

1 is a cross-sectional view showing a ketoprofen patch according to the present invention.

2 is a graph showing the amount of drug released over time in the ketoprofen patch according to an embodiment of the present invention.

3 is a graph showing the amount of drug released over time in the ketoprofen patch according to Comparative Example 1.

4 is a graph showing the amount of drug released over time in the ketoprofen patch according to Comparative Example 2.

* Explanation of symbols for main parts of the drawings

1 nonwoven fabric 2 adhesive layer

3: drug layer 4: skin adhesion and drug control layer

5: silicone coated paper

The present invention relates to ketoprofen patches suitable for treating arthritis. In general, ketoprofen patch is a transdermal administration of a ketoprofen composition known to be highly effective in the treatment of arthritis, lumatis, and the like. It is a kind.

Ketoprofen plata (Ketotop, Pacific Pharmaceuticals), which is distributed in the art as a therapeutic agent for arthritis for transdermal administration, is an acrylic adhesive, ketoprofen, which is a drug, and an enhancer for the skin penetration effect of propylene glycol monolaurate. The mixture, and polyisobutylene-based rubbery adhesive, are made by transfer coating on the nonwoven backing. Such ketoprofen plata does not significantly deviate from the scope of the conventional pars formulation.

In addition, in US 5,505,956, there are 2 to 5 layers of adhesive layer between the backing and the liner as a support, and if the backing fails to pass moisture, each layer is gradually lowered from the high water content to the surface layer that touches the skin. Conversely, when the backing passes moisture like a nonwoven fabric, a ketoprofen patch is described in which each layer is composed of gradually increasing layers from low water content to the surface layer touching the skin. At this time, in order to increase the water content, 0.1 to 30% by weight of hydrophilic polymer material such as water affinity polyvinyl alcohol, etc. is used, and 0.1 to 40% by weight of ketopropene is added to each layer to enhance the adhesive and propylene monoglycolate. It is in a mixed state with each other.

However, these ketoprofen patches exist in a state in which the ketoprofen drug is mixed with the adhesive at the same time, (1) there is no function to control the drug release uniformly, so after adhering to the skin, the amount of drug release is initially high but time passes. There is a disadvantage that the amount of the drug can not be kept constant over time according to the amount is reduced, (2) non-adhesive polymer material such as ketoprofen or polyvinyl alcohol, powdered drug is mixed with acrylic adhesive Adhesion to the skin is very weak, in particular, if you want to re-attach after attaching to the skin once, there is a problem that adhesion is difficult. In particular, the patch agent is a drug carrier through the skin, and the drug efficacy is proportional to the area touching the skin. Therefore, the larger the area falling from the skin after the patch is attached, the drug is not delivered to the site, thereby significantly reducing the drug efficacy.

Therefore, there is a strong demand in the art for the development of ketoprofen patches with good adhesion and constant drug release per hour to sustain the drug for a long time.

In order to solve and improve these problems in the art, the present invention (1) has the ability to control drug release on its own, the drug efficacy is continuously maintained uniformly, and (2) the adhesion to the skin is also excellent, many times if necessary It is intended to provide a ketoprofen patch that can be attached and detached, and (3) adheres to the skin so that it can be adhered to the skin and sufficiently deliver the effect through the skin.

The inventors of the present invention, after coating the non-moisture adhesive on the stretchable nonwoven fabric through which moisture can pass, after coating the high moisture-containing drug layer thereon, the adhesive film layer having the drug composition again on this again. It was found to be achieved by coated ketoprofen patches.

The ketoprofen patch according to the present invention has a composite laminate structure in which the drug layer and the adhesive layer are completely separated from each other, and includes a stretchable nonwoven fabric capable of passing moisture, a non-aqueous adhesive layer to prevent back diffusion of the drug, and a drug. It consists of a highly water-soluble ketoprofen-containing drug layer composed only of a pure water-soluble polymer, and a skin adhesion and drug control layer having a drug control structure as an adhesive layer attached to the skin without containing the drug.

Ketoprofen patch as described above is (1) water-permeable stretchable nonwoven fabric, the ethyl acetate solvent-type acrylic adhesive containing a solid component without moisture, and coated on a silicone-coated paper, 1 to 2 at 80 ℃ Drying for about 30 to 50 microns, followed by transfer coating on the nonwoven fabric using a pressing roll, (2) a mixture of polyvinyl alcohol and water-soluble acrylic emulsion, ketoprofen dissolved in oleyl alcohol, and Coating the drug layer composition including an emulsifier on a silicon-coated paper to have a thickness of 30 to 50 microns after drying, and transferring the coating onto an adhesive-coated nonwoven fabric using a pressing roll, and (3) ethyl acetate After dissolving the bail salt or cholic acid dissolved in the acrylic adhesive, it was coated on a silicon-coated paper to give a rough thickness of 5 to 30 microns. It is prepared by the Keihan skin adhesive and a drug controlling layer on ketoprofen patch production method according to the invention, by using a press roll on a layer of the drug (2) comprising the step of coating transferred.

EMBODIMENT OF THE INVENTION Hereinafter, embodiment of this invention is described concretely.

In order to make the ketoprofen patch according to the present invention having a composite laminate structure as described above, after drying the silicon-coated paper or polyester film, the acrylic or polyisobutylene adhesive is coated with a thickness of 30 ~ 60㎛, It is coated on a nonwoven fabric that can pass moisture using a compression roll to prevent back diffusion of the drug so that the drug layer does not leak out of the nonwoven fabric or is lost into the nonwoven fabric.

A total of 30% by weight or more of the water-soluble polymer matrix is used to maximize the content and release of the drug, and the oil-soluble and poorly water-soluble ketopropene drug is used in an amount of 1 to 8 with 100-1000 ml of excess water per 1 g of the drug. It slowly dissolves for a long time, and instead of using a separate enhancer, propylene glycol monolate, it can be used as an enhancer as a skin penetrant, and its amount can be used within 15 minutes using oleyl alcohol, which can be used only about 1g per 1g of drug. It can also be dissolved effectively in. However, in order to coat such a drug and a water-soluble polyvinyl alcohol matrix mixture on a silicon-coated paper or a polyester film, there is a difference in surface tension, so it can be used as a skin penetration enhancer and an appropriate amount of a span-type emulsifier that can lower the surface tension. It is preferable to make it use and make thickness 40-40 micrometers after drying.

The adhesive layer that touches the skin simply needs to have a thin coating thickness or a long delay time to release the drug when only the adhesive is used to increase the adhesive force. However, when the coating thickness is thinner than 10㎛, there is a disadvantage that it is easily dropped during the activity even if it adheres well in the early stage because the holding force on the skin is low, and when the thickness of the coating layer is thickened such as more than 40 microns to increase the adhesive holding force, This is not so good, in order to form a control film that can release the drug at a constant rate while maintaining a strong adhesion to the skin 10 to 40㎛, preferably 20-30㎛ thick skin penetration of the salt component in the acrylic or rubber-based adhesive When the enhancer is used in an amount of 0.005 to 2% by weight, preferably 0.05 to 0.5% by weight based on the weight of the drug layer, water flowing through the skin dissolves the salts, thereby maintaining a constant micropath in the adhesive polymer structure without losing adhesion to the skin. You can get the effect that only a certain amount of the drug is released within a certain time.

Hereinafter, the present invention will be described in more detail with reference to Examples. However, this embodiment does not limit the scope of the invention according to the patent claims.

EXAMPLE

A. Preparation of Ketoprofen-Containing Compositions

(1) In order to maximize the water content in the drug layer, make a 20% PVA solution with 1g of PVA having a degree of polymerization of 500 and slowly stirring 4g of water at a temperature of 60 to 70 ° C for 30 to 40 minutes. In the case of using a polyvinyl alcohol having a degree of polymerization of 1500, only an aqueous solution of up to 7% can be made, and thus the polyvinyl content cannot be increased. 4.71 g (75 wt%) of PVA aqueous solution thus prepared was mixed well with 1.57 g (25 wt%) of a water-soluble acrylic emulsion having a solid content of 55 wt%.

(2) 0.5 g of ketoprofen powder as a drug is mixed with 0.45 g of oleyl alcohol and stirred at 70 to 80 ° C. for 10 to 15 minutes to completely dissolve it.

(3) After adding 1.65 g of the emulsifier of Span 80 to (1) and (2), the drug composition was prepared by stirring for about 10 minutes.

B. Preparation of Skin Adhesion and Drug Control Layer

After dissolving 0.9 g of the bail salt in 7.5 g of ethyl acetate, stirring well with 30 g of the water-soluble acrylic emulsion of 1), and coating it on a silicon-coated paper to have a thickness of 30 microns after drying.

C. Preparation of Ketoprofen Patches

(1) A water-permeable stretchable nonwoven fabric is coated with an ethyl acetate solvent-type acrylic adhesive containing 55% by weight of a solid component without moisture and coated on a silicone-coated paper and dried at 80 ° C. for 1 to 2 minutes to obtain a coating thickness of 40 After being made to micron, transfer coating is performed on the nonwoven fabric using a pressing roll. This prevents the back diffusion of the drug, thereby preventing the drug from leaking and the absorption of the drug layer in the nonwoven later in coating the drug layer.

(2) The drug composition prepared in A is coated on a silicon-coated paper to have a thickness of 50 microns after drying, and then transfer-coated on the pressure-sensitive adhesive-coated nonwoven fabric using a pressing roll.

(3) The skin adhesion and drug control layer prepared in B is transfer coated on the drug layer of the above (2) using a compression roll.

Comparative Example

The following comparative example is described for the comparison with this invention.

Comparative Example 1

A. Preparation of Drug Layer

A drug layer is prepared in the same manner as in Example A- (2).

B. Preparation of Skin Adhesion and Drug Control Layer

In the same manner as in Example B, except that the bail salt is not added, only the acrylic adhesive is coated on the silicon-coated paper to have a thickness of 30 μm after drying.

C. Preparation of Ketoprofen Patches

(1) The nonwoven fabric is manufactured as C- (1) of the said Example.

(2) On the coated nonwoven fabric, the drug layer prepared in A of Comparative Example 1 is transferred and coated using a pressing roll.

(3) On the drug layer, the skin adhesive and drug control layer prepared in B of Comparative Example 1 are transferred and coated using a compression roll.

Comparative Example 2

Ketoprofen platters in the art are used.

[Analysis of effects and functions]

For Examples 1 according to the present invention and Comparative Example 1 using different skin adhesion and drug control layers and commercial ketoprofen plata (Ketotop, Pacific Pharmaceuticals, Comparative Example 2), hairless mice (hairless mouth) was used to compare the amount of drug release, the release rate per unit time and the adhesion and retention to the skin, the results are shown in Table 1 and 2 and Figures 2 to 4, respectively.

As shown in Tables 1 and 2, and FIGS. 2 to 4, the ketoprofen patch prepared according to the embodiment of the present invention has a constant drug release per hour compared to conventional products, and adheres to the skin. And it can be seen that it is possible to maintain a long-term sustained efficacy by excellent adhesive holding power.

Claims (2)

A composite laminate structure consisting of a stretchable nonwoven fabric that can pass moisture, a non-moisture-sensitive adhesive layer, a highly water-containing ketoprofen-containing drug layer, and a skin adhesion and drug control layer having a drug control structure, and a drug layer and an adhesive layer completely separated. A ketoprofen patch having a drug layer, wherein the drug layer comprises a polyvinyl alcohol and a derivative thereof having a high water content of 65 to 75% by weight based on the weight of the entire drug layer, 25 to 35% by weight of a water-soluble acrylic emulsion, an oleyl alcohol and A ketoprofen patch comprising the fatty acid alcohol as a derivative thereof in a ratio of 0.1 to 3: 1 (oleyl alcohol: ketoprofen) with respect to the weight of ketoprofen. The ketoprofen according to claim 1, wherein the adhesion and drug control layer is selected from the group of organic salts including bail salt and cholic acid, and 0.0005 to 2% by weight based on the weight of the adhesion and drug control layer. Patch.