KR100552649B1 - Antiphlogistic and analgesic plaster comprising felbinac compound - Google Patents

Abstract

The present invention relates to an anti-inflammatory analgesic plaster containing felbinac as an effective drug, and in particular, an alkanolamine as a dissolving agent, N-alkyl-pyrrolidone as a cosolvent, and a nonionic surfactant as a transdermal absorption accelerator. Using fatty acids, fatty acid derivatives, etc. alone or in a mixture of two or more, all components in the plaster are uniformly dispersed without aggregation, and the anti-inflammatory analgesic effect by Pelbinac can be continuously obtained for a long time. And a felbinac-containing plaster excellent in adhesion.

Plaster, felbinac, anti-inflammatory

Description

Anti-inflammatory analgesic plaster containing felbinac {Antiphlogistic and analgesic plaster comprising felbinac compound}             

1 is a view showing a cross-section of the felbinac-containing plaster according to the present invention,

Figure 2 is a view showing the skin permeation amount by the time of attachment in the hairless mouse of the embodiment and the comparative example and the existing plaster of the present invention.

The present invention relates to an anti-inflammatory analgesic plaster, and in particular, it contains felbinac (felbinac: 4-biphenylacetic acid) as an effective drug, alkanolamine as a solubilizer, and N-alkyl-pyrrolidone as a cosolvent. Nonionic surfactants, fatty acids, fatty acid derivatives, etc. are used alone or in the form of a mixture of two or more kinds as a transdermal absorption accelerator, and all components in the plaster are uniformly dispersed without aggregation. The present invention relates to a felbinac-containing plaster which can be obtained continuously for a long time and which is also excellent in stability and adhesion of the formulation.

Pharmaceutical plasters, in particular the Transdermal Therapy System (TTS), have long been commercially employed in the treatment of various diseases. Devices for administering nitroglycerin for treating angina pectoris, nicotine for smoking cessation, estradiol for treating menopausal diseases, and clonidine for lowering blood pressure are commercially available and substantially recognized. In contrast to topical active-substance plaster, which is essentially only local action limited to the area of application, the use of TTS allows the active body to pre-absorb through the skin It is distributed throughout and acts systemically on other body tissues.

The anti-inflammatory pain includes arthritis, back pain, myalgia, etc. Arthritis is divided into acute and chronic inflammation of the joints caused by the infiltration of various bacteria such as Mycobacterium tuberculosis. Acute arthritis includes serous arthritis, serous fibrosis, and purulent arthritis. Chronic arthritis includes specific inflammatory arthritis, polyarthritis, and deformity. Osteoarthritis and hemophilia (관절 友 病 性) arthritis. Low back pain, unlike other animals, is a fatal disease caused by human evolution and standing on two feet.It is reported that more than 80% of all populations suffer from low back pain, regardless of age or gender. The causes and symptoms are very complex and diverse. Low back pain can be caused by spinal injuries, back injuries, back muscles and ligaments, and other organs, colds, tonsillitis, rheumatism, chronic kidney disease, and vitamin deficiency. And back pain can also occur when you have diabetes.

Pelbinac is a nonsteroidal anti-inflammatory drug that is used for arthritis, low back pain, myalgia, etc. and shows strong anti-inflammatory analgesic action. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used for arthritis with inflammation because they have anti-inflammatory effects, and can be used effectively even when cancer has spread to bone. However, nonsteroidal anti-inflammatory drugs have a number of limitations in the development of oral preparations due to side effects such as heartburn, gastritis and gastric bleeding because they inhibit the secretion of substances that protect the stomach from stomach acid. These side effects and lower the bioavailability of the drug by oral administration, improve the disadvantages of administering an excessive amount of drugs, and improve the discomfort of the medications such as injections can be used by the patient comfortably Development into external preparations is being actively carried out. Until now, gels, liquids, poultices and plasters containing felbinac have been developed and commercialized. However, gels and liquids have a problem in that the bioavailability is low due to difficulty in dose and quantitative administration on a timely basis, due to the discomfort in dosage and low skin permeability. In order to improve the problems of gels and liquids, poultices and plasters have been developed, but due to the properties of water-soluble polymers and hot-melt block copolymers used as respective substrates, the skin permeability of the drug is not increased. In order to increase the skin permeability of the drug, the skin permeability of the drug is proportional to the concentration of the drug in the preparation, so that crystals do not precipitate in the preparation, and the drug should be kept at a saturation concentration if possible within a range that maintains the preparation properties. Percutaneous absorption accelerators should be used to increase the amount of drug that is distributed and diffused into the stratum corneum. In addition, it is necessary to have proper adhesion and skin adhesion so that the drug can be continuously penetrated into the skin during the formulation time can increase the skin permeability of the drug.

As a related art for felbinac plaster, Japanese Patent No. Hei 4-321624 proposes an anti-inflammatory analgesic patch based on styrene-isoprene-styrene block copolymers and crotamiton as a solubilizer. Deterioration of the adhesive force due to the outflow of the surface of the used crotamiton becomes a problem, there was an inconvenience in the work process due to the use of crotamiton. In addition, anti-inflammatory analgesic patch containing styrene-isoprene-styrene block copolymer, rosin-based resin, plasticizer and pelvinac but not crotamiton as disclosed in International Publication No. WO98 / 24423 was used as an effective drug. Since the concentration of Binak is only 1 to 5% by weight, it is difficult to maximize skin penetration or to induce stable drug release during the formulation application time. Korean Patent 2002-0079811 proposes a formulation which improves skin permeability of felbinac by using a water-soluble additive in a hot melt adhesive base material, but shows a limitation in increasing the concentration of felbinac in the formulation as in the prior art.

Therefore, the inventors of the present invention intensively studied for the high concentration of felbinac in the formulation, securing the stability of the drug, and improving skin permeability. It contains pyrrolidone and the percutaneous absorption accelerator contains nonionic surfactants, fatty acids and fatty acid derivatives alone or in the form of a mixture of two or more thereof.It is used to prevent the drug from despreading to the support and to improve skin adhesion. Formulated in the form of a multilayer structure of two or more layers with a primer layer made of a rubber-based adhesive agent to maintain the anti-inflammatory analgesic effect by felbinac for a long time, to complete a felbinac-containing plaster excellent in stability and adhesion.

The present invention, in view of the problems of the existing technology, due to the deterioration of the adhesiveness due to the solvent and organic solvent, inconvenience in the work process, due to precipitation of the drug crystal when the drug in high concentration in the plaster containing no solvent It improves the disadvantages of lowering the skin permeability and poor adhesiveness of the drug, by containing a certain amount of solubilizer in a certain ratio, the skin adhesion is maintained for a long time, the drug stability and skin permeability in the formulation is excellent, and the drug efficacy for a long time It is intended to provide a felbinac containing plaster effective for anti-inflammatory analgesic.

In order to achieve the above object, the present invention provides a plaster containing a non-steroidal anti-inflammatory analgesic component of felbinac (felbinac, 4-biphenylacetic acid), containing a solvent, co-solvent, transdermal absorption accelerator, pressure-sensitive adhesive do.

Alkanolamine is used as the solubilizer, and N-alkyl-pyrrolidone is used as a cosolvent, and transdermal absorption accelerators include nonionic surfactants, fatty acids, fatty acid derivatives, pressure sensitive adhesives, acrylic adhesives, water soluble adhesives, and rubber adhesives. Pelbinac-containing plaster characterized in that the use, preferably 1 to 25% by weight of felbinac as an active ingredient, 0.1 to 7% by weight of alkanolamine as a dissolving agent, nonionic surface active agent as a transdermal absorption accelerator, fatty acid And a felbinac-containing plaster characterized by containing 1 to 20% by weight of fatty acid derivatives alone or in the form of a mixture of two or more, and 30 to 90% by weight of a pressure-sensitive adhesive.

In addition, the present invention is a plaster, in which a support, a primer layer, a drug layer containing an effective drug and a release paper is laminated, the support (1) that prevents the penetration of the drug and is located on the support (1) to prevent the back diffusion of the drug Pelbinac containing a primer layer (2) for preventing and improving skin adhesion, a drug layer (3) containing felbinac, and a release paper (4) attached to the drug layer (3) so that peeling is possible. Provide a plaster.

Hereinafter, the present invention will be described in detail.

The plaster according to the present invention contains an effective drug, a dissolving agent, a cosolvent, a percutaneous absorption accelerator, a pressure-sensitive adhesive and other commonly used additives. As an active ingredient, felbinac is contained in 1 to 25% by weight, preferably 3 to 20% by weight in the total composition. The compounding ratio maintains the skin permeability of the drug, the persistence of the drug and the drug stability, etc., and provides an economically excellent felbinac-containing plaster. Moreover, when the compounding quantity of felbinac is less than 1 weight%, sufficient drug efficacy cannot be acquired, and when a compounding quantity exceeds 25 weight%, there exist problems, such as crystal precipitation of a drug and reduction of adhesive force.

Alkanolamine used as a solubilizer in the present invention is a material used as an emulsifier, stabilizer, alkalizing agent, etc. in US Patent No. 4678666, US Patent No. 5436241, European Patent No. 0276561, Korean Patent No. 10-0212961, etc. Although it was used for the purpose of increasing the solubility of poorly soluble drugs, when the amount of the drug is used in excess of the effective drug, the solubility of the drug in the composition increases, but the skin permeability is rather reduced or the adhesion properties of the formulation are inferior. Due to the yellowing of alkanolamines in the phase, there is a limit to containing the required concentration of felbinac. Therefore, in the present invention, in order to improve the disadvantages of the above technology, by using N-alkyl-pyrrolidone as a co-solvent to increase the content of felbinac in the adhesive composition before application, a poorly soluble drug by using a certain amount of alkanolamine as a solvent By improving the solubility in the formulation of Infelbinac, the plaster containing high concentration of Pelvinac desired by the present invention can be produced without side reactions such as deterioration of adhesive properties or yellowing of the adhesive composition.

In addition, alkanolamine not only has good compatibility with the pressure-sensitive adhesive used in the present invention, but also acts as a plasticizer to the pressure-sensitive adhesive to improve adhesion, thereby improving skin adhesion, thereby improving skin permeability. As the alkanolamine of the present invention, methanolamine, ethanolamine, propanolamine, isopropanolamine, other amino alcohols are used, preferably ethanolamine, more preferably monoethanolamine, diethanolamine, Preference is given to using single or a mixture of two or more selected from triethanolamine and the like. It is preferable to contain 0.1-7 weight% of said alkanolamines in the whole composition, More preferably, it contains 1-5 weight% in the whole composition. If the above compounding amount is less than 0.1% by weight in the total composition, the uniformity of the pressure-sensitive adhesive agent and felbinac in the formulation is not sufficient, so that constant drug release property cannot be obtained. There is a concern that the release rate of the drug may be lowered due to interaction with drops, and that the adhesive property may be lowered due to the increase of the alkanolamine content in the formulation.

In addition, N-alkyl-pyrrolidone, preferably N-methyl-2-pyrrolidone, is used as the cosolvent of the present invention. N-methyl-2-pyrrolidone has excellent solubility in felbinac but is volatilized during drying and does not exist in the final formulation. Therefore, N-methyl-2-pyrrolidone is a substance that helps improve skin permeability and minimize skin irritation. It is preferred to administer 0.5 to 3 times the amount of felbinac in the composition. If the dose of N-methyl-2-pyrrolidone is less than 0.5 times that of felbinac, a separate solvent is required for dissolution of felbinac. If it exceeds 3 times of felbinac, it remains after drying to maintain adhesion and skin adhesion. There is a possibility that the physical properties of the plaster such as the castle deteriorate.

In addition, in the present invention, nonionic surfactants, fatty acids, fatty acid derivatives are used as transdermal absorption accelerators in addition to dissolving agents and co-solvents for maintaining the drug in a high concentration in the plaster to further promote skin penetration of Pelbinac. Nonionic surfactants contained in the composition as the transdermal absorption accelerators include monoglycerides, sorbitan esters, and sorbitan esteroxyethylenes. The fatty acid may be oleic acid, linoleic acid, capric acid, myristic acid and the like, and the fatty acid derivative may be oleyl alcohol, isopropyl myristate, propylene glycol laurate, polyethylene glycol laurate and the like. Such transdermal absorption accelerators are used alone or in combination of two or more thereof, and the total amount thereof is preferably contained in the range of 1 to 30% by weight, more preferably in the range of 5 to 20% by weight in the total composition of the drug layer. Do.

In addition, the pressure-sensitive adhesive used in the plaster of the present invention uses an acrylic adhesive made of an acrylate polymer, in addition to the tackifying resins, such as petroleum resin, rosin resin, terpene resin, oil, antioxidants in natural or synthetic rubber Rubber-based adhesives and water-soluble adhesives to which additives such as these are added are used. The pressure-sensitive adhesive is used alone or in combination of two or more, to be contained in the total composition constituting the drug layer in the range of 30 to 90% by weight, preferably 45 to 70% by weight, the amount of pressure-sensitive adhesive If the content is less than 30% by weight, the cohesiveness of the preparation may be destroyed, resulting in problems such as skin metastasis. If the content is more than 90% by weight, the amount of the effective drug and other compositions is limited and the adhesion is worsened.

In the present invention, in order to improve the physical properties of the formulation in addition to the above composition, additives such as essential oil components such as l-menthol and peppermint oil, antioxidants, preservatives and inorganic fillers, and the amount of the total composition of the drug layer may be used. 0.1 to 10% by weight, preferably 0.2 to 5% by weight.

The felbinac-containing plaster of the present invention is uniformly dispersed without aggregation of all the components in the formulation having the above composition, sufficient uniform dispersion of felbinac is maintained, high skin permeability is stably maintained, and sufficient anti-inflammatory by felbinac The analgesic effect can be maintained for a long time, and the stability and adhesion of the formulation are also excellent.

The present invention includes a plaster formulated using the composition as described above, the structure of the plaster according to the invention is shown in FIG.

Pelbinac-containing plaster shown in Figure 1 is composed of four components to effectively administer the drug transdermal when applied to the skin, that is, the support (1) to prevent the penetration of the drug, prevents the back diffusion of the drug and the skin adhesion It consists of a primer layer (2), a drug layer (3) made of the above-described felbinac-containing composition, and a release paper (4) attached to the drug layer to enable peeling.

The support 1 is a material having no interaction with the drug and other compositions in the drug layer 3, preferably made of a material having good moisture permeability and elasticity, and it is not preferable to affect the release of the drug. Examples of the support usable in the present invention include synthetic resin films such as polyethylene, polypropylene, polyester, polyurethane, and the like, sheets, sheet-like foams, woven or nonwoven fabrics, and laminates thereof. The preferred support has a thickness of 30 to 200 μm, and when it is out of the thickness range, elasticity may be reduced when applied to the skin of the bent portion, thereby deteriorating the skin adhesion due to the decrease in adhesive force.

The primer layer (2) on the inner surface of the support (1) prevents the back diffusion of the drug to the support to increase the skin permeability of the drug and improve the skin adhesion, and the adhesive resin to natural and synthetic rubber It consists of a rubber-based adhesive to which additives such as oils and antioxidants are added. The preferred primer layer has a thickness of 5 to 40 μm, and when it is out of the above range, it does not help to improve adhesion and prevent dediffusion of the drug or breaks the cohesion of the patch to reduce the skin adhesion.

The drug layer 3 mainly consists of felbinac, pressure-sensitive adhesives and solubilizers, cosolvents, dispersants, transdermal absorption accelerators, and the like, and skin irritation inhibitors or plasticizers may be added as necessary. The drug layer containing felbinac and other compositions has a single layer or a multilayer structure of two to three layers, and the thickness of each layer is 10 to 150 mu m, preferably 20 to 120 mu m. The thickness of all the adhesion layers is 30-500 micrometers, Preferably 50-200 micrometers is suitable. If necessary, it can be formed into a single layer or a double layer, in the case of forming a double layer, the composition of each layer is the same, or the composition is changed differently so that the layers located close to the skin are overlapped in order while allowing the fastest skin penetration. It is preferable to form a so that the case where the penetration rate of the effective drug is the lowest is located closest to the primer layer (2).

The release paper 4 may be a polyester film, polyethylene film, paper or the like coated on the surface of the release layer 4 in contact with the drug layer 3.

A suitable example of the felbinac-containing plaster of the present invention will be described;

All the components except the alkanolamine and the pressure-sensitive adhesive in the above composition components are administered, stirred and dissolved in a predetermined ratio, respectively, and then a pressure-sensitive adhesive is added to obtain a uniform adhesive material. Next, alkanolamine is added to the sticky substance, and the mixture is sufficiently stirred. Then, bubbles are removed, coated on release paper, dried in a drier, and the support is compressed and transferred to prepare a plaster.

Plaster of the present invention can be modified and improved to a shape or shape well known in the art as required, such as round, square, oval.

In addition, the order of mix | blending each composition in the said manufacturing method is only describing the example, The manufacturing method of the patch of this invention is not limited to the method of this mixing procedure.

Hereinafter, the present invention will be described in detail by Examples and Experimental Examples.

However, the following Examples and Experimental Examples are merely illustrative of the present invention, and the content of the present invention is not limited by the following Examples and Experimental Examples.

Unless the pharmacological activity and cohesiveness of the plaster of the present invention does not change, details may be omitted, added, or substituted as deemed appropriate, and the above variations are complemented within the technical scope of the present invention.

REFERENCE EXAMPLE 1 Preparation of Pelbinac-Containing Plaster Comparative Example (1)

 As a transdermal absorption accelerator, 15% by weight of sorbitan monooleate and 5% by weight of felbinac were added to the cosolvent N-methyl-2-pyrrolidone (equivalent to the content of felbinac) and stirred until completely dissolved. 77 wt% of the rubber-based adhesive was added to the pressure-sensitive adhesive, and the mixture was sufficiently stirred for 30 minutes. Then, 3 wt% of triethanol amine was added to the solvent, followed by stirring for 30 minutes to remove bubbles. The mixture was applied to a release paper with an appropriate thickness such that the drug content was 0.17 mg / cm 2, and then dried at 90 ° C. for 20 minutes to remove the cosolvent and the pressure-sensitive adhesive volatile component. After drying, the exposed drug layer was covered with a support on which a primer layer prepared in advance was applied. The plaster thus prepared was cut to an appropriate size to prepare a felbinac-containing plaster of Comparative Example (1).

REFERENCE EXAMPLE 2 Preparation of Pelbinac-Containing Plaster Comparative Example (2)

15% by weight of sorbitan monooleate as a transdermal absorption accelerator, 15% by weight of felbinac, 67% by weight of a rubber-based adhesive as a pressure-sensitive adhesive and 3% by weight of triethanolamine as a solvent, and a drug content of 0.50 mg / A Pelbinac-containing plaster of Comparative Example (2) was prepared in the same manner as in Reference Example 1 except that it was made to be cm 2.

Reference Example 3. Preparation of Pelbinac-Containing Plaster Comparative Example (3)

15% by weight of sorbitan monooleate, 15% by weight of felvinol, 70% by weight of an acrylic pressure-sensitive adhesive as a percutaneous absorption accelerator and a drug content of 0.50 mg / cm 2, with the exception of the composition. By the same method as in Example 1, a Pelbinac-containing plaster of Comparative Example (3) was prepared.

Example 1. Preparation of Pelbinac-containing plaster Example (1)

15% by weight of sorbitan monooleate as a transdermal absorption accelerator, 5% by weight of felbinac, 77% by weight of an acrylic pressure-sensitive adhesive and 3% by weight of triethanolamine as a solvent and a drug content of 0.17 mg / A Pelbinac-containing plaster of Example (1) was prepared in the same manner as in Reference Example 1 except that the size was cm 2.

Example 2. Preparation of Pelbinac-Containing Plaster Example (2)

15% by weight of sorbitan monooleate as a percutaneous absorption accelerator, 10% by weight of felbinac, 72% by weight of an acrylic pressure-sensitive adhesive and 3% by weight of triethanolamine as a solvent, and a drug content of 0.34 mg / A Pelbinac-containing plaster of Example (2) was prepared in the same manner as in Reference Example 1, except that it was made to be cm 2.

Example 3. Preparation of Pelbinac-Containing Plaster Example (3)

15% by weight of sorbitan monooleate as a transdermal absorption accelerator, 20% by weight of felbinac, 62% by weight of an acrylic pressure-sensitive adhesive and 3% by weight of triethanolamine as a solvent, and a drug content of 0.67 mg / A Pelbinac-containing plaster of Example (3) was prepared in the same manner as in Reference Example 1, except that it was made to be cm 2.

Example 4 Preparation of Pelbinac-Containing Plaster Example (4)

15% by weight of sorbitan monooleate, 15% by weight of felbinol as a transdermal absorption accelerator, 67% by weight of an acrylic pressure-sensitive adhesive and 3% by weight of triethanolamine as a solvent, and a drug content of 0.50 mg / A Pelbinac-containing plaster of Example (4) was prepared in the same manner as in Reference Example 1, except that it was made to be cm 2.

Example 5 Preparation of Pelbinac-Containing Plaster Example (5)

15% by weight of oleic acid as a percutaneous absorption accelerator, 15% by weight of felbinac, 67% by weight of an acrylic pressure sensitive adhesive and 3% by weight of triethanolamine as a solvent, and a drug content of 0.50 mg / cm2 Except that except that it was carried out in the same manner as in Reference Example 1, to prepare a felbinac-containing plaster of Example (5).

Example 6 Preparation of Pelbinac-Containing Plaster Example (6)

15% by weight of oleyl alcohol as a percutaneous absorption accelerator in the proportion of the composition, 15% by weight of felbinac, 67% by weight of an acrylic pressure sensitive adhesive as a pressure-sensitive adhesive and 3% by weight of triethanolamine as a solvent, and a drug content of 0.50 mg / ㎠ A Pelbinac-containing plaster of Example (6) was prepared in the same manner as in Reference Example 1, except that it was made.

Example 7 Preparation of Pelbinac-Containing Plaster Example (7)

5% by weight of oleyl alcohol as a transdermal absorption accelerator and 10% by weight of sorbitan monooleate, 15% by weight of felbinac, 67% by weight of an acrylic pressure sensitive adhesive as a pressure-sensitive adhesive, and 3% by weight of triethanolamine as a solvent And it was carried out in the same manner as in Reference Example 1 except that the drug content is 0.50mg / ㎠, Pelbinac-containing plaster of Example (7) was prepared.

Example 8 Preparation of Pelbinac-Containing Plaster Example (8)

15% by weight of sorbitan monooleate as a percutaneous absorption accelerator, 15% by weight of felbinac, 15% by weight of an acrylic pressure-sensitive adhesive and 3% by weight of monoethanolamine as a solvent and a drug content of 0.50 mg A Pelbinac-containing plaster of Example (8) was prepared in the same manner as in Reference Example 1 except that it was adjusted to / cm 2.

Example 9 Preparation of Pelbinac-Containing Plaster Example (9)

15% by weight of sorbitan monooleate as a transdermal absorption accelerator, 15% by weight of felbinac, 65% by weight of an acrylic pressure sensitive adhesive as a pressure-sensitive adhesive and 5% by weight of triethanolamine as a solvent, and a drug content of 0.50 mg / A Pelbinac-containing plaster of Example (9) was prepared in the same manner as in Reference Example 1 except that only cm 2 was used.

Example 10 Preparation of Pelbinac-Containing Plaster Example (10)

15% by weight of sorbitan monooleate as a transdermal absorption accelerator, 15% by weight of felbinac, 65% by weight of an acrylic pressure sensitive adhesive as a pressure-sensitive adhesive and 5% by weight of monoethanolamine as a solvent, and a drug content of 0.50 mg. A Pelbinac-containing plaster of Example (10) was prepared in the same manner as in Reference Example 1, except that the / cm 2 was used.

Experimental Example 1: Skin Permeation Test

In order to examine the skin permeability of the manufactured Pelbinac-containing plaster and the conventional plaster products, skin-free and Franz diffusion cells (effective area: 0.64 cm ² , volume of aqueous phase: 5.2 mL) were used for immersion ( Skin permeation test was performed under sink condition.

The aqueous phase was filled with Franz diffusion cell using PBS pH 7.4 (sigma), maintained at 32 ± 0.5 ° C., and then skin mounted, and a sample was attached to the epidermal layer of the skin for permeation experiments. The skin was removed from the 4 week-old hairless rat, and then the skin layer was removed, and the fat layer of the dermal layer was used. The skin was mounted on a diffusion device, and the aqueous phase was stirred at 600 rpm using a magnetic stirrer during the experiment. After a certain period of time after application to quantify the drug permeated, 0.25 ml of the aqueous phase was taken to perform high performance liquid chromatography (HPLC), and the Franz diffusion cell was again filled with the aqueous phase. For high performance liquid chromatography, a Capsel Pack C18 (UG120, 4.6mm × 150mm, Shiseido, Japan) column was installed in an HPLC column holder, the flow rate was set to 1.0 ml / min, and the wavelength of the UV detector was set to 260 nm. Acetonitrile: phosphate buffer solution = 60: 40 It was performed using a mixed solvent. Phosphate buffer solution was prepared to pH 1.5 with potassium phosphate (potassium phosphate) 0.01M and a mixture of phosphate. 20 μl of the sample was injected, and the HPLC system was operated at a column temperature of 40 ° C. to quantify the permeated drug, and the test results for skin permeability are shown in Table 1 below.

Furtherance Example (% by weight) Comparative Example (Weight%) One 2 3 4 5 6 7 8 9 10 One 2 3 Pelby Nak 5 10 20 15 15 15 15 15 15 15 5 15 15 Solvent Triethanolamine 3 3 3 3 3 3 3 5 3 3 Monoethanolamine 3 5 Percutaneous Absorption Accelerator Oleic acid 15 Oleyl alcohol 15 5 Sorbitan monooleate 15 15 15 15 10 15 15 15 15 15 15 Pressure sensitive adhesive Acrylic Adhesive 77 72 62 67 67 67 67 67 65 65 70 Rubber adhesive 77 67 Drug content (mg / ㎠) 0.17 0.34 0.67 0.50 0.50 0.50 0.50 0.50 0.50 0.50 0.17 0.50 0.50 Skin Permeability (㎍ / ㎠ / h) 4.05 5.48 20.71 14.29 17.02 12.15 13.93 19.17 5.01 4.87 3.57 15.83 5.12 Co-solvent: N-methyl-2-pyrrolidone, felbinac and the same dose

 According to the results of Table 1, the skin permeability increases with increasing concentration of felbinac in the formulation, and the skin permeability is affected by the type and the type of solubilizer and percutaneous absorption accelerator used when the same amount of felbinac is administered. In the case of rubber-based pressure-sensitive adhesives, the skin permeability was high when the same amount of Pelbinac was administered, but crystals were easily precipitated, which reduced the storage stability of the formulation. The present invention was able to stably increase the content of felbinac by using alkanolamine as a dissolving agent of felbinac in the formulation, and even if a large amount (about 15% by weight) of felbinac is contained, it is present in high concentration without precipitation and thus high skin. It was shown to show the transmittance.

Experimental Example 2 Stability Experiment

The Pelbinac-containing plasters prepared in Examples 1 to 10 and Reference Examples 1 to 3 were sealed and shielded, and safety experiments were performed at 40 ° C. under accelerated conditions of 75% relative humidity, and the results are shown in Table 2 below. It was.

division Storage period (months) One 2 3 4 5 6 Example 1 × Example 2 × Example 3 △ Example 4 × Example 5 × Example 6 × Example 7 × Example 8 × Example 9 × Example 10 × Comparative Example 1 △ ◇ Comparative Example 2 △ ◇ Comparative Example 3 ◇ △: Partial generation ◇: All generation ×: No determination

According to the present invention, the anti-inflammatory analgesic effect by felbinac can be continuously obtained for a long time, and the felbinac-containing plaster useful as an effective medicine for anti-inflammatory analgesic can be provided by excellent stability and adhesion of the preparation.

Claims (8)

5 to 20% by weight of felbinac as active ingredient, 1 to 5% by weight of ethanol amine as solubilizer, 5 to 20% by weight of N-methyl-pyrrolidone as cosolvent, oleic acid, oleyl alcohol or sodium monooleate as transdermal absorption accelerator Pelbinac-containing plaster composition comprising 5 to 20% by weight of the sole alone or a mixture of two or more, and 50 to 84% by weight of the acrylic adhesive as a pressure-sensitive adhesive delete delete delete delete delete delete delete

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