US 20130035391A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0035391 A1 Katayama et al. (43) Pub. Date: Feb. 7, 2013 (54) FELBINAC-CONTAINING TRANSDERMALLY Publication Classi?cation ABSORBABLE PREPARATION (51) Int. Cl. (75) Inventors: Akiko Katayama, HigashikagaWa-shi A61K31/192 (200601) (JP); Katsuyuki [1100’ (52) US. Cl. ..................................................... .. 514/570 HigashikagaWa-shi (JP) (57) ABSTRACT (73) Assignee: TEIKOKU SEIYAKU CO., LTD., An adhesive patch is a felbinac-containing transdermally KanagaWa (JP) absorbable preparation substantially free of a solubiliZer for felbinac in a ?nal preparation but still having high releasing of (21) Appl. NO.I 13/516,008 felbinac. The adhesive patch in Which lidocaine and felbinac are formulated has the releasing of felbinac Without losing the (22) PCT Filed: Dec- 14: 2010 releasing of lidocaine. The felbinac-containing transderrnally absorbable adhesive patch contains felbinac as an active com (86) PCT N05 PCT/JP2010/072453 ponent and lidocaine or a pharmaceutically acceptable salt § 371 (OX1), thereof as an absorption promoter. In particular, the content of (2)’ (4) Date; Aug 16, 2012 felbinac is from 0.1% to 10% by Weight to the total Weight of the drug-containing plaster and the content of lidocaine or the (30) Foreign Application Priority Data pharmaceutically acceptable salt thereof is from 0.01% to 20% by Weight to the total Weight of the drug-containing Dec. 15, 2009 (JP) ............................... .. 2009-284325 plaster. Patent Application Publication Feb. 7, 2013 Sheet 1 0f 3 US 2013/0035391 A1 [FIG. 1] FELB l NAG PERMEAB | L l TY 41. 000 8 12 086%%0 TIME (hr) —x— COMPARATIVE EXAMPLE 1 EXAMPLE 1 L | DOOAI NE PERMEABI LITY m0 33 0 m 2 5 O 2. U D 235E555M222855%15 11 505 00“U0 TIME-‘(1.10 I ‘*"FGOMPARATIVE EXAMPLE 2! + EXAMPLE 1 Patent Application Publication Feb. 7, 2013 Sheet 2 0f 3 US 2013/0035391 A1 LFIIIG. ‘ s1 KETOPROFEN PERMEABILITY ' 100 600. D .U TIME (hr) ‘ l —-‘+— COMPARATIVE EXAMPLE 3] +GQMPARAT|VE EXAMPLE 4 I [FIG. 4], LIDQCALNE PERMEABILITY" ' TIME (hrY -' K- COMPARATIVE EXAMPLE 2% —-—.i:—-COMPARATIVE EXAMPLE 4_‘ Patent Application Publication Feb. 7, 2013 Sheet 3 0f 3 US 2013/0035391 A1 [FIG. 5], INDOMETHACIN PERMEABI LlTY L 5U @65353%‘@?EmEM5525 TIME (hr) ~2M-0OMPARATIME EXAMPLE 5 COMPARATIVE EXAMPLE 6 [FIG. 6]‘ LIDOCAINE PERMEAB] LITY \nn a.“ ___L LIMA A_ TM w.@m%5 4W U8O \wi. TIME Khl’)‘ -><- COMPARATIVE EXAMPLE 21+,c0MPARAnvE EXAMPLE 6! US 2013/0035391A1 Feb. 7, 2013 FELBINAC-CONTAINING TRANSDERMALLY patch, these formed salts and inhibited the drug releasing of ABSORBABLE PREPARATION each other, thereby failing to obtain a desired medicinal effect. TECHNICAL FIELD PRIOR ART DOCUMENTS [0001] The present invention relates to a transdermally absorbable preparation, and more particularly, to an adhesive Patent Documents patch containing felbinac, a non-steroidal anti-in?ammatory analgesic, as a medicinal component and lidocaine or a phar [0009] Patent Document 1: Japanese Patent Application maceutically acceptable salt thereof being a local anesthetic Laid-Open No. Hei. 4-321624 and as an absorption promoter to felbinac. [0010] Patent Document 2: Japanese Patent Application Laid-Open No. 2001-342130 BACKGROUND ART [0011] Patent Document 3: Japanese Patent Application [0002] Felbinac, Which is a non-steroidal anti-in?amma Laid-Open No. 2003-286162 tory analgesic, is an active metabolite of fenbufen and a drug [0012] Patent Document 4: Japanese Patent Application having high anti-in?ammatory and analgesic activity. Felbi Laid-Open No. 2002-128699 nac has been transdermally administered to avoid systemic [0013] Patent Document 5: International Publication No. side effects and available as external preparations such as a WO 01/047559 gel, a liquid, a cataplasm, and a plaster. [0014] Patent Document 6: Japanese Patent Application [0003] Felbinac itself has very loW solubility in various Laid-Open No. 2005-145931 solvents. Thus, a variety of solubiliZers have been conven [0015] Patent Document 7: Japanese Patent Application tionally used in such external preparations to enhance the Laid-Open No. 2005-145932 transdermal absorption of felbinac. [0016] Thus, as for the adhesive patch in Which a non [0004] For example, Patent Document 1 has proposed a steroidal anti-in?ammatory analgesic and a local anesthetic felbinac -containing plaster Which contains crotamiton having as a transdermal absorption promoter are formulated, it has high solubiliZing ability for felbinac as an essential compo been desired to develop the transdermally absorbable prepa nent. Also, Patent Document 2 has proposed a plaster in ration Which achieves high anti-in?ammatory and analgesic Which N-methyl-2-pyrrolidone and polyethylene glycol are effects Without inhibiting drug releasing of each other. formulated as the solubiliZers. Many of such solubiliZers, hoWever, have caused irritation to the skin. Moreover, When [0017] Under such circumstances, as for felbinac among such liquid components are formulated in an adhesive patch, non-steroidal anti-in?ammatory analgesics, the present a change of the physical properties of the adhesive patch may inventors have intensively studied development of the trans be caused over time by the bleed-out to the surface (the dermally absorbable preparation, Which achieves high anti exudation to the surface) of the adhesive patch. in?ammatory and analgesic effects Without inhibiting the drug releasing of each other, by formulating felbinac With a [0005] In addition, Patent Document 3 has proposed a plas local anesthetic as a transdermal absorption promoter. ter free of crotamiton and containing a styrene-isoprene-sty rene block copolymer, a rosin resin, a plasticiZer, l-menthol, [0018] As a result, When lidocaine Was selected as the and felbinac. This plaster is an adhesive patch in Which fel absorption promoter and formulated together With the non binac is uniformly dispersed in a semi-molten state in the steroidal anti-in?ammatory analgesic felbinac in an adhesive adhesive layer, i.e., in a state Wherein felbinac is present in a patch base, it Was found that a uniform drug-containing plas molten state and in a ?ne crystalline state simultaneously. The ter Was obtained even substantially free of the solubiliZer for drug permeability hoWever Was not suf?cient because part of felbinac to provide a felbinac-containing transdermally felbinac Was present in a crystalline state. absorbable preparation having high releasing of main drugs While the transdermally absorbable preparation had excellent [0006] Further, a combination preparation in Which a non analgesic and anti-in?ammatory activity Without losing the steroidal anti-in?ammatory analgesic and a local anesthetic transdermal absorption of lidocaine as the local anesthetic, are formulated has been studied Wherein the preparation has thereby completing the present invention. both an anti-in?ammatory activity of the non-steroidal anti in?ammatory analgesic and an analgesic activity of the local SUMMARY OF THE INVENTION anesthetic. [0007] For example, Patent Document 4 and Patent Docu Problems to be Solved by the Invention ment 5 have proposed a cataplasm in Which a non-steroidal anti-in?ammatory analgesic such as indomethacin, felbinac, [0019] Thus, it is a ?rst object of the present invention to diclofenac sodium and loxoprofen sodium and a local anes provide a felbinac-containing transdermally absorbable thetic such as lidocaine, benZocaine and dibucaine are formu preparation substantially free of a solubiliZer for felbinac in a lated. Also, Patent Document 6 and Patent Document 7 have ?nal preparation but still having high releasing of felbinac to proposed a tape in Which a non-steroidal anti-in?ammatory solve the above-mentioned conventional problems. analgesic and a local anesthetic are formulated respectively. [0020] Further, it is a second object of the present invention [0008] In general, hoWever, many local anesthetics are to provide an adhesive patch in Which a local anesthetic and basic drugs, While many non-steroidal anti-in?ammatory felbinac, Which is the non-steroidal anti-in?ammatory anal analgesics to be formulated together are acidic drugs includ gesic, are formulated, Wherein the adhesive patch has excel ing indomethacin and ketoprofen. Accordingly, When these lent releasing of the non-steroidal anti-in?ammatory analge both drugs Were simultaneously formulated in the adhesive sic Without losing the releasing of the local anesthetic. US 2013/0035391A1 Feb. 7, 2013 Means for Solving the Problem [0033] FIG. 6 is a graph shoWing the result of in vitro rat skin permeability test for lidocaine based on Comparative [0021] A basic aspect of the present invention to solve such Study (3) of Test Example 1. problems is a felbinac-containing transdermally absorbable adhesive patch, Which contains felbinac as an active compo EMBODIMENTS FOR CARRYING OUT THE nent and lidocaine or a pharmaceutically acceptable salt INVENTION thereof as an absorption promoter. [0022] Speci?cally, the present invention is the felbinac [0034] The basic aspect of the present invention, as containing transdermally ab sorbable adhesive patch Wherein described above, is the felbinac-containing transdermally the content of felbinac is from 0.1% to 10% by Weight to the absorbable adhesive patch, Which contains felbinac as an total Weight of the drug-containing plaster base material and anti-in?ammatory analgesic medicinal component and the content of lidocaine or the pharmaceutically acceptable lidocaine or a pharmaceutically acceptable salt thereof as an salt thereof is from 0.01% to 20% by Weight to the total absorption promoter. Weight of the drug-containing plaster base material. [0035] The formulated amount of the active component [0023] Especially, the present invention is the felbinac-con felbinac in the adhesive patch of the present invention is from taining transdermally absorbable adhesive patch Wherein an 0.1% to 10% by Weight and particularly preferably from 0.2% adhesive patch base is a rubber polymer and the rubber poly to 5% by Weight to the total Weight of the drug-containing mer is a styrene-isoprene-styrene block copolymer.