(IO)  Patent No.:  US 7,943,176 B2  May 17, 2011  (45)  Date of Patent:  c12)  United States Patent  Gramatte et al.  (54)  ORAL DOSAGE FORM FOR PROPIVERINE  OR ITS PHARMACEUTICALLY  ACCEPTABLE SALTS WITH AN EXTENDED  RELEASE OF THE ACTIVE INGREDIENT  (75)  Inventors:  Thomas Gramatte,  Dresden (DE);  Peter Gruber,  Merzhausen (DE);  Michael Heschel,  Pima (DE);  Dirk  Pamperin,  Dresden (DE);  Jan Ploen,  Dresden (DE);  Steffen Scheithauser,  Dresden (DE);  Wolfgang Wehner,  Barthen (DE);  Peter Guldner,  Dresden  (DE)  (73)  Assignee:  Apogepha Arzneimittel GmbH,  Dresden (DE)  ( *)  Notice:  Subject to any disclaimer, the term ofthis  patent is extended or adjusted under 35  U.S.C. 154(b) by 1151 days.  (21)  Appl. No.:  10/492,270  (22)  PCT Filed:  Oct. 8, 2002  (86)  PCT No.:  PCT /EP02/11253  § 371 (c)(l),  (2), ( 4) Date:  Apr. 8, 2004  (87)  PCT Pub. No.:  WO03/030869  (51)  Int. Cl.  A61K 9/14  (2006.01)  (52)  U.S. Cl.  ........  424/489;  424/490; 424/494; 424/451;  424/457; 424/461; 514/317  (58)  Field of Classification Search  ........................ None  See application file for complete search history.  (65)  Prior Publication Data  (30)  Foreign Application Priority Data  (56)  References Cited  U.S. PATENT DOCUMENTS  FOREIGN PATENT DOCUMENTS  OTHER PUBLICATIONS  (57)  ABSTRACT  19 Claims, 6 Drawing Sheets  AU  DE  DE  DE  764469  29 37 489  100 16 356  100 16 356 Al  8/2000  4/1980  10/2001  10/2001  5,178,868 A *  5,912,268 A  6,962,717 Bl *  7,138,405 B2 *  1/1993 Malmqvist-Granlund  et al. ............................. 424/490  6/1999 Guittard et al ................ 514/534  11/2005 Huber et al. .................. 424/490  11/2006 Wyllie .......................... 514/272  2001/0005728 Al*  2002/0010216 Al*  2003/0064036 Al *  6/2001 Guittard et al ................ 514/534  1/2002 Rogosky et al ............... 514/649  4/2003 Petereit et al. .................. 424/49  US 2004/0258749 Al  US 2008/0317848 A2  Dec. 23, 2004  Dec. 25, 2008  DE  101 49 674  4/2003  EP  0032562  3/1984  EP  0069259  1/1985  EP  0 253 541  1/1988  EP  0 365 947  5/1990  EP  497977  10/1990  EP  0068191  9/1991  EP  1229026 Al  11/2000  EP  1 064 938  1/2001  EP  1123705 Al  2/2001  EP  1123705  *  8/2001  EP  1 273 301 A2  1/2003  GB  2031727  11/1982  JP  63-23814  2/1988  JP  63-154619  6/1988  JP  2164821  6/1990  JP  9501445  10/1997  JP  11505264  5/1999  JP  2001-39873  2/2001  JP  2001039873  2/2001  JP  2001048783  2/2001  JP  2002-535353  10/2002  JP  2003-503341  1/2003  JP  2003-513033  4/2003  WO  95/23593  9/1995  WO  WO  95/23593  9/1995  WO  96/12477  5/1996  WO  96/37202  11/1996  WO  WO  96/37202  11/1996  WO  WO  9709980  *  3/1997  WO  97/12605  4/1997  WO  97/37640  10/1997  WO  98/18610  5/1998  WO  98/32425  7 /1998  (Continued)  PCT Pub. Date:  Apr. 17, 2003  Oct. 9, 2001  (DE) .................................. 101 49 674  US007943176B2  Laicher et al.-Theophyllin, "Die Pellet-Technologie",  Arzneim› Forsch./Drug Res.  48(1), Nr. 5a (1998), pp. 540-547.  Grunenberg et al.-Theophyllin, "Erfahrungen bei der Ubertragung  des Filmcoating-Prozessess fur Theophyllin-Retardpellets in den  ProduktionsmaBstab",  Arzneim-Forsch./Drug Res.  48(1), Nr. 5a  (1998), pp. 547-551.  Fuchs et al.-Theophyllin, "EinfluB verschiedener Variablen auf die  ln-vitro-Freisetzung eines Theophyllin-Retardpraparates",  Arzneim› Forsch./Drug Res.  48(1), Nr. 5a (1998), pp. 552-556.  Fuchs et al.-Theophyllin, Anforderungen an die Produktqualitat  von Theophyllin-Retardpraparaten,  Arzneim-Forsch./Drug Res.  48(1), Nr. 5a ( 1998), pp. 556-561.  Wilson et al.-Theophyllin, "Wirkung der Vorbenhandlung mit  Ranitidin auf Pharmakokinetik und gastrointestinale Passage eines  Theophyllin Retard-Praparates",  Arzneim-Forsch./Drug Res.  48(1),  Nr.  5a (1998), pp. 561-568.  (Continued)  Primary Examiner  - Robert A. Wax  Assistant Examiner  - Hasan S Ahmed  (74)  Attorney, Agent, or Firm  - Vidas, Arrett & Steinkraus  By suitable retardation oral pharmaceutical compositions  containing propiverine or one or several pharmaceutically  acceptable salts thereof in an amount of 4 mg to 60 mg  propiverine and having a prolonged release of the active agent  are produced. Preferably a blend of active agent and option› ally one or more acidic substances having a  pKa  value ofless  than 6.65 are provided with a retarding coating or are embed› ded in a matrix which is then optionally coated with further  retarding layers. 