Patent DE-10118305-A1 (DE)
Title: Composition for intranasal administration of cGMP PDE inhibitor for treatment of erectile dysfunction, also containing local anesthetic to prevent nasal blockage and improve absorption
Inventor: SERNO PETER
IPC: A61K9/72
Filed: 2001-04-12
Abstract: A new composition comprises: (1) at least one cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) inhibitor (I); and (2) at least one local anesthetic (II) (other than benzyl alcohol). A new composition comprises: (1) at least one cyclic guanosine monophosphate phosphodiesterase (cGMP PDE) inhibitor (I); and (2) at least one local anesthetic (II) (other than benzyl alcohol). (I) are selected from pyrazolo-pyrimidinone derivatives of formula (I'), pyrazino-pyridino-indole derivatives of formula (I'') and their salts, isomers and/or hydrates.  R1 = H, 1-3C alkyl, 1-3C perfluoroalkyl or 3-5C cycloalkyl; R2 = T (optionally substituted (os) by 3-6C cycloalkyl), 1-3C perfluoroalkyl or 3-6C cycloalkyl; T = 1-6C alkyl; R3 = T (os by 3-6C cycloalkyl), 1-6C perfluoroalkyl, 3-5C cycloalkyl, 3-6C alkenyl or 3-6C alkynyl; R4 = 1-4C alkyl (os by OH, NR5R6, CN, CONR5R6 or COOR7); 2-4C alkenyl (os by CN, CONR5R6 or COOR7); 2-4C alkanoyl (os by NR5R6); 2-4C hydroxyalkyl (os by NR5R6); (2-3C) alkoxy-(1-2C) alkyl (os by OH or NR5R6); CONR5R6; COOR7; halo; NR5R6; NHSO2NR5R6; NHSO2R8; SO2NR9R10; or phenyl, pyridinyl, pyrimidinyl, imidazolyl, oxazolyl, thiazolyl, thienyl or triazolyl (all os by Me); R5, R6 = H or 1-4C alkyl; or NR5R6 = pyrrolidino, piperidino, morpholino, 4-(R11)-piperazino or imidazolyl (all os by Me or OH); R7 = H or 1-4C alkyl; R8 = 1-3C alkyl (os by NR5R6); NR9R10 = pyrrolidino, piperidino, morpholino or 4-(R12)-piperazino (all os by 1-4C alkyl, 1-3C alkoxy, NR13R14 or CONR13R14); R11 = H, 1-3C alkyl (os by Ph), 2-3C hydroxyalkyl or 1-4C alkanoyl; R12 = H; T (os by CONR13R14); 2-6C alkyl substituted by 1-3C alkyl, OH or NR13R14; or CONR13R14, CSNR13R14 or C(NH)NR13R14; Q = H, halo or T; Q1 = H, T (os by halo), 2-6C alkenyl, 2-6C alkynyl, 3-8C cycloalkyl, 3-8C cycloalkyl-(1-3C) alkyl or Ar-(1-3C) alkyl; Ar = phenyl, thienyl, furyl or pyridyl (all os by 1-3 of halo, T, OT and OCH2O); Q2 = phenyl, thienyl, furyl or pyridyl (all os); or phenyl fused with a 5- or 6-membered saturated or partially or completely unsaturated ring containing 0-2 of O, N and S as heteroatoms; Q3 = H or 1-3C alkyl; or Q1 + Q3 = 3- or 4-membered alkylene or alkenylene chain completing a 5- or 6-membered ring. (II) is selected from: (1) compounds of formula (II'); (2) compounds of formula (II''); (3) 2-methoxycarbonyl-4-methyl-3-(2-(propylamino)-propionamido)-thiophene; (4) 2-butoxy-4-(N-(2-diethylaminoethyl)-carbamoyl)-quinoline;  (5) 3-butyl-1-(2-dimethylaminoethyl)-isoquinoline;  (6) N-(N-(1,1-dimethylpropyl)-N-methylcarbamoylmethyl)-N-(2-hydroxyethyl)- glycine N-(1,1-dimethyl-2-phenylethyl)-N-methylamide;  (7) polydodecanol; and (8) benoxinate. or their salts or hydrates.  A1 = H, NH2, NHT, OT or OCH2Ph; A2 = OT (optionally substituted by NHT, NT2 or Het) or -(CH2)p-Het; Het = saturated 5- or 6-membered heterocycle, which contains and is bonded via N, optionally contains 1 or 2 other N, O or S heteroatoms and is optionally substituted by 1-3 T; A3 = H, halo or OT; B1 = H or OH; B2 = -T'-NT2 or Het'; T' = 1-6C alkylene (optionally substituted by one or more T); Het' = as for Het, but not necessarily bonded via N; B3 = T, halo or COOT; n  = 1 or 2. Independent claims are included for nasal spray applicators or powder inhalers (both preferably of unit dose type) containing the compositions.