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Composition for intranasal administration of cGMP PDE inhibitor for treatment of erectile dysfunction, also containing local anesthetic to prevent nasal blockage and improve absorption
Composition for intranasal administration of cGMP PDE inhibitor for treatment of erectile dysfunction, also containing local anesthetic to prevent nasal blockage and improve absorption
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.
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