INHIBITING MOBILIZATION OF CALCIUM PHOSPHATE INHIBITING MOBILIZATION OF CALCIUM PHOSPHATE

摘要

1401548 Pharmaceutical compositions PROCTER & GAMBLE CO 8 June 1973 [8 June 1972 17 May 1973] 27457/73 Heading A5B Pharmaceutical compositions for inhibiting mobilisation of calcium phosphate in animal tissue useful in the treatment of osteoporosis and Paget's disease comprises (1) at least one polyphosphonate selected from the compounds wherein each R is H or CH 2 OH and n is an integer of from 3 to 10 wherein R 1 is H, C 1-20 alkyl, C 2-20 alkenyl, aryl (e.g. phenyl or naphthyl), phenylethenyl, benzyl, halogen (e.g. Cl, Br, or F), hydroxy, amino, substituted amino (e.g. dimethylamino, diethylamino, N-hydroxy-N-ethylamino or acetylamino), -CH 2 COOH, -CH 2 PO 3 H 2 , -CH- (PO 3 H 2 )(OH) or -[CH 2 C(PO 3 H 2 ) 2 ] n -H wherein n is 1 to 15, and R 2 is hydrogen, C 1-4 alkyl, amino, benzyl, halogen, hydroxyl, -CH 2 COOH, -CH 2 PO 3 H 2 , or -CH 2 CH 2 PO 3 H 2 , wherein n is from 3 to 9, wherein each R 3 is hydrogen or C 1-4 alkyl, wherein n is from 2 to 4, wherein X and Y are each hydrogen or hydroxy or a pharmaceutically acceptable salt thereof e.g. an alkali metal (Na or K), alkaline earth metal (Ca or Mg), non-toxic heavy metal (stannous or indium), ammonium or substituteed ammonium (mono-, di- or triethanolamine) salts, and (2) at least one antirachitic compound selected from vitamin D 2 , vitamin D 3 , dihydroxytachysterol 2 , dihydrotachysterol 3 , 25-hydroxydihydrotachysterol 3 , 25-hydroxyergocalciferol, 25-hydroxycholecalciferol, 1α, 25-. dihydroxycholecalciferol, 5, 6-trans-cholecalciferol, 5, 6-trans-25-hydroxycholecalciferol, 24- nor-25-hydroxycholecalciferol, 24-nor-5, 6-trans 25-hydroxycholecalciferol, 21, 25-dihydroxycholecalciferol, 25, 26-dihydroxycholecalciferol, 24, 25-dihydroxycholecalciferol, and 1α- hydroxycholecalciferol. The polyphosphonate is preferably ethane-1-hydroxy-1, 1-diphosphonic acid, dichloromethandiphosphonic acid, tris(phosphonomethyl)amine, methanecyclohexylhydroxydiphosphonic acid 3, 3, 4, 4, 5, 5- hexafluoro-1, 2-diphosphonocyclopent-1-ene, cyclic tetraphosphonic acid, ethene-1, 2-dicarboxy-1-phosphonic acid or ethane-1, 2-dicarboxy-1, 2-diphosphonic acid. The compositions may be administered orally or parenterally in the form of solutions, elixiers, capsules, tablets, or pills.