USRE34313EExpiredUtility

Pharmaceutical compositions

50
Priority: Sep 23, 1983Filed: Oct 1, 1991Granted: Jul 13, 1993
Est. expirySep 23, 2003(expired)· nominal 20-yr term from priority
C07F 15/025A61K 31/44C07D 213/89
50
PatentIndex Score
21
Cited by
80
References
28
Claims

Abstract

Compounds which are a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to ring carbon atoms are replaced by a substituent selected from aliphatic acyl, aliphatic amide, aliphatic amine, carboxy, cyano, aliphatic ester, halogen, hydroxy and sulpho groups, alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic amine, aliphatic ester, halogen or hydroxy group, aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, but excluding compounds in which said replacement of hydrogen atoms in the compound is effected only by substituents selected from aliphatic hydrocarbon groups, halogen groups and aliphatic hydrocarbon groups substituted by a halogen group, or a salt thereof containing a physiolgically acceptable ion or ions, are of value in the treatment of patients having a toxic concentration of a metal, particularly iron, in the body whilst the iron complexes of such compounds are of value in the treatment of iron deficiency anaemia.

Claims

exact text as granted — not AI-modified
We claim: 
     
       1. A method for the treatment of a patient having a toxic concentration of iron in the body which comprises administering to said patient a compound being a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to ring carbon atoms are replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, but excluding compounds in which said replacement of hydrogen atoms is effected only by substituents selected from aliphatic hydrocarbon groups, halogen groups and aliphatic hydrocarbon groups substituted by a halogen group, or a salt thereof containing a physiologically acceptable cation in an amount effective to reduce said toxic concentration of the metal. 
     
     
       2. The method according to claim 1, in which at least one of the ring carbon atom substituents is a hydroxy, alkoxy or substituted alkoxy group, or a hydroxy- or alkoxy-substituted aliphatic hydrocarbon group. 
     
     
       3. The method according to claim 2 in which at least one of the ring carbon atom substituents is a hydroxy group, an alkoxy group of 1 to 5 carbon atoms, an alkoxy group of 2 to 4 carbon atoms substituted by a hydroxy group, or an alkoxy group of 2 to 4 carbon atoms substituted by an alkoxy group of 1 to 4 carbon atoms, the total number of carbon atoms in the alkoxyalkoxy group being 3 to 6. 
     
     
       4. The method according to claim 3, in which the ring carbon atoms of the 1-hydroxypyrid-2-one are substituted by a single one of said substituents and additionally by one or more aliphatic hydrocarbon groups of 1 to 4 carbon atoms. 
     
     
       5. The method according to claim 3, in which the ring carbon atoms of the 1-hydroxypyrid-2-one are substituted only by a single one of said substituents. 
     
     
       6. The method according to claim 5, in which the single one of said substituents is located at the 4-position of the 1-hydroxypyrid-2-one. 
     
     
       7. The method according to claim 1, in which the 1-hydroxypyrid-2-one is 1-hydroxy-4-methoxypyrid-2-one, 4-ethoxy-1-hydroxypyrid-2-one, 1,4-dihydroxypyrid-2-one, 1-hydroxy-4-(2'-hydroxyethoxy)-pyrid-2-one, 1-hydroxy-4-(3'-hydroxypyropoxy)-pyrid-2-one or 1-hydroxy-4-(2'-methoxyethoxy)-pyrid-2-one. 
     
     
       8. The method according to claim 1, wherein said at least one substituent is an alkoxy group substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group.[., and wherein at least one additional hydrogen atom may be substituted by a hydroxy group.].. 
     
     
       9. The method of claim 8, wherein one of the said hydrogen atoms attached to the ring carbon atoms of the 1-hydroxypyrid-2-one is replaced by a C 2-4  alkoxy group substituted by a hydroxy group or by a C 1-4  alkoxy group, with the total number of carbon atoms in the alkoxyalkoxy group ranging from 3 to 6, and wherein at least one more of the said hydrogen atoms can be replaced by an aliphatic .Iadd.hydrocarbon .Iaddend.group of 1 to 4 carbon atoms. 
     
     
       10. A method for the treatment of a patient to effect an increase in the level of iron in the patient's bloodstream which comprises adminstering to said patient a compound being an iron complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to ring carbon atoms are replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, but excluding compounds in which said replacement of hydrogen atoms is effected only by substituents selected from aliphatic hydrocarbon groups, halogen groups and aliphatic hydrocarbon groups substituted by a halogen group, in an amount effective to achieve such an increase. 
     
     
       11. The method according to claim 10, in which at least one of the ring carbon atom substituents is a hydroxy, alkoxy or substituted alkoxy, group, or a hydroxy- or alkoxy-substituted aliphatic hydrocarbon group. 
     
     
       12. The method according to claim 11, in which at least one of the ring carbon atom substituents is a hydroxy group, an alkoxy group of 1 to 5 carbon atoms, an alkoxy group of 2 to 4 carbon atoms substituted by a hydroxy group, or an alkoxy group of 2 to 4 carbon atoms substituted by an alkoxy group of 1 to 4 carbon atoms, the total number of carbon atoms in the alkoxyalkoxy group being 3 to 6. 
     
     
       13. The method according to claim 12, in which the ring carbon atoms of the 1 -hydroxypyrid-2-one are substituted by a single one of said substituents and additionally by one or more aliphatic hydrocarbon groups of 1 to 4 carbon atoms. 
     
     
       14. The method according to claim 12, in which the ring carbon atoms of the 1-hydroxypyrid-2-one are substituted only by a single one of said substituents. 
     
     
       15. The method according to claim 14 in which the single one of said substituents is located at the 4-position of the 1-hydroxypyrid-2-one. 
     
     
       16. The method according to claim 10, in which the 1-hydroxypyrid-2-one is 1-hydroxy-4-methoxypyrid-2-one, 4-ethoxy-1-hydroxypyrid-2-one, 1,4-dihydroxypyrid-2-one, 1-hydroxy-4-(2'-hydroxyethoxy)-pyrid-2-one, 1-hydroxy-4-(3'-hydroxypropoxy)-pyrid-2-one or 1-hydroxy-4-(2'-methoxyethoxy)-pyrid-2-one. 
     
     
       17. The method according to claim 16, in which the iron complex is the neutral 3:1 1-hydroxypyrid-2-one:iron(III) complex. 
     
     
       18. The method according to claim 10, in which the iron complex is the neutral 3:1 1-hydroxypyrid-2-one:iron(III) complex. 
     
     
       19. A pharmaceutical composition comprising a neutral 3:1 1-hydroxypyrid-2-one:iron(III) complex of a 1-hydroxypyrid-2-one in which one .[.or more.]. of the hydrogen atoms attached to ring carbon atoms .[.are.]. .Iadd.is .Iaddend.replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, .[.halogen.]. or hydroxy group, .[.aliphatic hydrocarbon groups.]. and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, .[.halogen.]. or hydroxy group, .[.but excluding compounds in which said replacement of hydrogen atoms is effected only by substituents selected from aliphatic hydrocarbon groups, halogen groups and aliphatic hydrocarbon groups substituted by a halogen group,.]. together with a physiologically acceptable diluent or carrier. 
     
     
       20. The pharmaceutical composition according to claim 19, which comprises a sterile, pyrogen-free diluent. 
     
     
       21. The pharmaceutical composition according to claim 19 which comprises a solid carrier. 
     
     
       22. The pharmaceutical composition according to claim 21 which is adapted to release of the iron complex in the intestine rather than in the stomach. 
     
     
       23. The pharmaceutical composition according to claim 19 in unit dosage form. 
     
     
       24. The pharmaceutical composition according to claim 19, in which .[.at least one of.]. the ring carbon atom .[.substituents.]. .Iadd.substituent .Iaddend.is a hydroxy group, an alkoxy group of 1 to 5 carbon atoms, an alkoxy group of 2 to 4 carbon atoms substituted by a hydroxy group, or an alkoxy group of 2 to 4 carbon atoms substituted by an alkoxy group of 1 to 4 carbon atoms, the total number of carbon atoms in the alkoxyalkoxy group being 3 to 6. 
     
     
       25. A compound being a neutral 3:1 1-hydroxypyrid-2-one:iron (III) complex of a 1-hydroxypyrid-2-one in which one .[.or more.]. of the hydrogen atoms attached to ring carbon atoms .[.are.]. .Iadd.is .Iaddend.replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, .[.halogen.]. or hydroxy group, .[.aliphatic hydrocarbon groups.]. and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, .[.halogen.]. or hydroxy group .[.but excluding compounds in which said replacement of hydrogen atoms is effected only by substituents selected from aliphatic hydrocarbon groups, halogen groups and aliphatic hydrocarbon groups substituted by a halogen group.].. 
     
     
       26. The compound according to claim 25, in which .[.at least one of the ring carbon atom substituents.]. .Iadd.the ring carbon atom substituent .Iaddend.is a hydroxy, alkoxy, substituted alkoxy, or hydroxy- or alkoxy-substituted aliphatic hydrocarbon group. 
     
     
       27. The compound according to claim 26, in which .[.at least one of the ring carbon atom substituents.]. .Iadd.the ring carbon atom substituent .Iaddend.is a hydroxy group, an alkoxy group of 1 to 5 carbon atoms, an alkoxy group of 2 to 4 carbon atoms substituted by a hydroxy group or an alkoxy group of 2 to 4 carbon atoms substituted by an alkoxy group of 1 to 4 carbon atoms, the total number of carbon atoms in the alkoxyalkoxy group being 3 to 6. .[. 
     
     
       28.  The compound according to claim 27, in which the ring carbon atoms of the 1-hydroxypyrid-2-one are substituted by a single one of said substituents and additionally by one or more aliphatic hydrocarbon groups of 1 to 6 carbon atoms..]. .[.29. The compound according to claim 27, in which the ring carbon atoms of the 1-hydroxypyrid-2-one are substituted 
     
     
        only by a single one of said substituents..]. 30. The compound according to claim .[.29.]. .Iadd.27.Iaddend., in which the .[.single one of.]. said .[.substituents.]. .Iadd.substituent .Iaddend.is located at the 4-position 
     
     
        of the 1-hydroxypyrid-2-one. 31. The compound according to claim 30, in which the 1-hydroxypyrid-2-one is 1-hydroxy-4-methoxypyrid-2-one, 4-ethoxy-1-hydroxy-pyrid-2-one, 1,4-dihydroxypyrid-2-one, 1-hydroxy-4-(2-(2'-hydroxyethoxy)pyrid-2-one, 1-hydroxy-4-(3'-hydroxypropoxy)-pyrid-2-one or 
     
     
        1-hydroxy-4-(2'-methoxyethoxy)-pyrid-2-one. .Iadd.32.  A pharmaceutical composition, comprising a neutral 3:1 1-hydroxypyrid-2-one:iron(III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to ring carbon atoms are replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, but excluding compounds in which said replacement of hydrogen atoms is effected only by substituents selected from aliphatic hydrocarbon groups, halogen groups and aliphatic hydrocarbon groups substituted by a halogen group, together with a physiologically acceptable diluent or carrier, wherein said composition is adapted to release of the iron complex in the intestine 
     
     
        rather than the stomach. .Iaddend. .Iadd.33.  A pharmaceutical composition comprising a neutral 3:1 1-hydroxypyrid-2-one:iron(III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to ring carbon atoms are replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, C 2-5  alkoxy groups and alkoxy groups substituted by a alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, but excluding compounds in which said replacement of hydrogen atoms is effected only by substituents selected from aliphatic hydrocarbon groups, halogen groups and aliphatic hydrocarbon groups substituted by a halogen group, together with a physiologically acceptable solid carrier. .Iaddend. .Iadd.34. A pharmaceutical composition comprising a neutral 3:1 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to ring carbon atoms are replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, C 2-5  alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, but excluding compound in which said replacement of hydrogen atoms is effected only by substituents selected from aliphatic hydrocarbon groups, halogen groups and aliphatic hydrocarbon groups substituted by a halogen group, together with a physiologically acceptable diluent or carrier, wherein said composition is adapted to release of the iron complex in the intestine rather than in the stomach. .Iaddend. .Iadd.35. A pharmaceutical composition comprising a neutral 3:1 1-hydroxypyrid-2-one:iron(III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to the ring carbon atoms are replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, C 2-5  alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, at least one of the ring carbon atom substituents being a hydroxy group, an alkoxy group of 2 to 5 carbon atoms, an alkoxy group of 2 to 4 carbon atoms substituted by a hydroxy group, or an alkoxy group of 2 to 4 carbon atoms substituted by an alkoxy group of 1 to 4 carbon atoms, the total number of carbon atoms in the alkoxyalkoxy group being 3 to 6, together with a physiologically acceptable diluent or carrier. .Iaddend. .Iadd.36. A pharmaceutical composition comprising a neutral 3:1 1-hydroxypyrid-2-one:iron(III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to the ring carbon atoms are replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, C 2-6  aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, but excluding compounds in which said replacement of hydrogen atoms is effected only by substituents selected from aliphatic hydrocarbon groups, halogen groups and aliphatic hydrocarbon groups substituted by a halogen group, together with a 
     
     
        physiologically acceptable solid carrier. .Iaddend. .Iadd.37.  The pharmaceutical composition according to claim 36 which is adapted to release of the iron complex in the intestine rather than in the stomach. 
     
     
        .Iaddend. .Iadd.38.  A pharmaceutical composition comprising a neutral 3:1 1-hydroxypyrid-2-one:iron(III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to the ring carbon atoms are replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, C 2-6  aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, at least one of the ring carbon atoms substituents being a hydroxy group, an alkoxy group of 1 to 5 carbon atoms, an alkoxy group of 2 to 4 carbon atoms substituted by a hydroxy group, or an alkoxy group of 2 to 4 carbon atoms substituted by an alkoxy group of 1 to 4 carbon atoms, the total number of carbon atoms in the alkoxyalkoxy group being 3 to 6, together with a physiologically acceptable diluent or carrier. .Iaddend. .Iadd.39. A compound being a neutral 3:1 1-hydroxypyrid-2-one:iron(III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to the ring carbon atoms are replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, C 2-5  alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, at least one of the ring carbon atom substituents being a hydroxy, alkoxy, substituted alkoxy, or hydroxy- or alkoxy-substituted aliphatic hydrocarbon group. 
     
     
        .Iaddend. .Iadd.40.  The compound according to claim 38, in which at least one of the ring carbon atom substituents is a hydroxy group, an alkoxy group of 2 to 5 carbon atoms, an alkoxy group of 2 to 4 carbon atoms substituted by a hydroxy group, or an alkoxy group of 2 to 4 carbon atoms substituted by an alkoxy group of 1 to 4 carbon atoms, the total number of 
     
     
        carbon atoms in the alkoxyalkoxy group being 3 to 6. .Iaddend. .Iadd.41. The compound according to claim 40, in which the ring carbon atoms of the 1-hydroxypyrid-2-one are substituted by a single one of said substituents and additionally by one or more aliphatic hydrocarbon groups of 1 to 6 carbon atoms. .Iaddend. .Iadd.42. The compound according to claim 40, in which the ring carbon atoms of the 1-hydroxypyrid-2-one are substituted only by a single one of said substituents. .Iaddend. .Iadd.43. The compound according to claim 42, in which the single one of said substituents is located at the 4-position of the 1-hydroxypyrid-2-one. 
     
     
        .Iaddend. .Iadd.44.  A compound being a neutral 3:1 1-hydroxypyrid-2-one:iron (III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to ring carbon atoms are replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, C 2-6  aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, at least one of the ring carbon atom substituents being a hydroxy, alkoxy, substituted alkoxy, or hydroxy- or 
     
     
        alkoxy-substituted aliphatic hydrocarbon group. .Iaddend. .Iadd.45.  The compound according to claim 44, in which at least one of the ring carbon atom substituents is a hydroxy group, an alkoxy group of 1 to 5 carbon atoms, an alkoxy group of 2 to 4 carbon atoms substituted by a hydroxy group, or an alkoxy group of 2 to 4 carbon atoms substituted by an alkoxy group of 1 to 4 carbon atoms, the total number of carbon atoms in the 
     
     
        alkoxyalkoxy group being 3 to 6. .Iaddend. .Iadd.46.  The compound according to claim 45, in which the ring carbon atoms of the 1-hydroxypyrid-2-one are substituted by a single one of said substituents and additionally by one or more aliphatic hydrocarbon groups of 2 to 6 carbon atoms. .Iaddend. .Iadd.47. The compound according to claim 45, in which the ring carbon atoms of the 1-hydroxypyrid-2-one are substituted only by a single one of said substituents. .Iaddend. .Iadd.48. The compound according to claim 47, in which the single one of said substituents is located at the 4-position of the 1-hydroxypyrid-2-one. .Iaddend. .Iadd.49. The pharmaceutical composition according to claim 32, which comprises a sterile, pyrogen-free diluent. .Iaddend. .Iadd.50. The pharmaceutical composition according to claim 32 which comprises a solid carrier. .Iaddend. .Iadd.51. The pharmaceutical composition according to claim 32, in which at least one of the ring carbon atom substituents is a hydroxy group, an alkoxy group of 1 to 5 carbon atoms, an alkoxy group of 2 to 4 carbon atoms substituted by a hydroxy group or an alkoxy group of 2 to 4 carbon atoms substituted by an alkoxy group of 1 to 4 carbon atoms, the total number of carbon atoms in the alkoxyalkoxy group being 3 to 6. 
     
     
        .Iaddend. .Iadd.52.  A compound being a neutral 3:1 1-hydroxypyrid-2-one:iron(III) complex of a 1-hydroxypyrid-2-one of the formula ##STR8## wherein one of the hydrogen atoms attached to ring carbon atoms is 
     
     
        replaced by an aliphatic amide substituent. .Iaddend. .Iadd.53.  The compound of claim 52, wherein one of said hydrogen atoms attached to ring carbon atoms is replaced by an aliphatic amide of the formula --CONH 2  or a group --CONH 2  wherein one or more of the hydrogen atoms of this group is replaced by a C 1-3  aliphatic hydrocarbon group. .Iaddend. .Iadd.54. The compound of claim 52, wherein one of said hydrogen atoms attached to ring carbon atoms is replaced by an aliphatic amide of the formula --CONH 2  or --CONHCH 3 . .Iaddend. .Iadd.55. The pharmaceutical composition of claim 32 in which more than one hydrogen atom attached to ring carbon atoms are replaced by one of said 
     
     
        substituent. .Iaddend. .Iadd.56.  A pharmaceutical composition comprising a neutral 3:1 1-hydropyrid-2-one:iron (III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to ring carbon atoms are replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, C 2-5  alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, but excluding compounds in which said replacement of hydrogen atoms is effected only by substituents selected from aliphatic hydrocarbon groups, halogen groups and aliphatic hydrocarbon groups substituted by a halogen group, together with a physiologically acceptable diluent or carrier. .Iaddend. .Iadd.57. A pharmaceutical composition comprising a neutral 3:1 1-hydropyrid-2-one:iron (III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to ring carbon atoms are replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, C 2-6  aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, but excluding compounds in which said replacement of hydrogen atoms is effected only by substituents selected from aliphatic hydrocarbon groups, halogen groups and aliphatic hydrocarbon groups substituted by a halogen group, together with a physiologically acceptable diluent or carrier. .Iaddend. .Iadd.58. A compound being a neutral 3:1 1-hydroxypyrid-2-one:iron (III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to ring carbon atoms are replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, C 2-5  alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, at least one of the ring carbon atom substituents being a hydroxy, alkoxy, substituted alkoxy, or hydroxy- or alkoxy-substituted aliphatic hydrocarbon group. .Iaddend. .Iadd.59. A compound being a neutral 3:1 1-hydroxypyrid-2-one:iron (III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to ring carbon atoms are replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, C 2-6  aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, at least one of the ring carbon atom substituents being a hydroxy, alkoxy, substituted alkoxy, or hydroxy- or alkoxy-substituted aliphatic hydrocarbon group. 
     
     
        .Iaddend. .Iadd.60.  A pharmaceutical composition, comprising a neutral 3:1 1-hydropyrid-2-one:iron (III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to ring carbon atoms are replaced by a substituent selected from aliphatic acyl, cyano, aliphatic ester, halogen and hydroxy groups, alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, but excluding compounds in which said replacement of hydrogen atoms is effected only by substituents selected from aliphatic hydrocarbon groups, halogen groups and aliphatic hydrocarbon groups substituted by a halogen group, together with a physiologically acceptable diluent or carrier, wherein said composition is adapted to release of the iron complex in the intestine rather than the stomach. .Iaddend. .Iadd.61. A pharmaceutical composition comprising a neutral 3:1 1-hydropyrid-2-one:iron (III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to ring carbon atoms are replaced by a substituent selected from aliphatic acyl, cyano, aliphatic ester, halogen and hydroxy groups, C 2-5  alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, but excluding compounds in which said replacement of hydrogen atoms is effected only by substituents selected from aliphatic hydrocarbon groups, halogen groups and aliphatic hydrocarbon groups substituted by a halogen group, together with a physiologically acceptable diluent or carrier. .Iaddend. .Iadd.62. A pharmaceutical composition comprising a neutral 3:1 1-hydropyrid-2-one:iron (III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to ring carbon atoms are replaced by a substituent selected from aliphatic acyl, cyano, aliphatic ester, halogen and hydroxy groups, alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, C 2-6  aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, but excluding compounds in which said replacement of hydrogen atoms is effected only by substituents selected from aliphatic hydrocarbon groups, halogen groups and aliphatic hydrocarbon groups substituted by a halogen group, together with a physiologically acceptable diluent or carrier. .Iaddend. .Iadd.63. A compound being a neutral 3:1 1-hydropyrid-2-one:iron (III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to ring carbon atoms are replaced by a substituent selected from aliphatic acyl, cyano, aliphatic ester, halogen and hydroxy groups, C 2-5  alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, but excluding compounds in which said replacement of hydrogen atoms is effected only by substituents selected from aliphatic hydrocarbon groups, halogen groups and aliphatic hydrocarbon groups substituted by a halogen group. .Iaddend. .Iadd.64. A compound being a neutral 3:1 1-hydropyrid-2-one:iron (III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to ring carbon atoms are replaced by a substituent selected from aliphatic acyl, cyano, aliphatic ester, halogen and hydroxy groups, alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, C 2-6  aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, but excluding compounds in which said replacement of hydrogen atoms is effected only by substituents selected from aliphatic hydrocarbon groups, halogen groups and aliphatic hydrocarbon groups substituted by a halogen group. .Iaddend. .Iadd.65. The method according to claim 8, wherein at least one additional hydrogen atom is substituted by an hydroxy group. .Iaddend. .Iadd.66. A pharmaceutical composition comprising a neutral 3:1 1-hydropyrid-2-one:iron (III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to ring carbon atoms are replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, but excluding compounds in which said replacement of hydrogen atoms is effected only by substituents selected from aliphatic hydrocarbon groups, halogen groups and aliphatic hydrocarbon groups substituted by a halogen group, wherein at least one substituent is an alkoxy group substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, together with a physiologically acceptable diluent or carrier. .Iaddend. .Iadd.67. A pharmaceutical composition according to claim 66, wherein the 1-hydroxypyrid-2-one contains one of said substituted alkoxy group substituents and can contain one or more substituents which are an aliphatic hydrocarbon group. .Iaddend. .Iadd.68. A pharmaceutical composition according to claim 67, wherein one or more of the hydrogen atoms attached to the ring carbon atoms is replaced by a C 2-4  alkoxy group substituted either by a hydroxy group or by a C 1-4  alkoxy group, with the total number of carbon atoms in the alkoxyalkoxy group ranging from 3 to 6, and wherein at least one more of the said hydrogen atoms can be replaced by an aliphatic hydrocarbon group of 1 to 4 carbon atoms. .Iaddend. .Iadd.69. A compound being a neutral 3:1 1-hydropyrid-2-one:iron (III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to ring carbon atoms are replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, but excluding compounds in which said replacement of hydrogen atoms is effected only by substituents selected from aliphatic hydrocarbon groups, halogen groups and aliphatic hydrocarbon groups substituted by a halogen group, wherein at least one substituent is an alkoxy group substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group. .Iaddend. .Iadd.70. A compound according to claim 69, wherein the 1-hydroxypyrid-2-one contains one of said substituted alkoxy group substituents and can contain one or more substituents which are an aliphatic hydrocarbon group. .Iaddend. 
     
     
        .Iadd.     A compound according to claim 69, wherein one or more of the hydrogen atoms attached to the ring carbon atoms is replaced by a C 2-4  alkoxy group substituted either by a hydroxy group or by a C 1-4  alkoxy group, with the total number of carbon atoms in the alkoxyalkoxy group ranging from 3 to 6, and wherein at least one or more of the said hydrogen atoms can be replaced by an aliphatic hydrocarbon 
     
     
        group of 1 to 4 carbon atoms. .Iaddend. .Iadd.72.  The pharmaceutical composition according to claim 35, in which the 4-position of the 
     
     
        1-hydroxypyrid-2-one is substituted. .Iaddend. .Iadd.73.  The pharmaceutical composition according to claim 38, in which the 4-position of the 1-hydroxypyrid-2-one is substituted. .Iaddend. .Iadd.74. The pharmaceutical composition according to claim 56, in which the 4-position of the 1-hydroxypyrid-2-one is substituted. .Iaddend. .Iadd.75. The pharmaceutical composition according to claim 57, in which the 4-position of the 1-hydroxypyrid-2-one is substituted. .Iaddend. .Iadd.76. The pharmaceutical composition according to claim 61, in which the 4-position of the 1-hydroxypyrid-2-one is substituted. .Iaddend. .Iadd.77. The pharmaceutical composition according to claim 62, in which the 4-position of the 1-hydroxypyrid-2-one is substituted. .Iaddend. .Iadd.78. The compound according to claim 39, in which the 4-position of the 1-hydroxypyrid-2-one is substituted. .Iaddend. .Iadd.79. The compound according to claim 44, in which the 4-position of the 1-hydroxypyrid-2-one is substituted. .Iaddend. .Iadd.80. The compound according to claim 58, in which the 4-position of the 1-hydroxypyrid-2-one is substituted. .Iaddend. .Iadd.81. The compound according to claim 59, in which the 4-position of the 1-hydroxypyrid-2-one is substituted. .Iaddend. .Iadd.82. The compound according to claim 63, in which the 4-position of the 1-hydroxypyrid-2-one 
     
     
        is substituted. .Iaddend. .Iadd.83.  The compound according to claim 64, in which the 4-position of the 1-hydroxypyrid-2-one is substituted. .Iaddend. .Iadd.84. A pharmaceutical composition comprising a neutral 3:1 1-hydropyrid-2-one:iron (III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to the ring carbon atoms are replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, but excluding compounds in which said replacement of hydrogen atoms is effected only by substituents selected from aliphatic hydrocarbon groups, halogen groups and aliphatic hydrocarbon groups substituted by a halogen group, together with a physiologically acceptable diluent or carrier. .Iaddend. .Iadd.85. A pharmaceutical composition comprising a neutral 3:1 1-hydropyrid-2-one:iron (III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to ring carbon atoms are replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, but excluding compounds in which said replacement of hydrogen atoms is effected only by substituents selected from halogen groups and aliphatic hydrocarbon groups substituted by a halogen group, together with a physiologically acceptable diluent or carrier. .Iaddend. .Iadd.86. A compound being a neutral being a a neutral 3:1 1-hydropyrid-2-one:iron (III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to ring carbon atoms are replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, but excluding compounds in which said replacement of hydrogen atoms is effected only by substituents selected from aliphatic hydrocarbon groups, halogen groups and aliphatic hydrocarbon groups substituted by a halogen group. .Iaddend. .Iadd.87. A compound being a neutral 3:1 1-hydropyrid-2-one:iron (III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to ring carbon atoms are replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, but excluding compounds in which said replacement of hydrogen atoms is effected only by substituents selected from halogen groups and aliphatic hydrocarbon groups substituted by a halogen group. .Iaddend. .Iadd.88. A pharmaceutical composition comprising a neutral 3:1 1-hydropyrid-2-one:iron (III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to the ring carbon atoms are replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, at least one of the ring carbon atom substituents being an aliphatic amide group, together with a physiologically acceptable diluent or carrier. .Iaddend. .Iadd.89. A pharmaceutical composition according to claim 88, in which the 4-position of the 1-hydroxypyrid-2-one is substituted by said aliphatic amide group. .Iaddend. .Iadd.90. A compound being a neutral 3:1 1-hydropyrid-2-one:iron (III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to the ring carbon atoms are replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, at least one of the substituents being an aliphatic amide group. .Iaddend. .Iadd.91. A compound according to claim 90, in which the 4-position of the 1-hydroxypyrid-2-one is substituted by said aliphatic amide group. .Iaddend. .Iadd.92. A pharmaceutical composition comprising a neutral 3:1 1-hydropyrid-2-one:iron (III) complex of a 1-hydroxypyrid-2-one in which one or more of the hydrogen atoms attached to ring carbon atoms are replaced by a substituent selected from aliphatic acyl, aliphatic amide, cyano, aliphatic ester, halogen and hydroxy groups, alkoxy groups and alkoxy groups substituted by an alkoxy, aliphatic amide, aliphatic ester, halogen or hydroxy group, aliphatic hydrocarbon groups and aliphatic hydrocarbon groups substituted by an alkoxy, aliphatic ester, halogen or hydroxy group, but excluding compounds in which said replacement of hydrogen atoms is effected only by substituent selected from aliphatic hydrocarbon groups, halogen groups and aliphatic hydrocarbon groups substituted by a halogen group, together with a physiologically acceptable solid carrier. .Iaddend. .Iadd.93. A method for the treatment of a patient having a toxic concentration of iron in the body which comprises administering to said patient a 1-hydroxypyrid-2-one of the formula ##STR9## wherein one of the hydrogen atoms attached to the ring carbon atoms is replaced by an aliphatic amide substituent, or a salt thereof containing a physiologically acceptable cation in an amount effective to reduce said 
     
     
        toxic concentration of the metal. .Iaddend. .Iadd.94.  The method according to claim 93, wherein one of said hydrogen atoms attached to ring carbon atoms is replaced by an aliphatic amide of the formula --CONH 2  or a group --CONH 2  wherein one or more of the hydrogen atoms of this group is replaced by a C 1-3  aliphatic hydrocarbon group. .Iaddend. .Iadd.95. The method according to claim 93, wherein one of said hydrogen atoms attached to ring carbon atoms is replaced by an aliphatic amide of the formula --CONH 2  or --CONHCH 3 . .Iaddend. .Iadd.96. A method for the treatment of a patient to effect an increase in the level of iron in the patient's blood-stream which comprises administering to said patient a compound being a neutral 3:1 1-hydropyrid-2-one:iron (III) complex of a 1-hydroxypyrid-2-one of the formula ##STR10## wherein one of the hydrogen atoms attached to the ring carbon atoms is replaced by an aliphatic amide substituent, or a salt thereof containing a physiologically acceptable cation in an amount effective to achieve such 
     
     
        an increase. .Iaddend. .Iadd.97.  The method according to claim 96, wherein one of said hydrogen atoms attached to ring carbon atoms is replaced by an aliphatic amide of the formula --CONH 2  or a group --CONH 2  wherein one or more of the hydrogen atoms of this group is replaced by a C 1-3  aliphatic hydrocarbon group. .Iaddend. .Iadd.98. The method according to claim 96, wherein one of said hydrogen atoms attached to ring carbon atoms is replaced by an aliphatic amide of the formula --CONH 2  or --CONHCH 3 . .Iaddend.

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