Pharmaceutically Active Compounds, their Manufacture, Compositions Containing them, and their Use
A substance for use as a medicament, comprises a solid mixed metal compound of formula (I): M II 1−a M III a O b A n− c .zH 2 O (I) where M II is at least one bivalent metal: M III bis at least one trivalent metal; A n− is at least one n-valent anion; 2+a=2 b +Σcn; and Σcn<0.9 a . The substance may be made by heating at a temperature of from 200° C. to 600° C. preferably from 250° C. to 500° C. of a substance comprising a compound of formula (II): M II 1−x M III x (OH) 2 A n− y .mH 2 O (II) where M II is at least one bivalent metal; M III is at least one trivalent metal; A n− is at least one n-valent anion; x=Σyn 0<x≦0.5, 0<y≦1 and 0<m≦10.
1 . A substance for use as a medicament, comprising a solid mixed metal compound of formula (I):
M II 1−a M III a 0 b A n− c .z H 2 0 (I)
where M II is at least one bivalent metal; M III is at least one trivalent metal, wherein M III is Fe 3+ ; A n− is at least one n-valent anion; 2+a=2b+Σcn and Σcn<0.9a, and z is 2 or less.
2 . A substance according to claim 1 , wherein in formula (I), a is >0.3.
3 . A substance according to claim 1 , wherein in formula (I), a is <0.3.
4 . A substance according to claim 2 , wherein in formula (I), 0.03a<Σcn<0.5a.
5 . A substance according to claim 3 , wherein in formula (I), 0.03a<Σcn<0.7a.
6 . A solid mixed metal compound according to any preceding claim, having less than 2%, preferably less than 1.5%, more preferably less than 1% by weight crystallite-surface absorbed water.
7 . A substance for use as a medicament, comprising a solid mixed metal compound obtained or obtainable by heating a starting material comprising a layered double hydroxide structure at a temperature of from 250° C. to 500° C.
8 . A substance according to claim 7 , wherein the starting material comprises a compound of formula (II):
M II 1−x M III x (OH) 2 A n− y .m H 2 O (II)
where M II is at least one bivalent metal; M III is at least one trivalent metal; A n− is at least one n-valent anion; x=Σyn, 0<x≦0.5, 0<y≦1 and 0<m≦10.
9 . A substance according to claim 8 , wherein in formula (II), x is ≧0.3.
10 . A substance according to claim 8 , wherein in formula (II), x is <0.3.
11 . A substance according to any of claims 7 to 10 , wherein the substance has a 10% higher phosphate binding capacity relative to the compound of formula (II) from which it is obtainable.
12 . Use in the manufacture of a medicament for binding of phosphate of a substance comprising a solid mixed metal compound of formula (I):
M II 1−a M III aob A n− c .z H 2 o (I)
where M II is at least one bivalent metal; M III is at least one trivalent metal, wherein M III is Fe 3+ ; A n− is at least one n-valent anion; 2+a=2b+Σcn and Σcn<0.9a, and z is 2 or less.
13 . Use in the manufacture of a medicament for prophylaxis or treatment of hyperphosphataemia, of a substance comprising a solid mixed metal compound of formula (I):
M II 1−a M III a o b A n− c z H 2 O (I)
where M II is at least one bivalent metal; M III is at least one trivalent metal, wherein M III is Fe 3+ ; A n− is at least one n-valent anion; 2+a=2b+Σcn and Σcn<0.9a, and z is 2 or less.
14 . Use, according to claim 12 or claim 13 , wherein in formula (I), a is ≧0.3 and preferably 0.03a<Σcn<0.5a.
15 . Use according to claim 12 or claim 13 , wherein in formula (I), a is <0.3 and preferably 0.03a<Σcn<0.7a.
16 . Use in the manufacture of a medicament, for binding of phosphate in an animal in need thereof, of a substance obtainable by heating a starting material comprising a layered double hydroxide structure at a temperature of from 250° C. to 500° C.
17 . Use in the manufacture of a medicament, for prophylaxis or treatment of hyperphosphataemia, of a substance obtainable by heating a starting material comprising a layered double hydroxide structure at a temperature of from 250° C. to 500° C.
18 . Use according to claim 16 or claim 17 , wherein the starting material comprises a compound of formula (II):
M II 1−x M III x (OH) 2 A n− y .m H 2 O (II)
where M II is at least one bivalent metal; M III is at least one trivalent metal; A n− is at least one n-valent anion; x=Σny; and 0<x≦0.5; 0≦m≦10.
19 . Use according to claim 18 , wherein in formula (II), x is ≧0.3.
20 . Use according to claim 18 , wherein in formula (II), x is <0.3.
21 . A method of preparing a substance for use as a medicament, the method comprising heating a starting material comprising a layered double hydroxide structure at a temperature of from 250° C. to 500° C.
22 . A method according to claim 21 , wherein the starting material comprises a compound of formula (II):
M II 1−x M III x (OH) 2 A n− y .m H 2 O (II)
where M II is at least one bivalent metal; M III is at least one trivalent metal; A n− is at least one n-valent anion; x=Σny; and 0<x≦0.5, 0≦m≦10.
23 . A method according to claim 22 , wherein in formula (II), x is ≧0.3.
24 . A method according to claim 22 , wherein in formula (II), x is <0.3.
25 . A method according to any of claims 21 to 24 , wherein the starting material is substantially free of particles greater than 100 μm.
26 . A pharmaceutical formulation comprising a solid mixed metal compound of formula (I):
M II 1−a M III a O b A n− c .z H 2 0 (I)
where M II is at least one bivalent metal; M III is at least one trivalent metal, wherein M III is Fe 3+ ; A n− is at least one n-valent anion; 2+a=2b+Σcn and Σcn<0.9a, and z is 2 or less; and a pharmaceutically acceptable carrier.
27 . A pharmaceutical formulation according to claim 26 , wherein in formula (I), a is ≧0.3 and preferably 0.03a<Σcn<0.5a.
28 . A pharmaceutical formulation according to claim 26 , wherein in formula (I), a is <0.3 and preferably 0.03a<Σcn<0.7a.
29 . A pharmaceutical formulation comprising a solid mixed metal compound obtainable by heating a starting material comprising a layered double hydroxide structure at a temperature of from 250° C. to 500° C., and a pharmaceutically acceptable carrier.
30 . A pharmaceutical formulation according to claim 27 , wherein the starting material comprises a compound of formula (II):
M II 1−x M III x (OH) 2 A n− y .m H 2 O (H)
where M II is at least one bivalent metal; M III is at least one trivalent metal; A n− is at least one n-valent anion; x=Σny; and 0<x≦0.5, 0≦m≦10.
31 . A pharmaceutical formulation according to claim 30 , wherein in formula (II), x is ≧0.3.
32 . A pharmaceutical formulation according to claim 30 , wherein in formula (II), x is <0.3.
33 . A method of preparing a pharmaceutical formulation according to any of claims 26 to 32 , the method comprising admixing the solid mixed metal compound, the pharmaceutically acceptable carrier and optionally, any other ingredients.