Method for inhibiting immune response
AssigneeProcept, Inc.
InventorsCecilia M. Bastos, Timothy D. Ocain
Life of this patent
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Abstract
Use of ruthenium complexes as immunosuppressive agents to prevent or significantly reduce graft rejection in organ and bone marrow transplantation is described. The ruthenium complexes can also be used as immunosuppressant drugs for T-lymphocyte mediated autoimmune diseases, such as diabetes, and may be useful in alleviating psoriasis and contact dermatitis. The ruthenium complexes can also be used therapeutically in the treatment of hyperproliferative vascular disease.
Claims28
A method of preventing or substantially reducing a T-lymphocyte mediated immune response associated with autoimmune disease in a mammal in need thereof comprising administering to a mammal, a ruthenium complex having the general formula:
- RuM.sub.m B.sub.b T.sub.t P.sub.p !Z
- wherein Ru is ruthenium having an oxidation state of 2, 3 or 4;
- wherein M is a monodentate ligand selected from the group consisting of nitrogen containing ligands, phosphorus containing ligands, sulfur containing ligands, oxygen containing ligands and halide;
- wherein m is 0, 1, 2, 3, 4 or 6;
- wherein b is 0, 1, 2 or 3;
- wherein t is 0, 1 or 2;
- wherein p is 0 or 1;
- wherein m+b+t+p is 1, 2, 3, 4, 5 or 6;
- wherein B is a bidentate ligand selected from the group consisting of aliphatic amines, heterocyclic aromatic amines, sulfur containing ligands, oxygen containing ligands and phosphorus containing ligands;
- wherein T is a tridentate ligand selected from the group consisting of nitrogen containing ligands, sulfur containing ligands, oxygen containing ligands and phosphorus containing ligands;
- wherein P is a polydentate ligand selected from the group consisting of nitrogen containing ligands, oxygen containing ligands, sulfur containing ligands and phosphorus containing ligands;
- and
- wherein when the complex is charged then Z is at least counterion of appropriate charge to render the overall charge of the complex neutral.
A method of preventing or substantially reducing a T-lymphocyte mediated immune response associated with autoimmune disease in a mammal, comprising administering to the mammal a ruthenium complex having the general formula:
- (RuM.sub.m B.sub.b T.sub.t)-O-(RuM'.sub.m' B'.sub.b' T'.sub.t')!Z
- wherein Ru is ruthenium having an oxidation state of 2, 3 or 4;
- wherein M and M' are independently a monodentate ligand selected from the group consisting of nitrogen containing ligands, phosphorus containing ligands, sulfur containing ligands and oxygen containing ligands and halide;
- wherein m and m' are independently 0, 1, 2, 3 or 5;
- wherein b and b' are independently 0, 1 or 2;
- wherein t and t' are independently 0 or 1;
- wherein m+b+t and m'+b'+t' are independently 2, 3 or 5;
- wherein B and B' are independently a bidentate ligand selected from the group consisting of aliphatic amines, heterocyclic aromatic amines, sulfur containing ligands, oxygen containing ligands and phosphorus containing ligands;
- wherein T and T' are independently a tridentate ligand selected from the group consisting of nitrogen containing ligands, sulfur containing ligands, oxygen containing ligands and phosphorus containing ligands;
- and
- wherein when the complex is charged then Z is at least one counterion of appropriate charge to render the overall charge of the complex neutral.
A method of preventing or substantially reducing a T-lymphocyte mediated immune response associated with autoimmune disease in a mammal in need thereof comprising administering to a mammal, a ruthenium complex having the general formula:
- (RuM.sub.m B.sub.b T.sub.t)--O--(RuM".sub.m" B".sub.b" T".sub.t")--O--(RuM'.sub.m' B'.sub.b' T'.sub.t')!Z
- wherein Ru is ruthenium having an oxidation state of 2, 3 or 4;
- wherein M, M' and M" are independently a mono-dentate ligand selected from the group consisting of nitrogen containing ligands, phosphorus containing ligands, sulfur containing ligands, oxygen containing ligands;
- wherein m and m' are independently 0, 1, 2, 3 or 5;
- wherein m" is 0, 1, 2 or 4;
- wherein b, b' and b" are independently 0, 1 or 2;
- wherein t, t' and t" are independently 0 or 1;
- wherein m+b+t and m'+b'+t' are independently 2, 3 or 5 and wherein m"+b"+t"is 2, 3 or 4;
- wherein B, B' and B" are independently a bidentate ligand selected from the group consisting of aliphatic amines, heterocyclic aromatic amines, sulfur containing ligands, oxygen containing ligands and phosphorus containing ligands;
- wherein T, T' and T" are independently a tridentate ligand selected from the group consisting of nitrogen containing ligands, sulfur containing ligands, oxygen containing ligands and phosphorus containing ligands;
- and
- wherein when the complex is charged then Z is at least one counterion of appropriate charge to render the overall charge of the complex neutral.
A method for treating hyperproliferative vascular disorders comprising administering a ruthenium complex having the general formula:
- RuM.sub.m B.sub.b T.sub.t P.sub.p !Z
- wherein Ru is ruthenium having an oxidation state of 2, 3 or 4;
- wherein M is a monodentate ligand selected from the group consisting of nitrogen containing ligands, phosphorus containing ligands, sulfur containing ligands, oxygen containing ligands and halide;
- wherein m is 0, 1, 2, 3, 4 or 6;
- wherein b is 0, 1, 2 or 3;
- wherein t is 0, 1 or 2;
- wherein p is 0 or 1;
- wherein m+b+t+p is 1, 2, 3, 4, 5 or 6;
- wherein B is a bidentate ligand selected from the group consisting of aliphatic amines, heterocyclic aromatic amines, sulfur containing ligands, oxygen containing ligands and phosphorus containing ligands;
- wherein T is a tridentate ligand selected from the group consisting of nitrogen containing ligands, sulfur containing ligands, oxygen containing ligands and phosphorus containing ligands;
- wherein P is a polydentate ligand selected from the group consisting of nitrogen containing ligands, oxygen containing ligands, sulfur containing ligands and phosphorus containing ligands;
- and
- wherein when the complex is charged then Z is at least one counterion of appropriate charge to render the overall charge of the complex neutral.
A method of preventing or substantially reducing a T-lymphocyte mediated immune response associated with graft rejection in a mammal in need thereof comprising administering to a mammal, a ruthenium complex having the general formula:
- RuM.sub.m B.sub.b T.sub.t P.sub.p !Z
- wherein Ru is ruthenium having an oxidation state of 2, 3 or 4;
- wherein M is a monodentate ligand selected from the group consisting of nitrogen containing ligands, phosphorus containing ligands, sulfur containing ligands, oxygen containing ligands and halide;
- wherein m is 0, 1, 2, 3, 4 or 6;
- wherein b is 0, 1, 2 or 3;
- wherein t is 0, 1 or 2;
- wherein p is 0 or 1;
- wherein m+b+t+p is 1, 2, 3, 4, 5 or 6;
- wherein B is a bidentate ligand selected from the group consisting of aliphatic amines, heterocyclic aromatic amines, sulfur containing ligands, oxygen containing ligands and phosphorus containing ligands;
- wherein T is a tridentate ligand selected from the group consisting of nitrogen containing ligands, sulfur containing ligands, oxygen containing ligands and phosphorus containing ligands;
- wherein P is a polydentate ligand selected from the group consisting of nitrogen containing ligands, oxygen containing ligands, sulfur containing ligands and phosphorus containing ligands;
- and
- wherein when the complex is charged then Z is at least one counterion of appropriate charge to render the overall charge of the complex neutral.
A method of preventing or substantially reducing a T-lymphocyte mediated immune response associated with graft rejection in a mammal comprising administering to a mammal, a ruthenium complex having the general formula:
- Ru(Im).sub.6 !Cl.sub.2
- wherein Im is imidazole.
Dependencies are inferred from the claim text.