1. A method for inhibiting angiogenesis in a patient comprising administering to said patient an anti-angiogenically effective amount of a 1,2-dithiol-3-thione derivative selected from the group consisting of 5-(2-pyrazinyl)-1,2-diothiol-3-thione (ADT), and 5-(2-pyrazinyl)-4-methyl-1,2-diothiol-3-thione or a metabolite thereof and determining the anti-angiogenic effect on said patient produced by said derivative or metabolite thereof.
2. The method according to claim 1 wherein said 1,2-dithiol-3-thione derivative is 5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione.
3. A method for inhibiting the growth or metastasis of an angiogenesis-dependent tumor in a patient comprising administering to said patient an effective amount of an anti-angiogenic agent, wherein said anti-angiogenic agent comprises a compound of the following formula (I):
wherein:
Ar is a monocyclic or bicyclic aryl group or a monocyclic or bicyclic heteroaryl group containing 1 to 3 \u2014O\u2014, \u2014S\u2014 or N(R2)m heteroatoms, wherein m is 0 or 1; and
R1 and R2 are independently hydrogen or an alkyl group; or a steroisomer, prodrug, metabolite, or pharmaceutically acceptable salt, hydrate or N-oxide thereof and determining the anti-angiogenic effect on said tumor produced by said compound.
4. The method according to claim 3 wherein Ar is a monocyclic or bicyclic heteroaryl group containing 1 to 3 oxygen, sulfur or nitrogen heteroatoms.
5. The method according to claim 4 wherein Ar is a monocylic heteroaryl group containing 1 to 2 nitrogen atoms.
6. The method according to claim 5 wherein Ar is selected from the group consisting of pyridyl, pyridazinyl, pyrimidinyl and pyrazinyl.
7. The method according to claim 6 wherein Ar is pyrazinyl.
8. The method according to claim 3 wherein R1 is hydrogen.
9. The method according to claim 3 comprising administering to said patient a metabolite of the compound of formula (I).
10. The method according to claim 9 wherein said metabolite has the following formula (II):
wherein:
X1 is C(R6)y or N(R7)n in which y is an integer 1 or 2, and n is an integer 0 or 1;
X2 and X3 are each independently \u2014O\u2014, \u2014S(O)x\u2014 where x is an integer 0, 1 or 2, or \u2014N(R8);
X4 is C(R6)y or C(\u2550O), in which y is an integer 1 or 2;
R3 is hydrogen, alkyl, the residue of glucuronic acid, or the radical
R4, R5 and R6 are each independently hydrogen or alkyl;
R7 is hydrogen or the residue of glucuronic acid;
R8 is hydrogen or alkyl; and X1, X2, X3 and X4 are as previously defined.
11. The method according to claim 10 wherein:
X1 is N;
X2 and X3 are \u2014S\u2014; and
R3, R4 and R5 are methyl.
12. The method according to claim 3, wherein said anti-angiogenic effect is determined by measuring the tumor burden in said patient.
13. A method for inhibiting the growth or metastasis of an angiogenesis-dependent tumor in a patient comprising administering to said patient an effective amount of an anti-angiogenic agent, wherein said anti-angiogenic agent comprises a 1,2-dithiol-3-thione derivative selected from the group consisting of 5-(2-pyrazinyl)-1,2-diothiol-3-thione (ADT), and 5-(2-pyrazinyl)-4-methyl-1,2-diothiol-3-thione or a metabolite thereof and determining the anti-angiogenic effect on said tumor produced by said 1,2-diothiol-3-thione derivative or metabolite thereof.
14. The method according to claim 13 wherein said 1,2-dithiol-3-thione derivative is 5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione.
15. The method according to claim 13, wherein said anti-angiogenic effect is determined by measuring the tumor burden in said patient.
16. A method for treating a disease or disorder associated with angiogensesis in a patient, said disease or disorder being selected from the group consisting neoplastic diseases, restenosis, rheumatoid arthritis, Crohn’s disease, diabetic retinopathy, psoriasis, endometriosis, macular degeneration, neovascular glaucoma, and adiposity, comprising administering to said patient an effective amount of an anti-angiogenic agent, wherein said anti-angiogenic agent comprises a compound of the following formula (I):
wherein:
Ar is a monocyclic or bicyclic aryl group or a monocyclic or bicyclic heteroaryl group containing 1 to 3 \u2014O\u2014, \u2014S\u2014 or \u2014N(R2)m heteroatoms, wherein m is 0 or 1; and
R1 and R2 are independently hydrogen or an alkyl group; or a steroisomer, prodrug, metabolite, or pharmaceutically acceptable salt, hydrate or N-oxide thereof and determining the anti-angiogenic effect on said patient produced by said compound.
17. The method according to claim 16 wherein Ar is a monocyclic or bicyclic heteroaryl group containing 1 to 3 oxygen, sulfur or nitrogen heteroatoms.
18. The method according to claim 17 wherein Ar is a monocylic heteroaryl group containing 1 to 2 nitrogen atoms.
19. The method according to claim 18 wherein Ar is selected from the group consisting of pyridyl, pyridazinyl, pyrimidinyl and pyrazinyl.
20. The method according to claim 19 wherein Ar is pyrazinyl.
21. The method according to claim 16 wherein R1 is hydrogen.
22. The method according to claim 16 comprising administering to said patient a metabolite of the compound of formula (I).
23. The method according to claim 22 wherein said metabolite has the following formula (II):
wherein:
X1 is C(R6)y or N(R7)n in which y is an integer 1 or 2, and n is an integer 0 or 1;
X2 and X3 are each independently \u2014O\u2014, \u2014S(O)x\u2014 where x is an integer 0, 1 or 2, or \u2014N(R8);
X4 is C(R6)y or C(\u2550O), in which y is an integer 1 or 2;
R3 is hydrogen, alkyl, the residue of glucuronic acid, or the radical
R4, R5 and R6 are each independently hydrogen or alkyl;
R7 is hydrogen or the residue of glucuronic acid;
R8 is hydrogen or alkyl and X1, X2, X3 and X4 are as previously defined.
24. The method according to claim 23 wherein:
X1 is N;
X2 and X3 are \u2014S\u2014; and
R3, R4 and R5 are methyl.
25. The method according to claim 16, wherein said disease or disorder is a neoplastic disease.
26. The method according to claim 25, wherein said neoplastic disease is cancer.
27. The method according to claim 25, wherein said an anti-angiogenic effect is determined on the basis of neoplasm regression.
28. The method according to claim 27, wherein neoplasm regression is demonstrated by reduced size.
29. The method according to claim 27, wherein neoplasm regression is demonstrated by reduced neoplasm number.
30. The method according to claim 25, wherein said anti-angiogenic effect is determined on the basis of reduced neovascularization.
31. A method for treating a disease or disorder associated with angiogenesis in a patient, said disease or disorder being selected from the group consisting of neoplastic diseases, restenosis, rheumatoid arthritis, Crohn’s disease, diabetic retinopathy, psoriasis, endometriosis, macular degeneration, neovascular glaucoma, and adiposity, comprising administering to said patient an effective amount of an anti-angiogenic agent, wherein said anti-angiogenic agent comprises a 1,2-dithiol-3-thione derivative selected from the group consisting of 5-(2-pyrazinyl)1,2-diothiol-3-thione (APT), and 5-(2-pyrazinyl)-4-methyl-1,2-diothiol-3-thione or a metabolite thereof and determining the anti-angiogenic effect on said patient produced by said 1,2-dithiol-3-thione derivative or metabolize thereof.
32. The method according to claim 31 wherein said 1,2-dithiol-3-thione derivative is 5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione.
The claims below are in addition to those above.
All refrences to claim(s) which appear below refer to the numbering after this setence.
1. A combustion device for combusting particulate matters comprising:
an introduction portion which connects to an exhaust port of an internal combustion engine and is used to introduce a particulate matter-containing gas discharged from the exhaust port;
a charging unit which is provided on the downstream side of the introduction portion, and in which all or part of the particulate matters are negatively charged by bringing the particulate matter-containing gas into contact with;
an electric discharge unit which is provided in an insulation pipe which is connected to the downstream side of the charging unit, and in which the particulate matters, all or part of which are negatively charged, are introduced into a silent discharge area, the silent discharge area being generated between an anode and a cathode;
a discharge portion which is connected to the insulation pipe at the downstream side of the electric discharge unit and which discharges the combusted gas; and
a power source unit which applies an electric field to the charging unit and the electric discharge unit, and wherein
the electric discharge unit includes:
a planar metal fiber mesh cathode provided orthogonal to a flow channel of the particulate matter-containing gas; and
an anode which is spaced from the planar metal fiber mesh cathode at predetermined gap on the upstream side of the planar metal fiber mesh cathode, and faces to the planar metal fiber mesh cathode, the predetermined gap being a silent discharge area.
2. A device for combusting particulate matters, comprising:
an introduction portion which connects to an exhaust port of an internal combustion engine and is used to introduce a particulate matter-containing gas discharged from the exhaust port;
a charging unit which is provided on the downstream side of the introduction portion, and in which all or part of the particulate matters are negatively charged by bringing the particulate matter-containing gas into contact with;
an electric discharge unit which is provided in an insulation pipe which is connected to the downstream side of the charging unit, and in which the particulate matters, all or part of which are negatively charged, are introduced into a silent discharge area, the silent discharge area being generated between an anode and a cathode; and
a discharge portion which is connected to the insulation pipe at the downstream side of the electric discharge unit and which discharges the combusted gas; and
a power source unit which applies an electric field to the charging unit and the electric discharge unit, wherein
the introduction portion has a gas flow conversion member which changes the flow of the particulate matter-containing gas to a spiral flow;
the charging unit has a ring anode provided along the internal circumference of the pipe where the spiral flow flows; and
the electric discharge unit has a cylindrical cathode provided on inner wall of the insulation pipe, a cylindrical dielectric provided inside the cathode and a cylindrical mesh anode is spaced from the cylindrical dielectric at predetermined gap on the inside of the cylindrical dielectric.
3. A combustion device for combusting particulate matters, comprising:
an introduction portion which connects to an exhaust port of an internal combustion engine and is used to introduce a particulate matter-containing gas discharged from the exhaust port;
a charging unit which is provided on the downstream side of the introduction portion, and in which all or part of the particulate matters are negatively charged by bringing the particulate matter-containing gas into contact with;
an electric discharge unit which is provided in an insulation pipe which is connected to the downstream side of the charging unit, and in which the particulate matters, all or part of which are negatively charged, are introduced into a silent discharge area, the silent discharge area being generated between an anode and a cathode; and
a discharge portion which is connected to the insulation pipe at the downstream side of the electric discharge unit and which discharges the combusted gas; and
a power source unit which applies an electric field to the charging unit and the electric discharge unit, wherein
the charging unit has a planar mesh anode provided orthogonal to a flow channel of the particulate matter-containing gas;
the electric discharge unit has:
a cylindrical cathode spaced from the inner wall of the insulation pipe at predetermined gap;
a cylindrical dielectric provided inside the cathode;
a cylindrical mesh anode spaced from the cylindrical dielectric on the inside of the cylindrical dielectric; and
a gas flow conversion member which introduces the particulate matters charged by the planar mesh anode into the silent discharge area between the cylindrical dielectric and the cylindrical mesh anode.
4. The combustion device for combusting particulate matters according to claim 1, wherein openings of the planar metal fiber mesh cathode is smaller in size than the particulate matters.
5. A method for combusting particulate matters comprising:
negatively charging all or part of particulate matters included in a particulate matter-containing gas discharged from an internal combustion engine;
electrically attracting or repelling the negatively charged particulate matters in order to reduce the speed of the negatively charged particulate matters;
increasing retention time for the particulate matters to be retained in a silent discharge area in order to extend time for applying discharge energy at the silent discharge area; and
combusting the particulate matters in the silent discharge area, wherein
the silent discharge area is formed of a planar metal fiber mesh cathode and an anode, the planar metal fiber mesh cathode being provided orthogonal to a flow channel of the particulate matter-containing gas, the anode being spaced from the planar metal fiber mesh cathode at predetermined gap on the upstream side of the planar metal fiber mesh cathode, and faces to the planar metal fiber mesh cathode.
6. The method for combusting particulate matters according to claim 5, wherein
the anode has a mesh form and is provided on the downstream side of a flow channel of the particulate matter-containing gas, and
the retention time is increased at the silent discharge area by electrostatically attracting the negatively charged particulate matters on the anode.
7. The method for combusting particulate matters according to claim 5, wherein
the anode has a mesh form and is provided on the downstream side of a flow channel of the particulate matter-containing gas in order to capture the negatively charged particulate matters, and
the retention time is increased at the silent discharge area by attracting and depositing the negatively charged particulate matters on the anode.
8. The method for combusting particulate matters according to claim 5, wherein
the anode has a mesh form and is provided on the downstream side of a flow channel of the particulate matter-containing gas, and
the retention time is increased at the silent discharge area by electrostatically repelling the negatively charged particulate matters by the mesh cathode.