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A method of and apparatus for forming chamfers in an orifice of a workpiece. The orifice has an axis, which extends between a first surface and second surface of the workpiece, where the first and second surfaces are parallel to each other. The chamfers are disposed between the first surface and the

A method of and apparatus for forming chamfers in an orifice of a workpiece. The orifice has an axis, which extends between a first surface and second surface of the workpiece, where the first and second surfaces are parallel to each other. The chamfers are disposed between the first surface and the second surface. The method includes forming an orifice in a workpiece with a source of non-collimated light directed at the workpiece at a predetermined first time interval, and forming a chamfer with a source of collimated light at a second time interval during the first time interval. The apparatus includes at least one source of collimated and non-collimated light, various spatial filters that can be used with the laser light source, a non-collimated light generating arrangement, and at least one shutter and at least one iris that direct collimated and non-collimated light at the workpiece to form the orifice. The apparatus is configured such that the orifice has a surface roughness of between approximately 0.05 micron and approximately 0.13 micron and a coefficient ratio of at least approximately 0.

대표청구항 ▼

A method of and apparatus for forming chamfers in an orifice of a workpiece. The orifice has an axis, which extends between a first surface and second surface of the workpiece, where the first and second surfaces are parallel to each other. The chamfers are disposed between the first surface and the

A method of and apparatus for forming chamfers in an orifice of a workpiece. The orifice has an axis, which extends between a first surface and second surface of the workpiece, where the first and second surfaces are parallel to each other. The chamfers are disposed between the first surface and the second surface. The method includes forming an orifice in a workpiece with a source of non-collimated light directed at the workpiece at a predetermined first time interval, and forming a chamfer with a source of collimated light at a second time interval during the first time interval. The apparatus includes at least one source of collimated and non-collimated light, various spatial filters that can be used with the laser light source, a non-collimated light generating arrangement, and at least one shutter and at least one iris that direct collimated and non-collimated light at the workpiece to form the orifice. The apparatus is configured such that the orifice has a surface roughness of between approximately 0.05 micron and approximately 0.13 micron and a coefficient ratio of at least approximately 0. a pharmaceutical composition comprising (a) an amount of a first compound, said first compound being a GABA agonist or a pharmaceutically acceptable salt of said GABA agonist; and (b) an amount of a second compound, said second compound being an aldose reductase inhibitor or a pharmaceutically acceptable salt of said ARI. 9. A method of claim 8 wherein said pharmaceutical composition additionally comprises a pharmaceutically acceptable vehicle, carrier or diluent. 10. A method of claim 8 wherein said diabetic complication is diabetic neuropathy, diabetic nephropathy, diabetic retinopathy, diabetic cardiomyopathy, diabetic microangiopathy, diabetic macroangiopathy, cataracts or foot ulcers. 11. A pharmaceutical composition comprising: a. an amount of a GABA agonist or a pharmaceutically acceptable salt of said GABA agonist; and b. an amount of an ARI or a pharmaceutically acceptable salt of said ARI. 12. A pharmaceutical composition of claim 11 additionally comprising a pharmaceutically acceptable vehicle, carrier or diluent. 13. A pharmaceutical composition of claim 12 wherein said GABA agonist is muscimol, progabide, riluzole, baclofen, gabapentin, vigabatrin, valproic acid, tiagabine, lamotrigine, pregabalin, phenytoin, carbamazepine, topiramate, or a pharmaceutically acceptable salt of said GABA agonist. 14. A pharmaceutical composition of claim 13 wherein said GABA agonist is gabapentin, tiagabine, lamotrigine, phenytoin, carbamazepine, topiramate, pregabalin, or a pharmaceutically acceptable salt of said GABA agonist. 15. A pharmaceutical composition of claim 14 wherein said GABA agonist is pregabalin or a pharmaceutically acceptable salt of said pregabalin. 16. A pharmaceutical composition of claim 14 wherein said GABA agonist is gabapentin or a pharmaceutically acceptable salt of said gabapentin. 17. A pharmaceutical composition of claim 12 wherein said ARI is fidarestat, epalrestat, minalrestat, SPR-210, zenarestat, zopoir stat, or a pharmaceutically acceptable salt of said ARI. 18. A pharmaceutical composition of claim 17 wherein said GABA agonist is muscimol, progabide, riluzole, baclofen, gabapentin, vigabatrin, valproic acid, tiagabine, lamotrigine, pregabalin, phenytoin, carbamazepine, topiramate, or a pharmaceutically acceptable salt of said GABA agonist. 19. A pharmaceutical composition of claim 18 wherein said GABA agonist is gabapentin, tiagabine, lamotrigine, phenytoin, carbamazepine, topiramate and pregabalin, or a pharmaceutically acceptable salt of said GABA agonist. 20. A pharmaceutical composition of claim 19 wherein said GABA agonist is pregabalin or a pharmaceutically acceptable salt of said pregabalin. 21. A pharmaceutical composition of claim 19 wherein said GABA agonist is gabapentin or a pharmaceutically acceptable salt of said gabapentin. 22. A kit for achieving a therapeutic effect in a mammal comprising: a. an amount of a GABA agonist, or a pharmaceutically acceptable salt of said GABA agonist, and a pharmaceutically acceptable vehicle, carrier or diluent in a first unit dosage form; b. an amount of an ARI, or a pharmaceutically acceptable salt of said ARI, and a pharmaceutically acceptable vehicle, carrier or diluent in a second unit dosage form; and c. a container. 23. A method for treating a mammal in need of therapeutic treatment comprising administering to said mammal (a) an amount of a first compound, said first compound being a GABA agonist or a pharmaceutically acceptable salt of said GABA agonist; and (b) an amount of a second compound, said second compound being an ARI or a pharmaceutically acceptable salt of said ARI wherein said first compound and said second compound are each optionally and independently administered together with a pharmaceutically acceptable vehicle, carrier or diluent. 24. A method of claim 23 wherein said GABA agonist is muscimol, progabide, riluzole, baclofen, gabapentin, vigabatrin, valproic acid, tiagabine, lamotrigine, pregabalin, ph enytoin, carbamazepine, topiramate, or a or a pharmaceutically acceptable salt of said GABA agonist. 25. A method of claim 24 wherein said GABA agonist is gabapentin, tiagabine, lamotrigine, phenytoin, carbamazepine, topiramate, pregabalin, pharmaceutically acceptable salt of said GABA agonist. 26. A method of claim 25 wherein said GABA agonist is pregabalin or a pharmaceutically acceptable salt of said pregabalin. 27. A method of claim 25 wherein said GABA agonist is gabapentin or a pharmaceutically acceptable salt of said gabapentin. l or arylC1-6alkylene; R6,R7,and R8are independently hydrogen, fluoro, chloro, bromo, CF3,--OCF3,--N(R10)2,C1-6alkyl, C1-6alkoxy, heteroaryl or aryl; each R10is independently hydrogen, or --C1-6alkyl; wherein any C1-6alkyl, C1-6alkylene, or C1-6alkoxy of R1,R2,R3,R4,R5,R6,R7,R8,R9,and R10is optionally partially unsaturated; wherein any heteroaryl or aryl is optionally substituted with one or two substituents independently selected from halo, --CF3,--OCF3,C1-6alkoxy, --N(R10)2,and C1-6alkyl; or a pharmaceutically acceptable salt thereof. 2. The compound of claim 1, wherein R1is hydrogen. 3. The compound of claim 1, wherein R1is C1-6alkyl, C3-6cycloalkyl, or (C3-6cycloalkyl)C1-6alkyl. 4. The compound of claim 1, wherein R1is C2-6alkyl, C3-6cycloalkyl, or (C3-6cycloalkyl)C1-6alkyl. 5. The compound of claim 1, wherein R1is C3-6alkyl, C3-6cycloalkyl, or (C3-6cycloalkyl)C1-6alkyl. 6. The compound of claim 1, wherein R1is methyl, ethyl, propyl, isopropyl, or cyclopropylmethyl. 7. The compound of claim 1, wherein R1is ethyl, propyl, isopropyl, or cyclopropylmethyl. 8. The compound of claim 1, wherein R1is propyl, isopropyl, or cyclopropylmethyl. 9. The compound of claim 1, wherein R2is hydrogen. 10. The compound of claim 1, wherein R2is C1-6alkyl, C3-6cycloalkyl, or (C3-6cycloalkyl)C1-6alkyl. 11. The compound of claim 1, wherein R2is C2-6alkyl, C3-6cycloalkyl, or (C3-6cycloalkyl)C1-6alkyl. 12. The compound of claim 1, wherein R2is C3-6alkyl, C3-6cycloalkyl, or (C3-6cycloalkyl)C1-6alkyl. 13. The compound of claim 1, wherein R2is methyl, ethyl, propyl, isopropyl, or cyclopropylmethyl. 14. The compound of claim 1, wherein R2is ethyl, propyl, isopropyl, or cyclopropylmethyl. 15. The compound of claim 1, wherein R2is propyl, isopropyl, or cyclopropylmethyl. 16. The compound of claim 10, wherein R1is hydrogen. 17. The compound of claim 1, wherein R1is C2-3alkyl and R2is hydrogen, or C2-6alkyl. 18. The compound of claim 1, wherein R1is hydrogen, or C2-3alkyl; and R2is C2-6alkyl. 19. The compound of claim 1, wherein R1is C2-3alkyl and R2is C2-6alkyl. 20. The compound of claim 1, wherein R1is ethyl or propyl and R2is ethyl, propyl or butyl. 21. The compound of claim 1, wherein R3is hydrogen. 22. The compound of claim 1, wherein R3is C1-6alkyl. 23. The compound of claim 22, wherein R3is methyl, ethyl, propyl, or butyl. 24. The compound of claim 23, wherein R3is methyl or ethyl. 25. The compound of claim 1, wherein R4and R5are independently hydrogen, methyl, ethyl, propyl, butyl, 2-phenylethyl, or benzyl. 26. The compound of claim 25, wherein R4and R5are independently hydrogen, methyl, ethyl, propyl, or benzyl. 27. The compound of claim 25, wherein R4and are independently methyl, ethyl, or benzyl. 28. The compound of claim 1, wherein R6,R7,or R8is phenyl optionally substituted with one or two substituents independently selected from halo, --CF3,--OCF3,C1-6alko