초록 ▼

A gas administering method for administering gas to an airway of a patient having a nasal vestibule and for use with a gas administering apparatus comprises a primary gas source that is operable to provide gas and a nasal vestibular portion arranged so as to receive the gas from the primary gas sour

A gas administering method for administering gas to an airway of a patient having a nasal vestibule and for use with a gas administering apparatus comprises a primary gas source that is operable to provide gas and a nasal vestibular portion arranged so as to receive the gas from the primary gas source. Further, the nasal vestibular portion is capable of releasing the primary gas into the nasal vestibule. The method comprises inserting the nasal vestibular portion into the nasal vestibule, forming a seal between the nasal vestibular portion and an inner surface of the nasal vestibule, administering an amount of a gas from the primary gas source at a constant flow rate into the nasal vestibule via the nasal vestibular portion, and administering an anesthetic to the patient. The anesthetic induces depression of a portion of the nervous system of the patient. Furthermore, the seal promotes airway pressure buildup that is sufficient to prevent obstruction of the airway during depression of at least a portion of the nervous system and prevents escape of the gas from between the nasal vestibule and the nasal vestibular portion.

대표청구항 ▼

A gas administering method for administering gas to an airway of a patient having a nasal vestibule and for use with a gas administering apparatus comprises a primary gas source that is operable to provide gas and a nasal vestibular portion arranged so as to receive the gas from the primary gas sour

A gas administering method for administering gas to an airway of a patient having a nasal vestibule and for use with a gas administering apparatus comprises a primary gas source that is operable to provide gas and a nasal vestibular portion arranged so as to receive the gas from the primary gas source. Further, the nasal vestibular portion is capable of releasing the primary gas into the nasal vestibule. The method comprises inserting the nasal vestibular portion into the nasal vestibule, forming a seal between the nasal vestibular portion and an inner surface of the nasal vestibule, administering an amount of a gas from the primary gas source at a constant flow rate into the nasal vestibule via the nasal vestibular portion, and administering an anesthetic to the patient. The anesthetic induces depression of a portion of the nervous system of the patient. Furthermore, the seal promotes airway pressure buildup that is sufficient to prevent obstruction of the airway during depression of at least a portion of the nervous system and prevents escape of the gas from between the nasal vestibule and the nasal vestibular portion. aid compound, pharmaceutically active metabolite of said compound, or pharmaceutically acceptable salt of said compound or metabolite. 2. A compound, prodrug, metabolite, or salt according to claim 1 selected from: 3. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of formula VII: wherein: n is 1 to 3; and Q is a substituted or unsubstituted aryl or heteroaryl; or a pharmaceutically acceptable prodrug of said compound, pharmaceutically active metabolite of said compound, or pharmaceutically acceptable salt of said compound or metabolite. 4. The pharmaceutical composition according to claim 3 selected from: 5. The composition according to claim 3, wherein said composition is administered as a sterile solution, suspension or emulsion, in a single or divided dose. 6. The composition according to claim 3, wherein said composition is administered as a capsule or tablet containing a single or divided dose of said compound. 7. The composition according to claim 3, wherein the composition is a solid implant. 8. The composition according to claim 3, wherein the carrier comprises a biodegradable polymer. 9. The composition according to claim 8, wherein the biodegradable polymer releases the compound of formula VII over a prolonged time. 10. A method of modulating or inhibiting PARG by administering a compound of Formula VII according to claim 1, or a pharmaceutically acceptable prodrug, pharmaceutically active metabolite, or pharmaceutically acceptable salt of such compound or metabolite thereof, to treat diseases and disorders selected from acute pain, arthritis, atherosclerosis, cachexia, cardiovascular disorders, chronic pain, degenerative diseases, diabetes, head trauma, hyperglycemia, immune senescence, inflammatory bowel disorders, ischemia, macular degeneration, muscular dystrophy, tissue damage resulting from ischemia and reperfusion injury, neurological disorders and neurodegenerative diseases, neuronal tissue damage or disease, neuropathic pain, nervous insult, osteoarthritis, osteoporosis, peripheral nerve injury, renal failure, resuscitated hemorrhagic shock, retinal ischemia, septic shock, skin aging, vascular stroke, diseases or disorders relating to lifespan or proliferative capacity of cells, and diseases or disease conditions induced or exacerbated by cellular senescence. 11. The method according to claim 10 wherein the diseases or conditions are selected from diabetes, head trauma, inflammatory bowel disorders, ischemia, tissue damage resulting from ischemia and reperfusion injury, neurological disorders and neurodegenerative diseases, neuronal tissue damage disease, neuropathic pain, nervous insult, peripheral nerve injury, retinal ischemia, vascular stroke, and diseases or disorders relating to lifespan or proliferative capacity of cells. 12. The method according to claim 11 wherein the disease or condition is tissue damage resulting from ischemia and reperfusion injury. 13. A compound of the Formula VIII: wherein: R5is hydrogen, and R6is a substituted or unsubstituted lower alkyl, lower alkenyl, heterocycloalkyl, alkoxy, aryloxy, alkylamino, arylamino, or R5and R6are taken together to form a substituted or unsubstituted five to seven membered heterocyclic ring that contains 1-3 heteroatoms of O, N, or S; or a pharmaceutically acceptable prodrug of said compound, pharmaceutically active metabolite of said compound, or pharmaceutically acceptable salt of said compound or metabolite. 14. A compound, prodrug, metabolite, or salt according to claim 13, wherein: R5is hydrogen, and R6is a substituted or unsubstituted lower alkyl, or R5and R6are taken together to form a substituted or unsubstituted six membered heterocyclic ring that contains 1-2 heteroatoms of N. 15. A compound, prodrug, metabolite, or salt according to claim 14 selected from: 16. A pharmaceutical c omposition comprising a pharmaceutically acceptable carrier and a compound of formula VIII: wherein: R5is hydrogen, and R6is a substituted or unsubstituted lower alkyl, lower alkenyl, heterocycloalkyl, alkoxy, aryloxy, alkylamino, arylamino, or R5and R6are taken together to form a substituted or unsubstituted five to seven membered heterocyclic ring that contains 1-3 heteroatoms of O, N, or S; or a pharmaceutically acceptable prodrug of said compound, pharmaceutically active metabolite of said compound, or pharmaceutically acceptable salt of said compound or metabolite. 17. The pharmaceutical composition according to claim 16, wherein: R5is hydrogen, and R6is a substituted or unsubstituted lower alkyl, or R5and R6are taken together to form a substituted or unsubstituted six membered heterocyclic ring that contains 1-2 heteroatoms of N. 18. The pharmaceutical composition according to claim 17 selected from: 19. The composition according to claim 16, wherein said composition is administered as a sterile solution, suspension or emulsion, in a single or divided dose. 20. The composition according to claim 16, wherein said composition is administered as a capsule or tablet containing a single or divided dose of said compound. 21. The composition according to claim 16, wherein the composition is a solid implant. 22. The composition according to claim 16, wherein the carrier comprises a biodegradable polymer. 23. The composition according to claim 22, wherein the biodegradable polymer releases the compound of formula VIII over a prolonged time. 24. A method of modulating or inhibiting PARG by administering a compound of Formula VIII according to claim 13, or a pharmaceutically acceptable prodrug, pharmaceutically active metabolite, or pharmaceutically acceptable salt of such compound or metabolite thereof, to treat diseases and disorders selected from acute pain, arthritis, atherosclerosis, cachexia, cardiovascular disorders, chronic pain, degenerative diseases, diabetes, head trauma, hyperglycemia, immune senescence, inflammatory bowel disorders, ischemia, macular degeneration, muscular dystrophy, tissue damage resulting from ischemia and reperfusion injury, neurological disorders and neurodegenerative diseases, neuronal tissue damage or disease, neuropathic pain, nervous insult, osteoarthritis, osteoporosis, peripheral nerve injury, renal failure, resuscitated hemorrhagic shock, retinal ischemia, septic shock, skin aging, vascular stroke, diseases or disorders relating to lifespan or proliferative capacity of cells, and diseases or disease conditions induced or exacerbated by cellular senescence. 25. The method according to claim 24 wherein the diseases or conditions are selected from diabetes, head trauma, inflammatory bowel disorders, ischemia, tissue damage resulting from ischemia and reperfusion injury, neurological disorders and neurodegenerative diseases, neuronal tissue damage disease, neuropathic pain, nervous insult, peripheral nerve injury, retinal ischemia, vascular stroke, and diseases or disorders relating to lifespan or proliferative capacity of cells. 26. The method according to claim 25 wherein the disease or condition is tissue damage resulting from ischemia and reperfusion injury. 985).* Poindexter, G. S. et al., "The Use of 2-Oxazolidinones as Latent Aziridine Equivalents. 2. Aminoethylation of Aromatic Amines, Phenols, and Thiophenols", J. Org. Chem., 1992, pp. 6257-6265, vol. 57. Botella, J. M. et al., "Aminolyse de Carbamates Cycliques analogues de la Carboxybiotine; Catalyse Metallique et Modelisation de Transfert de Carboxyle", Tetrahedron, 1992, pp. 5111-5122, vol. 48, No. 24. Abstract Only. Herweh, J. E. et al., "N-p-Toluenesulfonyl-2-oxazolidones Via the Cycloaddition Reaction of p-Toluenesulfonyl Isocyanate and Epoxides", J. of Heterocyclic Chem., 1971, pp. 983-987, vol. 8, No. 6. Yamawaki, J. et al., "N-Alkylation of Amides and N-heterocycles with Potassium Fluoride on Alumina", Chemistry Letters, 1981, pp. 1143-1146, No. 8. Buchstaller, H-P, "Solid Phase Synthesis of Oxazolidinones via a Novel Cyclisation/Cleavage Reaction", Tetrahedron, 1998, pp. 3465-3470, vol. 54, No. 14. Hole, P. T. et al., "Solid-Phase Synthesis of 3,5-Disubstituted 1,3-Oxazolidin-2-ones by an Activation/Cyclo-elimination Process", Tetrahedron, 1998, vol. 39, No. 40. Blass, B. E. et al., "A Facile KF/AL2O3Mediated Method for the Synthesis of Substituted Oxazolidinones", Tetrahedron Letters, 1999, pp. 6545-6547, vol. 40, No. 36.