Methods for treatment of sleep-related breathing disorders 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
AU2011240843 A1 2012-12-06 [AU2011240843] / 2012-12-06
申请号/申请日
2011AU-0240843 / 2011-04-11
发明人
SNYDER SOLOMON H;GADALLA MOATAZ M;PRABHAKAR NANDURI R;STEIN GREGORY;PACE GARY;
申请人
JOHNS HOPKINS UNIVERSITY;SOVA PHARMACEUTICALS;UNIVERSITY OF CHICAGO;
主分类号
IPC分类号
A01N-043/16
摘要
(AU2011240843) Described herein are methods for modulation of the activity of the carotid body that afford therapeutic benefit for sleep -related breathing disorders and related conditions.
机翻摘要
暂无翻译结果,您可以尝试点击头部的翻译按钮。
地址
代理人
代理机构
;
优先权号
2010US-61323621 2010-04-13 2010US-61347069 2010-05-21 2011WO-US31977 2011-04-11
主权利要求
(AU2011240843) 1. A method of treating or preventing or reducing incidence of a sleep-related breathing disorder in an individual in need thereof comprising administration of a therapeutically effective amount of an agent that modulates the activity of the carotid body to the individual in need thereof. 2. The method of claim 1, wherein the individual is suffering from or suspected to be suffering from a sleep-related breathing disorder selected from central sleep apnea (CSA), Cheyne-Stokes breathing -central sleep apnea (CSB-CSA), obesity hypoventilation syndrome (OHS), congenital central hypoventilation syndrome (CCHS), obstructive sleep apnea (OSA), idiopathic central sleep apnea (ICSA), narcotic-induced CSA, high altitude periodic breathing, chronic mountain sickness, impaired respiratory motor control associated with stroke, or impaired respiratory motor control associated with a neurologic disorder. 3. The method of claim 1, wherein the agent that modulates the activity of the carotid body is an agent that inhibits or partially inhibits the activity of cystathionine-y-lyase (CSE). 4. The method of claim 3, wherein the agent that inhibits or partially inhibits the activity of CSE reduces the chemosensitivity of the carotid body in an individual in need thereof 5. The method of claim 3, wherein the agent that inhibits or partially inhibits the activity of CSE reduces the chemosensitivity of the carotid body to the partial pressure of oxygen in arterial blood, reduces the chemosensitivity of the carotid body to the partial pressure of carbon dioxide in arterial blood, reduces the loop gain of the ventilatory drive control system, lowers blood pressure, or dampens carotid sinus nerve activity in an individual in need thereof. 6. The method of claim 3, wherein the agent that inhibits or partially inhibits the activity of CSE is DL-propargylglycine (PAG), beta cyano L-alanine (BCA), or analog or derivative thereof 7. The method of claim 1, wherein the agent that modulates the activity of the carotid body is an agent that inhibits or partially inhibits hemeoxygenase-2 enzyme (HO-2), or is an H2S donor. 8. The method of claim 7, wherein the agent that inhibits or partially inhibits hemeoxygenase-2 enzyme is an agent that stimulates the chemosensitivity of the carotid body in an individual in need thereof 9. The method of claim 7, wherein the agent that inhibits or partially inhibits hemeoxygenase-2 enzyme decreases production of carbon monoxide in the carotid body, increases production of H2S in the carotid body, or increases carotid sinus nerve activity in an individual in need thereof 10. The method of claim 7, wherein the agent that inhibits or partially inhibits hemeoxygenase-2 enzyme is Cr(III) mesoporphyrin IX chloride, or analog or derivative thereof 11. The method of claim 7, wherein the agent that inhibits or partially inhibits hemeoxygenase-2 enzyme is CI z'"-----(NH 2 OH,CI",or IS, CI CI 12. The method of claim 7, wherein the agent that is an H2S donor is an agent that stimulates the chemosensitivity of the carotid body in an individual in need thereof. 13. The method of claim 7, wherein the agent that is an H2S donor decreases production of carbon monoxide in the carotid body, increases concentration of H2S in the carotid body, or increases carotid sinus nerve activity in an individual in need thereof 14. The method of claim 7, wherein the agent that is an H2S donor is WO 2011/130181 PCT/US2011/031977 NH2 CI CI CI, or 15. A method of treatment of CSB-CSA comprising administering to an individual in need thereof a therapeutically effective amount of an agent that inhibits or partially inhibits CSE. 16. A method of treatment of obesity hypoventilation syndrome (OHS) and/or other alveolar hypoventilation syndromes comprising administering to an individual in need thereof a therapeutically effective amount of an agent that inhibits or partially inhibits HO2, or is an H2S donor. 17. The method of any one of claims 1-16, further comprising administration of a second agent selected from carbonic anhydrase inhibitors, cholinesterase inhibitors, adenosine inhibitors, progestational agents, opiod antagonists, central nervous system stimulants, selective serotonin reuptake inhibitors (SSR1s), antidepressants, antihypertensives, calcium channel antagonists, ACE inhibitors, respiratory stimulants, alpha-2 adrenergic agonists, gamma aminobutyric acid agonists, and glutamate antagonists. 18. The method of any one of claims 1-16, further comprising administration of a second agent selected from acetazolamide, theophylline, progesterone, donepezil, naloxone, nicotine, paroxetine, protriptyline, metoprolol, cilazapril, propranolol, atenolol, hydrochlorothiazide, isradipine, spirapril, doxapram, clonidine, baclofen, and sabeluzole. 19. The method of any one of claims 1-16, wherein the agent that modulates the activity of the carotid body is administered orally, subcutaneously, topically, intramuscularly, or intravenously. 20. The method of any one of claims 1-16 wherein the agent that modulates the activity of the carotid body is administered orally. 21. A single pill co-formulation comprising (i) an agent that modulates the activity of the carotid body and (ii) an agent selected from carbonic anhydrase inhibitors, cholinesterase inhibitors, adenosine inhibitors, progestational agents, opiod antagonists, central nervous system stimulants, selective serotonin reuptake inhibitors (SSRIs), antidepressants, antihypertensives, calcium channel antagonists, ACE inhibitors, respiratory stimulants, alpha-2 adrenergic agonists, gamma aminobutyric acid agonists, and glutamate antagonists. 22. The single pill co-formulation of claim 21, wherein the agent that modulates the activity of the carotid body is a CSE inhibitor. 23. The single pill co-formulation of claim 21, wherein the agent that modulates the activity of the carotid body is a hemeoxygenase-2 inhibitor. 24. A method of identifying a CSE inhibitor comprising (a) administration of a test compound to a test animal; (b) preparing carotid body homogenates from the test animal; (c) determining H2S concentration in the homogenate; wherein a decrease in H2S concentration indicates that the test compound is a CSE inhibitor 25. A method of identifying a CSE inhibitor comprising (a) administration of a test compound to a test animal; (b) isolating carotid bodies along with carotid sinus nerves from the test animal; (c) challenging the carotid bodies with varying levels of oxygen and carbon dioxide; and (d) recording action potentials of the nerve bundles; wherein a decrease in action potential indicates that the test compound is a CSE inhibitor. 26. A method of identifying a HO-2 inhibitor comprising (a) administration of a test compound to a test animal; (b) isolating carotid bodies along with carotid sinus nerves from the test animal; (c) challenging the carotid bodies with varying levels of oxygen and carbon dioxide; and (d) recording action potentials of the nerve bundles; wherein an increase in action potential indicates that the test compound is a HO-2 inhibitor.
法律状态
(AU2011240843) LEGAL DETAILS FOR AU2011240843  Actual or expected expiration date=2014-12-11    Legal state=DEAD    Status=LAPSED     Event publication date=2011-04-11  Event code=AU/APP  Event indicator=Pos  Event type=Examination events  Application details  Application country=AU AU2011240843  Application date=2011-04-11  Standardized application number=2011AU-0240843     Event publication date=2012-12-06  Event code=AU/A1  Event indicator=Pos  Event type=Examination events  Open to public inspection  Publication country=AU  Publication number=AU2011240843  Publication stage Code=A1  Publication date=2012-12-06  Standardized publication number=AU2011240843     Event publication date=2014-12-11  Event code=AU/MK1  Event indicator=Neg  Event type=Event indicating Not In Force  Application lapsed section 142(2)(a) - no request for examination in relevant period
专利类型码
A1
国别省市代码
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