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1. (WO2019050923) METHODS OF USING DANTROLENE TO TREAT NERVE AGENT EXPOSURE
ملاحظة: نص مبني على عمليات التَعرف الضوئي على الحروف. الرجاء إستخدام صيغ PDF لقيمتها القانونية

What is claimed:

1. A method of protecting a subject from neural necrosis after the subject has been exposed to a nerve agent comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of dantrolene or a pharmaceutically acceptable salt thereof.

2. The method of claim 1, wherein the fronto-parietal cortex, the hippocampus, and/or the thalamus is protected from neural necrosis.

3. A method of treating a subject exposed to a nerve agent comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of dantrolene or a pharmaceutically acceptable salt thereof.

4. A method of protecting a subject from a decrease in central nervous system function resulting from exposure to a nerve agent comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of dantrolene or a pharmaceutically acceptable salt thereof.

5. A method of treating nerve agent-induced seizures, in particular status epilepticus,

comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of dantrolene or a pharmaceutically acceptable salt thereof.

6. A method of protecting a subject from a central nervous system dysfunction resulting from exposure to a nerve agent comprising administering to the subject a pharmaceutical composition comprising a therapeutically effective amount of dantrolene or a pharmaceutically acceptable salt thereof.

7. A method of treating behavioral changes resulting from exposure to a nerve agent

comprising administering to the subject a pharmaceutical composition comprising a

therapeutically effective amount of dantrolene or a pharmaceutically acceptable salt thereof.

8. The method of any one of the preceding claims, wherein the nerve agent is an

acetylcholinesterase inhibitor.

9. The method of any one of the preceding claims, wherein the nerve agent is an

organophosphate.

10. The method of any one of the preceding claims, wherein the nerve agent is O-pinacolyl methylphosphonofluoridate (soman), ethyl N,N-dimethylphosphoramidocyanidate (tabun), propan-2-yl methylphosphonofluoridate (sarin), cyclohexyl

methylphosphonofluoridate (cyclosarin), or 2-(Dimethylamino)ethyl (GV).

11. The method of any one of claims 1 to 9, wherein the nerve agent is O-cyclopentyl S-(2- diethylaminoethyl) methylphosphonothiolate (EA-3148), (S)-(ethyl {[2- (diethylamino)ethyl]sulfanyl}(ethyl)phosphinate) (VE), 0,0-Diethyl S-[2- (diethylamino)ethyl] phosphorothioate (VG), S-[2-(Diethylamino)ethyl] O-ethyl methylphosphonothioate (VM), N,N-diethyl-2-(methyl-(2- methylpropoxy)phosphoryl)sulfanylethanamine (VR), or Ethyl ({2-[bis(propan-2- yl)amino] ethyl } sulfanyl)(methyl)phosphinate (VX).

12. The method of any one of the preceding claims, wherein the subject is a mammal.

13. The method of any one of the preceding claims, wherein the subject is a human.

14. The method of claim 13, wherein the therapeutically effective amount is 1 mg/kg to about 30 mg/kg of dantrolene.

15. The method of any one of the preceding claims, wherein the dantrolene is administered to the subject 24 hours or less after the subject has been exposed to the nerve agent.

16. The method of any one of the preceding claims wherein the pharmaceutical composition is administered to the subject in one or more doses.

17. The method of any one of the preceding claims, further comprising administering to the subject an acetylcholinesterase reactivator, a reverse antagonist of acetylcholine receptors, an anti-seizure medication, or a combination thereof.

18. The method of claim 17, wherein the acetylcholinesterase reactivator is asoxime chloride (HI-6).

19. The method of claim 1, wherein the reverse antagonist of acetylcholine receptors is atropine methyl nitrate.

20. The method of claim 17, wherein the anti-seizure medication is a benzodiazepine.

21. The method of claim 19, wherein the benzodiazepine is midazolam.

22. The method of claim 17, wherein the pharmaceutical composition is administered after the administration of the acetylcholinesterase reactivator.

23. The method of claim 17, wherein the pharmaceutical composition is administered after the administration of the acetylcholinesterase reactivator and after the administration of the reverse antagonist of acetylcholine receptors.

24. The method of claim 23, wherein the pharmaceutical composition is administered

concurrently or substantially concurrently with the administration of the anti-seizure medication.

25. The method of claim 23, wherein the pharmaceutical composition is administered after the administration of the anti-seizure medication.

26. The method of any one of the preceding claims, wherein the pharmaceutical composition is administered intravenously, subcutaneously, intramuscularly, intraosseously, or transdermally.

27. The method of any one of the preceding claims, wherein the pharmaceutical composition comprises dantrolene or a pharmaceutically acceptable salt thereof, mannitol, a polysorbate, a povidone, an optional pH adjustor, and water.

28. The method of any one of the preceding claims, wherein the administration of the

pharmaceutical composition comprising dantrolene or a pharmaceutically acceptable salt thereof results in improved neurobehavioral performance, as compared to a subject exposed to the nerve agent that was not administered the pharmaceutical composition comprising dantrolene or a pharmaceutically acceptable salt thereof.