US2024000748A1PendingUtilityA1
Formulations and methods for treating acute cannabinoid overdose
Assignee: ANEBULO PHARMACEUTICALS INCPriority: Nov 18, 2020Filed: Nov 17, 2021Published: Jan 4, 2024
Est. expiryNov 18, 2040(~14.3 yrs left)· nominal 20-yr term from priority
A61P 43/00A61P 25/30A61K 31/397A61K 9/0043A61K 9/006A61K 9/0019A61K 9/02A61K 9/0073A61K 9/7023A61P 39/00
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Claims
Abstract
Described herein are uses of the CB1 inhibitors (e.g., antagonists, neutral antagonists, inverse agonists) and various methods of using and administering a CB1 inhibitor to a patient, especially patients showing symptoms of drug overdose or suspected of a drug overdose. Further described herein are uses wherein the CB1 inhibitor is ANEB-001. Further described herein are treatments with a CB1 inhibitor for THC or synthetic cannabinoid overdose.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A method of using a pharmaceutical composition comprising a CB1 inhibitor, the method comprising administering to a patient an effective amount of the CB1 inhibitor and a pharmaceutically acceptable carrier or excipient, wherein the patient has a known or suspected acute drug overdose reaction, wherein the CB1 inhibitor has the structure of formula (I):
or a pharmaceutically acceptable salt or prodrug thereof,
wherein
R 1 is aryl or heteroaryl;
R 2 is alkyl, aryl or heteroaryl;
R 3 is alkyl, aryl, heteroaryl, NR 9 R 10 , OR 15 , or NR 16 C(O)R 17 ;
Y is C═O, C═S, SO 2 , or (CR 7 R 8 ) p ;
R 7 and R 8 are independently selected from H and lower alkyl;
R 9 is selected from H, alkyl, aryl, heteroaryl, and non-aromatic heterocyclic groups, or together with R 10 forms a saturated 4, 5, 6, or 7 membered ring optionally containing an additional heteroatom selected from N and 0;
R 10 is selected from H and lower alkyl, or together with R 9 forms a saturated 4, 5, 6, or 7 membered ring optionally containing an additional heteroatom selected from N and 0;
R 11 and R 12 are independently selected from H and lower alkyl;
R 15 is selected from alkyl and aryl;
R 16 is selected from H and lower alkyl;
R 17 is selected from alkyl, aryl and heteroaryl;
m is 1 or 2;
n is 1 or 2; and
p is 1, 2, 3 or 4.
2 . The method of claim 1 , wherein m is 1 and n is 1.
3 . The method of claim 1 or 2 , wherein R 1 and R 2 are independently aryl.
4 . The method of any one of claims 1 - 3 , wherein at least one of R 1 and R 2 has a non-hydrogen substituent in the ortho-position(s) thereof relative to the point of attachment to the [—CH—O—] group.
5 . The method of any one of claims 1 - 4 , wherein R 11 and R 12 are hydrogen.
6 . The method of any one of claims 1 - 5 , wherein R 3 is NR 9 R 10 , and R 9 and R 10 are independently lower alkyl or hydrogen.
7 . The method of claim 1 , wherein the CB1 inhibitor comprises the structure of formula (Ia):
or a pharmaceutically acceptable salt or prodrug thereof.
8 . The method of claim 7 , wherein R 1 and R 2 are independently selected from a group of formula (II):
wherein
R 4 , R 5 , and R 6 are independently selected from hydrogen, halo, alkyl (including haloalkyl), thioalkyl, alkoxy (including haloalkoxy), alkylsulfonyl, amino, mono- and di-alkyl amino, mono- and di-aryl amino, alkylarylamino, aminoalkyl, alkylaminoalkyl, dialkylaminoalkyl,
NR 14 C(O)R 19 , NR 14 SO 2 R 20 , COOR 19 , OC(O)R 20 , CONR 13 R 14 and SO 2 NR 13 R 14 ,
R 13 and R 14 are independently selected from hydrogen and alkyl or form a 5 or 6 membered ring optionally containing 1 or 2 additional heteroatoms selected from N, O and S;
R 19 is selected from H, alkyl, aryl and heteroaryl, and
R 20 is selected from alkyl, aryl and heteroaryl.
9 . The method of claim 8 , wherein at least one of R 4 , R 5 , and R 6 are chloro or trifluoromethyl.
10 . The method of claim 1 , wherein the CB1 inhibitor has the structure:
11 . The method of any one of claims 1 - 10 , wherein the patient shows signs of an acute cannabinoid overdose.
12 . The method of any one of claims 1 - 10 , wherein the patient shows signs of cannabinoid hyperemesis syndrome.
13 . The method of any one of claims 1 - 10 , wherein the method comprises treatment for drug overdose prior to treatment with the CB1 inhibitor.
14 . The method of any one of claims 1 - 10 , wherein the prior treatment comprises one or more of administration of an opiate antagonist, activated charcoal, or emetic.
15 . The method of claim 14 , wherein the prior treatment comprises one or more of orogastric lavage or whole bowel irrigation.
16 . The method of any one of claims 1 - 10 , wherein the method further comprises a diagnostic test prior to treatment with the CB1 inhibitor.
17 . The method of claim 16 , wherein the diagnostic test is a blood test.
18 . The method of claim 1 , wherein the patient has a cannabinoid plasma concentration of at least 50 μg/L.
19 . The method of claim 18 , wherein the patient has a cannabinoid plasma concentration of at least 100 μg/L.
20 . The method of claim 1 , wherein the patient has a cannabinoid plasma concentration of 50 g/L to 300 μg/L.
21 . The method of any one of claims 1 - 20 , wherein the pharmaceutical composition is prepared as an oral, sublingual, buccal, rectal, nasal, or parenteral dose.
22 . The method of any one of claims 1 - 20 , wherein the dose of the CB1 inhibitor is 1 mg to 200 mg.
23 . The method of claim 22 , wherein the dose of the CB1 inhibitor is 25 mg to 200 mg.
24 . The method of claim 22 , wherein the dose of the CB1 inhibitor is 50 mg to 200 mg.
25 . The method of claim 22 wherein the dose of the CB1 inhibitor delivers a therapeutically effective amount of the CB1 inhibitor in no more than 10 minutes.
26 . The method of claim 22 wherein the dose of the CB1 inhibitor delivers a therapeutically effective amount of the CB1 inhibitor in no more than 5 minutes.
27 . The method of claim 22 wherein the amount of the CB1 inhibitor in the bloodstream of the subject reaches at least 200 ng/mL within one hour after oral administration.
28 . The method of claim 22 wherein the amount of the CB1 inhibitor in the bloodstream of the subject reaches at least 200 ng/mL within 30 minutes after oral administration.
29 . The method of claim 22 , wherein the method is capable of ameliorating one or more symptoms of the acute drug overdose reaction in no more than 30 min.
30 . The method of claim 22 , wherein the method is capable of ameliorating one or more symptoms of the acute drug overdose reaction in no more than 1 hour.
31 . The method of any one of claims 1 - 20 , wherein the CB1 inhibitor is formulated as an oral, parenteral, intravenous (IV), intramuscular (IM), subcutaneous (SC), endotracheal, sublingual, buccal, intralingual, submental, transdermal, suppository, or intranasal administration.
32 . The method of any one of claims 1 - 31 , further comprising administering a pharmaceutically acceptable alkaline agent.
33 . The method of any one of claims 1 - 32 , wherein the pharmaceutical composition is formulated to deliver an effective dose of the CB1 inhibitor in no more than 10 min.
34 . A method of using a CB1 inhibitor as a pre-exposure prophylactic therapy comprising administering an effective amount of the CB1 inhibitor prior to exposure to a cannabinoid.
35 . The method of claim 34 , wherein the cannabinoid is tetrahydrocannabinol.
36 . The method of claim 34 or 35 wherein CB1 inhibitor is formulated for oral, parenteral, intravenous (IV), intramuscular (IM), subcutaneous (SC), endotracheal, sublingual, buccal, intralingual, submental, suppository, or intranasal administration.
37 . The method of any one of claims 34 - 36 , wherein the CB1 inhibitor has the structure
38 . The method of any one of claims 1 - 37 , wherein the excipient comprises a cyclodextrin.
39 . The method of claim 34 , wherein the dose of the CB1 inhibitor is 1 mg to 200 mg.
40 . A method of treating a patient suspected of a drug overdose comprising administering an effective amount of a CB1 inhibitor to a patient and monitoring the patient for reduced symptoms associated with overdose.
41 . The method of claim 40 , wherein monitoring comprises monitoring heart rate or respiration.
42 . The method of claim 40 or 41 , wherein the CB1 inhibitor has the structure:
43 . The method of claim 42 , wherein the dose of the CB1 inhibitor is 1 mg to 200 mg.
44 . The method of claim 42 , wherein the dose of the CB1 inhibitor is 25 mg to 200 mg.
45 . The method of claim 42 , wherein the dose of the CB1 inhibitor is 50 mg to 200 mg.
46 . An injectable composition for treating a suspected drug overdose, the composition comprising a CB1 inhibitor, an opioid antagonist, and a benzodiazepine antagonist.
47 . The injectable composition of claim 46 , wherein the benzodiazepine antagonist is flumazenil.
48 . The injectable composition of claim 46 or 47 , wherein the opioid antagonist is naloxone.
49 . The injectable composition of any one of claims 46 - 48 , wherein the injectable composition is formulated in a single dose injectable device.
50 . The injectable composition of any one of claims 46 - 49 , wherein the CB1 inhibitor has the structure
51 . The injectable composition of claim 50 , wherein the dose of the CB1 inhibitor is 1 mg to 200 mg.
52 . A composition for treating a suspected drug overdose, the composition comprising a CB1 inhibitor and an anxiolytic agent.
53 . The composition of claim 52 , wherein the anxiolytic agent is a cannabinoid.
54 . The composition of claim 53 , wherein the cannabinoid is cannabidiol (CBD).
55 . The composition of any one of claims 52 - 54 , wherein composition is formulated for intranasal delivery.
56 . The composition of any one of claims 52 - 55 , wherein the CB1 inhibitor has the structure
57 . The composition of claim 56 , wherein the dose of the CB1 inhibitor is 1 mg to 200 mg.Join the waitlist — get patent alerts
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