Agonist/antagonist compositions and methods of use

Patent metadata

Field	Value
Publication number	US-9277748-B2
Application number	US-201113634447-A
Country	US
Kind code	B2
Filing date	Mar 11, 2011
Priority date	Mar 12, 2010
Publication date	Mar 8, 2016
Grant date	Mar 8, 2016

Abstract

The present invention relates to novel compositions comprising an agonist and an antagonist, in certain ratios which allow for the onset of agonist action followed quickly by alleviation by antagonist action, and methods of use in personal defense and law enforcement.

First claim

What is claimed:

1. A method for incapacitating a mammal, comprising:
(a) providing a non-lethal temporarily incapacitating composition suitable for use in an aerosol or spray application, the incapacitating formulation comprising an effective amount of a TRPV1 agonist, an effective amount of a TRPV1 antagonist, and a solvent system;
(b) applying the non-lethal temporarily incapacitating formulation to the mammal, wherein the agonist and antagonist are administered simultaneously to the mammal; and
(c) temporarily incapacitating the mammal,

wherein the amount of antagonist does not decrease a maximal response to agonist by more than 20%, compared to agonist alone, at time 0, and the amount of antagonist reduces the response to agonist by at least 80% at 20 minutes.

2. The method of claim 1 , wherein the TRPV1 agonist is capsaicin, dibenzoxazepine (CR), oleoresin capscium (OC), oleoresin paprika, paprika, capsicums (chili peppers), trans-8-methyl N-vanillyl-6-nonenamide (capsaicin), 8-methyl-N-vanillyl-nonamide (dihydrocapsaicin), 7-methyl-N-vanillyl-octamide (nordihydrocapsaicin), 9-methyl-N-vanillyl-decamide (homodihydrocapsaicin), trans-9-methyl-N-vanillyl-7-decenamide (homocapsaicin), (3R, 3, 5 R)-3,3′-dihydroxy-a,k-caroten-6-one (capsanthin), N-vanillyl-octamide, N-vanillyl-nonamide, N-vanillyl-decanamide, N-vanillyl-undecanamide, N-vanillyl-paaiperic acid amide, nonivamide, civamide, olvanil, Nb-VNA, Nv-VNA, SB-705498, or anadamide.

3. The method of claim 2 , wherein the TRPV1 agonist is capsaicin.

4. The method of claim 1 , wherein the TRPV1 antagonist is BCTC, IodoRTX, JYL-827, AMG9810, or capsazepine, SB-705498, Aprepitant, Lanpepitant, CP-99,994, SDZ NKT 343, Ezlopitant, CP-96345, CP-99994, CP-122721, MK-869, GR 205171. RP 67580, Dapitant, Lanepitant, Noloitanium, Sarefutant, Casopitant, or Vestipitant.

5. The method of claim 4 , wherein the TRPV1 antagonist is BCTC, IodoRTX, JYL-827, AMG9810, or capsazepine.

6. The method of claim 1 wherein the solvent system comprises approximately equal amounts of the propylene glycol dicaprylate/caprate and glycerol tris (2-ethylhexanoate).

7. The method of claim 1 wherein said applying comprises spraying the non-lethal temporarily incapacitating formulation into the eyes of the subject.

8. The method of claim 1 , wherein the non-lethal temporarily incapacitating composition further comprises a propellant.

9. The method of claim 8 wherein said propellant is miscible in said solvent system.

10. The method of claim 9 wherein said propellant is carbon dioxide.

11. The method of claim 1 , wherein the TRPV1 agonist is antagonized by 80% by the TRPV1 antagonist in between 1 minute and 20 minutes.

12. The method of claim 11 , wherein the TRPV1 agonist is antagonized by 80% by the TRPV1 antagonist in between 1 minute and 5 minutes.

13. The method of claim 1 , wherein the TRPV1 agonist and TRPV1 antagonist are present in an amount of about 0.01% to about 5% by weight of the solvent system.

14. The method of claim 13 , wherein the TRPV1 agonist and TRPV1 antagonist are present in an amount of 0.1% to about 3% by weight of the solvent system.

15. The method of claim 1 , wherein said incapacitating composition is formulated to cause, upon application of the system to the facial area of a recipient, inflammation to the facial area of the recipient.

16. The method of claim 1 , wherein said application of the composition into the facial area of the subject causes the subject to experience a symptom selected from the group consisting of immediate closing of the eyes, shortness of breath, and burning sensation.

17. The method of claim 16 , wherein the symptom lasts from 1 minute to 45 minutes.

18. The method of claim 1 , wherein the TRPV1 agonist and TRPV1 antagonist are present in a ratio of 300:1, 30:1, 10:1, 3:1, 1:1, 3:10, 1:10, 1:20, or 3:100.

19. The method of claim 4 , wherein the TRPV1 antagonist is BCTC or IodoRTX.

20. The method of claim 1 , wherein the TRPV1 agonist exhibits a rate of penetration that is faster than the TRPV1 antagonist rate of penetration.

Assignees

• Blumberg Peter M
• Pearce Larry V
• Us Health

Inventors

• Blumberg Peter M
• Pearce Larry V

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• C06D7/00 Primary

  Compositions for gas-attacks · CPC title

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title

• A61K31/55

  having seven-membered rings, e.g. azelastine, pentylenetetrazole · CPC title

• A61K31/4468

  having a nitrogen directly attached in position 4, e.g. clebopride, fentanyl · CPC title