Agonist/antagonist compositions and methods of use

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.

What is claimed: 
     
         1 . A composition comprising an effective amount of an agonist and an effective amount of an antagonist,
 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 composition of  claim 1 , wherein the agonist is a TRPV1 agonist and the antagonist is a TRPV1 antagonist,
 wherein the TRPV1 agonist has a rate of penetration that is faster than the TRPV1 antagonist.   
     
     
         3 . The composition of  claim 2 , wherein the TRPV1 agonist is antagonized by 80% by the TRPV1 antagonist, in about 1 minute to about 20 minutes. 
     
     
         4 . The composition of  claim 3 , wherein the TRPV1 agonist is antagonized by 80% by the TRPV1 antagonist, in about 1 minute to about 5 minutes. 
     
     
         5 . The composition of  claim 2 , 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), trams-9-methyl-N-vanillyl-7-decenamide (homocapsaicin), (3R,3,5R)-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. 
     
     
         6 . The composition of  claim 5 , wherein the TRPV1 agonist is capsaicin. 
     
     
         7 . The composition of  claim 2 , wherein the TRPV1 antagonist is BCTC, IodoRTX, JYL-827, AMG9810, 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. 
     
     
         8 . The composition of  claim 7 , wherein the TRPV1 antagonist is BCTC, IodoRTX, JYL-827, AMG9810, or capsazepine. 
     
     
         9 . The composition of  claim 1 , wherein the agonist is an opiate agonist and the antagonist is an opiate antagonist. 
     
     
         10 . The composition of  claim 9 , wherein the opiate agonist is fentanyl. 
     
     
         11 . The composition of  claim 10 , wherein the opiate antagonist is diphenyl-6beta-naltrexamate or 6-beta-tosylnaltrexamate. 
     
     
         12 . The composition of  claim 1 , wherein the agonist and antagonist are in a ratio of about 1:1 to about 10:1. 
     
     
         13 . The composition of  claim 1 , wherein the agonist and antagonist are in a ratio of about 1:1 to about 1:10. 
     
     
         14 . The composition of  claim 1 , further comprising an additional therapeutic agent. 
     
     
         15 . The composition of  claim 1 , further comprising a surfactant, solubilizer, or emulsifier. 
     
     
         16 . A biocontrol agent comprising the composition of  claim 1 . 
     
     
         17 . A method for incapacitating a subject, 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; and   (b) applying the non-lethal temporarily incapacitating formulation to the subject;   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.   
     
     
         18 . The method of  claim 17 , wherein the non-lethal temporarily incapacitating composition further comprises a propellant. 
     
     
         19 . The method of  claim 18  wherein said propellant is miscible in said solvent system. 
     
     
         20 . The method of  claim 19  wherein said propellant is carbon dioxide. 
     
     
         21 . The method of  claim 17 , wherein the TRPV1 agonist is antagonized by 80% by the TRPV1 antagonist, in about 1 minute to about 20 minutes. 
     
     
         22 . The method of  claim 21 , wherein the TRPV1 agonist is antagonized by 80% by the TRPV1 antagonist, in about 1 minute to about 5 minutes. 
     
     
         23 . The method of  claim 17 , 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,3,5R)-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. 
     
     
         24 . The method of  claim 23 , wherein the TRPV1 agonist is capsaicin 
     
     
         25 . The method of  claim 17 , 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. 
     
     
         26 . The method of  claim 25 , wherein the TRPV1 antagonist is BCTC, IodoRTX, JYL-827, AMG9810, or capsazepine. 
     
     
         27 . The method of  claim 17  wherein the TRPV1 agonist and antagonist are present in an amount of about 0.01% to about 5% by weight of the solvent system. 
     
     
         28 . The method of  claim 27  wherein the TRPV1 agonist and antagonist are present in an amount of 0.1% to about 3% by weight of the solvent system. 
     
     
         29 . The method of  claim 17  wherein the solvent system comprises approximately equal amounts of the propylene glycol dicaprylate/caprate and glycerol tris(2-ethylhexanoate). 
     
     
         30 . The method of  claim 17  wherein said applying comprises spraying the non-lethal temporarily incapacitating formulation into the eyes of the subject. 
     
     
         31 . The method of  claim 17  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. 
     
     
         32 . The method of  claim 17 , 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 breadth, and burning sensation. 
     
     
         33 . The method of  claim 32 , wherein the symptom lasts about 1 minute to about 45 minutes. 
     
     
         34 . A method for subduing a subject, 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 an opiate agonist, an effective amount of an opiate antagonist, and a solvent system; and   (b) applying the non-lethal temporarily incapacitating formulation to the subject;   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.   
     
     
         35 . A pharmaceutical composition in the form of a solid carrier comprising: (a) an agonist, (b) an antagonist, (c) an effective solubilizing amount of at least one hydrophiliac surfactant, which is effective to partially or fully solubilize the agonist and antagonist in the solid carrier, and optionally (d) an additive;
 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.   
     
     
         36 . The composition of  claim 35 , wherein the hydrophilic surfactant selected from the group consisting of (i) polyoxyethylene sorbitan fatty acid esters, (ii) polyoxyethylene-polyoxypropylene block copolymers, (iii) polyglycerol fatty acid esters, (iv) polyoxyethylene glycerides, (v) polyoxyethylene sterols, deriviatives, and analogues thereof, (vi) polyoxyehtylene vegetable oils, (vii) polyoxyethylene hydrogenated vegetable oils, (viii) reaction mixtures of polyols and at least one member of the group consisting of fatty acids, glycerides, vegetable oils, hydrogenated vegetable oils, and sterols (ix) tocopheryl polyethylene glycol succinates, (x) sugar esters, (xi) sugar ethers, (xii) sucroglycerides, and (xiii) mixtures thereof; and (c) an additive to provide for controlled release of the active ingredient following administration to a patient, said additive selected from the group consisting of polyvinylpyrrolidone, polyethylene glycol, hydroxypropyl methylcellulose, hyrosypropyl cellulose and other cellulose derivatives and mixtures thereof. 
     
     
         37 . The composition of  claim 35 , wherein the additive is selected from the group consisting of solubilizers, enzyme inhibitors, anti-adherents, anticoagulants, antifoaming agents, antioxidants, binders, bufferants, chelating agents, coagulants, colorants, opaquants, coolants, cryoprotectants, diluents, fillers, disintegrants, super disintegrants, hydrogen bonding agents, flavorants, desensitizers, ion-exchange resins, plasticizers, preservatives, solvents, sweeteners, thickeners, and mixtures thereof.