US2008293695A1PendingUtilityA1
Salts of physiologically active and psychoactive alkaloids and amines simultaneously exhibiting bioavailability and abuse resistance
Est. expiryMay 22, 2027(~0.9 yrs left)· nominal 20-yr term from priority
A61K 31/55A61P 25/30A61K 31/235A61K 31/195A61K 31/205A61K 31/192
67
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Claims
Abstract
Drug substances comprising a pharmaceutically acceptable organic acid addition salt 6f amine containing pharmaceutically active compounds useful for the treatment of a therapeutic ailment administration and exhibiting prophylactic properties when employed in non-therapeutic administration.
Claims
exact text as granted — not AI-modified1 . A drug substance comprising a pharmaceutically acceptable organic acid addition salt of an amine containing pharmaceutically active compound useful for the treatment of an ailment by therapeutic administration and exhibiting anti-abuse properties when employed in non-therapeutic administration.
2 . The drug substance of claim 1 wherein said therapeutic administration is selected from gastrointestinal tract bio-availability; gastrointestinal tract permeability; gastrointestinal tract dissolution; gastrointestinal tract efficacy and pH dependent release in a gastrointestinal tract.
3 . The drug substance of claim 1 wherein said non-therapeutic administration is selected from mucosal membrane bio-unavailability; non-permeability in mucosal membranes; essentially no dissolution in the mucosal membranes; non-efficacy for mucosal membranes and non-release properties when delivered to mucosal membranes.
4 . The drug substance of claim 3 wherein said mucosal membranes are selected from ocular, nasal, pulmonary, buccal, sublinqual, gingival, rectal, and vaginal mucosa.
5 . The drug substance of claim 4 wherein said mucosal membranes have a pH in a range of about 4 to about 9.
6 . The drug substance of claim 1 wherein said non-therapeutic administration occurs at a pH of 4-9 and said therapeutic ailment administration is at a pH of below 4 or above 9.
7 . The drug substance of claim 1 wherein said pharmaceutically active compound comprises a material selected from acetaminophen, caffeine, acetorphine, acetylmethadol, allylprodine, alphacetylmethadol, bufotenine, dextromoramide, diethyltryptamine, etorphine, heroin, ibogaine, ketobemidone, lysergic acid diethylamide, mescaline, methaqualone, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, N-ethyl-1-phenylcyclohexylamine, peyote, 1-(1-phenylcyclohexyl)pyrrolidine, psilocybin, psilocin, 1-{1-(2-thienyl)-cyclohexyl}-piperidine, alphaprodine, anileridine, cocaine, dextropropoxyphene, diphenoxylate, ethylmorphine, glutethimide, hydrocodone, hydromorphone, levo-alphaacetylmethadol, levorphanol, meperidine, methadone, morphine, opium, oxycodone, oxymorphone, poppy straw, thebaine, amphetamine, methamphetamine, methylphenidate, phencyclidine, codeine, benzphetamine, ketamine, alprazolam, chlorodiazepoxide, clorazepate, diethylpropion, fenfluramine, flurazepam, halazepam, lorazepam, mazindol, mebutamate, midazolam, oxazepam, pemoline, pentazocine, phentermine, prazepam, quazepam, temazepam, triazolam, zolpidem, and buprenorphine.
8 . The drug substance of claim 1 wherein said amine containing pharmaceutically active material is selected from the group consisting of opiates, morphinoids, amphetamines, compounds containing a piperidine or substituted piperidine sub-structure within a molecule, benzodiazapines, benzazepines, tropinoids and compounds containing a phenethyl amine or substituted phenethylamine sub-structure within a molecule.
9 . The drug substance of claim 1 wherein said organic acid addition salt is selected from:
wherein R 1 -R 4 are independently selected from H, alkyl of 1-6 carbons, adjacent groups may be taken together to form a cyclic alkyl, cyclic alkyl-aryl, or cyclic aryl moiety;
R 5 is selected from H, or an alkali earth cation;
R 6 and R 7 are independently selected from H, alkyl of 1-6 carbons, an alkali earth cation, and aryl of 6 to 12 carbons, in a number sufficient to complete the valence bonding of X, and
wherein X is selected from nitrogen, oxygen or sulfur.
10 . The drug substance of claim 9 wherein said organic acid addition salt is selected from the group consisting of:
wherein R 5 , R 6 and R 7 remain as defined for Structure A;
wherein X, R 5 , R 6 and R 7 remain as defined above for Structure A;
wherein X, R 1 , R 2 , R 5 , R 6 and R 7 remain as defined above for Structure A;
wherein X, R 1 , R 4 , R 5 , R 6 and R 7 remain as defined above for Structure A;
wherein X, R 1 , R 5 , R 6 and R 7 are independently defined as above for Structure A; and
wherein X, R 5 , R 6 and R 7 are independently defined as above for Structure A.
11 . The drug substance of claim 10 wherein for Structure D X is O; R 1 and R 2 are hydrogen.
12 . The drug substance of claim 10 wherein for Structure E X is O, R 1 and R 4 are hydrogen.
13 . The drug substance of claim 10 wherein for Structure F at least one X is O and at least one R 1 is hydrogen.
14 . The drug substance of claim 10 wherein for Structure G X is O and R 5 is hydrogen.
15 . The drug substance of claim 10 wherein said organic acid comprises a material selected from the group consisting of pamoic acid, disodium pamoate, di-ammonium pamoate, di-potassium pamoate, lower molecular weight di-alkyl amine pamoate, lower molecular weight di-aryl amine pamoate, lower molecular weight di-alkyl esters of pamoic acid, lower molecular weight di-aryl esters of pamoic acid, lower molecular weight di-alkylacyl O-esters of pamoic acid and lower molecular weight di-arylacyl O-esters of pamoic acid.
16 . The drug substance of claim 10 wherein the organic acid comprises a material selected from the group consisting of ortho isomers of hydroxy naphthoic acid, sodium hydroxy naphthoic acid, ammonium hydroxy naphthoate, potassium hydroxy naphthoate, lower molecular weight alkyl amine salts of hydroxy naphthoic acid, lower molecular weight aryl amine salts of hydroxy naphthoic acid, lower molecular weight alkyl esters of hydroxy naphthoic acid, lower molecular weight aryl esters of hydroxy naphthoic acid, lower molecular weight alkylacyl O-esters of hydroxyl naphthoic acid and lower molecular weight arylacyl O-esters of hydroxyl naphthoic acid.
17 . The drug substance of claim 10 wherein the organic acid is selected from the group consisting of salicylic acid, sodium salicylate, ammonium salicylate, potassium salicylate, lower molecular weight alkyl amine salts of salicylic acid, lower molecular weight aryl amine salts of salicylic acid, lower molecular weight alkyl esters of salicylic acid, lower molecular weight aryl esters of salicylic acid, lower molecular weight alkylacyl O-esters of salicylic acid and lower molecular weight arylacyl O-esters of salicylic acid.
18 . The drug substance of claim 10 wherein said organic acid salt comprises an acid selected from pamoic acid or a synthetic equivalent thereof; salicylic acid or a synthetic equivalent thereof and hydroxy naphthoic acid or a synthetic equivalent thereof.
19 . The drug substance of claim 1 in a form selected from the group consisting of a tablet, a capsule, a caplet, and an oral suspension.
20 . The drug substance of claim 1 wherein said pharmaceutically acceptable organic acid addition salt of an amine containing pharmaceutically active compound has a phase transition temperature of at least 100° C.
21 . The drug substance of claim 1 wherein said pharmaceutically active organic acid addition salt is bio-unavailable when exposed to mucosal membranes and exhibits recovery from aqueous solution at about pH 4.5 of at least 85 weight percent.
22 . The drug substance of claim 1 wherein said pharmaceutically active orgainc acid addition salt is bio-unavailable when exposed to mucosal membranes and exhibits recovery from aqueous solution at about pH 7.0 of at least 85 weight percent.
23 . The drug substance of claim 1 wherein said pharmaceutically active organic acid addition salt comprises a mixture of physical forms.
24 . The drug substance of claim 23 wherein said mixture of physical forms comprises an amorphous material and at least one polymorph.
25 . The drug substance of claim 1 designed for immediate release in the gastrointestinal tract and for essentially non-release in the mucosal membranes.
26 . The drug substance of claim 1 wherein said pharmaceutically active organic acid addition salt of an amine containing pharmaceutically active compound is selected from the group consisting of phentermine pamoate, ephedrine pamoate, pseudophedrine pamoate, benzphetamine pamoate, imipramine pamoate, phentermine xinafoate, ephedrine xinafoate, pseudophedrine xinafoate, benzphetamine xinafoate, imipramine xinafoate, phentermine salicylate, ephedrine salicylate, pseudophedrine salicylate, benzphetamine salicylate and imipramine salicylate.
27 . The drug substance of claim 1 administered for at least one purpose selected from pain management, anti-convulsant, anti-depressant, analgesic, anesthetic, anxiolytic, psychotropic, hallucinogenic, hypnotic, anorexic, cough, cold and sinus.
28 . The drug substance of claim 1 administered by one method delivery presentation selected from solid oral delivery, parenteral delivery, transdermal delivery and inhalation delivery.
29 . A drug substance as a pharmaceutically acceptable organic acid addition salt of an amine containing pharmaceutically active compound exhibiting at least two dissolution profiles one of which provides for drug efficacy when administered in a formulated oral dosage and one which does not provide drug efficacy when administered as a non-oral dosage.
30 . The drug substance of claim 29 wherein said pharmaceutically active compound comprises a material selected from acetaminophen, caffeine, acetorphine, acetylmethadol, allylprodine, alphacetylmethadol, bufotenine, dextromoramide, diethyltryptamine, etorphine, heroin, ibogaine, ketobemidone, lysergic acid diethylamide, mescaline, methaqualone, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, N-ethyl-1-phenylcyclohexylamine, peyote, 1-(1-phenylcyclohexyl)pyrrolidine, psilocybin, psilocin, 1-{1-(2-thienyl)-cyclohexyl}-piperidine, alphaprodine, anileridine, cocaine, dextropropoxyphene, diphenoxylate, ethylmorphine, glutethimide, hydrocodone, hydromorphone, levo-alphaacetylmethadol, levorphanol, meperidine, methadone, morphine, opium, oxycodone, oxymorphone, poppy straw, thebaine, amphetamine, methamphetamine, methylphenidate, phencyclidine, codeine, benzphetamine, ketamine, alprazolam, chlorodiazepoxide, clorazepate, diethylpropion, fenfluramine, flurazepam, halazepam, lorazepam, mazindol, mebutamate, midazolam, oxazepam, pemoline, pentazocine, phentermine, prazepam, quazepam, temazepam, triazolam, zolpidem, and buprenorphine.
31 . The drug substance of claim 29 wherein said amine containing pharmaceutically active material is selected from the group consisting of opiates, morphinoids, amphetamines, compounds containing a piperidine or substituted piperidine sub-structure within a molecule, benzodiazapines, benzazepines, tropinoids and compounds containing a phenethyl amine or substituted phenethylamine sub-structure within a molecule.
32 . The drug substance of claim 29 wherein said organic acid addition salt is selected from:
wherein R 1 -R 4 are independently selected from H, alkyl of 1-6 carbons, adjacent groups may be taken together to form a cyclic alkyl, cyclic alkyl-aryl or cyclic aryl moiety;
R 5 is selected from H, or an alkali earth cation;
R 6 and R 7 are independently selected from H, alkyl of 1-6 carbons, an alkali earth cation, and aryl of 6 to 12 carbons, in a number sufficient to complete the valence bonding of X, and
wherein X is selected from nitrogen, oxygen or sulfur.
33 . The drug substance of claim 32 wherein said organic acid addition salt is selected from the group consisting of:
wherein R 5 , R 6 and R 7 remain as defined for Structure A;
wherein X, R 5 , R 6 and R 7 remain as defined above for Structure A;
wherein X, R 1 , R 2 9 R 5 , R 6 and R 7 remain as defined above for Structure A;
wherein X, R 1 , R 4 , R 5 , R 6 and R 7 remain as defined above for Structure A;
wherein X, R 1 , R R 6 and R 7 are independently defined as above for Structure A; and
wherein X, R 5 , R 6 and R 7 are independently defined as above for Structure A.
34 . The drug substance of claim 33 wherein for Structure D X is O; R 1 and R 2 are hydrogen.
35 . The drug substance of claim 33 wherein for Structure E X is O, R 1 and R 4 are hydrogen.
36 . The drug substance of claim 33 wherein for Structure F at least one X is O and at least one R 1 is hydrogen.
37 . The drug substance of claim 33 wherein for Structure G X is O and R 5 is hydrogen.
38 . The drug substance of claim 33 wherein said organic acid comprises a material selected from the group consisting of pamoic acid, disodium pamoate, di-ammonium pamoate, di-potassium pamoate, lower molecular weight di-alkyl amine pamoate, lower molecular weight di-aryl amine pamoate, lower molecular weight di-alkyl esters of pamoic acid, lower molecular weight di-aryl esters of pamoic acid, lower molecular weight di-alkylacyl O-esters of pamoic acid and lower molecular weight di-arylacyl O-esters of pamoic acid.
39 . The drug substance of claim 33 wherein the organic acid comprises a material selected from the group consisting of ortho isomers of hydroxy naphthoic acid, sodium hydroxy naphthoic acid, ammonium hydroxy naphthoate, potassium hydroxy naphthoate, lower molecular weight alkyl amine salts of hydroxy naphthoic acid, lower molecular weight aryl amine salts of hydroxy naphthoic acid, lower molecular weight alkyl esters of hydroxy naphthoic acid, lower molecular weight aryl esters of hydroxy naphthoic acid, lower molecular weight alkylacyl O-esters of hydroxyl naphthoic acid and lower molecular weight arylacyl O-esters of hydroxyl naphthoic acid.
40 . The drug substance of claim 33 wherein the organic acid is selected from the group consisting of salicylic acid, sodium salicylate, ammonium salicylate, potassium salicylate, lower molecular weight alkyl amine salts of salicylic acid, lower molecular weight aryl amine salts of salicylic acid, lower molecular weight alkyl esters of salicylic acid, lower molecular weight aryl esters of salicylic acid, lower molecular weight alkylacyl O-esters of salicylic acid and lower molecular weight arylacyl O-esters of salicylic acid.
41 . The drug substance of claim 33 wherein said organic acid salt comprises an acid selected from pamoic acid or a synthetic equivalent thereof; salicylic acid or a synthetic equivalent thereof and hydroxy naphthoic acid or a synthetic equivalent thereof.
42 . The drug substance of claim 29 in a form selected from the group consisting of a tablet, a capsule, a caplet, and an oral suspension.
43 . The drug substance of claim 29 wherein said pharmaceutically acceptable organic acid addition salt of an amine containing pharmaceutically active compound has a phase transition temperature of at least 100° C.
44 . The drug substance of claim 29 wherein said pharmaceutically active organic acid addition salt is bio-unavailable when exposed to mucosal membranes and exhibits recovery from aqueous solution at about pH 4.5 of at least 85 weight percent.
45 . The drug substance of claim 29 wherein said pharmaceutically active organic acid addition salt is bio-unavailable when exposed to mucosal membranes and exhibits recovery from aqueous solution at about pH 7.0 of at least 85 weight percent.
46 . The drug substance of claim 29 wherein said pharmaceutically active organic acid addition salt comprises a mixture of physical forms.
47 . The drug substance of claim 46 wherein said mixture of physical forms comprises an amorphous material and at least one polymorph.
48 . The drug substance of claim 29 designed for immediate release in the gastrointestinal tract and for essentially non-release in the mucosal membranes.
49 . The drug substance of claim 29 wherein said pharmaceutically active organic acid addition salt of an amine containing pharmaceutically active compound is selected from the group consisting of phentermine pamoate, ephedrine pamoate, pseudophedrine pamoate, benzphetamine pamoate, imipramine pamoate, phentermine xinafoate, ephedrine xinafoate, pseudophedrine xinafoate, benzphetamine xinafoate, imipramine xinafoate, phentermine salicylate, ephedrine salicylate, pseudophedrine salicylate, benzphetamine salicylate and imipramine salicylate.
50 . The drug substance of claim 29 administered for at least one purpose selected from anti-convulsant, anti-depressant, analgesic, anesthetic, anxiolytic, psychotropic, hallucinogenic, hypnotic, anorexic, cough, cold and sinus.
51 . The drug substance of claim 29 administered by one method delivery presentation selected from solid oral delivery, parenteral delivery, transdermal delivery and inhalation delivery.
52 . A drug substance comprising an organic acid addition salt of an amine containing pharmaceutically active compound used to treat a combination of two or more therapeutic ailments, at least one of which is drug abuse.
53 . The drug substance of claim 52 wherein said pharmaceutically active compound comprises a material selected from acetaminophen, caffeine, acetorphine, acetylmethadol, allylprodine, alphacetylmethadol, bufotenine, dextromoramide, diethyltryptamine, etorphine, heroin, ibogaine, ketobemidone, lysergic acid diethylamide, mescaline, methaqualone, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, N-ethyl-1-phenylcyclohexylamine, peyote, 1-(1-phenylcyclohexyl)pyrrolidine, psilocybin, psilocin, 1-{1-(2-thienyl)-cyclohexyl}-piperidine, alphaprodine, anileridine, cocaine, dextropropoxyphene, diphenoxylate, ethylmorphine, glutethimide, hydrocodone, hydromorphone, levo-alphaacetylmethadol, levorphanol, meperidine, methadone, morphine, opium, oxycodone, oxymorphone, poppy straw, thebaine, amphetamine, methamphetamine, methylphenidate, phencyclidine, codeine, benzphetamine, ketamine, alprazolam, chlorodiazepoxide, clorazepate, diethylpropion, fenfluramine, flurazepam, halazepam, lorazepam, mazindol, mebutamate, midazolam, oxazepam, pemoline, pentazocine, phentermine, prazepam, quazepam, temazepam, triazolam, zolpidem, and buprenorphine.
54 . The drug substance of claim 52 wherein said amine containing pharmaceutically active material is selected from the group consisting of opiates, morphinoids, amphetamines, compounds containing a piperidine or substituted piperidine sub-structure within a molecule, benzodiazapines, benzazepines, tropinoids and compounds containing a phenethyl amine or substituted phenethylamine sub-structure within a molecule.
55 . The drug substance of claim 46 wherein said organic acid addition salt is selected from:
wherein R 1 -R 4 are independently selected from H, alkyl of 1-6 carbons, adjacent groups may be taken together to form a cyclic alkyl, cyclic alkyl-aryl or cyclic aryl moiety;
R 5 is selected from H, or an alkali earth cation;
R 6 and R 7 are independently selected from H, alkyl of 1-6 carbons, an alkali earth cation, and aryl of 6 to 12 carbons, in a number sufficient to complete the valence bonding of X, and
wherein X is selected from nitrogen, oxygen or sulfur.
56 . The drug substance of claim 55 wherein said organic acid addition salt is selected from the group consisting of:
wherein R 5 , R 6 and R 7 remain as defined for Structure A;
wherein X, R 5 , R 6 and R 7 remain as defined above for Structure A;
wherein X, R 1 , R 2 , R 5 , R 6 and R 7 remain as defined above for Structure A;
wherein X, R 1 , R 4 , R 5 , R 6 and R 7 remain as defined above for Structure A;
wherein X, R 1 , R 5 , R 6 and R 7 are independently defined as above for Structure A; and
wherein X, R 5 , R 6 and R 7 are independently defined as above for Structure A.
57 . The drug substance of claim 56 wherein for Structure D X is O; R 1 and R 2 are hydrogen.
58 . The drug substance of claim 56 wherein for Structure E X is O, R 1 and R 4 are hydrogen.
59 . The drug substance of claim 56 wherein for Structure F at least one X is O and at least one R 1 is hydrogen.
60 . The drug substance of claim 56 wherein for Structure G X is O and R 5 is hydrogen.
61 . The drug substance of claim 56 wherein said organic acid comprises a material selected from the group consisting of pamoic acid, disodium pamoate, di-ammonium pamoate, di-potassium pamoate, lower molecular weight di-alkyl amine pamoate, lower molecular weight di-aryl amine pamoate, lower molecular weight di-alkyl esters of pamoic acid, lower molecular weight di-aryl esters of pamoic acid, lower molecular weight di-alkylacyl O-esters of pamoic acid and lower molecular weight di-arylacyl O-esters of pamoic acid.
62 . The drug substance of claim 56 wherein the organic acid comprises a material selected from the group consisting of ortho isomers of hydroxy naphthoic acid, sodium hydroxy naphthoic acid, ammonium hydroxy naphthoate, potassium hydroxy naphthoate, lower molecular weight alkyl amine salts of hydroxy naphthoic acid, lower molecular weight aryl amine salts of hydroxy naphthoic acid, lower molecular weight alkyl esters of hydroxy naphthoic acid, lower molecular weight aryl esters of hydroxy naphthoic acid, lower molecular weight alkylacyl O-esters of hydroxyl naphthoic acid and lower molecular weight arylacyl O-esters of hydroxyl naphthoic acid.
63 . The drug substance of claim 56 wherein the organic acid is selected from the group consisting of salicylic acid, sodium salicylate, ammonium salicylate, potassium salicylate, lower molecular weight alky amine salts of salicylic acid, lower molecular weight aryl amine salts of salicylic acid, lower molecular weight alkyl esters of salicylic acid, lower molecular weight aryl esters of salicylic acid, lower molecular weight alkylacyl O-esters of salicylic acid and lower molecular weight arylacyl O-esters of salicylic acid.
64 . The drug substance of claim 56 wherein said organic acid salt comprises an acid selected from pamoic acid or a synthetic equivalent thereof; salicylic acid or a synthetic equivalent thereof and hydroxy naphthoic acid or a synthetic equivalent thereof.
65 . The drug substance of claim 52 in a form selected from the group consisting of a tablet, a capsule, a caplet, and an oral suspension.
66 . The drug substance of claim 52 wherein said pharmaceutically acceptable organic acid addition salt of an amine containing pharmaceutically active compound has a phase transition temperature of at least 100° C.
67 . The drug substance of claim 52 wherein said pharmaceutically active organic acid addition salt is bio-unavailable when exposed to mucosal membranes and exhibits recovery from aqueous solution at about pH 4.5 of at least 85 weight percent.
68 . The drug substance of claim 52 wherein said pharmaceutically active organic acid addition salt is bio-unavailable when exposed to mucosal membranes and exhibits recovery from aqueous solution at about pH 7.0 of at least 85 weight percent.
69 . The drug substance of claim 52 wherein said pharmaceutically active organic acid salt comprises a mixture of physical forms.
70 . The drug substance of claim 69 wherein said mixture of physical forms comprises an amorphous material and at least one polymorph.
71 . The drug substance of claim 69 designed for immediate release in the gastrointestinal tract and for essentially non-release in the mucosal membranes.
72 . The drug substance of claim 52 wherein said pharmaceutically active organic acid addition salt of an amine containing pharmaceutically active compound is selected from the group consisting of phentermine pamoate, ephedrine pamoate, pseudophedrine pamoate, benzphetamine pamoate, imipramine pamoate, phentermine xinafoate, ephedrine xinafoate, pseudophedrine xinafoate, benzphetamine xinafoate, imipramine xinafoate, phentermine salicylate, ephedrine salicylate, pseudophedrine salicylate, benzphetamine salicylate and imipramine salicylate.
73 . The drug substance of claim 52 administered for at least one purpose selected from pain management, anti-convulsant, anti-depressant, analgesic, anesthetic, anxiolytic, psychotropic, hallucinogenic, hypnotic, anorexic, cough, cold and sinus.
74 . The drug substance of claim 52 administered by one method delivery presentation selected from solid oral delivery, parenteral delivery, transdermal delivery and inhalation delivery.
75 - 288 . (canceled)
289 . An organic acid addition salt of amine-containing pharmaceutically active compounds wherein the organic acid comprises a compound of Formula A:
wherein R 1 -R 4 are independently selected from H, alkyl of 1-6 carbons, adjacent groups may be taken together to form a cyclic alkyl, cyclic alkyl-aryl or cyclic aryl moiety;
R 5 is selected from H, or an alkali earth cation;
R 6 is selected from H, alkyl of 1-6 carbons, an alkali earth cation, and aryl of 6 to 12 carbons, in a number sufficient to complete the valence bonding of X, and
wherein X is selected from nitrogen, oxygen or sulfur.
290 - 309 . (canceled)
310 . Organic acid addition salts of amine containing pharmaceutically active compounds selected for their targeted release characteristic in the gastro intestinal tract and bio-unavailability in mucosal membranes, and formulated into a drug product wherein said amine containing pharmaceutically active compounds can not be directly isolated.
311 - 336 . (canceled)
337 . A tamper resistant oral dosage drug product comprising an organic acid salt of an amine-containing pharmaceutically active compound formulated wherein said organic acid and said amine-containing pharmaceutically active compound can not be directly isolated.
338 - 381 . (canceled)
382 . A pharmaceutically active compound comprising the organic acid addition salt of an amine-containing pharmaceutically active material wherein said compound is essentially bio-unavailable when exposed to mucosal membranes and exhibits recovery from aqueous solution at pH 4.5 of at least 85 weight percent.
383 - 403 . (canceled)
404 . A pharmaceutically active compound comprising the organic acid addition salt of an amine-containing pharmaceutically active material wherein said compound is essentially bio-unavailable when exposed to human mucosal membranes and exhibits recovery from aqueous solution at pH 7.0 of at least 85 weight percent.
405 - 427 . (canceled)
428 . A pharmaceutically active compound comprising an organic acid addition salt of an amine-containing pharmaceutically active compound wherein said compound is essentially bio-unavailable when exposed to mucosal membranes unless processed by the steps of:
a) dissolution in an aqueous solution of pH greater than 8; b) extraction of the active pharmaceutical ingredient into a water immiscible solvent; c) separation of the aqueous layer from the solvent; d) washing of the solvent layer with an aqueous solution of pH greater than 8; and e) drying the solvent layer to remove traces of water.
429 - 455 . (canceled)
456 . A pharmaceutically active compound comprising an organic acid addition salt of an amine-containing pharmaceutically active compound wherein said compound is essentially bio-unavailable when exposed to mucosal membranes unless processed by the steps of:
a. dissolution in an aqueous solution of pH greater than about 1; b. filtration of the precipitated organic acid; c. adjustment of the filtrate to a pH of about 8; d. addition of a water immiscible solvent in which the pharmaceutically active compound is soluble; e. separation of the aqueous layer from the solvent; f. washing of the solvent layer with an aqueous solution of pH greater than 8; and g. drying the solvent layer to remove traces of water.
457 - 507 . (canceled)
508 . A drug substance comprising a pharmaceutically acceptable organic acid addition salt of an amine containing pharmaceutically active compound useful for the treatment of a therapeutic ailment administration and exhibiting anti-abuse properties when employed in non-therapeutic administration wherein said pharmaceutically active compound comprises a material selected from acetaminophen, caffeine, acetorphine, acetylmethadol, allylprodine, alphacetylmethadol, bufotenine, dextromoramide, diethyltryptamine, etorphine, heroin, ibogaine, ketobemidone, lysergic acid diethylamide, mescaline, methaqualone, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, N-ethyl-1-phenylcyclohexylamine, peyote, 1-(1-phenylcyclohexyl)pyrrolidine, psilocybin, psilocin, 1 -{1-(2-thienyl)-cyclohexyl}-piperidine, alphaprodine, anileridine, cocaine, dextropropoxyphene, diphenoxylate, ethylmorphine, glutethimide, hydrocodone, hydromorphone, levo-alphaacetylmethadol, levorphanol, meperidine, methadone, morphine, opium, oxycodone, oxymorphone, poppy straw, thebaine, amphetamine, methamphetamine, methylphenidate, phencyclidine, codeine, benzphetamine, ketamine, alprazolam, chlorodiazepoxide, clorazepate, diethylpropion, fenfluramine, flurazepam, halazepam, lorazepam, mazindol, mebutamate, midazolam, oxazepam, pemoline, pentazocine, phentermine, prazepam, quazepam, temazepam, triazolam, zolpidem, and buprenorphine and wherein said organic acid addition salt comprises a material selected from the group consisting of pamoic acid, disodium pamoate, di-ammonium pamoate, di-potassium pamoate, lower molecular weight di-alkyl amine pamoate, lower molecular weight di-aryl amine pamoate, lower molecular weight di-alkyl esters of pamoic acid, lower molecular weight di-aryl esters of pamoic acid, lower molecular weight di-alkylacyl O-esters of pamoic acid and lower molecular weight di-arylacyl O-esters of pamoic acid.
509 . The drug substance of claim 1 comprising oxycodone pamoate.
510 . A drug substance comprising a pharmaceutically acceptable organic acid addition salt of an amine containing pharmaceutically active compound useful for the treatment of an ailment by therapeutic administration and exhibiting anti-abuse properties when employed in non-therapeutic administration;
wherein said non-therapeutic administration is selected from mucosal membrane bio-unavailability, non-permeability in mucosal membranes, essentially no dissolution in the mucosal membranes, non-efficacy for mucosal membranes and non-release properties when delivered to mucosal membranes; wherein said pharmaceutically active compound comprises a material selected from acetaminophen, caffeine, acetorphine, acetylmethadol, allylprodine, alphacetylmethadol, bufotenine, dextromoramide, diethyltryptamine, etorphine, heroin, ibogaine, ketobemidone, lysergic acid diethylamide, mescaline, methaqualone, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, N-ethyl-1-phenylcyclohexylamine, peyote, 1-(1-phenylcyclohexyl)pyrrolidine, psilocybin, psilocin, 1-{1-(2-thienyl)-cyclohexyl}-piperidine, alphaprodine, anileridine, cocaine, dextropropoxyphene, diphenoxylate, ethylmorphine, glutethimide, hydrocodone, hydromorphone, levo-alphaacetylmethadol, levorphanol, meperidine, methadone, morphine, opium, oxycodone, oxymorphone, poppy straw, thebaine, amphetamine, methamphetamine, methylphenidate, phencyclidine, codeine, benzphetamine, ketamine, alprazolam, chlorodiazepoxide, clorazepate, diethylpropion, fenfluramine, flurazepam, halazepam, lorazepam, mazindol, mebutamate, midazolam, oxazepam, pemoline, pentazocine, phentermine, prazepam, quazepam, temazepam, triazolam, zolpidem, imipramine and buprenorphine; and wherein said organic acid comprises a material selected from the group consisting of pamoic acid, disodium pamoate, di-ammonium pamoate, di-potassium pamoate, lower molecular weight di-alkyl amine pamoate, lower molecular weight di-aryl amine pamoate, lower molecular weight di-alkyl esters of pamoic acid, lower molecular weight di-aryl esters of pamoic acid, lower molecular weight di-alkylacyl O-esters of pamoic acid and lower molecular weight di-arylacyl O-esters of pamoic acid.
511 . The drug substance of claim 510 wherein said pharmaceutically active compound is oxycodone.
512 . The drug substance of claim 511 wherein said organic acid is pamoic acid.
513 . A drug substance comprising a pharmaceutically acceptable organic acid addition salt of an amine containing pharmaceutically active compound useful for the treatment of an ailment by therapeutic administration and exhibiting anti-abuse properties when employed in non-therapeutic administration;
wherein said non-therapeutic administration is selected from mucosal membrane bio-unavailability, non-permeability in mucosal membranes, essentially no dissolution in the mucosal membranes, non-efficacy for mucosal membranes and non-release properties when delivered to mucosal membranes; wherein said pharmaceutically active compound comprises a material selected from acetaminophen, caffeine, acetorphine, acetylmethadol, allylprodine, alphacetylmethadol, bufotenine, dextromoramide, diethyltryptamine, etorphine, heroin, ibogaine, ketobemidone, lysergic acid diethylamide, mescaline, methaqualone, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, N-ethyl-1-phenylcyclohexylamine, peyote, 1-(1-phenylcyclohexyl)pyrrolidine, psilocybin, psilocin, 1-{1-(2-thienyl)-cyclohexyl}-piperidine, alphaprodine, anileridine, cocaine, dextropropoxyphene, diphenoxylate, ethylmorphine, glutethimide, hydrocodone, hydromorphone, levo-alphaacetylmethadol, levorphanol, meperidine, methadone, morphine, opium, oxymorphone, poppy straw, thebaine, amphetamine, methamphetamine, methylphenidate, phencyclidine, codeine, benzphetamine, ketamine, alprazolam, chlorodiazepoxide, clorazepate, diethylpropion, fenfluramine, flurazepam, halazepam, lorazepam, mazindol, mebutamate, midazolam, oxazepam, pemoline, pentazocine, phentermine, prazepam, quazepam, temazepam, triazolam, zolpidem, imipramine and buprenorphine; and wherein said organic acid comprises a material selected from the group consisting of pamoic acid, disodium pamoate, di-ammonium pamoate, di-potassium pamoate, lower molecular weight di-alkyl amine pamoate, lower molecular weight di-aryl amine pamoate, lower molecular weight di-alkyl esters of pamoic acid, lower molecular weight di-aryl esters of pamoic acid, lower molecular weight di-alkylacyl O-esters of pamoic acid and lower molecular weight di-arylacyl O-esters of pamoic acid.
514 . A drug substance comprising a pharmaceutically acceptable organic acid addition salt of an amine containing pharmaceutically active compound useful for the treatment of an ailment by therapeutic administration and exhibiting anti-abuse properties when employed in non-therapeutic administration;
wherein said non-therapeutic administration is selected from mucosal membrane bio-unavailability, non-permeability in mucosal membranes, essentially no dissolution in the mucosal membranes, non-efficacy for mucosal membranes and non-release properties when delivered to mucosal membranes; wherein said pharmaceutically active compound comprises a material selected from acetaminophen, caffeine, acetorphine, acetylmethadol, allylprodine, alphacetylmethadol, bufotenine, dextromoramide, diethyltryptamine, etorphine, heroin, ibogaine, ketobemidone, lysergic acid diethylamide, mescaline, methaqualone, 3,4-methylenedioxyamphetamine, 3,4-methylenedioxymethamphetamine, N-ethyl-1-phenylcyclohexylamine, peyote, 1-(1-phenylcyclohexyl)pyrrolidine, psilocybin, psilocin, 1-{1-(2-thienyl)-cyclohexyl}-piperidine, alphaprodine, anileridine, cocaine, dextropropoxyphene, diphenoxylate, ethylmorphine, glutethimide, hydrocodone, hydromorphone, levo-alphaacetylmethadol, levorphanol, meperidine, methadone, morphine, opium, oxycodone, oxymorphone, poppy straw, thebaine, amphetamine, methamphetamine, methylphenidate, phencyclidine, codeine, benzphetamine, ketamine, alprazolam, chlorodiazepoxide, clorazepate, diethylpropion, fenfluramine, flurazepam, halazepam, lorazepam, mazindol, mebutamate, midazolam, oxazepam, pemoline, pentazocine, phentermine, prazepam, quazepam, temazepam, triazolam, zolpidem, imipramine and buprenorphine; and wherein said organic acid comprises a material selected from the group consisting of disodium pamoate, di-ammonium pamoate, di-potassium pamoate, lower molecular weight di-alkyl amine pamoate, lower molecular weight di-aryl amine pamoate, lower molecular weight di-alkyl esters of pamoic acid, lower molecular weight di-aryl esters of pamoic acid, lower molecular weight di-alkylacyl O-esters of pamoic acid and lower molecular weight di-arylacyl O-esters of pamoic acid.
515 . The drug substance of claim 1 further comprising at least one additional anti-abuse formulation selected from incorporation of an antagonist, incorporation of a prodrug; a coating and a matrix.Cited by (0)
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