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(12) United States Patent (10) Patent No.: US 8,093,300 B2 Lederman (45) Date of Patent: Jan USOO8093300B2 (12) United States Patent (10) Patent No.: US 8,093,300 B2 Lederman (45) Date of Patent: Jan. 10, 2012 (54) COMPOSITIONS AND METHODS FOR WO WO96,354.25 11, 1996 INCREASING COMPLIANCE WITH WO WO96,37199 11, 1996 WO WO99,21540 5, 1999 THERAPESUSING ALDEHYDE WO WOOOf 45846 8, 2000 DEHYDROGENASE INHIBITORS AND WO WOOOf71109 11, 2000 TREATING ALCOHOLISM WO WOO3,0395.25 5, 2003 (75) Inventor: Seth Lederman, New York, NY (US) OTHER PUBLICATIONS NIAAA “Etiology and Natural history of alcoholism.” http://pubs. (73) Assignee: Krelle Pharmaceuticals, Inc., Saddle niaaa.nih.gov/publications/social/Module2Etiology&NaturalHis Brook, NJ (US) tory/Module2.html.* DeMaster et al., Biochem. Biophy's. Res. Com. 107:1333-1339 (*) Notice: Subject to any disclaimer, the term of this (1982). patent is extended or adjusted under 35 Ferguson, Canad M.A.J. 74:793-795 (1956). U.S.C. 154(b) by 566 days. Hart, et al., Alcohol 7: 165 (1990). Jimerson, D.C., et al., Biomed. Mass.Spectrom. 8:256-259 (1981). (21) Appl. No.: 12/145,792 Keung, Chemico-Bio. Int. 130-132:919-930 (2001). Keung, W.M. et al., Proc. Natl. Acad. Sci. USA95:2198-2203 (1998). (22) Filed: Jun. 25, 2008 Kick, S., Hospital Practice 95-106(1999). Madan, et al., Drug Metab. Dispos. 23: 1153-1162 (1995). (65) Prior Publication Data Major, L.F., et al., J. Neurochem. 39:229-231 (1979). McRae et al., “Alcohol and Substance Abuse,” in: Advances in the US 2009/OOO5441 A1 Jan. 1, 2009 Pathophysiology and Treatment of Psychiatric Disorders: Implica tions for Internal Medicine, 85(3):779-801 (2001). Related U.S. Application Data Murphy, D.L., et al., Biochem. Med. 16:254-265 (1976). Murphy, D.L., et al., Clinical Pharmacology in Psychiatry,3"Series, (62) Division of application No. 10/287,153, filed on Nov. Eds. Dahl, Gram, Paul, and Potter, Springer-Verlag: 1987. 4, 2002. Murphy, D.L., et al., Psychopharm. 62:129-132 (1979). (60) Provisional application No. 60/338,901, filed on Nov. Reilly, Lancet 911-912 (1976). 5, 2001. Sinclair et al., Adv. Exp. Med. Biol. 132:481-487 (1980). Swift, R.M., New England J. Med. 340: 1482-1490 (1999). (51) Int. C. Youricket al., Alcohol 4:463 (1987). A6 IK3I/35 (2006.01) Youricket al., Biochem. Pharmacol. 38:413 (1989). A6 IK3I/6 (2006.01) International Search Report, International Application No. PCT/ USO2/35376 of Jun. 23, 2004. (52) U.S. C. ......... 514/654; 514/649; 514/599; 514/811 Swift, R.M. (May 13, 1999). Drug Therapy for Alcohol Dependence. (58) Field of Classification Search .................. 514/649, The New England Journal of Medicine 34019), 1482-1490. 514/654.599, 811 Krystal, J. H., Cramer, J. A., Krol, W. F., Kirk, G. F. & Rosenheck, R. See application file for complete search history. A. (2001). Naltrexone in the Treatment of Alcohol Dependence. The New England Journal of Medicine, 345, 1734-1739. (56) References Cited Hermos, J. A. Young, M. M. Gagnon, D. R. & Fiore, L. D. (2004). Patterns of dispensed disulfiram and naltrexone for alcoholism treat U.S. PATENT DOCUMENTS ment in a veteran patient population. Alcohol Clin. Exp.Res., 28. 2,567,814 A 9, 1951 Jacobsen et al. 1229-1235. 3,155,584 A 11, 1964 Martin Garbutt, J. C., West, S. L., Carey, T. S., Lohr, K. N. & Crews, F.T. 4,076,840 A 2f1978 Carlsson et al. (1999). Pharmacological treatment of alcohol dependence: a review 4,565,689 A 1, 1986 Revici of the evidence. JAMA, 281, 1318-1325. 4,678,809 A 7/1987 Phillips Berglund, M., Thelander, S., Salaspuro, M., Franck, J., Andreasson, 4,861,800 A 8/1989 Buyske S., & Ojehagen, A. (2003). Pharmacological treatment of alcohol 4,868,218 A 9/1989 Buyske dependence. Alcohol Clin.Exp.Res. 27(10). 1645-1656. 5,128,145 A 7/1992 Edgren et al. 5, 190,763. A 3/1993 Edgren et al. (Continued) 5, 192,550 A 3/1993 Edgren et al. 5,204,369 A 4, 1993 Vallee et al. 5,242.950 A 9/1993 Hastings Primary Examiner — Shengjun Wang 5,886,028 A 3, 1999 Vallee et al. 5,952.388 A 9, 1999 LOScher (74) Attorney, Agent, or Firm — Kelley Drye & Warren LLP 6,121,010 A 9, 2000 Vallee et al. 6,239,181 B1 5, 2001 Bobotas 6.255.497 B1 7/2001 Vallee et al. (57) ABSTRACT 6,500,868 B2 12/2002 Bobotas 2003, OO87814 A1 5, 2003 Lederman Compositions and methods for treating, preventing, or reduc ing alcoholism, in particular methods for increasing patient FOREIGN PATENT DOCUMENTS compliance with therapies that require the intake of an ALDH EP A 404807 10, 1989 EP A 509761 4f1992 inhibitor comprising the step of administering a monoamine EP O520325 A1 6, 1992 oxidase B inhibitor. EP A 593807 10, 1992 WO WO 92,05787 4f1992 WO WO92,21333 12/1992 6 Claims, No Drawings US 8,093,300 B2 Page 2 OTHER PUBLICATIONS Yasar, S. & Bergman, J. (1994). Amphetamine-like effect of 1-deprenyl (selegiline) in drug discrimination studies. Clin. DeLuca, A. (1996). Medications that can Help Us Avoid Relapse in Pharmacol. Ther:, 56,768-773. Early Recovery. Addiction, Pain, and Public Health website Wu, W. R. & Zhu, X. Z. (1999). The amphetamine-like reinforcing (doctordeluca.com) On-line). Available: http://www.doctordeluca. effect and mechanism of L-deprenyl on conditioned place preference com/Documents/SobrietyMeds 11-1.htm. in mice. Eur.J Pharmacol., 364, 1-6. Schultz, W. (1998). Predictive reward signal of dopamine neurons. J Yasar, S., Schindler, C. W., Thorndike, E. B., & Goldberg, S. R. Neurophysiol. 80.1-27. (1994). Evaluation of deprenyl for cocaine-like discriminativestimu Bowirrat, A. & Oscar-Berman, M. (2004). Relationship between dopaminergic neurotransmission, alcoholism, and reward deficiency lus effects in rats. Eur:J Pharmacol., 259, 243-250. syndrome. Am J Med Genet. Fuller, R.K., Branchey, L. Brightwell, D.R., Derman, R.M., Emrick, Cohen, C., Curet, O. Perrault, G., & Sanger, D.J. (1999). Reduction C. D., Iber, F. L., et al. (1986). Disulfiram treatment of alcoholism. A of oral ethanol self-administration in rats by monoamine oxidase VeteransAdministration cooperative study. JAMA. The Journal of the inhibitors. Pharmacol. Biochem. Behav., 64, 535-539. American Medical Association, 256, 1449-1455. Porsolt, R. D., Pawelec, C. Roux, S. & Jalfre, M. (1984). Discrimi Fuller, R. K. & Gordis, E. (2004). Does disulfiram have a role in nation of the amphetamine cue. Effects of A, B and mixed type alcoholism treatment today? Addiction, 99, 21-24. inhibitors of monoamine oxidase. Neuropharmacology, 23,569-573. Hughes, J. C. & Cook, C. C. (1997). The efficacy of disulfiram: a Oldfield, V., et al., “Oxycodone/Ibuprofen combination tabled: . .” review of outcome studies. Addiction, 92, 381-395. Drugs 2005 65(16): 2337-2354. Glover, V. Elsworth, J. D., & Sandler, M. (1980). Dopamine oxida Litkowski, L.J. et al., “Analgesic Efficacy and Tolerability of tion and its inhibition by (-)-deprenyl in man. J Neural Transm. Oxycodone 5 mg. .” Clin. Ther. Apr. 2005; 27(4): 418-429. Suppl. 163-172. Kapil, R., “Pharmacokinetic Properties of Combination Oxycodoen Houtsmuller, E.J., Thornton, J. A., & Stitzer, M. L. (2002). Effects of plus Racemic Ibuprofen . .” Clin. Ther. Dec. 2004; 26(12): 2015 Selegiline (L-deprenyl) during Smoking and short-term abstinence. 2025. Psychopharmacology (Berl), 163, 213-220. Van, D.T. et al., "Combination Oxycodone 5 mg/Ibuprofen 400 Houtsmuller, E. J. Notes, L. D., Newton, T., van, S.N., Chiang, N., mg . .” Clin. Ther. Dec. 2004, 26(12): 2003-2014. Elkashef, A. et al. (2004). Transdermal selegiline and intravenous Zelcer, S., et al., “Selective Potentiation of Opioid Analgesia . .” cocaine: safety and interactions. Psychopharmacology (Berl), 172, Brain Res., Apr. 8, 2005: 1040(1-2): 151-156. 31-40. Sachs, C. “Oral Analgesics For Acute Nonspecific Pain.” Am. Fam. Tariot, P.N., et al., (1987), L-deprenyl in Alzheimer's disease, Pre Physician, Mar. 1 2005, 71(5);913-918. liminary evidence for behaviroral change with monoamine oxidase B Singla, N., et al., “Combination Oxycodone 5 mg/Ibuprofen 400 inhibition, Archives of General Psychiatry, vol. 44, pp. 427-433. mg . .” Clin. Ther. Jan. 2005, 27(1): 45-57. Koob. G. F. (2003), "Alcoholism: Allostasis and Beyond.” Alcohol Huynk, M.P. et al., “Current Concepts in Acute Pain Management.” Clin. Exp. Res., 27, pp. 232-243. J. Calif Dent Assoc. May 2003; 31(5): 419-427. Physician's Desk Reference 51 Edition 1997, p. 2802-2803. Palangio, M., et al., “Combination Dydrocodone and Ibuprofen....” U.S. Appl. No. 60/338,901, Lederman. Clin. Ther. Jan. 2002; 24(1): 87-99. Baker, J. et al., 2007 Disulfiram effects on responses to intravenous Barkin, R.L. "Acetaminophen, Aspirin, or Ibuprofen . .” Am. J. cocaine administration, Drug and Alcohol Dependence 87,202-209. Ther. Nov. 2001; 8(6): 433-442. Bartzolis, Georgeet. al., 1999 Selegiline Effects on Cocaine-Induced Palangio, M., et al., “Combination Hydrocodone and Ibuprofen....” Changes in Medial Temporal Lobe Metabolism and Subjective Rat Clin. Ther. May 2000; 22(5): 600-612. ings of Euphoria, Neuropsychopharmacology 20, No. 6 published by Tobias, J.D., “WeakAnalgesics and Nonsteroidal....” Pediatric Clin. Elsevier Science. North Am. Jun. 2000; 47(3): 527-543. Singh, R. et al., 1995 Acute Organic Brain Syndrome after Dionne, R.A., “Additive Analgesic Effects of Oxycodone....” J. Oral Fluoxetine Treatment Am. J. Psychiatry 152: 2 p. 295. Maxillofac Surg, Jun. 1999, 57(6): 673-678. Carroll, K. et al., 1998 Treatment of Cocaine and Alcohol Depen Stambaugh, J.E. et al., “The Combination of Ibuprofen and dence with Psychotherapy and Disulfiram in Addiction 93(5), 713 Oxycodone? Acetaminophen In the Management of Chronic Cancer 728.
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