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Title:
Pharmaceutic formulation for the treatment of alcoholism
Document Type and Number:
United States Patent 5519017

Abstract:
Galanthamine and the pharmaceutically suitable acid addition salts thereof can be used for the treatment of alcoholism; these compounds are released from adequate pharmaceutic formulations which are administered, e.g., orally, transdermally, or otherwise parenterally, in a continuous and controlled manner.
Inventors:
Opitz, Klaus (Munster, DE)
Application Number:
08/238550
Publication Date:
05/21/1996
Filing Date:
05/05/1994
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Referenced by:
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Assignee:
LTS Lohmann Therapie-Systeme GmbH + Co. KG (Neuwied, DE)
Hefa-Frenon Arzneimittel GmbH & Co. KG (Werne, DE)
Primary Class:
514/215
Other Classes:
514/811
International Classes:
A61K9/70; A61K31/55; A61K31/55
Field of Search:
514/215, 514/811
US Patent References:
4663318Method of treating Alzheimer's diseaseMay, 1987Davis514/252
4761429Enkephalinase and endorphinase inhibitors as anti-craving compositionsAugust, 1988Blum et al.514/561
4777173Method for treatment of alcohol abuseOctober, 1988Shrotryia et al.514/561
4954504N.sub.9 -cyclopentyl-substituted adenine derivatives having adenosine-2 receptor stimulating activitySeptember, 1990Chen et al.514/265
5152994Rapid method for interrupting or attenuating poly-drug dependency syndromesOctober, 1992Lotsof424/436
Other References:
Bickel, U., Thomsen, T., Weber, W., Fischer, J. P., Bachus, R., Nitz, M., Kewitz, H.: "Pharmacokinetics of galanthamine in humans and corresponding cholinesterase inhibition." Clin. Pharmacol. Ther., 50: 420-28 (1991).
Cozanitis, D. A., Toivakka, E.: "Treatment of respiratory depression with the anticholinesterase drug galanthamine hydrobromide." Aneasthesia, 29: 581-84 (1974).
Cozanitis, D. A.: "Galanthamine hydrobromide, a longer acting anticholinesterase drug, in the treatment of the central effects of Scopolamine (Hyoscine)." Anaesthesist, 26: 649-50 (1977).
Cozanitis, D. A., van de Pol, F., van Wezel, H., Crul, J. F.: "Antagonistic activity of galanthamine on constant infusion of pancuronium in rats." Experientia, 37: 1326-27 (1981).
Cozanitis, D. A., Friedmann, T., Furst, S.: "Study of the analgesic effects of Galanthamine, a Cholinesterase Inhibitor." Archives Intern. de Pharmacodynamie et de Therapie, 266: 229-38 (1983).
Foitzik, H., Lawin, P.: "Klinische Erfahrungen mit Galanthamin (Nivalin) als Antidot von Pancuronium." Z. prakt. Anasth., 7: 203-7 (1972).
Gopel, W., Bertram, W.: "Erfahrungen mit Nivalin in der neurologischen Therapie." Psychiat. Neurol. med. Psychol., 23: 712-18 (1971).
Mayrhofer, O.: "Erfahrungen mit Galanthamin (Nivalin als Antagonist der Relaxantien vom Curaretyp." Bull. schweiz. Akad. med. Wiss., 23: 48-52 (1967).
Mihailova, D., Yamboliev, I., Zhivkova, Z., Tencheva, J., Jovovich, V.: "Pharmacokinetics of Galanthamine Hydrobromide after single subcutaneous and oral dosage in humans." Pharmacology, 39: 50-58 (1989).
Naranjo, C. A., Sellers, E. M. (Ed.): "Drug treatments for alcoholism: The need for innovation." in: Research Advances in New Psychoparm. Treatments for Alcoholism, 1-9 Elsevier Science Publishers B.V. (1985).
Paskov, D. S.: "Galanthamine." in: New Neuromuscular Blocking Agents, 31:653-72 Springer-Verlag Berlin, Heidelberg, New York, Tokyo (Ed.) (1986).
Snorrason, E., Stefansson, J. G.: "Galanthamine hydrobromide in mania." Lancet, 337: 557 (1991).
Stojek, A., Napierala, K.: "Physostigmine in eyedrops decreases craving for alcohol in early with withdrawal treated with carbamazepine." Materia Medica Polona, 4: 249-54 (1986).
Tanahashi, T., Poulev, a., Zenk, M. H.: "Radioimmunoassay for the quantitative determination of Galanthamine." Planta Medica, 56: 77-81 (1990).
Tencheva, J., Yamboliev, I., Zhivkova, Z.: "Reversed-phase liquid chromatography for the determination of galanthamine and its metabolites in human plasma and urine." Journal of Chromatography, 421: 396-400 (1987).
Thomsen, T., Bickel, U., Fischer, J. P., Kewitz, H.: "Stereoselectivity of cholinesterase inhibition by galanthamine and Eur. J. Clin. Pharmacol. and tolerance in humans" 39: 603-5 (1990).
Thomsen, T., Zendeh, B., Fischer, J. P., Kewitz, H.: "In vitro effects of various cholinesterase inhibitors on acetyl-- and butyrylchloinesterase of healthy volunteers." Biochemical Pharmacology, 41: 139-41 (1991).
Thomsen, T., Kaden, B. Fischer, J. P., Bickel, U., Barz, H., Gusztony, G., Cervos-Navarro, J. Kewitz, H.: "Inhibition of Acetylcholinesterase activity in human brain tissue and erythrocytes by Galanthamine, Physostigmine and Tacrine." Eur. J. Clin. Chem. Clin. Biochem., 29: 487-92 (1991).
Thomsen, T., Kewitz, H.: "Selective inhibition of human acetylcholinsterase by Galanthamine in vitro and in vivo." Life Sciences, 46: 1553-58 (1990).
Vlahov, R., Krikorian, D., Spassov, G., Chinova, M., Vlahov, I., Parushev, S., Snatzke, G., Ernst, L., Kieslich, K., Abraham, W.-R., Sheldrick, W. S.: "Synthesis of Galanthamine and related alkaloids-New approaches." Tetrahedron, 45: 3329-45 (1989).
J. Ruprecht et al: "The involvement of the central cholinergic and endorphinergic systems in the nitrous oxide withdrawal syndrome in mice." Anesthesiology, V. 58, No. 6, 1983, pp. 524-526.
Haboubi, N. A. et al, Ann. Clin. Biochem. 23(4): 458-62, 1986.
Hsu, L. L. et al., Alcohol Clin Exp Res 7(3); 249-55, 1983.
Stojek, A. et al., BR J Addict 82(8): 927-30; 1907.
Daunderer, M., Fortschr Med 101 (17); 778-80, 1983.
Power, J. S. et al.; J. Clin. Pharmacol. 21(1); 57-60, 1981.
Riley, E. P. et al., Alcohol Clin Exp Res 10(1); 50-53, 1986.
Rupreht, J. et al., Anesthesiology, 58(6), pp. 524-526, 1983.
Goodman Gilman et al., The Pharmacological Basis of Therapeutics (6th Ed.) Macmillan Publ. Co., N.Y., 1980, pp. 552-553.
Primary Examiner:
Cintins, Marianne M.
Assistant Examiner:
Moezie M.
Attorney, Agent or Firm:
Sprung Horn Kramer & Woods
Parent Case Data:
Claims:
I claim:

1. A method of reducing the desire for alcohol in a patient suffering from alcoholism which comprises administering to such patient an amount effective to reduce the desire for alcohol of a material comprising galanthamine (4a, 5, 9, 10, 11, 12-hexahydro-3-methoxy-11-methyl-6H-benzofuro [3a, 3, 2-ef][2] benzazepine-6-ol) of the formula ##STR2## or a pharmaceutically acceptable acid addition salt thereof.

2. The method according to claim 1, wherein the material is administered orally.

3. The method according to claim 1, wherein the material is administered parenterally.

4. The method according to claim 1, wherein the material is administered transdermally.

5. The method according to claim 1, wherein the material is dissolved or dispersed in a liquid.

6. The method according to claim 4, wherein the material is in the form of an applicator comprising

7. The method according to claim 6, wherein the applicator also contains a membrane controlling the release of the active substance.

8. The method according to claim 6, wherein the applicator contains a removable protective layer.

9. The method according to claim 7, wherein the applicator contains a removable protective layer.

Description:





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