Benzoylecgonine compositions and methods for producing them

Details Benzoylecgonine compositions and methods for producing them Benzoylecgonine compositions and methods for producing them

2002-11-13

2004-09-14

Aulakh, Charanjit S. (Department: 1625)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Having -c-, wherein x is chalcogen, bonded directly to...

C546S131000, C546S130000, C546S127000, C546S124000, C546S112000, C514S299000

Reexamination Certificate

active

06790857

ABSTRACT:

TECHNICAL FIELD
This invention relates to novel compositions comprising benzoylecgonine and structurally related compounds, and methods for producing them.
BACKGROUND
Compositions comprising benzoylecgonine and structurally-related chemical compounds (such as ecgonine, ecgonidine and derivative thereof) are useful in preventing and treating a number of important diseases and disorders (see, for example, U.S. Pat. Nos. 4,469,700; 4,512,996; 4,556,663; 5,376,667; 5,559,123 and 5,663,345; each of which is hereby incorporated herein in its entirety). Particularly useful benzoylecgonine-related compounds include the 2-hydroxypropyl ester derivatives of benzoylecgonine, ecgonine, and ecgonidine. Methods for producing compositions comprising these 2-hydroxypropyl esters have been described in U.S. Pat. No. 5,376,667. The preferred method described in U.S. Pat. No. 5,376,667 utilizes the step of heating cocaine base in a propylene glycol/water solution (95% propylene glycol/5% water w/w) at 50° C. for 12 days, after which time less than 0.1% of the cocaine base starting material remained (see column 7, lines 3-17). The composition produced by this method comprises approximately 5% w/w of an active component mixture in propylene glycol, wherein the active component mixture comprises approximately 65% benzoylecgonine, 2% ecgonidine and 5% and 6%, respectively, of the 2-hydroxypropyl derivatives of benzoylecgonine and ecgonidine. It has recently been discovered by the inventors hereof that removal of water during the reaction used to produce the 2-hydroxypropyl derivatives of benzoylecgonine and ecgonidine helps drive the reaction to the desired products and, furthermore, removal of water during or subsequent to the reaction results in a composition with enhanced stability. The novel method for the production of the compositions comprising 2-hydroxypropyl derivatives of benzoylecgonine and ecgonidine and the enhanced stability of the resulting composition may provide advantages over the prior art methods and compositions that can be appreciated by one of skill in the art.
SUMMARY
The invention described herein fulfills the needs described above. In one embodiment, this invention provides a method for preparing a benzoylecgonine composition comprising the steps of:
(a) contacting benzoylmethylecgonine and propylene glycol in the presence or absence of water to form a reaction mixture;
(b) maintaining the reaction mixture at a temperature between about 50° and 100° C; and
(c) subsequently or simultaneously removing water from the reaction mixture.
In another embodiment, this invention provides novel benzoylecgonine compositions comprising at least about 2% 2-hydroxypropyl benzoylecgonine esters, at least about 2% 2-hydroxypropyl ecgonidine esters, less than about 0.1% benzoylmethylecgonine and between about 0% and about 4% water.
The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims.


REFERENCES:
patent: 2893996 (1959-07-01), Rudner et al.
patent: 2948730 (1960-08-01), Rudner et al.
patent: 4469700 (1984-09-01), Somers
patent: 4512996 (1985-04-01), Somers
patent: 4556663 (1985-12-01), Somers
patent: 5376667 (1994-12-01), Somers et al.
patent: 5525613 (1996-06-01), Wynn et al.
patent: 5559123 (1996-09-01), Somers et al.
patent: 5663345 (1997-09-01), Somers et al.
patent: 5763456 (1998-06-01), Wynn et al.
patent: 6077848 (2000-06-01), Wynn et al.
patent: 2569563 (1986-03-01), None
patent: WO 94/15935 (1994-07-01), None
W.H. Anderson and D.T. Stafford, “Applications of Capillary Gas Chromatography in Routine Toxicological Analyses”,J. High Resolut. Chromatogr., Chromatogr. Commun., 6, pp. 247-254 (1983).
E.J. Ariens and A.M. Simonis, “A Molecular basis for drug action. The interaction of one or more drugs with different receptors”,J. Pharm. Pharmacol., 16, pp. 289-312 (1964).
M.R. Bell and S. Archer, “L(+)-2-Tropinone”,J. Amer. Chem. Soc., 82, pp. 4642-4644 (1960).
R. Bingham, “Esterene in the Treatment of Rheumatoid Arthritis”,Arthritis News Today, 2(7), pp. 1-4 (1980).
C.S. Boyer and D.R. Peterson, “Enzymatic Basis for the Transesterification of Cocaine in the Presence of Ethanol: Evidence for the Participation of Microsomal Carboxylesterases”,J. Pharmacol. Exp. Ther., 260(3), pp. 939-946 (1992).
M.R. Brzezinski et al., “Convenient Synthesis of Benzoylecgonine Ethyl Ester, a Homolog of Cocaine”,Synth. Commun., 22(7), pp. 1027-1032 (1992).
R.D. Budd, “Cocaine Radioimmunoassay—Stucture Versus Reactivity”,Clin. Toxicol., 18(7), pp. 773-782 (1981).
H. Bundgaard, Design of Prodrugs. Elsevier. Amsterdam, pp. 1-2 (1985).
D.T. Chia and J.A. Gere, “Rapid Drug Screening Using Toxi-Lab® Extraction Followed by Capillary Gas Chromatography/Mass Spectroscopy”,Clin. Biochem., 20(5), pp. 303-306 (1987).
A.J. Clark, “The Antagonism of Acetyl Choline by Atropine”,J. Physiol., 61, pp. 547-556 (1926).
E.J. Cone et al., “Testing Human Hair for Drug Abuse. II. Identification of Unique Cocaine Metabolites in Hair of Drug Abusers and Evaluation of Decontamination Procedures”,J. Anal. Toxicol., 15(5), pp. 250-255 (1991).
C. Csongar, et al., J. Prakt. Chem. 329(6) 1111-1115 (1987).
R.A. Dean et al., “Human Liver Cocaine Esterases: Ethanol-Mediated Formation of Ethylcocaine”,FASEB J., 5(12), pp. 2735-2739 (1991).
F. Fish and W.D.C. Wilson, “Excretion of Cocaine and its Metabolites in Man”,J. Pharm. Pharmac., 21 suppl., pp. 135S-138S (1969).
J.R. Fozard et al.,l “Structure-Activity Relationship of Compounds Which Block Receptors for 5-Hydroxytryptamine on the Sympathetic Nerves of the Rabbit Heart”,Br. J. Pharmacol., 61(3), pp. 499P-500P (1977).
J.R. Fozard et al., “Blockade of Serotonin Receptors on Autonomic Neurones by (−)-Cocaine and Some Related Compounds”,Eur. J. Pharmacol., 59(3-4), pp. 195-210 (1979).
J.H. Gaddum, “The Action of Adrenalin and Ergotamine on the Uterus of the Rabbit”,J. Physiol., 61, pp. 141-150 (1926).
J.H. Gaddum, “The Quantitative Effects of Antagonistic Drugs”,J. Physiol., 89, pp. 7-9 (1937).
J.M.G. Galvez and A.P. de Abram, “Cocaina: Avances en su Investigacion”,Bol. Soc. Ouim. Peru, 56(1), pp. 12-20 (1989).
C. Hansch and W.J. Dunn, “Linear Relationships between Lipophilic Character and Biological Activity of Drugs”,J. Pharm. Sci., 61, pp. 1-19 (1972).
W.L. Hearn et al., “Cocaethylene is More Potent than Cocaine in Mediating Lethality”,Pharmacol., Biochem. Behav., 39(2), pp. 531-533 (1991).
W.L. Hearn et al., “Cocaethylene: A Unique Cocaine Metabolite Displays High Affinity for the Dopamine Transporter”,J. Neurochem., 56(2), pp. 698-701 (1991).
G.W. Hime et al., “Analysis of Cocaine and Cocaethylene in Blood and Tissues by GC-NPD and GD-Ion Trap Mass Spectrometry”,J. Anal. Toxicol., 15(5), pp. 241-245 (1991).
P. Jatlow et al., “Cocaethylene: A Neuropharmacologically Active Metabolite Associated with Concurrent Cocaine-Ethanol Ingestion”,Life Sci., 48(18), pp. 1787-1794 (1991).
J.L. Katz et al., “Comparative Behavioral Pharmacology and Toxicology of Cocaine and its Ethanol-Derived Metabolite, Cocaine Ethyl-Ester (Cocaethylene)”,Life Sci., 50(18), pp. 1351-1361 (1992).
A. Leo et al., “Partition Coefficients and Their Uses”,Chemical Reviews, 71, pp. 525-616 (1971).
A.H. Lewin et al., “2&bgr;-Substituted Analogues of Cocaine. Synthesis and Inhibition of Binding to the Cocaine Receptor”,J. Med. Chem., 35(1), pp. 135-140 (1992).
T. Lukaszewski and W.K. Jeffery, “Impurities and Artifacts of Illicit Cocaine”,J. Forensic Sci., 25(3), pp. 499-507 (1980).
J. March, Advanced Organic Chemistry, McGraw Hill Book Company, New York, Second Edition, p. 363 (1977).
H.H. McCurdy, “Quantitation of Cocaine and Benzoylecgonine after JETUBE® Extraction and Derivitazation”,J. Anal. Toxicol., 4(2), pp. 82-85 (1980).
Medical World News, “FP Giving Cocaine for Arthritis is Beset But Gains a Major Ally”, pp. 19-20 (1979).
A.L. Misra et al., “Physiologic Disposition and Metabolism of [3H]-Ecgonine (

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