The present invention relates to a novel class of benzoylecgonine, ecgonine and ecgonidine derivatives which are useful for preventing and treating immunoregulatory disorders, neuromuscular disorders, joint disorders, connective tissue disorders, circulatory disorders and pain. The compounds of this invention are conveniently obtained by chemical synthesis. Accordingly, this invention also relates to methods for preparing the benzoylecgonine, ecgonine and ecgonidine derivatives and to pharmaceutical compositions containing these derivatives.

• Port Injection Chromatography Degradation Of Cocaine To Ecgonidine

Port Injection Chromatography Degradation Of Cocaine To Ecgonidine

1. Cocaine base is prepared by the following protocol: Cocaine HCl (5.0 g) is dissolved in 150 ml of distilled water. Volumes of 1N KOH are added with stirring to a final pH of about 10. The white solid formed is padded dry using filter paper and paper towel. The solid is then placed in a 500 ml beaker and allowed to melt in a 100.degree.
2. Ecgonidine, the major metabolite of methyl ecgonidine, was present in 77% of PM and 88% of the LV specimens, indicating smoking as the major route of cocaine administration.

The twelve types are: (1) Column Chromatography (2) Paper Chromatography (3) Thin Layer Chromatography (4) Gas Chromatography (5) High Performance Liquid Chromatography (6) Fast Protein Liquid Chromatography (7) Supercritical Fluid Chromatography (8) Affinity Chromatography (9) Reversed Phase Chromatography (10) Two Dimensional Chromatography (11) Pyrolysis Gas Chromatography and (12) Counter Current Chromatography.

CROSS-REFERENCE TO RELATED APPLICATIONThis application is a divisional of application Ser. 07/999,307, filed Dec. 31, 1992, U.S. TECHNICAL FIELD OF THE INVENTIONThe present invention relates to a novel class of benzoylecgonine, ecgonine and ecgonidine derivatives which are useful for preventing and treating immunoregulatory disorders, neuromuscular disorders, joint disorders, connective tissue disorders, circulatory disorders and pain.

The compounds of this invention are conveniently obtained by chemical synthesis. Accordingly, this invention also relates to methods for preparing the benzoylecgonine, ecgonine and ecgonidine derivatives and to pharmaceutical compositions containing these derivatives. BACKGROUND OF THE INVENTIONBenzoylecgonine, ecgonine and ecgonidine are known metabolites of cocaine (see, for example, S. Roberts et al., 'An Assay for Cocaethylene and Other Cocaine Metabolites in Liver Using High-Performance Liquid Chromatography' Anal Biochem., 202, pp 256-61 (1992); D. Gere, 'Rapid Drug Screening Using Toxi-Lab Extraction Followed by Capillary Gas Chromatography/Mass Spectroscopy', Clin. Biochem., 20, pp. 303-06 (1987)).

Routes for their preparation have been established (see, for example, A. Lewin et al., '2β-Substituted Analogues of Cocaine. Synthesis and Binding to the Cocaine Receptor', J.

Chem., 35, pp. 135-40 (1992); M. Archer, 'L(+)-2-Tropinone', J Amer. Soc., 82, pp.

4642-44 (1960)).We have demonstrated the pharmaceutical efficacy of benzoylecgonine and ecgonine in the treatment of rheumatoid arthritis and osteoarthritis (see, for example, U.S. 4,469,700, 4,512,996 and 4,556,663). Unfortunately, the original promise of these compounds has not been fully realized. Due to their low rate of absorption into the blood stream and their low solubility in solution, the effective dose must be relatively high and certain modes of administration (such as topical administration) are less practical. In addition, neither benzoylecgonine nor ecgonine cross the blood/brain barrier. Therefore, these compounds are not effective in treating disorders of the central nervous system.All the above-mentioned restrictions limit the number of potential uses for benzoylecgonine, ecgonine and ecgonidine.

Therefore, a need exists for easily synthesized, stable derivatives of these compounds which will be more easily absorbed into the bloodstream without adverse side effects, while maintaining a high level of therapeutic efficacy. The method according to claim 14, wherein the pharmaceutical composition is administered transdermally, topically or by inhalation.