Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1986-11-10
1990-01-23
Godlberg, Jerome D.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
A61K 31335
Patent
active
048958700
DESCRIPTION:
BRIEF SUMMARY
Chlamydia infect many vertebrate hosts including birds, mammals, and humans. Human diseases caused by Chlamydia trachomatis include trachoma, urethritis, inclusion conjunctivitis, lymphogranuloma venereum, cervicitis, salpingitis, infant pneumonitis syndrome and pelvic inflammatory disease.
C. trachomatis infections of the genital tract represent the major focus of recent clinical interest in chlamydia. C. trachomatis is now recognized as one of the chief causes of both non-gonococcal and post-gonococcal urethritis and cervicitis. In addition, infants born to mothers infected with C. trachomatis can also become infected and develop inclusion conjunctivitis, pneumonia, or otitis media. Studies have shown that 60-70% of exposed infants will develop some tupe of C. trachomatis infection.
C. trachomatis infections are amenable to chemotherapy, with the drugs of choice being tetracycline and erythromycin. However, the use of tetracycline is contraindicated for pregnant women and small children (two large target populations) and a significant number of patients (especially pregnant women) experience gastrointestinal distress from erythromycin and stop taking the drug. A clinical need, therefore, exists for a non-toxic antibiotic that inhibits C. trachomatis, Neisseria gonorrhoeae and Ureaplasma in combination, or C. trachomatis alone.
Evidence now indicates that Ureaplasma causes 7-10% of nongonococcal urethritis. Spectinomycin is useful for treating gonorrhea and nongonococcal urethritis (NGU) caused by Ureaplasma urealyticum. On the other hand, it has been shown to have only slight activity against C. trachomatis [W. M. McCormack and M. Finland, "Spectinomycin," Ann. Intern. Med., 84, pp. 712-16 (1976)]. Treatment with spectinomycin produces a significantly better response in chlamydia-negative, ureaplasma-positive NGU than in chlamydia-positive, ureaplasma-negative NGU [W. R. Bowie and K. K. Holmes, "Nongonococcal Urethritis", in Infectious Diseases, P. D. Hoeprich, ed., pp. 574-79 (1983)].
Spectinomycin is an aminocyclitol antibiotic with broad spectrum antibacterial activity [C. Lewis and H. W. Clapp, "Actinospectacin, A New Antibiotic III. In Vitro and In Vivo Evaluation", Antibiotics and Chemotherapy, 2, pp. 127-33 (1961); J. A. Washington and P. K. W. Yu, "In vitro Antibacterial Activity of Spectinomycin", Antimicrob. Agents Chemother., 2, pp. 427-30 (1972)]. Spectinomycin was first prepared by a microbiological process, Bergy et al. U.S. Pat. No. 3,234,092. Spectinomycin is not an aminoglycoside and lacks some of the potential toxicity of that antibiotic group [E. Novak et al., "Animal and Human Tolerance of High-Dose Intramuscular Therapy with Spectinomycin", J. Infect. Disease, 130, pp. 50-55 (1974)]. Spectinomycin achieves high serum and urine levels in humans [J. G. Wagner et al., "Absorption, Distribution and Elimination of Spectinomycin Dihydrochloride In Man", Int. J. Clin, Pharmacol., 14, pp. 261-85 (1967)] and has been successfully used to treat a variety of infections [C. E. Cornelius and G. Domescik, "Spectinomycin In the Treatment of Uncomplicated Gonorrhoea", Br. J. Vener. Dis., 46, pp. 212-13 (1970); R. I. Lindemeyer et al., "An Evaluation of a New Antibiotic, Actinospecticin, in Infections of the Urinary Tract", Am. J. Med. Sci., pp. 480-83, (October 1962)]. However, spectinomycin is generally less active in vitro than the amminoglycosides and has been used primarily for treatment of uncomplicated anogenital gonorrhea [Physicians Desk Reference, 35th ed., Medical Econimics Co. p. 1844 (1981)].
There are few references to spectinomycin analogs with modified sugar rings in the literature. For example, see U.S. Pat. Nos. 4,351,771, 4,361,701 and 4,173,647.
Modifications at the C-6' position to produce spectinomycin analogs with modified sugar rings are known. Such previously known modifications at the C-6' position can be found in U.S. Pat. Nos. 4,351,771 and 4,361,701 as well as in U.S. application Ser. No. 449,304, filed Dec. 13, 1982, now pending, which is a continuation-in-part of U.S. a
REFERENCES:
patent: 3234092 (1966-02-01), Bergy et al.
patent: 4173647 (1979-11-01), Maier et al.
patent: 4351771 (1982-09-01), White et al.
patent: 4361701 (1982-11-01), White
patent: 4465848 (1984-08-01), Thomas et al.
patent: 4532336 (1985-07-01), White
Manual of Antibiotics and Infectious Diseases, John E. Conte, Jr., and S. L. Barriere, pp. 292-93, (1984).
Medical Microbiology and Infections Diseases, A. I. Braude, pp. 516-22, (1981).
Zinsser Microbiology, by W. K. Joklik, et al., 18th ed., pp. 785-92, (1984).
Annals of Internal Medicine, vol. 84, "Spectinomycin", W. M. McCormack and M. Finland, pp. 712-16, (1976).
Infectious Diseases, 3rd ed., "Nongonococcal Urethritis," W. R. Bowie and K. K. Holmes, pp. 574-79, (1983).
Antibiotics and Chemotherapy, vol. XI, No. 2, "Actinospectacin, A New Antibiotic III . . . ," Charles Lewis and Howard W. Clapp, pp. 127-33, (1961).
Antimicrobial Agents and Chemotherapy, vol. 2, No. 6, "In Vitro Antibacterial Activity of Spectinomycin," John A. Washington II and Pauline K. W. Yu, pp. 427-30, (1972).
The Journal of Infectious Diseases, vol. 130, No. 1, "Animal and Human Tolerance of High--Dose Intramuscular Therapy with Spectinomycin," Ervin Novak et al., pp. 50-55, (1974).
International Journ. Clin. Pharmacol., 14, "Absorption Distribution and Elimination of Spectinomycin Dihydrochloride in Man," J. G. Wagner et al., pp. 261-85, (1967).
Brit. J. vener, Dis., 46, "Spectinomycin in the Treatment of Uncomplicated Gonorrhoea," Charles E. Cornelius III and Gerald Domescik, pp. 212-13, (1970).
Physicians Desk Reference, 35th ed., Medical Economics Co., p. 1844, (1981).
The Journal of Antibiotics, 26, No. 3, "Synthesis and In Vitro Antibacterial Properties . . . ," D. R. White et al., pp. 339-42, (1983).
The American Journal of the Medical Sciences, 244, "An Evaluation of a New Antibiotic, Actinospectacin . . . ," Robert I. Lindemeyer et al., pp. 480-83, (1962).
Thomas Richard C.
Vavra James J.
White David R.
Zurenko Gary E.
Godlberg Jerome D.
Koivuniemi Paul J.
The Upjohn Company
LandOfFree
Treating chlamydia infections using spectinomycin analogs does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Treating chlamydia infections using spectinomycin analogs, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Treating chlamydia infections using spectinomycin analogs will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-645504