Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1996-06-20
1999-02-02
Spivack, Phyllis G.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
A61K 3152
Patent
active
058665811
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/GB94/02156 filed Oct. 4, 1994.
FIELD OF THE INVENTION
This invention relates to treatment of post-herpetic neuralgia, and to the use of compounds in the preparation of a medicament for use in the treatment of such conditions.
When used herein, `treatment` includes prophylaxis as appropriate.
BACKGROUND OF THE INVENTION
EP-A-141927 (Beecham Group p.l.c.) discloses penciclovir, the compound of formula (A): ##STR2## and salts, phosphate esters and acyl derivatives thereof, as antiviral agents. The sodium salt hydrate of penciclovir is disclosed in EP-A-216459 (Beecham Group p.l.c.). Penciclovir and its antiviral activity is also disclosed in Abstract P.V11-5 p. 193 of `Abstracts of 14th Int. Congress of Microbiology`, Manchester, England 7-13 Sep. 1986 (Boyd et. al.).
Orally active bioprecursors of the compound of formula (A) are of formula (B): ##STR3## and salts and derivatives thereof as defined under formula (A); wherein X is C.sub.1-6 alkoxy, NH.sub.2 or hydrogen. The compounds of formula (B) wherein X is C.sub.1-6 alkoxy or NH.sub.2 are disclosed in EP-A-141927 and the compounds of formula (B) wherein X is hydrogen, disclosed in EP-A-182024 (Beecham Group p.l.c.) are preferred prodrugs. A particularly preferred example of a compound of formula (B) is that wherein X is hydrogen and wherein the two OH groups are in the form of the acetyl derivative, described in Example 2 of EP-A-1 82024, hereinafter referred to as famciclovir.
The compounds of formulae (A) and (B) and salts and derivatives thereof have been described as useful in the treatment of infections caused by herpesviruses, such as herpes simplex type 1, herpes simplex type 2, varicella-zoster and Epstein-Barr viruses.
Post-herpetic neuralgia (PHN) is by far the most common complication of herpes zoster infection and is one of the most intractable pain disorders (Strommen et al, Pharmacotherapy. 1988;8:52-68). Patients who develop PHN suffer from a debilitating and often intractable pain which can persist for months or even years. Although rare in patients under 50 years of age, the frequency of PHN rises steeply with increasing age.
There is currently no proven therapy for preventing PHN. The pain is due to injury of the nervous system and therefore seldom responds to analgesia used to treat pain associated with tissue damage. Hence, there is a need for therapy which alleviates or shortens the duration of post-herpetic neuralgia.
SUMMARY OF THE INVENTION
It has now been discovered that the above compounds are particularly effective in reducing the duration of PHN when given to the patient during the acute infection.
Accordingly, the present invention provides a method of treatment of PHN in humans, which method comprises the administration to the human in need of such treatment, an effective amount of a compound of formula (A): ##STR4## or a bioprecursor, or a pharmaceutically acceptable salt, phosphate ester and/or acyl derivative of either of the foregoing.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 shows a Kaplan-Meier Plot of Time to Loss of Postherpetic Neuralgia (PHN) in a Patient Population in which famciclovir doses significantly reduce the duration of PHN.
FIG. 2 shows a Kaplan-Meier Plot of Time to Loss of Postherpetic Neuralgia (PHN) in a Patient Population over >50 years of age in which famciclovir resolved PHN 2.6 times faster than in placebo treated patients.
DETAILED DESCRIPTION OF THE INVENTION
The term `acyl derivative` is used herein to include any derivative of the compounds of formula (A) in which one or more acyl groups are present. Such derivatives are included as bioprecursors of the compounds of formula (A) in addition to those derivatives which are per se biologically active.
The compound of formula (A) may be in one of the forms disclosed in EP-A-216459 (Beecham Group p.l.c.).
Examples of bioprecursors, pharmaceutically acceptable salts and derivatives are as described in the aforementioned European Patent references, the subject matter of which are incorporated herein by
REFERENCES:
Poster from ICAAC, Oct. 11-14, 1992.
Poster from ICAAC, Oct. 17-20, 1993.
Wood et al., Scand. J. Infect. Dis., 23(80), pp. 53-61, 1991.
Robertson et al., Br. Med. Bull., 46(1), pp. 113-123, 1990.
Klenerman et al., Biomed. Pharmacother., 44(9), pp. 455-459, 1990.
Schmader et al., J. Gen. Intern. Med., 4(2), pp. 83-89, 1989.
McKendrick, et al., British Medical Journal, vol. 293, pp. 1529-1532 (1986).
Huff, et al., The American Journal of Medicine, vol. 85 (Suppl 2A), pp. 84-89, (1988).
Morton, et al., The New Zealand Medical Journal, vol. 102, No. 863, pp. 93-95, (1989).
Huff, et al., Journal of Medical Virology, Supplement 1, pp. 93-96 (1993).
Wood, et al., The New England Journal of Medicine, vol. 330, pp. 896-900, (1994).
Beutner and The International Valaciclovir Zoster Study Group, Abstract (1994).
Wood, et al., Infection 15, Suppl. 1, pp. S9-S13, (1987).
Harding, Journal of Medical Virology, Suppl. 1, pp. 97-101 (1993).
Crooks, et al., Scand J. Infect, Suppl. 78, pp. 64-70 (1991).
McKendrick, et al., British Medical Journal, 298:431 (1988).
Boon Ronald James
Griffin David Ronald John
Dinner Dara L.
SmithKline Beecham p.l.c.
Spivack Phyllis G.
Venetianer Stephen
LandOfFree
Penciclovir for the treatment of post therapeutic neuralgia does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Penciclovir for the treatment of post therapeutic neuralgia, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Penciclovir for the treatment of post therapeutic neuralgia will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1117745