Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Patent
1995-02-15
1999-06-01
Harrison, Robert H.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
514929, A61K 3117, A61K 31155
Patent
active
059088532
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention involves the novel use of various classes of drugs, such as H.sub.2 agonists, as erectogenic agents in the treatment of erectile dysfunction.
BACKGROUND OF THE INVENTION
The year 1982 marked the beginning of a new era in the diagnosis and treatment of male sexual impotence. At that time, the new development was the use of papaverine as a drug which, when injected intracavernously, was capable of inducing a penile erection in humans, Virag, R. "Intracavernous injection of papaverine for erectile failure". Lancet 2: 938 (1982).
Regrettably, universal medical experience with this drug over several years revealed the severity of some of its side-effects, Junemann, K. P. and Alken, P. "Pharmacotherapy of erectile dysfunction: a review". Int. J. Impotence Res. 1, 71-93 (1988). A major disadvantage of papaverine was the occurrence of unduly prolonged erection with the danger of priapism. Papaverine was also tried in combination with the alpha sympathetic blocker phentolamine, Zorgniotti, A. W. and Lefleur, R. S. J. Urol., 133(1): 39-41, (1985). Phenoxybenzamine, another alpha-adrenergic blocker was also tested, Brindley, G. S., Br. J. {Psychiatry, 143: 332-337 (1983). The use of phenoxybenzamine for the management of impotence was abandoned at this time because of evidence obtained from experiments with animals suggesting that this drug could have carcinogenic activity. IARC. Phenoxybenzamine and phenoxybenzamine hydrochloride. IARC Monogr. Eval. Carcinog. Risk Chem. Hum., 24: 185-194, 1980; Hoffman, B. B., Lefkowitz, R. J. Adrenergic receptor antagonist., Goodman and Gilman's. The Pharmacological Basis of Therapeutics, eighth edition New York: Pergamon Press, c1990. p. 225.
Experiments with Cynomolgus monkeys showed that after 1 to 2 weekly intracavernous injections (of papaverine) led, after a period of 12 months, to extensive fibrosis in the distal areas of the erectile organ. In humans, this reaction could have very negative long term consequences: fibrotic corpora cavernosa become incapable of erection, Abozeid, M. et al. J. Urol., 138(5): 1263-1266 (1987).
In 1986, Ishii et al injected for the first time prostaglandin E.sub.1 into human corpora cavernosa for the treatment of organic impotence, Ishii, N. et al. "Therapeutic trial with prostaglandin E.sub.1 for organic impotence". Jap. J. Imp., 1: 54-962 (1986). See also Ishii, N. et al "Intracavernous injection of prostaglandin E.sub.1 for the treatment of erectile impotence". J. Urol., 141(2): 324-325 (1989). Since it is a drug of natural occurrence in the body and could be expected to cause fewer side-effects than papaverine, PGE.sub.1 became rapidly and universally accepted, Junemann, K. P. and Alken, P. Int. J. Imp. Res., 1: 71-93 (1988).
The use of a triple combination of PGE.sub.1, papaverine and phentolamine was introduced in 1991, Bennett et al. J. Urol., 146(6): 1564-1565 (1991). However, prolonged erections have been reported following the use of such a combination, von-Heyden et al. J. Urol., 149(5 Pt 2): 1288-1290 (1993). The use of prostaglandin E.sub.1 is often rejected by patients because of the painfulness of its injection. Waldhauser, M. et al., J. Urol., 140(3): 525-527 (1988).
In spite of initially promising evidences of a possible role of nitric oxide (NO) in the mechanics of normal human penile erection, Rajfer, J. et al., N. Eng. J. Med., 326:90-94 (1992) in 1992 Porst, (Porst, H., Int. J. Impotence Res., 4(Suppl. 2): A91 (1992)) compared the erectogenic efficiency of 1 mg of SIN-1 (Linsindomin-Corvasal.RTM.) against 20 .mu.g of PGE1 (Porstavasin.RTM.), both of them administered by intracavernous vias to 40 consecutive patient complaining of erectile failure. According to the latter author: " . . . SIN-1 is considerably bless effective than PGE1 and will therefore, not play a major role in the management of male impotence".
Virag, in 1982, was the first to demonstrate the erectogenic effect of a vasoactive drug injected directly into the patient's epigastric artery. The type of therapy in
REFERENCES:
patent: 4013659 (1977-03-01), Durant et al.
patent: 4126670 (1978-11-01), Durant et al.
patent: 4127118 (1978-11-01), Latorre
patent: 4311707 (1982-01-01), Birnbaum et al.
patent: 4472376 (1984-09-01), Kamishita
patent: 4521421 (1985-06-01), Foreman
patent: 4801487 (1989-01-01), Voss et al.
patent: 4801587 (1989-01-01), Voss et al.
patent: 4840952 (1989-06-01), Gamble et al.
patent: 4863911 (1989-09-01), Anderson et al.
patent: 4931445 (1990-06-01), Goldstein et al.
patent: 5059603 (1991-10-01), Rubin
patent: 5145852 (1992-09-01), Virag
patent: 5147855 (1992-09-01), Gozes et al.
patent: 5177070 (1993-01-01), Katz
patent: 5190967 (1993-03-01), Riley
patent: 5192806 (1993-03-01), Pill et al.
patent: 5214030 (1993-05-01), Stief
patent: 5242391 (1993-09-01), Place et al.
patent: 5242931 (1993-09-01), Place et al.
patent: 5256652 (1993-10-01), El-Rashidy
patent: 5270323 (1993-12-01), Milne et al.
patent: 5336678 (1994-08-01), Cavallini
patent: 5474535 (1995-12-01), Place et al.
patent: 5773457 (1998-06-01), Nahoum
Leslie et al., "Short Term Toxicological Studies With Impromidine (SK&F 92676): A Specific Histamine H2-Receptor Agonist", J. Appl. Toxicol., vol. 2, No. 5, pp. 265-268, issued 1982 (Abstract).
Minicozzi, "Identification of Histamine Receptors and Autacoid Potentiation By Histamine Antagonists in the Perfused Human Placenta", Dissertation Abstracts Intl., 44(5B), p. 1430, 1983 (Abstract Only).
Kim et al., "Characterization and Function of Histamine Receptors in Corpus Cavernosum", The Journal of Urology, vol. 153, No. 2, Published Feb., 1995, pp. 506-510.
Dinner Dara L.
Harrison Robert H.
Nahoum Cesar Roberto Dias
Venetianer Stephen
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