Pharmaceutical application of 15- or 16-substituted...

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Cyclopentanohydrophenanthrene ring system doai

Reexamination Certificate

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C514S170000, C514S178000

Reexamination Certificate

active

07943602

ABSTRACT:
The invention relates to pharmaceutical dosage units for oral, transmucosal or transdermal administration containing 15- or 16-substituted testosterone analogues, as well as to therapeutic methods that employ these testosterone analogues. More particularly, the invention is concerned with such pharmaceutical dosage units containing at least 10 μg of an androgenic steroid selected from the group consisting of 15-hydroxytestosterones, 16-hydroxytestosterones, precursors thereof and mixtures of these hydroxytestosterones and/or their precursors; and a pharmaceutically acceptable excipient. The term “15-hydroxytestosterones” encompasses both 15α-hydroxytestosterone (15α, 17β-dihydroxy-4-androsten-3-one) and 15β-hydroxytestosterone (15β, 17β-dihydroxy-4-androsten-3-one). Similarly, the term “16-hydroxytestosterones” encompasses both 16α-hydroxytestosterone hydroxytestosterone (16α, 17β-dihydroxy-4-androsten-3-one) and 16β-hydroxytestosterone (16β, 17β-dihydroxy-4-androsten-3-one). The androgenic steroids according to the invention are advantageously employed in e.g. a method of treating or preventing androgen deficiency or a method of hormonal contraception.

REFERENCES:
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Wood, et al., “Regio- and Stereoselective Metabolism of Two C19 Steroids by Five Highly Purified and Reconstituted Rat Hepatic Cytochrome P-450 Isozymes”, Journal of Biological Chemistry, 1983, 258 (14), pp. 8839-8847.
Yamazaki, “Progesterone and Testosterone Hydroxylation by Cytochromes P450 2C19, 2C9, and 3A4in Human Liver Microsomes1”, Archives of Biochemistry and Biophysics,vol. 346, No. 1, 1997, pp. 161-169.
Allen et al., “The Reaction of Alkoxalylated Steroid Ketones with Dibenzoyl Peroxide. A Synthesis of 16β-Hydroxytestosterone”, J. Org. Chem. (1962), 27(12) 4681-4682.
Yamashita, et al. “Microbial 16β-Hydroxylation of Steroids withAspergillus niger”, Agr. Biol. Chem. (1976) 40 (3), 505-509.
Rosenbrock, et al., “Testosterone Metabolism in Rat Brain Is Differentially Enhanced by Phenytoin-Inducible Cytochrome P450 Isoforms”, J. of Neuroendocrinology, (1999) 11, 597-604.

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