Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
  • A61K31/565—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
  • A61K31/568—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone

Definitions

• the present invention relates to the use of androst-5-ene-3 ⁇ , 17 ⁇ -diol for the preparation of a medicament useful for the treatment of deficiencies of delta 5-androsten hormones. More particularly, androst- 5-ene-3 ⁇ , 17 ⁇ 3-diol is used in the treatment of post- enopausal syndrome, in the treatment and prevention of osteoporosis, and for inducing a decrease in fat mass and an increase in lean body mass . Technological background
• Androst-5-ene-3j3,17 ⁇ -diol is a 19 carbon atoms steroid produced physiologically by the human adrenal gland.
• the mean blood concentrations of this hormone are usually of about 4.5 nanomols (1.3 ng/ml) per litre.
• the blood values of this hormone decrease in menopausal woman ( Cu mings AC, et al .. , J. Clin. Endocrinol. Metab. 14:1069-71, 1982), in obesity (Tchernof A, et al .. Metab. 44:517-19, 1995) and in ageing in both sexes (Parker LN . Academic. Press, New York, 615 pp , 1989).
• Androst-5-ene-3 ⁇ 3, 17 ⁇ -diol is known to be used as an anabolic agent, i.e. it promotes an increase in muscle bulk.
• Androstenediol is produced by the adrenal gland through hydroxylation of DHEA ( dehydroepiandrosterone ) .
• DHEA dehydroepiandrosterone
• the metabolic pathway of androstenediol is complex. This hormone is in part hydroxylated to both ⁇ and ⁇ androstenetriols . It should be stressed that DHEA, androstenediol and its 7 ⁇ -hydroxylated derivative are immune stimulators (Padgett DA. J. Immunol. 153 : 1544-52.
• the traditional hormone replacement therapy which has been used for a long time for the prevention and treatment of menopause, does not increases androstenediol blood levels nor modifies the fat mass/lean body mass ratio, which shifts towards fat mass.
• the estrogen treatment often does not restore sexuality, libido and well-being.
• compositions containing an effective amount of androst-5-ene-3 ⁇ , 17 ⁇ -diol as active ingredient in admixture with pharmaceutically acceptable excipients and carriers, more particularly a composition suitable for the oral administration, as well as a composition providing the administration of continuous doses of androst-5-ene-3 , 17 ⁇ -diol by the transdermal route.
• the use of androst-5-ene-3 ⁇ ,17 ⁇ - diol according to the present invention involves a very slight androgenic activity and the effective amounts of the active ingredient are very low.
• the medicament containing androst-5-ene-3 ⁇ , 17 ⁇ -diol is useful for the treatment of deficiencies of delta 5-androsten hormones " , produced by the adrenal gland:
• Androst-5-ene-3 ⁇ ,17 ⁇ -diol is a substantially harmless product present in the body as a natural component, so that it involves no toxicity problems.
• Androst-5-ene-3 ⁇ , 17 ⁇ -diol can be administered together with other active ingredients or directly combined therewith, in post-menopause and in ageing.
• it can be administered together with estrogens in the prevention and in the treatment of menopause symptoms and disturbances, without need for combining it with progestins.
• suitable doses of androst-5-ene-3 ⁇ ,17 ⁇ -diol range from 5 to 30 mg/day per os .
• the administration of androstenediol in post-menopausal women effectively counteracts menopausal symptoms and decreases fat mass, contrary to estrogens which do not affect it, thus suggesting a regulating activity of androstenediol on fatty tissue.
• This action is not likely to be exerted by dehydroepiandrosterone (DHEA), another C19 steroid precursor of androstenediol, having, like the latter, a protein anabolic action.
• DHEA dehydroepiandrosterone
• the treatment of obese patients with DHEA does not seem to cause a loss of fat mass (Usiskin KS, et al.. Int. J.
• a further advantage of the present invention is that the active ingredient is substantially non toxic.
• the medicaments according to the present invention are formulated as pharmaceutical compositions.
• Said compositions, which are a further object of the invention will be prepared according to conventional methods known to those skilled in the art. Said methods are, for example, described in "Remington's Pharmaceutical Sciences Handbook", Mack Publishing Company, New York, U.S.A.
• compositions according to the invention contain an effective amount of active ingredient in admixture with pharmaceutically acceptable carriers and excipients. More specifically, the compositions will be in the form of unitary dosages suitable for the administration of up to 30 mg of androst-5-ene-3 ⁇ , 17 ⁇ - diol, preferably 10 mg, daily. The dosage units can be single or subdivided in the therapeutical daily dose. Examples of pharmaceutical compositions include tablets, capsules, pills, solutions, syrups, injectable forms, topical forms such as creams or ointments, or transdermal formulations.
• Transdermal formulations are particularly preferred, and they are a further object of the invention. Such formulations have a good compliance and, more interestingly, are particularly suitable for long- term treatments, also considering the active principle half-life. These formulations provide an effective, homogeneous, cutaneous absorption, and they cause no blood peaks, as often occurs in topical treatments with conventional formulations.
• transdermal formulations consist of a solution of androst-5-ene-3 , 17 ⁇ - diol in a mixture of an alcohol (preferably absolute ethanol) and a glycol (preferably propylene glycol), added with one or more polymeric compounds, such as cellulose derivatives (for example ethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose), polyacrylic and/or polymethacrylic acid esters and the like, and further containing the conventional excipients and/or plasticizers .
• cellulose derivatives for example ethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose
• polyacrylic and/or polymethacrylic acid esters and the like polyacrylic and/or polymethacrylic acid esters and the like, and further containing the conventional excipients and/or plasticizers .
• Said formulations will be in contained in containers equipped with a dispenser to apply the correct dose of the formulation to the skin. After evaporation of the solvent, the film remaining on the skin releases the active principle in the space of 24 hr and can subsequently be removed by the usual detergents.
• the solution is distributed in an aluminium container coated internally with epoxy phenolic resins, equipped with a dispenser.
• Colloidal silica 1.000 Absolute ethanol q.s. to 100
• the solution is distributed in an aluminium container coated internally with epoxy phenolic resins, equipped with a dispenser.

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• Health & Medical Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Epidemiology (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Cosmetics (AREA)
• Materials For Medical Uses (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

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Cited By (4)

Citations (8)

• 1997
  • 1997-06-11 IT IT97MI001372A patent/IT1292129B1/it active IP Right Grant
• 1998
  • 1998-06-05 AU AU79187/98A patent/AU7918798A/en not_active Abandoned
  • 1998-06-05 WO PCT/EP1998/003392 patent/WO1998056386A1/en active Application Filing

Patent Citations (9)

Non-Patent Citations (6)

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