Therapeutic methods and delivery systems utilizing sex steroid precursors

• US 5,824,671 A
• Filed: 06/07/1995
• Issued: 10/20/1998
• Est. Priority Date: 01/19/1993
• Status: Expired due to Fees

• Current Assignee: Endorecherche
• Original Assignee: Endorecherche
• Inventors: Labrie, Fernand
• Primary Examiner(s): Clardy, S. Mark
• Assistant Examiner(s): Cebulak, Mary C.
• Application Number:
  US08/480,592
• Time in Patent Office: 1,231 Days
• Field of Search: 514/176, 514/178, 514/179, 514/180, 514/181
• US Class Current: 514/178
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/565 not substituted in position 17 beta by a carbon atom, e.g. estrane, estradiol
• CPC Class Codes: A61K 31/566 having an oxo group in position 17, e.g. estrone
• CPC Class Codes: A61K 31/5685 having an oxo group in position 17, e.g. androsterone
• CPC Class Codes: A61K 31/57 substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
• CPC Class Codes: A61K 31/58 containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin digitoxin A61K31/7048
• CPC Class Codes: A61K 8/63 Steroids; Derivatives thereof
• CPC Class Codes: A61P 13/00 Drugs for disorders of the urinary system
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 15/02 for disorders of the vagina
• CPC Class Codes: A61P 15/12 for climacteric disorders
• CPC Class Codes: A61P 15/18 Feminine contraceptives
• CPC Class Codes: A61P 17/00 Drugs for dermatological disorders
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 19/04 for non-specific disorders of the connective tissue
• CPC Class Codes: A61P 19/10 for osteoporosis
• CPC Class Codes: A61P 21/00 Drugs for disorders of the muscular or neuromuscular system
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 5/00 : Drugs for disorders of the endocrine system
• CPC Class Codes: A61P 5/26 : Androgens
• CPC Class Codes: A61P 5/34 : Gestagens
• CPC Class Codes: A61P 9/00 : Drugs for disorders of the cardiovascular system
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61Q 19/00 : Preparations for care of the skin
• CPC Class Codes: C07J 1/0011 : substituted in position 17 by a keto group
• CPC Class Codes: C07J 43/003 : not condensed
• CPC Class Codes: C07J 43/006 : spiro-condensed

Abstract

Sex steroid precursors such as dehydroepiandrosterone and dehydroepiandrosterone sulphate, and compounds converted in vivo to either of the foregoing, are utilized for the treatment of vaginal atrophy, hypogonadism, diminished libido, loss of collagen or connective tissues in the skin, and, in combination with an estrogen and/or progestin, for the treatment of menopause. The precursors may be formulated for percutaneous or transmucosal administration. Gels, solutions, lotions, creams, ointments and transdermal patches for the administration of these precursors are provided, as are certain pharmaceutical compositions and kits which can be used for the prevention and treatment of a wide variety of conditions related to decreased secretion of sex steroid precursors by the adrenals.

Claims

1. A therapeutic method of treating reduced or imbalanced concentrations of sex steroids comprising applying an effective amount of a pharmaceutical composition for percutaneous or transmucosal delivery to an outer surface of skin or mucosa of a patient in need of such treatment, said pharmaceutical composition comprising a carrier having dissolved therein at least one sex steroid precursor selected from the group consisting of dehydroepiandrosterone, dehydroepiandrosterone sulfate, and compounds converted in vivo into either of the foregoing, said precursor being present at a concentration of at least 7% by weight relative to the total pharmaceutical composition, and said carrier being compatible with skin or mucosa and allowing penetration of said precursor through said skin or mucosa, said carrier having sufficient viscosity to maintain said precursor on a localized area of skin or mucosa, without running or evaporating, for a time period sufficient to permit substantial penetration of said precursor through said localized area of said skin or mucosa to achieve a DHEA blood serum level of about 4 to about 13 micrograms per liter.

2. The method of claim 1 wherein said compound is dehydroepiandrosterone.

3. The method of claim 1 wherein said compound is applied to the skin in admixture with a base which is compatible with human skin and which allows percutaneous penetration of said compound through the skin.

4. The method of claim 1 wherein said compound is applied to vaginal mucosa in a mixture with a base which is compatible with human vaginal mucosa and which allows penetration of said compound through the mucosa.

5. The method of claim 1 for the inhibition of development or treatment of body fat accumulation.

6. The method of claim 1 for the inhibition of development or treatment of cardiovascular disease or atherosclerosis.

7. The method of claim 1 for inhibition of development and proliferation or treatment of breast cancer.

8. The method of claim 1 for inhibition of development and proliferation or treatment of endometrial cancer.

9. The method of claim 1 for the inhibition of the occurrence or treatment of loss of muscle mass.

10. The method of claim 1 for the inhibition of development or treatment of insulin resistance.

11. The method of claim 1 for the inhibition of development or treatment of fatigue or loss of energy.

12. The method of claim 1 for the inhibition of development or treatment of connective tissue diseases.

13. The method of claim 1 for inhibition or occurrence of loss of memory as associated with aging.

14. The method of claim 1 wherein said method is used for inhibition of development or treatment of physical symptoms of menopause.