Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Cyclopentanohydrophenanthrene ring system doai
Patent
1998-01-12
1999-11-30
Henley, III, Raymond
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Cyclopentanohydrophenanthrene ring system doai
A61K 3156
Patent
active
059943378
ABSTRACT:
The present invention relates to a method of using 17.alpha.-dihydroequilenin and metabolic conjugates thereof to prevent and reduce atherogenesis in males and females without causing endometrial proliferation in females and without producing feminizing changes in males. 17.alpha.-dihydroequilenin was evaluated for its effects on plasma lipid and lipoprotein, glucose, insulin concentrations, coronary artery vasomotor function, and reproductive organ and mammary gland proliferation in atherosclerotic mammals. 17.alpha.-dihydroequilenin was found to prevent endothelium-dependent vasoconstriction in males (p<0.05) and ovariectomized females (p<0.08). 17.alpha.-dihydroequilenin treatment increased plasma apolipoprotein A-l concentrations (p<0.05) and lowered fasting insulin concentrations (p<0.05) without changing fasting plasma glucose concentrations in males. 17.alpha.-dihydroequilenin had no other effects on plasma lipid and lipoprotein concentrations in either males or females. Also, 17.alpha.-dihydroequilenin exhibited no trophic effects on the uterus, endometrium, or breast, and no effect on either prostatic or testicular weight. Thus, 17.alpha.-dihydroequilenin may prevent breast and prostatic hyperplasia and neoplasia, and has no feminizing effects on the male urogenital system or mammary gland.
REFERENCES:
patent: 3507889 (1970-04-01), Marshall
patent: 4154820 (1979-05-01), Simoons
patent: 5545635 (1996-08-01), Bryant et al.
patent: 5719137 (1998-02-01), Washburn et al.
Washburn, S.A. et al., A Conjugated Equine Estrogen With Differential Effectsd on Uterine Weight and Plasma Cholesterol In the Rat. Am J Obstet Gynecol 1993; 169:251-6.
Wagner, J.D., et al., A Non-Feminizing Conjugated Equine Estrogen Decreases Artenal LDL Degradation and Improves Vascular Reactivity In Male Rhesus Monkeys (abstract). Circulation 1995; 92:1-627.
Merck Index; 10.sup.th Edition; (1983); p. 3159, #3154.
Cefalu, W.T. et al., The Effects of Hormone Replacement Therapy on Insulin Sensitivity in Surgically Postmenopausal Cynomolgus Monkeys (Macaca fascicularis). Am J Obstet Gynecol 1994;171:440-5.
Wagner, J.D. et al., Estrogen and Progesterone Replacement Therapy Reduces Lipoprotein Accumulation in the coronary Arteries of Surgically Postmenopausal cynomolgus macaques. J Clin Invest 1991;88-1995-2002.
Goodman A.L. et al., Composite Pattern of Circulating LH, FSH, estradiol, and Progsterone During the Menstrual Cycle in Cynomolgus Monkeys. Pro Soc Exp Biol Med 1977;155:479-81.
Wilson M.E. et al, Effects of a Natural Versus Artificial Environment on the Tempo of Maturation in in Female Rhesus Monkeys. Endocrinology 1988; 123:2653-61.
Williams J.K. et al., Effects of Hormone Replacement Therapy on Reactivity of Atherosclerotic Coronary Arteries in Cynomolgus Monkeys. J Am Coll Cardio 1994;24:1757-61.
Cline J.M. et al., Effects of Hormone Replacement Therapy on the Mammary gland of Surgically Postmenopausal Cynomolgus Macaues. Am J Obstet Gynecol 1996;174:93-100.
Cline J.M. et al., Divergent Effects of Hormone Replacement in Mammary and Endometrial Tissues of Macaques labstratct. Menopause 1995;2:255.
Cattoretti G. et al., Monoclonal Antibodies Against Recombinant Parts of the Ki-67 Antigen (MIB1 and MIB3) Detect Proliferating Cells in Microwave-Processed Formalin-Fixed Paraffin Sections. J Pathol 1992;168:357-63.
Lindholm J. et al., A Morphometric Filter Improves the Diagnostic Value of Morphometric Analyses of Frozen Histopathologic Sections from Mammary Tumors. Anal Cell Pathol 1992;4:443-9.
Williams J.K. et al., Determinants of Coronary Artery Reactivity in Premenopausal Female Cynomolgus Monkeys with Diet-Induced Atherosclerosis. Circulation 1994;90:983-7.
Hamm T.E. et al., Effects of Gender and Social Behavior on the Development of Coronary Artery Atherosclerosis in Cynomolgus Monkeys. Atherosclerosis 1983;221:48-57.
Collins P. et al., 17--Estradiol Attenuates Acetylcholine-Induced Coronary Arterial Constriction in Women but Not Men with Coronary Heart Disease. Circulation 1995;92:24-30.
Reis S.E. et al., Estrogen has an Acute Beneficial Effect on Coronary Vasoreactivity in Man [abstract]. Circulation 1995;92:1-249.
Subbiah M.T.R. et al., Antioxidant Potential of Specific Estrogens on Lipid Peroxidation. J Clin Endocrinol Metab 1993;77:1095-7.
Wilcox J.G. et al., The Biological Effects of Individual Estrogen Components in Conjugated Equine Estrogens (CEE) and Their Possible Modulation of Insulin Resistance and Oxidation of LDL [abstract]. J Soc Gynecol Invest 1995;2:153.
Lyman G.W. et al., Assay for Conjugated Estrogens in Tables U sing Fused-Silica Capillary Gas Chromatography. J Chromatogr 1982;234:234-9.
Stern M. Pharmacology of Conjugated Oestrogens; Maturitas 1982;4:33-9.
Bhavnani, B., The Saga of the Ring B Unsaturated Equine Estrogens; Endocrine Reviews, 1988.
Bhavnani, B., Interaction of Ring B Unsaturated Estrogens with Estrogen Receptors of Human Endometrium and Rat Uterus, Steroids, 1991, vol. 56, Apr. pp. 201-210.
Dodge, J.A., Premarin Components: Uterine,Cholesterol Lowering, and Bone Metabolic Effects, Jun. 1996 Endocrine Research, Lilly Research Laboratories.
Stern, M., Pharmacology of Conjugated Oestrogens; Elsener Bio-Medical Press, 1982 pp. 332-339.
Bhavnani, B., et al., The Metabolism of Equilin in Normal Men; J. Steriod Bio-chem, vol. 17, pp. 217-223, 1982.
Washburn, S. et al., Effects of 17.alpha.-Dihydroequilenin on Rat Hippocampal Dendritic Spine Density; (1990).
Washburn, S. et al., 17.alpha.-Dihydroequilenin Increases Hippocampal Dendritic Spine Density of Ovariectomized Rats (1988).
Pharmacokinetics of 17.beta.-Dihydroequilin Sulfate and 17.beta.-Dihydroequilin in Normal Postmenopausal Women; Journal of Clinical Endorcrinology and Metabolism, vol. 78 No. 1, pp. 197-204, 1994.
Pharmacokinetics of Equilin and Equilin Sulfate in Normal Postmenopausal Women and Men; J. of Clinical Endo. and Meta., 1983, vol. 56, No. 5, pp. 1048-1056.
Effect of 17.alpha.-dihydroequilin sulfate, a water-soluble estrogen of PremarinR, on atherosclerosis in cholesterol-fed rabbits, Tuesday, Oct. 11, 1994:Poster Abstracts, p. 102, #40.
Physicians' Desk Reference; p. 2787 1996.
Washburn, S.A., et al., 17.alpha.-Dihydroequilenin increases hippocampal dendritic spine density of ovariectomized rats, Brian Research, Accepted Feb. 25, 1997; pp. 241-244.
Adams Michael R.
Adelman Steven J.
Clarkson Thomas B.
Cline J. Mark
Register Thomas C.
American Home Products Corporation
Henley III Raymond
Kennedy, Esq. Pat Winston
Wake Forest University
LandOfFree
Effects of 17.alpha.-dihydroequilenin on plasma lipid and lipopr does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Effects of 17.alpha.-dihydroequilenin on plasma lipid and lipopr, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Effects of 17.alpha.-dihydroequilenin on plasma lipid and lipopr will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1672768