Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Cyclopentanohydrophenanthrene ring system doai
Patent
1995-11-06
1998-08-18
Robinson, Allen J.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Cyclopentanohydrophenanthrene ring system doai
540 94, A61K 3158, C07J 1700
Patent
active
057958831
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/DE94/00316 filed Mar. 18, 1994.
BACKGROUND OF THE INVENTION
The invention relates to novel androgens and derivatives and analogs thereof, such as anabolic agents, and to methods of using them.
Male hormones, that is, androgens, such as testosterone and dihydrotestosterone and various esters of testosterone, such as testosterone proprionate, testosterone enanthate, testosterone undecanoate or testosterone bucyclate, or derivatives and analogs, such as anabolic agents like mesterolone, are used in man to treat an androgen deficiency. This may be a primary androgen deficiency (testicular insufficiency), secondary androgen deficiency (hypothalamo-hypophyseal insufficiency) or "complex androgen deficiency" (hypothalamo-hypophyseal-testicular) in the aging male. This latter is also known as "male menopause", or more recently, "andropause".
Complex androgen deficiency in the male leads to an existential disturbance as a consequence of which, at an indefinite time but typically from the age of 45 on, signs of male hormone deficiency can arise, with continuously varying symptoms. These signs are predominantly in the form of mood fluctuations, along with psychosomatic performance problems. Often these problems are accompanied by increasing impotentia coeundi, as a consequence of which signs of depression and loss of self-esteem often occur; mental alertness can be impaired as well. Spermatogenesis is affected less severely. The drop in anabolic effectiveness of the androgens, often in combination with a lack of exercise, leads to increasing atrophy of the musculature. Bone mass is also reduced as a result, along the lines of osteoporosis. Hematopoiesis can be lessened as well.
It is notable that the occurrence of benign enlargement or hypertrophy of the prostate has a course that is parallel with these changes, although in that disease an increased enzymatic conversion of testosterone to dihydrotestosterone in the prostate is suspected. An analogy with iodine deficiency of the thyroid gland can be suspected, in which along with the formation of a tissue hyperplasia known as goiter, triiodothyronine is increasingly formed enzymatically from the reduced thyroxin substrate in the thyroid gland. A testosterone deficiency in the prostate can also increase the formation of dihydrotestosterone by increased enzymatic conversion, which represents a tissue hyperplastic stimulus in the prostate, resulting in the formation of tissue hyperplasia known as benign enlargement of the prostate. According to this hypothesis, benign enlargement of the prostate could be predominantly the result of a testosterone deficiency. The causation by androgens, and especially the metabolism of testosterone into dihydrotestosterone, in conjunction with the occurrence of arteriosclerosis, has not yet been explained in all its details. Yet precisely this causality should be paid particular attention in deciding whether to institute male hormone replacement.
Overall there is a need for more precise knowledge of the action of androgens in the aging male, but there is also a need for androgen derivatives that do not develop unfavorable effects in essential male target organs, such as the prostate and the vascular system.
Because of the lack of certainty about the safety of the effects and side effects of testosterone and its derivatives, including the anabolic agents, the indications for therapy or replacement (hormone replacement) with male hormones and their analogs are thus far only inadequately Office!.
Androgens are used for replacement in the human male only when primary or secondary androgen deficiency is found with certainty, and is generally done in the form of monthly depot injections. Other preparations, for instance for transdermal application, are in development. Oral replacement of male hormones is also being employed. The so-called first-pass effect of the action of the hormones on metabolism in the liver and protein synthesis (for instance, lipoprotein synthesis with a change in lipid metabolism) is o
REFERENCES:
patent: 5202316 (1993-04-01), Claussner et al.
BMJ Publications, "Androgens and Anabolic Steroids". British Med. J., vol. 1, 165-167, 1969.
Patel, Pharmacotherapy of cognitive impairment in Alzheimer's disease: A review. J. Geriatric Psychiatry and Neurology 8: 81-95, 1995.
Stein, Internal Medicine, 4th edition, chapters 71-72, pp. 699-715, 1995.
Role of Reactive Oxygen Species in Biological Processes, H. Sies, Klinisce Wochen Schrift, 1991.
Molecular and Cellular Biochemistry III, 1992, pp. 143-147, S. Chatterjee, "Role of Oxidized human plasma low density lipoproteins . . . ".
Journal of Cardiovascular Pharmacology, 1992, B. Weisser, et al, "Oxidized Low-Density Lipoproteins in Atherogenesis . . . ".
Klinische Wochenschrift, 1991, pp. 1032-1038, H.F. Hoff, et al, "Oxidation of LDL: Role in Atherogenesis".
Klinsche Wochenschrift, 1991, pp. 1039-1045, K.L.H. Carpenter, et al, "Oxygen Radicals and Atherosclerosis".
Annuals of Internal Medicine, vol. 116, No. 12 (Part 1), C.J. Bagatell, et al, "Physiologic Testosterone Levels in Normal Men . . . ".
Medicine and Science in Sports and Exercise, 1992, vol. 24, No. 3, Andrew S. Weyrich, et al, "The effects of testosterone on lipids . . . ".
Clinical and Experimental Pharmacology & Physiology, 1986, pp. 513-518, D.M. Crist, et al.
Int. Journal of Sports Med. 6, 1985, pp. 139-144, M. Alen, et al, "Serum Lipids in Power Athletes . . . ".
Int. J Fertil, 37, 1992, pp. 83-92, M.D.G. Gillmer, "Mechanism of Action/Effects of Androgens on Lipid Metabolism".
Bailliere's Clinical Andocrinology and Metabolism, 1990, vol. 4, No. 4, David Crook, et al, "Endocrine Control of Plasma Lipoprotein Metabolsim . . . ".
Godsland, et al, "Sex, Plasma Lipoproteins, and Atherosclerosis . . . ", 1987, pp. 1467-1503.
Maturitas 11 (1989), pp. 305-317, Hassager, et al "Nandrolone Decanoate Treatment of Post-Menopausal Osteoperosis . . . ".
Droescher Peter
Hesch Rolf-Dieter
Kaufmann Gunter
Menzenbach Bernd
Oettel Michael
Badio Barbara
Jenapharm GmbH
Robinson Allen J.
Striker Michael J.
LandOfFree
Androgens and anabolic agents does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Androgens and anabolic agents, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Androgens and anabolic agents will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1114921