Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Radical -xh acid – or anhydride – acid halide or salt thereof...
Patent
1998-09-28
2000-02-22
Jordan, Kimberly
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Radical -xh acid, or anhydride, acid halide or salt thereof...
514909, A61K 31195
Patent
active
06028109&
DESCRIPTION:
BRIEF SUMMARY
The present invention is concerned with medicaments, and more particularly medicaments for use in the treatment of obesity.
Obesity can be described as a state of excessive accumulation of body fat, and is widely considered to be a major public health problem, being associated with substantially increased morbidity and mortality, as well as psychological problems, reduced economic achievement, and discrimination. Examples of health and social problems thought to be caused or exacerbated by obesity include coronary heart disease, stroke, obstructive sleep apnoea, diabetes mellitus, gout, hyperlipidemia, osteoarthritis, reduced fertility, impaired psychosocial function, reduced physical agility and increased risk of accidents, impaired obstetrical performance, reduced economic performance and discrimination and prejudice.
Causes of obesity remain unclear, however whether obesity is of genetic origin or is promoted by a genotype-environment interaction, or both, it remains true that energy intake must have exceeded metabolic and physical (work) energy expenditure for there to have been surplus energy available for fat deposition. There remains considerable uncertainty, however, over the relative importance of different mechanisms in achieving this positive energy balance.
Treatment of obesity remains a problem. Although it is well established that morbidity and mortality are increased in obese individuals, it is unclear whether dieting results in decreased long-term risk of early death. The major obesity intervention has been the many different forms of dieting, which are often fads without a sound scientific basis. Results have shown that dieting is a component of the weight loss regimens of 84% of women and 76-78% of men attempting to lose weight. A further important obesity intervention is physical activity which increases energy expenditure, both during the actual period of exercise and during subsequent period of rest. Thus, exercise can promote negative energy balance provided that energy intake is not increased concomitantly. Exercise, however, in general, has been found to be only moderately successful in promoting weight loss. A program combining both dieting and exercise as well as behaviour modification is widely viewed as the optimal approach to weight loss. Food restriction alone can be very successful in promoting weight loss, but, a significant component of the weight loss can be lean tissue. In addition, food restriction results in a decline in total energy expenditure which serves to reduce the extent of negative energy balance. Studies have demonstrated that combination programs involving both food restriction and exercise promote a substantial loss of fat and, at the same time, promote a maintenance of lean tissue.
It can be appreciated from the above that obesity remains a problem, and that no reliable treatment thereof has been established. There is therefore a need to develop medicaments and treatment regimes effective in the alleviation of obesity. We have now unexpectedly found that a certain group of compounds are particularly advantageous for use in the treatment of obesity.
More particularly we have found that agonists of the peroxisome proliferator activated receptor alpha (hereinafter referred to as PPAR.alpha.) are useful in the treatment of obesity. Peroxisome proliferator activated receptor (hereinafter referred to as PPAR) is a known member of the steroid/retinoid/thyroid hormone receptor family of ligand activated transcription factors and is activated, interalia, by high micromolar concentrations of certain peroxisome proliferators. PPAR.alpha., peroxisome proliferator activated receptor gamma (hereinafter referred to as PPAR.gamma.) and peroxisome proliferator activated receptor delta (hereinafter referred to as PPAR.delta. or NUCI) have respectively been identified as subtypes of PPARs.
The present invention therefore provides PPAR.alpha. agonists for use in the treatment of obesity, and methods of treating obesity employing PPAR.alpha. agonists. More particularly, the pre
REFERENCES:
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Keller, H., et al., Proceedings of The National Academy of Sciences of USA, vol. 90, No. 6, Mar.15,1993, pp. 2160-2164, "Fatty Acids and Retinoids Control Lipid Metabolism Through Activation of Peroxisome Proliferator-Activated Receptor-Retinoid X Receptor Heterodimers".
Kliewer, S.A., et al., Proceedings of the National Academy of Sciences of USA, vol. 91, Jul. 1994, pp. 7355-7359, "Differential Expression and Activation of a Family of Murine Peroxisome Proliferator-Activaed Receptors".
Forman, B.M., et al., Proceedings of the National Academy of Sciences, vol. 94, No. 9, Apr. 1997, pp. 4312-4317, Hypolipidemic Drugs, Polyunsaturated Fatty.
Assimacopoulos, F., et al., American Journal of Physiology, vol. 260, No. 2, 1991, pp. R278-R283, "Effects of A Peroxisome Proliferator on Beta-Oxidation and Overall Energy Balance in Obese (fa/fa) Rats".
Brink Robert H.
Glaxo Wellcome Inc.
Jordan Kimberly
LandOfFree
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