Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1997-03-18
1998-09-15
Jordan, Kimberly
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
514171, 514173, 514211, 514451, 514460, 514510, 514824, A61K 31705, A61K 3156, A61K 3158, A61K 3155, A61K 3135, A61K 3121
Patent
active
058078347
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
This invention relates to a pharmaceutical combination of cholesterol absorption inhibitors and cholesterol synthesis inhibitors, kits containing such combinations and the use of such combinations to treat hypercholesterolemia and atherosclerosis, in mammals.
Plasma cholesterol levels have been positively correlated with the incidence of clinical events associated with coronary heart disease (CHD). Thus, pharmacological interventions that reduce cholesterol levels in mammals have a beneficial effect on CHD. In particular, decreased plasma low density lipoprotein (LDL) cholesterol levels are associated with decreased atherosclerosis and a decreased risk of CHD, and hypolipidemic agents used in either monotherapy or combination therapy are effective at reducing plasma LDL cholesterol levels and the subsequent risk of CHD.
Cholesterol metabolism in mammals involves a series of pathways including cholesterol absorption in the small intestine, cholesterol biosynthesis in numerous tissues (primarily the liver and small intestine), bile acid biosynthesis in the liver and reabsorption in the small intestine, synthesis of cholesterol-containing plasma lipoproteins by the liver and intestine, catabolism of the cholesterol-containing plasma lipoproteins by the liver and extrahepatic tissues and excretion of cholesterol and bile acids by the liver. These processes are interrelated, thus their regulation is intricate and intended to maintain cellular and plasma cholesterol levels in a fairly narrow range. Accordingly, perturbations in one facet of cholesterol metabolism can have multiple effects.
Such is the case with cholesterol absorption in the small intestine. For example, an increase or a decrease in the percentage of intestinal cholesterol flux that is absorbed ultimately increases or decreases plasma cholesterol concentrations. Examples of agents that inhibit cholesterol absorption include ACAT inhibitors such as Cl-976 (Krause, B. R. et al., Clin. Biochem., 25, 371-377, 1992), 58-035 (Heiden, J. G. et al., J. Up. Res., 24,1127-1134, 1983) and melinamide, stigmastanyl phosphorylcholine and analogs disclosed in EP-430,078A, .beta.-lactam cholesterol absorption inhibitors disclosed in WO 93/02048 and EP 524,595A, sulfated polysaccharides disclosed in U.S. Pat. No. 5,063,210 and other compounds such as neomycin and naturally occurring plant saponins. In addition, the steroidal glycosides described in WO 93/07167-A1 and U.S. Pat. Nos. 4,602,003 and 4,602,005 have been proposed as useful for the control of hypercholesterolemia. Also, other steroidal glycosides having superior hypocholesterolemic activity are disclosed in commonly assigned PCT application PCT/U.S.93/04092 published as WO 94/00480 (the disclosure of which is hereby incorporated by reference) and commonly assigned PCT applications PCT/IB94/00349 and PCT/IB94/00348 (the disclosures of which are hereby incorporated by reference). The steroidal glycosides specified above inhibit cholesterol absorption thereby decreasing plasma cholesterol levels.
Inhibition of cholesterol biosynthesis has also been demonstrated to be an effective LDL-lowering modality in man. Cholesterol synthesis occurs in multiple tissues, but principally the liver and the intestine. It is a multistep process starting from acetylcoenzyme A catalyzed by a series of enzymes including hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase, HMG-CoA synthase, squalene synthetase, squalene epoxidase, squalene cyclase and lanosterol demethylase. Inhibition of catalysis of these enzymes or blocking HMG-CoA reductase gene expression is recognized as an effective means to reduce cholesterol biosynthesis (thus they are referred to as cholesterol synthesis inhibitors) and can lead to a reduction in cholesterol levels. For example, there are known HMG-CoA reductase inhibitors (e.g., lovastatin, simvastatin, pravastatin, fluvastatin) that are used for the treatment of hypercholesterolemia.
Recently adopted National Cholesterol Education Program guidelines recommend aggressiv
REFERENCES:
patent: 4602005 (1986-07-01), Malinow
patent: 5661145 (1997-08-01), Davis
Benson Gregg C.
Jordan Kimberly
Olson A. Dean
Pfizer Inc.
Richardson Peter C.
LandOfFree
Combination of a cholesterol absorption inhibitor and a choleste does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Combination of a cholesterol absorption inhibitor and a choleste, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Combination of a cholesterol absorption inhibitor and a choleste will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-87152