Method for selective reduction of Lp(a)

Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...

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514562, 514574, 514706, 514948, 424439, 424440, A61K 31415, A61K 31195, A61K 3119, A61K 31095

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active

052721663

ABSTRACT:
The present invention relates to methods and corresponding agents for lowering plasma Lp(a) levels by the administration of agents that reduce Lp(a) and selectively separate therefrom the apo(a) component and/or prevent Lp(a) formation. Suitable agents include sulfhydryl reducers, such as N-acetylcysteine. The present method and agents may be administered alone or in conjunction with other therapy for the lowering of LDL cholesterol.

REFERENCES:
(Author Unknown) Opportunities in Biology, National Research Counsel (pp. 328-334), (1978).
Armstrong, Victor W., et al., "Isolation, characterization, and uptake in human fibroblasts of an apo(a)-free lipoprotein obtained on reduction of lipoprotein(a)" J. Lipid Res. 26:1314-1323 (1985).
Eldeib, M. M. R., et al., "Reversal of the Biological Activity of Escherichia coli Hear-Stable Enterotoxin by Dusulfide-reducing Agent Infection & Immunity" 51(1):24-30 (Jan., 1986).
Bihari-Varga, M., et al. "Interaction of Lippoprotein Lp(a) and Low Density Lipoprotein with Glycosaminoglycans from Human Aorta". Arteriosclerosis 8(6):851-857 (Nov.-Dec. 1988).
Reynolds, J.(ed) Martindale The Extra Pharmacopoeid (29th ed) (1989). Copies of the pages submitted herewith relate generally to sulfhydryl group reducing agents.
Dictionnaire Vidal (1989) contains a monograph in French pertaining to the commercially available product MUCOMYST. While a translation of this monograph has not been obtained, but a copy of the MUCOMYST product brochure which has been circulated in the United States is enclosed.
Hajjar, K. A., et al., "Lipoprotein (a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis" Nature 339(6222):303-305 (May 25, 1989).
Kostner, Gerhard M., et al., "HMG CoA Reductase Inhibitors Lower LDL Cholesterol Without Reducing Lp(a) Levels" Circulation 80(5):1313-1319 Nov. 1989.
Utermann, G. "The Mysteries of Lipoprotein (a)" Science 246:904-910 (Nov. 17, 1989).
Gavish, D., et al., "Plasma Lp(a) Concentration is Inversely Correlated with the Ratio of Kringle IV/Kringle v Encoding Domains in the Apo(a) Gene" J. Clin Invest. 84:2021-2027 (Dec. 1989).
Gavish, D., et al., "Lipoprotein(a) reduction by N-acetylcysteine" The Lancet 337(8735):203-204 (Jan. 26, 1991).
Stalenhoef, A., "N-acetylcysteine and lipoprotein": The Lancet 337(8739):491 (Feb. 23, 1991).
Hansen, P. R., "Lipoprotein(a) reduction by N-acetylcysteine" The Lancet 337(8742):672-673 (Mar. 16, 1991).
Chemical Abstracts (106: 101184a) 1987.
Chemical Abstracts (107: 114684j) 1987.

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