Enhancement of vascular function by modulation of endogenous nitric oxide production or activity
Patent 5891459 Issued on April 6, 1999. Estimated Expiration Date: November 9, 2015. Estimated Expiration Date is calculated based on simple USPTO term provisions. It does not account for terminal disclaimers, term adjustments, failure to pay maintenance fees, or other factors which might affect the term of a patent.
424/439, Food or edible as carrier for pharmaceutical424/441, Chewable tablet or wafer426/648, Nutritional or dietetic supplement, including table salt426/656, Protein, amino acid, or yeast containing514/564, Plural nitrogens nonionically bonded514/565N-N or N=C(-N)-N containing (e.g., hydrazines, hydrazones, or quanidines, etc.)
Vascular function and structure is maintained or improved by long term administration of physiologically acceptable compounds, namely L-arginine, L-lysine, physiologically acceptable salts thereof, and polypeptide precursors thereof, which enhance the level of endogenous nitric oxide or other intermediates in the NO induced relaxation pathway in the host. In or in combination, other compounds, such as B6, folate, B12, or an antioxidant, which provide for short term enhancement of nitric oxide, either directly or by physiological processes may be employed.
Other References
Ignarro et al. Basic Polyamino Acids Rich in Arginine . . . Circ. Res. Feb. 1989, vol. 64, No. 2, pp. 315-329
McNamara et al. L. Arginine Inhibits Balloon Catheter . . . Biochem. Biophys. Res. Comm. 28 May 1993, vol. 193, No. 1, pp. 291-296
Rock et al. L-arginyl-L-lysine and L-arginyl-L-arginine . . . Med.Sci.Res. 1990, vol. 18, pp. 165-166
Andrews et al., "Low-density Lipoproteins inhibit endothelium-dependent Relaxation in Rabbit Aorta", Nature (1987), 327:237-239
Bath et al., "Nitric Oxide and Prostacyclin: Divergence of Inhibitory Effects on Monocyte Chemotaxis and Adhesion to Endothelium in Vitro", Arterioscierosis and Thrombosis (1991), 11:254-260
Cooke, "Endothelial Dysfunction in Disease States", Current Opinion in Cardiology (1990), 5:637-644
Drexler et al., "Correction of Endothelial Dysfunction in Coronary Micocirculation of Hypercholesterolaemic Patients", The Lancet (1991), 338:1546-1550
Garg and Hassid, "Nitric Oxide-generating Vasodilators and 8-Bromo-Cyclic Guanosine Monophosphate Inhibit Mitrogenesis and Proliferation of Cultured Rat Vascular Smooth Muscle Cells", J. Clin. Invest. (1989), 83:1774-1777
Girerd et al., "L-Arginine Augments Endothelium-Dependent Vasodilation in Cholesterol-Fed Rabbits", Circulation Research (1990), 67:1301-1308
Heistad et al., "Augmented Responses to Vasoconstrictor Stimuli in Hypercholesterolemic and Atherosclerotic Monkeys", Circulation Research (1984), 54:711-718
Kubes et al., "Nitric Oxide: An Endogenous Modulator of Leukocyte Adhesion", PNAS USA (1991), 88:4651-4655
Kugiyama et al., "Impairment of Endothelium-Dependent Arterial Relaxation by Lysolecithin in Modified Low-density Lipoproteins", Nature (1990), 344:160-162
Kuo et al., "Pathophysiological Consequences of Atherosclerosis Extend Into the Coronary Microcirculation: Restoration of Endothelium-dependent Responses by L-Arginine", Circulation Research (19920, 70:465-476
Lefer et al., "Role of Endothelium-derived Relaxing Factor as a Cardioprotective Agent in Myocardial Ischemia", Basil, Karger (1990), 190-197
Minor et al., "Diet-induced Atherosclerosis Increases the Release of Nitrogen Oxides from Rabbit Aorta", J. Clin. Invest. (1990), 86:2109-2116
Mitchell et al., "Native LDL Inhibits the Release of Endothelial Derived Relaxing Factors by Reducing the Activity of Endothelial Nitric Oxide Synthase", (Abstract), J. Vasc. Res. (1992), 29:169
Pohl and Busse, "EDRF Increases Cyclic GMP in Platelets During Passage Through the Coronary Vascular Bed", Circulation Research (1989), 65:1798-1803
Radomski et al., "Comparative Pharmacology of Endothelium-derived Relaxing Factor, Nitric Oxide and Prostacyclin in Platelets", Br. J. Pharmacol. (1987), 92:181-187
Ross, "The Pathogenesis of Atherosclerosis--an Update", The New England Journal of Medicine (1986), 314:488-500
Rossitch, Jr. et al., "L-Arginine Normalizes Endothelial Function in Cerebral Vessels from Hypercholesterolemic Rabbits", J. Clin. Invest., 87:1295-1299 (1991)
Stamler et al., "N-Acetylcysteine Potentiates Platelet Inhibition by Endothelium-derived Relaxing Factor", Circulation Research (1989), 65:789-795
Tanner et al., "Oxidized Low Density Lipoproteins Inhibit Relaxations of Porcine Coronary Artieries: Role of Scavenger Receptor and Endotheiium-derived Nitric Oxide", Circulation, 83:2109-2116 (1991)
Tomita et al., "Rapid and Reversible Inhibition by Low Density Lipoprotein of the Endothelium-dependent Relaxation to Hemostatic Substances in Porcine Coronary Arteries", Circulation Research (1990), 66:18-27
Weidinger et al., "Persistent Dysfunction of Regenerated Endothelium After Balloon Angioplasty of Rabbit lliac Artery", Circulation (1990), 81:1667-1679
Yamamoto et al., "Videomicroscopic Demonstration of Defective Cholinergic Arteriolar Vasodilation in Atherosclerotic Rabbit", J. Clin. Invest. (1988), 81:1752-1758
Lankin, "Atherosclerosis as a Free Radical Pathology", Inst. Congr. Ser. Excerpta Med. (1992), 998:385-8
Zembowicz, "The Biological Role of L-Arginine/Nitric Oxide Pathway", Folia Med. Cracov. (1992), 33:103-11
November 9, 2015. Estimated Expiration Date is calculated based on simple USPTO term provisions. It does not account for terminal disclaimers, term adjustments, failure to pay maintenance fees, or other factors which might affect the term of a patent.
