Drug – bio-affecting and body treating compositions – Inorganic active ingredient containing – Aluminum – calcium or magnesium element – or compound containing
Patent
1997-08-26
1998-12-15
Jordan, Kimberly
Drug, bio-affecting and body treating compositions
Inorganic active ingredient containing
Aluminum, calcium or magnesium element, or compound containing
424702, 514249, 514419, 514458, 514474, 514929, A61K 3306, A61K 3304, A61K 31495, A61K 3150
Patent
active
058493387
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention is in the field of pharmacology, and relates specifically to the pharmacological treatment of conditions associated with the constriction of small blood vessels.
2. Description of the Prior Art
Vasoconstriction, or the reduction in the cross-sectional area of the lumen of small blood vessels, is a potentially lethal condition arising in a variety of pathologies, and is due either to vasospasm, inadequate vasodilatation, thickening of the vessel wall, or the accumulation of flow-restricting materials on the internal wall surfaces or within the wall itself. Vasoconstriction is a major factor in various diseases, including progressive generalized atherogenesis, heart attack, stroke, hypertension, glaucoma, migraine, hypertension of pregnancy, and diabetes mellitus, among others.
Vasoconstriction originates in a variety of ways. One example is the local conversion by dysfunctional endothelium of circulating low density lipoproteins (LDL) into oxidatively activated low density lipoproteins ((ox)LDL). (ox)LDL is internalized via cellular macrophage scavenger receptors creating lipid-engorged macrophages, called "foam cells." These cells are bound to the vascular endothelium and subendothelium, release a variety of growth factors and cytokines that stimulate vascular smooth muscle cell proliferation and trigger the increase of the local endothelial expression of leukocyte adhesion molecules and leukocyte chemotaxants; all precursors of progressive vascular atherosclerosis and its subsequent reduction of vascular cross-sectional area.
Another example is the endothelial cell release of endothelin-1, a powerful arterial vasoconstrictor. Repetitive or prolonged vasospasm results in mechanical hypertrophy, proliferation of the microvascular smooth muscle fibers (hyperplasia), and a consequent secondary thickening of the vascular media wall. Various mechanisms leading to the release of endothelin-1 are known. These mechanisms include: its induction by the increase in availability of intracellular ionic calcium which results from the opening of calcium channels in dysfunctional endothelium; and its induction by the reactive sulfhydryl group of homocysteine which is released by endothelial cells that have been damaged by "foam cells."
A third example of vasoconstriction is the activation, rolling, local accumulation, and eventual cell-to-cell adhesion of platelets and white blood cells on the endothelial surface and within the subendothelium. This accumulation stimulates the platelets to activate and attract those macrophages which will be converted into "foam cells," initiate smooth muscle cell proliferation, and release additional leukocyte chemoattractants. These events result in additive vasospastic and mechanical vascular blockade.
A fourth example is the conversion of glucose to sorbitol, which causes irregular vasoconstriction or vasodilatation due to the osmotically induced death of vascular pericytes in diabetes mellitus.
Magnesium is known to reduce the risk of vasoconstriction and also to influence a broad diversity of functions in physiology and pathology. In addition to improving adenosine triphosphate (cATP) energy-requiring metabolism and anaerobic phosphorylation, magnesium suppresses the conversion of LDL to (ox)LDL, reduces platelet and white blood cell aggregation and adhesion, and serves as a physiological calcium channel blocker, thereby reducing the production of endothelin-1 by atherosclerotic endothelial cells. Its action in improving cATP and prostacyclin synthesis of EDRF (Endothelial Derived Relaxation Factor--otherwise referred to as nitric oxide), reduces vasoconstriction by actively inducing vasorelaxation.
The recommended daily allowance of ionic magnesium for humans is 350 mg. Magnesium deficiencies have been documented in many segments of the world population. It is estimated that the average adult in Western society has a dietary magnesium shortfall of 90-178 mg per day. This fundamental deficiency is more clearly seri
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Pearson Don C.
Richardson Kenneth T.
ChronoRX LLC
Jordan Kimberly
LandOfFree
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