Arginine silicate inositol complex and use thereof

Details Arginine silicate inositol complex and use thereof Arginine silicate inositol complex and use thereof

1999-12-13

2000-12-05

Henley, III, Raymond

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Carbohydrate doai

514 63, 514565, 536121, 562561, 556 9, A61K 3170, A61K 31695, A61K 31195, C07D48722

Patent

active

061567353

DESCRIPTION:

BRIEF SUMMARY
FIELD OF THE INVENTION

The present invention relates to an arginine silicate complex and its use in the prevention and treatment of atherosclerosis, as a dietary supplement and for promotion of structural integrity of bones and cartilage.


BACKGROUND OF THE INVENTION

Atherosclerosis is a complex and chronic disease involving the gradual accumulation of lipids, collagen, elastic fibers and proteoglycans in the arterial wall. Current methods of managing atherosclerosis include a low-fat diet, exercise and various cholesterol-lowering drugs. Although these methods can significantly retard the progression of atherosclerosis, they are not entirely satisfactory.
Heparin sulfate proteoglycans (HSPGs) produced by vascular endothelium are believed to retard the migration, multiplication and phenotypic transition of vascular smooth muscle cells, events which play a central role in the atherogenic process, and to maintain an anticoagulant luminal surface by binding and activating antithrombin III (Clowes et al., Nature, 265:625-626, 1977; Guyton et al., Circ. Res., 46:625-634, 1980; Edelman et al., Proc. Natl. Acad. Sci. U.S.A., 87:3773-3777, 1990).
Various silicon compounds administered orally or parenterally have been demonstrated to inhibit cholesterol-induced intimal hyperplasia (atherosclerosis) in rabbits (Loeper et al., Athersclerosis, 33:397-408, 1979; Loeper et al., in Biochemistry of Silicon and Related Problems, Plenum Press, New York, 1978, pp 281-296; Garson et al., J. Pharm. Sci., 60:1113-1127, 1971). The injection or ingestion of nutritionally available silicon compounds (i.e. monomethyltrisilanol, lysine silicate, sodium silicate) prevented the characteristic intimal thickening and fragmentation of arterial elastic fibers observed in atherosclerosis. Additionally, several epidemiological studies report that increased dietary intakes of silicon are associated with a reduced risk of coronary heart disease in humans (Schwarz et al., Lancet, i:454-457, 1977; Schwarz et al., Lancet, i:538-539, 1977; Bassler, Brit. Med. J., 1:919, 1978; Parr, Lancet, i:1087, 1980).
Studies in growing young rats and chicks show that severe dietary silicon deficiency results in abnormal bone and joint structures, apparently due to subnormal production of collagen and mucopolysaccharides (Carlisle, J. Nutr. 106:478-484, 1976; Carlisle, J. Nutr. 110:1046-1055, 1980). Silicon promotes the synthesis of collagen and mucopolysaccharides in vitro (Carlisle et al., Fed. Proc. 37:404, 1978; Carlisle et al., Fed. Proc. 39:787, 1980). The biochemical method by which silicon achieves this effect are unknown. Silicone has been shown to enhance bone mineral density. When an organosilicon compound (monomethyltrisilanol) was administered to postmenopausal women by injection at a dose of 50 mg twice weekly, femoral density increased significantly by an average of 4.7% over 14 months of administration (Eisinger et al., Magnesium Res. 6:247-249, 1993). In ovariectomized rats, oral orthosilicic acid slowed bone turnover and increased the bone formation rate (Hott et al., Calcif. Tissue Int. 53:174-179, 1993).
Bone and cartilage are dynamic tissues in both juvenile and adult animals. In bone, osteoclasts solubilize the hydroxyapatite bone matrix and degrade collagen, whereas osteoblasts concurrently rebuild bone through collagen synthesis and hydroxyapatite deposition. Analogously, chondrocytes in cartilage simultaneously degrade the collagen and proteoglycan matrix and resynthesize it. The impact of silicone on bone and cartilage formation in adult animal is essentially unknown. However, it is highly unlikely that the role of silicon in bone and cartilage metabolism is limited to juvenile animals.
The nutritional role of silicon is to support adequate synthesis of mucopolysaccharides, proteoglycans and collagen (Schwarz et al., Nature, 239:333-334, 1972; Carlisle, Science, 178:619-621, 1972; Carlisle, J. Nutr., 106:478-484, 1976; Schwarz, in Biochemistry of Silicon and Related Problems, Plenum Press, New York, 1978, pp. 207-230). Optimal sili

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