Arginine-silicate-inositol complex and use thereof

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

2000-12-05

2002-02-05

Henley, III, Raymond (Department: 1614)

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Carbohydrate doai

C514S063000, C514S565000

Reexamination Certificate

active

06344444

ABSTRACT:

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,
178:619621, 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 silicon nutrition may promote production of protective HSPGs by endothelial cells.
Arginine, an essential amino acid, is the biosynthetic precursor for the nitric oxide (NO) produced by vascular endothelium (Moncada,
New Engl. J. Med.,
329:2002-2012, 1993). NO exerts vasodilatory, antiatherosclerotic and antithrombotic effects, and deficient endothelial production of NO may play a prominent pathogenic role in atherosclerosis, hypertension and diabetes (Calver et al.,
J. Hypertension,
10:1025-1031, 1992; Cooke et al.,
Arterioscler. Thromb.,
14:653-655, 1994; Rubanyi, in:
Cardiovascular Significance of Endothelium-Derived Vasoactive Factors,
Futura Publishing Co, Inc., New York, 1991, pp. xi-xix). In some though not all clinical studies, parenteral or oral administration of arginine has enhanced vascular NO synthesis (Drexler et al.,
Lancet,
338:1546-1550, 1991). In animal models of hypertension, arginine supplementation has moderated the increase in blood pressure (Chen et al.,
J. Clin. Invest.,
88:1559-1567, 1991; Laurant et al.,
Clin. Exp. Hyperten.,
17:1009-1024, 1995). Thus, under at least some circumstances, arginine availability can be rate-limiting for NO production. A recently published clinical study indicates that oral arginine can enhance endothelium-dependent relaxation in hypercholesterolemic young people (Creager et al.,
J. Clin. Invest.,
90:1248-1253, 1992; Clarkson et al.,
J. Clin. Invest.,
97:1989-1994, 1996) which is indicative of increased efficiency of vascular NO production.
There is a constant need for therapeutic/prophylactic agents capable of preventing or retarding the progression of atherosclerosis and promoting the formation of bone and cartilage. The present invention addresses these needs.
SUMMARY OF THE INVENTION
One embodiment of the present invention is a method of making an arginine-silicate-inositol complex comprising the steps of:
(a) combining arginine, a silicate salt and inositol to form a suspension;
(b) heating the suspension to promote gel formation;
(c) allowing the gel to crystallize;
(d) mixing the crystals formed in step (c) with an alcohol to promote crystallization; and
(e) collecting the crystals formed in step (d). Preferably, the silicate salt is potassium silicate. Advantageously, the heating is performed at about 95° C. The method may further comprise repeating step (d) prior to collecting the crystals. In one aspect of this preferred embodiment, the crystals are collected by filtration. Preferably, the crystallization-promoting alcohol is ethanol.
The present invention also provides an arginine-silicate-inositol complex formed by the method described above.
Another embodiment of the invention is a method for preventing or inhibiting atherosclerosis in a mammal, preferably a human, comprising the step of administering to the mammal an effective atherosclerosis-preventing or inhibiting amount of the arginine-silicon-inositol complex described above. Preferably, the administering step is parenteral or oral. Advantageously, the effective amount is between about 250 mg and about 2,500 mg; more advantageously, the effective amount is between about 500 mg and about 1,000 mg. For the average 70 kg man, this equals a dosage of between about 3.6 and 14 mg/kg (250-2,600 mg) and between about 7.1 mg/kg and 14 mg/kg (500 mg-1,000 mg), respectively.
Still another embodiment of the invention is a method for supplementing dietary arginine comprising administering to an individual the complex described above.
The present invention also provides an arginine-silicate-inositol complex, wherein the ratio of arginine to silicate to inositol is about 3:3:1.
Another embodiment of the present invention is the use of the arginine-silicon-inositol complex described above for supplementing dietary arginine.
The present invention also provides the use of the arginine-silicon-inositol complex described above for the prevention or inhibition of atherosclerosis.
Another embodiment of the invention is a met

Affiliated with

Also associated with

Rating

Arginine-silicate-inositol complex and use thereof does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Arginine-silicate-inositol complex and use thereof, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Arginine-silicate-inositol complex and use thereof will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2950752