Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Peptide containing doai
Patent
1988-12-22
1991-04-09
Stone, Jacqueline
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Peptide containing doai
514 2, 514815, 424542, A61K 3702, A61K 3558
Patent
active
050065122
ABSTRACT:
The invention provides novel therapeutic usages of inhibitors of a potassium channel of the cells. Since the increase of the intracellular calcium concentration is known to trigger various reactions which destroy the cells, the prevention of calcium entry by calcium channel blockers are known to be beneficial in protecting cell membranes in ischemic and traumatic injuries. However, the importance of potassium ions in cell injuries has not been well recognized. Using charybdotoxin (which is not a calcium channel blocker, but is a potassium channel blocker), the inventor found that this compound as well as related compounds have protecting effects in brain is chemia, liver ischemia and spinal cord injury at an extremely low concentration (0.05-0.14 mg/kg body weight). In in vitro experiments, these compounds inhibited the irreversible denaturation of sickle red cell membranes caused by sickling-unsickling stress at an extremely low concentration (2.times.10.sup.-8 M).
In an attempt to prepare a polypeptide molecule from charybdotoxin, the inventor digested charybdotoxin with an enzyme, fractionated by a size extrusion column chromatography, and obtained a polypeptide with the molecular weight of approximately 3,000. This new compound was named MR-117 for an identification purpose. It was demonstrated that MR-117 had protective effects on various organs and on sickle cells.
REFERENCES:
Sigma Chemical Company Catalog (1989), p. 1250.
Gelmers, Am. J. Cardiol. (1985), 55:144B-148B.
Ohnishi et al., Biol. Abstracts, vol. 82(13), 20391, 1986.
Miller et al., Nature, vol. 313 (Jan. 24, 1985), pp. 316-318.
Smith et al., J. Biol. Chem., vol. 261, No. 31 (Nov. 5, 1986), pp. 14607-14613.
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