Abstract
In a search for chemotherapeutic agents with specific osteotropic properties, a study was made of the general mechanism of drug fixation in bone. It has been shown in previous studies 1 that the following properties are necessary for the fixation of drugs in the inorganic material of bone tissue: 1. Electronegativity of the substance. 2. High degree of diffusibility in the dissolved state. 3. Low solubility of its calcium salt. 4. Formation in vitro of an insoluble complex with calcium phosphate. (Properties described under 3 and 4 are interrelated, in that only anions giving slightly soluble calcium salts are adsorbed irreversibly by calcium phosphate.
For the purposes of this study, a colored bismuth compound (sodium salt of bismuth 1.2-dihydroxy-anthraquinone 3.sulfonic acid) was prepared which meets the above conditions, namely: 1. In this compound Bi is anionic, as demonstrated by electrolysis. 2. The compound is highly diffusible in vivo and in vitro. In 1.5% agar, the speed of diffusion is 16 mm in 16 hours as compared to that of Congo Red with 10 mm in 16 hours.
In mice, urinary elimination of the bismuth complex occurred 15-20 minutes after i.p. injection of 0.18 mg of bismuth per kg body weight. 3. The calcium salt of the compound has a low solubility. By adding CaCl2 to a solution of the Bi preparation, the calcium salt is precipitated. 4. Ten grams of calcium phosphate adsorb the entire quantity present in 100 cc of a Mol/20 solution of the bismuth preparation. After filtering and washing the calcium phosphate with water, the adsorbed Bi compound can be detected quantitatively.
Sodium bismuth dihydroxy anthraquinone sulfonate, when injected into mice intraperitoneally in doses of 1.5 mg of bismuth per kg of body weight, produces a definite red coloration of bone.
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