Tannic acid: chemistry, analysis, and toxicology. An episode in the pharmaceutics of radiology.

Abstract

In october 1962, Clysodrast2 in a pre-measured powder dosage form containing 1.5 mg of bisacodyl tannex and 2.5 g of tannic acid was made available to American radiologists for cleansing and barium enemas. The association of three patient deaths with the use of tannic acid (1) and two with Clysodrast (2) was reported recently. Although several extenuating circumstances surrounded the association between Clysodrast and the two reported deaths, all shipments of Clysodrast in interstate commerce were voluntarily stopped in July 1964. This was done in order that the safety level could be re-evaluated. At that time, many meaningful studies concerning this question were initiated. More recently a re-evaluation of efficacy was undertaken. The cooperation and help of numerous scientists in completing these studies is gratefully acknowledged. Our contributions to this large pool of new knowledge were mainly on the chemistry, analysis, and toxicology of tannic acid. It is these aspects I wish to review. Chemistry The chemistry of tannic acid is complicated because it is of natural origin and consists of a mixture of complex substances. Although many plant species contain tannins, commercial tannic acid has its origin in Turkish nutgalls gathered from the young twigs of Quercus infectoria. The powdered galls are extracted with ether, alcohol, and water. Tannic acid is soluble in water. A yield of 50 to 70 per cent tannic acid is obtained from the water extract. Tannic acid may be obtained as an amorphous fluffy or dense powder, yellowish-white to light-brown in color. It is further characterized by having an acid reaction in water, essentially no odor, and a strongly astringent taste. The powder holds about 10 per cent water. The commercial tannic acid contains many ester linkages and is hydrolysable in the presence of acids, alkalies, or enzymes. Hydrolysis yields primarily glucose and gallic acid. Small amounts of other polyhydric alcohols and other phenolic acids such as m-digallic, ellagic and chebulic acids which are chemically related to gallic acid are also found. Gallic acid is always found in commercial tannic acid in small amounts. When purified tannic acid is chromatographed, gallotannin consisting of an isomeric mixture of polygalloylated glucose appears as one spot. Hydrolysis of purified gallotannin yields glucose and gallic acid. An average structural approximation for gallotannin can be given as eight or nine gallic acid molecules for each glucose molecule. The gallic acid is bound to glucose as well as to other gallic acid molecules through ester linkages. The polyphenolic groups in the tannic acid are responsible for its astringent action. This astringent action is caused by its ability to precipitate protein. The ability to precipitate protein is partly due to the high molecular weight of gallotannin. Other noteworthy chemical properties of tannic acid include: Darkens on exposure to air and light.