Picosulphate, 4,4'-(2-pyridylmethylene)-bisphenol-bis(hydrogen sulfate) (ester) disodium salt, is disclosed in the Merck Index , 11th ed. (1989), S. Budavari, ed., No. 7377, p.1175. Picosulphate is a known active ingredient for use as a laxative. Picosulphate is an inactive prodrug that is hydrolyzed by colonic bacteria to bis-(p-hydroxyphenyl)-pyridyl-2-methane (commonly known as "desacetyl bisacodyl") which is the active species). Contact of the desacetyl bisacodyl with the mucosa stimulates sensory nerve endings to produce increased propulsive peristaltic contractions of the colon which accelerate movement of contents through the colon. Administration of picosulphate has also been shown to promote fluid and ion accumulation in the colon, which increases its laxative effect. Since desacetyl bisacodyl acts upon contact with lumenal mucosa of the large intestine, its laxative effect is dependent upon generation of sufficient levels of the drug in the lumen of the colon.
Commercially available picosulphate laxatives are designed to deliver the picosulphate to the small intestine. Although these dose forms provide effective laxative activity, doses which produce maximal laxation also evoke undesirable side effects such as secondary episodes of diarrhea or repeat bowel movements.
It has been surprisingly discovered that delivery of picosulphate to the colon as a rapidly dissolving matrix, or in a solubilized form, produces maximal laxation at doses which do not evoke secondary episodes of diarrhea.
An advantage of providing picosulphate to patients using the compositions of this invention is that laxation benefits are generally achieved without the secondary diarrhea commonly associated with conventional picosulphate compositions. Another advantage is that such laxation benefits are often achieved more quickly than with conventional picosulphate compositions. Another advantage is that a lesser dosage amount of picosulphate is needed to achieve laxation than is needed with conventional picosulphate compositions. Another advantage is that due to the lesser dosage amount and the more prompt onset of laxation activity, the side effects of cramping and pain are lessened.