beta glucuronidase activity and / or ph dependent lekemedel and a procedure for framstellning of such lekemedel and anvendning for selective treatment of diseases

摘要

Glucuronide having a cytotoxic aglycone which escorts a more active toxic effect in acid medium than in alkaline medium or which is water-soluble in alkaline medium and insoluble or only slightly water-soluble in acid medium. The cpds. is pref. a beta-D-glucronic acid derivative of 2,4-dinitrophenol, m-chlorocresol, 4,6-dinitroocersol, 4-chloro-3,5-zylanol, chlorothymol, 2-phenyl-6-chlorophenyl, 5-chloro-7-iodo-quinoline-8-o-, podophyllotoxin. p-codo-phenol, phenylsuphazole or pref. methacrylonitrile. Used for treating tumours esp. those having a strong beta-glucuronidose activity. The hyper acidification of the tumour cells causes. decongugation of the glucuronide with release of the aglycone at the site of the tumour cells whilst healthy cells are maintained at an alkaline pH. The aglycone may also contain a radio-active isotope to give an in-situ radio-therapeutic effect. These radioactive glucoronide-aglycones can be used to diagnose and pin-point the presence of tumour cells by hyper acidification and use of a radio-isotope e.g. 131I, 133 I or 35S, which emits a ray capable of being detected in a complete body scan. The invention also allows detection of tumours and bacteria having a beta-glucuronidase, activity by detection of the quantity of free glucuronic acid present in the urine. The invention also allows treatment of bacterial injections where the bacteria has strong beta-ducuronidase activity e.g. streptococcus, staphylococcus and E. coli infections.