ZUSAMMENFASSUNG:Poly [2-(methylsulfinyl)athylacrylat] (2a) und Poly[2-(methylsulfinyl)athylmethacrylat] (2b) wurden synthetisiert und auf ihre vermittelnde Wirkung bei transkutaner Resorption einiger Pharmaka untersucht. 2b verbesserte die Resorption der Phosphorsaureester Dimethoat@ und Paraoxon@ und der p-Aminohippursaure und war etwa mit der Wirksamkeit von DMSO vergleichbar.Ein geringer penetrationsfordernder Effekt ergab sich fur Dinitrochlorbenzol. Nicht beeinflurjt wurde die dermale Resorption von Isoprenalinsulfat. Die beiden Polymeren zeigten eine gute Lokalvertraglichkeit und 2b auch keine akute Allgemeintoxizitat bei systematischer Anwendung. Der fur DMSO charakteristische knoblauchartige Geruch trat nach lokaler und systemischer Anwendung der beiden Polymeren nicht auf. SUMMARY:Poly[2-(methylsulfinyl)ethyl acrylate] (2a) and poly[2-(methylsulfinyl)ethyl methacrylate] (2b) were synthesized in order to examine their ability to enhance the penetration of pharmaceutical agents through the skin. 2b improved the absorption of the two phosphoric acid esters Dimethoat@ and Paraoxon' as well as that of p-aminohippuric acid by an amount which was comparable to the effect shown by DMSO.A smaller effect was observed in thecase ofdinitrochlorobenzene. The dermal absorption of isoprenalin sulfate was not influenced. Both polymers showed a good local compatibility and 2b no acute common toxicity at systemic levels of application. The characteristic garlic-like odor of DMSO was not observed after either local or systemic application of the polymers. '1 7. Mitteilung cf. ''.

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A number of acryl and methacryl derivatives of different sulfanilamides (la-I) were prepared and polymerized. The fixation of the sulfonamide to the polymerizable group was carried out directly, using the acryl-and methacrylamides, and by means of spacer groups, to favour the enzymatic or hydrolytic release of the drug moiety. Selected sulfonamide types of different pKA values were used, and the pH-dependant solubility of the corresponding polymers was studied.The monomeric acryloyl and methacryloyl sulfonamides were homopolymerized radically by AIBN. Fordistributionstudiespolysulfadiazineacrylamide, ''C-labelledin the main chain (W), was synthesized. Copolymerization with 2-methylsulfinylethy1 methacrylate (Sa) yielded water soluble polymers of lower toxicity. Eventually biodegradable polymers containing sulfonamide units in the backbone were obtained by anionic polymerization of acryloyl and methacryloyl sulfanilamide.The new monomers and polymers were characterized by elemental analysis, IR-and NMR-spectroscopy, pyrolysis mass spectrometry, and hydrolytic degradation. ZUSAMMENFASSUNG:Eine Reihe von Acryl-und Methacrylderivaten verschiedener Sulfanilamide (la-I) wurde hergestellt und polymerisiert. Die Fixierung der Sulfonamide erfolgte direkt, als Acrylund Methacrylamid, und mit Hilfe von Spacergruppen, zur Aktivierung der enzymatischen oder hydrolytischen Abspaltung des Pharmakons. Es wurden Sulfonamide mit verschiedenen pKs-Werten verwendet und die pH-abhangige Loslichkeit der entsprechenden Polymeren untersucht.Die monomeren Acryloyl-und Methacryloylsulfonamide wurden radikalisch mit AIBN homopolymerisiert. Zur Untersuchung der Korperverteilung wurde ' 4C hauptkettenmar-*) kiertes Polysulfadiazinacrylamid (2e') dargestellt. Durch Copolymerisation mit 2-Methylsulfinylathylmethacrylat (5a) wurden wasserlosliche Polymere mit geringerer Toxizitat erhalten. Eventuell biologisch abbaubare Polymere mit Sulfonamidgruppen in der Hauptkette wurden durch anionische Polymerisation von Acryloyl-und Methacryloylsulfanilamid dargestellt. Die neuen Monomeren und Polymeren wurden durch Elementaranalyse, IR-und NMR-Spektroskopie, Pyrolyse-Massenspektrometrie und hydrolytischen Abbau charakterisiert.

Poly[2-(methylsulfinyl)ethyl acrylate](1) was synthesized as well as derivatives 14C-labelled in side groups (6) or 14C-labelled in the main chain (11). Polymer 11 with the 14C-labelled main chain was fractionated by precipitation. The q-M-relation determined by measurements of unlabelled polymers in the ultracentrifuge for comparison was used to establish the viscosimetrically determined molecular weights of the labelled fractions. After intravenous application of aqueous solutions of the polymer in rats the excretion rate up to 72 h after treatment was ascertained to ca. 50%; the concentration in the blood serum was found to be strikingly high. A tendency to reinforced storage in organs of high phagwytose activity by growing molecular weight was observed. The tumor affinity wasif at alllow.

Sulfadiazinacrylamid was absorbed after oral and intraperitoneal application in rats to a high extent; the absorption from the intraperitoneum was retarded. Glucose treatment delayed the absorption after both application forms. At comparatively high renal and enteral excretion rates the biological half life time of the monomer was estimated to 8 h. A tumouraffinity was not found but there were indications for a preferred storage in the RES.Poly[sulfadiazinacrylamide] was absorbed after intraperitoneal injection to a clear extent, where at the beginning of the treatment under simultaneous glucose load the absorption was delayed. 24 h after injection higher concentrations in metabolic organs and those of the RES were established. After oral application of the polymer an effective resorption was excluded. The elimination of the intraperitoneally injected polymer happened at negligibly low dose rates; after oral application the elimination process was finished within 24 h after treatment of the test animals. The polymer showed no tumouraffinity.