Kabushiki Kaisha Yakult Honsha

Arai Seisakusho Co., Ltd

Eiichi Sugino

Tadashi Miyasaka

Seigo Sawada

Masahiko Mutai

Kenichiro Nokata

Yoshio Arai

Eigoro Tsukagoshi

An oil seal of the type having a metallic reinforcement rig whose outer peripheral portion is oil-tightly fitted into a housing, characterized in that after the formation of fabrication of said metallic reinforcement ring, the latter is subjected to a nitriding hardening process so that its durability of a raw material of said metallic reinforcement ring; and a seal lip of formed over the inner peripheral edge portion of an annular flange portion of said metallic reinforcement ring.

Oil seal comprising lip seal with thermal expansion controlled

New camptothecin derivatives possessing high anti-tumor activity with slight toxicity, represented by the general formula: ##STR1## wherein R.sup.1 is a hydrogen atom, a halogen atom or an alkyl group with 1-4 carbon atoms and X is a chlorine atom or --NR.sup.2 R.sup.3 where R.sup.2 and R.sup.3 are the same or different and each represents a hydrogen atom, a substituted or unsubstituted alkyl group with 1-4 carbon atoms or a substituted or unsubstituted carbocyclic or heterocyclic group, with the proviso that when both R.sup.2 and R.sup.3 are the substituted or unsubstituted alkyl groups, they may be combined together with the nitrogen atom, to which they are bonded, to form a heterocyclic ring which may be interrupted with --O--, --S-- and/or &gt;N--R.sup.4 in which R.sup.4 is a hydrogen atom, a substituted or unsubstituted alkyl group with 1-4 carbon atoms or a substituted or unsubstituted phenyl group and wherein the grouping --O--CO--X is bonded to a carbon atom located in any of the 9-, 10- and 11-positions in the ring A of camptothecin, as well as an ammonium salt or an alkali metal salt thereof. These new camptothecin derivatives are prepared by reacting a 7-R.sup.1 -camptothecin derivative having a hydroxyl group in any of the 9-, 10- and 11-positions on the ring A thereof with phosgen and then reacting, if necessary, the resultant 7-R.sup.1 -camptothecin derivative having a chlorocarbonyloxy group in the same position on the ring A thereof with an amine HNR.sup.2 R.sup.3 or by reacting a 7-R.sup.1 -camptothecin derivative having a hydroxyl group in any of the 9-, 10- and 11-positions on the ring A thereof with a carbamoyl chloride Cl-CONR.sup.2 R.sup.3.

Camptothecin derivatives and process for preparing same

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Tokyo, Japan

Eiichi Sugino