Katakura R, Mori T, Mineura K, Suzuki J
No Shinkei Geka. 1980 Nov;8(11):1057-62.
We reported a new dosage-form for intracranial administration which releases Bleomycin (BLM) for more than twenty days. The new dosage-form is a tablet which is a compressed form of lactose and BLM, further capsulized by ethylcellulose or Eudragit retard S. Two kinds of tablets were prepared: early-releasing type and late-releasing type, which differ with regard to ingredients and thickness of the capsule. In a buffer solution at 37 degrees C, the early-release tablet released BLM for 7 days and the late-type for between 20 and 30 days. The late-releasing type was used in the following experiments. BLM tablets were implanted into femoral muscle and peritoneal cavity of rats, and the residual BLM content in each tablet was measured after various periods. In femoral muscle, the half life of BLM in the tablet was 13 days and BLM was no longer found in the tablet after 30 days. In peritoneal cavity, the half life of BLM in the tablet was 15 days and 20% of the BLM still remained in the tablet after 30 days. The half life was 11 days in tablets implanted into the cerebrum of dogs. Following implantation of 4 tablets (12mg. p) into the cerebrum of dogs, CSF levels of BLM could be measured till the 20th day. Histological studies on dog cerebrum revealed a thin capsule consisting of collagenous fibers surrounding the tablet and small round cells or gliosis were seen around the capsule.
我们报道了一种用于颅内给药的新剂型，它能使博来霉素（BLM）释放超过20天。这种新剂型是一种片剂，由乳糖和BLM压缩而成，再用乙基纤维素或Eudragit缓释S包囊。制备了两种片剂：早期释放型和晚期释放型，它们在成分和胶囊厚度方面有所不同。在37℃的缓冲溶液中，早期释放片剂释放BLM达7天，晚期释放型则释放20至30天。在以下实验中使用了晚期释放型。将BLM片剂植入大鼠的股肌和腹腔，并在不同时间段后测量每片片剂中残留的BLM含量。在股肌中，片剂中BLM的半衰期为13天，30天后片剂中不再检测到BLM。在腹腔中，片剂中BLM的半衰期为15天，30天后仍有20%的BLM残留在片剂中。植入犬脑的片剂半衰期为11天。将4片（12mg.p）植入犬脑后，直到第20天仍可检测到脑脊液中BLM的水平。对犬脑的组织学研究显示，片剂周围有一层由胶原纤维组成的薄囊，囊周围可见小圆形细胞或胶质增生。
