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In vitro release of 1,3-bis(2-chloroethyl)-1-nitrosourea sustained-release microspheres and the distribution in rat brain tissues

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Neural Regeneration Research 2006年第9期1卷 793-796页

作者： Xia Li1, Liping Guo2, Qin Li3 1Central Pharmacy, General Hospital of Chinese People’s Armed Police Forces, Beijing 100039, China 2Department of Pharmaceutics, Zhengzhou Central Hospital, Zhengzhou 450007, Henan Province, China 3Teda International Cardiovascular Hospital, Tianjin 300457, China Central Pharmacy General Hospital of Chinese People's Armed Police Forces Beijing 100039 China Department of Pharmaceutics Zhengzhou Central Hospital Zhengzhou 450007 Henan Province China Teda International Cardiovascular Hospital Tianjin 300457 China

BACKGROUND: The implantation of released chemotherapeutic drugs, which takes biodegradable polymer as vector, into the tumor site can get high concentration and release the drug for a long time, it can directly act on the tumor cells, and reduce the general toxicity. OBJECTIVE: To explore the in vitro and in vivo course of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) sustained-release from BCNU-loaded polylactide (PLA) microspheres (MS) and location in rat brain tissue. DESIGN: A repetitive measurement. SETTING:Central Pharmacy, General Hospital of Chinese People’s Armed Police Forces. MATERIALS: Thirty male SD rats were used. PLA (Mr5000, batch number: KSL8377) was produced by Wako Pure Chemical Inc.,Ltd. (Japan); BCNU (batch number: 021121) by Tianjin Jinyao Amino Acid Co., Ltd.; BCNU-PLA-MS was prepared by the method of solvent evaporation and pressed into tablets (10 mg/tablet). High-performance liquid chromatography (HPLC) Agilent 1100 (USA); LS9800 liquid-scintillation radiometric apparatus (Beckman). Chromatographic conditions: Elite Hypersil ODS2 C18 chromatographic column (5 μm, 4.6 mm×150 mm); Mobile phase: methanol: water (50:50), flow rate was 1.0 mL per minute, wave length of ultraviolet detection was 237 nm, and the inlet amount of samples was 10 μL. METHODS: The experiments were carried out in the experimental animal center of the General Hospital of Chinese Armed Police from May 2004 to July 2005. ① In vitro BCNU-PLA-MS release test: BCNU-PLA-MS was prepared by the method of solvent evaporation, then placed in 0.1 mol/L phosphate buffered solution (PBS, pH 7.4, 37 ℃), part of MS were taken out at 1, 2, 3, 7, 10 and 15 days respectively, and the rest amount of BCNU in MS was determined by HPLC, then the curve of BCNU-PLA-MS release was drawn. ②In vivo BCNU-PLA-MS release and distribution test: The rats were anesthetized, then BCNU-PLA-MS were implanted to the site 1 mm inferior to the cortex of frontal lobe. Five rats were killed postoperatively at 4 hours, 1, 2, 3, 7 and 15 days, the residual MS wa

关键词： BCNU MS PLA nitrosourea sustained-release microspheres and the distribution in rat brain tissues chloroethyl

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MOLECULAR STRUCTURE OF 2-[BIS(2-chloroethyl)-AMINO]-6-BUTYLOXYMETHYL-TETRAHYDRO-2H-1, 3,2-OXA-ZAPHOSPHORINE-2-OXIDE

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Chinese Journal of Structural Chemistry 1993年第4期12卷 303-306页

作者： Chen Ru-Yu Zhang MingInstitute of Elemento-Organic Chemistry,Nankai University,Tianjin,300071Wang Ru-Ji Wang Hong-GenCentral Laboratory,Nankai University,Tianjin,300071 南开大学天津

The molecular structure of 2-[bis(2-chloroethyl)-amino]-6-t-butyloxymethyl-tetrahydro-2H-1,3,2-oxazaphosphorine-2-oxide has been determined by X-ray diffraction method.The crystal(C12H25Cl2NaO3P)is monoclinic with space group P21/a,a=11.965(2),b=10.335(3),c=14.543(5)A,β=102.24(2)°,V=1758(2)A3,Mr=347.22,Z=4,Dx=1.31 g/cm3,μ=4.66 cm-1,F(000)=736,R=0.051,Rw=0.054.The six-membered ring in this compound is in a distorted chair conformation with the t-butyloxymethyl group and the phosphoryl oxygen atom in equatorial positions which lead to cis-configuration.

关键词： BIS OXA-ZAPHOSPHORINE-2-OXIDE AMINO BUTYLOXYMETHYL-TETRAHYDRO-2H-1 chloroethyl MOLECULAR STRUCTURE OF 2

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TUMOUR CHEMOTHERAPY Ⅴ. SYNTHESIS OF SOME o-SUBSTITUTED-p-[BIS-(2-chloroethyl)-AMINO]-PHENYLALANINE AND TEST OF ANTITUMOUR ACTION

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Science in China,Ser.A 1962年第4期 483-498页

作者：潘百川高怡生陈瑞婷胥彬 Institute of Materia Medica Academia Sinica Shanghai Institute of Materia Medica Academia Sinica Shanghai

Nitrogen mustards are of significant importance in chemotherapy of cancer. Recently, numerous nitrogen mustard derivatives of the biologically active substances, such as vitamines, amino acids, pyrimidins, etc., have been synthesized and proved to possess definite antitumour activities. Bergel et al. and Larionov et al. synthesized the nitrogen mustard derivative of phenyl-

关键词： chloroethyl PHENYLALANINE AND TEST OF ANTITUMOUR ACTION SYNTHESIS OF SOME o-SUBSTITUTED-p TUMOUR CHEMOTHERAPY AMINO BIS

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