SYNTHESIS AND ANTITUMOR-ACTIVITY OF CONJUGATES OF POLY(ALPHA-MALIC ACID) AND 5-FLUOROURACILS BOUND VIA ESTER, AMIDE OR CARBAMOYL BONDS

被引：43

作者：

OUCHI, T

FUJINO, A

TANAKA, K

BANBA, T

机构：

[1] Department of Applied Chemistry, Faculty of Engineering, Kansai University, Suita-shi, Osaka

来源：

JOURNAL OF CONTROLLED RELEASE | 1990年 / 12卷 / 02期

关键词：

5-fluorouracil; antitumor activity; biodegradable polymer; poly (α-malic acid);

D O I：

10.1016/0168-3659(90)90090-G

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Since poly(malic acid) is a biodegradable and bioabsorbable lactic acid-type polyester having pendent modifiable carboxylic acid groups, it is of interest as a polymeric carrier of drugs. In order to provide macromolecular pro-drugs of 5-fluorouracil (5FU), and so reduce the side-effects of 5FU, the covalent attachment of 5FUs to poly(α-malic acid) and poly(α-malic acid-co-lactic acid) through amide, ester or carbamoyl bonds was carried out. The antitumor activity of the resulting 5FU conjugates with poly(α-malic acid) was tested against P-388 lymphocytic leukemia in mice in vivo (i.p./i.p.). When the unreacted pendent carboxylic acid groups in the polyα-malic acid)-5FU conjugates were masked by methyl groups, conjugates were obtained which prolonged life and did not display acute toxicity at a dose of 200-800 mg/kg. These samples were therefore considered to be macromolecular pro-drugs of 5FU. Furthermore, for the purpose of elucidating the nature of 5FU release and main-chain cleavage in vivo, the hydrolyses of the pendent amide, ester or carbamoyl bonds and the main-chain ester bonds in poly(α-malic acid)-5FU conjugates and poly(α-malic acid-co-lactic acid)-5FU conjugates were studied in vitro at 37° C in aqueous solutions of various kinds. © 1990.

引用

页码：143 / 153

页数：11

共 25 条

[11]

Ouchi, Hagita, Inoi, Kawashima, Tashiro, Synthesis of vinyl polymer by fixing 5-fluorouracils through organosilicon groups via carbamoyl bonds and its antitumor activity, J. Bioact. Compat. Polym., 3, (1988)

[12]

Ouchi, Banba, Fujimoto, Hamamoto, Synthesis and antitumor activity of chitosan carrying 5-fluorouracils, Die Makromolekulare Chemie, 190, (1989)

[13]

Shimada, Matsushima, A protease inhibitor from Penicillium cyclopium Part I Purification and partial characterization, Agricultural and Biological Chemistry, 33, (1969)

[14]

Shimada, Matsushima, A protease inhibitor from Penicillium cyclopium Part II Some properties of the inhibitor, Agricultural and Biological Chemistry, 33, (1969)

[15]

Shimada, Matsushima, Fukumoto, Yamamoto, Poly -(l) -malic acid

[16]

a new protease inhibitor from Penicillium cyclopium, Biochem. Biophys. Res. Commun., 35, (1969)

[17]

Matsushima, Shimada, A protease inhibitor from Penicillium cyclopium Part III The mode of action of the inhibitor, Agricultural and Biological Chemistry, 34, (1970)

[18]

Matsushima, Action of poly-l-malic acid on various proteolytic enzymes, Agricultural and Biological Chemistry, 34, (1970)

[19]

Lenz, Vert, Malic acid polymers, (1981)

[20]

Braud, Vert, Poly(β-malic acid) derivatives, a new type of polyvalent polymeric drug carrier, Polym. Prepr., Amer. Chem. Soc. Div. Polym. Chem., 24, (1983)

← 1 2 3 →