MACROMOLECULAR PRODRUGS .2. ESTERS OF L-DOPA AND ALPHA-METHYLDOPA

被引：20

作者：

ZORC, B ^{[1
]}

LJUBIC, M ^{[1
]}

ANTOLIC, S ^{[1
]}

FILIPOVICGRCIC, J ^{[1
]}

MAYSINGER, D ^{[1
]}

ALEBICKOLBAH, T ^{[1
]}

JALSENJAK, I ^{[1
]}

机构：

[1] MCGILL UNIV,DEPT PHARMACOL & THERAPEUT,MONTREAL H3A 2T5,QUEBEC,CANADA

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 1993年 / 99卷 / 2-3期

关键词：

POLYMERIC PRODRUG; MACROMOLECULAR CARRIER; ALPHA; BETA-POLY(N-HYDROXYETHYL)-DL-ASPARTAMIDE; L-DOPA ESTER; ALPHA-METHYLDOPA ESTER; 1-BENZOTRIAZOLYLCARBONYL GROUP; MICRODIALYSIS;

D O I：

10.1016/0378-5173(93)90355-J

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

L-Dopa and alpha-methyldopa were attached by an ester linkage to alpha,beta-poly(N-hydroxyethYl)-DL-aspartamide (PHEA), a hydrophilic polymer, previously proposed as a drug carrier. Ester bonding was achieved by means of 1-benzotriazolylcarbonyl (Btc) group as both an N-protecting and C-activating group in the starting amino acids. In the same way several simple esters Of L-dopa and alpha-methyldopa were prepared. Release of active substances based on hydrolysis of PHEA adducts was studied in vitro, and the following (pseudo) first order release rate constants for L-dopa and alpha-methyldopa were obtained, 1.06 X 10(-3) and 6.91 X 10(-4) min-1, respectively. In addition, characterization of the PHEA-L-dopa adduct was carried out in vivo using an intracerebral microdialysis technique in order to evaluate the prolonged release eventually achieved.

引用

页码：135 / 143

页数：9

共 28 条

[1] HYDROPHILIC-INTERACTION CHROMATOGRAPHY FOR THE SEPARATION OF PEPTIDES, NUCLEIC-ACIDS AND OTHER POLAR COMPOUNDS [J].

ALPERT, AJ .

JOURNAL OF CHROMATOGRAPHY, 1990, 499 :177-196

[2] HYDRODYNAMIC PROPERTIES OF A NEW PLASMA EXPANDER - POLYHYDROXYETHYLASPARTAMIDE [J].

ANTONI, G ;

NERI, P ;

PEDERSEN, TG ;

OTTESEN, M .

BIOPOLYMERS, 1974, 13 (09) :1721-1729

[3]

ANTONI G, 1979, FARM ED PRAT, V34, P146

[4]

BIANCHINE J R, 1976, Clinical Pharmacokinetics, V1, P313, DOI 10.2165/00003088-197601050-00001

[5] IMPROVED DELIVERY THROUGH BIOLOGICAL-MEMBRANES .4. PRODRUGS OF L-DOPA [J].

BODOR, N ;

SLOAN, KB ;

HIGUCHI, T ;

SASAHARA, K .

JOURNAL OF MEDICINAL CHEMISTRY, 1977, 20 (11) :1435-1445

[6]

Butula I., 1981, CROAT CHEM ACTA, V54, P435

[7]

BUTULA I, 1907, CROAT CHEM ACTA, V49, P837

[8]

BUTULA L, 1983, SYNTHESIS-STUTTGART, P327

[9] SYNTHETIC MODEL POLYMERS IN THE STUDY OF PROTEIN IMMOBILIZATION ON GLYCIDYL METHACRYLATE CARRIERS [J].

DROBNIK, J ;

VLASAK, J ;

PILAR, J ;

SVEC, F ;

KALAL, J .

ENZYME AND MICROBIAL TECHNOLOGY, 1979, 1 (02) :107-112

[10]

DROBNIK J, 1979, J POLYM SCI PS, V66, P65

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