Synthesis and properties of dextran-nalidixic acid ester as a colon-specific prodrug of nalidixic acid
| Autor: | Jeoung Soo Lee, Yun Jin Jung, Min Ju Doh, Young Mi Kim |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
Nalidixic acid Colon Pharmaceutical Science Hydrochloric acid Rats Sprague-Dawley chemistry.chemical_compound Nalidixic Acid Drug Delivery Systems Anti-Infective Agents Culture Techniques Drug Discovery medicine Organic chemistry Animals Prodrugs Solubility Antibacterial agent Pharmacology Dextranase Depolymerization Organic Chemistry Anticoagulants Dextrans Esters Prodrug Hydrogen-Ion Concentration Rats Dextran chemistry Hydrochloric Acid medicine.drug Nuclear chemistry |
| Zdroj: | Drug development and industrial pharmacy. 27(4) |
| ISSN: | 0363-9045 |
| Popis: | Dextran-nalidixic acid ester (dextran-NA) with a varied degree of substitution (DS) was synthesized as a colon-specific prodrug of nalidixic acid (NA). Solubility in water (mg/ml) of dextran-NA with DS (mg NA/100 mg dextran-NA) of 7, 19, or 32 was 57.57 (equivalent to 4.00 mg NA/ml), 0.53 (equivalent to 0.10 mg NA/ml), or 0.03 (equivalent to 0.01 mg NA/ml), respectively, and that for NA was 0.03 at 25 degrees C. To ensure the chemical stability of dextran-NA at conditions similar to those of the stomach and small intestine, dextran-NA was placed in a solution of pH 1.2 hydrochloric acid buffer or pH 6.8 phosphate buffer and incubated at 37 degrees C; no NA was detected during the 6 h of the incubation period, which indicated that dextran-NA might be chemically stable during the transit through the gastrointestinal tract. Degree of depolymerization (%) by dextranase determined by the 2,4-dinitrosalicylic acid (DNS) method at 37 degrees C for dextran-NA with DS of 7, 19, or 32 was 81, 68, or 8, respectively, in 8 h, and that for dextran was 91. When dextran-NA (equivalent to 50 microg of NA) with a DS of 7 or 17 was incubated with cecal contents (100 mg) of rats at 37 degrees C, the extent of NA released in 24 h was 41% or 32% of the dose, respectively. NA was not liberated from the incubation of dextran-NA with the homogenate of tissue and contents of the small intestine. |
| Databáze: | OpenAIRE |
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