Colonic mucosa-specific "pro-antedrugs" for oral treatment of ulcerative colitis

design, synthesis and fate of methyl 20-glucopyranosyloxyprednisolonates

Toshikiro Kimura, Takehiro Yamaguchi, Kumi Usuki, Yuji Kurosaki, Taiji Nakayama, Yukiko Fujiwara, Yasuyuki Matsuda, Katsuo Unno, Toshio Suzuki

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Hydrophilic steriod derivatives, methyl 20-β-glucopyranosyloxyprednisolonates (15 and 16), were synthesizd from prenisolone via methyl 20(R/S)-dihydroprednisolonates (2 and 1) based on a novel colonic mucosa-specific drug delivery system. Optimal conditions for the syntheses of each isomer 1 and 2 were found by the extensive studies on the reaction rates from prednisolone under various concentrations of cupric acetate in dry methanol. Their configurations at C-20 in compounds 1 and 2 were determined by their formation mechanism. The fate of compounds 15 and 16 after the oral administration was examined in rats ang guinea-pigs. The glycosides were stable in the small-intestinal contents, but the glycoside bonds were cleaved by the action of bacteria in the large-intestinal contents to release compounds 1 and 2, respectively, which were rapidly hydrolysed to the inactive carboxylates in the plasma. The high recovery of the glycosides and the aglycons in the large-intestinal contents after intrajejunal administration of compounds 15 and 16 may be orally effective 'pro-antedrugs', which specifically express the anti-inflammatory acitivity in the glycosides 15 and 16 may be orally effective 'pro-antedrugs', which specifically express the anti-inflammatory activity in the colonic mucosa with no systemic effect.

Original languageEnglish
Pages (from-to)125-135
Number of pages11
JournalJournal of Controlled Release
Volume30
Issue number2
DOIs
Publication statusPublished - 1994

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Glycosides
Ulcerative Colitis
Gastrointestinal Contents
Mucous Membrane
Anti-Inflammatory Agents
Therapeutics
Drug Delivery Systems
Prednisolone
Oral Administration
Methanol
Guinea Pigs
Bacteria

Keywords

  • Antedrug
  • Colonic mucosa-targeted drug delivery system
  • Methyl 20-β-glucopyranosyloxyprednisolonate
  • Pro-antedrug
  • Prodrug

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Colonic mucosa-specific "pro-antedrugs" for oral treatment of ulcerative colitis : design, synthesis and fate of methyl 20-glucopyranosyloxyprednisolonates. / Kimura, Toshikiro; Yamaguchi, Takehiro; Usuki, Kumi; Kurosaki, Yuji; Nakayama, Taiji; Fujiwara, Yukiko; Matsuda, Yasuyuki; Unno, Katsuo; Suzuki, Toshio.

In: Journal of Controlled Release, Vol. 30, No. 2, 1994, p. 125-135.

Research output: Contribution to journalArticle

Kimura, Toshikiro ; Yamaguchi, Takehiro ; Usuki, Kumi ; Kurosaki, Yuji ; Nakayama, Taiji ; Fujiwara, Yukiko ; Matsuda, Yasuyuki ; Unno, Katsuo ; Suzuki, Toshio. / Colonic mucosa-specific "pro-antedrugs" for oral treatment of ulcerative colitis : design, synthesis and fate of methyl 20-glucopyranosyloxyprednisolonates. In: Journal of Controlled Release. 1994 ; Vol. 30, No. 2. pp. 125-135.
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