YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Solubilization of Quercetin , and Permeability Study of Quercetin and Rutin to Rabbit Duodenal Mucosa

퀘르세틴의 가용화 , 퀘르세틴 및 루틴의 토끼 십이지장 점막 투과성

  • Chun, In-Koo (College of Pharmacy, Dongduk Women's University) ;
  • Seo, Eun-Ha (College of Pharmacy, Dongduk Women's University)
  • 전인구 (동덕여자대학교 약학대학) ;
  • 서은하 (동덕여자대학교 약학대학)
  • Published : 1998.02.01
Download PDF
⟨ Previous Next ⟩

Abstract

To increase the solubility of quercetin, which is a practically insoluble flavonoid of Ginkgo biloba leaf, the effects of nonaqueous vehicles. Their cosolvents, water-sol uble polymers and modified cyclodextrins (CDs) were observed. Polyethylene glycols, diethyleneglycol monoethyl ether, and their cosolvents with water showed a good solvency toward quercetin. Also the aqueous solutions of povidone, copolyvidone and Cremophor RH 40 was effective in solubilizing quercetin. Complex formation of quercetin with ${\beta}$-cyclodextrin (${\beta}$-CD), dimethyl-${\beta}$-cyclodextiin (DMCD), 2-hydroxypropyl-${\beta}$-cyclodextrin (HPCD) and ${\beta}$-cyclodextrin sulfobutyl ether (SBCD) in water was investigated by solubility method at $37^{\circ}C$. The addition of CDs in water markedly increased the solubility of quercetin with increasing the concentration. AL type phase solubility diagrams were obtained with CDs studied. Solubilizaton efficiency by CDs was in the order of SBCD >> DMCD > HPCD > ${\beta}$-CD. The dissolution rates of quercetin from solid dispersions with copolyvidone, povidone and HPCD were much faster than those of drug alone and corresponding physical mixtures, and exceeded the equilibrium solubility (3.03${\pm}1.72{\mu}$g/ml). The permeation of quercetin through duodenal mucosa did not occur even in the presence of enhancers such as bile salts, but the permeation was observed when the mucus layer was scraped off. This was due to the fact that quercetin had a strong binding to mucin ($58.5{\mu}$g/mg mucin). However rutin was permeable to the duodenal mucosa. The addition of enhancer significantly increased the permeation of rutin in the order of sodium glycocholate.

Keywords

References

  1. J. Immunol. v.127 Quercetin: an inhibitor of antigen-induced human basophil histaminej release Middleton, E., Jr.;Drzewiecki, G.;Krishnarao, D.
  2. Natural Product Sciences v.2 Flavonoids: potential antiinflammatory agents Kim, H. P.;Son, K. H.;Kang, S. S.
  3. Agents Action Suppl. v.10 Influence of flavonoids on capillary permeability, carrageenan edema and histamine and PGE₂spasm Matzner, J.;Bekemeier, H.;Weber, F. G.
  4. Biochem. Pharmacol. v.42 Inhibition of mammalian 5-lipoxygenase and cyclo-oxygenase by flavonoids and phenolic dietary addivites. Relationship to antioxidant activity and to iron ionreducing ability Laughton, M. J.;Evans, P. J.;Moroney, M. A.;Hoult, J. R.;Halliwell, B.
  5. Pharmazie v.45 Inhibition of sheep platelet arachidonate metabolism by flavonoids from Spanish and Indian medicinal herbs Ferrandiz, M. L.;Nair, A. G.;Alcaraz, M. J.
  6. Biochemical, Cellular, and Medicinal Properties Plant flavonoids in biology and medicine Ⅱ Berg, P. A.;Daniel, P. T.;Cody(et al.)(ed.)
  7. Pol. J. Pharmacol. Pharm. v.36 Antiag-gregatory effects of flavonoids in vivo and their influence on lipoxigenase and cyclooxygenase in vitro Swies, J.;Robak, J.;Dabrowski, L.;Duniec, Z.;Michalska, Z.;Gryglewski, R. J.
  8. Biochem. Pharmacol. v.36 On the mechanism of antithrombotic action of flavonoids Gryglewski, R. J.;Korbut, R.;Robak, J.;Swies, J.
  9. Meth. Enzymol. v.186 Flavonoids as antioxidants : determination of radical-scavenging efficiencies Bors, W.;Heller, w.;Michel, C.;Saran, M.
  10. Biochem. Pharmacol. v.38 Chelating and free radical scavenging mechanisms of inhibitory action of rutin and quercetin in lipid peroxidation Afanasev, I. B.;Dorozhko, A. I.;Brodskii, A. V.;Kostyuk, V. A.;Potapovitch, A. I.
  11. Phytochem. v.31 Effect of flavonoids on OH radical formation by Fenton-type reactions : influence of iron chelator Puppo, A.
  12. Biochem. Pharmacol. v.45 Antioxidant and iron-chelating activities of the flavonoids catechin, quercetin and diosmetin on iron-loaded rat hepatocyte cultures Morrel, I.;Lescost, G.;Cogrel, P.;Sergent, O.;Pasdeloup, N.;Brissot, P.;Cillard, P.
  13. The Flavonoids: Advances in Research since 1986 Middleton, E., Jr.;Kandaswami, C.;Harborne, J. B.(ed.)
  14. Arch. Exptl. Path. Pharmakol v.64 The pharmacological effects of flavone groups Fukuda, T.
  15. Rutin and Related Flavonoids Griffith, J. Q.;Krewson, C. F.;Naghski, J.
  16. Eur. J. Clin. Pharmacol. v.9 Disposition of quercetin in human after single oral and intravenous doses Gugler, R.;Leschik, M.;Dengler, H. J.
  17. Trends Pharmacol. Sci. v.5 The flavonoids Middleton, E., Jr.
  18. Biochem. Pharmacol. v.32 Flavonoids, a class of natural products of high pharmacological potency Havsteen, B.
  19. Biochem. J. v.130 Metabolism of myricetin and related compounds in the rat: metabolite formation in vivo and by the intestinal microflora in vitro Griffiths, L. A.;Smith, G. E.
  20. Mutat. Res. v.75 A review of the genetic effects of naturally occurring flavonoids. anthraquinones and related compounds Brown, J. P.
  21. Proc. Natl. Acad. Sci. USA v.77 Fecalase : a model for activation of dietry glycosides to mutagens by intestinal flora Tamura, G.;Gold, C.;Ferro-Luzzi, A.;Ames, B. N.
  22. Compt. Rend. v.216 The presence of rutinoside in the flower of certain Magnolia Plouvier, V.
  23. Can. J. Microbiol. v.17 Identification of products produced by the anaerobic degradation of naringin by Butyrovivrio sp. C₃ Gheng, K. J.;Krishnamurty, H. G.;Jones, G. A.;Simpson, F. J.
  24. Can. J. Microbiol. v.16 Identification of products produced by the anaerobic degradation of rutin and related flavonoids by Butyrovivrio sp. C₃ Krishnamurty, H. G.;Gheng, K. J.;Jones, G. A.;Simpson, F. J.
  25. Appl. Environ. Microbiol. v.55 C-ring cleavage of flavonoids by human intestinal bacteria Winter, J.;Moore, L.H.;Dowell, V.R.;Bokkenheuser, V. D.
  26. J. Pharm. Sci. v.85 Pharmaceutical applications of cyclodextrins. 1. Drug solubilization and stabilization Loftsson, T.;Brewster, M. E.
  27. Adv. Anal. Chem. Instr. v.4 Phase-solubility techniques Higuchi, T.;Connors, K. A.
  28. Chem. Pharm. Bull. v.31 Dissolution behavior and gastrointestinal absorption of dicumarol from solid dispersion systems of dicumarol-polyvinylpyrrolidone and dicumarol-β-cyclodextrin Sekikawa, H.;Fukuda, N.;Takada, M.;Ohtani, K.;Arita, T.;Nakano, M.
  29. Int. J. Pharm. v.80 Preparation of drug : hydroxypropylcyclodextrin complexes by a method using ethanol or aquous ammonium hydroxide as cosolubilizers Pitha, J.;Hoshino, T.;Torres-Labandeira, J.;Irie, T.
  30. Int. J. Pharm. v.30 Binding of antibiotics to rat intestinal mucin Niibuchi, J.;Aramaki, Y.;Tsuchiya, S.
  31. Int. J. Phram. v.128 Characterization and bioavailability of danazol-hydroxypropyl β-cyclodextrin coprecipitates Badawy, S. I. F.;Ghorab, M. M.;Adeyeye, C. M.
  32. Yakhak Hoeji v.37 Solubilization and dissolution enhancement of benzimidazole antelmintic drugs by cyclodexation Chun, I. K.;Park, I. S.
  33. Int. J. Pharm. v.96 Inclusion complexation of hydrocortisone butyrate with cyclodextrins and dimethyl-β-cyclodextrin aqueous solution and in solid state Chun, I. K.;Yun, D. S.
  34. Can. J. Microbiol. v.7 Degradation of rutin by Aspergillus flavus and characterization of rutinose Hay, G. W.;Westlake, D. W. S.;Simpson, F. J.
  35. Mutat. Res. v.122 The role of rutin and quercitrin in stimulating flavonol glycosodase activity by cultured cell-free microbial preparations of human feces and saliva McDonald, I. A.;Mader, J. A.;Bussard, R. G.
  36. Biochem. J. v.248 Hydrolysis of dietary flavonoid glycosides by strains of intestinal Bacteriodes from humans Bokkenheuser, V. D.;Shackleton, H. L.;Winter, J.
  37. Yakhak Hoeji v.37 Metabolism of poncirin by intestinal bacteria Yoon, W. G.;Hyun, S. H.;Kim, D. H.;Kim, N. J.;Hong, N. D.
  38. Yakhak Hoeji v.38 Metabolism of poncirin and naringin by human intestinal bacteria Kim, D. H.;Jang, I. S.;Kim, N. J.;Yoon, W. G.
  39. Int. J. Pharm. v.62 Comparison of enzymic activities of tissues lining portals of drug absorption, using the rat as a model Zhou, X. H.;Li Wan Po, A.
  40. Mucus and Mucosa (Ciba Foundation Symposium 109) Mucus glycoprotein structure, gel formation and gastrointestinal mucus function Allen, A.;Hutton, D. A.;Person, J. P.;Sellers, L. A.
  41. Int. J. Pharm. v.14 Effect of polyoxyethylene cetyl ether on the absorption of 3',4'-dideoxykanamycin B from rat rectum Tsuchiya, S.;Aramaki, Y.;Ozawa, S.;Matsumaru, H.
  42. Forstner, J. F.;Forstner, G. G.