YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Improvement of Analgesic and Anti-inflammatory Effects by Mixing with Bucillamine and Lornoxicam

Bucillamine과 Lornoxicam의 혼합에 의한 진통소염 효과 향상

  • Received : 2011.08.12
  • Accepted : 2011.09.02
  • Published : 2011.10.31
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Abstract

The aim of this study was to reduce the side effects and to develop effective drugs using bucillamine (B), lornoxicam (L), and its mixtures on the analgesic and anti-inflammatory effects. With this goal, we compared their effects on the four different mixtures with a sole treatment (B 40 mg/kg and L 1.60 mg/kg). The mixture 1, 2, 3, and 4 ratios of B to L (mg/kg) were 20 to 0.80, 40 to 1.60, 80 to 3.20, and 40 to 1.14, respectively. In terms of acetic acid-induced vascular permeability, B and L inhibited the amount of dye leakage approximately 37.8 and 66.5%, respectively. And mixture 1, 2 and 3 showed inhibition of 47.4%, 81.5%, and 84.3%. The mixture 4 inhibited approximately 49.4%. In carrageenan- induced paw edema model, mixtures of B and L effectively inhibited paw edema measured 1/2~3 hours after carrageenan injection. Especially, mixture 2 inhibited 50.7%, 52.7%, 50.9% of paw edema after 1, 2, and 3 hr, significantly. We also examined an analgesic effect using the writhing test. In terms of the acetic acid-induced writhing syndrome, the control group showed writhing syndrome 18.5 times. B and L showed 9 and 6.3 times, inhibiting 51.6% and 65.9% respectively. And aspirin, as a positive control drug, showed the 7.1 times writhing syndrome. The mixture 1, 2, 3, and 4 also significantly inhibited the writhing syndrome to 62.2%, 93.0%, 51.4%, and 77.8%, respectively. From these results, we could suggest that the range of B and L ratio of 25 : 1 to 35 : 1 may be applicable to developing analgesic and anti-inflammatory drugs.

Keywords

References

  1. Tizard, I. R. : An introduction of inflammation, Immunology, 2nd ed., Saunders College Publishing, Philadelphia, 432-441 (1986).
  2. Land, W. E. : Mechanisms of action of anti-inflammatory drugs. Advan. Drug. Res., Academic Press, London 14, 147 (1985).
  3. Samuelsson, B., Hammarstom, S. and Borgeat, P. : Pathways of arachidonic acid metabolism. Advan. Inflamm. Res., Raven Press, New York 405-412 (1979).
  4. Brent, R. L. : Teratogen update: reproductive risks of leflunomide (Arava); a pyrimidine synthesis inhibitor: counseling women taking leflunomide before or during pregnancy and men taking leflunomide who are contemplating fathering a child. Teratology 63, 106 (2001). https://doi.org/10.1002/1096-9926(200102)63:2<106::AID-TERA1017>3.0.CO;2-R
  5. Weinblatt, M. E., Dixon, J. A. and Lchuk, K. R. : Serious liver disease in a patient receiving methotrexate and leflunomide. Arthritis Rheum. 43, 2609 (2000). https://doi.org/10.1002/1529-0131(200011)43:11<2609::AID-ANR32>3.0.CO;2-R
  6. Cleland, L. G., James, M. J., Stamp, L. K. and Penglis, P. S. : COX-2 inhibition and thrombotic tendency: a need for surveillance. Med. J. Aust. 175, 214 (2001).
  7. Koh, E. M. : Medical treatment of rheumatoid arthritis (I): Nonsteroidal anti-inflammatory drugs, disease modifying antirheumatic drugs and glucocorticoids. J. Korean Med. Assoc 53, 871 (2010). https://doi.org/10.5124/jkma.2010.53.10.871
  8. van Roon, E. N., Jansen, T. L., Houtman, N. M., Spoelstra, P. and Brouwers, J. R. : Leflunomide for the treatment of rheumatoid arthritis in clinical practice: incidence and severity of hepatotoxicity. Drug. Saf. 27, 345 (2004). https://doi.org/10.2165/00002018-200427050-00006
  9. Chambers, C., Koren, G., Tutuncu, Z. N., Johnson, D. and Jones, K. L. : Are new agents used to treat rheumatoid arthritis safe to take during pregnancy? Organization of Teratology Information Specialists (OTIS) study. Can. Fam. Physician. 53, 409 (2007).
  10. Schneider, F., Meziani, F., Chartier, C., Alt, M. and Jaeger, A. : Fatal allergic vasculitis associated with celecoxib. Lancet 359, 852 (2002). https://doi.org/10.1016/S0140-6736(02)07922-9
  11. Pomp, E. : A critical evaluation of side effect data on COX-2 inhibitors. Tidsskr Nor Laegeforen. 122, 476 (2002).
  12. Park, Y. B. and Lee, S. K. : Leflunomide; A new disease modifying anti-rheumatic drug. Journal of the Korean Rheumatism Association 7, 323 (2010).
  13. Hur, J. W., Lee, C. W. and Yoo, D. H. : Bucillamine-induced pemphigus vulgaris in a patient with rheumatoid arthritis and polymyositis overlap syndrome. J. Korean Med. Sci. 21, 585 (2006). https://doi.org/10.3346/jkms.2006.21.3.585
  14. Kim, Y. H., Ji, H. Y., Park, E. S., Chae, S. W. and Lee, H. S. : Liquid chromatography-electrospray ionization tandem mass spectrometric determination of lornoxicam in human. Plasma Archives of Pharmacol Research 30, 905 (2007). https://doi.org/10.1007/BF02978844
  15. Pruss, T. P., Stroissnig, H., Radhofer-Welte, S., Wendtlandt, W., Mehdi, N., Takacs, F. and Fellier, H. : Overview of the pharmacological properties, pharmacokinetics and animal safety assessment of lornoxicam. Postgrad. Med. J. 66, S18 (1990)..
  16. Whittle, B. A. : The use of changes in capillary permeability in mice to distinguish between narcotic analgesics. Brit. J. Pharmacol. 22, 246 (1964).
  17. Winter, C. A., Risley, E. A. and Nuss, G. W. : Carrageenininduced edema in hind paw of the rat as an assay for antiinflammatory drugs. Proc. Soc. Exp. Biol. Med. 111, 544 (1962). https://doi.org/10.3181/00379727-111-27849
  18. Koster, R., Anderson, M. and Beer, E. J. : Acetic acid for anafesic and screening. Fed. Proc. 18, 412 (1959).
  19. Park, Y. H., Lim, S. H., Ham, H. J., Kim, H. Y., Jeong, H. N., Kim, K. H. and Kim, S. M. : Isolation of anti-inflammatory active substance -sitosterol from seabuckthorn (Hippophae rhamnoides L.) stem. J. Korean Soc. Food Sci. Nutr. 39, 980 (2010). https://doi.org/10.3746/jkfn.2010.39.7.980
  20. Bonney, R. J., Grey, I., Lin, T. Y., Meyenhofer, M. F., Acevedo, W. and Davies, P. : Mononuclear phagocytes from carrageenaninduced granulomas. Isolation, cultivation, and characterization. J. Exp. Med. 148, 261 (1978). https://doi.org/10.1084/jem.148.1.261