Effect of Treatment with Transdermal Ketoprofen on Adjuvant-Induced Arthritis

Adjuvant-induced arthritis에 대한 경피용 ketoprofen 제제의 치료효과

  • Shim, Kyung-Mi (College of Veterinary Medicine and Biotechnogy Research Institute, Chonnam National University) ;
  • Kim, Se-Eun (College of Veterinary Medicine and Biotechnogy Research Institute, Chonnam National University) ;
  • Bae, Chun-Sik (College of Veterinary Medicine and Biotechnogy Research Institute, Chonnam National University) ;
  • Choi, Seok-Hwa (College of Veterinary Medicine, Chungbuk National University) ;
  • Kang, Seong-Soo (College of Veterinary Medicine and Biotechnogy Research Institute, Chonnam National University)
  • 심경미 (전남대학교 수의과개학 및 생물공학 연구소) ;
  • 김세은 (전남대학교 수의과개학 및 생물공학 연구소) ;
  • 배춘식 (전남대학교 수의과개학 및 생물공학 연구소) ;
  • 최석화 (충북대학교 수의과대학 및 동물의학연구소) ;
  • 강성수 (전남대학교 수의과개학 및 생물공학 연구소)
  • Published : 2006.12.30

Abstract

This study demonstrates the anti-arthritic effect of topical application of ketoprofen gel containing N-methyl-2-pyrrolidone (NMP) in adjuvant arthritis therapy. Adjuvant arthritis was induced by a single injection of Freund's complete adjuvant (FCA). Mature female Sprague-Dawley rats were designated to 3 groups such as control group, K10 group (ketoprofen 10 mg/rat), and NK10 group (ketoprofen 10 mg/rat containing NMP). The anti-arthritic activity of ketoprofen containing NMP was tested not only as to its capability to suppress the inflammatory edema, but also bone damage (X-ray score and regional bone uptake) of the hind paw in arthritis-induced rats. These results showed a higher efficacy of ketoprofen containing NMP than ketoprofen treatment in the adjuvant-induced arthritis. Ketoprofen containing NMP has good intrinsic characteristics for formulation in an efficacious anti-inflammatory topical application.

본 연구는 랫드의 우측 후지 발바닥에 Freund's complete adjuvant를 투여하여 관절염을 유발한 후에 N-methyl-2-pyrrolidone (NMP) 기제를 첨가한 경피용 ketoprofen 제제의 관절염 치료 효과를 확인하기 위해서 수행되었다. NMP를 함유한 ketoprofen 경피용 제제의 관절염 치료 효과를 알아보기 위해서 Sprague-Dawley 암칫 랫드를 대조군과 약물 투여군으로 분리하고, 약물 투여군은 ketoprofen 10mg/rat 투여군(K10군)과 NMP가 함유된 ketoprofen 10mg/rat 투여군(NK10군)으로 분류하였다. 실험적 관절염을 유발시킨 후 $^{99m}Tc-MDP$을 이용한 bone scan에서 골병변이 나타난 7일 후부터 14일 동안 약물을 매일 한번씩 랫드의 등에 극소 도포하여 다음과 같은 결론을 얻었다. NMP의 기제를 첨가한 ketoprofen 경피용 제제가 ketoprofen단독 경피용 제제 보다 후지 부종을 현저하게 감소시켰고 단순 방사선 사진과 scintigraphy에서 관절염에 의한 골 파괴를 효과적으로 억제하였다. 이상의 연구 결과를 기초로 하여 관절염 치료에 있어 NMP를 함유한 ketoprofen 경피용 제제가 ketoprofen단독 제제보다 효과가 있다는 결론을 얻을 수 있었다.

Keywords

References

  1. Berba J, Goranson S, Langle J, Banakar UV. In vitro release of selected on-steroidal anti-inflammatory analgesic from reservoir type transdermal formulations. Drug Dev Ind Pharm 1991; 146: 255-262
  2. Berner B, Mazzenga GC, Otte JH, Steffens RJ, Juang RH, Ebert CD. Ethanol: water mutually enhanced transdermal therapeutic system. II. Skin permeation of ethanol and nitroglycerin. J Pharm Sci 1989; 78(5): 402-407 https://doi.org/10.1002/jps.2600780512
  3. Brune K, Beck WS. Towards safer nonsteroidal anti-inflammatory drugs. Agents Actions Suppl 1991; 32: 13-25
  4. Fujii M, Bouno M, Fujita S, Yoshida M, Watanabe Y, Matsumoto M. Preparation of griseofulvin for topical application using N-Methyl-2-pyrrolidone. Biol Pharm Bull 2000; 23(11): 1341-1345 https://doi.org/10.1248/bpb.23.1341
  5. Garcia MT, de Paula da Silva CH, de Oliveira DC, Braga EC, Thomazini JA, Lopes Badra Bentley MV. Transdermal delivery of ketoprofen: The influence of drug-dioleylphos-phatidylcholine interactions. Pharm Res 2006; 23(8): 1776-1785 https://doi.org/10.1007/s11095-006-9040-3
  6. He N, Li SK, Suhonen TM, Warner KS, Higuchi WI. Mechanistic study of alkyl azacycloheptanones as skin permeation enhancers by permeation and partition experiments with hairless mouse skin. J Pharm Sci 2003; 92: 297-310 https://doi.org/10.1002/jps.10269
  7. Johnson AG, Day RO. The problems and pitfalls of NSAID therapy in the elderly (Part I). Drugs Aging 1991; 1(2): 130-143 https://doi.org/10.2165/00002512-199101020-00005
  8. May SA, Lees P. Nonsteroidal anti-inflammatory drugs. In: Joint Disease in the Horse, McIlwraith CW, Trotter GT. (eds.) Philadelphia: Saunders. 1996: 223-237
  9. Osterwalder A, Reiner V, Reiner G, Lualdi P. Tissue absorption and distribution of ketoprofen after patch application in subjects undergoing knee arthroscopy or endoscopic carpal ligament release. Arzneimittelforschung 2002; 52(11): 822-827
  10. Sasai M, Saeki Y, Ohshima S, Nishioka K, Mima T, Tanaka T, Katada Y, Yoshizaki K, Suemura M, Kishimoto T. Delayed onset and reduced severity of collagen-induced arthritis in interleukin-6-deficient mice. Arthritis Rheum 1999; 42: 1635-1643 https://doi.org/10.1002/1529-0131(199908)42:8<1635::AID-ANR11>3.0.CO;2-Q
  11. Scheuplein RJ, Blank IH. Permeability of the skin. Physiol Rev, 1971; 51(4): 702-747 https://doi.org/10.1152/physrev.1971.51.4.702
  12. Tarantino R, Bishop E, Chen FC, Iqbal K, Malick AW. N-methyl-2-pyrrolidone as a cosolvent: relationship of cosolvent effect with solute polarity and the presence of protondonating groups on model drug compounds. J Pharm Sci 1994; 83(9): 1213-1216 https://doi.org/10.1002/jps.2600830905
  13. Wanders A, Heijde D, Landewe R, Behier JM, Calin A, Olivieri I, Zeidler H, Dougados M. Nonsteroidal anti-inflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: a randomized clinical trial. Arthritis Rheum 2005; 52(6): 1756-1765 https://doi.org/10.1002/art.21054
  14. Williams AC, Barry BW. Penetration enhancers. Adv Drug Deliv Rev. 2004; 56(5): 603-618 https://doi.org/10.1016/j.addr.2003.10.025