The Korean journal of internal medicine

  • 제29권2호
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  • Pages.191-202
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  • 2014
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  • 1226-3303(pISSN)
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  • 2005-6648(eISSN)
대한내과학회 (The Korean Association of Internal Medicine)
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Evaluation of the effect of D-002, a mixture of beeswax alcohols, on osteoarthritis symptoms

  • Puente, Roberto (Surgical Medical Research Centre) ;
  • Illnait, Jose (Surgical Medical Research Centre) ;
  • Mas, Rosa (Centre of Natural Products, National Centre for Scientific Research) ;
  • Carbajal, Daisy (Centre of Natural Products, National Centre for Scientific Research) ;
  • Mendoza, Sarahi (Centre of Natural Products, National Centre for Scientific Research) ;
  • Fernadez, Julio Cear (Centre of Natural Products, National Centre for Scientific Research) ;
  • Mesa, Meilis (Surgical Medical Research Centre) ;
  • Gaez, Rafael (Centre of Natural Products, National Centre for Scientific Research) ;
  • Reyes, Pablo (Software Group, National Centre for Scientific Research)
  • 투고 : 2013.05.16
  • 심사 : 2013.08.05
  • 발행 : 2014.03.01
⟨ 이전 논문 다음 논문 ⟩

초록

Background/Aims: Nonsteroidal anti-inflammatory drugs relieve osteoarthritis (OA) symptoms but cause adverse effects. D-002, a mixture of beeswax alcohols, is effective against experimental OA. A pilot study found that D-002 (50 mg/day) for 8 weeks improves OA symptoms. The aim of this study was to investigate the effects of D-002 (50 to 100 mg/day) administered for 6 weeks on OA symptoms. Methods: Patients with OA symptoms were double-blindly randomized to D-002 (50 mg) or placebo for 6 weeks. Symptoms were assessed by the Western Ontario and McMaster Individual Osteoarthritis Index (WOMAC) and the visual analog scale (VAS) scores. Patients without symptom improvement at week 3 were titrated to two daily tablets. The primary outcome was the total WOMAC score. WOMAC pain, joint stiffness and physical function scores, VAS score, and use of rescue medications were secondary outcomes. Results: All randomized patients (n = 60) completed the study, and 23 experienced dose titration (two in the D-002 and 21 in the placebo groups). At study completion, D-002 reduced total WOMAC (65.4%), pain (54.9%), joint stiffness (76.8%), and physical function (66.9%) WOMAC scores, and the VAS score (46.8%) versus placebo. These reductions were significant beginning in the second week, and became enhanced during the trial. The use of rescue medication by the D-002 (6/30) group was lower than that in the placebo (17/30) group. The treatment was well tolerated. Seven patients (two in the D-002 and five in the placebo group) reported adverse events. Conclusions: These results indicate that D-002 (50 to 100 mg/day) for 6 weeks ameliorated arthritic symptoms and was well tolerated.

키워드

참고문헌

  1. Lozada C, Steigelfest E. Osteoarthritis. Med Rheumatol 2010;15:12-23.
  2. Iagnocco A, Naredo E. Osteoarthritis: research update and clinical applications. Rheumatology (Oxford) 2012;51 Suppl 7:vii2-vii5.
  3. Litwic A, Edwards MH, Dennison EM, Cooper C. Epidemiology and burden of osteoarthritis. Br Med Bull 2013;105:185-199. https://doi.org/10.1093/bmb/lds038
  4. Lee YC, Shmerling RH. The benefit of nonpharmacologic therapy to treat symptomatic osteoarthritis. Curr Rheumatol Rep 2008;10:5-10. https://doi.org/10.1007/s11926-008-0002-0
  5. Bannwarth B. Acetaminophen or NSAIDs for the treatment of osteoarthritis. Best Pract Res Clin Rheumatol 2006;20:117-129. https://doi.org/10.1016/j.berh.2005.09.004
  6. Zhang W, Moskowitz RW, Nuki G, et al. OARSI recommendations for the management of hip and knee osteoarthritis, part I: critical appraisal of existing treatment guidelines and systematic review of current research evidence. Osteoarthritis Cartilage 2007;15:981-1000. https://doi.org/10.1016/j.joca.2007.06.014
  7. Moore RA, Derry S, McQuay HJ. Cyclo-oxygenase-2 selective inhibitors and nonsteroidal anti-inf lammatory drugs: balancing gastrointestinal and cardiovascular risk. BMC Musculoskelet Disord 2007;8:73. https://doi.org/10.1186/1471-2474-8-73
  8. Cherubino P, Sarzi-Puttini P, Zuccaro SM, Labianca R. The management of chronic pain in important patient subgroups. Clin Drug Investig 2012;32 Suppl 1:35-44. https://doi.org/10.2165/11630060-000000000-00000
  9. McCarberg B, Tenzer P. Complexities in the pharmacologic management of osteoarthritis pain. Curr Med Res Opin 2013;29:539-548. https://doi.org/10.1185/03007995.2013.785391
  10. Merashly M, Uthman I. Management of knee osteoarthritis: an evidence-based review of treatment options. J Med Liban 2012;60:237-242.
  11. Mas R. D-002: antiulcer, antioxidant, antiinflammatory. Drugs Future 2001;26:731-744. https://doi.org/10.1358/dof.2001.026.08.630956
  12. Leone S, Ottani A, Bertolini A. Dual acting anti-inflammatory drugs. Curr Top Med Chem 2007;7:265-275. https://doi.org/10.2174/156802607779941341
  13. Carbajal D, Molina V, Valdes S, Arruzazabala ML, Mas R, Magraner J. Anti-inflammatory activity of D-002: an active product isolated from beeswax. Prostaglandins Leukot Essent Fatty Acids 1998;59:235-238. https://doi.org/10.1016/S0952-3278(98)90135-1
  14. Ravelo Y, Molina V, Carbajal D, et al. Evaluation of anti- inf lammatory and antinociceptive effects of D-002 (beeswax alcohols). J Nat Med 2011;65:330-335. https://doi.org/10.1007/s11418-010-0496-4
  15. Mendoza S, Noa M, Valle M, Mendoza N, Mas R. Ameliorating effects of D-002, a mixture of beeswax alcohols, on monosodium iodoacetate-induced osteoarthritis in rats. Int J Pharm Sci Rev Res 2013;19:10-15.
  16. Rodriguez I, Mendoza S, Illnait J, et al. Effects of D-002, a mixture of beeswax alcohols, on osteoarthritis symptoms: a randomized placebo-controlled study. IOSR J Pharm 2012;2:1-9.
  17. Altman R, Asch E, Bloch D, et al. Development of criteria for the classification and reporting of osteoarthritis: classification of osteoarthritis of the knee. Diagnostic and Therapeutic Criteria Committee of the American Rheumatism Association. Arthritis Rheum 1986;29:1039-1049. https://doi.org/10.1002/art.1780290816
  18. Altman R, Alarcon G, Appelrouth D, et al. The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hip. Arthritis Rheum 1991;34:505-514. https://doi.org/10.1002/art.1780340502
  19. Batlle-Gualda E, Esteve-Vives J, Piera MC, Hargreaves R, Cutts J. Adaptacion transcultural del cuestionario WOMAC especifico para artrosis de rodilla y cadera. Rev Esp Reumatol 1999;26:38-45.
  20. Angst T, Aeschlimann A, Stucki G. Smallest detectable and minimal clinically important differences of rehabilitation intervention with their implications for required simple sizes using WOMAC and SF-36 quality of life measurement instruments in patients with osteoarthritis of the lower extremities. Arthritis Rheum 2001;45:384-391. https://doi.org/10.1002/1529-0131(200108)45:4<384::AID-ART352>3.0.CO;2-0
  21. Jinks C, Jordan K, Croft P. Measuring the population impact of knee pain and disability with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Pain 2002;100:55-64. https://doi.org/10.1016/S0304-3959(02)00239-7
  22. Salaffi F, Leardini G, Canesi B, et al. Reliability and validity of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index in Italian patients with osteoarthritis of the knee. Osteoarthritis Cartilage 2003;11:551-560. https://doi.org/10.1016/S1063-4584(03)00089-X
  23. Gonzalez VL, Marrero D, Sierra R, Velazquez C, Vicente R. Nuevo metodo por Cromatografia Gaseosa Capilar para el analisis del ingrediente activo D002. Rev CENIC Cienc Quim 2008;39:123-124.
  24. Gruenwald J, Petzold E, Busch R, Petzold HP, Graubaum HJ. Effect of glucosamine sulfate with or without omega-3 fatty acids in patients with osteoarthritis. Adv Ther 2009;26:858-871. https://doi.org/10.1007/s12325-009-0060-3
  25. Goregaonkar A, Mathiazhagan KJ, Shah RR, et al. Comparative assessment of the effectiveness and tolerability of lornoxicam 8 mg BID and diclofenac 50 mg TID in adult indian patients with osteoarthritis of the hip or knee: a 4-week, double-blind, randomized, comparative, multicenter study. Curr Ther Res 2009;70:56-68. https://doi.org/10.1016/j.curtheres.2009.02.006
  26. Naranjo CA, Busto U, Sellers EM, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-245. https://doi.org/10.1038/clpt.1981.154
  27. Lequesne MG, Mery C, Samson M, Gerard P. Indexes of severity for osteoarthritis of the hip and knee. Validation: value in comparison with other assessment tests. Scand J Rheumatol Suppl 1987;65:85-89.
  28. Lequesne M. Indices of severity and disease activity for osteoarthritis. Semin Arthritis Rheum 1991;20(6 Suppl 2):48-54. https://doi.org/10.1016/0049-0172(91)90027-W
  29. Lequesne MG. The algofunctional indices for hip and knee osteoarthritis. J Rheumatol 1997;24:779-781.
  30. Srikanth VK, Fryer JL, Zhai G, Winzenberg TM, Hosmer D, Jones G. A meta-analysis of sex differences prevalence, incidence and severity of osteoarthritis. Osteoarthritis Cartilage 2005;13:769-781. https://doi.org/10.1016/j.joca.2005.04.014
  31. Rizzoli R, Boonen S, Brandi ML, et al. Vitamin D supplementation in elderly or postmenopausal women: a 2013 update of the 2008 recommendations from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO). Curr Med Res Opin 2013;29:305-313. https://doi.org/10.1185/03007995.2013.766162
  32. Cuban Health Ministry, National Direction of Medical Register and Health Statistics, Health Annual Report 2010, 41 [Internet]. Habana (CU): Oficina Nacional de Estadisticas e Informacion, Republica de Cuba, 2010 [cited 2013 Jun 10]. Available from: http://www.one.cu/ publicaciones/03estadisticassociales/Salud%20en%20 Cifras%20Cuba%202010/edo.pdf.
  33. Singh G, Miller JD, Lee FH, Pettitt D, Russell MW. Prevalence of cardiovascular disease risk factors among US adults with self-reported osteoarthritis: data from the Third National Health and Nutrition Examination Survey. Am J Manag Care 2002;8(15 Suppl):S383-S391.
  34. Zhang W, Robertson J, Jones AC, Dieppe PA, Doherty M. The placebo effect and its determinants in osteoarthritis: meta-analysis of randomised controlled trials. Ann Rheum Dis 2008;67:1716-1723. https://doi.org/10.1136/ard.2008.092015
  35. Clegg DO, Reda DJ, Harris CL, et al. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med 2006;354:795-808. https://doi.org/10.1056/NEJMoa052771
  36. Selvan T, Rajiah K, Nainar MS, Mathew EM. A clinical study on glucosamine sulfate versus combination of glucosamine sulfate and NSAIDs in mild to moderate knee osteoarthritis. ScientificWorldJournal 2012;2012:902676.
  37. Schneider H, Maheu E, Cucherat M. Symptom-modifying effect of chondroitin sulfate in knee osteoarthritis: a meta-analysis of randomized placebo-controlled trials performed with structum((R)). Open Rheumatol J 2012;6:183-189. https://doi.org/10.2174/1874312901206010183
  38. Carbajal D, Molina V, Valdes S, Arruzazabala L, Mas R. Anti-ulcer activity of higher primary alcohols of beeswax. J Pharm Pharmacol 1995;47:731-733. https://doi.org/10.1111/j.2042-7158.1995.tb06732.x
  39. Carbajal D, Molina V, Valdes S, et al. Possible cytoprotective mechanism in rats of D-002, an anti-ulcerogenic product isolated from beeswax. J Pharm Pharmacol 1996;48:858-860. https://doi.org/10.1111/j.2042-7158.1996.tb03987.x
  40. Carbajal D, Molina V, Noa M, et al. Effect of D-002 on gastric mucus composition in ethanol-induced ulcer. Pharmacol Res 2000;42:329-332. https://doi.org/10.1006/phrs.2000.0693
  41. Molina V, Valdes S, Carbajal D, Arruzazabala L, Menendez R, Mas R. Antioxidant effect of D-002 on gastric mucosa of rats with experimentally induced injury. J Med Food 2001;4:79-83. https://doi.org/10.1089/109662001300341734
  42. Perez Y, Oyarzabal A, Mas R, Molina V, Jimenez S. Protective effect of D-002, a mixture of beeswax alcohols, against indomethacin-induced gastric ulcers and mechanism of action. J Nat Med 2013;67:182-189. https://doi.org/10.1007/s11418-012-0670-y
  43. Menendez R, Amor AM, Gonzalez RM, Jimenez S, Mas R. Inhibition of rat microsomal lipid peroxidation by the oral administration of D002. Braz J Med Biol Res 2000;33:85-90. https://doi.org/10.1590/S0100-879X2000000100012
  44. Menendez R, Mas R, Illnait J, et al. Effects of D-002 on lipid peroxidation in older subjects. J Med Food 2001;4:71-77. https://doi.org/10.1089/109662001300341725
  45. Lopez E, Illnait J, Molina V, et al. Effects of D-002 (beeswax alcohols) on lipid peroxidation in middle-aged and older subjects. Lat Am J Pharm 2008;27:695-703.
  46. Rodriguez I, Illnait J, Molina V, et al. Comparison of the antioxidant effects of D-002 (beeswax alcohols) and grape seed extract (GSE) on plasma oxidative variables in healthy subjects. Lat Am J Pharm 2010;29:255-262.

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