Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – 3,10-dihydroxy-2-naphthacene carboxamide or derivative doai
Patent
1996-08-30
1998-08-04
Weber, Jon P.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
3,10-dihydroxy-2-naphthacene carboxamide or derivative doai
435184, 435190, 435191, A61K 3165, C12N 999, C12N 904, C12N 906
Patent
active
057893950
ABSTRACT:
A method is disclosed for inhibiting endogenous production of nitric oxide (NO) in an in vivo, in vitro, or ex vivo mammalian system. The method employs a tetracycline compound to inhibit production of NO and/or to inhibit the expression or activity of an inducible isoform of nitric oxide synthase (iNOS). Preferably, the tetracycline compound has inhibitory activity for metalloproteinases. Also it is preferred that the tetracycline compound is provided to the mammalian system in an amount which has little or no antibacterial activity in the system. Accordingly, preferred tetracycline compounds are tetracycline compounds which have be modified to reduce or eliminate their antimicrobial activity. The method can be used to treat medical conditions in mammals characterized by NO production mediated by iNOS, including, for example, inflammatory conditions.
REFERENCES:
patent: 5216025 (1993-06-01), Gross et al.
patent: 5246970 (1993-09-01), Williamson et al.
patent: 5246971 (1993-09-01), Williamson et al.
patent: 5266594 (1993-11-01), Dawson et al.
patent: 5296466 (1994-03-01), Kilbourn et al.
patent: 5358969 (1994-10-01), Williamson et al.
patent: 5449688 (1995-09-01), Wahl et al.
patent: 5468630 (1995-11-01), Billiar et al.
patent: 5478946 (1995-12-01), Murad et al.
patent: 5480999 (1996-01-01), De Lassauniere et al.
Amin AR, Di Cesare P, Vyas P, Attur M, Tzeng E, Billiar TR, Stuchin SA, and Abramson SB, J Exp Med 182:2097-2102 (1995a).
Amin AR, Vyas P, Attur M, Leszczynska-Piziak J, Patel IR, Weissmann G, and Abramson SB, Proc. Natl Acad Sci USA 92:7926-2930 (1995b).
Brinckerhoff CE, Arthritis Rheum 34:1073-1075 (1991).
Cao M, Westerhausen-Larson A, Niyibizi C, Kavalkovich K, Georgescu HI, Rizzo CF, Stefanovic-Racic M, and Evans CH, 42nd Ann Mtg Orthoped Res Soc, p. 533 (1996).
Murrell GAC, Jang D, and Williams RJ, Biochem Biophys Res Comm 206:15-21 (1995).
Pfeilschifter J, Walker G, Eberhardt W, and Kunz D, Endothelium 3 (suppl.), S51 (1995).
Schmidt HHHW and Walter U, Cell 78:919-925 (1994).
Vernillo AT, Ramamurthy NS, Lee HM, Mallya S, Auszmann J, Golub LM, and Rifkin BR, J Dent Res 73:367A (1993).
Vodovotz Y, Bogdan C, Paik J, Xie QW, and Nathan C, J Exp Med 178:605-613 (1993).
Vyas P, Attur M, Ou GM, Haines KA, Abramson SB, and Amin AR, p. 44 In The Biology of Nitric Oxide, Part 5, Moncada S, Stamler J, Gross S, and Higgs EA, eds., Portland Press Proceedings, (1996).
Yu LP Jr, Smith GN Jr, Hasty KA, and Brandt KD, J Rheumatol 18:1450-1452 (1991).
Ramamurthy N, Greenwald R, Moak S, Scuibba J, Goren A, Turner G, Rifkin B, and Golub L, "CMT/Tenidap treatment inhibits temporomandibular joint destruction in adjuvant arthritic rats," Annals NY Acad Sci 732:427-430 (1994).
Cole AA, Chubinskaya S, Chlebek K, Orth MW, Luchene LL, and Schmid TM, "Doxycycline inhibition of cartilage matrix degradation," Annals NY Acad Sci 732:414-415 (1994).
De Clerck YA, Shimada H, Taylor SM, and Langley KE, "Matrix metalloproteinases and their inhibitors in tumor progression," Annals NY Acad Sci 732:222-232 (1994).
Golub LM, Suomalainen K, and Sorsa T, "Host modulation with tetracyclines and their chemically modified analogues,"0 Periodontol Restor Dent, 80-90 (1992).
Greenwald RA, "Treatment of destructive arthritic disorders with MMP inhibitors," Annals NY Acad Sci 732:181-198 (1994).
Mallya SK, Hall JE, Lee HM, Roemer EJ, Simon SR, and Golub LM, "Interaction of matrix metalloproteinases with serine protease inhibitors," Annals NY Acad Sci 732:303-314 (1994).
Mitchell PG, Lopresti-Morrow L, Yocum SA, Sweeney FJ, and Reiter LA, "Inhibition of Interleukin-1-stimulated collagen degradation in cartilage explants," Annals NY Acad Sci 732:395-397 (1994).
Smith GN Jr, Brandt KD, and Hasty KA, "Procollagenase is reduced to inactive fragments upon activation in the presence of doxycycline," Annals NY Acad Sci 732:436-438 (1994).
Suomalainen K, Sorsa T, Golub LM, Rammaurthy N, Lee HM, Uitto VJ, Saari H, and Konttinen YT, "Specificity of the anticollagenase action of tetracyclines: Relevance to their anti-inflammatory potential," Antimicrob Agents Chemother, 36(1):227-229 (1992).
Uitto VJ, Firth JD, Nip L, and Golub LM, "Doxycycline and chemically modified tetracyclines inhibits gelatinasae A (MMP-2) gene expression in human skin keratinocytes," Annals NY Acad Sci 732:140-151 (1994).
Yu LP Jr, Burr DB, Brandt KD, O'Connor BL, Rubinow A, and Albrecht M, "Effects of oral doxycycline administration on histomorphometry and dynamics of subchondral bone in a canine model of osteoarthritis,"J Rheumatol 23(1):137-142 (1996).
Smith GN Jr, Brandt KD, and Hasty KA, "Activation of recombinant human neutrophil procollagenase in the presence of doxycycline results in fragmentation of the enzyme and loss of enzyme activity," Arthrit Rheum 39(2):235-244 (1996).
Tilley BC, Alarcon GS, Heyse SP, Trentham DE, Neuner R, Kaplan DA, Clegg DO, Leisen JCC, Buckley L, Cooper SM, Duncan H, Pillemer SR, Tuttleman M, and Fowler SE, "Minocycline in rheumatoid arthritis," Annals Intern Med 122(2):81-89 (1995).
Stefanovic-Racic M, Meyers K, Meschter C, Coffey JW, Hoffman RA, and Evans CH, "N-Monomethyl arginine, an inhibitor of nitric oxide synthase, suppresses the development of adjuvant arthritis in rats," Arthrit Rheum 37(7):1062-1069 (1994).
Sakuari H, Kohsaka H, Liu MF, Higashiyama H, Hirata Y, Kanno K, Saito I, and Miyasaka N, "Nitric oxide production and inducible nitric oxide synthase expression in inflammatory arthritides," J Clin Invest 96:2357-2363 (1995).
McCartney-Francis N, Allen JB, Mizel DE, Albina JE, Xie QW, Nathan CF, and Wahl SM, "Suppression of arthritis by an inhibitor of nitric oxide synthase," J Exper Med 178:749-754 (1993).
Pipili-Synetos E, Sakkoula E, and Maragoudakis ME, "Nitric oxide is involved in the regulation of angiogenesis," Br J Pharmacol 108(4):855-857 (1993).
Pipili-Synetos E, Sakkoula E, Haralabopoulos G, Andriopoulou P, Peristeris P, and Maragoudakis ME, "Evidence that nitric oxide is an endogenous antiangiogenic mediator," Br J Pharmacol 111(3):894-902 (1994).
Maragoudakis ME, Peristeris P, Missirlis E, Aletras A, Andriopoulou P, and Haralabopoulos G, "Inhibition of angiogenesis by anthracyclines and titanocene dichloride," Annals NY Acad Sci, 732:280-293 (1994).
Kasten TP, Collin-Osdoby P, Patel N, Osdoby P, Krukowski M, Misko TP, Settle SL, Currie MG, and Nickos GA, "Potentiation of osteoclast bone-resorption activity by inhibition of nitric oxide synthase," Proc Natl Acad Sci USA 91(9):3569-3573 (1994).
Farias-Eisner R, Sherman MP, Aeberhard E, and Chaudhuri G, "Nitric oxide is an important mediator for tumoricidal activity in vivo," Proc. Natl. Acad. Sci. USA, 91(20):9407-9411 (1994).
Taskiran D, Stefanovic-Racic M, Georgescu H, and Evans C, "Nitric oxide mediates suppression of cartilage proteoglycan synthesis by Interleukin-1," Biochem Biophys Res Commun 200(1):142-148 (1994).
Yu LP Jr, Smith GN Jr, Brandt KD, Myers SL, O'Connor BL, and Brandt DA, "Reduction of the severity of canine osteoarthritis by prophylactic treatment with oral doxycycline," Arthrit Rheum 35(10):1150-1159 (1992).
Golub et al. (1987a) J. Dent. Res., 66(8), "A Non-Antibacterial Chemically-Modified Tetracycline Inhibits Mammalian Collagenase Activity", pp. 1310-1314.
Golub et al. (1991) Crit. Rev. Oral Biol. Path., 2(3), "Tetracyclines Inhibit Connective Tissue Breakdown: New Therapeutic Implications for an Old Family of Drugs", pp. 297-321 in Medline AN 91370196.
Vernillo et al. (1994) Curr. Opin. Periodont., "The Nonantimicrobial Properties of Tetracycline for the Trreatment of Periodontal Disease", pp. 111-118, in Medline AN 94305629.
Webster et al. (1994) Arch. Dermatol., 130(6), "Inhibition of a Model of in vitro Granuloma Formation by Tetracyclines and Ciprofloxacin. Involvment of Protein Kinase C", pp. 748-752, in Medline AN 94270837.
Weller et al. (1996) J. Invest. Dermatol., 107(3), "Nitric Oxide is Generated on the Skin Surface by Reduction of Sweat Nitrate", pp. 327-331.
Shapira et al. (1996) Infect. Immun., 64(3), "Protection Against Endotoxic Shock and Lipopolysaccharide-Induced Local Inflammation by Tetracycl
Abramson Steven B.
Amin Ashok R.
Golub Lorne M.
Greenwald Robert A.
McNamara Thomas F.
Hospital for Joint Diseases
The Research Foundation of State University of New York
Weber Jon P.
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