Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form
Reexamination Certificate
2006-07-18
2006-07-18
Padmanabhan, Screenivasan (Department: 1616)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
C422S430000, C422S413000, C422S413000, C422S413000, C514S838000
Reexamination Certificate
active
07078045
ABSTRACT:
A pharmaceutical composition for treatment and prevention of liver fibrosis and cirrhosis, which comprises 5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione (oltipraz) and dimethyl-4,4′-dimethoxy-5,6,5′,6′-dimethylene dioxybiphenyl-2,2′-dicarboxylate (DDB) as major components, is provided. The ratio of oltipraz and DDB of said composition is preferably 25:0–25, more preferably 5:0.1–5, particularly preferably 5:1. Oltipraz/DDB formulations according to the present invention exhibit surprisingly good effect on the treatment and prevention of liver fibrosis and cirrhosis and are safe drugs that have low toxicity in the human body.
REFERENCES:
patent: 3850991 (1974-11-01), Chabardes et al.
patent: 4105855 (1978-08-01), Schulz et al.
patent: 4248892 (1981-02-01), Kanamaru et al.
patent: 4883887 (1989-11-01), Bernhard et al.
patent: 5449678 (1995-09-01), Pines et al.
patent: 5658913 (1997-08-01), Kim et al.
patent: 5686436 (1997-11-01), Van Dyke
patent: 5786344 (1998-07-01), Ratain et al.
patent: 5942511 (1999-08-01), Kwon et al.
patent: 5993845 (1999-11-01), Geerts et al.
patent: 6046199 (2000-04-01), Pamukcu et al.
patent: 6242478 (2001-06-01), Welker et al.
patent: 6294350 (2001-09-01), Peterson
patent: 6517824 (2003-02-01), Kohn et al.
patent: 2004/0053989 (2004-03-01), Prendergast et al.
patent: 02268116 (1990-11-01), None
patent: WO 96/01127 (1996-01-01), None
patent: WO 01/76604 (2001-10-01), None
Fu T et al, Protective effects of biphenyl dimethyl dicarboxylate on damage in isolated rat hepatocytes by carbon tetrachloride and galactosamine, Apr. 1990, 70(4): 201-4.
Liu et al, Protection of Oltipraz against the hepatotoxicity of Aflatoxin B in the rat, Toxicology and Applied Pharmacology, vol. 93, 442-451 (1988).
Kensler et al, J Cell Biochem Suppl, 1995; 22:101-7.
International Search Report for International Application No. PCT/KR01/00319 dated Jun. 21, 2001.
M.H. Davies, et al., “Oltipraz-Induced Amelioration and Acetaminophen Hepatotoxicity in Hamsters”, Toxicology and Applied Pharmacology 109, 29-40 (1991).
T.W. Kensler et al., “Mechanism of Protection against Aflatoxin Tumorigenicity in Rats Fed Oltipraz and Related 1,2-Dithiol-3-thiones and 1,2-Dithiol-3-ones”, Cancer Research 47, 4271-4277, Aug. 15, 1987.
A.M. Di Bisceglie et al., “Hepatocellular Carcinoma”, Hepatology vol. 28, No. 4, 1998, pp. 1161-1165.
P.J. O'Dwyer et al., “Modulation of Gene Expression in Subjects at Risk for Colorectal Cancer by the Chemopreventive Dithiolethione Oltipraz”, J. Clin. Invest., The American Society for Clinical Investigation, Inc., vol. 98, No. 5, pp. 1210-1217, Sep. 1996.
S.G. Kim et al., “Enhancement of Radiation-Inducible Hepatic Glutathione-S-Transferases Ya, Yb1, Yb2, Yc1, and Yc2 Gene Expression by Oltipraz: Possible Role in Radioprotection”, Molecular Pharmacology, 51, pp. 225-233 (1997), The American Society for Pharmacology and Experimental Theraputics.
P. Pepin et al., “Effects of sulindac and oltipraz on the tumorigenicity of 4-(methylnitrosamino)1-(3-pyridyl)-1-butanone in A/J mouse lung”, Carinogenesis, vol. 13, No. 3, pp. 341-348, (1992).
R.W. Ruddon, M.D., Ph.D., Cancer Biology, Third Edition, Oxford University Press, 1995, pp. 61-95, 496-509.
S.S. Ansher et al., “Chemoprotective Effects of Two Dithiolthiones and of Butylhydroxyanisole Against Carbon Tetrachloride and Acetaminophen Toxicity”, Hepatology, vol. 3, No. 6, pp. 932-935, 1983.
W.J. Chi et al., “Oltipraz, a novel inhibitor of hepatitis B virus transcription through elevation of p53 protein”, Carcinogenesis vol. 19 No. 12, pp. 2133-2138, 1998.
E. Grupta et al., “Pharmacokinetics and Pharmacodynamics of Oltipraz as a Chemopreventive Agent”, Clinical Cancer Research vol. 1, pp. 1133-1138, Oct. 1995.
M.L. Clapper et al., “Coordinate Induction of Glutathione S-Transferase α, μ, and πExpression in Murine Liver after a Single Administration of Oltipraz”, Molecular Pharmacology, 45:469-474.
N.E. Davidson et al., “Transcriptional Control of Glutathione S-Transferase Gene Expression by the Chemoprotective Agent Oltipraz in Rat Liver”, Cancer Research 50, pp. 2251-2255, Apr. 15, 1990.
S.J. Chavan, et al., “Inactivation of Human Immunodeficiency Virus Type 1 Reverse Transcriptase by Oltipraz: Evidence for the Formation of a Stable Adduct”, Archives of Biochemistry and Biophysics vol. 324, No. 1, Dec. 1, pp. 143-152, 1995.
H.J. Prochaska et al., “Inhibition of Human Immunodeficiency Virus Type 1 Replication by 7-Methyl-6,8-bis(methylthio)pyrrolo[1,2-α]pyrazine, anIn VivoMetabolite of Oltipraz”, Molecular Pharmacology, 48:15-20 (1995).
Y.Y. Maxuitenko et al., “Identification of dithiolethiones with better chemopreventive properties than oltipraz”, Carcinogenesis vol. 19 No. 9 pp. 1609-1615, 1998.
J. Seong et al., “Early alteration in TGF-beta mRNA expression in irradiated rat liver”, Pub/Med, National Library of Medicine, one page.
Surh et al., Inhibition of covalent DNA binding and . . . , Mutation research, 1996, vol. 367, pp. 219-224.
Bu et al., Stability, blood partition and protein binding of . . . , Res Commun. Mol. Pathol. Pharmacol., (abstract only), 2001, vol. 109(5-6), pp. 333-344.
Kim, et al., Molecular Basis for hepatic detoxifying . . . , Drug metabolism and disposition, Jun. 1999, vol. 27(6), pp. 667-673.
Bruix et al., Hepatitis B virus and Hepatocellular carcinoma., EASL International Concensus Conference on Hepatitis B(Reproduced from Hepatol.), 2001, vol. 35, p. 421-430.
Mary G. Bolton et al.; “Transient Intervention with Oltipraz Protects against Aflatoxin-induced Hepatic Tumorigenesis”; Cancer Research 53, 3499-3504, Aug. 1, 1993.
James A. Crowell et al.; “Chronic Toxicity Studies of 5-(2-Pyrazinyl)-4-methyl-1,2-dithiole-3-thione, a Potential Chemopreventive Agent”, Fundemental and Applied Toxicology 35 (1997), Article No. FA962256, pp. 9-21.
Kenji Kawamura, M.D., et al., “Intranuclear Localization of Proliferating Cell Nuclear Antigen During the Cell Cycle in Renal Cell Carcinoma”, 2ndQuantitative Cytology and Histology; vol. 22, No. 2/Apr. 2000; p. 107-113.
Linda E. Greenbaum et al.; “CCAAT Enhancer-binding Protein βis Required for Normal Hepatocyte Proliferation in Mice after Partial Hepatectomy”; The American Society for Clinical Investigations, Inc., vol. 102, No. 5, Sep. 1998, pp. 996-1007.
Davies, M.H. et al: Oltipraz-Induced Changes in Acetaminophen Disposition in Male Hamsters; The Toxicologist, 25thAnniversary Meeting, vol. 6, No. 1, Mar. 1986.
Supplementary Partial European Search Report Dated Jun. 9, 2004.
Kang Keon Wook, et al: “The anti-fibrogenic effect of a pharmaceutical composition of ′5-(2-pyrazinyl)-4-methyl-1,2-dithiol-3-thione! (oltipraz) and dimethyl-4,-4′-dimethoxy-5,6,5′,6′-dimethylene dioxybiphenyl-2,2′-dicarboxylate (DDB).” Archives of Pharmacal Research, Oct. 2002, vol. 25, No. 5, Oct. 2002, pp. 655-663, XP009031942.
Williams et al., “Human aflatoxicosis in developing countries: a review of toxicology, exposure, potential health consequences, and interventions”, Am J Clin Nutr (2004) 80: 1160-22.
Kang Keon-Wook
Kim Sang-Geon
Cantor & Colburn LLP
Gollamudi Sharmila
Padmanabhan Screenivasan
Sang-Geon Kim
LandOfFree
Pharmaceutical composition for treatment and prevention of... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Pharmaceutical composition for treatment and prevention of..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Pharmaceutical composition for treatment and prevention of... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3555530