Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – C-o-group doai
Reexamination Certificate
1999-09-21
2001-04-17
Aulakh, Charanjit S. (Department: 1612)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
C-o-group doai
C568S716000, C562S433000, C562S454000, C514S567000
Reexamination Certificate
active
06218437
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates generally to the treatment and prevention of hepatic fibrosis, and more particularly to the administration of pharmacologically active compounds for the treatment and prevention of viral hepatitis C.
BACKGROUND OF THE INVENTION
The majority of patients suffering from chronic hepatitis are infected with either chronic hepatitis B virus (HBV), chronic hepatitis C virus (HCV) or autoimmune disease. While each type is associated with certain distinct characteristics, generally speaking, chronic hepatitis can progress to cirrhosis and hepatic failure. Unfortunately, there are few effective treatments for hepatitis. For example, treatment of autoimmune chronic hepatitis is generally limited to immunosuppressive treatment with corticosteroids. For the treatment of hepatitis B and C, the FDA has approved administration of recombinant interferon alpha. However, interferon alpha is associated with a number of dose-dependent adverse effects, including thrombocytopenia, leukopenia, bacterial infections, and influenza-like symptoms. Indeed, normal interferon alpha dosing parameters for the treatment of chronic hepatitis B require discontinuance or dosing adjustment in approximately 20-50% of patients. Other agents used to treat chronic hepatitis B or C include the nucleoside analog ribovirin and ursodeoxycholic acid; however, neither has been shown to be very effective. [See Medicine, (D. C. Dale and D. D. Federman, eds.) (Scientific American, Inc., New York), 4: VIII:1-8 (1995)].
Indeed, current therapies do not effectively prevent or cure hepatitis C or the hepatic fibrosis associated with the disease. Clearly, new alternative treatment methods and agents are needed and would be welcomed by those plagued by hepatitis C who either cannot tolerate available treatment regimens or who are refractory to those regimens.
SUMMARY OF THE INVENTION
The present invention discloses the administration of vitamin E and other pharmacologically active compounds for the treatment and prevention of liver fibrosis associated with viral hepatitis C and other chronic liver diseases. Indeed, treatment with high doses of vitamin E may be effective in treating chronic hepatitis C in patients refractory to interferon.
The present invention also describes new methods for the treatment and prevention of hepatic fibrosis and hepatic conditions manifesting hepatic fibrosis involving the administration of compounds with antioxidant properties. In preferred embodiments, these new methods involve the administration of butylated hydroxytoluene and a metabolite of pentoxifylline, 1-[3-carboxypropyl]-3, 7-dimethylxanthine (metabolite 5 of pentoxifylline).
Specifically, the present invention contemplates a method of treating hepatitis C, comprising: a) providing i) a subject having symptoms of hepatitis C, and ii) an antioxidant; and b) administering a therapeutic amount of the antioxidant to the subject under conditions such that the symptoms are diminished. In one embodiment, the subject is refractory to interferon. In some embodiments, the antioxidant is administered orally to the subject, whereas it is administered parenterally in other embodiments. In further embodiments, the antioxidant is d-&agr;-tocopherol. In some embodiments, the method further comprises the step prior to step b) of measuring the symptoms by liver biopsy; moreover, some embodiments of the method further comprise the step subsequent to step b) of measuring the symptoms by liver biopsy.
The present invention also contemplates a method of treating hepatitis C, comprising: a) providing i) a subject with hepatitis C having symptoms indicating fibrosis, and ii) d-&agr;-tocopherol; and b) administering a therapeutic amount of d-&agr;-tocopherol to the subject under conditions such that the symptoms are diminished. In particular embodiments, the subject is refractory to interferon. In certain embodiments, the d-&agr;-tocopherol is administered orally to the subject, while it is administered parenterally in other embodiments. When administered orally, the therapeutic amount of d-&agr;-tocopherol is from 800 units daily to 1600 units daily in preferred embodiments, and from 1000 units daily to 1400 units daily in more preferred embodiments. In some embodiments, the method further comprises the step prior to step b) of measuring the symptoms by liver biopsy. Moreover, some embodiments of the method further comprise the step subsequent to step b) of measuring the symptoms by liver biopsy.
As indicated above, the present invention also contemplates the administration of other antioxidants for the treatment of hepatic fibrosis. For example, the present invention contemplates a method of treating hepatic fibrosis, comprising: a) providing i) a subject with hepatic fibrosis, and ii) 1-[3-carboxypropyl]-3, 7-dimethylxanthine or butylated hydroxytoluene; and b) administering a therapeutic amount of 1-[3-carboxypropyl]-3, 7-dimethylxanthine or butylated hydroxytoluene to the subject under conditions such that the hepatic fibrosis is diminished. In particular embodiments, the 1-[3-carboxypropyl]-3, 7-dimethylxanthine or butylated hydroxytoluene is administered orally to the subject. When administered orally, the therapeutic amount of the 1-[3-carboxypropyl]-3, 7-dimethylxanthine is from 400 mg daily to 1200 mg daily in some embodiments. Other embodiments and aspects of the present invention will become apparent to those skilled in the art based upon the description that follows.
Furthermore, the present invention provides new methods for the treatment and prevention of hepatic fibrosis and hepatic conditions manifesting hepatic fibrosis involving the administration of 2,6-di-tert-butylphenols. Specifically, the present invention contemplates a method of treating hepatitis C, comprising: a) providing i) a subject having symptoms of hepatitis C, and ii) a 2,6-di-tert-butylphenol derivative; and b) administering a therapeutic amount of the 2,6-di-tert-butylphenol derivative to the subject under conditions such that the symptoms are diminished. In one embodiment, the subject is refractory to interferon. In some embodiments, the method further comprises the step prior to step b) of measuring the symptoms by liver biopsy; moreover, some embodiments of the method further comprise the step subsequent to step b) of measuring the symptoms by liver biopsy.
In one embodiment, the methods of the present invention involve the administration of a 2,6-di-tert-butylphenol selected from the group consisting of 4-propynoyl-2,6-di-tert-butylphenol, 4-(1′-hydroxy-2′-propynyl)-2,6-di-tert-butylphenol, 4-(3′-butynoyl)-2,6-di-tert-butylphenol, 4-butadienoyl-2,6-di-tert-butylphenol, 4-(4′-pentynoyl)-2,6-di-tert-butylphenol, 4-(4′-pentenoyl)-2,6-di-tert-butylphenol, 4-(2′-dimethoxymethyl-4′-pentynoyl)-2,6-di-tert-butylphenol, 4-(2′,2′-dimethyl-4′-pentynoyl)-2,6-di-tert-butylphenol, 4-(3′,3′-dimethyl-4′-pentynoyl)-2,6-di-tert-butylphenol, 4-(4′-pentyn-3′one)-2,6-di-tert-butylphenol, 4-(5′-hexynoyl)-2,6-di-tert-butylphenol, 4-(5′-hexenoyl)-2,6-di-tert-butylphenol, 4-(2′-methyl-5′-hexynoyl)-2,6-di-tert-butylphenol, 4-(1′-hydroxy-5′-hexynyl)-2,6-di-tert-butylphenol, 4-(5′-hexynyl)-2,6-di-tert-butylphenol, 4-(1′-methylidine-5′-hexynyl)-2,6-di-tert-butylphenol, 4-[(S)-(−)-3′-methyl-5′-hexynoyl]-2,6-di-tert-butylphenol, 4-[(R)-(+)-3′-methyl-5′-hexynoyl)-2,6-di-tert-butylphenol, 4-(6′-heptynoyl)-2,6-di-tert-butylphenol, 4-(6′-heptyn-3′-one)-2,6-di-tert-butylphenol, 4-[4′-(2″-propynyl)-6′-heptyn-3′-one]-2,6-di-tert-butylphenol, 4-(7′-octynoyl)-2,6-di-tert-butylphenol, 4-[(E)-1′-penten-4′-yn-3′-one)-2,6-di-tert-butylphenol, 4-[(E)-1′,6′-heptadiene-3′-one)-2,6-di-tert-butylphenol, 4-(3′,3&pri
Aulakh Charanjit S.
Medlen & Carroll LLP
The Regents of the University of California
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