Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Implant or insert
Patent
1997-09-03
1999-11-30
Azpuru, Carlos
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Implant or insert
A61F 202
Patent
active
059938455
ABSTRACT:
Compounds of submicromolar concentrations of a histone deacetylase inhibitor, useful as anti-fibrotic agents. The compounds strongly inhibit three main features of myofibroblastic differentiation of cultured hepatic stellate cells and of skin fibroblasts: (1) synthesis of collagens type I and III, the predominant collagens in fibrosis of liver and other organs; (2) cellular proliferation; and (3) expression of smooth muscle .alpha.-actin, a marker for activated myofibroblasts. Preferred compounds include trichostatin A or a pharmaceutically acceptable salt thereof, and sodium butyrate.
REFERENCES:
M. Yoshida et al., "Reversible Arrest of Proliferation of Rat 3Y1 Fibroblasts in Both the G1 and G2 Phases by Trichostatin A," Experimental Cell Research, 177(1988) 122-131.
M. Yoshida et al., "Potent and Specific Inhibition of Mammalian Histone Deacetylase both in Vivo and in Vitro by Trichostatin A," J. Biological Chemistry, vol. 265, No. 28 (1990) 17174-17179.
M. Kijima et al., "Trapoxin, an Antitumor Cyclic Tetrapeptide, Is an Irreversible Inhibitor of Mammalian Histone Deacetylase," J. Biological Chemistry, vol. 268, No. 30 (1993) 22429-22435.
A. Gressner et al., "Effect of n-Butyrate on the Synthesis of Sulfated Glycosaminoglycans and Hyaluronate by Rat Liver Rat-Storing Cells (Ito Cells)," Biochemical Pharmacology, vol. 37, No. 19 (1988) 3771-3776.
Geerts Albert Emmanuel Corneille
Niki Toshiro
Azpuru Carlos
Vrije Universiteit Brussel
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