Drug – bio-affecting and body treating compositions – Preparations characterized by special physical form – Liposomes
Reexamination Certificate
1992-12-11
2004-07-20
Page, Thurman K. (Department: 1615)
Drug, bio-affecting and body treating compositions
Preparations characterized by special physical form
Liposomes
C424S400000, C424S422000, C424S434000, C424S045000
Reexamination Certificate
active
06764693
ABSTRACT:
BACKGROUND AND INTRODUCTION
The present invention relates to a free radical quenching composition comprising a liposome containing at least two antioxidants selected from the following groups: beta-carotene, vitamin E, vitamin C, glutathione, niacin, and optionally trace metals (Zn, Se, Cr, Cu, Mn). The present invention also concerns a method for reducing the undesirable side effects of free radicals in a mammal by administering to a mammal in need of such antioxidants an effective amount of liposomes containing at least two antioxidants.
Previously there has not existed a composition or method for increasing the entire spectrum of non-enzymatic antioxidants in either the extracellular and/or intracellular milieu, either simultaneously or sequentially or selectively. Previous experiments that have attempted to alter free radical reactions in mammals have increased antioxidant levels by diet, intraperitoneal injections, or by the addition of one or two non-enzymatic or enzymatic antioxidants (but not within the same liposome).
Turrens and others (J. Clin. Invest; Vol. 73, 1984:87-95) injected mice with liposomes containing superoxide dismutase and catalase in an effort to examine its possible protective effects against oxygen toxicity. There were several beneficial effects described for those rats injected with liposomes containing these antioxidant enzymes: increased survival, less fluid in the pleural cavity, an increase of superoxide dismutase and catalase concentrations of 1.7 and 3.1 fold respectively, superoxide activity increased over controls. It was also noted that the half lives for the liposome entrapped antioxidants were also markedly prolonged in comparison to the injection of free enzymes.
The antioxidant glutathione (GSH) was entrapped in liposomes and administered intravenously to rats. Wendel et al. demonstrated significant hepatic protection from lipid peroxidation which had been induced by paractomel. There was significant uptake of the glutathione entrapped in liposomes in the liver and spleen. This was the first demonstration of the efficacy of liposome encapsulated non-enzymatic antioxidant levels being increased in vivo. Free GSH intravenously administered has a t
½
of approximately 1.6 minutes; in contrast, intravenously administered liposomes encapsulating GSH are postulated to have a longer half life.
These previous methods of increasing cellular antioxidant levels have serious shortcomings with little use in the clinical setting. Previous works involving the administration of antioxidants have failed to appreciate the potpourri of different oxidants generated in various pathological conditions.
SUMMARY OF THE INVENTION
In order for a composition to be effective in the elimination of a variety of free radicals, it must contain antioxidants that are specific for such free radicals. The present invention concerns a composition that contains at least two members of the following: beta-carotene, alpha-tocopherol (vitamin E), ascorbic acid (vitamin C), glutathione, niacin, with or without trace metals, all of which are contained in the same liposome or in a multiple liposomal arrangement. The liposomes participate in the pathologic free radical reactions by undergoing peroxidation, thereby bursting and releasing the antioxidants.
The present invention also relates to a method of delivering non-enzymatic antioxidants and a method for reducing the undesirable side effects of free radicals in a mammal.
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Amaox, Ltd.
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Greenberg & Traurig, LLP
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Page Thurman K.
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