United States Patent:   5,942,245

Assignee:  Polymun Scientific Immunbiologische Forschung GmbH (AT)

Filed:  May 5, 1997

Superoxide dismutase (SOD), preferably rhSOD, is used in liposomes, optionally mixed with hyaluronic acid and/or at least one physiologically acceptable carrier, and other optional additives, to prepare a pharmaceutical composition useful against increased concentrations of superoxide radicals and/or the damage caused thereby. These compositions can be administered topically, orally and/or parenterally to prevent and/or heal burns, skin lesions due to radiation, inflammations, rheumatic and arthritic diseases, bronchitis, ARDS, emphysema, allergic oedemas and other inflammatory process, possibly trigged by microbial infections. They may also be used in the cosmetic treatment of furuncles, acne and the like. They may also be used to improve the preservability of organic, preferably biogenic, materials, in particular organ transplants and liquids with organic components, as well as foodstuffs.

Summary of the Invention

The primary object of the present invention is to provide pharmaceutical compositions for transporting SOD, preferably rhSOD enclosed in protective liposomes, in a gentle, effective manner and with better bioavailability, to those parts of the body which are to be treated. In spite of a continuing general prejudice on the part of those skilled in the art, the inventors have been able in particular to use liposomally packaged SOD successfully for burns and scalds and for radiation damage, caused, for example, by UV radiation or ionizing radiation, in particular by external application. In the case of exposure to radiation, prophylactic use, for example together with a radiation-filtering or radiation-absorbing screening agent, is also possible in addition to therapeutic use.

A further object is to provide a pharmaceutical composition based on SOD in liposomes, which overcomes the stated disadvantages of the prior art and thus opens up additional fields of use, in particular in the area of cosmetics.

It is a further object of the present invention to transport SOD, preferably rhSOD enclosed in protective liposomes, in a gentle, effective manner and with better stability and a longer lasting effect, to the organic materials to be treated, for example vegetable or animal tissues, organs, organ or tissue transplants, cosmetic preparations based on organic substances and/or foods.

A particular object of the present invention is the use of the synergistic effect of a mixture of hyaluronic acid and SOD. Hyaluronic acid has also recently become known to those skilled in the art for its "free radical acceptor properties", and its use in wound treatment has repeatedly been described (Amgen, NO 9214480, 1992). The use of hyaluronic acid together with Colony Stimulating Factor (CSF) or Platelet Derived Growth Factor (PDGF) for accelerating wound healing has also been described in the literature (Zymogenetics, U.S. Pat. No. 5,128,321, 1992), and hyaluronic acid has also been described as an additive in cosmetics and pharmaceutical preparations (Shiseido, WO 9104279, 1991).

On the other hand--surprisingly--a combination of hyaluronic acid and SOD, in particular a mixture of hyaluronic acid and liposomally incorporated SOD, has not been described to date. To what extent this represents or represented a prejudice on the part of those skilled in the art cannot be adequately assessed at the present time. In any case, it was surprisingly found, in the course of the experiments which have finally led to the present invention, that hyaluronic acid supports and reinforces the effect of SOD, also of liposomally incorporated SOD, in an almost ideal manner.

Claim 1 of 20 Claims

1. A pharmaceutical composition comprising a low-fat or fat free carrier together with recombinant human Cu, Zn--SOD (rhSOD) in unilamellar liposomes having an average diameter of 200 nm or less, wherein the rhSOD is present in a concentration of 0.01 to 5% by weight based on the composition, for topical administration to a human body or part thereof.

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