Title:  Protease inhibitors for use in the treatment of psoriasis

United States Patent:  6,288,025

Assignee:  Biotech Australia Pty Limited (Roseville, AU)

Filed:  August 5, 1999

Foreign Application Priority Data:  Aug 05, 1998[AU] (PP 5087)

Psoriasis may be treated by topical administration of a urokinase inhibitor, such as PAI-2, or a combination of protease inhibitors, such as PAI-2 with other serine protease inhibitors and/or with protease inhibitors such as inhibitors of metalloproteinases, acid proteases, and thiol proteases.

SUMMARY OF THE INVENTION

The present invention relates to the use of a urokinase inhibitor for treating psoriasis. Thus, the present invention provides a method of treating psoriasis comprising administering to a patient in need thereof an effective amount of a urokinase inhibitor, wherein said inhibitor is topically administered to the affected area of the skin. In one embodiment of the invention, the urokinase inhibitor is selected from the group consisting of PAI-2, a variant thereof having plasminogen activating inhibitory properties, a derivative of PAI-2, and a variant of said derivative.

According to one aspect of the invention, the derivative is obtained by biochemical modification of PAI-2, wherein said modification is selected from the group consisting of chemical linking with polyethylene glycol, phosphate group attachment, sulfate group attachment, peptidase treatment, treatment with a sugar chain-modifying enzyme, and treatment with a sugar attachment enzyme. In one embodiment, the variant is obtained by deletion or addition of amino acid residues from the amino terminal end of PAI-2. In another embodiment, the variant is obtained by deletion or addition of amino acid residues from the carboxy terminal end of PAI-2.

According to another aspect of the invention, the urokinase inhibitor is administered in a gel formulation. In one embodiment, the gel is a cellulose gel further comprising a detergent. In another embodiment of the invention, the detergent is Tween-80.

According to yet another aspect of the invention, the PAI-2 is administered in a range of 0.1-2000 .mu.g/cm² of wound. According to yet another aspect of the invention, the PAI-2 is administered at least once a day for at least five days.

The present invention also provides a method of treating psoriasis comprising administering to a patient in need thereof an effective amount of a therapeutic agent comprising PAI-2 and at least one other serine protease inhibitor, wherein said therapeutic agent is topically administered to the affected area of the skin. In one embodiment, the other serine protease inhibitor is a uPA inhibitor.

According to one aspect of the invention, the therapeutic agent further comprises a protease inhibitor selected from the group consisting of thiol protease inhibitors, acid protease inhibitors, and metalloproteinase inhibitors. In one embodiment, these protease inhibitors are co-administered with PAI-2.

The present invention further relates to a pharmaceutical composition comprising PAI-2 in a gel containing a detergent. According to one aspect of the invention, the pharmaceutical composition comprises PAI-2 and at least one other serine protease inhibitor. According to another aspect of the invention, the pharmaceutical composition further comprising a protease inhibitor selected from the group consisting of thiol protease inhibitors, acid protease inhibitors, and metalloproteinase inhibitors. In one embodiment, the detergent is Tween-80. In another embodiment, the gel is a cellulose gel. In another embodiment, the gel contains at least one further component that reduces the formation of aggregates, enhances the stability of PAI-2, and that may act as a penetration enhancer. In a preferred embodiment, that component is propylene glycol.

Claim 1 of 20 Claims

We claim:

1. A method of treating psoriasis comprising administering to a patient in need thereof an effective amount of a urokinase inhibitor selected from the group consisting of PAI-2, a variant thereof having plasminogen activating inhibitory properties, a derivative of PAI-2, and a variant of said derivative, wherein said inhibitor is topically administered to the affected area of the skin.

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