Prostaglandin compositions and methods for the treatment of vasospasm

Abstract

Compositions and methods for the treatment of vasospasm are provided comprising applying an amount of a semi-solid vasoactive prostaglandin composition to the affected tissue. Also provided are methods of improving microcirculation in a replanted body part.

Description

BACKGROUND OF THE INVENTION Vasospasm is a constriction of blood vessels, resulting in ischemia of the tissue supplied by the blood vessels. Prolonged spasm in arteries, veins, and vein grafts has been described as a physiologic complication in microsurgery for over 20 years (Buncke, H. J, Microsurgery: Transplantation-Replantation, on-line edition, Chapter 36, http: / / buncke.org / textbook.html, accessed Dec. 13, 2002). Vasospasm results from several processes including intrinsic smooth muscle contraction, local noradrenaline metabolism, neurogenic and hormonal processes, and prostaglandin metabolism. Topical agents, such as magnesium sulfate, lidocaine, papaverine and chlorpromazine have been reported to successfully relieve vasospasm. Other described methods for relieving vasospasm include nerve blocks, systemic adrenergic agents and systemic vasodilating agents such as sodium nitroprusside (Buncke, on-line edition, http: / / buncke.org / book / ch36 / ch36—2.html). Experimental attempts to...

AI Technical Summary

Benefits of technology

We have found that administration of prostaglandin compositions comprising a penetration enhancer relieves constriction of a blood vessel in vasospasm and restores blood flow. The method and compositions are useful for the relief of vasospasm in several conditions, including vasospasm occurring during and following replantation surgery. In other aspects, the invention provides methods and compositions for improving microcirculation in a replanted body part. In other embodiments, the present invention provides methods of treating tissue ischemia. In further preferred embodiments, the present invention provides compositions and methods for preventing reperfusion injury.

In preferred embodiments, the present invention provides a method of preventing reperfusion injury of ischemic tissue by providing a composition of the present invention, applying the composition to the surface of the affected tissue, and optionally, applying the composition to the vascular extima of blood vessels supplying the affected tissue. In preferred embodiments, the vascular perfusion volume to the tissue returns to normal within 30 minutes, more preferably in 10 minutes, optimally less than 10 minutes after the application of the composition. In other aspects, the present invention provides a composition useful in the manufacture of a medicament for the treatment of vasospasm, for improving local microcirculation, especially in a replanted body part, or for preventing reperfusion injury.

Problems solved by technology

Vasospasm is a constriction of blood vessels, resulting in ischemia of the tissue supplied by the blood vessels.

Experimental attempts to find roles for modifiers of prostaglandin function, sympatholytics, calcium channel blockers and numerous other drugs have generally not succeeded in producing either clearly applicable models or reproducibly positive results (Buncke, on-line edition, http: / / buncke.org / book / ch36 / ch36—5.html).

If circulation is not re-established in time, tissue damage may result due to reperfusion injury.

Tissue reperfusion injury, seen in its full clinical extent as the no-reflow phenomenon, appears as inflammatory response to reperfusion, resulting in the ultimate death of the tissue.

While the potential benefits from transdermal delivery of prostaglandin E1 have long been recognized, prior efforts at developing a topical composition for prostaglandin delivery have not been fully successful.

Working alone, most drugs, prostaglandin formulations included, do not sufficiently permeate the skin to provide drug concentration levels comparable to those obtained from other drug delivery routes.

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