Queen's University at Kingston

Strakan International Limited

James D Banting

Michael A Adams

Jeremy P W Heaton

Jeremy P Heaton

Methods for treating vascular conditions associated with localized imbalance in vascular tone, which are hypothesized to be largely due to elevated endothelin (ET) are provided. The methods involve administration of nitric oxide (NO), agents which are able to provide NO, such as NO donors, agents which activate guanyl cyclase, such as YC-1, or agents which prolong the actions of endogenous NO or cyclic guanosine monophosphate (cGMP; a 2nd messenger molecule), such as phosphodiesterase (PDE) inhibitors. According to the invention, such agents are administered in minimal doses or microdoses by any route known in the art, so as to provide dosages which are about one half to about one twentieth (&#xbd; to 1/20) of those known to induce vasodilation in 'normal' circulations. The low doses of these agents effectively alleviate vascular conditions associated with a reduction in NO production or an attenuation of NO effect, by restoring balance in vascular tone while exerting almost no systemic effect in normal vasculature.

Microdose therapy

Methods for treating vascular conditions associated with localized imbalance in vascular tone, which are hypothesized to be largely due to elevated endothelin (ET) are provided. The methods involve administration of nitric oxide (NO), agents which are able to provide NO, such as NO donors, agents which activate guanyl cyclase, such as YC-1, or agents which prolong the actions of endogenous NO or cyclic guanosine monophosphate (cGMP; a 2nd messenger molecule), such as phosphodiesterase (PDE) inhibitors. According to the invention, such agents are administered in minimal doses or microdoses by any route known in the art, so as to provide dosages which are about one half to about one twentieth (&frac12; to {fraction (1/20)}) of those known to induce vasodilation in &ldquo;normal&rdquo; circulations. The low doses of these agents effectively alleviate vascular conditions associated with a reduction in NO production or an attenuation of NO effect, by restoring balance in vascular tone while exerting almost no systemic effect in normal vasculature.

The mechanism of hypertension following acute NO synthase blockage is via endothelin-mediated vasoconstriction. Thus, NO appears to inhibit endothelin activity by blocking its expression and not as a chronic direct acting vasodilator. Administration of an endothelin antagonist to a patient in a 'normal' physiological state may result in specific regional vasodilation. This treatment finds utility in the treatment of erectile dysfunction.

Method of ameliorating erectile dysfunction

Antagonism of endothelin actions

An everting toroid for use in delivering a powdered, fluid, or aerosolized pharmaceutical composition, or other composition, to an internal body cavity, such as the urethra, or other cavity, is contained within a tubular housing and may be extended therefrom and retracted back into the tubular housing. The composition may be distributed on the surface of the everting toroid when made from an impermeable membrane, contained within the toroid when made from a permeable membrane, or may be injected through the lumen thereof via an aerosol wand which releases the composition as the toroid and/or wand are withdrawn from the cavity.

Everting toroid device for insertion into a body cavity

A method of treatment, in an organism, of a vascular condition, comprising administration of at least one agent at a level which enhances NO and which does not appreciably alter normal systemic vascular tone in said organism. At least one agent is an NO donor selected from the group consisting of glyceryl trinitrate, isosorbide 5-mononitrate, isosorbide dinitrate, pentaerythritol tetranitrate, erythrityl tetranitrate, sodium nitroprusside, 3-morpholinosydnonimine molsidomine, S-nitroso-N-acetylpenicillamine, S-nitrosoglutathione, and N-hydroxy-L-arginine.

An everting toroid for use in delivering a powdered or liquid or aerosolized drug to an internal body cavity, such as the urethra, is described. The drug may be distributed on the surface of the everting toroid or may be injected through the lumen thereof via an aerosol wand which is designed to release the drug as the toroid and/or wand are withdrawn from the body cavity.

Everting toroid device for delivering a drug into a body cavity

The mechanism of hypertension following acute NO synthase blockade is via endothelin mediated vasoconstriction. Thus, NO appears to inhibit endothelin activity by blocking its expression and not as a chronic direct acting vasodilator. Administration of an endothelin antagonist to a patient in a `normal` physiological state may result in specific regional vasodilation. This treatment finds utility in the treatment of erectile dysfunction.

Growing community of inventors

Kingston, Canada

James D Banting