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Eye drops for the delivery of an anti-glycation agent that prevents and treats diabetes- and age-related pathologies (L-11323)

Details

Project TitleEye drops for the delivery of an anti-glycation agent that prevents and treats diabetes- and age-related pathologies (L-11323)
Track CodeNRC no. 11323
Websitehttp://www.nrc-cnrc.gc.ca/eng/licensing/bri/eye-drops.html
Short Description

Glycation is a non enzymatic chemical process in which human DNA, lipids and proteins are damaged by the attachment of reducing sugars such as glucose, ultimately leading to the formation of highly reactive Advanced Glycation Endproducts (AGEs). This process has been associated with deleterious health effects. The present invention provides a potent inhibitor of protein glycation and AGEs formation that is particularly advantageous for eye-drop delivery in the prevention and treatment of diabetes- and age-related pathologies.

Abstract
 
Tagsage-related pathologies, anti-aging, anti-glycation, diabetes, eye, eye drops
 
Posted DateSep 19, 2007 10:47 AM

Researcher

Name
Yasuo Konishi

Contact

Name
Yves Quenneville

Description

Glycation is a non enzymatic chemical process in which human DNA, lipids and proteins are damaged by the attachment of reducing sugars such as glucose, ultimately leading to the formation of highly reactive Advanced Glycation Endproducts (AGEs). This process has been associated with deleterious health effects. The present invention provides a potent inhibitor of protein glycation and AGEs formation that is particularly advantageous for eye-drop delivery in the prevention and treatment of diabetes- and age-related pathologies.

Potential Applications

·  An anti-glycation agent that inhibits the glycation process and prevents the formation of AGEs (e.g. free radicals, a-dicarbonyl species, protein cross-links, etc.).

·  Eye drops for prevention and treatment of ocular pathologies such as diabetic retinopathy.

·  Anti-aging protection of long-lived ocular proteins, such as collagen and lens crystalline.

Features and Benefits

Prevents initial step of protein glycation
D-isoproterenol directly protects amino groups of proteins against glycation, especially those of lysine residues, by blocking the initial reaction with a reducing sugar. This in turn prevents the formation of highly reactive AGEs that increase the oxidative stress of biological systems.

High potency anti-glycation
The anti-glycation activity of D-isoproterenol (IC50 of 21 μM) compares favorably to that of aminoguanidine (IC50 of 350 μM). This value is also within the effective concentration range reported for the choroid/retinal distribution of dipivefrin, a structurally related anti-glaucoma eye drop.

Non-toxicity to the surface of the eye at high concentration
Response to a single eye drop application of D-isoproterenol at high concentration (10-20% solution) was reported to be physiologically acceptable however long term use was not tested. The anticipated concentration of D-isoproterenol prodrug is 0.1%.

Enhanced absorption of prodrug formulation
Dipivalyl D-isoproterenol is a prodrug of D-isoproterenol that can be administered topically by eye drop. The dipivalyl portion of the drug facilitates absorption and penetration of the prodrug across the corneal epithelium as is well documented for the prodrug dipivalyl D,L-adrenaline (dipivefrin).

Suitable for long-term preventive treatment

The previously described low beta-adrenergic receptor affinity of D-isoproterenol and the absence of systemic toxicity make this drug suitable for long-term use. Continuous eye drop administration of its prodrug will ultimately prevent glycation allowing for ocular protection from diabetic retinopathy and other diabetes-and age-related complications.

Files

File Name Description
L-11323 Eye drops for the delivery of an anti-glycation agent that prevents and treats diabetes- and age-related pathologies Download

Intellectual Property

Patent Number Issue Date Type Country of Filing
http://patents1.ic.gc.ca/details?patent_number=2463624&language=EN None Other Patent Canada