Derivatized chitosan polymers and methods of treating vascular disorders
Inventors
Baker, Shenda • Wiesmann, William P.
Assignees
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Publication Number
US-11077135-B2
Publication Date
2021-08-03
Expiration Date
Abstract
Described herein are methods for treating inflammation, swelling and secondary damage of the vascular and lymphatic system in a subject, for example of the brain, spinal cord, and lungs; from organ reperfusion, e.g., resulting from endothelial leakage, glycocalyx dysfunction or loss of structural integrity of the glycocalyx.
Core Innovation
The invention relates to a method of treating a disorder of the vascular system by intravenously administering a polymer to a subject in need thereof, wherein the disorder is traumatic brain injury. The polymer is defined as a compound of a specified structure with an integer n between 20 and 6000 and R1 substituents independently selected from hydrogen and acetyl. The composition constraints require that at least 25% of the R1 substituents are H, at least 1% of the R1 substituents are acetyl, and that specific IV substituents meet stated minimum compositional limits.
The invention addresses vascular-system dysfunction during traumatic brain injury, including endothelial injury and deterioration affecting endothelial integrity. The disclosed approach aims to restore or stabilize endothelial glycocalyx integrity in the context of vascular disorders, including injuries associated with inflammation and capillary leak. The disclosed targeting of the endothelial surface is presented as a basis for therapeutic treatment following traumatic brain injury.
Dependent claim features further define the polymer’s functional relationship to vascular components and deterioration pathways. The polymer is described as interacting with the glycocalyx surface and reducing blood-brain barrier permeability. The invention additionally specifies reduction of VEGF-mediated deterioration, thereby linking therapeutic benefit to glycocalyx-related endothelial effects and vascular barrier protection in traumatic brain injury.
Claims Coverage
The document provides one independent claim directed to treating traumatic brain injury via intravenous administration of a defined polymer structure, with multiple dependent claims refining the inventive features and adding quantitative polymer constraints.
Intravenous treatment of traumatic brain injury with a defined cationic polymer structure
A method of treating a disorder of the vascular system by intravenously administering a polymer to a subject in need thereof, thereby treating the disorder, wherein the disorder is traumatic brain injury, and wherein the polymer is a compound of a specified structure, with n between 20 and 6000 and R1 substituents independently selected for each occurrence from hydrogen and acetyl, with compositional requirements including at least 25% R1 substituents as H, at least 1% R1 substituents as acetyl, and additional stated IV substituent compositional limits.
Interaction with the glycocalyx surface
The method further characterizes that the polymer interacts with the glycocalyx surface.
Reduction of blood-brain barrier permeability
The method further provides a way to reduce the permeability of the blood brain barrier.
Reduction of VEGF-mediated deterioration
The method is further characterized by reducing VEGF-mediated deterioration.
Polydispersity index constraint for the polymer
The method is carried out using a polymer having a polydispersity index in the range of about 1.0 to about 2.5.
Molecular weight constraint for the polymer
The method further specifies that the polymer used has a molecular weight (MW) between 30 and 300 kDa.
Overall, the claim set centers on intravenous administration of a polymer with a specific structure and compositional constraints to treat traumatic brain injury, with dependent claims further requiring glycocalyx interaction and limiting effects to blood-brain barrier permeability and VEGF-mediated deterioration, while constraining polymer polydispersity index and molecular weight.
Stated Advantages
Treating a disorder of the vascular system when the disorder is traumatic brain injury.
Reducing blood brain barrier permeability.
Reducing VEGF-mediated deterioration.
Documented Applications
Use in treating traumatic brain injury as a vascular-system disorder.
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