# US 11,077,135 B2 · Derivatized chitosan polymers and methods of treating vascular disorders

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- Number: US 11,077,135 B2
- Document ID: US11077135B2
- Status: Granted
- Kind: B2
- Application number: 15/752,852
- Filed: 2016-08-12
- Published: 2018-08-23
- Granted: 2021-08-03
- Earliest claimed: 2015-08-14
- Assignees: Synedgen, Inc.
- Applicants: Synedgen, Inc.
- Inventors: Shenda Baker; William P. Wiesmann
- Web page: https://patentgrep.com/patent/US11077135B2

## CPC

- A61K 31/726: Glycosaminoglycans, i.e. mucopolysaccharides (chondroitin sulfate, dermatan sulfate A61K31/737)
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 31/7008: Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
- A61K 31/715: Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## 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.

## Claims

### Claim 1

A method of treating a disorder of the vascular system, the method comprising 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 the following structure:
wherein:
n is an integer between 20 and 6000; and
each R1 is independently selected for each occurrence from hydrogen, acetyl,
wherein at least 25% of R1 substituents are H, at least 1% of R1 substituents are acetyl, and at least 2% of IV substituents are

### Claim 2 (depends on 1)

The method of claim 1, wherein the method restores normal blood transport or reduces abnormal fluid transport in the subject.

### Claim 3 (depends on 1)

The method of claim 1, wherein the method reduces the permeability of the blood brain barrier.

### Claim 4 (depends on 1)

The method of claim 1, wherein the method enhances the integrity of the blood brain barrier.

### Claim 5 (depends on 1)

The method of claim 1, wherein the disorder is a result of dysfunction of the glycocalyx or loss of structural integrity of the glycocalyx.

### Claim 6 (depends on 1)

The method of claim 1, wherein the method reduces VEGF-mediated deterioration.

### Claim 7 (depends on 1)

The method of claim 1, wherein the polymer is soluble at physiologic pH.

### Claim 8 (depends on 1)

The method of claim 1, wherein the polymer has a molecular weight (MW) between 30 and 300 kDa.

### Claim 9 (depends on 1)

The method of claim 1, wherein the polymer is 10-35% functionalized.

### Claim 10 (depends on 1)

The method of claim 1, wherein the polymer interacts with the glycocalyx surface.

### Claim 11 (depends on 1)

The method of claim 1, wherein the polymer is soluble at pH 6 to pH 8.

### Claim 12 (depends on 1)

The method of claim 1, wherein the polymer has a polydispersity index of about 1.0 to about 2.5.