# US 10,766,970 B2 · Modified carbohydrates, compositions comprising the same, and methods of making and using the same

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- Number: US 10,766,970 B2
- Document ID: US10766970B2
- Status: Granted
- Kind: B2
- Application number: 16/311,992
- Filed: 2017-06-30
- Published: 2019-12-12
- Granted: 2020-09-08
- Earliest claimed: 2016-07-01
- Assignees: Wake Forest University Health Sciences; Wake Forest University
- Applicants: Wake Forest University Health Sciences; Wake Forest University
- Inventors: Mark E. Welker; Emmanuel C. Opara; Surya R. Banks; Amber N. Weissenfluh
- Web page: https://patentgrep.com/patent/US10766970B2

## CPC

- C08B 37/0084: {Guluromannuronans, e.g. alginic acid, i.e. D-mannuronic acid and D-guluronic acid units linked with alternating alpha- and beta-1,4-glycosidic bonds; Derivatives thereof, e.g. alginates}
- A61K 31/734: Alginic acid
- A61K 47/61: the organic macromolecular compound being a polysaccharide or a derivative thereof
- A61K 47/6903: {the form being semi-solid, e.g. an ointment, a gel, a hydrogel or a solidifying gel}
- C08L 5/04: Alginic acid; Derivatives thereof
- C08B: POLYSACCHARIDES; DERIVATIVES THEREOF (polysaccharides containing less than six saccharide radicals attached to each other by glycosidic linkages C07H; fermentation or enzyme-using processes C12P19/00; sugar industry C13; production of cellulose D21)
- 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)
- C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06)

## Abstract

Modified alginates are described herein along with hydrogels comprising the same. A modified alginate may be prepared by reacting alginate and an aromatic compound (e.g., an aromatic amine) and/or pH sensitive compound. The modified alginates, hydrogels, and/or methods described herein may be used to coat and/or encapsulate at least a portion of a bioactive substance, optionally for oral delivery in humans and other animals.

## Claims

### Claim 1

A compound comprising at least one unit having a structure of Formula I:
wherein
Y is absent or a C1-C4 alkyl or C1-C4 alkenyl;
R1 is each independently selected from the group consisting of —H, —OH, —NH2, —COOH, —NO2, —CN, —Br, —Cl, —F, —C1-C6 alkylhalide, unsubstituted or substituted —C1-C6 alkyl, unsubstituted or substituted —C1-C6 alkenyl, —SO2H, —SO3H, —COCH3, —Si(OH)3, —SO2NH2, —PO(OR′)2, and —B(OH)2, wherein R′ is unsubstituted or substituted alkyl, alkenyl, alkynyl, or aryl;
n is from 1 to 1,000,000; and
o is 1, 2, 3, 4, or 5,
wherein at least one R1 is in the para position and is selected from the group consisting of —NH2, —COOH, —NO2, —CN, —Br, —Cl, —F, —C1-C6 alkylhalide, unsubstituted or substituted —C1-C6 alkyl, unsubstituted or substituted —C1-C6 alkenyl, —SO2H, —SO3H, —COCH3, —Si(OH)3, —SO2NH2, —PO(OR′)2, and —B(OH)2, and wherein R′ is unsubstituted or substituted alkyl, alkenyl, alkynyl, or aryl, and
wherein the compound is an alginate polymer.

### Claim 2

A compound comprising at least one unit having a structure of Formula II:
wherein
Y is absent or a C1-C4 alkyl or C1-C4 alkenyl;
R1 is each independently selected from the group consisting of —H, —OH, —NH2, —COOH, —NO2, —CN, —Br, —Cl, —F, —C1-C6 alkylhalide, unsubstituted or substituted —C1-C6 alkyl, unsubstituted or substituted —C1-C6 alkenyl, —SO2H, —SO3H, —COCH3, —Si(OH)3, —SO2NH2, —PO(OR′)2, and —B(OH)2, wherein R′ is unsubstituted or substituted alkyl, alkenyl, alkynyl, or aryl;
n is from 1 to 1,000,000; and
o is 0, 1, 2, 3, 4, or 5, and
wherein the compound is an alginate polymer.

### Claim 3 (depends on 1)

The compound of claim 1, wherein at least one R1 has a pKa in a range of about 3 to about 6.

### Claim 4 (depends on 1)

The compound of claim 1, wherein the compound comprises at least one pH sensitive functional group.

### Claim 5 (depends on 1)

The compound of claim 1, wherein the compound is prepared by reacting alginate with a reactant.

### Claim 6 (depends on 5)

The compound of claim 5, wherein the alginate is an oxidized alginate.

### Claim 7 (depends on 5)

The compound of claim 5, wherein the reactant is incorporated into the alginate in an amount of about 1% to about 15% of the polysaccharide units of the alginate.

### Claim 8 (depends on 5)

The compound of claim 5, wherein at least 90% of the reactant is chemically bonded to the alginate.

### Claim 9 (depends on 1)

A hydrogel comprising the compound of claim 1, wherein the compound is present in the hydrogel in an amount of about 0.1% to about 10% w/v of the hydrogel.

### Claim 10 (depends on 9)

The hydrogel of claim 9, wherein the hydrogel is cross-linked.

### Claim 11 (depends on 9)

The hydrogel of claim 9, wherein the hydrogel further comprises a bioactive substance.

### Claim 12 (depends on 11)

The hydrogel of claim 11, wherein the bioactive substance is uniformly distributed within the hydrogel.

### Claim 13 (depends on 9)

The hydrogel of claim 9, wherein the hydrogel further comprises a divalent cation in an amount of about 0.1 mmol to about 1 mmol.

### Claim 14 (depends on 9)

The hydrogel of claim 9, wherein the hydrogel has an elastic modulus in a range of 1 kPa to about 20 kPa.

### Claim 15 (depends on 9)

The hydrogel of claim 9, wherein the hydrogel is in the form of a bead, microcapsule, and/or pellet.

### Claim 16 (depends on 9)

A method of treating a subject, the method comprising administering the hydrogel of claim 9 to a subject, wherein the hydrogel comprises at least one bioactive substance, thereby treating the subject.

### Claim 17 (depends on 9)

A method of increasing the stability and/or shelf life of a bioactive substance, the method comprising providing a hydrogel of claim 9, wherein the hydrogel comprises at least one bioactive substance, thereby increasing the stability and/or shelf life of the bioactive substance.

### Claim 18 (depends on 2)

The compound of claim 2, wherein o is 5 and each R1 is —H.

### Claim 19 (depends on 2)

The compound of claim 2, wherein o is 1, 2, 3, 4, or 5 and at least one R1 is an unsubstituted or substituted C1-C6 alkyl.

### Claim 20 (depends on 2)

The compound of claim 2, wherein o is 1, 2, 3, 4, or 5 and at least one R1 is —COCH3.