Anti-adhesive barrier membrane using alginate and hyaluronic acid for biomedical applications

• US 10,314,950 B2
• Filed: 05/16/2017
• Issued: 06/11/2019
• Est. Priority Date: 10/08/2010
• Status: Active Grant

• Current Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Original Assignee: Board of Regents of the University of Texas System (University of Texas System)
• Inventors: Mayes, Sarah, Schmidt, Christine E.
• Primary Examiner(s): Basquill, Sean M
• Application Number:
  US15/596,685
• Publication Number:
  US 20170312397A1
• Time in Patent Office: 756 Days
• CPC Class Codes: A61K 31/192 having aromatic groups, e.g. sulindac, 2-aryl-propionic acids, ethacrynic acid cannabinoids A61K31/658
• CPC Class Codes: A61K 31/195 having an amino group
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/43 Hormones, e.g. dexamethasone
• CPC Class Codes: A61L 2300/62 Encapsulated active agents, e.g. emulsified droplets
• CPC Class Codes: A61L 31/041 Mixtures of macromolecular compounds
• CPC Class Codes: A61L 31/145 Hydrogels or hydrocolloids
• CPC Class Codes: A61L 31/148 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61P 17/02 for treating wounds, ulcers, burns, scars, keloids, or the like
• CPC Class Codes: A61P 19/00 Drugs for skeletal disorders
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 41/00 Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 9/00 Drugs for disorders of the cardiovascular system
• CPC Class Codes: C08L 5/04 Alginic acid; Derivatives thereof
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

A non-synthetic, hydrophilic, biodegradable, biocompatible polysaccharide based non-toxic anti-adhesion hydrogel barrier is disclosed herein. The barrier of the present invention is formed by constructing a unique interpenetrating, crosslinked network with a unique porosity. Furthermore, the barrier of the present invention is comprised of tunable biopolymers for controllable mechanical robustness and degradation. The barrier of the present invention effectively reduces unwanted adhesions using non-synthetic components.

Claims

1. Articles of manufacture comprising:

a first hydrogel film;

a second hydrogel film;

wherein the first hydrogel film;

(a) is translucent, desiccated, amorphous, non-synthetic, and non-cytotoxic, (b) includes alginate that is negatively charged and crosslinked with at least one cation;

(c) includes a first concentration of hyaluronic acid, (d) includes a first matrix that encapsulates a drug, and (e) includes layers that each include the alginate and which are fused to each other;

wherein the second hydrogel film;

(a) is translucent, desiccated, amorphous, non-synthetic, and non-cytotoxic, (b) includes alginate that is negatively charged and crosslinked with the at least one cation;

(c) includes a second concentration of hyaluronic acid, (d) includes a second matrix that encapsulates the drug, and (e) includes layers that each include the alginate and which are fused to each other;

wherein;

(a) the first concentration of hyaluronic acid is greater than the second concentration of hyaluronic acid, and (b) the second hydrogel film is configured to degrade faster than the first hydrogel film, when implanted in a patient, in response to the first concentration of hyaluronic acid being greater than the second concentration of hyaluronic acid.

2. The articles of manufacture of claim 1 wherein the at least one cation includes calcium.

3. The articles of manufacture of claim 1 wherein:

the first hydrogel film is no less than 1% hyaluronic acid by dry weight and no greater than 33% hyaluronic acid by dry weight;

the second hydrogel film is no less than 1% hyaluronic acid by dry weight and no greater than 33% hyaluronic acid by dry weight.

4. The articles of manufacture of claim 3 wherein:

the first hydrogel film is bonded to a first surface coating, the first surface coating comprising ester bonds and at least one biopolymer selected from the group consisting of collagen, chitosan, or gelatin;

the second hydrogel film is bonded to a second surface coating, the second surface coating comprising ester bonds and at least one biopolymer selected from the group consisting of collagen, chitosan, or gelatin.

5. The articles of manufacture of claim 3 wherein;

the hyaluronic acid of the first hydrogel film and the alginate of the first hydrogel film are both formed around a first pore network;

the hyaluronic acid of the second hydrogel film and the alginate of the second hydrogel film are both formed around a second pore network.

6. The articles of manufacture of claim 3 wherein:

the first hydrogel film is unpatterned; and

the second hydrogel film is unpatterned.

7. The articles of manufacture of claim 3 wherein:

a surface of the first hydrogel film is anti-adhesive and non-attractive to cells; and

a surface of the second hydrogel film is anti-adhesive and non-attractive to cells.

8. The articles of manufacture of claim 7 wherein:

at least one of the layers of the first hydrogel film is adhesive to cells and another of the layers of the first hydrogel film includes the surface of the first hydrogel film that is anti-adhesive and non-attractive to cells;

at least one of the layers of the second hydrogel film is adhesive to cells and another of the layers of the second hydrogel film includes the surface of the second hydrogel film that is anti-adhesive and non-attractive to cells.

19. The articles of manufacture of claim 1 wherein:

the second hydrogel film is configured to release the hyaluronic acid faster than the first hydrogel film, when implanted in the patient, in response to the first concentration of hyaluronic acid being greater than the second concentration of hyaluronic acid;

the first and second hydrogel films are not coupled to each other.

9. Articles of manufacture comprising:

a first hydrogel film;

a second hydrogel film;

wherein the first hydrogel film;

(a) is translucent and non-synthetic, (b) includes alginate that is negatively charged and crosslinked;

(c) includes a first concentration of hyaluronic acid, (d) encapsulates at least one of a drug, growth factor, hormone, protein, or combinations thereof, and (e) includes layers that each include the alginate and which are fused to each other;

wherein the second hydrogel film;

(a) is translucent and non-synthetic, (b) includes alginate that is negatively charged and crosslinked;

(c) includes a second concentration of hyaluronic acid, (d) encapsulates the at least one of the drug, growth factor, hormone, protein, or combinations thereof, and (e) includes layers that each include the alginate and which are fused to each other;

wherein;

(a) the first concentration of hyaluronic acid is greater than the second concentration of hyaluronic acid, and (b) the second hydrogel film is configured to degrade faster than the first hydrogel film, when implanted in a patient, in response to the first concentration of hyaluronic acid being greater than the second concentration of hyaluronic acid.

10. The articles of manufacture of claim 9 wherein the alginate of the first hydrogel film is crosslinked with at least one cation;

the alginate of the second hydrogel film is crosslinked with the at least one cation;

the at least one cation includes calcium.

11. The articles of manufacture of claim 9 wherein:

the first hydrogel film is no less than 1% hyaluronic acid by dry weight and no greater than 33% hyaluronic acid by dry weight;

the second hydrogel film is no less than 1% hyaluronic acid by dry weight and no greater than 33% hyaluronic acid by dry weight.

12. The articles of manufacture of claim 11 wherein:

the first hydrogel film is bonded to a first surface coating, the first surface coating comprising ester bonds and at least one biopolymer selected from the group consisting of collagen, chitosan, or gelatin;

the second hydrogel film is bonded to a second surface coating, the second surface coating comprising ester bonds and at least one biopolymer selected from the group consisting of collagen, chitosan, or gelatin.

13. The articles of manufacture of claim 11 wherein;

the hyaluronic acid of the first hydrogel film and the alginate of the first hydrogel film are both formed around a first pore network;

the hyaluronic acid of the second hydrogel film and the alginate of the second hydrogel film are both formed around a second pore network.

14. The articles of manufacture of claim 11 wherein:

the first hydrogel film is unpatterned;

the second hydrogel film is unpatterned;

the first hydrogel film encapsulates the drug; and

the second hydrogel film encapsulates the drug.

15. The articles of manufacture of claim 11 wherein:

a surface of the first hydrogel film is anti-adhesive and non-attractive to cells; and

a surface of the second hydrogel film is anti-adhesive and non-attractive to cells.

16. The articles of manufacture of claim 15 wherein:

at least one of the layers of the first hydrogel film is adhesive to cells and another of the layers of the first hydrogel film includes the surface of the first hydrogel film that is anti-adhesive and non-attractive to cells;

at least one of the layers of the second hydrogel film is adhesive to cells and another of the layers of the second hydrogel film includes the surface of the second hydrogel film that is anti-adhesive and non-attractive to cells.

20. The articles of manufacture of claim 9 wherein:

the second hydrogel film is configured to release the hyaluronic acid faster than the first hydrogel film, when implanted in the patient, in response to the first concentration of hyaluronic acid being greater than the second concentration of hyaluronic acid;

the first and second hydrogel films are not coupled to each other.

17. Articles of manufacture comprising:

a first hydrogel film;

a second hydrogel film;

wherein the first hydrogel film;

(a) is translucent and non-synthetic, (b) includes alginate that is negatively charged and crosslinked with at least one cation;

(c) includes a first concentration of hyaluronic acid, (d) includes a first matrix that encapsulates a drug, and (e) includes layers that each include the alginate and which are fused to each other;

wherein the second hydrogel film;

(a) is translucent and non-synthetic, (b) includes alginate that is negatively charged and crosslinked with the at least one cation;

(c) includes a second concentration of hyaluronic acid, (d) includes a second matrix that encapsulates the drug, and (e) includes layers that each include the alginate and which are fused to each other;

wherein;

(a) the first concentration of hyaluronic acid is greater than the second concentration of hyaluronic acid, and (b) the second hydrogel film is configured to degrade faster than the first hydrogel film, when implanted in a patient, in response to the first concentration of hyaluronic acid being greater than the second concentration of hyaluronic acid.

18. The articles of manufacture of claim 17 wherein:

the first hydrogel film is no less than 1% hyaluronic acid by dry weight and no greater than 33% hyaluronic acid by dry weight;

the second hydrogel film is no less than 1% hyaluronic acid by dry weight and no greater than 33% hyaluronic acid by dry weight.

21. The articles of manufacture of claim 17 wherein:

the second hydrogel film is configured to release the hyaluronic acid faster than the first hydrogel film, when implanted in the patient, in response to the first concentration of hyaluronic acid being greater than the second concentration of hyaluronic acid;

the first and second hydrogel films are not coupled to each other.