System for forming a biocompatible foam using polymerizable alpha(1-4)glucopyranose polymers and gas-producing component

• US 8,999,377 B2
• Filed: 09/19/2008
• Issued: 04/07/2015
• Est. Priority Date: 09/19/2007
• Status: Active Grant

• Current Assignee: Surmodics Incorporated
• Original Assignee: Surmodics Incorporated
• Inventors: Rolfes, Emily R., Chudzik, Stephen J.
• Primary Examiner(s): Orwig, Kevin S
• Application Number:
  US12/284,210
• Publication Number:
  US 20090093550A1
• Time in Patent Office: 2,391 Days
• Field of Search: None
• US Class Current: 424/444
• CPC Class Codes: A61K 9/122 Foams; Dry foams edible foams A61K9/0056
• CPC Class Codes: A61L 15/28 Polysaccharides or their derivatives A61L15/225 takes precedence
• CPC Class Codes: A61L 15/425 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 15/62 Compostable, hydrosoluble or hydrodegradable materials
• CPC Class Codes: A61L 26/0023 Polysaccharides
• CPC Class Codes: A61L 26/0085 Porous materials, e.g. foams or sponges
• CPC Class Codes: A61L 26/009 Materials resorbable by the body
• CPC Class Codes: C08J 2201/024 Preparation or use of a blowing agent concentrate, i.e. masterbatch in a foamable composition
• CPC Class Codes: C08J 2303/02 Starch; Degradation products thereof, e.g. dextrin
• CPC Class Codes: C08J 2303/14 Amylose derivatives; Amylopectin derivatives
• CPC Class Codes: C08J 2305/00 Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2301/00 or C08J2303/00
• CPC Class Codes: C08J 2305/16 Cyclodextrin; Derivatives thereof
• CPC Class Codes: C08J 2371/02 Polyalkylene oxides
• CPC Class Codes: C08J 2403/00 Characterised by the use of starch, amylose or amylopectin or of their derivatives or degradation products
• CPC Class Codes: C08J 2405/00 Characterised by the use of polysaccharides or of their derivatives not provided for in groups C08J2401/00 or C08J2403/00
• CPC Class Codes: C08J 2471/00 Characterised by the use of polyethers obtained by reactions forming an ether link in the main chain of polyacetals C08J2459/00; of epoxy resins C08J2463/00; of polythioether-ethers C08J2481/02; of polyethersulfones C08J2481/06; Derivatives of such polymers
• CPC Class Codes: C08J 9/0004 Use of compounding ingredients, the chemical constitution of which is unknown, broadly defined, or irrelevant
• CPC Class Codes: C08J 9/0061 characterized by the use of several polymeric components
• CPC Class Codes: C08J 9/08 developing carbon dioxide

Abstract

Biocompatible foams having excellent physical and chemical properties are described. The biocompatible foams can be formed in situ or applied as a pre-formed foam for the treatment of tissue. The invention provides biocompatible degradable foams formed with a poly-α(1→4)glucopyranose macromer. The invention also provides biostable foams formed with a poly(alkylene oxide) macromer.

Claims

1. A system for forming a biocompatible biodegradable foam comprising:

a) a first covalently crosslinkable polymer comprising poly-α

(1→

4)glucopyranose and pendent free-radically polymerizable groups, wherein the poly-α

(1→

4)glucopyranose is maltodextrin;

b) a second covalently crosslinkable polymer comprising an alkylene oxide polymer comprising pendent polymerizable groups;

c) a polymerization initiator; and

d) a gas-producing component comprising a bicarbonate salt and a biocompatible acid.

2. The system of claim 1 wherein the polymerizable groups are pendent from the poly-α

(1→

4)glucopyranose in an amount in the range of 0.05 mmol/gram to 0.4 mmol/gram (polymerizable groups/poly-α

(1→

4)glucopyranose).

3. The system of claim 2 wherein the polymerizable groups are pendent from the poly-α

(1→

4)glucopyranose in an amount in the range of 0.1 mmol/gram to about 0.35 mmol/gram (polymerizable groups/poly-α

(1→

4)glucopyranose).

4. The system of claim 1 wherein the covalently crosslinkable polymer comprising poly-α

(1→

4)glucopyranose has a molecular weight of 500,000 Da or less.

5. The system of claim 1 having a ratio of the first covalently crosslinkable polymer comprising poly-α

(1→

4)glucopyranose to the second covalently crosslinkable polymer in the range of 1;

1 to 3;

1 by weight.

6. The system of claim 1 wherein the polymerization initiator comprises a peroxide-based initiator.

7. The system of claim 1 further comprising a poloxamer surfactant.

8. The system of claim 1 comprising a first liquid composition in which the covalently crosslinkable polymer comprising poly-α

(1→

4)glucopyranose is present at a concentration in the range of 200 mg/mL to 1000 mg/mL.

9. The system of claim 8 wherein the covalently crosslinkable polymer comprising poly-α

(1→

4)glucopyranose is present at a concentration in the range of 400 mg/mL to 700 mg/mL.

10. The system of claim 1 comprising a first liquid composition comprising a first member of a redox pair at a concentration in the range of 2.0 mM to 25 mM.

11. The system of claim 1 comprising a first liquid composition comprising the biocompatible acid at a concentration in the range of 20 mg/mL to 80 mg/mL.

12. The system of claim 1 comprising a second liquid composition comprising a second member of a redox pair at a concentration in the range of 2.0 mM to 25 mM.

13. The system of claim 1 comprising a second liquid composition comprising the bicarbonate salt at a concentration in the range of 20 mg/mL to 80 mg/mL.

14. The system of claim 1 comprising a second liquid composition including the second covalently crosslinkable polymer at a concentration in the range of 100 mg/mL to 500 mg/mL.

15. The system of claim 1 comprising a first liquid composition comprising ferrous lactate at a concentration in the range of 4 mM to 30 mM, citric acid at a concentration in the range of 60 mg/mL to 120 mg/mL, and the covalently crosslinkable polymer comprising poly-α

(1→

4)glucopyranose and pendent polymerizable groups at a concentration in the range of 500 mg/mL to 700 mg/mL, and a second liquid composition comprising hydrogen peroxide at a concentration in the range of 4 mM to 30 mM, potassium bicarbonate at a concentration in the range of 60 mg/mL to 120 mg/mL, and the second covalently crosslinkable polymer at a concentration in the range of 350 mg/mL to 550 mg/mL.

16. The system of claim 1 wherein the pendent free radically polymerizable groups are selected from the group consisting of acrylate, methacrylate, ethacrylate, 2-phenyl acrylate, acrylamide, methacrylamide, itaconate groups, and styrene.

17. The system of claim 1 wherein the polymerization initiator comprises an activating component that is a Fe²⁺-based activator.

18. The system of claim 17 wherein the polymerization initiator comprises an activating component selected from the group consisting of ferrous gluconate, ferrous ascorbate, ferrous acetylacetonate, and ferrous lactate.

19. The system of claim 1 wherein the system comprises an aqueous liquid, and the first and second covalently crosslinkable polymers, the polymerization initiator, and the gas-producing component are dissolvable in the aqueous liquid.

20. A system for forming a biocompatible biodegradable foam comprising:

a) a first covalently crosslinkable polymer comprising a linear poly-α

(1→

4)glucopyranose having a molecular weight of 500,000 Da or less and comprising pendent free radically polymerizable groups;

b) a second covalently crosslinkable polymer comprising an alkylene oxide polymer comprising pendent polymerizable groups;

c) a Fe²⁺-based activator;

d) a biocompatible acid; and

e) a bicarbonate salt.

21. A system for forming a biocompatible biodegradable foam comprising:

a) a first covalently crosslinkable polymer comprising poly-α

(1→

4)glucopyranose and pendent free-radically polymerizable groups;

b) a second covalently crosslinkable polymer comprising an alkylene oxide polymer comprising pendent polymerizable groups;

c) a polymerization initiator; and

d) a water-soluble gas-producing component comprising a bicarbonate salt and a biocompatible acid;

wherein the first and second covalently crosslinkable polymers, polymerization initiator, and gas-producing component are dissolvable in a physiologically compatible aqueous composition having a pH in the range of about 6.5 to about 7.5.

22. The system of claim 21 wherein the water-soluble gas-producing component is present in an amount sufficient to cause formation of pores in the biocompatible biodegradable foam when combined with the polymer and polymerization initiator.

23. The system of claim 21 wherein the first covalently crosslinkable polymer comprising poly-α

(1→

4)glucopyranose has a molecular weight of 500,000 Da or less.