Methods for the preparation of cellular hydrogels

• US 6,608,117 B1
• Filed: 05/11/2001
• Issued: 08/19/2003
• Est. Priority Date: 05/11/2001
• Status: Active Grant

• Current Assignee: Hydromedica, LLC
• Original Assignee: Nanosystems Research, Inc.
• Inventors: Gvozdic, Nedeljko Vladimira
• Primary Examiner(s): Foelak, Morton
• Application Number:
  US09/853,517
• Time in Patent Office: 830 Days
• Field of Search: 521/64, 521/61, 521/141, 264/41, 264/42
• US Class Current: 521/141
• CPC Class Codes: C08J 2201/0446 Elimination of NaCl only
• CPC Class Codes: C08J 9/26 by elimination of a solid phase from a macromolecular composition or article, e.g. leaching out

Abstract

What is disclosed herein are physically cross-linked, cellular hydrogels and methods for their preparation. The cellular materials are highly resilient, hydrophilic materials having broad uses. The cellular materials are prepared by the physical crosslinking of frothed polymers and providing materials that have cellular pores provided by the use of removable materials during the formation of the cellular materials.

Claims

1. A method of preparing hydrogel sponges having collapsed walls, said method comprising the steps of:

(I) providing a polymer capable of being physically cross-linked;

(II) dissolving said polymer in a material selected from the group consisting essentially of;

(i) a single solvent for the polyvinyl alcohol and,

(ii) a mixture of solvents for the polyvinyl alcohol, to form a solution;

(III) mixing the solution formed in (II) with a pore-forming material;

(IV) providing conditions for the mixture of (III) in which the polymer will undergo physical cross linking;

(V) bringing the mixture from (IV) to about room temperature;

(VI) removing essentially all of the solvents by a method which does not significantly affect the cross-linking or pore-forming material;

(VII) heating the mixture at an elevated temperature for a period of from ten seconds to eight hours, and

(VIII) cooling the mixture from (VII) to about room temperature and removing the pore-forming material by means which does not significantly affect the cross-linking, whereby a sponge having collapsed walls is obtained.

2. A method of preparing hydrogel sponges having expanded walls, said method comprising the steps of:

(I) providing a polymer capable of being physically cross-linked;

(II) dissolving said polymer in a material selected from the group consisting essentially of;

(i) a single solvent for the polyvinyl alcohol and,

(ii) a mixture of solvents for the polyvinyl alcohol, to form a solution;

(III) mixing the solution formed in (II) with a pore-forming material;

(IV) providing conditions at which the polymer from (III) will undergo physical cross linking;

(V) bringing the mixture from (IV) to about room temperature;

(VI) removing the pore-forming material by a means which does not significantly affect the cross-linking, whereby a hydrogel sponge having expanded walls is obtained.

3. A method of preparing physically cross-linked cellular hydrogels, said method comprising the steps of:

(I) providing a polymer capable of being physically cross-linked;

(II) dissolving said polymer in a material selected from the group consisting essentially of;

(i) a single solvent for the polyvinyl alcohol and,

(ii) a mixture of solvents for the polyvinyl alcohol, to form a solution;

(III) mixing the solution formed in (II) with a pore-forming material capable of partially dissolving in solution (II) and its solution capable of causing formation of physical cross-linking in the polyvinyl alcohol;

(IV) providing conditions at which the polymer from (III) will undergo physical cross-linking caused by the presence of partially dissolved pore-forming material;

(V) bringing the mixture from (IV) to about room temperature;

(VI) removing the pore-forming material by a means which does not significantly affect the cross-linking, whereby a hydrogel sponge having partially collapsed walls is obtained.

4. A method of preparing physically cross-linked cellular hydrogels, said method comprising the steps of:

(I) providing a polymer capable of being physically cross-linked;

(II) dissolving said polymer in a material selected from the group consisting essentially of;

(i) a single solvent for the polyvinyl alcohol and,

(ii) a mixture of solvents for the polyvinyl alcohol, to form a solution;

(III) mixing the solution formed in (II) with a pore-forming material capable of partially dissolving in solution (II) and its solution capable of causing formation of physical cross-links in the polyvinyl alcohol;

(IV) providing conditions at which the polymer from (III) will undergo physical cross-linking caused by the presence of partially dissolved pore-forming material;

(V) bringing the mixture from (IV) to about room temperature;

(VI) removing all of the solvents by a means which does not significantly affect the cross-linking or pore forming material;

(VII) heating the material at an elevated temperature for a period of time of ten seconds to eight hours, and

(VIII) cooling the mixture from (VII) to about room temperature and removing the pore-forming material by a means which does not significantly affect the cross-linking, whereby a sponge having collapsed walls is obtained.

5. Method of preparing physically cross-linked cellular hydrogels, said method comprising the steps of:

(I) providing a polymer capable of being physically cross-linked;

(II) dissolving said polymer in a material selected from the group consisting essentially of;

(i) a single solvent for the polyvinyl alcohol and,

(ii) a mixture of solvents for the polyvinyl alcohol, to form a solution;

(III) mixing the solution formed in (II) with a pore-forming material;

(IV) submersing the mixture from (III) in a bath consisting of a material selected from the group consisting essentially of;

(a) a solvent for the polyvinyl alcohol polymer wherein the solvent is at a low temperature;

(b) a non-solvent for the polyvinyl alcohol polymer;

(c) a poor solvent for the polyvinyl alcohol polymer, and

(d) an aqueous solution of a material selected from the group consisting essentially of;

(i) a salt;

(ii) an acid at a low temperature, and

(iii) a base, to induce crystallization, gellation, coagulation, or a mixture of crystallization, gellation, or coagulation, of the polyvinyl alcohol polymer;

(V) bringing the mixture from (IV) to about room temperature and removing essentially all of the pore-forming materials by means which do not significantly affect the cross-linking, whereby a physically cross-linked cellular polyvinyl alcohol hydrogel is obtained.

6. Method of preparing physically cross-linked cellular hydrogels, said method comprising the steps of:

(I) providing a polymer capable of being physically cross-linked;

(II) dissolving said polymer in a material selected from the group consisting essentially of;

(i) a single solvent for the polyvinyl alcohol and,

(ii) a mixture of solvents for the polyvinyl alcohol, to form a solution;

(III) mixing the solution formed in (II) with a pore-forming material;

(IV) submersing the mixture from (III) into a material selected from the group consisting of;

(i) a solvent for the polyvinyl alcohol at low temperature;

(ii) a non-solvent for the polyvinyl alcohol, and

(iii) a poor solvent, to induce crystallization, gellation, coagulation, or a mixture of crystallization, gellation, or coagulation, of the polymer;

(V) bringing the mixture from (IV) to about room temperature and removing essentially all of the pore-forming material by means which do not significantly affect the cross-linking, whereby a physically cross-linked cellular polymer is obtained.

7. A method of preparing physically cross-linked cellular hydrogels, said method comprising the steps of:

(I) providing a polymer capable of being physically cross-linked;

(II) dissolving said polymer in a material selected from the group consisting essentially of;

(i) a single solvent for the polyvinyl alcohol and,

(ii) a mixture of solvents for the polyvinyl alcohol to form a solution;

(III) mixing the solution formed in (II) with a pore-forming material;

(IV) submersing the mixture from (III) in a bath consisting of an aqueous solution of a material selected from a group consisting essentially of;

a. a salt,

b. an acid at low temperature and,

c. a base, to induce crystallization, gellation, coagulation, or a combination of crystallization, gellation, or coagulation, of the polymer;

(V) bringing the mixture from (IV) to about room temperature and removing essentially all of the pore-forming materials by means which do not significantly affect the cross-linking, whereby a physically cross-linked cellular polyvinyl alcohol is obtained.

8. Method of preparing physically cross-linked cellular hydrogels, said method comprising the steps of:

(A) providing a polymer capable of being physically cross-linked;

(B) dissolving said polymer in a material selected from the group consisting essentially of;

(i) a single solvent for the polyvinyl alcohol and,

(ii) a mixture of solvents for the polyvinyl alcohol, to form a solution;

(C) mixing the solution from (B) with a material selected from the group consisting essentially of;

(i) a surface active agent and,

(ii) a mixture of surface active agents and frothing said mixture;

(D) cooling the frothed mixture from (C) to a temperature at which the polymer will undergo physical cross-linking;

(E) essentially removing any solvent present in the frothed mixture by a means which does not significantly affect the cross-linking;

(F) bringing the mixture to an elevated temperature for a period of time and cooling the mixture to about room temperature whereby a physically cross-linked cellular hydrogel is obtained.

9. A method of preparing a physically cross-linked cellular hydrogels, said method comprising the steps of:

(A) providing a polymer capable of being physically cross-linked;

(B) dissolving said polymer in a material selected from the group consisting essentially of;

(i) a single solvent for the polyvinyl alcohol and,

(ii) a mixture of solvents for the polyvinyl alcohol to form a solution;

(C) mixing the solution from (B) with a material selected from the group consisting essentially of;

(i) a surface active agent and,

(ii) a mixture of surface active agents and frothing said mixture;

(D) cooling the frothed mixture from (C) to a temperature at which the polymer will undergo physical cross-linking;

(E) bringing the mixture to about room temperature whereby a physically cross-linked cellular hydrogel is obtained.

10. Method of preparing physically cross-linked cellular hydrogels, said method comprising the steps of:

(A) providing a polymer capable of being physically cross-linked;

(B) dissolving said polymer in a material selected from the group consisting essentially of;

(i) a single solvent for the polyvinyl alcohol and,

(ii) a mixture of solvents for the polyvinyl alcohol, to form a solution;

(C) mixing the solution formed in (B) with a material selected from the group consisting essentially of;

(i) a surface active agent and,

(ii) a mixture of surface active agents, and frothing said mixture;

(D) cooling the frothed mixture from (C) to a temperature at which the polymer will undergo physical cross-linking;

(E) submersing the mixture from (D) into a bath consisting essentially of a material selected from the group consisting of;

(i) a solvent at low temperature for the polyvinyl alcohol,

(ii) a non-solvent for the polyvinyl alcohol,

(iii) a poor solvent for the polyvinyl alcohol,

(iv) an aqueous solution of a salt,

(v) an aqueous solution of an acid at low temperature, and,

(vi) an aqueous solution of a base, to induce crystallization, gellation, coagulation, or a mixture of crystallization, gellation, or coagulation of said polymer whereby a physically cross-linked cellular polymer is obtained.

11. A method of preparing physically cross-linked cellular hydrogels, said method comprising the steps of:

(A) providing a polymer capable of being physically cross-linked;

(B) dissolving said polymer in a material selected from the group consisting essentially of;

(i) a single solvent for the polyvinyl alcohol and,

(ii) a mixture of solvents for the polyvinyl alcohol, to form a solution;

(C) mixing the solution formed in (B) with a material selected from the group consisting essentially of;

(i) a surface active agent and,

(ii) a mixture of surface active agents, and frothing said mixture;

(D) cooling the frothed mixture from (C) to a temperature at which the polymer will undergo physical cross-linking;

(E) submersing the mixture from (D) into a bath consisting of an aqueous solution of a material selected from the group consisting essentially of;

(i) a salt,

(ii) an acid at low temperature, and,

(iii) a base, to induce crystallization, gellation, coagulation or a mixture of crystallization, gellation or coagulation of said polymer whereby a physically cross-linked cellular polyvinyl alcohol is obtained.

12. A method of preparing physically cross-linked cellular hydrogels, said method comprising the steps of:

(I) providing a polymer capable of being physically cross-linked;

(II) dissolving said polymer in a material selected from the group consisting essentially of;

(a) a single solvent for the polyvinyl alcohol and,

(b) a mixture of solvents for the polyvinyl alcohol, to form a solution;

(III) mixing the solution from (II) with material selected from the group consisting essentially of;

(a) a surface active agent and,

(b) a mixture of surface active agents;

(IV) mixing the solution formed in (III) with a pore forming material consisting essentially of;

(a) a non solvent for the polyvinyl alcohol;

(b) a poor solvent for the polyvinyl alcohol; and

dispersing the pore forming material by subjecting the solution to high shear mixing;

(V) providing conditions at which the polymer from (IV) will undergo physical cross-linking;

(VI) bringing the mixture from (V) to about room temperature;

(VII) removing essentially all the solvents by a means which does not significantly affect the cross-linking or pore-forming material,

(VIII) heating the material at an elevated temperature for a period of time from ten seconds to eight hours, and,

(IX) cooling the mixture from (VIII) to about room temperature and removing the pore-forming material by a means which does not significantly affect the cross-linking, whereby a sponge having collapsed walls is obtained.

13. A method of preparing physically cross-linked cellular hydrogels, said method comprising the steps of:

(I) providing a polymer capable of being physically cross-linked;

(II) dissolving said polymer in a material selected from the group consisting essentially of;

(a) a single solvent for the polyvinyl alcohol and,

(b) a mixture of solvents for the polyvinyl alcohol, to form a solution;

(III) mixing the solution from (II) with material selected from the group consisting essentially of;

(a) a surface active agent and,

(b) a mixture of surface active agents;

(IV) mixing the solution formed in (III) with a pore forming material consisting essentially of;

(a) a non-solvent for the polyvinyl alcohol and,

(b) a poor solvent for the polyvinyl alcohol, and dispersing the pore forming material by subjecting the solution to high shear mixing;

(V) providing conditions at which the polymer from (IV) will undergo physical cross-linking;

(VI) bringing the mixture from (V) to about room temperature;

(VII) removing essentially all the solvents by a means which does not significantly affect the cross-linking or pore-forming material,

(VIII) heating the material at an elevated temperature for a period of time from ten seconds to eight hours, and,

(IX) cooling the mixture from (VIII) to about room temperature and removing the pore-forming material by a means which does not significantly affect the cross-linking, whereby a sponge having collapsed walls is obtained.