Hydrogels having enhanced elasticity and mechanical strength properties

• US 6,960,617 B2
• Filed: 04/22/2003
• Issued: 11/01/2005
• Est. Priority Date: 04/22/2002
• Status: Expired due to Fees

• Current Assignee: Purdue Research Foundation (The Trustees of Purdue University (d/b/a Purdue University))
• Original Assignee: Purdue Research Foundation (The Trustees of Purdue University (d/b/a Purdue University))
• Inventors: Qiu, Yong, Yang, Shicheng, Park, Kinam, Omidian, Hossein, Kim, Dukjoon, Park, Haesun
• Primary Examiner(s): Seidleck, James J.
• Assistant Examiner(s): ZEMEL, IRINA SOPJIA
• Application Number:
  US10/420,323
• Publication Number:
  US 20030232895A1
• Time in Patent Office: 924 Days
• Field of Search: 521/142, 521/146, 521/149, 521/182, 521/183, 521/186, 521/187, 521/84.1, 521/102, 521/109.1
• US Class Current: 521/102
• CPC Class Codes: A61K 9/0065 Forms with gastric retention, e.g. floating on gastric juice, adhering to gastric mucosa, expanding to prevent passage through the pylorus
• CPC Class Codes: C08F 2/44 Polymerisation in the presence of compounding ingredients, e.g. plasticisers, dyestuffs, fillers
• CPC Class Codes: C08F 220/06 Acrylic acid; Methacrylic acid; Metal salts or ammonium salts thereof
• CPC Class Codes: C08F 220/56 Acrylamide; Methacrylamide
• CPC Class Codes: C08F 251/00 Macromolecular compounds obtained by polymerising monomers on to polysaccharides or derivatives thereof
• CPC Class Codes: C08F 289/00 Macromolecular compounds obtained by polymerising monomers on to macromolecular compounds not provided for in groups C08F251/00 - C08F287/00

Abstract

Hydrogels having improved elasticity and mechanical strength properties are obtained by subjecting a hydrogel formulation containing a strengthening agent to chemical or physical crosslinking conditions subsequent to initial gel formation. Superporous hydrogels having improved elasticity and mechanical strength properties are similarly obtained whenever the hydrogel formulation is provided with a foaming agent. Interpenetrating networks of polymer chains comprised of primary polymer(s) and strengthening polymer(s) are thereby formed. The primary polymer affords capillary-based water sorption properties while the strengthening polymer imparts significantly enhanced mechanical strength and elasticity to the hydrogel or superporous hydrogel. Suitable strengthening agents can be natural or synthetic polymers, polyelectrolytes, or neutral, hydrophilic polymers.

Claims

1. A method of forming a hydrogel material having enhanced mechanical strength properties comprising:

(i) combining at least one ethylenically-unsaturated monomer and a multi-olefinic crosslinking agent to form an admixture thereof;

(ii) subjecting the admixture to polymerization conditions, optionally further subjecting the admixture to foaming conditions substantially concurrent therewith, effective to form a hydrogel composite thereof;

(iii) combining at least one strengthening agent with the admixture prior to or after performing step (ii) so that said hydrogel composite contains said at least one strengthening agent; and

(iv) subjecting the hydrogel composite containing strengthening agent to strengthening conditions effective to afford the hydrogel material having enhanced strength properties, wherein said strengthening conditions entail (a) contacting the hydrogel composite with a chemical strengthening agent selected from at least one of an ionotropic gellation agent, a polyphenolic complexing agent, an acid, a latex compound, and a glue, or (b) cryogellation conditions.

2. The method of claim 1, wherein said admixture is subjected to foaming conditions in step (ii), thereby affording a strengthened superporous hydrogel.

3. The method of claim 1, wherein the strengthening agent is combined with said admixture prior to performing step (ii).

4. The method of claim 1, wherein the at least one ethylenically-unsaturated monomer is selected from (meth)acrylic acid, salts of (meth)acrylic acid, esters of (meth)acrylic acid and hydroxyl derivatives thereof, itaconic acid, salts and acids of esters of (meth)acrylic acid, amides of (meth)acrylic acid, N-alkyl amides of (meth)acrylic acid, salts and acids of N-alkyl amides of(meth)acrylic acid, N-vinyl pyrrolidone, (meth)acrylamide, N-alkyl derivatives of (meth)acrylamide, alkyl ammonium salts, N-alkyl derivatives of an alkyl (meth)acrylate, 2-acrylamido-2-methyl-1-propanesulfonic acid, potassium salt of 3-sulfopropyl acrylate, and 2-(acryloyloxy)ethyl trimethyl ammonium methyl sulfate.

5. The method of claim 4, wherein the ethylenically-unsaturated monomer is selected from acrylamide (AAm), N-isopropyl acrylamide (NIPAM), 2-hydroxyethyl (meth)acrylate (HEA, HEMA), acrylic acid (AAc), salts of acrylic acid (potassium, sodium and ammonium), potassium salt of 3-sulfopropyl acrylate (SPAK), poly(ethylene glycol)acrylate, poly(ethylene glycol)alkyl ether acrylate, methacrylic acid-2-dimethylaminoethyl ester, dimethylaminoethyl acrylate and diallyldimethylammonium chloride (DADMAC).

6. The method of claim 1, wherein the crosslinking agent is selected from the group consisting of N,N′

-methylenebisacrylamide (BIS), N,N′

-ethylenebisacrylamide (EBA), (poly)ethylene glycol di(meth)acrylate, ethylene glycol diglycidyl ether, glycidyl methacrylate, polyamidoamine epichlorohydrin resin, trimethylolpropane triacrylate (TMPTA), piperazine diacrylamide, glutaraldehyde, epichlorohydrin, crosslinkers containing 1,2-diol structures, and functionalized peptides and proteins.

7. The method of claim 1, wherein the at least one strengthening agent is a monomer, polymer, or polyphenolic complexing agent.

8. The method of claim 7, wherein the monomer is an amino acid.

9. The method of claim 7, wherein the polymer is a polysaccharide selected from the group consisting of alginate and derivatives thereof, chitins, chitosan and derivatives thereof, cellulose and derivatives thereof, starch and derivatives thereof, cyclodextrin, dextran and derivatives thereof, gums, lignins, pectins, saponins, deoxyribonucleic acids, and ribonucleic acids.

10. The method of claim 7, wherein the polymer is a polypeptide or protein selected from the group consisting of albumin, bovine serum albumin, casein, collagen, fibrinogen, gelatin and derivatives thereof, gliadin, sodium glycine carbonate, bacterial cell membrane enzymes, and poly(amino acids).

11. The method of claim 10, wherein the poly(amino acid) is selected from polyproline, poly(L-arginine), poly(L-lysine), polysarcosine, poly(L-hydroxyproline), poly(glutamic acid), poly(S-carboxymethyl-L-cysteine), and poly(aspartic acid).

12. The method of claim 7, wherein the polymer is a homo- or co-polymer comprised of a monomer selected from the group consisting of acrolein potassium, (meth)acrylamides, (meth)acrylic acid and salts thereof, (meth)acrylates, acrylonitrile, ethylene, ethylene glycol, ethyleneimine, ethyleneoxide, styrene sulfonate, vinyl acetate, vinyl alcohol, vinyl chloride, and vinylpyrrolidone.

13. The method of claim 7, wherein the polyphenolic complexing agent is selected from the group consisting of gallotannins, ellagitannins, taragallotannins, caffetannins, proanthocyanidins, catechin, epicatechin, chlorogenic acid, and arbutin.

14. The method of claim 1, wherein the at least one strengthening agent is selected from natural and synthetic polyclectrolytes, and neutral, hydrophilic polymers.

15. The method of claim 14, wherein the at least one strengthening agent is selected from the group consisting of sodium carboxymethylcellulose, sodium starch glycolate, sodium carboxymethyl starch, dextran, dextran sulfate, chitosan, xanthan, gellan, hyaluronic acid, sodium alginate, pectinic acid, deoxyribonucleic acids, ribonucleic acid, gelatin, albumin, polyacrolein potassium, sodium glycine carbonate, poly(acrylic acid) and its salts, polyacrylonitrile, polyacrylamide, poly(styrene sulfonate), poly(aspartic acid), polylysine, polyvinylpyrrolidone, polyvinyl alcohol, CARBOPOL, ultramylopectin, poly(ethylene glycol), neutral cellulose derivatives, microcrystalline cellulose, powdered cellulose, cellulose fibers, and starch.

16. The method of claim 1, wherein the ionotropic gellation agent is selected from calcium chloride, cupric sulfate, ammonium cerium (IV) nitrate, ferric chloride hexahydrate, sodium tetraborate decahydrate, zinc chloride, aluminum chloride hexahydrate, chromium chloride, and pentasodium tripolyphosphate.

17. The method of claim 1, wherein the polyphenolic complexing agent is selected from the group consisting of gallotannins, ellagitannins, taragallotannins, caffetannins, proanthocyanidins, catechin, epicatechin, chlorogenic acid, and arbutin.

18. The method of claim 1, wherein the cryogellation conditions comprise applying a freeze-thaw cycle on PVOH and the hydrogel composite.

19. A strengthened hydrogel or superporous hydrogel formed by the method of claim 1.

20. The superporous hydrogel of claim 19 having an average pore size of about 1 μ

m to about 5000 μ

m.

21. The superporous hydrogel of claim 20, wherein the average pore size is about 10 μ

m to about 3000 μ

m.

22. The superporous hydrogel of claim 19, wherein the relative compression strength of the superporous hydrogel is at least 50-fold greater than the compression strength of a superporous hydrogel absent said strengthening agent.

23. The superporous hydrogel of claim 19, wherein the tensile strength at breaking point of the strengthened superporous hydrogel is at least about 2.0 kPa.

24. The superporous hydrogel of claim 19, wherein the equilibrium volume swelling ratio of the strengthened superporous hydrogel is in the range of about 8 to about 18.

25. A pharmaceutical composition in solid dosage form comprising a pharmacologically effective dose of a drug and a strengthened hydrogel or superporous hydrogel made by the method of claim 1.

26. The pharmaceutical composition of claim 25, wherein the strengthened hydrogel or superporous hydrogel contains at least one strengthening agent selected from alginate, chitosan, carboxymethyl cellulose, tannic acid, and gelatin.

27. The pharmaceutical composition of claim 25, which is in tablet, capsule, or particulate form.

28. The pharmaceutical composition of claim 25, which is a tablet or capsule formed by a molding, direct compression, or press coating compression technique.