Process for the preparation of aqueous dispersions of particles of water-soluble polymers and the particles obtained

• US 6,544,503 B1
• Filed: 05/01/2000
• Issued: 04/08/2003
• Est. Priority Date: 06/06/1995
• Status: Expired due to Term

• Current Assignee: C.R. Bard, Inc. (Becton, Dickinson & Co), Lehigh University
• Original Assignee: C.R. Bard, Inc. (Becton, Dickinson & Co), Lehigh University
• Inventors: Lee, Clarence C., Lu, Cheng Xun, Vanderhoff, John W., Tsai, Chi-Chun
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): DI NOLA BARON, LILIANA
• Application Number:
  US09/563,037
• Time in Patent Office: 1,072 Days
• Field of Search: 514/772.1, 514/772.2, 514/772.3, 514/772.4, 514/54, 514/23, 514/58, 514/59, 514/60, 523/113, 604/502, 424/78.17, 424/489, 424/423, 424/422
• US Class Current: 424/78.17
• CPC Class Codes: A61L 27/16 obtained by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/20 Polysaccharides
• CPC Class Codes: A61L 27/50 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: A61L 31/042 Polysaccharides
• CPC Class Codes: A61L 31/048 obtained by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/14 Materials characterised by their function or physical properties , e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
• CPC Class Codes: C08J 2300/14 Water soluble or water swellable polymers, e.g. aqueous gels
• CPC Class Codes: C08J 3/16 by coagulating dispersions C08J3/122 takes precedence
• CPC Class Codes: C08J 3/26 of latex

Abstract

The invention is a process for the preparation of crosslinked water-swellable polymer particles. First, an aqueous polymer solution containing a water-soluble polymer having at least one functional group or charge, is combined with aqueous medium. The aqueous polymer solution is then mixed under moderate agitation with an oil medium and an emulsifier to form an emulsion of droplets of the water-soluble polymer. A crosslinking agent capable of crosslinking the functional groups and/or charges in the water-soluble polymer is then added to the emulsion to form crosslinked water-swellable polymer particles. The invention also includes the particles formed by the process and aqueous dispersions containing the particles which are useful for administering to an individual. The particles of the invention are useful for implantation, soft tissue augmentation, and scaffolding to promote cell growth.

Claims

1. A method of soft tissue augmentation comprising administering to a patient in need of soft tissue augmentation an aqueous dispersion of crosslinked water-swellable polymer particles in an amount to effectively augment the affected tissue of the patient, wherein the particles are substantially homogeneous in size, wherein the particles are between about 10 micrometers in diameter and about 250 micrometers in diameter, and wherein at least 80% of the particles are spherical.

2. The method of claim 1, wherein the particles contain at least one water-soluble polymer selected from the group consisting of proteins, polysaccharides, peptidoglycans, glycoproteins, proteoglycans, celluloses, teichoic acids, lipopolysaccharides, and synthetic hydrophilic polymers, sodium alginate, poly(N-vinyl pyrrolidone), methyl cellulose, chitin, chitosan, agarose, dextrans, poly(vinyl alcohol), chondroitin sulfate, xanthans, dermatan sulfate, keratin sulfate, amylose, amylopectin, carrageenans, glycogen, starch, heparin sulfate, limit dextians and fragments thereof, emulsan, gellan, curdlan, hyaluronic acid, poly(ethylene oxide), bovine serum albumin, human gamma globulin, and mixtures thereof.

3. The method of claim 1, wherein the particles comprise at least one water-soluble polymer which is a polysaccharide.

4. The method of claim 3, wherein the polysaccharide is selected from the group consisting of hyaluronic acid, sodium alginate, chondroitin sulfate, celluloses, chitin, chitosan, agarose, dextrans, xanthans, dermatan sulfate, amylose, emulsan, gellan, curdlan, amylose, carrageenans, amylopectin, glycogen, starch, heparin sulfate, and limit dextrins or fragments thereof.

5. The method of claim 1, wherein the aqueous dispersion of crosslinked water-swellable polymer particles is administered to a patient in an amount effective to treat a defect selected from the group consisting of urinary incontinence, vesicoureteral reflux, glottic insufficiency, gastroesophageal reflux, and skin defects.

6. The method of claim 1, wherein the particles further comprise a bioactive agent.

14. The method of claim 1, wherein the particles contain at least one water-soluble polymer selected from the group consisting of polysaccharides, peptidoglycans, glycoproteins, proteoglycans, celluloses, teichoic acids, lipopolysaccharides, and synthetic hydrophilic polymers, sodium alginate, poly(N-vinyl pyrrolidone), methyl cellulose, chitin, chitosan, agarose, dextrans, poly(vinyl alcohol), chondroitin sulfate, xanthans, dermatan sulfate, amylose, amylopectin, carrageenans, glycogen, starch, heparin sulfate, limit dextrins and fragments thereof, emulsan, gellan, curdlan, hyaluronic acid, poly(ethylene oxide), and mixtures thereof.

7. A method of promoting tissue growth comprising administering to a patient in need of tissue growth an aqueous dispersion of crosslinked water-swellable polymer particles in an amount which provides a scaffold sufficient to promote tissue growth in the patient, wherein the particles are substantially homogeneous in size, wherein the particles are between about 10 micrometers in diameter and about 250 micrometers in diameter, and wherein at least 80% of the particles are spherical.

8. The method of claim 7, wherein the particles contain at least one water-soluble polymer selected from the group consisting of proteins, polysaccharides, peptidoglycans, glycoproteins, proteoglycans, celluloses, teichoic acids, lipopolysaccharides, and synthetic hydrophilic polymers, sodium alginate, poly(N-vinyl pyrrolidone), methyl cellulose, chitin, chitosan, agarose, dextrans, poly(vinyl alcohol), chondroitin sulfate, xanthans, dermatan sulfate, keratin sulfate, amylose, amylopectin, carrageenans, glycogen, starch, heparin sulfate, limit dextrans and fragments thereof, emulsan, gellan, curdlan, hyaluronic acid, poly(ethylene oxide), bovine serum albumin, human gamma globulin, and mixtures thereof.

9. The method of claim 7, wherein the particles comprise at least one water-soluble polymer which is a polysaccharide.

10. The method of claim 9 , wherein the polysaccharide is selected from the group consisting of hyaluronic acid, sodium alginate, chondroitin sulfate, celluloses, chitin, chitosan, agarose, dextrans, xanthans, dermatan sulfate, amylose, emulsan, gellan, curdlan, amylose, carrageenans, amylopectin, glycogen, starch, heparin sulfate, and limit dextrins or fragments thereof.

11. The method of claim 7, wherein the aqueous dispersion of crosslinked water-swellable polymer particles is administered to a patient in an amount effective to promote cell growth of tissue in the breast, lip, penis, bone, cartilage, or tendon.

12. The method of claim 7, wherein the aqueous dispersion of water-swellable polymer particles is administered to a patient in an amount effective to promote wound healing.

13. The method of claim 7, wherein the particles further comprise a bioactive agent.

15. The method of claim 7, wherein the particles contain at least one water-soluble polymer selected from the group consisting of polysaccharides, peptidoglycans, glycoproteins, proteoglycans, celluloses, teichoic acids, lipopolysaccharides, and synthetic hydrophilic polymers, sodium alginate, poly(N-vinyl pyrrolidone), methyl cellulose, chitin, chitosan, agarose, dextrans, poly(vinyl alcohol), chondroitin sulfate, xanthans, dermatan sulfate, amylose, amylopectin, carrageenans, glycogen, starch, heparin sulfate, limit dextrins and fragments thereof, emulsan, gellan, curdlan, hyaluronic acid, poly(ethylene oxide), and mixtures thereof.