Medical devices and applications of polyhydroxyalkanoate polymers

• US 7,268,205 B2
• Filed: 01/16/2007
• Issued: 09/11/2007
• Est. Priority Date: 03/25/1999
• Status: Expired due to Term

• Current Assignee: Tepha Incorporated (Becton, Dickinson & Co)
• Original Assignee: Metabolix Incorporated
• Inventors: Skraly, Frank A., Martin, David P., Williams, Simon F.
• Primary Examiner(s): BOYKIN, TERRESSA M
• Application Number:
  US11/623,593
• Publication Number:
  US 20070135929A1
• Time in Patent Office: 238 Days
• Field of Search: 361/503, 361/504, 361/505, 361/506, 361/507, 361/508, 438/773, 521/27, 523/124, 525/411, 528/354
• US Class Current: 528/354
• CPC Class Codes: A61F 2/07 Stent-grafts
• CPC Class Codes: A61F 2210/0004 bioabsorbable
• CPC Class Codes: A61K 31/715 Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
• CPC Class Codes: A61L 17/12 Homopolymers or copolymers of glycolic acid or lactic acid
• CPC Class Codes: A61L 2300/00 Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• 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 31/148 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: C08G 63/06 derived from hydroxycarboxylic acids
• CPC Class Codes: C08J 2201/0444 Salts
• CPC Class Codes: C08J 2201/0482 the liquid phase being organic
• CPC Class Codes: C08J 2367/04 Polyesters derived from hydroxy carboxylic acids, e.g. lactones C08J2367/06 takes precedence
• CPC Class Codes: C08J 9/26 by elimination of a solid phase from a macromolecular composition or article, e.g. leaching out
• CPC Class Codes: C08K 5/0033 Additives activating the degradation of the macromolecular compound
• CPC Class Codes: C08L 67/04 Polyesters derived from hydroxycarboxylic acids, e.g. lactones C08L67/06 takes precedence
• CPC Class Codes: C12P 7/625 Polyesters of hydroxy carboxylic acids
• CPC Class Codes: Y10S 606/911 Memory material

Abstract

Devices formed of or including biocompatible polyhydroxyalkanoates are provided with controlled degradation rates, preferably less than one year under physiological conditions. Preferred devices include sutures, suture fasteners, meniscus repair devices, rivets, tacks, staples, screws (including interference screws), bone plates and bone plating systems, surgical mesh, repair patches, slings, cardiovascular patches, orthopedic pins (including bone filling augmentation material), adhesion barriers, stents, guided tissue repair/regeneration devices, articular cartilage repair devices, nerve guides, tendon repair devices, atrial septal defect repair devices, pericardial patches, bulking and filling agents, vein valves, bone marrow scaffolds, meniscus regeneration devices, ligament and tendon grafts, ocular cell implants, spinal fusion cages, skin substitutes, dural substitutes, bone graft substitutes, bone dowels, wound dressings, and hemostats. The polyhydroxyalkanoates can contain additives, be formed of mixtures of monomers or include pendant groups or modifications in their backbones, or can be chemically modified, all to alter the degradation rates. The polyhydroxyalkanoate compositions also provide favorable mechanical properties, biocompatibility, and degradation times within desirable time frames under physiological conditions.

Claims

1. A device comprising a biodegradable polyhydroxyalkanoate composition that has a controlled degradation rate, under physiological conditions,

wherein the degradation rate of the polyhydroxyalkanoate polymer is manipulated through addition of components to the polymeric composition, selection of the chemical composition, molecular weight, processing conditions, or form of the composition,

wherein the polyhydroxyalkanoate polymer has a weight average molecular weight of between 10,000 and 10,000,000, and

wherein the degradation rates of the polyhydroxyalkanoates are manipulated through addition of components to the polymeric composition, selection of the chemical composition, molecular weight, processing conditions, or form of the composition,

wherein the device is selected from the group consisting of sutures, suture fasteners, meniscus repair devices, rotator cuff repair devices, temporary wound support devices, bladder patches, pledgets, soft tissue reinforcement devices, vascular patches, devices for atrial wall repair, bone marrow scaffolds, ligament repair devices, rods, washers, screws, pins, struts, plates, and staples used in spinal fusion cages, rivets, tacks, staples, screws, bone plates and bone plating systems, surgical mesh, repair patches, slings, cardiovascular patches, orthopedic pins, adhesion barriers, stents, guided tissue repair/regeneration devices, articular cartilage repair devices, sewing rings, stiffeners used in heart valve supports, cell encapsulation devices, coated devices, defect filling devices, organ patches, organ salvage devices, staple line reinforcement devices, pelvic floor reconstruction devices, devices for closure of ventricular septal defects, nerve guides, tendon repair devices, atrial septal defect repair devices, pericardial patches, bulking and filling agents, vein valves, bone marrow scaffolds, meniscus regeneration devices, ligament and tendon grafts, ocular cell implants, spinal fusion cages, skin substitutes, dural substitutes, bone graft substitutes, bone dowels, wound dressings, hemostats and drug delivery devices.

2. The device of claim 1 wherein the chemical composition of the polyhydroxyalkanoate is altered through selection of monomers which are incorporated into the polymer, or by alteration of the linkages, chemical backbone or pendant groups.

3. The device of claim 1 wherein the polyhydroxyalkanoate composition comprises additives altering the degradation rate of the composition, wherein the additives are selected from the group consisting of hydrophilic substances, hydrophobic substances, and coating which alter water uptake by the composition.

4. The device of claim 1 wherein the polyhydroxyalkanoate comprises a polymer selected from the group of consisting of poly-4-hydroxybutyrate, poly-4-hydroxybutyrate-co-3-hydroxybutyrate, poly-4-hydroxybutyrate-co-2-hydroxybutyrate, and copolymers and blends thereof.

5. The device of claim 1 wherein the polyhydroxyalkanoate comprises a polymer selected from the group consisting of poly-3-hydroxybutyrate-co-3-hydroxyhexanoate, poly-3-hydroxybutyrate-co-3-hydroxyoctanoate, poly-3-hydroxybutyrate-co-3-hydroxydecanoate, and copolymers and blends thereof.

6. The device of claim 1 wherein the polyhydroxyalkanoate comprises one or more units which alter the chemical stability of the polymer backbone.

7. The device of claim 1 comprising units promoting chain scission.

8. The device of claim 7 wherein the units contain more than two functional groups.

9. The device of claim 1 wherein a heteroatom is incorporated into the polymer backbone chain.

10. The device of claim 9 wherein the heteroatom is selected from the group consisting of oxygen, sulfur or nitrogen.

11. The device of claim 7 wherein the units are incorporated into the polymer backbone with chemical linkages selected from the group consisting of ester, amide, ether, carbamate, anhydride, and carbonate.

12. The device of claim 7 wherein the units are selected from the group consisting of 2-hydroxyacids, 2-hydroxyalkaoxyacetic acids, amino acids, amino alcohols, diacids, triols, and tetraols.

13. The device of claim 12 wherein the 2-hydroxyacids are 2-hydroxyalkanoic acids.

14. The device of claim 13 wherein the 2-hydroxyalkanoic acid is lactic acid or glycolic acid.

15. The device of claim 12 wherein the 2-hydroxyalkoxyacetic acids are selected from the group consisting of 2-hydroxyethoxy acetic acid and 3-hydroxypropoxy acetic acid.

16. The device of claim 1 wherein the polymer comprises pendant groups that catalyze the degradation of the polymer backbone.

17. The device of claim 16 wherein the pendant groups are selected from acidic and basic groups.

18. The device of claim 16 comprising reactant pendant groups that cause polymer chain scission.

19. The device of claim 18 wherein the reactant pendant groups are selected from nucleophiles and electrophiles.

20. The device of claim 16 wherein the pendant groups are selected from the group consisting of alcohols, acids, and amine groups.

21. The device of claim 1 comprising providing additives altering the chemical stability of the polyhydroxyalkanoate.

22. The device of claim 21 wherein the additives promote chain scission.

23. The device of claim 21 wherein the additives are selected from the group consisting of acids, bases, electrophiles, nucleophiles, plasticizers, polymers, pore forming agents, and agents designed to reduce the polymer crystallinity.

24. The device of claim 1 comprising providing pore forming agents.

25. The device of claim 24 wherein the pore forming agents are lyophilizable particles.

26. The device of claim 24 wherein the pore forming agents absorb water.

27. The device of claim 1 further comprising one or more active agents.

28. The device of claim 27 wherein the active agent is selected from the group consisting of growth factors, alginates, silver salts, antiseptics, analgesics, and preservatives.

29. The device of claim 1 wherein the device is a drug delivery device and the drug is selected from the group consisting of biological factors, antibodies, enzymes, antigens, inhibitors, clot dissolving agents, and hormones.

30. The device of claim 1 wherein the device is a drug delivery device and the drug is selected from the group consisting of proteins, peptides, polysaccharides, organic drugs, inorganic drugs, nucleic acids, and lipids.