Polyhydroxyalkanoate compositions having controlled degradation rates

• US 6,828,357 B1
• Filed: 03/28/2003
• Issued: 12/07/2004
• Est. Priority Date: 07/31/1997
• Status: Expired due to Term

• Current Assignee: Tepha Incorporated (Becton, Dickinson & Co)
• Original Assignee: Metabolix Incorporated
• Inventors: Martin, David P., Williams, Simon F., Skraly, Frank
• Primary Examiner(s): SZEKELY, PETER A
• Application Number:
  US10/403,242
• Time in Patent Office: 620 Days
• Field of Search: 523/124, 606/72, 606/77, 604/890.1, 604/891.1
• US Class Current: 523/124
• CPC Class Codes: A61K 47/593 Polyesters, e.g. PLGA or polylactide-co-glycolide
• CPC Class Codes: A61K 47/6957 the form being a device or a kit, e.g. stents or microdevices
• CPC Class Codes: A61K 9/1647 Polyesters, e.g. poly(lactide-co-glycolide)
• CPC Class Codes: A61L 15/26 Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds; Derivatives thereof A61L15/225 takes precedence
• CPC Class Codes: A61L 17/10 containing macromolecular materials
• CPC Class Codes: A61L 17/12 Homopolymers or copolymers of glycolic acid or lactic acid
• CPC Class Codes: A61L 24/0042 Materials resorbable by the body
• CPC Class Codes: A61L 26/0019 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 26/009 Materials resorbable by the body
• CPC Class Codes: A61L 27/18 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/58 Materials at least partially resorbable by the body
• CPC Class Codes: A61L 29/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• 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: C08G 63/06 derived from hydroxycarboxylic acids
• CPC Class Codes: C08G 63/64 Polyesters containing both carboxylic ester groups and carbonate groups
• CPC Class Codes: C08G 63/6852 derived from hydroxy carboxylic acids
• CPC Class Codes: C08G 63/6882 derived from hydroxy carboxylic acids
• CPC Class Codes: C08G 63/912 derived from hydroxycarboxylic acids
• 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: C12N 2533/30 : Synthetic polymers
• CPC Class Codes: C12N 5/0068 : General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: C12P 7/625 : Polyesters of hydroxy carboxylic acids
• CPC Class Codes: Y10S 606/911 : Memory material

Abstract

Biocompatible polyhydroxyalkanoate compositions with controlled degradation rates have been developed. In one embodiment, the polyhydroxyalkanoates contain additives to alter the degradation rates. In another embodiment, the polyhydroxyalkanoates are formed of mixtures of monomers or include pendant groups or modifications in their backbones to alter their degradation rates. In still another embodiment, the polyhydroxyalkanoates are chemically modified. Methods for manufacturing the devices which increase porosity or exposed surface area can be used to alter degradability. For example, as demonstrated by the examples, porous polyhydroxyalkanoates can be made using methods that creates pores, voids, or interstitial spacing, such as an emulsion or spray drying technique, or which incorporate leachable or lyophilizable particles within the polymer. Examples describe poly(4HB) compositions including foams, coatings, meshes, and microparticles. As demonstrated by the examples, these polyhydroxyalkanoate compositions have extremely favorable mechanical properties, as well as are biocompatible and degrade within desirable time frames under physioogical conditions. These polyhydroxyalkanoate materials provide a wider range of polyhydroxyalkanoate degradation rates than are currently available. Methods for processing these materials, particularly for therapeutic, prophylactic or diagnostic applications, or into devices which can be implanted or injected, are also described.

Claims

1. A biocompatible polymeric device for implantation or injection into a patient in need thereof comprising a biocompatible and porous polyhydroxyalkanoate, wherein the degradation rate is controlled by the porosity of the polyhydroxyalkanoate at the surface of the device, and

wherein the mass loss, as measured by gas chromatography, is greater than 5% over a six week period in vivo, or

wherein the average molecular mass of the polymer, as measured by gel permeation chromatography, decreases 20% to 50% over a ten week period in vivo.

8. The device of claim 1 wherein the mass loss is from about 5% to about 75%.

2. A medical device comprising a biocompatible and porous polyhydroxyalkanoate, wherein the degradation rate is controlled by the porosity of the polyhydroxyalkanoate, and

wherein the mass loss, as measured by gas chromatography, is greater than 5% over a six week period in vivo, or

wherein the average molecular mass loss, as measured by gel permeation chromatography decreases 20% to 50% over a ten week period in vivo.

3. The device of claim 2, wherein the device is resorbable.

4. The device of claim 2 comprising a therapeutic agent for use in controlled drug delivery.

5. The device of claim 2 comprising an imaging agent selected from the group of agents detectable by a method consisting of ultrasound, MRI, CAT, x-ray, and fluorescence.

6. The device of claim 3, wherein the resorbable device maintains its molecular mass during resorption.

7. The device of claim 2 in the form of microparticles.

9. The device of claim 2 wherein the mass loss is from about 5% to about 75%.