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Polyhydroxyalkanoate compositions having controlled degradation rates

Assignee: Tepha Inc
•
Filing: 2003-03-28
•
Granted: 2005-04-12
•
Expires: 2023-03-28
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Abstract

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.

Inventors

  • 👤 David P. Martin
  • 👤 Frank Skraly
  • 👤 Simon F. Williams

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-10-23 19:18
CPC Classifications
C; C08; C08G; C08G63/00; C08G63/91; C08G63/912; A; A61; A61K; A61K47/00; A61K47/50; A61K47/51; A61K47/56; A61K47/59; A61K47/593; A61K47/69; A61K47/6957; A61K9/00; A61K9/14; A61K9/16; A61K9/1605; A61K9/1629; A61K9/1641; A61K9/1647; A61L; A61L15/00; A61L15/16; A61L15/22; A61L15/26; A61L17/00; A61L17/06; A61L17/10; A61L17/12; A61L24/00; A61L24/001; A61L24/0042; A61L26/00; A61L26/0009; A61L26/0019; A61L26/0061; A61L26/009; A61L27/00; A61L27/14; A61L27/18; A61L27/28; A61L27/34; A61L27/50; A61L27/58; A61L29/00; A61L29/04; A61L29/06; A61L31/00; A61L31/04; A61L31/06; A61L31/14; A61L31/148; C08G63/02; C08G63/06; C08G63/64; C08G63/68; C08G63/685; C08G63/6852; C08G63/688; C08G63/6882; C08J; C08J9/00; C08J9/26; C08K; C08K5/00; C08K5/0008; C08K5/0033; C12; C12N; C12N5/00; C12N5/0068; C12P; C12P7/00; C12P7/62; C12P7/625; C08J2201/00; C08J2201/04; C08J2201/044; C08J2201/0444; C08J2201/048; C08J2201/0482; C08J2367/00; C08J2367/04; C12N2533/00; C12N2533/30

Claims Analysis

Total Claims: 27
Claim 1
Independent Claim 129 words
A method for preparing a biocompatible biodegradable polyhydroxyalkanoate composition that has a controlled degradation rate under physiological conditions, wherein the mass loss, as measured bvxas 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, comprising (a) incorporating monomeric units as chemical linkages into the polymer backbone which alter the chemical stability of the polymer backbone; (b) replacing linkages in said polymer backbone which alter the chemical stability of the polymer backbone; (c) incorporating pendant groups into the polymer which alter the chemical stability of the polymer backbone; (d) incorporating additives which alter the chemical stability of the polymer; or (e) combinations thereof.
Claim 2
Independent Claim 129 words
A method for preparing a biocompatible biodegradable polyhydroxyalkanoate composition that has a controlled degradation rate under physiological conditions, wherein the mass loss, as measured bvxas 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, comprising (a) incorporating monomeric units as chemical linkages into the polymer backbone which alter the chemical stability of the polymer backbone; (b) replacing linkages in said polymer backbone which alter the chemical stability of the polymer backbone; (c) incorporating pendant groups into the polymer which alter the chemical stability of the polymer backbone; (d) incorporating additives which alter the chemical stability of the polymer; or (e) combinations thereof.
Claim 3
Dependent Claim 32 words
The method of claim 1 further comprising forming the polyhydroxyalkanoate composition using a method selected from the group consisting of fermentation, enzymatic synthesis, chemical synthesis, melt processing, reactive blending, and recombinant techniques.
Claim 4
Dependent Claim 15 words
The method of claim 2 wherein the composition is derived by fermentation using a co-feed.
Claim 5
Dependent Claim 12 words
The method of claim 2 wherein the fermentation process uses transgenic bacteria.
Claim 6
Dependent Claim 20 words
The method of claim 2 wherein the chemical synthesis is selected from the group consisting of insertion, transesterification and metathesis.
Claim 7
Dependent Claim 15 words
The method of claim 1 wherein the presence of the additional unit(s) promotes chain scission.
Claim 8
Dependent Claim 14 words
The method of claim 1 wherein the units contain more than two functional groups.
Claim 9
Dependent Claim 16 words
The method of claim 1 wherein a heteroatom grouping is incorporated into the polymer backbone chain.
Claim 10
Dependent Claim 20 words
The method of claim 8 wherein the heteroatom grouping is selected from the group consisting of oxygen, sulfur and nitrogen.
Claim 11
Dependent Claim 30 words
The method of claim 1 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.
Claim 12
Dependent Claim 26 words
The method of claim 1 wherein the units are selected from the group consisting of 2-hydroxyacids; 2-hydroxyalkoxyacetic acids; amino acids; amino alcohols; diacids; triols; and tetraols.
Claim 13
Dependent Claim 11 words
The method of claim 11 wherein the 2-hydroxyacids are 2-hydroxyalkanoic acids.
Claim 14
Dependent Claim 12 words
The method of claim 12 wherein the 2-hydroxyalkanoic acid is lactic acid.
Claim 15
Dependent Claim 12 words
The method of claim 12 wherein the 2-hydroxyalkanoic acid is glycolic acid.
Claim 16
Dependent Claim 11 words
The method of claim 11 wherein the 2-hydroxyacids are 2-hydroxyalkenoic acids.
Claim 17
Dependent Claim 23 words
The method of claim 11 wherein the 2-hydroxyalkoxyacetic acids are selected from the group consisting of 2-hydroxyethoxy acetic acid and 3-hydroxypropoxy acetic acid.
Claim 18
Dependent Claim 16 words
The method of claim 1 comprising pendant groups that catalyze the degradation of the polymer backbone.
Claim 19
Dependent Claim 16 words
The method of claim 17 wherein the pendant groups are selected from acidic and basic groups.
Claim 20
Dependent Claim 14 words
The method of claim 17 comprising reactant pendant groups that cause polymer chain scission.
Claim 21
Dependent Claim 16 words
The method of claim 19 wherein the reactant pendant groups are selected from nucleophiles and electrophiles.
Claim 22
Dependent Claim 21 words
The method of claim 17 wherein the pendant groups are selected from the group consisting of alcohols, acids and amine groups.
Claim 23
Dependent Claim 11 words
The method of claim 1 wherein the additives promote chain scission.
Claim 24
Dependent Claim 32 words
The method of claim 22 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.
Claim 25
Dependent Claim 9 words
The method of claim 23 comprising pore forming agents.
Claim 26
Dependent Claim 13 words
The method of claim 24 wherein the pore forming agents are lyophilizable particles.
Claim 27
Dependent Claim 12 words
The method of claim 24 wherein the pore forming agents absorb water.

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3.5 Years (Year 4) 2008-04-11 2008-10-11 2009-04-12 $2000.00 Window Closed / Lapsed
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