Metabolix, Inc.

Daniel M Horowitz

Tillman U Gerngross

David P Martin

Simon F Williams

Edward M Muller

Elaine M Brennan

Anna Egozy

Polyhydroxyalkanoates (PHAs) from which pyrogen has been removed are provided. PHAs which have been chemically modified to enhance physical and/or chemical properties, for targeting or to modify biodegradability or clearance by the reticuloendothelial system (RES), are described. Methods for depyrogenating PHA polymers prepared by bacterial fermentation processes are also provided, wherein pyrogens are removed from the polymers without adversely impacting the polymers' inherent chemical structures and physical properties. PHAs with advantageous processing characteristics, including low melting points and/or solubility in non-toxic solvents, are also described. The PHAs are suitable for use in in vivo applications such as in tissue coatings, stents, sutures, tubing, bone, other prostheses, bone or tissue cements, tissue regeneration devices, wound dressings, drug delivery, and for diagnostic and prophylactic uses.

Medical device comprising polyhydroxyalkanoate having pyrogen removed using oxidizing agent

Polyhydroxyalkanoates (PHAs) from which pyrogen has been removed are provided for use in numerous biomedical applications. PHAs which have been chemically modified to enhance physical and/or chemical properties, for targeting or to modify biodegradability or clearance by the reticuloendothelial system (RES), are described. Methods for depyrogenating PHA polymers prepared by bacterial fermentation processes are also provided, wherein pyrogens are removed from the polymers without adversely impacting the polymers' inherent chemical structures and physical properties. PHAs with advantageous processing characteristics, including low melting points and/or solubility in non-toxic solvents, are also described. PHAs are provided which are suitable for use in in vivo applications such as in tissue coatings, stents, sutures, tubing, bone and other prostheses, bone or tissue cements, tissue regeneration devices, wound dressings, drug delivery, and for diagnostic and prophylactic uses. Properties which are selected for include degradability, elasticity, inclusion of functional groups or derivatized groups, which can in turn be used to attach targeting agents, and bioadhesion.

Method of forming medical devices having pyrogen removed for in vivo application

Polyhydroxyalkanoates (PHAs) from which pyrogen has been removed are provided for use in numerous biomedical applications. PHAs which have been chemically modified to enhance physical and/or chemical properties, for targeting or to modify biodegradability or clearance by the reticuloendothelial system (RES), are described. Methods for depyrogenating PHA polymers prepared by bacterial fermentation processes are also provided, wherein pyrogens are removed from the polymers without adversely impacting the polymers' inherent chemical structures and physical properties. PHAs with advantageous processing characteristics, including low melting points and/or solubility in non-toxic solvents, are also described. PHAs are provided which are suitable for use in vivo applications such as in tissue coatings, stents, sutures, tubing, bone and other prostheses, bone or tissue cements, tissue regeneration devices, wound dressings, drug delivery, and for diagnostic and prophylactic uses. Properties which are selected for include degradability, elasticity, inclusion of functional groups or derivatized groups, which can in turn be used to attach targeting agents, and bioadhesion.

Medical device comprising polyhydroxyalkanoate having pyrogen removed

Method for making devices using polyhydroxyalkanoate having pyrogen removed

Polyhydroxyalkanoate (PHA) that contains a pyrogen such as an endotoxin due to a process of producing the PHA is treated to remove the pyrogen by a process that does not affect the inherent chemical and physical properties of the PHA to obtain a biocompatible PHA. PHA produced by fermentation with a Gram negative bacteria can be treated with an oxidizing agent such as hydrogen peroxide or benzoyl peroxide to reduce the endotoxin content to less than 20 endotoxin units/gram of PHA to produce PHA that does not elicit an acute inflammatory response when implanted in an animal. The PHA may have a melting point or glass transition temperature less than 136&deg; C., and can be chemically modified or derivatized such as by covalently coupling an attachment or targeting molecule. The PHA may be used to form various medical devices, and can be used for in vivo applications including tissue coatings, stents, sutures, tubing, bone and other prostheses, bone and tissue cements, issue regenerating devices, wound dressings, drug delivery, and diagnostic and prophylactic uses.

Medical device containing polyhydroxyalkanoate treated with oxidizing agent to remove endotoxin

Methods and apparati have been developed for producing a suspension of predominately amorphous polymer particles, wherein the method includes thermally treating a suspension that includes crystalline or semi-crystalline polymer particles. The thermal treatment includes (a) heating a suspension of polymer particles of an appropriate size to a temperature effective to cause the polymer to become amorphous, and then (b) cooling the suspension of amorphous polymer particles below the melting point of the polymer at a rate effective to prevent substantial coalescence of the polymer particles. The method and apparati are effective for use with a variety of polymers having suitable crystallization parameters, although polyhydroxyalkanoate (PHA) polymers are preferred, particularly in an aqueous suspension medium. For PHA polymers, the polymer particles subjected to treatment preferably are of a size of less than 5 &mgr;m, or more preferably less than 1.5 &mgr;m in diameter.

Methods and apparatus for the production of amorphous polymer suspensions

Polymer emulsion compositions presenting low levels of residue after thermolytic decomposition are provided. The compositions, based on polyhydroxyalkanoates or acrylics, are useful in a variety of applications, including the metallization of cathode ray tube phosphor screens, where use of the compositions provides enhanced luminosity and ease of manufacture. Other applications include use of the emulsion in additives used in powder molding techniques and in the manufacture of ceramic tiles.

Polymer compositions providing low residue levels and methods of use thereof

Methods for the recovery and cation of polyhydroxyalkanoates (PHAs)from biomass containing PHAs, wherein the methods include treating the biomass or partially purified PHA with ozone, in at least one step of a purification process, have been developed. Treatment of PHA-containing biomass or partially purified PHA with ozone yields an enhanced level of purity suitable for coating and other applications. The ozone treatment also has the added advantage that be resulting PHA polymer or polymer latex is essentially odor-free. The ozone treatment may be used alone or in combination with other treatment, extraction, and separation stages, and is especially suitable for the treatment of PHA-containing latexes slurries, suspensions, and organic solutions.

Method of decolorizing or deodorizing polyhydroxyalkanoates from biomass with ozone

A method is provided for isolating and purifying PHA from microbial or plant biomass that contains PHA. The method includes the step of extracting PHA from the biomass using at least one solvent while simultaneously subjecting the biomass to a filtration process to remove cells. In a preferred embodiment of the method, an aqueous slurry of the biomass is directly extracted by diafiltration using an organic solvent. In a preferred diafiltration process, an aqueous slurry of microbial cells comprising PHA is recirculated through a filtration membrane, wherein the membrane has a pore size sufficiently small to reject individual cells or such aggregates of cells as may exist in the slurry. As liquid is progressively removed from the biomass slurry (by flowing out from the filtration membrane), an organic solvent, preferably a water-miscible solvent that also is a solvent for the PHA, is added to the biomass slurry at a rate which approximates the rate of liquid permeation through the filter, thereby maintaining the volume of the biomass slurry. Impurities which are insoluble in water become dissolved in the solvent-water mixture and pass through the filter membrane, and when the organic solvent concentration reaches a certain level, the PHA becomes soluble and flows through the filtration membrane and can be desolventized to recover the polymer.

Methods for purifying polyhydroxy alkanoates

Polyhydroxyalkanoate (PHA) that contains a pyrogen such as endotoxin due to a process of producing the PHA is treated to remove the pyrogen by a process that does not affect the inherent chemical and physical properties of the PHA to obtain a biocompatible PHA. PHA produced by fermentation with a Gram negative bacteria can be treated with an oxidizing agent such as hydrogen peroxide or benzoyl peroxide to reduce the endotoxin content to less than 20 endotoxin units/gram of PHA to produce PHA that does not elicit an acute inflammatory response when implanted in an animal. The PHA may have a melting point or glass transition temperature less than 136&deg; C., and can be chemically modified or derivatized such as by covalently coupling an attachment or targeting molecule. The PHA may be used to form various medical devices, and can be used for in vivo applications including tissue coatings, stents, sutures, tubing, bone and other prostheses, bone and tissue cements, tissue regenerating devices, wound dressings, drug delivery, and for diagnostic and prophylactic uses.

Removing endotoxin with an oxdizing agent from polyhydroxyalkanoates produced by fermentation

Molding compositions including polyhydroxyalkanoates are provided. The use of polyhydroxyalkanoates as a binder in molding compositions provides improved binder removal in the finished molded product, and offers a wide range of physical properties suitable for use in a variety of processing conditions. The composition preferably includes a powdered material, such as a metal powder, ceramic powder, or blend, admixed with a polyhydroxyalkanoate binder. The compositions are useful in powder processing techniques, such as injection molding, slip casting, tape casting, or extrusion.

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Somerville, MA, United States of America

Daniel M Horowitz