公开(公告)号：US20040053381A1

公开(公告)日：2004-03-18

申请号：US10642026

申请日：2003-08-15

Applicant: Metabolix, Inc.

Inventor： Simon F. Williams ,  David P. Martin ,  Tillman Gerngross ,  Daniel M. Horowitz

IPC: C12P007/62 ,  C08G063/78 ,  C08G063/82 ,  C08G063/87

CPC classification number: C12P7/625 ,  A61B17/06166 ,  A61B42/00 ,  A61K47/593 ,  A61K47/6957 ,  A61L15/26 ,  A61L17/10 ,  A61L27/18 ,  A61L27/34 ,  A61L29/06 ,  A61L31/06 ,  C08G63/06 ,  C08G63/6852 ,  C08G63/6882 ,  C08G63/912 ,  C12N5/0068 ,  C12N2533/30 ,  Y10S977/775 ,  Y10T428/139 ,  C08L67/04

Abstract: 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.

Abstract translation: 已经除去热原的聚羟基链烷酸酯（PHA）被提供用于许多生物医学应用。 已经化学改性以增强物理和/或化学性质的PHA用于通过网状内皮系统（RES）靶向或修饰生物降解性或清除的PHA。 还提供了通过细菌发酵方法制备的去氢原位PHA聚合物的方法，其中热原从聚合物中除去而不会不利地影响聚合物固有的化学结构和物理性质。 还描述了具有有利处理特性的PHA，包括低熔点和/或在无毒溶剂中的溶解度。 提供适用于体内应用的PHA，例如在组织涂层，支架，缝线，管，骨和其他假体，骨或组织水泥，组织再生装置，伤口敷料，药物递送以及用于诊断和预防用途 。 选择的性质包括降解性，弹性，包含官能团或衍生基团，其又可用于附着靶向剂，以及生物粘附。

公开(公告)号：US20020058316A1

公开(公告)日：2002-05-16

申请号：US10052434

申请日：2002-01-18

Applicant: Metabolix, Inc.

Inventor： Daniel M. Horowitz

IPC: C12P007/62 ,  C08G063/90

CPC classification number: C08G63/90 ,  C08G63/06 ,  C08G63/89 ,  C12P7/625

Abstract: 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.

Abstract translation: 提供了一种从含有PHA的微生物或植物生物量中分离和纯化PHA的方法。 该方法包括使用至少一种溶剂从生物质中提取PHA的步骤，同时使生物质经过过滤以除去细胞。 在该方法的优选实施方案中，通过使用有机溶剂的渗滤直接提取生物质的含水浆料。 在优选的渗滤方法中，包含PHA的微生物细胞的含水浆液通过过滤膜再循环，其中膜具有足够小的孔径以排除浆液中可能存在的单个细胞或细胞聚集体。 随着液体逐渐从生物质浆料中除去（从过滤膜流出），向生物质浆料中加入有机溶剂，优选与PHA的溶剂相溶的水混溶性溶剂，其速率接近于 通过过滤器的液体渗透速率，从而保持生物质浆料的体积。 不溶于水的杂质溶解在溶剂 - 水混合物中并通过过滤膜，当有机溶剂浓度达到一定水平时，PHA变得可溶，流过过滤膜，可以脱溶剂回收聚合物 。