Localized delivery of factors enhancing survival of transplanted cells
    121.
    发明授权
    Localized delivery of factors enhancing survival of transplanted cells 失效
    移植细胞存活的因子的局部递送

    公开(公告)号:US06281015B1

    公开(公告)日:2001-08-28

    申请号:US08358235

    申请日:1994-12-16

    IPC分类号: C12N500

    摘要: Growth factors and/or angiogenic factors are administered in combination with dissociated cells to be transplanted, preferably in microspheres with the cells on or in a polymeric matrix, to enhance survival and proliferation of the transplanted cells. Examples demonstrate that epidermal growth factor (EGF) was incorporated into microspheres fabricated from a copolymer of lactic and glycolic acid using a double emulsion technique, the incorporated EGF was steadily released over one month in vitro, and it remained biologically active, as determined by its ability to stimulate DNA synthesis, division, and long-term survival of cultured hepatocytes. EGF-containing microspheres were mixed with a suspension of hepatocytes, seeded onto porous sponges, and implanted into the mesentery of two groups of Lewis rats, to demonstrate efficacy in vivo. Two weeks after implantation in PCS animals, devices which included EGF-containing microspheres showed a two-fold increase in the number of engrafted hepatocytes, as compared to implants which received blank microspheres.

    摘要翻译: 生长因子和/或血管生成因子与待移植的解离的细胞组合施用,优选在具有在聚合物基质上或聚合物基质中的细胞的微球体中,以增强移植细胞的存活和增殖。 实例表明,使用双重乳液技术将表皮生长因子(EGF)掺入由乳酸和乙醇酸共聚物制成的微球体中,结合的EGF在体外稳定释放一个月,并且其保持生物活性,如 刺激培养的肝细胞的DNA合成,分裂和长期存活的能力。 将含EGF的微球与肝细胞悬浮液混合,接种到多孔海绵上,并植入两组Lewis大鼠的肠系膜,以体现体内效力。 植入PCS动物两周后,与含有空白微球的植入物相比,包含含EGF的微球的装置显示出移植肝细胞数量增加了两倍。

    Method for high supercoiled DNA content microspheres
    122.
    发明授权
    Method for high supercoiled DNA content microspheres 失效
    高超螺旋DNA含量微球的方法

    公开(公告)号:US06197229B1

    公开(公告)日:2001-03-06

    申请号:US09209032

    申请日:1998-12-10

    IPC分类号: B01J1302

    摘要: A method for formulation of high supercoiled DNA content microspheres is described herein. A primary emulsion is formed which optionally contains a DNA nicking inhibitor in addition to DNA with or without buffer. The temperature of the primary emulsion is lowered below the freezing point of the aqueous inner phase which provides increased encapsulation efficiency by decreasing the rate of diffusion of DNA out of the aqueous phase. Thereafter, the primary emulsion is transferred to a water-based surfactant solution and subjected to homogenization to form a secondary microsphere emulsion. The organic phase is removed and the microspheres hardened which are then isolated, frozen and lyophilized.

    摘要翻译: 本文描述了制备高超螺旋DNA含量微球的方法。 除了具有或不具有缓冲液的DNA之外,形成任选含有DNA切口抑制剂的初级乳液。 初级乳液的温度降低到内层水相的凝固点以下,通过降低DNA从水相中扩散的速率来提高包封效率。 此后,将初级乳液转移到水性表面活性剂溶液中并进行均化以形成二次微球体乳液。 除去有机相,然后将微球硬化,然后分离,冷冻并冻干。

    Supercritical fluid sterilization method
    123.
    发明授权
    Supercritical fluid sterilization method 失效
    超临界流体灭菌方法

    公开(公告)号:US6149864A

    公开(公告)日:2000-11-21

    申请号:US104775

    申请日:1998-06-25

    IPC分类号: A61L2/18 A61L2/00

    CPC分类号: A61L2/18 A61L2/16

    摘要: A method is provided for sterilizing materials, particularly polymers, for drug delivery and implantation, wherein the material is treated with supercritical fluid carbon dioxide at pressures in the range of 2000 to 3000 psi (140 to 210 bar) and temperatures preferably between 30 and 45.degree. C. for periods between 20 minutes and six hours, more preferably between 0.5 and 2 hours. Agitation, pressure cycling, and the presence of water were found to enhance the sterilization method, which promotes diffusion of the supercritical fluid carbon dioxide into the cells of the microorganism to thereby alter the pH within the cells, killing them. The magnitude and frequency of the pressure cycling, as well as the process time and temperature, may vary according to the type and form of the material to be sterilized and the type of organisms to be killed.

    摘要翻译: 提供了一种用于消毒材料,特别是用于药物递送和植入的聚合物的方法,其中用超临界流体二氧化碳在2000-3000psi(140-210巴)范围内的压力下处理材料,温度优选在30和45之间 时间为20分钟至6小时,更优选为0.5小时至2小时。 发现搅拌,压力循环和水的存在增强灭菌方法,促进超临界流体二氧化碳向微生物细胞的扩散,从而改变细胞内的pH,从而杀死它们。 压力循环的大小和频率以及工艺时间和温度可以根据要灭菌的材料的类型和形式以及要杀死的生物体的类型而变化。

    Aerodynamically light particles for pulmonary drug delivery
    124.
    发明授权
    Aerodynamically light particles for pulmonary drug delivery 有权
    用于肺部药物递送的空气动力学轻微颗粒

    公开(公告)号:US6136295A

    公开(公告)日:2000-10-24

    申请号:US211940

    申请日:1998-12-15

    摘要: Improved aerodynamically light particles for drug delivery to the pulmonary system, and methods for their synthesis and administration are provided. In a preferred embodiment, the aerodynamically light particles are made of a biodegradable material and have a tap density less than 0.4 g/cm.sup.3 and a mass mean diameter between 5 .mu.m and 30 .mu.m. The particles may be formed of biodegradable materials such as biodegradable polymers. For example, the particles may be formed of a functionalized polyester graft copolymer consisting of a linear .alpha.-hydroxy-acid polyester backbone having at least one amino acid group incorporated therein and at least one poly(amino acid) side chain extending from an amino acid group in the polyester backbone. In one embodiment, aerodynamically light particles having a large mean diameter, for example greater than 5 .mu.m, can be used for enhanced delivery of a therapeutic agent to the alveolar region of the lung. The aerodynamically light particles incorporating a therapeutic agent may be effectively aerosolized for administration to the respiratory tract to permit systemic or local delivery of wide variety of therapeutic agents.

    摘要翻译: 提供用于向肺系统输送药物的空气动力学轻微颗粒,以及用于其合成和给药的方法。 在优选的实施方案中,空气动力学轻微颗粒由可生物降解的材料制成,并且具有小于0.4g / cm 3的振实密度和5μm-30μm之间的质量平均直径。 颗粒可以由可生物降解的材料如可生物降解的聚合物形成。 例如,颗粒可以由官能化的聚酯接枝共聚物形成,该聚酯接枝共聚物由具有至少一个氨基酸基团的直链α-羟基酸聚酯主链和至少一个从氨基酸延伸的聚(氨基酸)侧链组成 集团在聚酯骨干。 在一个实施方案中,具有大平均直径(例如大于5μm)的空气动力学轻的颗粒可用于增强治疗剂递送至肺的肺泡区域。 掺入治疗剂的空气动力学轻微颗粒可以被有效地雾化,用于给予呼吸道以允许全身或局部递送多种治疗剂。

    Biodegradable synthetic polymeric fibrous matrix containing chondrocyte
for in vivo production of a cartilaginous structure
    126.
    发明授权
    Biodegradable synthetic polymeric fibrous matrix containing chondrocyte for in vivo production of a cartilaginous structure 失效
    含有软骨细胞的可生物降解的合成聚合物纤维基质用于体内产生软骨结构

    公开(公告)号:US5736372A

    公开(公告)日:1998-04-07

    申请号:US509952

    申请日:1990-04-16

    摘要: Methods and artificial matrices for the growth and implantation of cartilaginous structures and surfaces and bone are disclosed. In the preferred embodiments, chondrocytes are grown on biodegradable, biocompatible fibrous polymeric matrices. Optionally, the cells are proliferated in vitro until an adequate cell volume and density has developed for the cells to survive and proliferate in vivo. One advantage of the matrices is that they can be cast or molded into a desired shape, on an individual basis, so that the final product closely resembles a patient's own ear or nose. Alternatively, flexible matrices can be used which can be manipulated at the time of implantation, as in a joint, followed by remodeling through cell growth and proliferation in vivo. The cultured cells can also be maintained on the matrix in a nutrient media for production of bioactive molecules such as angiogenesis inhibiting factor. Examples are provided showing the growth of hyaline cartilage for joint relinings, the growth of elastic cartilage for plastic or reconstructive replacement of cartilage structures, and repair of large bone defects.

    摘要翻译: 公开了用于生长和植入软骨结构和表面和骨的方法和人造基质。 在优选的实施方案中,软骨细胞生长在可生物降解的生物相容的纤维聚合物基质上。 任选地,细胞在体外增殖,直至形成足够的细胞体积和密度,使细胞在体内存活和增殖。 基质的一个优点是它们可以在个体的基础上铸造或模制成所需的形状,使得最终产品非常类似于患者自己的耳朵或鼻子。 或者,可以使用可在植入时操作的柔性基质,如在关节中,随后通过体内细胞生长和增殖重塑。 培养的细胞也可以在营养培养基中维持在基质上,用于生产生物活性分子如血管生成抑制因子。 提供了示例,其显示用于联合放置的透明软骨的生长,塑料的弹性软骨的生长或软骨结构的重建置换以及大的骨缺损的修复。

    Functionalized polyester graft copolymers
    127.
    发明授权
    Functionalized polyester graft copolymers 失效
    官能化聚酯接枝共聚物

    公开(公告)号:US5654381A

    公开(公告)日:1997-08-05

    申请号:US491490

    申请日:1995-06-16

    摘要: Synthetic, functionalized, graft copolymers of polyesters and amino acids are provided. The copolymers are formed in one embodiment by providing a linear polyester-poly(amino acid) copolymer, and reacting the amino acid groups in the linear polymer with an amino acid derivative in a polymerization reaction to form a comb-like, graft copolymer including a polyester-amino acid backbone and polyamino acid side chains extending from the amino acid groups in the backbone. The poly(amino acid) includes functional groups which permit the covalent or ionic attachment of a biological molecule to the graft copolymer. The functionalized graft copolymers can be used in a wide range of biomedical applications including tissue engineering and drug delivery.

    摘要翻译: 提供了聚酯和氨基酸的合成官能化接枝共聚物。 在一个实施方案中,通过提供线性聚酯 - 聚(氨基酸)共聚物并在聚合反应中使线性聚合物中的氨基酸与氨基酸衍生物反应形成共聚物,以形成梳状接枝共聚物,包括 聚酯 - 氨基酸主链和从主链中的氨基酸延伸的聚氨基酸侧链。 聚(氨基酸)包括允许生物分子与接枝共聚物共价或离子连接的官能团。 官能化接枝共聚物可用于广泛的生物医学应用,包括组织工程和药物递送。

    Biodegradable polymer matrices for sustained delivery of local
anesthetic agents
    129.
    发明授权
    Biodegradable polymer matrices for sustained delivery of local anesthetic agents 失效
    用于持续输送局部麻醉剂的可生物降解聚合物基质

    公开(公告)号:US5618563A

    公开(公告)日:1997-04-08

    申请号:US119958

    申请日:1993-09-10

    摘要: An improved biodegradable controlled release system consisting of a polymeric matrix incorporating a local anesthetic for the prolonged administration of the local anesthetic agent, and a method for the manufacture thereof, are disclosed. The polymers and method of manufacture used to form the PLAMs are selected on the basis of their degradation profiles: release of the topical anesthetic in a linear, controlled manner over a period of preferably two weeks and degradation in vivo with a half-life of less than six months, more preferably two weeks, to avoid localized inflammation. Alternatively, a non-inflammatory can be incorporated into the polymer with the local anesthetic to prevent inflammation.

    摘要翻译: 公开了一种改进的可生物降解控制释放系统及其制备方法,该系统由掺入局部麻醉剂用于延长给药局部麻醉剂的聚合物基质组成。 基于它们的降解曲线选择用于形成PLAM的聚合物和制造方法:在优选两周的时间内以线性控制的方式释放局部麻醉剂,并且在半衰期较小的情况下体内降解 超过六个月,更优选两周,以避免局部发炎。 或者,非局部麻醉剂可以将非炎症性物质掺入到聚合物中以防止炎症。