Controlled local delivery of chemotherapeutic agents for treating solid tumors
    121.
    再颁专利
    Controlled local delivery of chemotherapeutic agents for treating solid tumors 有权
    用于治疗实体瘤的化疗药物的局部控制

    公开(公告)号:USRE37410E1

    公开(公告)日:2001-10-16

    申请号:US09363519

    申请日:1999-07-29

    IPC分类号: A61K914

    摘要: A method and devices for localized delivery of a chemotherapeutic agent to solid tumors, wherein the agent does not cross the blood-brain barrier and is characterized by poor bioavailability and/or short half-lives in vivo, are described. The devices consist of reservoirs which release drug over an extended time period while at the same time preserving the bioactivity and bioavailability of the agent. In the most preferred embodiment, the device consists of biodegradable polymeric matrixes, although reservoirs can also be formulated from non-biodegradable polymers or reservoirs connected to implanted infusion pumps. The devices are implanted within or immediately adjacent the tumors to be treated or the site where they have been surgically removed. The examples demonstrate the efficacy of paclitaxel and camptothecin delivered in polymeric implants prepared by compression molding of biodegradable and non-biodegradable polymers, respectively. The results are highly statistically significant.

    摘要翻译: 描述了用于将化学治疗剂局部递送至实体瘤的方法和装置,其中所述药物不穿过血脑屏障并且其特征在于体内生物利用度差和/或半衰期短。 这些装置包括在延长的时间段内释放药物的储存器,同时保持药剂的生物活性和生物利用度。 在最优选的实施方案中,该装置由可生物降解的聚合物基质组成,尽管储存器也可以由与植入的输注泵连接的不可生物降解的聚合物或储存器配制。 这些装置被植入到待治疗的肿瘤内或紧邻其中,或被手术切除的部位。 这些实施例证明分别通过压缩成型可生物降解和不可生物降解的聚合物制备的聚合物植入物中递送的紫杉醇和喜树碱的功效。 结果具有很高的统计学意义。

    Localized delivery of factors enhancing survival of transplanted cells
    122.
    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
    123.
    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。

    Biodegradable synthetic polymeric fibrous matrix containing chondrocyte
for in vivo production of a cartilaginous structure
    125.
    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。

    Biodegradable polymer matrices for sustained delivery of local
anesthetic agents
    127.
    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。

    Gas-filled polymeric microbubbles for ultrasound imaging
    129.
    发明授权
    Gas-filled polymeric microbubbles for ultrasound imaging 失效
    用于超声成像的气体填充聚合物微泡

    公开(公告)号:US5487390A

    公开(公告)日:1996-01-30

    申请号:US182216

    申请日:1994-01-14

    摘要: Compositions, methods for preparing and methods of using air-filled polymeric microcapsules for ultrasound imaging are disclosed. Air-encapsulating microcapsules are formed by ionotropically gelling synthetic polyelectrolytes such as poly(carboxylatophenoxy)phosphazene, poly(acrylic acid), poly(methacrylic acid) and methacrylic acid copolymers (Eudragit's) by contact with multivalent ions such as calcium ions. In the preferred embodiment, the average size of the microcapsules is less than seven .mu.m so that they are suitable for injection intravenously. The polymeric microcapsules are stable to imaging and display high echogenicity, both in vitro and in vivo. Due to their in vivo stability their potential application is extended beyond vascular imaging to liver and renal diseases, fallopian tube diseases, detecting and characterizing tumor masses and tissues, and measuring peripheral blood velocity. The microcapsules can optionally be linked with ligands that minimize tissue adhesion or that target the microcapsules to specific regions.

    摘要翻译: 公开了组合物,制备方法和使用空气填充的聚合物微胶囊用于超声成像的方法。 通过与多价离子如钙离子接触,通过离子交换胶凝聚合电解质如聚(羧基苯氧基)磷腈,聚(丙烯酸),聚(甲基丙烯酸)和甲基丙烯酸共聚物(Eudragit's))形成空气封装的微胶囊。 在优选的实施方案中,微胶囊的平均尺寸小于7μm,使得它们适合静脉内注射。 聚合物微胶囊在体外和体内都能稳定成像并显示高回波性。 由于其体内稳定性,其潜在应用范围超出血管成像,肝肾疾病,输卵管疾病,检测和表征肿瘤块和组织,并测量外周血速度。 微胶囊可以任选地与使组织粘附最小化或将微胶囊靶向特定区域的配体连接。

    Controlled drug delivery using polymer/pluronic blends
    130.
    发明授权
    Controlled drug delivery using polymer/pluronic blends 失效
    使用聚合物/ pluronic混合物控制药物递送

    公开(公告)号:US5330768A

    公开(公告)日:1994-07-19

    申请号:US726349

    申请日:1991-07-05

    IPC分类号: A61K9/16 A61K9/70

    摘要: A new series of degradable polymeric matrices were prepared by blending polymers that degrade by hydrolysis such as poly(L-lactic acid)(PLA), and nonionic Pluronic.TM. surfactants, block copolymers of polyethyleneoxide (PEO) and polypropyleneoxide (PPO). The water content of the polymer blend films was controlled by mixing different types of block copolymers and by adjusting their amount. In aqueous solution, the blends revealed the typical liquid-crystalline phase transition of Pluronic.TM. polymers, suggesting the formation of a gel-like structure within the polymer skeleton. Poly(lactic acid) degradation rates were not affected by the blending procedure, although the hydration degree in these matrices was higher. When used as drug-releasing matrices, these blends extended protein release and minimized the initial protein burst, as compared to the pure polymer.

    摘要翻译: 通过混合通过水解降解的聚合物如聚(L-乳酸)(PLA)和非离子Pluronic TM表面活性剂,聚环氧乙烷(PEO)和聚环氧丙烷(PPO)的嵌段共聚物)来制备新的可降解聚合物基质系列。 通过混合不同类型的嵌段共聚物并通过调节它们的量来控制聚合物共混物膜的含水量。 在水溶液中,共混物显示Pluronic TM聚合物的典型液晶相变,表明在聚合物骨架内形成凝胶状结构。 尽管这些基质中的水合度较高,但聚(乳酸)降解速率不受共混程序的影响。 当用作药物释放基质时,与纯聚合物相比,这些共混物延长了蛋白质释放并使初始蛋白质爆发最小化。