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91. 发明申请

WO2003083070A3 ENDOTHELIAL CELLS DERIVED FROM HUMAN EMBRYONIC STEM CELLS 审中-公开
公开(公告)号：WO2003083070A3
公开(公告)日：2003-10-09
申请号：PCT/US2003/009457
申请日：2003-03-26
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , TECHNION RESEARCH AND DEVELOPMENT FOUNDATION, LTD. , AMIT, Michal , ITSKOVITZ-ELDOR, Joseph , LEVENBERG, Shulamit , LANGER, Robert, S.
发明人： AMIT, Michal , ITSKOVITZ-ELDOR, Joseph , LEVENBERG, Shulamit , LANGER, Robert, S.
IPC分类号： C12N5/00
摘要： The invention is a population of embryonic endothelial cells produced in vitro from human embryonic stem cells. The cells produce platelet endothelial cell adhesion molecule-1 and are vasculogenic. The cells may be combined with a cell support substrate, seeded on a polymer matrix, or combined with a cell-support substrate that is infused into a polymer matrix. The cells may also be injected directly into a tissue site.

92. 发明申请

WO2002031025A3 BIODEGRADABLE POLY(BETA-AMINO ESTERS) AND USES THEREOF 审中-公开
公开(公告)号：WO2002031025A3
公开(公告)日：2002-04-18
申请号：PCT/US2001/031270
申请日：2001-10-05
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY
发明人： LANGER, Robert, S. , LYNN, David, M. , PUTNAM, David , AMIJI, Mansoor, M. , ANDERSON, Daniel, G.
IPC分类号： C08G73/02
摘要： Poly(β amino esters)prepared from the conjugate addition of bis(secondary amines) or primary amines to a bis (acylate ester) are described. Methods of preparing these polymers from commercially available starting materials are also provided. These tertiary amine-containing polymers are preferably biodegradable and biocompatible and may be used in a variety of drug delivery systems. Given the poly(amine) nature of these polymers, they are particularly suited for the delivery of polynucleotides. Nanoparticles containing polymer/polynucleotide complexes have been prepared. The inventive polymers may also be used to encapsulate other agents to be delivered. They are particularly useful in delivering labile agents given their ability to buffer the pH of their surroundings.

93. 发明申请

WO1997030104A1 BIODEGRADABLE POLYMER NETWORKS FOR USE IN ORTHOPEDIC AND DENTAL APPLICATIONS 审中-公开
标题翻译：可生物降解的聚合物网络用于正畸和牙科应用
公开(公告)号：WO1997030104A1
公开(公告)日：1997-08-21
申请号：PCT/US1997002618
申请日：1997-02-19
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY
发明人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , ANSETH, Kristi, S. , LANGER, Robert, S. , SHASTRI, Venkatram, R.
IPC分类号： C08G67/04
CPC分类号： A61L27/58 , A61K9/2027 , A61L24/0042 , A61L31/148 , C08F267/02
摘要： Biodegradable polymer networks are provided which are useful in a variety of dental and orthopedic applications. The biodegradable polymer networks can be formed in one embodiment by polymerizing anhydride prepolymers including cross-linkable groups, such as unsaturated moieties. The anhydride prepolymers can be cross-linked, for example in a photopolymerization reaction by irradiation of the prepolymer with light in the presence of a free radical initiator. Suitable anhydride prepolymers include dianhydrides of a dicarboxylic acid and a carboxylic acid molecule comprising a cross-linkable group. For example, methacrylic acid dianhydrides of monomers or oligomers of a diacid such as sebacic acid or 1,3-bis(p-carboxyphenoxy)-hexane can be used. The anhydride prepolymers can be applied in vivo to a site where an orthopedic implant is needed, and then may be cross-linked, for example, by irradiation with UV light, to form a biodegradable implant such as a rod, pin or plate. The implants advantageously provide mechanical support and also are capable of slow surface degradation to permit bone ingrowth.
摘要翻译：提供可生物降解的聚合物网络，其可用于各种牙科和矫形应用。可生物降解的聚合物网络可以在一个实施方案中通过聚合包括可交联基团（例如不饱和部分）的酸酐预聚物来形成。可以将酸酐预聚物交联，例如通过在自由基引发剂的存在下用光照射预聚物进行光聚合反应。合适的酸酐预聚物包括二羧酸的二酐和包含可交联基团的羧酸分子。例如，可以使用二酸的单体或低聚物的甲基丙烯酸二酐，例如癸二酸或1,3-双（对羧基苯氧基） - 己烷。酸酐预聚物可以体内施用于需要整形外科植入物的部位，然后可以例如通过用紫外线照射进行交联，形成可生物降解的植入物，例如杆，针或板。植入物有利地提供机械支撑并且还能够缓慢的表面退化以允许骨向内生长。

94. 发明申请

WO1996018411A1 LOCALIZED DELIVERY OF FACTORS ENHANCING SURVIVAL OF TRANSPLANTED CELLS 审中-公开
标题翻译：局部递送因子增强移植细胞存活
公开(公告)号：WO1996018411A1
公开(公告)日：1996-06-20
申请号：PCT/US1995016356
申请日：1995-12-14
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , CHILDREN'S MEDICAL CENTER CORPORATION
发明人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , CHILDREN'S MEDICAL CENTER CORPORATION , MOONEY, David, J. , LANGER, Robert, S. , VACANTI, Joseph, P.
IPC分类号： A61K38/18
CPC分类号： A61K9/0024 , A61K35/407 , A61K38/1808 , C12N5/0075 , C12N5/067 , C12N2501/11 , C12N2531/00 , C12N2533/40
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 profileration 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分化。实施例表明，使用双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动物后两周，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。

95. 发明申请

WO1994009760A1 BIODEGRADABLE POLYMERS FOR CELL TRANSPLANTATION 审中-公开
标题翻译：用于细胞移植的生物可降解聚合物
公开(公告)号：WO1994009760A1
公开(公告)日：1994-05-11
申请号：PCT/US1993010655
申请日：1993-11-05
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , CHILDREN'S HOSPITAL
发明人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , CHILDREN'S HOSPITAL , BARRERA, Denise , LANGER, Robert, S. , LANSBURY, Peter, T., Jr. , VACANTI, Joseph, P.
IPC分类号： A61K09/14
CPC分类号： A61L27/54 , A61K47/593 , A61K47/645 , A61L27/18 , A61L27/38 , A61L2300/25 , A61L2300/604 , A61L2300/64 , C07K14/001 , C08G63/6852 , C12N5/0068 , C12N2533/40 , Y10S530/815 , C08L67/04
摘要： Polymers more suitable for use in organ transplantation are formed by coupling biologically active moieties to the free amino groups of polymers formed by incorporation of alpha amino acids into polymers formed of alpha hydroxy acids such as lactic acids. In the preferred embodiment, the peptides are coupled to the free amino groups.
摘要翻译：更适合用于器官移植的聚合物通过将生物活性部分与通过将α-氨基酸掺入由α-羟基酸如乳酸形成的聚合物形成的聚合物的游离氨基上而形成。在优选的实施方案中，肽与游离氨基偶联。

96. 发明申请

WO1993008850A1 PREVASCULARIZED POLYMERIC IMPLANTS FOR ORGAN TRANSPLANTATION 审中-公开
标题翻译：用于组织移植的预混合聚合物植入物
公开(公告)号：WO1993008850A1
公开(公告)日：1993-05-13
申请号：PCT/US1992009142
申请日：1992-10-28
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , CHILDREN'S MEDICAL CENTER CORPORATION
发明人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , CHILDREN'S MEDICAL CENTER CORPORATION , STEIN, James, E. , GILBERT, James, C. , INGBER, Donald, E. , LANGER, Robert, S. , VACANTI, Joseph, P.
IPC分类号： A61L27/00
CPC分类号： A61L27/3886 , A61F2/02 , A61F2/022 , A61L27/38 , A61L27/3804 , A61L27/56 , C12N5/00
摘要： A method is disclosed whereby cells having a desired function are seeded on and into biocompatible, biodegradable or non-degradable polymer scaffolding, previously implanted in a patient and infiltrated with blood vessels and connective tissue, to produce a functional organ equivalent. The resulting organoid is a chimera formed of parenchymal elements of the donated tissue and vascular and matrix elements of the host. The matrix should be a non-toxic, injectable porous template for vascular ingrowth. The pore size, usually between approximately 100 and 300 microns, should allow vascular and connective tissue ingrowth throughout approximately 10 to 90 % of the matrix, and the injection of cells such as hepatocytes without damage to the cells or patient. The introduced cells attach to the connective tissue and are fed by the blood vessels. Immediately prior to polymer implantation portacaval shunts can be created to provide trophic stimulatory factors to the implants to enhance replication and function.
摘要翻译：公开了一种方法，其中具有期望功能的细胞接种在生物相容性，可生物降解或不可降解的聚合物支架中，其预先植入患者体内并渗入血管和结缔组织以产生功能性器官当量。所得的有机体是由捐赠的组织的实质元素和宿主的血管和基质元素形成的嵌合体。基质应是一种无毒，可注射的多孔模板，用于血管向内生长。通常在约100和300微米之间的孔径应允许血管和结缔组织在基质的约10至90％内向内生长，以及注射细胞如肝细胞而不损伤细胞或患者。引入的细胞附着于结缔组织并由血管进食。在聚合物植入之前，可以创建口腔分流术，以向植入物提供营养刺激因子以增强复制和功能。

97. 发明申请

WO1993007913A1 NEOMORPHOGENESIS OF UROLOGICAL STRUCTURES IN VIVO FROM CELL CULTURE 审中-公开
标题翻译：细胞培养的血液中的尿毒症结构的细胞发生异常发生
公开(公告)号：WO1993007913A1
公开(公告)日：1993-04-29
申请号：PCT/US1992009038
申请日：1992-10-23
申请人： CHILDREN'S MEDICAL CENTER CORPORATION , MASSACHUSETTS INSTITUTE OF TECHNOLOGY
发明人： CHILDREN'S MEDICAL CENTER CORPORATION , MASSACHUSETTS INSTITUTE OF TECHNOLOGY , ATALA, Anthony , VACANTI, Joseph, P. , FREEMAN, Michael, R. , LANGER, Robert, S.
IPC分类号： A61L27/00
CPC分类号： A61L27/3804 , A61F2/062 , A61L27/3882 , C12N5/0068 , C12N2533/40
摘要： Methods and artificial matrices for the growth and implantation of urological structures and surfaces are disclosed in which urothelial cells are grown in culture on biodegradable, biocompatible, fibrous matrices formed of polymers, such as polyglycolic acid, polylactic acid, or other polymers which degrade over time. The cells can be cultured in vitro until an adequate cell volume and density has developed for the cells to survive and proliferate in vivo. Alternatively, when adequate cell numbers for implantation are available, the cells can be attached to the matrix and implanted directly, without proliferation in vivo. The implants approximate the desired urological structure to be replaced or repaired, such as the kidney, ureter, bladder, urethra, and the like. Implantation is followed by remodeling through cell growth and proliferation in vivo. In another aspect of the inventin, techniques are disclosed for selectively extracting or harvesting urothelial cells either from excised urological tissue in vitro or from intact urological tissue in vivo by treating the tissue with a digestive enzyme, such as collagenase.
摘要翻译：公开了用于生长和植入泌尿结构和表面的方法和人造基质，其中尿素上皮细胞在可生物降解的生物相容性的生物相容的纤维基质上生长培养，所述生物相容性由聚合物形成，例如聚乙醇酸，聚乳酸或其它随时间降解的聚合物。细胞可以在体外培养，直到细胞体积和密度发展得足以使细胞在体内存活和增殖。或者，当有足够的植入细胞数量可用时，可以将细胞连接到基质上并直接注入，而不会在体内增殖。植入物近似于要更换或修复的所需泌尿系统结构，例如肾，输尿管，膀胱，尿道等。植入之后，通过体内细胞生长和增殖重塑。在本发明的另一方面，公开了用于通过用消化酶（例如胶原酶）处理组织来选择性地从体外来自切除的泌尿组织或从体内的完整泌尿组织中提取或收获尿路上皮细胞的技术。

98. 发明申请

WO1990001971A1 ULTRASOUND ENHANCEMENT OF TRANSBUCCAL DRUG DELIVERY 审中-公开
标题翻译：超声波药物递送的超声波增强
公开(公告)号：WO1990001971A1
公开(公告)日：1990-03-08
申请号：PCT/US1989003563
申请日：1989-08-18
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY
发明人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , KOST, Joseph , LANGER, Robert, S.
IPC分类号： A61M37/00
CPC分类号： A61K41/0047 , A61K9/0009 , A61M35/00 , A61M37/00 , A61M37/0092
摘要： A method using ultrasound for enhancing and controlling transbuccal permeation of a molecule, including drugs, antigens, vitamins, inorganic and organic compounds, and various combinations of these substances, through the buccal membranes and into the circulatory system. The frequency and intensity of ultrasonic energy which is applied, and the length of time of exposure are determined according to the location and nature of the buccal membrane and the substance to be infused. Levels of the infused molecules in the blood and urine measured over a period of time are initially used to determine under what conditions optimum transfer occurs. In a variation of the method whereby ultrasound is applied directly to the compound and site where the compound is to be infused through the buccal membranes, the compound can be placed within a delivery device. In one variation, the ultrasound can control release both by direct interaction with the compound and membrane but also with the delivery device. In another variation, the delivery device helps to modulate release and infusion rate. The compound can also be administered in combination with a chemical agent which alters permeability of the buccal membrane, thereby aiding infusion of the compound into the circulatory system.
摘要翻译：一种使用超声波增强和控制分子（包括药物，抗原，维生素，无机和有机化合物）以及这些物质的各种组合的跨颊渗透通过颊膜进入循环系统的方法。应用超声能量的频率和强度以及暴露时间长短根据颊膜和待注射物质的位置和性质来确定。在一段时间内测量的血液和尿液中输注的分子的水平最初用于确定什么条件下最佳转移发生。在使超声波直接施加到化合物和通过颊膜输注化合物的部位的方法的变型中，化合物可以放置在递送装置内。在一个变化中，超声波可以通过与化合物和膜的直接相互作用来控制释放，而且还可以通过递送装置控制释放。在另一个实施例中，递送装置有助于调节释放和输注速率。化合物还可以与改变颊膜渗透性的化学试剂组合施用，由此帮助化合物输注到循环系统中。

99. 发明申请

WO1989012464A1 CONTROLLED RELEASE SYSTEMS CONTAINING HEPARIN AND GROWTH FACTORS 审中-公开
标题翻译：含有HEPARIN和生长因子的控制释放系统
公开(公告)号：WO1989012464A1
公开(公告)日：1989-12-28
申请号：PCT/US1989002575
申请日：1989-06-13
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY
发明人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , EDELMAN, Elazer, R. , LANGER, Robert, S. , KLAGSBURN, Michael , MATHIOWITZ, Edith
IPC分类号： A61K47/00
CPC分类号： A61K9/5036 , A61K9/167 , A61K38/1825 , A61K47/61 , Y10S530/813 , Y10S530/815 , Y10S530/816
摘要： A system for stabilizing fibroblast-derived growth factors, maintaining their bioactivity over a prolonged period of time and controllably releasing them for use is disclosed. The system uses growth factors bound to biocompatible substrates via heparin or heparin derived compounds to maintain the bioactivity of the growth factors. A growth factor bound to a heparin coated substrate can be used independently as a controlled release device, or can be incorporated into a reservoir or matrix type controlled release device to further enhance the controlled release properties. The stabilized growth factors can be implanted into a patient, thereby providing a means for producing an in vivo controlled release of a growth factor to the patient.

100. 发明申请

WO1989001006A1 UNSATURATED POLYANHYDRIDES 审中-公开
标题翻译：不饱和聚异氰酸酯
公开(公告)号：WO1989001006A1
公开(公告)日：1989-02-09
申请号：PCT/US1988002570
申请日：1988-07-28
申请人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY
发明人： MASSACHUSETTS INSTITUTE OF TECHNOLOGY , DOMB, Abraham, J. , LANGER, Robert, S.
IPC分类号： C08G67/04
CPC分类号： C08G67/04 , A61K9/2031 , A61L24/0042 , A61L24/046 , A61L2430/02 , C08L73/02
摘要： A class of unsaturated polyanhydrides having double bonds available for secondary polymerization is disclosed. A crosslinked material having improved or different physical and mechanical properties can be prepared from these polyanhydrides, via secondary polymerization. The synthesis and characteristics of one unsaturated polyanhydride based on fumaric acid and its copolymers with aliphatic and aromatic diacids, prepared by either the melt-polycondensation method or by solution polymerization, is described in detail. These polymers are well suited for use in controlled release drug delivery devices. The polymers can also be used as a bioerodible bone cement where the polymer is first cast as a solution onto a bone fracture and then crosslinked by radiation or radical polymerization to yield a strong, adhesive material.

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