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1. 发明申请

US20130189230A1 INJECTABLE POLYMER COMPOSITION FOR USE AS A CELL DELIVERY VEHICLE 有权
标题翻译：用作单元交付车辆的可注射聚合物组合物
公开(公告)号：US20130189230A1
公开(公告)日：2013-07-25
申请号：US13516846
申请日：2010-12-17
申请人： Molly Sandra Shoichet , Tasneem Zahir , Brian Ballios , Derek Van Der Kooy , MIchael Cooke
发明人： Molly Sandra Shoichet , Tasneem Zahir , Brian Ballios , Derek Van Der Kooy , MIchael Cooke
IPC分类号： A61K47/48
CPC分类号： A61K47/48169 , A61K9/0024 , A61K47/36 , A61K47/38 , A61K47/61 , A61L27/16 , A61L27/20 , A61L2300/62 , A61L2300/64 , A61L2400/06 , C08L1/28 , C08L5/08 , C08L5/04
摘要： This invention provides a polymer composition comprising at least one thermal gelling polymer and at least one anionic polymer for cell delivery applications. These injectable polymer compositions are shear-thinning, thixotropic and resorbable. More specifically there is described a hyaluronan (HA) and methylcellulose (MC) based thermogelling cell delivery system (HAMC) that promotes cell survival both in vitro and in vivo. Importantly, HAMC (relative to media alone) enhances survival of transplanted stem/progenitor cells in the injured CNS. HAMC provides a minimally-invasive cell delivery strategy where the microenvironment can be further defined and the differentiation and regenerative capacity further explored. This hydrogel system has applications for minimally-invasive cell delivery to other tissues/organs in the body as well.
摘要翻译：本发明提供一种包含至少一种热胶凝聚合物和至少一种用于细胞递送应用的阴离子聚合物的聚合物组合物。这些可注射聚合物组合物是剪切稀化，触变性和可再吸收的。更具体地，描述了在体外和体内促进细胞存活的透明质酸（HA）和甲基纤维素（MC））的热胶凝细胞递送系统（HAMC）。重要的是，HAMC（相对于单独的介质）增强受损CNS中移植的干细胞/祖细胞的存活。 HAMC提供了微创细胞递送策略，其中可以进一步定义微环境，并进一步探索分化和再生能力。该水凝胶体系也适用于微体细胞递送到体内其他组织/器官。

2. 再颁专利

USRE36665E Polyoxypropylene/polyoxyethylene copolymers with improved biological activity 失效
公开(公告)号：USRE36665E
公开(公告)日：2000-04-18
申请号：US089043
申请日：1998-06-02
申请人： R. Martin Emanuele , Robert L. Hunter , Paula H. Culbreth
发明人： R. Martin Emanuele , Robert L. Hunter , Paula H. Culbreth
IPC分类号： A61K31/765 , A61K31/77 , A61K45/06 , A61K47/48 , A61P7/02 , C07C43/11 , C08G65/02 , C08G65/08 , C08G65/26 , C08G65/28 , C08G65/30
CPC分类号： A61K47/48215 , A61K31/765 , A61K31/77 , A61K45/06 , A61K47/48169 , C08G65/08 , C08G65/2609 , C08G65/2624 , C08G65/30
摘要： The present invention comprises novel preparations of polyoxypropylene/polyoxyethylene copolymers which retain the therapeutic activity of the commercial preparations, but are substantially free from the undesirable effects which are inherent in the prior art preparations. Because the preparations of polyoxypropylene/polyoxyethylene copolymers which comprise the present invention are a less polydisperse population of molecules than the prior art polyoxypropylene/polyoxyethylene copolymers, the biological activity of the copolymers is better defined and more predictable.

3. 发明授权

US5919442A Hyper comb-branched polymer conjugates 失效
标题翻译：超梳状支化聚合物共轭物
公开(公告)号：US5919442A
公开(公告)日：1999-07-06
申请号：US694787
申请日：1996-08-09
申请人： Rui Yin , Donald A. Tomalia , David M. Hedstrand , Douglas R. Swanson , James R. Baker, Jr. , Jolanta F. Kukowska-Latallo
发明人： Rui Yin , Donald A. Tomalia , David M. Hedstrand , Douglas R. Swanson , James R. Baker, Jr. , Jolanta F. Kukowska-Latallo
IPC分类号： A61K8/90 , A61K31/74 , A61K47/48 , A61K48/00 , A61K49/00 , A61K51/02 , A61Q13/00 , C08G83/00 , C12N15/87 , A01N25/10
CPC分类号： A61Q13/00 , A61K47/48169 , A61K47/48176 , A61K47/48192 , A61K47/482 , A61K47/48207 , A61K47/4823 , A61K47/48253 , A61K47/487 , A61K47/48961 , A61K49/0043 , A61K49/0054 , A61K8/90 , B82Y5/00 , C08G83/005 , C12N15/87 , A61K2800/54 , A61K2800/57 , A61K48/00 , Y10S424/16 , Y10S525/902
摘要： A novel class of hyper comb-branched polymers conjugated with carried materials are disclosed.
摘要翻译：公开了一种与携带材料共轭的新型超梳状支化聚合物。

4. 发明授权

US5869466A Vitamin B.sub.12 mediated oral delivery systems for GCSF 失效
标题翻译：维生素B12介导的GCSF口服递送系统
公开(公告)号：US5869466A
公开(公告)日：1999-02-09
申请号：US651541
申请日：1996-05-22
申请人： Gregory John Russell-Jones , Steven William Westwood
发明人： Gregory John Russell-Jones , Steven William Westwood
IPC分类号： A61K31/714 , A61K38/00 , A61K47/48 , C07K1/113 , C07K14/505 , C07K14/535 , C07K17/02 , C07K17/08 , C07K17/10 , A61K31/70 , C07H23/00 , C07K1/00
CPC分类号： A61K47/48169 , A61K47/48023 , A61K47/48176 , C07K14/505 , C07K14/535 , C07K17/02 , A61K38/00
摘要： The invention describes complexes between VB.sub.12 analogues and either GCSF or EPO that retain both significant affinity for intrinsic factor (IF) in the VB.sub.12 portion of the complex and significant bioactivity of the GCSF or EPO portion of the complex. The invention also concerns a process for the synthesis of these complexes. This is achieved at least in part, by using a spacer compound, which is linked covalantly between the VB.sub.12 portion and the GCSF or EPO. The complexes preferably have the formulaV--X--A--Y--ZwhereinV is vitamin B.sub.12 or a vitamin B.sub.12 analogue, or derivative, bonded to X either through a carboxylate group pendant to the corrin nucleus of VB.sub.12 or through the central cobalt atom or to a functional group introduced onto the VB.sub.12 molecule, X is selected from: --NHNH--, --NH--, --O--, --S--, --SS--or --CH.sub.2 --, and A is an optionally substituted, saturated or unsaturated, branched or linear, C.sub.1-50 alkylene, cycloalkylene or aromatic group, optionally with one or more carbons within the linear chain being replaced with N, O or S, and wherein the optional substituents are selected from carbonyl, carboxy, hydroxy, amino and other groups, and Y is the covalent linkage between A and Z where Y is selected from --NHCO--, --CONH--, --CONHNHCO--, --N.dbd.N--, --N.dbd.CH--,--NHCH--, --NHN.dbd.CH--, --NHNHCH.sub.2 --, --SS--, --SCH.sub.2 --, --CH.sub.2 S--, --NHCRNH--, --COO--, --OCO--, and R is O, S or NH.sub.2, and Z is GCSF or EPO. The invention also describes reagents that can be used as probes for the detection of buried thiol groups of a protein or peptide, said reagent comprising a complex of either vitamin B.sub.12 (or an analogue thereof) or more generally of any instrumentally or visually detectable label, covalently linked to a diradical spacer, said spacer having a terminal reactive group capable of forming a disulphide bond with a free thiol in said protein or peptides.
摘要翻译：本发明描述了VB12类似物和GCSF或EPO之间的复合物，其在复合物的VB12部分中保留对内在因子（IF）的显着亲和力，并且复合物的GCSF或EPO部分具有显着的生物活性。本发明还涉及合成这些络合物的方法。这通过使用在VB12部分和GCSF或EPO之间共价连接的间隔体化合物至少部分地实现。络合物优选具有式VXAYZ，其中V是维生素B12或维生素B12类似物或衍生物，其通过悬浮于VB12的corrin核的羧酸酯基团或通过中心钴原子或导入到 VB12分子，X选自：-NHN - ， - NH - ， - O - ， - S - ， - S - 或-CH 2 - ，A是任选取代的，饱和或不饱和的，支链或直链的C1-50 任选与线性链中的一个或多个碳原子的亚烷基，亚环烷基或芳族基团被N，O或S取代，其中任选的取代基选自羰基，羧基，羟基，氨基和其它基团，Y是共价键其中Y选自-NHCO - ， - CONH - ， - CONHNHCO - ， - N = N - ， - N = CH - ， - NHCH - ， - NHN = CH - ， - NHNHCH2-，-SS - ， - CH 2 - ， - CH 2 S - ， - NHCRN - ， - COO - ， - OCO-，R是O，S或NH 2，Z是GCSF或EPO。本发明还描述了可用作检测蛋白质或肽的掩埋硫醇基团的探针的试剂，所述试剂包含维生素B12（或其类似物）或更通常的任何仪器上或视觉上可检测的标记物的复合物，共价连接到双基间隔物上，所述间隔物具有能与所述蛋白质或肽中的游离硫醇形成二硫键的末端反应基团。

5. 发明授权

US5681811A Conjugation-stabilized therapeutic agent compositions, delivery and diagnostic formulations comprising same, and method of making and using the same 失效
公开(公告)号：US5681811A
公开(公告)日：1997-10-28
申请号：US509422
申请日：1995-07-31
申请人： Nnochiri Nkem Ekwuribe
发明人： Nnochiri Nkem Ekwuribe
IPC分类号： C07D307/20 , A61K9/107 , A61K9/48 , A61K31/47 , A61K31/4709 , A61K31/52 , A61K31/55 , A61K31/554 , A61K31/70 , A61K31/7028 , A61K31/7034 , A61K31/704 , A61K31/7042 , A61K31/7048 , A61K31/7052 , A61K31/706 , A61K31/7064 , A61K31/7068 , A61K31/7072 , A61K31/7076 , A61K31/7088 , A61K31/715 , A61K31/726 , A61K31/727 , A61K38/00 , A61K38/28 , A61K38/46 , A61K47/48 , A61K49/00 , C07K1/107 , C07K14/62 , C08L59/00 , A61K37/16
CPC分类号： C07K1/1077 , A61K31/7072 , A61K38/28 , A61K38/465 , A61K47/48169 , A61K47/48215 , A61K9/1075 , C07K14/62 , C12Y301/03001 , A61K9/4858
摘要： A stabilized conjugated therapeutic agent complex comprising a therapeutic agent conjugatively coupled to a polymer including lipophilic and hydrophilic moieties, wherein the therapeutic agent may for example be selected from the group consisting of insulin, calcitonin, ACTH, glucagon, somatostatin, somatotropin, somatomedin, parathyroid hormone, erythropoietin, hypothalamic releasing factors, prolactin, thyroid stimulating hormones, endorphins, enkephalins, vasopressin, non-naturally occurring opioids, superoxide dismutase, interferon, asparaginase, arginase, arginine deaminease, adenosine deaminase, ribonuclease, trypsin, chymotrypsin, papain, Ara-A (Arabinofuranosyladenine), Acylguanosine, Nordeoxyguanosine, Azidothymidine, Dideoxyadenosine, Dideoxycytidine, Dideoxyinosine Floxuridine, 6-Mercaptopurine, Doxorubicin, Daunorubicin, or I-darubicin, Erythormycin, Vancomycin, oleandomycin, Ampicillin; Quinidine and Heparin. In a particular aspect, the invention comprises an insulin composition suitable for parenteral as well as non-parenteral administration, preferably oral or parenteral administration, comprising insulin covalently coupled with a polymer including (i) a linear polyalkylene glycol moiety and (ii) a lipophilic moiety, wherein the insulin, the linear polyalkylene glycol moiety and the lipophilic moiety are conformationally arranged in relation to one another such that the insulin in the composition has an enhanced in vivo resistance to enzymatic degradation, relative to insulin alone. One, two, or three polymer constituents may be covalently attached to the therapeutic agent molecule, with one polymer constituent being preferred. The conjugates of the invention are usefully employed in therapeutic as well as non-therapeutic, e.g., diagnostic, applications, and the therapeutic agent and polymer may be covalently coupled to one another, or alternatively may be associatively coupled to one another, e.g., by hydrogen bonding or other associative bonding relationship.

6. 发明授权

US5438040A Conjugation-stabilized polypeptide compositions, therapeutic delivery and diagnostic formulations comprising same, and method of making and using the same 失效
标题翻译：缀合稳定的多肽组合物，包含其的治疗递送和诊断制剂，及其制备和使用方法
公开(公告)号：US5438040A
公开(公告)日：1995-08-01
申请号：US276890
申请日：1994-07-19
申请人： Nnochiri N. Ekwuribe
发明人： Nnochiri N. Ekwuribe
IPC分类号： A61K38/00 , A61K9/107 , A61K9/48 , A61K38/04 , A61K38/11 , A61K38/21 , A61K38/22 , A61K38/23 , A61K38/26 , A61K38/27 , A61K38/28 , A61K38/35 , A61K38/43 , A61K38/44 , A61K38/46 , A61K38/48 , A61K47/48 , A61K49/00 , A61P3/10 , A61P5/50 , C07K1/107 , C07K14/00 , C07K14/62 , C08G65/26 , C08G69/10 , C08G69/40 , C08G81/02 , C08L71/02 , C12N9/96 , C08H1/02
CPC分类号： C12N9/96 , A61K47/48169 , A61K47/48215 , A61K9/1075 , C07K1/1077 , C07K14/62 , A61K38/00 , A61K9/4858
摘要： A stabilized conjugated peptide complex comprising a peptide conjugatively coupled to a polymer including lipophilic and hydrophilic moieties, wherein the peptide may, for example, be selected from the group consisting of insulin, calcitonin, ACTH, glucagon, somatostatin, somatotropin, somatomedin, parathyroid hormone, erythropoietin, hypothalamic releasing factors, prolactin, thyroid stimulating hormones, endorphins, enkephalins, vasopressin, non-naturally occurring opioids, superoxide dismutase, interferon, asparaginase, arginase, arginine deaminease, adenosine deaminase, ribonuclease, trypsin, chymotrypsin, and papain. In a particular aspect, the invention comprises an insulin composition suitable for parenteral as well as non-parenteral administration, preferably oral or parenteral administration, comprising insulin covalently coupled with a polymer including (i) a linear polyalkylene glycol moiety and (ii) a lipophilic moiety, wherein the insulin, the linear polyalkylene glycol moiety and the lipophilic moiety are conformationally arranged in relation to one another such that the insulin in the composition has an enhanced in vivo resistance to enzymatic degradation, relative to insulin alone. One, two, or three polymer constituents may be covalently attached to the insulin molecule, with one polymer constituent being preferred. The conjugates of the invention are usefully employed in therapeutic as well as non-therapeutic, e.g., diagnostic, applications, and the peptide and polymer may be covalently coupled to one another, or alternatively may be associatively coupled to one another, e.g., by hydrogen bonding or other associative bonding relationship.
摘要翻译：一种稳定的共轭肽复合物，其包含与包含亲脂和亲水部分的聚合物共轭偶联的肽，其中所述肽可以例如选自胰岛素，降钙素，ACTH，胰高血糖素，生长抑素，生长激素，生长因子，甲状旁腺激素，促红细胞生成素，下丘脑释放因子，催乳素，促甲状腺激素，内啡肽，脑啡肽，加压素，非天然存在的阿片样物质，超氧化物歧化酶，干扰素，天冬酰胺酶，精氨酸酶，精氨酸脱胺酶，腺苷脱氨酶，核糖核酸酶，胰蛋白酶，胰凝乳蛋白酶和木瓜蛋白酶。在一个特定方面，本发明包括适于肠胃外和非肠胃外给药的胰岛素组合物，优选口服或非肠道给药，其包含与聚合物共价偶联的胰岛素，所述聚合物包括（i）线性聚亚烷基二醇部分和（ii）亲脂性部分，其中胰岛素，线性聚亚烷基二醇部分和亲脂性部分相对于彼此构象地排列，使得组合物中的胰岛素相对于单独的胰岛素具有增强的体内抗酶降解性。一个，两个或三个聚合物组分可以共价连接到胰岛素分子上，其中一种聚合物成分是优选的。本发明的缀合物有用地用于治疗和非治疗，例如诊断，应用，并且肽和聚合物可以彼此共价偶联，或者可以彼此相互偶联，例如通过氢键合或其他缔合键合关系。

7. 发明授权

US5206370A Certain pyridyl hydrazines and hydrazides useful for protein labeling 失效
标题翻译：某些吡啶基肼和酰肼可用于蛋白质标记
公开(公告)号：US5206370A
公开(公告)日：1993-04-27
申请号：US888282
申请日：1992-05-26
申请人： David A. Schwartz , Michael J. Abrams , Christen M. Giadomenico , Jon A. Zubieta
发明人： David A. Schwartz , Michael J. Abrams , Christen M. Giadomenico , Jon A. Zubieta
IPC分类号： A61K47/48 , C07D207/40 , C07D207/404 , C07D207/46 , C07D277/56 , C07D401/04 , C07D401/12 , C07D417/12 , G01N33/534
CPC分类号： C07D207/404 , A61K47/48169 , A61K47/48384 , A61K47/48715 , C07D207/46 , C07D277/56 , C07D401/04 , C07D401/12 , C07D417/12 , G01N33/534 , Y10S436/804
摘要： Bifunctional aromatic compounds which are capable of linking metal ions to biologically useful molecules. The bifunctional compounds are characterized as having a hydrazine or hydrazide group and a protein reactive group. The hydrazine or hydrazide group may be protected as a lower alkyl hydrazone. Conjugates of the bifunctional compounds with macromolecules are also described and labelled macromolecules comprised of the conjugates and metal ions are provided. Additionally, a method is provided for forming a labelled macromolecule by reacting a conjugate with a metal species The compounds and method of this invention are particularly useful in the fields of biology and medicine for imaging and/or therapy.
摘要翻译：能够将金属离子连接到生物有用分子的双功能芳族化合物。双官能化合物的特征在于具有肼或酰肼基团和蛋白质反应性基团。肼或酰肼基团可以被保护为低级烷基腙。还描述了双官能化合物与大分子的缀合物，并且提供了由缀合物和金属离子组成的标记的大分子。另外，提供了通过使结合物与金属物质反应形成标记的大分子的方法本发明的化合物和方法在用于成像和/或治疗的生物学和医学领域中特别有用。

8. 发明授权

US5124471A Bifunctional DTPA-type ligand 失效
标题翻译：双功能DTPA型配线
公开(公告)号：US5124471A
公开(公告)日：1992-06-23
申请号：US498319
申请日：1990-03-26
申请人： Otto A. Gansow , Martin W. Brechbiel
发明人： Otto A. Gansow , Martin W. Brechbiel
IPC分类号： A61K38/00 , A61K38/43 , A61K39/385 , A61K45/00 , A61K47/48 , A61K51/00 , A61K51/04 , A61P3/06 , A61P35/00 , C07B59/00 , C07C229/16 , C07C233/43 , C07C331/28 , C07F1/08 , C07F5/00 , C07F7/24 , C07K16/00 , C07K17/02 , C07K19/00 , G01N33/534
CPC分类号： G01N33/534 , A61K47/48023 , A61K47/48076 , A61K47/48169 , A61K51/048 , C07C229/16 , C07C331/28 , A61K2123/00 , C07C2101/14
摘要： The subject matter of the present invention relates to bifunctional cyclohexyl DPTA ligands and methods for utilizing these compounds.
摘要翻译：本发明的主题涉及双官能环己基DPTA配体和利用这些化合物的方法。

9. 发明授权

US5945514A Antiviral raw materials 失效
标题翻译：抗病毒原料
公开(公告)号：US5945514A
公开(公告)日：1999-08-31
申请号：US43871
申请日：1998-03-30
申请人： Mitsuru Akashi , Masanori Baba , Makoto Onishi
发明人： Mitsuru Akashi , Masanori Baba , Makoto Onishi
IPC分类号： A61K9/08 , A61K31/70 , A61K38/16 , A61K47/48 , A61L15/44 , A61P31/12 , A61P31/18 , C07K1/00 , C07K14/00
CPC分类号： A61K47/48176 , A01N37/46 , A01N65/00 , A01N65/20 , A61K38/168 , A61K47/48169 , Y10S977/906 , Y10S977/915 , Y10S977/92 , Y10S977/963
摘要： The present invention relates to an antiviral raw material having mannose-binding type lectin bound, through a hydrophilic high-molecular chain, to a base material composed of a hydrophobic high-molecular chain. The raw material has excellent shape stability and at the same time has excellent antiviral activity so that it can be used in a wide range of fields.
摘要翻译： PCT No.PCT / JP97 / 02501 Sec。 371日期1998年3月30日 102（e）1998年3月30日PCT PCT 1997年7月18日PCT公布。第WO98 / 06266号公报日期：1998年2月19日本发明涉及具有通过亲水性高分子链结合到由疏水性高分子链构成的基材的甘露糖结合型凝集素的抗病毒原料。该原料具有优异的形状稳定性，同时具有优异的抗病毒活性，因此可用于广泛的领域。

10. 发明授权

US5718915A Antiviral liposome having coupled target-binding moiety and hydrolytic enzyme 失效
标题翻译：具有偶联的靶结合部分和水解酶的抗病毒脂质体
公开(公告)号：US5718915A
公开(公告)日：1998-02-17
申请号：US424874
申请日：1995-04-19
申请人： Jorma Virtanen , Sinikka Virtanen
发明人： Jorma Virtanen , Sinikka Virtanen
IPC分类号： G01N33/531 , A61K9/127 , A61K31/70 , A61K38/00 , A61K38/46 , A61K47/48 , A61P9/10 , A61P31/12 , C07H21/00 , C07K14/73 , C07K16/00 , C07K16/10 , C07K17/00 , C07K19/00 , C12N15/09 , C12N15/88 , C12Q1/68 , G01N33/535 , C12N7/04 , C12N11/00
CPC分类号： C07K16/1063 , A61K47/48169 , A61K47/48369 , A61K47/484 , A61K47/48523 , A61K9/1271 , C07K19/00 , C12N15/88 , C12Q1/68 , G01N33/535 , A61K38/00 , C07K2319/00 , Y10S977/728 , Y10S977/729 , Y10S977/754 , Y10S977/882 , Y10S977/898 , Y10S977/907
摘要： Complexes are prepared containing two or more different effector molecules joined to each other by a joining component. At least one of the effector molecules can bind to a target molecule and at least one of the other effector molecules has therapeutic properties. The joining component can be liposomes, proteins and organic polymers including dendrimer polymers, and can be of sufficient length and/or flexibility to permit the therapeutic effector molecule to interact with a target at the same time as the binding molecules. An antiviral liposome is prepared by coupling to a liposome outer surface a hydrolytic enzyme capable of digesting a viral component and a target-binding moiety which may be a polypeptide, glycoprotein or glycoprotein fragment having specificity for viruses such as HIV-1, influenza virus and hepatitis virus. The hydrolytic enzyme may be a glycosidase, phospholipase, lipase, cholesterol esterase, nuclease or protease. A second hydrolytic enzyme and target-binding moiety may also be present, and albumin may be coupled to the liposome surface. Within the liposome may be an internal hydrolytic enzyme capable of digesting a viral component.
摘要翻译：制备的复合物含有通过接合组分彼此连接的两个或更多个不同的效应分子。至少一个效应分子可以结合靶分子，并且至少一个其它效应分子具有治疗性质。连接组分可以是脂质体，蛋白质和包括树状聚合物聚合物的有机聚合物，并且可以具有足够的长度和/或柔性，以允许治疗效应分子与结合分子同时与靶相互作用。通过将脂质体外表面与能够消化病毒组分的水解酶和靶结合部分（其可以是具有对HIV-1，流感病毒等病毒具有特异性的多肽，糖蛋白或糖蛋白片段）进行偶联来制备抗病毒脂质体，肝炎病毒。水解酶可以是糖苷酶，磷脂酶，脂肪酶，胆固醇酯酶，核酸酶或蛋白酶。也可以存在第二水解酶和靶结合部分，并且白蛋白可以偶联到脂质体表面。在脂质体内可以是能够消化病毒成分的内部水解酶。

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