公开(公告)号：US20090012033A1

公开(公告)日：2009-01-08

申请号：US12224644

申请日：2007-03-03

申请人： Cordell R. DeMattei ,  Baohua Huang ,  Lori A. Reyna ,  Sonke Svenson ,  Douglas R. Swanson ,  Donald A. Tomalia ,  Michael A. Zhuravel ,  Veera Reddy Pulgam

发明人： Cordell R. DeMattei ,  Baohua Huang ,  Lori A. Reyna ,  Sonke Svenson ,  Douglas R. Swanson ,  Donald A. Tomalia ,  Michael A. Zhuravel ,  Veera Reddy Pulgam

IPC分类号： A61K48/00 ,  C08G73/02 ,  C08G63/08 ,  C12Q1/68 ,  A61P43/00 ,  C12N15/63 ,  C08G63/91 ,  A61K31/7052

CPC分类号： A61K48/00 ,  A61K9/5146 ,  A61K47/59 ,  A61K47/595 ,  A61K47/60 ,  C08G83/003 ,  Y02A50/463

摘要： The present invention concerns core-shell tecto (dendritic polymers) that are associated with biologically active materials (such as nucleic acids for use for RNAi and in transfection). Also included are formulations for their use. The constructs are useful for the delivery of drugs to an animal or plant and may be in vivo, in vitro or ex vivo.

摘要翻译： 本发明涉及与生物活性物质（例如用于RNAi和转染的核酸）相关的核 - 壳结构（树枝状聚合物）。 还包括其使用的配方。 所述构建体可用于将药物递送至动物或植物，并且可以在体内或体外进行。

公开(公告)号：US07985424B2

公开(公告)日：2011-07-26

申请号：US11630044

申请日：2005-12-21

申请人： Donald A. Tomalia ,  Douglas R. Swanson ,  Baohua Huang ,  Veera Reddy Pulgam ,  Joseph R. Heinzelmann ,  Sonke Svenson ,  Lori A. Reyna ,  Michael A. Zhuravel ,  Abhay Singh Chauhan ,  Cordell R. DeMattei

发明人： Donald A. Tomalia ,  Douglas R. Swanson ,  Baohua Huang ,  Veera Reddy Pulgam ,  Joseph R. Heinzelmann ,  Sonke Svenson ,  Lori A. Reyna ,  Michael A. Zhuravel ,  Abhay Singh Chauhan ,  Cordell R. DeMattei

IPC分类号： A61K9/14

CPC分类号： C08G63/46 ,  A01N25/10 ,  A61K8/85 ,  A61K9/0019 ,  A61K9/5146 ,  A61Q15/00 ,  A61Q17/005 ,  C08G83/003 ,  H01M4/86 ,  H01M8/10 ,  Y02P70/56

摘要： Dendritic polymers with enhanced amplification and interior functionality are disclosed. These dendritic polymers are made by use of fast, reactive ring-opening chemistry (or other fast reactions) combined with the use of branch cell reagents in a controlled way to rapidly and precisely build dendritic structures, generation by generation, with cleaner chemistry, often single products, lower excesses of reagents, lower levels of dilution, higher capacity method, more easily scaled to commercial dimensions, new ranges of materials, and lower cost. The dendritic compositions prepared have novel internal functionality, greater stability (e.g., thermal stability and less or no reverse Michael's reaction), and reach encapsulation surface densities at lower generations. Unexpectedly, these reactions of polyfunctional branch cell reagents with polyfunctional cores do not create cross-linked materials. Such dendritic polymers are useful as demulsifiers for oil/water emulsions, wet strength agents in the manufacture of paper, proton scavengers, polymers, nanoscale monomers, calibration standards for electron microscopy, making size selective membranes, and agents for modifying viscosity in aqueous formulations such as paint. When these dendritic polymers have a carried material associated with their surface and/or interior, then these dendritic polymers have additional properties for carrying materials due to the unique characteristics of the dendritic polymer, such as for drug delivery, transfection, and diagnostics.

摘要翻译： 公开了具有增强的扩增和内部功能的树枝状聚合物。 这些树枝状聚合物通过使用快速，反应性开环化学（或其他快速反应）结合使用分支细胞试剂以受控方式快速和精确地构建树突状结构，一代代，具有更清洁的化学，通常 单一产品，较低的试剂过量，较低的稀释水平，更高的容量方法，更容易缩放到商业尺寸，新的材料范围以及更低的成本。 制备的树枝状组合物具有新颖的内部功能，更高的稳定性（例如，热稳定性和较少的或没有反向的迈克尔反应），并且在较低的代次下达到包封表面密度。 出乎意料的是，多官能分支细胞试剂与多官能核心的这些反应不产生交联材料。 这种树枝状聚合物可用作油/水乳液的破乳剂，纸张制造中的湿强剂，质子清除剂，聚合物，纳米尺寸单体，用于电子显微镜的校准标准品，制备尺寸选择性膜，以及用于在水性制剂中改性粘度的试剂 作为油漆。 当这些树枝状聚合物具有与其表面和/或内部相关的载体材料时，由于树枝状聚合物的独特特征，例如用于药物递送，转染和诊断，这些树枝状聚合物具有携带材料的附加性质。

公开(公告)号：US20080221300A1

公开(公告)日：2008-09-11

申请号：US11885244

申请日：2006-03-27

申请人： Donald A. Tomalia ,  Veera Reddy Pulgam ,  Douglas R. Swanson ,  Baohua Huang

发明人： Donald A. Tomalia ,  Veera Reddy Pulgam ,  Douglas R. Swanson ,  Baohua Huang

IPC分类号： C08G75/00

CPC分类号： C08G83/003 ,  C08G81/00

摘要： This invention provides a cost effective process and new Janus dendrimers where at least two dendrons are attached at the core (with or without a connector group) and where at least two of the dendrons have different functionality. Preferred are those Janus dendrimers where at least one dendron is a PEHAM dendron. Thus these Janus dendrimers are heterobifunctional in character and use unique ligation chemistry with single site functional dendrons, di-dendrons and multi-dendrons. Also included are Janus dendrons which maybe used as intermediates to make the Janus dendrimers or to further react with another reactive moiety. These Janus dendrimers can provide several new dendrimer moieties, namely: combinatorial libraries of bifunctional structures; combined target director and signaling dendrimers; specific targeting entities for diagnostic and therapeutic applications, such as for example targeted MRI agents, targeted radionuclide delivery for diseases such as cancer, and targeted photosensitive or radiowave sensitive agents.

摘要翻译： 本发明提供了一种成本有效的方法和新的Janus树枝状大分子，其中至少两个树突状物连接在核心处（具有或不具有连接基团），并且其中至少两个枝状突起具有不同的功能。 那些Janus树枝状大分子是首选，其中至少有一个树突是PEHAM树突。 因此，这些Janus树枝状大分子在性质上是异双功能的，并且使用独特的连接化学物质，其具有单位点功能性树突，二树枝状突起和多枝状突起。 还包括Janus dendron，其可以用作中间体来制备Janus树枝状大分子或进一步与另一反应性部分反应。 这些Janus树枝状大分子可以提供几个新的树枝状大分子部分，即：双功能结构的组合文库; 组合目标主任和信号树枝状大分子; 用于诊断和治疗应用的特异性靶向实体，例如靶向MRI剂，用于诸如癌症的疾病的靶向放射性核素递送，以及靶向感光或无线电波敏感剂。

公开(公告)号：US20100086482A1

公开(公告)日：2010-04-08

申请号：US12448513

申请日：2007-12-28

申请人： Donald A. Tomalia ,  Douglas R. Swanson ,  Baohua Huang ,  Veera Reddy Pulgam

发明人： Donald A. Tomalia ,  Douglas R. Swanson ,  Baohua Huang ,  Veera Reddy Pulgam

IPC分类号： A61K49/00 ,  C07D487/00 ,  C07D491/00 ,  A61K31/395 ,  C07D245/00 ,  A61K31/495 ,  A61K31/16 ,  G01N33/566

CPC分类号： C08G83/003 ,  Y10T436/143333

摘要： The present invention describes a process for preparing new looped dendrimer and dendron compounds by controlling the molar amount of branch cell reagent monomer that is combined with various cores bearing core-XR functionalities (e.g., primary, or secondary amines, thiol, or epoxy functionalities). These looped, macrocyclic structures are more robust to various conditions, with greater resistance to acid/base hydrolysis. Alternatively, the looped, macrocyclic structure may offer new orientations that would qualify it as a better chelation ligand for metals, and other similar uses.

摘要翻译： 本发明描述了通过控制与具有核-XR官能团的各种核心（例如伯，仲胺，硫醇或环氧官能团）组合的分支细胞试剂单体的摩尔量来制备新的环状树枝状聚合物和树枝状化合物的方法， 。 这些环状的大环结构对各种条件更加坚固，具有较强的抗酸/碱水解的能力。 或者，环状的大环结构可以提供新的取向，其将其作为金属的更好的螯合配体和其它类似的用途。

公开(公告)号：US07981444B2

公开(公告)日：2011-07-19

申请号：US10594776

申请日：2005-04-20

申请人： Donald A. Tomalia ,  Douglas R. Swanson ,  Baohua Huang ,  Veera Reddy Pulgam

发明人： Donald A. Tomalia ,  Douglas R. Swanson ,  Baohua Huang ,  Veera Reddy Pulgam

IPC分类号： A61K9/14

CPC分类号： C08G83/003 ,  C08G59/1477 ,  C08G59/32 ,  C08G59/3227 ,  C08G59/5026

摘要： Poly(ester-acrylate) and poly(ester/epoxide) dendrimers. These materials can be synthesized by utilizing the so-called “sterically induced stoichiometric” principles. The preparation of the dendrimers is carried out by reacting precursor amino/polyamino-functional core materials with various branch cell reagents. The branch cell reagents are dimensionally large, relative to the amino/polyamino-initiator core and when reacted, produce generation=1 dendrimers directly in one step. There is also a method by which the dendrimers can be stabilized and that method is the reaction of the dendrimers with surface reactive molecules to pacify the reactive groups on the dendrimers.

摘要翻译： 聚（酯 - 丙烯酸酯）和聚（酯/环氧化物）树枝状大分子。 这些材料可以通过利用所谓的“空间诱导化学计量”原理来合成。 树枝状大分子的制备通过使前体氨基/聚氨基官能的核心材料与各种分支细胞试剂反应来进行。 分支细胞试剂相对于氨基/聚氨基 - 引发剂核心在尺寸上是大的，并且当反应时，在一个步骤中直接产生生成= 1个树枝状大分子。 还有一种树枝状聚合物可以稳定的方法，该方法是树枝状聚合物与表面反应性分子的反应，以平衡树枝状聚合物上的反应性基团。

公开(公告)号：US07977452B2

公开(公告)日：2011-07-12

申请号：US11885244

申请日：2006-03-27

申请人： Donald A. Tomalia ,  Veera Reddy Pulgam ,  Douglas R. Swanson ,  Boahua Huang

发明人： Donald A. Tomalia ,  Veera Reddy Pulgam ,  Douglas R. Swanson ,  Boahua Huang

IPC分类号： C08G75/00

CPC分类号： C08G83/003 ,  C08G81/00

摘要： This invention provides a cost effective process and new Janus dendrimers where at least two dendrons are attached at the core (with or without a connector group) and where at least two of the dendrons have different functionality. Preferred are those Janus dendrimers where at least one dendron is a PEHAM dendron. Thus these Janus dendrimers are heterobifunctional in character and use unique ligation chemistry with single site functional dendrons, di-dendrons and multi-dendrons. Also included are Janus dendrons which may be used as intermediates to make the Janus dendrimers or to further react with another reactive moiety. These Janus dendrimers can provide several new dendrimer moieties, namely: combinatorial libraries of bifunctional structures; combined target director and signaling dendrimers; specific targeting entities for diagnostic and therapeutic applications, such as for example targeted MRI agents, targeted radionuclide delivery for diseases such as cancer, and targeted photosensitive or radiowave sensitive agents.

摘要翻译： 本发明提供了一种成本有效的方法和新的Janus树枝状大分子，其中至少两个树突状物连接在核心处（具有或不具有连接基团），并且其中至少两个枝状突起具有不同的功能。 那些Janus树枝状大分子是首选，其中至少有一个树突是PEHAM树突。 因此，这些Janus树枝状大分子在性质上是异双功能的，并且使用独特的连接化学物质，其具有单位点功能性树突，二树枝状突起和多枝状突起。 还包括Janus dendron，其可以用作中间体以制备Janus树枝状大分子或进一步与另一反应性部分反应。 这些Janus树枝状大分子可以提供几个新的树枝状大分子部分，即：双功能结构的组合文库; 组合目标主任和信号树枝状大分子; 用于诊断和治疗应用的特异性靶向实体，例如靶向MRI剂，用于诸如癌症的疾病的靶向放射性核素递送，以及靶向感光或无线电波敏感剂。

公开(公告)号：US5705573A

公开(公告)日：1998-01-06

申请号：US708677

申请日：1996-09-05

申请人： Douglas R. Swanson ,  Donald A. Tomalia

发明人： Douglas R. Swanson ,  Donald A. Tomalia

IPC分类号： C08F8/00

CPC分类号： C08F8/32

摘要： A novel process for preparing poly(2-isopropenyl-2-oxazoline or oxazine) and its methyl methacrylate copolymer, which are useful as water borne curing agents, particularly in the non-stick coating industry. The process converts commercially available poly(methyl methacrylate) into poly(2-isopropenyl-2-oxazoline or oxazine) polymers or copolymers with methyl methacrylate, while circumventing the use of the highly toxic monomer, 2-isopropenyl-2-oxazoline or oxazine. The process involves converting a poly(methacrylic ester) to the corresponding poly(.beta.-hydroxy-N-ethyl or propyl methacrylamide) and activating the ring-forming .beta.-hydroxy-N-ethyl or propyl methacrylamide moiety to form an oxazoline or oxazine ring.

摘要翻译： 制备聚（2-异丙烯基-2-恶唑啉或恶嗪）及其甲基丙烯酸甲酯共​​聚物的新方法，其可用作水性固化剂，特别是在不粘涂料工业中。 该方法将市售的聚（甲基丙烯酸甲酯）转化成聚（2-异丙烯基-2-恶唑啉或恶嗪）聚合物或与甲基丙烯酸甲酯共​​聚物，同时避免使用高毒性单体2-异丙烯基-2-恶唑啉或恶嗪。 该方法包括将聚（甲基丙烯酸酯）转化为相应的聚（β-羟基-N-乙基或丙基甲基丙烯酰胺）并活化成环β-羟基-N-乙基或丙基甲基丙烯酰胺部分以形成恶唑啉或恶嗪环 。

公开(公告)号：US06635720B1

公开(公告)日：2003-10-21

申请号：US09913050

申请日：2002-01-24

申请人： Donald A. Tomalia ,  Srinivas Uppuluri ,  Douglas R. Swanson ,  Herbert M. Brothers, II

发明人： Donald A. Tomalia ,  Srinivas Uppuluri ,  Douglas R. Swanson ,  Herbert M. Brothers, II

IPC分类号： C08L7700

CPC分类号： C08G83/003 ,  C08G69/02 ,  C08G69/04 ,  C08G69/48 ,  Y10S424/16 ,  Y10S977/754 ,  Y10S977/788 ,  Y10S977/835

摘要： Core-shell tecto(dendrimers) useful in biomedicine, pharmaceuticals, personal care products, and in other ways analogous to the known uses for dendrimers, hypercomb branched polymers, and other dendritic polymers are the reaction product of a core dendritic polymer molecule having a plurality of terminal functional groups of a first type which are not reactive with each other, and a plurality of shell dendritic polymer molecules having a plurality of terminal functional groups of a second type which are not reactive with each other, but which are reactive with the terminal functional groups of the first type. Each of the shell dendritic polymer molecules is chemically bonded to the core dendritic polymer molecule by a reaction of at least one of the terminal functional groups of the second type with at least one of the terminal functional groups of the first type.

摘要翻译： 可用于生物医学，药物，个人护理产品的核壳结构（树枝状大分子），以及类似于已知用于树枝状大分子，超支化支化聚合物和其它树枝状聚合物的其它方式是具有多个核心树枝状聚合物分子的反应产物 不具有反应性的第一种类型的末端官能团，以及具有多个彼此不反应但与末端反应的第二类型的末端官能团的多个壳状树枝状聚合物分子 第一类功能组。 每个壳树枝状聚合物分子通过第二类型的至少一个末端官能团与至少一个第一类型的末端官能团的反应与核心树枝状聚合物分子化学键合。

公开(公告)号：US6020457A

公开(公告)日：2000-02-01

申请号：US941527

申请日：1997-09-30

申请人： June W. Klimash ,  Herbert M. Brothers, II ,  Douglas R. Swanson ,  Rui Yin ,  Ralph Spindler ,  Donald A. Tomalia ,  Yong Hsu ,  Roberta C. Cheng

发明人： June W. Klimash ,  Herbert M. Brothers, II ,  Douglas R. Swanson ,  Rui Yin ,  Ralph Spindler ,  Donald A. Tomalia ,  Yong Hsu ,  Roberta C. Cheng

IPC分类号： C08G83/00 ,  C08G69/00 ,  C08G73/00

CPC分类号： C08G83/003 ,  B82Y30/00 ,  B82Y40/00 ,  Y10S424/16

摘要： Dendritic polymers containing disulfide functional groups which are essentially inert under non-reducing conditions, but which form sulfhydryl groups upon being subjected to a reducing agent are prepared by synthesizing dendritic polymers having a core with a disulfide linkage or by reacting a dendritic polymer with a molecule containing a disulfide linkage and reactive terminal groups. In one aspect of the invention, dendritic polymers having a single disulfide functional group at the core are provided. The single disulfide group at the core can be reduced to form two sulfhydryl groups to which other molecules, such as proteins, oligonucleotides, peptides, hormones, other dendritic polymers, non-dendritic polymers, etc., can be bound. Applications for the disulfide functionalized dendritic polymers include formation of differentiated dendrimers, formation of binding reagents for diagnostics, drug delivery, gene therapy and magnetic resins imaging, and in the preparation of self-assembled dendrimer monolayers on a quartz crystal resonators to provide dendrimer-modified electrodes which are useful for detecting various ions or molecules. In another aspect of the invention, dendritic polymers having sulfhydryl terminals are provided. The sulfhydryl terminated dendritic polymers can be used to prepare stable, curable resins composition which can undergo cross linking when subjected to a reducing agent.

摘要翻译： 通过合成具有核心与二硫键的树枝状聚合物或通过使树枝状聚合物与分子反应而制备的含二硫键官能团的树枝状聚合物在非还原条件下基本上为惰性但在形成巯基后形成巯基的树枝状聚合物 含有二硫键和反应性末端基团。 在本发明的一个方面，提供了在核心具有单个二硫键官能团的树枝状聚合物。 可以将核心上的单个二硫基团还原形成两个巯基，其中可以结合其它分子，例如蛋白质，寡核苷酸，肽，激素，其他树状聚合物，非树枝状聚合物等。 用于二硫化物官能化树枝状聚合物的应用包括形成分化的树枝状大分子，形成用于诊断的结合试剂，药物递送，基因治疗和磁性树脂成像，以及在石英晶体共振器上制备自组装树枝状聚合物单层以提供树枝状聚合物修饰 用于检测各种离子或分子的电极。 在本发明的另一方面，提供了具有巯基末端的树枝状聚合物。 巯基封端的树枝状聚合物可用于制备当经受还原剂时可以进行交联的稳定的可固化树脂组合物。

公开(公告)号：US5631329A

公开(公告)日：1997-05-20

申请号：US408833

申请日：1995-03-21

申请人： Rui Yin ,  Donald A. Tomalia ,  David M. Hedstrand ,  Douglas R. Swanson

发明人： Rui Yin ,  Donald A. Tomalia ,  David M. Hedstrand ,  Douglas R. Swanson

IPC分类号： A61K47/48 ,  C08G69/44 ,  C08G69/48 ,  C08G73/02 ,  C08G83/00 ,  C08G85/00 ,  C08F293/00

CPC分类号： B82Y5/00 ,  A61K47/48961 ,  C08G69/44 ,  C08G69/48 ,  C08G73/0206 ,  C08G73/0233 ,  C08G83/005 ,  C08G85/00 ,  Y10S525/902

摘要： The specification discloses a process for producing poly-branched polymer having relatively high molecular weight by forming a first set of branches by polymerizing monomers which are either protected against or are non-reactive to branching and grafting during polymerization, grafting that first set of branches to a core having a plurality of reactive sites capable of reacting with the reactive end units of said branches, either deprotecting or activating a plurality of monomeric units on each of said branches to create branch reactive sites, forming a second set of branches in the same manner as the first set of branches were formed, grafting the second set of branches to the first set of branches by reacting the reactive end units of the second set of branches with each said branch reactive site on said first set of branches and repeating the foregoing steps reiteratively to form and attach subsequent sets of branches to prior branch sets until a desired number of iterations has been effected.

摘要翻译： 本说明书公开了一种制备具有相对较高分子量的多支化聚合物的方法，通过聚合单体聚合形成第一组分支，所述单体在聚合过程中被保护为不支化或不反应支化和接枝，将第一组分支移植到 具有能够与所述分支的反应性末端单元反应的多个反应性位点的核心，在每个所述分支上去保护或活化多个单体单元以产生分支反应位点，以相同方式形成第二组分支 作为第一组分支形成，通过使第二组分支的反应性末端单元与所述第一组分支上的每个所述分支反应位点反应，将第二组分支移植到第一组分支，并重复上述步骤 重复地将随后的分支集合形成并附加到先前的分支集合，直到所需的迭代次数为蜜蜂 n影响。