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    Cationic polymers formed from amino group-bearing monomers and heterocyclic linkers
    1.
    发明授权
    Cationic polymers formed from amino group-bearing monomers and heterocyclic linkers 有权
    由含氨基的单体和杂环接头形成的阳离子聚合物

    公开(公告)号：US09163107B2

    公开(公告)日：2015-10-20

    申请号：US13977973

    申请日：2012-01-05

    申请人： Tuo Jin ,  Shiyue Duan

    发明人： Tuo Jin ,  Shiyue Duan

    IPC分类号： C08G12/06 ,  C08G73/02 ,  A61K9/50 ,  A61K47/34 ,  C08G73/18 ,  C12N15/87 ,  C12N11/08 ,  A61K47/30 ,  A61K48/00

    CPC分类号： C08G12/06 ,  A61K9/5031 ,  A61K47/34 ,  C08G73/0273 ,  C08G73/18 ,  C12N15/87

    摘要： The present invention is directed to a design of and a method to synthesize polycations for gene (DNA and RNA) delivery. According to this design, the polycations (also said cationic polymers) are formed by polymerization of endogenous monomers bearing sufficient amino groups through degradable bonds with linker molecules. The amino group-bearing monomers are those naturally existing or nontoxic to human body. The linker molecules are those which are not only degradable to nontoxic fragments but also able to release the amino group-bearing monomers in their native state upon degradation. Some examples for the endogenous amino group-bearing monomers are spermine and spermidine (or their derivatives). Examples for the degradable chemical bonds formed between the amino group-bearing monomers are imines. In order to improve degradability or proton sponging effect, low pKa (

    摘要翻译： 本发明涉及用于合成基因（DNA和RNA）递送聚阳离子的设计和方法。 根据该设计，聚阳离子聚合物（也称为阳离子聚合物）通过具有足够氨基的内源单体通过可降解键与连接分子的聚合形成。 含氨基的单体是天然存在的或对人体无毒的单体。 连接子分子是不仅可降解成无毒片段的那些，而且还能够在降解时以其天然状态释放带氨基的单体。 内源性含氨基单体的一些实例是精胺和亚精胺（或其衍生物）。 在含氨基的单体之间形成的可降解化学键的实例是亚胺。 为了提高降解性或质子海绵效应，低pKa（<8）氨基，通过聚合物降解产生的游离氨基（例如由亚胺键降解产生的那些）或其它给电子基团 因为咪唑，吡唑，吡啶，嘧啶或甚至苯被并入两个（或三个）反应性基团之间的接头中，用于连接含氨基的单体。 这些聚阳离子载体体系可用于纳米包封和转染基因材料。

    Polysaccharide Microparticles Containing Biological Agents: Their Preparation and Applications
    2.
    发明申请
    Polysaccharide Microparticles Containing Biological Agents: Their Preparation and Applications 有权
    含有生物制剂的多糖微粒：的制备与应用

    公开(公告)号：US20080248098A1

    公开(公告)日：2008-10-09

    申请号：US12065310

    申请日：2006-07-20

    申请人： Tuo Jin ,  Fei Wu ,  Weien Yuan

    发明人： Tuo Jin ,  Fei Wu ,  Weien Yuan

    IPC分类号： A61K9/127 ,  A61K47/36 ,  A61K38/02 ,  A61K38/16 ,  A61K47/38 ,  A61P43/00 ,  A61K9/14 ,  A61K31/7052 ,  A61K39/00 ,  A61K39/395

    CPC分类号： A61K9/1694 ,  A61K9/0024 ,  A61K9/1623 ,  A61K9/1647 ,  A61K9/1652 ,  A61K9/19 ,  A61K9/7007 ,  A61K39/00 ,  A61L27/48 ,  A61L31/10 ,  A61L31/129

    摘要： A method of preparing polysaccharide glassy microparticles which are less than 10 μum in diameter and contain structurally delicate agents, such as proteins, peptides, gene materials, vaccines, antibodies, viruses and liposomes using low-temperature aqueous-aqueous emulsification (free of polyelectrolytes) and freezing-induced phase separation. When delicate agents are added to a polysaccharide-PEG two phase system followed by homogenization (or other shear adding process), the agents partition into the polysaccharide dispersed phase preferentially. These processes help to avoid aggregation of proteins caused by interaction with charged polyelectrolytes used for stabilizing the polysaccharide dispersed phase in our previously reported aqueous-aqueous emulsion. When this system is frozen and lyophilized, glassy particles less than 10 μm in diameter containing delicate agents can be formed. These fine polysaccharide particles protect proteins within their hydrophilic glassy matrix, and can therefore be easily suspended in hydrophobic polymer solutions and formulated to various forms of sustained release devices such microsphere, sheets, fibers, coating layers, and scaffolds. The particles can also be dispersed in hydrophilic gels to improve releasing kinetics and to deliver vaccines and antibodies for immune therapy.

    摘要翻译： 一种制备多糖玻璃状微粒的方法，其使用低温水性乳化（不含聚电解质），其直径小于10um，并含有结构上脆弱的物质，例如蛋白质，肽，基因材料，疫苗，抗体，病毒和脂质体。 和冷冻诱导相分离。 当将精制剂加入到多糖-PEG两相体系中，随后进行均质化（或其他剪切加料法）时，试剂优先分配到多糖分散相中。 这些过程有助于避免与我们以前报道的水性乳液中稳定多糖分散相的带电聚电解质相互作用引起的蛋白质聚集。 当该系统被冷冻和冻干时，可以形成含有微细剂的直径小于10微米的玻璃状颗粒。 这些细多糖颗粒保护其亲水性玻璃质基质内的蛋白质，因此可以容易地悬浮在疏水性聚合物溶液中并配制成各种形式的缓释装置如微球，片，纤维，涂层和支架。 颗粒也可以分散在亲水性凝胶中，以改善释放动力学和递送用于免疫治疗的疫苗和抗体。

    FABRICATION PROCESS OF PHASE-TRANSITION MICRONEEDLE PATCH
    4.
    发明申请
    FABRICATION PROCESS OF PHASE-TRANSITION MICRONEEDLE PATCH 审中-公开
    相转移麦克风贴片的制造工艺

    公开(公告)号：US20160158511A1

    公开(公告)日：2016-06-09

    申请号：US14906857

    申请日：2014-07-22

    申请人： Tuo JIN

    发明人： Tuo Jin

    IPC分类号： A61M37/00 ,  B29C65/00 ,  B29C69/00 ,  B29C39/02 ,  B29C39/42

    CPC分类号： A61M37/0015 ,  A61K9/0021 ,  A61M2037/0023 ,  A61M2037/0046 ,  A61M2037/0053 ,  B29C39/026 ,  B29C39/42 ,  B29C65/002 ,  B29C69/00 ,  B29K2029/04 ,  B29K2105/0035 ,  B29K2105/0073 ,  B29K2827/18 ,  B29L2031/753

    摘要： The application discloses a method to fabricate microneedle patches, comprising a) casting (painting and pasting) an aqueous polymer solution on a mold of array of micro-holes which is made of porous materials; b) sucking the polymer solution into the micro-holes by applying vacuum at the back of the mold; d) freezing and thawing the casted polymer solution to induce gelation; and e) drying the gelled polymer solution. Specifically, the present invention describes a process and composition of polymeric microneedlepatch which overcomes the limitations of existing microneedles systems and may be used for transdermal delivery system for therapeutics and other applications.

    摘要翻译： 该申请公开了一种制造微针贴片的方法，其包括：a）在由多孔材料制成的微孔阵列的模具上铸造（涂覆和粘贴）聚合物水溶液; b）通过在模具背面施加真空将聚合物溶液吸入微孔中; d）冷冻和融化浇铸的聚合物溶液以引起凝胶化; 和e）干燥胶凝聚合物溶液。 具体地，本发明描述了克服现有微针系统的限制的聚合物微针装置的方法和组合物，并且可用于治疗剂和其它应用的透皮递送系统。

    Phase-transition polymeric microneedles
    5.
    发明授权
    Phase-transition polymeric microneedles 有权
    相转移聚合物微针

    公开(公告)号：US09320878B2

    公开(公告)日：2016-04-26

    申请号：US13122873

    申请日：2009-05-12

    申请人： Tuo Jin

    发明人： Tuo Jin

    IPC分类号： A61K9/00 ,  A61K38/00 ,  A61K39/00 ,  A61K48/00 ,  A61K38/28 ,  A61P3/10 ,  A61M37/00

    CPC分类号： A61M37/0015 ,  A61K9/0021 ,  A61M2037/0023 ,  A61M2037/0046 ,  A61M2037/0053

    摘要： This invention discloses a novel microneedle system, phase-transition microneedles (PTM), of which the microneedles formed of hydrophilic polymers are swelling but insoluble when absorbing water due to their internal cross-linked network through microcrystalline domains functioning as cross-linking junctions. The microneedles are sufficiently hard to penetrate the epidermis of the skin at dry state, but are converted to hydrogel state to release their loaded cargos by absorbing the body fluid in the dermis layer, and able to be withdrawn from the skin completely (without depositing needle tip materials in the skin) because of their insoluble network. Moreover, formation of the insoluble polymeric network through microcrystalline domains of PTM is achieved by a mild freeze-thaw treatment, for which bio-active agents may be loaded safely in the microneedle tips by adding in the polymer solution prior to molding without denaturing.

    摘要翻译： 本发明公开了一种新型的微针系统，相转移微针（PTM），其亲水性聚合物形成的微针由于其内部交联网络通过用作交联结的微晶畴吸收水而溶胀而不溶。 微针足以在干燥状态下穿透皮肤的表皮，但通过吸收真皮层中的体液而转化为水凝胶状态以释放其装载的载体，并且能够完全从皮肤中取出 皮肤上的尖端物质），因为它们的不溶性网络。 此外，通过PTM的微晶畴形成不溶性聚合物网络是通过温和的冷冻 - 融化处理实现的，通过在模塑之前加入聚合物溶液中，生物活性剂可以安全地负载在微针尖端中，而不变性。

    PROCESS FOR PRODUCING POLYMERIC MICROSPHERES
    7.
    发明申请
    PROCESS FOR PRODUCING POLYMERIC MICROSPHERES 审中-公开

    公开(公告)号：US20180116962A1

    公开(公告)日：2018-05-03

    申请号：US15567840

    申请日：2016-01-21

    申请人： Tuo Jin

    发明人： Tuo Jin

    IPC分类号： A61K9/16 ,  A61K38/26 ,  A61K38/18

    CPC分类号： A61K9/1694 ,  A61K9/0019 ,  A61K9/1647 ,  A61K38/1816 ,  A61K38/26

    摘要： The present invention disclosure disclosed a microsphere-producing process involving three integrated unit operations, 1) microspheres formation; 2) microsphere quality control; 3) post formation microsphere treatment. The first unit operation, i.e. unit operation 1) is integrated with four essential functions: forcing the particle forming materials to pass through a porous membrane to form embryonic micropsheres; enforcing the embryonic microspheres to detach the porous membrane; solidifying the embryonic microspheres; collecting and outputting the solidified microspheres. The quality control unit operation consists discrimination and ejection of oversized microspheres. The post treatment unit operation is integrated with two essential functions, smoothing the microsphere surfaces and reducing organic solvents trapped inside of microsphere matrix.

    MICROSPHERES FOR CONTROLLED- OR SUSTAINED-RELEASE DELIVERY OF THERAPEUTICS
    8.
    发明申请
    MICROSPHERES FOR CONTROLLED- OR SUSTAINED-RELEASE DELIVERY OF THERAPEUTICS 有权
    用于控制或持续释放治疗药物的微生物

    公开(公告)号：US20140314853A1

    公开(公告)日：2014-10-23

    申请号：US14362575

    申请日：2012-12-05

    申请人： Tuo Jin ,  Zhenhua Hu ,  Weien Yuan

    发明人： Tuo Jin ,  Zhenhua Hu ,  Weien Yuan

    IPC分类号： A61K9/16 ,  A61K38/31 ,  A61K38/25 ,  A61K38/22 ,  A61K38/26 ,  A61K38/23

    CPC分类号： A61K9/1647 ,  A61K9/1611 ,  A61K9/1694 ,  A61K38/22 ,  A61K38/23 ,  A61K38/25 ,  A61K38/26 ,  A61K38/31

    摘要： A new microsphere formulation (composition) for controlled- or sustained-release delivery of therapeutic ingredient(s), mainly peptides and proteins not over 10K in molecular weight, comprises at least a therapeutic ingredient, a helping agent (such as PH sensitive agent whose solubility is a function of pH) and a biodegradable polymer. The therapeutic ingredient(s) and the helping agent are in the form of fine particles, less than 1O um in diameter, encapsulated in the polymer which forms the microsphere matrix. A method for preparing the composition comprises a step of in-situ precipitating the therapeutic ingredient(s) and the helping agent to the fine particles and successive steps for forming the microspheres. Such a microsphere formulation offers a well-controlled release profile for prolonged period and encapsulation efficiency over 95%.

    摘要翻译： 治疗成分（主要是分子量不超过10K的肽和蛋白质）的受控或持续释放递送的新的微球制剂（组合物）至少包含治疗成分，助剂（例如PH敏感剂 溶解度是pH的函数）和可生物降解的聚合物。 治疗成分和助剂为直径小于10μm的细颗粒形式，包封在形成微球基质的聚合物中。 制备组合物的方法包括将治疗成分和辅助剂原位沉淀到细颗粒和用于形成微球的连续步骤的步骤。 这种微球制剂提供了良好控制的释放曲线，其延长的时间和包封效率超过95％。

    POLYCATIONIC GENE CARRIERS FORMED OF ENDOGENOUS AMINO GROUP-BEARING MONOMERS
    9.
    发明申请
    POLYCATIONIC GENE CARRIERS FORMED OF ENDOGENOUS AMINO GROUP-BEARING MONOMERS 审中-公开
    内源性氨基团承载单体形成的聚合基因载体

    公开(公告)号：US20110076307A1

    公开(公告)日：2011-03-31

    申请号：US12843691

    申请日：2010-07-26

    申请人： Tuo Jin ,  Zixiu Du

    发明人： Tuo Jin ,  Zixiu Du

    IPC分类号： A61K9/00 ,  A61K31/7105 ,  A61K31/711 ,  A61P43/00 ,  C08G63/685 ,  C08G69/00 ,  C08G63/91 ,  C08G73/06 ,  C08G73/02

    CPC分类号： C12N15/87 ,  A61K9/1271 ,  A61K9/1272 ,  A61K47/34 ,  A61K48/00

    摘要： The present invention is directed to a design of and a method to synthesize polycations for gene (DNA and RNA) delivery. According to this design, the polycations (also said cationic polymers) are formed by polymerization of endogenous monomers bearing sufficient amino groups through degradable bonds with linker molecules or with themselves. The amino group-bearing monomers are those naturally existing in or nontoxic to human body. The linker molecules are those which are not only degradable to nontoxic fragments but also able to release the amino group-bearing monomers in their native state upon degradation. Some examples for the endogenous amino group-bearing monomers are spermine, spermidine, serine or N,N-dimethyl serine, and histidine. Examples for the degradable chemical bonds formed between the amino group-bearing monomers are carbamate, imine, amide, carbonate, and ester. In order to improve degradability or proton sponging effect, low pKa (

    摘要翻译： 本发明涉及用于合成基因（DNA和RNA）递送聚阳离子的设计和方法。 根据该设计，聚阳离子聚合物（也称为阳离子聚合物）通过具有足够氨基的内源单体通过可降解键与连接分子或其自身聚合形成。 含氨基的单体是天然存在于人体或对人体无毒的单体。 连接子分子是不仅可降解成无毒片段的那些，而且还能够在降解时以其天然状态释放含氨基的单体。 内源性含氨基单体的一些实例是精胺，亚精胺，丝氨酸或N，N-二甲基丝氨酸和组氨酸。 在含有氨基的单体之间形成的可降解化学键的实例是氨基甲酸酯，亚胺，酰胺，碳酸酯和酯。 为了提高降解性或质子海绵效应，将低pKa（<8）氨基或其他给电子基团引入两个（或三个）反应性基团之间的连接基中，用于连接含氨基的 单体。 这些聚阳离子载体体系可用于纳米包封和转染基因材料。

    Aquespheres, their preparation and uses thereof
    10.
    发明授权
    Aquespheres, their preparation and uses thereof 失效

    公开(公告)号：US06998393B2

    公开(公告)日：2006-02-14

    申请号：US10291327

    申请日：2002-11-08

    申请人： Tuo Jin ,  Hua Zhu ,  Jiahao Zhu

    发明人： Tuo Jin ,  Hua Zhu ,  Jiahao Zhu

    IPC分类号： A61K9/62

    CPC分类号： A61K9/0043 ,  A61K9/0024 ,  A61K9/0073 ,  A61K9/1075 ,  A61K9/113 ,  A61K9/1652 ,  A61K9/19 ,  A61K9/5031 ,  A61K9/5036 ,  A61K9/5073 ,  A61K38/00

    摘要： This invention provides method for sustained release delivery of structurally delicate agents such as proteins and peptides. Using a unique emulsion system (Stable polymer aqueous-aqueous emulsion), proteins and peptides can be microencapsulated in polysacchride glassy particles under a condition free of any chemical or physical hazard such as organic solvents, strong interfacial tension, strong shears, elevated temperature, large amount of surfactants, and cross-linking agents. Proteins loaded in these glassy particles showed strong resistance to organic solvents, prolonged activity in hydrated state, and an excellent sustained release profile with minimal burst and incomplete release when being further loaded in degradable polymer microspheres. This invention provides a simple yet effective approach to address all the technical challenges raised in sustained release delivery of proteins.