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1. 发明申请

WO2016131363A1 PROCESS FOR PRODUCING POLYMERIC MICROSPHERES 审中-公开
标题翻译：生产聚合物微球的方法
公开(公告)号：WO2016131363A1
公开(公告)日：2016-08-25
申请号：PCT/CN2016/071572
申请日：2016-01-21
申请人： JIN, Tuo
发明人： JIN, Tuo
IPC分类号： A61K9/14
CPC分类号： A61K9/1694 , A61K9/0019 , A61K9/1647 , A61K38/1816 , A61K38/26
摘要： Disclosed a microsphere-producing process involving three integrated unit operations: 1) microspheres formation; 2) microspheres quality control; 3) post formation microspheres treatment. The first unit operation is integrated with four essential functions: forcing the particle forming materials to pass through a porous membrane to form embryonic microsphere; 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 of 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.
摘要翻译：公开了涉及三个一体化单元操作的微球制备方法：1）微球形成; 2）微球质量控制; 3）后形成微球处理。第一个单元操作集成了四个基本功能：强制成粒材料通过多孔膜形成胚胎微球; 强化胚胎微球分离多孔膜; 凝固胚胎微球; 收集和输出凝固的微球。质量控制单元的操作包括歧视和超大尺寸微球的排出。后处理单元操作集成了两个基本功能：平滑微球表面和还原被捕获在微球体内部的有机溶剂。

2. 发明申请

WO2009100645A1 POLYCATIONIC GENE CARRIERS FORMED OF ENDOGENOUS AMINO GROUP-BEARING MONOMERS 审中-公开
标题翻译：内源性氨基团承载单体形成的聚合基因载体
公开(公告)号：WO2009100645A1
公开(公告)日：2009-08-20
申请号：PCT/CN2009/000116
申请日：2009-01-24
申请人： JIN, Tuo , DU, Zixiu
发明人： JIN, Tuo , DU, Zixiu
IPC分类号： C12N11/08 , A61K9/50 , A61K47/30 , A61K48/00
CPC分类号： C12N15/87 , A61K9/1271 , A61K9/1272 , A61K47/34 , A61K48/00
摘要： A cationic polymer formed of and degradable to human endogenous amino group-bearing monomers can be used for gene (DNA and RNA) delivery. The cationic polymer is 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, such as spermine, spermidine, serine, N,N-dimethyl serine, and histidine. The linker molecules are those which are not only degradable to nontoxic fragments but also able to release the amino group-bearing monomers as their native state upon degradation. Examples for the degradable chemical bonds are carbamate, imine, amide, carbonate, and ester.
摘要翻译：由人内源性氨基负载单体形成并可降解的阳离子聚合物可用于基因（DNA和RNA）递送。通过使具有足够氨基的内源性单体通过可降解的键与接头分子或其自身聚合形成阳离子聚合物。含氨基的单体是天然存在于人体中或无毒无机的单体，如精胺，亚精胺，丝氨酸，N，N-二甲基丝氨酸和组氨酸。连接子分子是不仅可以降解成无毒片段，而且能够在降解时释放带氨基的单体作为其天然状态。可降解化学键的实例是氨基甲酸酯，亚胺，酰胺，碳酸酯和酯。

3. 发明申请

WO2015010599A1 FABRICATION PROCESS OF PHASE-TRANSITION MICRONEEDLE PATCH 审中-公开
标题翻译：相转移麦克风贴片的制造工艺
公开(公告)号：WO2015010599A1
公开(公告)日：2015-01-29
申请号：PCT/CN2014/082699
申请日：2014-07-22
申请人： JIN, Tuo
发明人： JIN, Tuo
IPC分类号： A61M31/00 , A61M37/00 , A61K39/00
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。

4. 发明申请

WO2014139168A1 PREPARATION PROCESS OF POLYMERIC MICROSPHERES 审中-公开
标题翻译：聚合微球的制备工艺
公开(公告)号：WO2014139168A1
公开(公告)日：2014-09-18
申请号：PCT/CN2013/072749
申请日：2013-03-15
申请人： JIN, Tuo
发明人： JIN, Tuo
IPC分类号： A61K9/16 , A61J3/00 , A61K38/22 , A61P3/10
CPC分类号： A61K9/1694 , A61K9/1611 , A61K9/1647 , A61K38/1816 , A61K38/193 , A61K38/21 , A61K38/23 , A61K38/26 , A61K38/27 , A61K38/37
摘要： The present invention disclosed a microsphere-producing process involving three essential elementary steps, 1) forcing the particle forming materials to pass through a porous wall; 2) solidifying the embryonic microspheres come out through the porous wall without breaking and fusing (between the particles); 3) collecting and/or outputting the solidified microspheres. This invention also comprises an apparatus to enable the unit operations of the invented process. The apparatus consists an embryonic microsphere-forming unit, a stirring-free microsphere hardening unit, and a microsphere collecting unit and a microsphere out-putting unit.
摘要翻译：本发明公开了一种涉及三个基本步骤的微球制备方法，1）迫使成粒材料通过多孔壁; 2）固化胚胎微球通过多孔壁出来，不破裂和融合（颗粒之间）; 3）收集和/或输出凝固的微球。本发明还包括能够实现本发明方法的单元操作的装置。该装置包括胚胎微球形成单元，无搅拌微球固化单元和微球收集单元和微球输出单元。

5. 发明申请

WO2013083041A1 MICROSPHERES FOR CONTROLLED- OR SUSTAINED-RELEASE DELIVERY OF THERAPEUTICS 审中-公开
标题翻译：用于控制或持续释放治疗药物的微生物
公开(公告)号：WO2013083041A1
公开(公告)日：2013-06-13
申请号：PCT/CN2012/085930
申请日：2012-12-05
申请人： JIN, Tuo
发明人： JIN, Tuo , HU, Zhenhua , YUAN, Weien
IPC分类号： A61K9/16 , A61K9/52 , A61K38/22 , A61P3/10 , A61J3/00
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 lOum 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。治疗成分和助剂是直径小于10μm的细颗粒的形式，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％。

6. 发明申请

WO2012092865A1 CATIONIC POLYMERS FORMED FROM AMINO GROUP-BEARING MONOMERS AND HETEROCYCLIC LINKERS 审中-公开
标题翻译：从氨基团轴承单体和杂环连接体形成的阳离子聚合物
公开(公告)号：WO2012092865A1
公开(公告)日：2012-07-12
申请号：PCT/CN2012/070055
申请日：2012-01-05
申请人： JIN, Tuo , DUAN, Shiyue
发明人： JIN, Tuo , DUAN, Shiyue
IPC分类号： C08G73/02 , C12N11/08 , A61K47/30 , A61K48/00 , A61K9/50
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含氨基的单体。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。

7. 发明申请

WO2010148653A1 POLYMER VESICLES OF ASYMMETRIC MEMBRANE 审中-公开
标题翻译：不对称膜的聚合物Vesic
公开(公告)号：WO2010148653A1
公开(公告)日：2010-12-29
申请号：PCT/CN2010/000968
申请日：2010-06-28
申请人： SHANGHAI JIAO TONG UNIVERSITY , JIN, Tuo , ZHANG, Yulong
发明人： JIN, Tuo , ZHANG, Yulong
IPC分类号： A61K9/51 , A61K31/715 , A61K31/74 , A61K47/34 , C08J3/07
CPC分类号： A61K31/715 , A61K9/1273 , A61K9/5146 , A61K9/5153 , A61K31/74 , A61K47/34 , C08J3/07
摘要： This invention demonstrated a new polymer vesicle system structured with an asymmetric membrane which is formed from two amphiphilic di-block (A-B type) copolymers having different hydrophilic blocks or from a tri-block copolymer (A-B-C type) with two different hydrophilic blocks at each end. With this system bio-molecules or macromolecules can be nano- or submicron encapsulated by thermodynamic partition and be stabilized thermodynamically. This system is applicable in particulate and delivery of bio-therapeutics. What equally important in this invention is the method for forming polymer vesicles of asymmetric membrane: phase-guided self-assembly. This method involving hydrophilic two-phase system to guide the block copolymers above to align on the hydrophilic interface in designed orientation. This method will have great application in functionizing or bio-functionizing particulate surfaces.
摘要翻译：本发明证明了一种新型的聚合物囊泡系统，其结构为不对称膜，其由具有不同亲水嵌段的两个两亲性二嵌段（AB型）共聚物或三端嵌段共聚物（ABC型）形成，每个末端具有两个不同的亲水嵌段。通过该系统，生物分子或大分子可以通过热力学分隔进行纳米或亚微米封装，并在热力学上稳定。该系统适用于生物治疗的颗粒物和递送。在本发明中同样重要的是形成非对称膜的聚合物囊泡的方法：相位引导的自组装。该方法涉及亲水性两相体系以引导上述嵌段共聚物以在设计取向的亲水界面上取向。这种方法在颗粒表面的功能化或生物功能化方面将具有很大的应用。

8. 发明申请

WO2010040271A1 PHASE-TRANSITION POLYMERIC MICRONEEDLES 审中-公开
标题翻译：相转移聚合物微球
公开(公告)号：WO2010040271A1
公开(公告)日：2010-04-15
申请号：PCT/CN2009/000510
申请日：2009-05-12
申请人： JIN, Tuo
发明人： JIN, Tuo
IPC分类号： A61M31/00 , A61M37/00 , A61K39/00
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 microneedle patch, which overcomes all the limitations that existing microneedles encountered. The microneedle patch is formed of an integrated polymeric piece consisting of a microneedle array and a plate (called holding plate) on which the needles stand. The microneedles of the patch are hard and strong enough to penetrate epidermis at dry state but turn to be hydrogel state soft and permeable to hydrophilic agents when absorbing body fluid. The hydrogel state of the patch is a hydrophilic network held by physical or chemical cross-linking junctions. The pores of the network are opened up by body fluid for drugs and macromolecules to diffuse through. The polymeric materials used to form the microneedle patch have been used in the pharmaceutical field for years and have proven compatibility with the skin and with proteins. The drugs may be stored in the matrix of the microneedle array as well as the holding plate so that the requirement for high dose applications may be full filled. In addition, molding (casting) of this type of microneedle patch is simple, easy to achieve and needs no microfabrication systems and organic solvents. By a programmed molding (casting), the patch may be assembled in a layered structure with desired drug concentration in each layer, respectively. Due to this design, a programmed pulse or a zero order release of drugs may easily be achieved. In addition, delicate proteins loaded in the patch are kept in a dry and hydrophilic glassy state before being released, the most favored state for protein storage. Finally, during the swelling-based drug release, the microneedle patch increases their thickness gradually between the skin and the back cover (which holds the needles) to create a sustained pressure to ensure good contact of the microneedles inside epidermis.
摘要翻译：本发明公开了一种新颖的微针系统，相变微针贴片，克服了现有微针遇到的所有限制。微针贴片是由一个由微针阵列和针（所谓的保持板）组成的整体聚合物片形成的，针架在其上。贴剂的微针硬度足够强，能够在干燥状态下穿透表皮，但是当吸收体液时，水凝胶状态变得柔软，可渗透亲水剂。贴剂的水凝胶状态是由物理或化学交联结合物保持的亲水网络。通过体液打开网络孔，使药物和大分子扩散通过。用于形成微针贴片的聚合物材料已经在制药领域中使用了多年，并已经证明与皮肤和蛋白质的相容性。药物可以储存在微针阵列和保持板的基质中，使得高剂量应用的需求可以被充满。此外，这种微针贴片的成型（铸造）简单，易于实现，不需要微细加工系统和有机溶剂。通过编程成型（铸造），贴片可以分别以每层中所需药物浓度的层状结构组装。由于该设计，可以容易地实现编程脉冲或零次释放药物。此外，装载在贴片中的精细蛋白质在被释放之前保持在干燥和亲水的玻璃状态，这是最有利的蛋白质储存状态。最后，在基于溶胀的药物释放期间，微针贴片在皮肤和后盖（保持针头）之间逐渐增加它们的厚度，以产生持续的压力，以确保表皮中的微针的良好接触。

9. 发明申请

WO2003101600A3 HAZARD-FREE MICROENCAPSULATION FOR STRUCTURALLY DELICATE AGENTS, AN APPLICATION OF STABLE AQUEOUS-AQUEOUS EMULSION 审中-公开
公开(公告)号：WO2003101600A3
公开(公告)日：2003-12-11
申请号：PCT/CN2003/000431
申请日：2003-06-03
申请人： JIN, Tuo
发明人： JIN, Tuo , ZHU, Hua , ZHU, Jiahao
IPC分类号： A61K9/107 , A61K9/50 , A61K38/00 , A61K39/12
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.

10. 发明申请

WO2008141496A1 SUSTAINED-RELEASE SYSTEM FOR EPO AND GM-CSF 审中-公开
标题翻译： EPO和GM-CSF的持续释放系统
公开(公告)号：WO2008141496A1
公开(公告)日：2008-11-27
申请号：PCT/CN2007/002962
申请日：2007-10-16
申请人： JIN, Tuo , GENG, Yan , WU, Fei , YUAN, Weien
发明人： JIN, Tuo , GENG, Yan , WU, Fei , YUAN, Weien
IPC分类号： A61K9/16 , A61K38/18 , A61K38/19 , A61K47/34 , A61K47/36 , A61P9/04 , A61P35/00
CPC分类号： A61K47/36 , A61K9/1652 , A61K9/19 , A61K38/1816 , A61K38/193
摘要： This patent disclosed sustained-release microsphere dosage forms of EPO and GM-CSF respectively and methods for their preparation. The proteins are first loaded in solvent-resistant polysaccharide particles using a stabilized aqueous-aqueous emulsion consisting of polysaccharide dispersed phase and polyethylene glycol (PEG) continuous phase, followed by freeze-drying. This particle forming process avoids exposing proteins to water-oil or water-air (or intra-particle cross-linking reagent), factors known to denature proteins. The lyophilized powder was then washed using organic solvent to remove the PEG continuous phase. The proteins loaded in the solvent-resistant polysaccharide particles can easily be sustained-release microsphere formulation without denaturing, aggregation, adsorption and deactivation.
摘要翻译：该专利公开了EPO和GM-CSF的缓释微球剂形式及其制备方法。首先使用由多糖分散相和聚乙二醇（PEG）连续相组成的稳定的水性乳液将蛋白质负载在耐溶剂的多糖颗粒中，然后冷冻干燥。这种颗粒形成过程避免将蛋白质暴露于已知会使蛋白质变性的因素的水油或水 - 空气（或颗粒内交联试剂）中。然后使用有机溶剂洗涤冻干的粉末以除去PEG连续相。负载在耐溶剂的多糖颗粒中的蛋白质可以容易地是缓释微球制剂，而不变性，聚集，吸附和失活。

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