公开(公告)号：US20140017300A1

公开(公告)日：2014-01-16

申请号：US13940116

申请日：2013-07-11

申请人： Keelung Hong ,  Wei-Wen Zheng ,  Daryl C. Drummond ,  Dmitri B. Kirpotin ,  Mark Eamon Hayes

发明人： Keelung Hong ,  Wei-Wen Zheng ,  Daryl C. Drummond ,  Dmitri B. Kirpotin ,  Mark Eamon Hayes

IPC分类号： A61K9/127 ,  A61K31/711

CPC分类号： A61K9/1272 ,  A61K9/127 ,  A61K9/1271 ,  A61K31/711 ,  A61K48/0025 ,  A61K48/0041 ,  A61K48/0091

摘要： Provided herein is a process for preparing a microparticulate complex of a particle-forming component (“PFC”) and a nucleic acid-like component (“NAC”) in a monophasic composition comprising water and a water-miscible organic solvent. Also provided is a microparticulate complex that comprises a particle-forming component complexed to a nucleic acid-like component, and a composition comprising water and the microparticulate complex. Further provided is a method of delivery of a nucleic acid-like component to a cell or to a patient by contacting the cell with or administering to the patient a composition comprising water and the microparticulate complex described herein. Still further, a charge-changing composition represented by the formula A-X—B is provided.

摘要翻译： 本文提供了在包含水和水混溶性有机溶剂的单相组合物中制备颗粒形成组分（“PFC”）和核酸样组分（“NAC”）的微粒复合物的方法。 还提供了包含与核酸样组分复合的颗粒形成组分的微粒复合物，以及包含水和微粒复合物的组合物。 还提供了通过使细胞与患者接触或给予患者包含水和本文所述的微粒复合物的组合物将核酸样成分递送至细胞或患者的方法。 此外，提供了由式A-X-B表示的电荷变化组合物。

公开(公告)号：US20090171077A1

公开(公告)日：2009-07-02

申请号：US12401454

申请日：2009-03-10

申请人： Keelung Hong ,  Wei-Wen Zheng ,  Daryl C. Drummond ,  Dmitri B. Kirpotin ,  Mark Eamon Hayes

发明人： Keelung Hong ,  Wei-Wen Zheng ,  Daryl C. Drummond ,  Dmitri B. Kirpotin ,  Mark Eamon Hayes

IPC分类号： C07H21/00

CPC分类号： A61K9/1272 ,  A61K9/127 ,  A61K9/1271 ,  A61K31/711 ,  A61K48/0025 ,  A61K48/0041 ,  A61K48/0091

摘要： A process for preparing a microparticulate complex is provided. The process comprises (a) combining a particle-forming component (“PFC”) and a nucleic acid-like component (“NAC”) in a monophasic composition comprising water and a water-miscible, organic solvent to form a mixture wherein the PFC and the NAC are independently molecularly or micellarly soluble in the aqueous/organic solvent system, and (b) reducing the amount of the organic solvent in the mixture. This effects formation of the microparticulate complex of the NAC and the PFC. Also provided is a microparticulate complex that comprises a particle-forming component complexed to a nucleic acid-like component forming an approximately spherical particle, wherein the particle-forming component encloses an interior of the particle containing the nucleic acid-like component and the so-enclosed interior volume has less than about 50% (preferably less than 20%) of the volume containing free water. Also disclosed composition comprising water and particles of the microparticulate complex. According to the invention a nucleic acid-like component is delivered to a cell by (a) contacting the cell with a composition comprising water and the microparticulate complex, and (b) maintaining the contact for a time sufficient to allow the nucleic acid-based moiety to enter the cell. A therapeutic nucleic acid-like component is delivered into a patient in need thereof by administering a composition comprising water and particles of the microparticulate complex. Also disclosed is a charge-changing composition represented by the formula A-X-B, wherein X represents a chemical bond capable of irreversible dissociation in reaction to a factor in a physiological or bioprocess environment; A represents a molecular moiety that upon dissociation of the bond X produces a ionically charged product; and B represents a molecular moiety, which upon the dissociation of bond X, separates from the composition leaving the remaining ionically charged product more positive than that of A-X-B itself.

公开(公告)号：US08496961B2

公开(公告)日：2013-07-30

申请号：US10439856

申请日：2003-05-15

申请人： Keelung Hong ,  Wei-Wen Zheng ,  Daryl C. Drummond ,  Dmitri B. Kirpotin ,  Mark Eamon Hayes

发明人： Keelung Hong ,  Wei-Wen Zheng ,  Daryl C. Drummond ,  Dmitri B. Kirpotin ,  Mark Eamon Hayes

IPC分类号： A61K9/127

CPC分类号： A61K9/1272 ,  A61K9/127 ,  A61K9/1271 ,  A61K31/711 ,  A61K48/0025 ,  A61K48/0041 ,  A61K48/0091

摘要： A process for preparing a microparticulate complex is provided. The process comprises (a) combining a particle-forming component (“PFC”) and a nucleic acid-like component (“NAC”) in a monophasic composition comprising water and a water-miscible, organic solvent to form a mixture wherein the PFC and the NAC are independently molecularly or micellarly soluble in the aqueous/organic solvent system, and (b) reducing the amount of the organic solvent in the mixture. This effects formation of the microparticulate complex of the NAC and the PFC. Also provided is a microparticulate complex that comprises a particle-forming component complexed to a nucleic acid-like component forming an approximately spherical particle, wherein the particle-forming component encloses an interior of the particle containing the nucleic acid-like component and the so-enclosed interior volume has less than about 50% (preferably less than 20%) of the volume containing free water.

摘要翻译： 提供了一种制备微粒复合物的方法。 该方法包括（a）在包含水和水混溶性有机溶剂的单相组合物中将颗粒形成组分（“PFC”）和核酸样组分（“NAC”）组合以形成混合物，其中PFC 并且NAC独立地在水/有机溶剂系统中分子或胶束溶解，和（b）减少混合物中有机溶剂的量。 这会影响NAC和PFC的微粒复合物的形成。 还提供了一种微粒复合物，其包含与形成近似球形颗粒的核酸样成分复合的颗粒形成组分，其中所述颗粒形成组分包含含有核酸样组分的颗粒的内部， 封闭的内部容积小于含有游离水的体积的约50％（优选小于20％）。