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公开(公告)号：US10751426B2
公开(公告)日：2020-08-25
申请号：US15771305
申请日：2016-10-28
IPC分类号： A61K31/7105 , A61K31/7125 , A61K47/02 , A61K47/12 , A61K47/16 , A61K47/18 , A61K47/26 , A61P11/00 , C07H21/02 , C12N15/09 , C12N15/10 , C12N15/11 , A61K48/00 , C12N15/113 , A61K9/08 , C07H21/04
摘要： The present invention provides a composition containing a single-stranded nucleic acid molecule consisting of a nucleotide sequence shown by 5′-AGCAGAGUACACACAGCAUAUACC-P-GGUAUAUGCUGUGUGUACUCUGCUUC-P-G-3′ (SEQ ID NO: 1)(in the sequence, P is a proline derivative linker represented by (I) in the DESCRIPTION) and a buffer, and having the following features: (a) being in the form of a solution at ambient temperature; and (b) a content of the nucleic acid molecule after storage at 25° C., relative humidity 60% for 4 weeks, of not less than 80% relative to the content at the time of start of the storage.
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2.发明申请公开(公告)号：US20180339064A1
公开(公告)日：2018-11-29
申请号：US15771305
申请日：2016-10-28
摘要： The present invention provides a composition containing a single-stranded nucleic acid molecule consisting of a nucleotide sequence shown by 5′-AGCAGAGUACACACAGCAUAUACC-P-GGUAUAUGCUGUGUGUACUCUGCUUC-P-G-3′ (SEQ ID NO: 1) (in the sequence, P is a proline derivative linker represented by (I) in the DESCRIPTION) and a buffer, and having the following features:(a) being in the form of a solution at ambient temperature; and (b) a content of the nucleic acid molecule after storage at 25° C., relative humidity 60% for 4 weeks, of not less than 80% relative to the content at the time of start of the storage.
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公开(公告)号：US09315828B2
公开(公告)日：2016-04-19
申请号：US12532949
申请日：2008-03-26
IPC分类号： A61K48/00 , C07H21/02 , C12N15/88 , C12N15/87 , A61K9/127 , A61K31/7088 , A61K31/713 , C12N15/11
CPC分类号： C12N15/87 , A61K9/127 , A61K31/7088 , A61K31/713 , A61K48/00 , C12N15/111 , C12N2310/14 , C12N2320/32
摘要： An object of the present invention is to provide a carrier composition for nucleic acid delivery, which can efficiently deliver a nucleic acid into cells when a nucleic acid such as siRNA is administered to animal-derived cells or animals, and also has low toxicity and high safety, and a composition for nucleic acid delivery containing the carrier composition and nucleic acid.A carrier for nucleic acid delivery is prepared by using (A) a diacylphosphatidylcholine, (B) at least one member selected from the group consisting of cholesterol and derivatives thereof, and (C) an aliphatic primary amine. Also, a composition for nucleic acid delivery is prepared by mixing the carrier for nucleic acid delivery with a nucleic acid.
摘要翻译： 本发明的目的是提供一种用于核酸递送的载体组合物，当向动物来源的细胞或动物施用siRNA等核酸时，可以将核酸有效地递送到细胞中，并且还具有低毒性和高 安全性和用于含有载体组合物和核酸的核酸递送的组合物。 通过使用（A）二酰基磷脂酰胆碱，（B）至少一种选自胆固醇及其衍生物的组分和（C）脂族伯胺制备核酸递送载体。 而且，通过将用于核酸递送的载体与核酸混合来制备用于核酸递送的组合物。
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公开(公告)号：US09090912B1
公开(公告)日：2015-07-28
申请号：US13254770
申请日：2010-03-04
CPC分类号： C12N15/88 , A61K9/1271 , A61K9/1272 , A61K9/1278 , A61K31/7088 , A61K31/7105 , A61K47/36 , A61K47/40 , C12N15/111 , C12N2310/14 , C12N2310/3515 , C12N2320/32
摘要： This invention relates to a nucleic acid complex with low toxicity and high safety that can maintain a nucleic acid molecule capable of RNA interference or translation inhibition, such as siRNA or the like, in a cell; and a nucleic acid delivery composition that can efficiently deliver the nucleic acid complex into a cell. A nucleic acid complex with low toxicity and high safety that can maintain a nucleic acid in a cell can be obtained by forming a complex using a nucleic acid molecule capable of RNA interference or translation inhibition and a cycloamirose. Further, by using a carrier comprising (A) a diacylphosphatidylcholine, (B) cholesterol and/or a derivative thereof, and (C) an aliphatic primary amine as a nucleic acid delivery carrier to introduce the nucleic acid complex into a cell, the safety, efficiency of intracellular delivery, and persistence of the nucleic acid in the cell can be further improved.
摘要翻译： 本发明涉及一种具有低毒性和高安全性的核酸复合物，其能够在细胞中维持能够进行RNA干扰或翻译抑制的核酸分子，例如siRNA等; 以及可以有效地将核酸复合物递送到细胞中的核酸递送组合物。 可以通过使用能够进行RNA干扰或翻译抑制的核酸分子和循环波形来形成复合物来获得能够维持细胞中核酸的低毒性和高安全性的核酸复合物。 此外，通过使用包含（A）二酰基磷脂酰胆碱，（B）胆固醇和/或其衍生物的载体，和（C）作为核酸递送载体的脂族伯胺将核酸复合物引入细胞， 可以进一步提高细胞内递送的效率和核酸在细胞中的持续性。
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公开(公告)号：US20140105968A1
公开(公告)日：2014-04-17
申请号：US14108826
申请日：2013-12-17
CPC分类号： A61K9/1277 , A61K9/007 , A61K9/0078 , A61K9/1271 , A61K45/06 , A61K47/32 , A61K47/36 , A61K48/00 , A61K48/0075 , C12N15/88 , C12N2810/10
摘要： An object of the present invention is to provide a liposome which is excellent in intrapulmonary delivery controllability of drugs or genes and is suited for pulmonary administration.By modifying the surface of a liposome using a terminal hydrophobized polyvinyl alcohol and/or chitosan, retention of drugs or genes encapsulated in the liposome on the surface of lung tissue and transfer of drugs or genes into lung tissue can be properly modulated, and thus in vivo behavior can be controlled.
摘要翻译： 本发明的目的是提供一种在药物或基因的肺内递送可控性优异且适于肺部给药的脂质体。 通过使用末端疏水化聚乙烯醇和/或壳聚糖改性脂质体的表面，可以适当地调节将包封在脂质体中的药物或基因保留在肺组织表面上并将药物或基因转移到肺组织中， 可以控制体内行为。
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公开(公告)号：US08658204B2
公开(公告)日：2014-02-25
申请号：US12593827
申请日：2008-03-28
CPC分类号： A61K9/1277 , A61K9/007 , A61K9/0078 , A61K9/1271 , A61K45/06 , A61K47/32 , A61K47/36 , A61K48/00 , A61K48/0075 , C12N15/88 , C12N2810/10
摘要： An object of the present invention is to provide a liposome which is excellent in intrapulmonary delivery controllability of drugs or genes and is suited for pulmonary administration.By modifying the surface of a liposome using a terminal hydrophobized polyvinyl alcohol and/or chitosan, retention of drugs or genes encapsulated in the liposome on the surface of lung tissue and transfer of drugs or genes into lung tissue can be properly modulated, and thus in vivo behavior can be controlled.
摘要翻译： 本发明的目的是提供一种脂质体，该脂质体在药物或基因的肺内递送可控性方面优异，适用于肺部给药。 通过使用末端疏水化聚乙烯醇和/或壳聚糖改性脂质体的表面，可以适当地调节将包封在脂质体中的药物或基因保留在肺组织表面上并将药物或基因转移到肺组织中， 可以控制体内行为。
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公开(公告)号：US08338584B2
公开(公告)日：2012-12-25
申请号：US12741457
申请日：2008-11-06
CPC分类号： A61K47/40 , A61K9/1272 , A61K47/543 , A61K47/6951 , A61K48/005 , B82Y5/00 , C12N15/88
摘要： The present invention provides a nucleic acid complex with low toxicity and high safety that can persistently maintain a nucleic acid, such as siRNA or the like, in a cell; and a nucleic acid delivery composition that can efficiently deliver the nucleic acid complex into a cell. A nucleic acid complex with low toxicity and high safety that can persistently maintain a nucleic acid in a cell can be obtained by forming a complex using a nucleic acid to be introduced into a cell, and a highly branched cyclic dextrin. Moreover, when a carrier comprising (A) a diacylphosphatidylcholine, (B) cholesterol and/or a derivative thereof, and (C) an aliphatic primary amine is used as a nucleic acid delivery carrier to introduce the nucleic acid complex into a cell, the safety, the efficiency of intracellular delivery, and the persistence of the nucleic acid in the cell can be further improved.
摘要翻译： 本发明提供了一种具有低毒性和高安全性的核酸复合物，其可以在细胞中持续保持核酸如siRNA等; 以及可以有效地将核酸复合物递送到细胞中的核酸递送组合物。 可以通过使用待引入细胞的核酸和高度支化的环糊精形成复合物来获得能够持续维持细胞中核酸的低毒性和高安全性的核酸复合物。 此外，当使用包含（A）二酰基磷脂酰胆碱，（B）胆固醇和/或其衍生物和（C）脂肪族伯胺的载体作为核酸递送载体以将核酸复合物引入细胞时， 可以进一步提高安全性，细胞内递送的效率和核酸在细胞中的持续性。
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8.发明授权公开(公告)号：US08105630B2
公开(公告)日：2012-01-31
申请号：US10554921
申请日：2004-04-28
申请人： Hiroshi Miura , Makoto Kanebako , Masayuki Kanishi , Toshio Inagi , Hirofumi Takeuchi , Tsutomu Kajino , Yoshiaki Fukushima , Haruo Takahashi
发明人： Hiroshi Miura , Makoto Kanebako , Masayuki Kanishi , Toshio Inagi , Hirofumi Takeuchi , Tsutomu Kajino , Yoshiaki Fukushima , Haruo Takahashi
CPC分类号： A61K31/50 , A61K9/1611 , A61K9/1694 , A61K9/2077 , Y10S977/906
摘要： A composition containing an extremely poorly water-soluble drug and obtained by treating, with a supercritical fluid or subcritical fluid of carbon dioxide, a mixture comprising a porous silica material and the extremely poorly water-soluble drug; and its production process. The porous silica material has an average pore diameter in a range of from 1 to 20 nm, pores having diameters within ±40% of the average pore size account for at least 60% of a total pore volume of the porous silica material, and in X-ray diffractometry, the porous silica material has at least one peak at a position of diffraction angle (2θ) corresponding to a d value of at least 1 nm.The composition according to the present invention, which contains the extremely poorly water-soluble drug, is excellent in the dissolution of the extremely poorly water-soluble drug.
摘要翻译： 通过用超临界流体或二临界流体二氧化碳处理包含多孔二氧化硅材料和极难水溶性药物的混合物获得的组合物，其含有极差水溶性药物， 及其生产工艺。 多孔二氧化硅材料的平均孔径在1至20nm的范围内，直径在平均孔径的±40％范围内的孔占多孔二氧化硅材料的总孔体积的至少60％，并且在 X射线衍射法，多孔二氧化硅材料在与至少1nm的ad值相对应的衍射角（2θ）处具有至少一个峰。 含有极差水溶性药物的本发明组合物，极难溶于水的药物溶解性优异。
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公开(公告)号：US20100305190A1
公开(公告)日：2010-12-02
申请号：US12741457
申请日：2008-11-06
IPC分类号： C07H21/02 , C07H21/00 , A61K31/7105 , C12N5/00
CPC分类号： A61K47/40 , A61K9/1272 , A61K47/543 , A61K47/6951 , A61K48/005 , B82Y5/00 , C12N15/88
摘要： The present invention provides a nucleic acid complex with low toxicity and high safety that can persistently maintain a nucleic acid, such as siRNA or the like, in a cell; and a nucleic acid delivery composition that can efficiently deliver the nucleic acid complex into a cell. A nucleic acid complex with low toxicity and high safety that can persistently maintain a nucleic acid in a cell can be obtained by forming a complex using a nucleic acid to be introduced into a cell, and a highly branched cyclic dextrin. Moreover, when a carrier comprising (A) a diacylphosphatidylcholine, (B) cholesterol and/or a derivative thereof, and (C) an aliphatic primary amine is used as a nucleic acid delivery carrier to introduce the nucleic acid complex into a cell, the safety, the efficiency of intracellular delivery, and the persistence of the nucleic acid in the cell can be further improved.
摘要翻译： 本发明提供了一种具有低毒性和高安全性的核酸复合物，其可以在细胞中持续保持核酸如siRNA等; 以及可以有效地将核酸复合物递送到细胞中的核酸递送组合物。 可以通过使用待引入细胞的核酸和高度支化的环糊精形成复合物来获得能够持续维持细胞中核酸的低毒性和高安全性的核酸复合物。 此外，当使用包含（A）二酰基磷脂酰胆碱，（B）胆固醇和/或其衍生物和（C）脂肪族伯胺的载体作为核酸递送载体以将核酸复合物引入细胞时， 可以进一步提高安全性，细胞内递送的效率和核酸在细胞中的持续性。
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公开(公告)号：US20050191357A1
公开(公告)日：2005-09-01
申请号：US10508337
申请日：2002-09-12
申请人： Yoshiaki Kawashima , Masuo Hosokawa , Hirofumi Takeuchi , Hiromitsu Yamamoto , Masaru Iwato , Kazuki Suhara , Toyokazu Yokoyama , Hiroyuki Tsujimoto , Akira Kondo , Tsunehiro Yoshidomi , Yoshiyuki Inoue , Hisato Eitoku , Naotoshi Kinoshita
发明人： Yoshiaki Kawashima , Masuo Hosokawa , Hirofumi Takeuchi , Hiromitsu Yamamoto , Masaru Iwato , Kazuki Suhara , Toyokazu Yokoyama , Hiroyuki Tsujimoto , Akira Kondo , Tsunehiro Yoshidomi , Yoshiyuki Inoue , Hisato Eitoku , Naotoshi Kinoshita
CPC分类号： A61K9/0075 , A61K9/143 , A61K9/145 , A61K9/146 , A61K9/1652 , A61K9/167 , A61K31/00 , B01J2/10
摘要： A strong pressure and a strong shearing force are exerted to a mixture, constituted of two kinds or more of powder materials including a drug powder, while causing the mixture to pass between a press section (26) of a press head (24) and a receiving surface (25) of a cylindrical rotator (23), thereby combining the drug powder with the other powder material. For example, at least one of a drug and a biocompatible polymer is made into a nano particle whose average particle diameter is less than 1000 nm, and the nano particle is made into a composite in accordance with a dry mechanical particle combining method, so as to form a polymer nano composite particle. Thus, it is possible to produce a composite particle, which contains a drug under a stable condition, in a short time, and it is possible to remarkably improve its handling property without losing advantages of the nano particle. As a result, it is possible to favorably apply the foregoing technique to DDS of a powdery drug taken into the body through the lung or a similar drug.
摘要翻译： 在由压粉头（24）的压榨部（26）和压头（24）的压入部（26）之间通过的情况下，对由包含药物粉末的粉末材料构成的混合物施加强大的压力和强的剪切力， 圆柱形旋转器（23）的接收表面（25），从而将药物粉末与其它粉末材料组合。 例如，将药物和生物相容性聚合物中的至少一种制成平均粒径小于1000nm的纳米粒子，根据干燥机械粒子组合法将纳米粒子制成复合体， 以形成聚合物纳米复合颗粒。 因此，可以在短时间内制造含有稳定状态的药物的复合粒子，并且可以显着提高其处理性能而不损失纳米粒子的优点。 结果，可以有利地将上述技术应用于通过肺或类似药物摄入体内的粉末状药物的DDS。
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