公开(公告)号：EP3360576A1

公开(公告)日：2018-08-15

申请号：EP16853305.7

申请日：2016-06-29

申请人： NOF Corporation ,  National University Corporation Hokkaido University

发明人： TANGE, Kota ,  NAKAI, Yuta ,  AKITA, Hidetaka ,  TANAKA, Hiroki ,  WATANABE, Ayaka ,  MIURA, Naoya ,  HARASHIMA, Hideyoshi

IPC分类号： A61K47/20 ,  A61K9/107 ,  A61K31/37 ,  A61K31/573 ,  A61K45/00 ,  A61K47/22 ,  A61K47/24 ,  A61K47/28 ,  A61K47/34 ,  A61P3/06 ,  A61P29/00 ,  A61P31/00 ,  A61P31/04 ,  A61P31/10 ,  A61P35/00 ,  A61P37/06

CPC分类号： A61K9/107 ,  A61K31/37 ,  A61K31/573 ,  A61K45/00 ,  A61K47/20 ,  A61K47/22 ,  A61K47/24 ,  A61K47/28 ,  A61K47/34

摘要： The present invention provides an O/W type emulsion having a volume median diameter of not more than 100 nm and containing a compound represented by the formula (1)

wherein X a and X b are each independently X 1 , X 2 or a 1,4-piperazinediyl group;

s is 1 or 2,
R 4 is an alkyl group having 1 - 6 carbon atoms,
n a and n b are each independently 0 or 1,
R 1a , R 1b , R 2a and R 2b are each independently an alkylene group having 1 - 6 carbon atoms,
Y a and Y b are each independently an ester bond, or the like, and
R 3a and R 3b are each independently a liposoluble vitamin residue or the like.

公开(公告)号：EP3252043A1

公开(公告)日：2017-12-06

申请号：EP16743545.2

申请日：2016-01-29

申请人： NOF Corporation ,  National University Corporation Hokkaido University

发明人： NAKAI, Yuta ,  TANGE, Kota ,  AKITA, Hidetaka ,  HARASHIMA, Hideyoshi ,  TOGASHI, Ryohei ,  MIURA, Naoya ,  MAETA, Mio

IPC分类号： C07D295/088 ,  A61K9/127 ,  A61K31/7088 ,  A61K45/00 ,  A61K47/22 ,  A61K48/00 ,  A61P43/00 ,  C07D311/00

摘要： The present invention aims to provide a cationic lipid that can be used as a nucleic acid delivery carrier, a lipid membrane structure using a cationic lipid, a nucleic acid-introducing agent using a cationic lipid, and a method of achieving nucleic acid introduction by using a nucleic acid-introducing agent containing a cationic lipid. A lipid membrane structure containing a cationic lipid represented by the formula (1)

wherein each symbol is as defined in the DESCRIPTION, is superior in the stability in blood and tumor accumulation property. A nucleic acid-introducing agent using the cationic lipid can achieve high nucleic acid delivery efficiency of nucleic acid to be delivered into the cytoplasm.

摘要翻译： 本发明的目的在于提供可用作核酸递送载体的阳离子性脂质，使用阳离子脂质的脂质膜结构体，使用阳离子性脂质的核酸导入剂，以及使用阳离子脂质的核酸导入剂的使用方法 含有阳离子脂质的核酸引入剂。 包含由式（1）表示的阳离子脂质的脂质膜结构体，其中每个符号如说明书中所定义，在血液稳定性和肿瘤积聚性方面优异。 使用阳离子脂质的核酸引入剂可以实现待递送到细胞质中的核酸的高核酸递送效率。

公开(公告)号：EP3184506A1

公开(公告)日：2017-06-28

申请号：EP15833801.2

申请日：2015-08-07

申请人： NOF Corporation ,  National University Corporation Hokkaido University

发明人： SASAKI, Shota ,  OTA, Masaki ,  KUBO, Kazuhiro ,  HARASHIMA, Hideyoshi ,  AKITA, Hidetaka ,  HATAKEYAMA, Hiroto ,  NOGUCHI, Yuki ,  TANGE, Kota ,  NAKAI, Yuta ,  SHIMIZU, Nayuta

IPC分类号： C07C229/12 ,  A61K31/7088 ,  A61K47/18 ,  A61K48/00 ,  A61P43/00

CPC分类号： A61K47/543 ,  A61K9/107 ,  A61K9/127 ,  A61K31/7088 ,  A61K47/18 ,  A61K48/00 ,  C07C229/12 ,  C12P7/6445 ,  Y02P20/55

摘要： An object of the present invention is to provide a cationic lipid capable of achieving higher intracellular delivery efficiency than conventional cationic lipids, when used as a lipid membrane structure which is a carrier for delivering functional nucleic acid.
A cationic lipid represented by the formula (1):

wherein each symbol is as defined in the present DESCRIPTION.

摘要翻译： 本发明的一个目的是提供当用作递送功能性核酸的载体的脂质膜结构时，能够获得比常规阳离子脂质更高的细胞内递送效率的阳离子脂质。 由式（1）表示的阳离子脂质：其中每个符号如本说明书中所定义。

公开(公告)号：EP2781507A1

公开(公告)日：2014-09-24

申请号：EP12850198.8

申请日：2012-11-09

申请人： NOF Corporation ,  National University Corporation Hokkaido University

发明人： TANGE, Kota ,  ARAI, Masaya ,  KUBO, Kazuhiro ,  AKITA, Hidetaka ,  HARASHIMA, Hideyoshi ,  HATAKEYAMA, Hiroto ,  ISHIBA, Ryohei ,  UKAWA, Masami ,  TANAKA, Hiroki

IPC分类号： C07C323/25 ,  A61K47/20 ,  A61K47/44 ,  A61K48/00

CPC分类号： C12N15/88 ,  A61K9/0019 ,  A61K9/1271 ,  A61K9/1272 ,  A61K47/20 ,  A61K47/22 ,  C07C323/25 ,  C07C2601/16 ,  C07D311/72

摘要： Provided is a cationic lipid capable of achieving high intracellular expression efficiency when used as a nucleic acid delivery carrier.
A compound represented by the formula (1)

wherein X a and X b are each independently X 1 or X 2 ;


s is 1 or 2,
R 4 is an alkyl group having 1 - 6 carbon atoms,
n a and n b are each independently 0 or 1,
R 1a and R 1b are each independently an alkylene group having 1 - 6 carbon atoms,
R 2a and R 2b are each independently an alkylene group having 1 - 6 carbon atoms,
Y a and Y b are each independently an ester bond, an amide bond, a carbamate bond, an ether bond or a urea bond, and
R 3a and R 3b are each independently a sterol residue, a liposoluble vitamin residue or an aliphatic hydrocarbon group having 12 - 22 carbon atoms.

公开(公告)号：EP3252043B1

公开(公告)日：2020-09-30

申请号：EP16743545.2

申请日：2016-01-29

申请人： NOF Corporation ,  National University Corporation Hokkaido University

发明人： NAKAI, Yuta ,  TANGE, Kota ,  AKITA, Hidetaka ,  HARASHIMA, Hideyoshi ,  TOGASHI, Ryohei ,  MIURA, Naoya ,  MAETA, Mio

IPC分类号： C07D295/088 ,  A61K9/127 ,  A61K31/7088 ,  A61K45/00 ,  A61K47/22 ,  A61K48/00 ,  A61P43/00 ,  C07D311/00

公开(公告)号：EP3184506B1

公开(公告)日：2019-07-24

申请号：EP15833801.2

申请日：2015-08-07

申请人： NOF Corporation ,  National University Corporation Hokkaido University

发明人： SASAKI, Shota ,  OTA, Masaki ,  KUBO, Kazuhiro ,  HARASHIMA, Hideyoshi ,  AKITA, Hidetaka ,  HATAKEYAMA, Hiroto ,  NOGUCHI, Yuki ,  TANGE, Kota ,  NAKAI, Yuta ,  SHIMIZU, Nayuta

IPC分类号： C07C229/12 ,  A61K31/7088 ,  A61K47/18 ,  A61K48/00 ,  A61P43/00

公开(公告)号：EP2781507B1

公开(公告)日：2017-03-22

申请号：EP12850198.8

申请日：2012-11-09

申请人： NOF CORPORATION ,  NATIONAL UNIVERSITY CORPORATION HOKKAIDO UNIVERSITY

发明人： TANGE, Kota ,  ARAI, Masaya ,  KUBO, Kazuhiro ,  AKITA, Hidetaka ,  HARASHIMA, Hideyoshi ,  HATAKEYAMA, Hiroto ,  ISHIBA, Ryohei ,  UKAWA, Masami ,  TANAKA, Hiroki

IPC分类号： C07C323/25 ,  A61K47/20 ,  A61K47/44 ,  A61K48/00

CPC分类号： C12N15/88 ,  A61K9/0019 ,  A61K9/1271 ,  A61K9/1272 ,  A61K47/20 ,  A61K47/22 ,  C07C323/25 ,  C07C2601/16 ,  C07D311/72

公开(公告)号：EP2514760B1

公开(公告)日：2015-10-21

申请号：EP10837604.7

申请日：2010-12-14

申请人： National University Corporation Hokkaido University

发明人： HARASHIMA, Hideyoshi ,  FUJIWARA, Takahiro ,  AKITA, Hidetaka

IPC分类号： A61K9/127 ,  A61K47/42 ,  A61K38/08

CPC分类号： C07K7/06 ,  A61K9/1271 ,  A61K38/00 ,  A61K47/60 ,  A61K47/62 ,  A61K47/6911

公开(公告)号：EP2514760A1

公开(公告)日：2012-10-24

申请号：EP10837604.7

申请日：2010-12-14

申请人： National University Corporation Hokkaido University

发明人： HARASHIMA, Hideyoshi ,  FUJIWARA, Takahiro ,  AKITA, Hidetaka

IPC分类号： C07K7/06 ,  A61K9/127 ,  A61K47/42 ,  C07K14/47

CPC分类号： C07K7/06 ,  A61K9/1271 ,  A61K38/00 ,  A61K47/60 ,  A61K47/62 ,  A61K47/6911

摘要： Provided are peptides imparting cell permeability to a lipid membrane structure and/or enhancing the cell permeability of a lipid membrane structure, and a lipid membrane structure which comprises, as a constituent lipid, a lipid bound to such a peptide and has cell permeability or shows enhanced cell permeability. The amino acid sequences of the peptides imparting cell permeability to a lipid membrane structure and/or enhancing the cell permeability of a lipid membrane structure are represented by: LX 1 X 2 X 1 X 1 X 1 L, LLX 2 X 1 X 1 X 1 L and LX 1 X 2 X 1 X 1 L (wherein L represents a leucine residue; X 1 represents a polar amino acid residue; and X 2 represents a polar, non-charged and branched chain amino acid residue).

摘要翻译： 提供赋予脂质膜结构的细胞渗透性和/或增强脂质膜结构的细胞渗透性的肽以及脂质膜结构，其包含作为构成脂质的结合到这种肽上的脂质并具有细胞渗透性或显示 增强细胞渗透性。 赋予细胞对脂质膜结构的渗透性和/或提高脂质膜结构的细胞渗透性的肽的氨基酸序列由下式表示：LX 1 X 2 X 1 X 1 X 1 L，LLX 2 X 1 X 1 X 1 L和LX 1 X 2 X 1 X 1 L（其中L表示亮氨酸残基; X 1表示极性氨基酸残基; X 2表示极性，无电荷和支链氨基酸残基）。

公开(公告)号：EP2138192A1

公开(公告)日：2009-12-30

申请号：EP08720286.7

申请日：2008-02-27

申请人： National University Corporation Hokkaido University ,  President, Kyoto University ,  Shionogi Co., Ltd.

发明人： HARASHIMA, Hideyoshi ,  KOGURE, Kentaro ,  AKITA, Hidetaka ,  IWASA, Akitada ,  NAKAMURA, Yoshio ,  FUTAKI, Shiroh

IPC分类号： A61K47/42 ,  A61K9/127 ,  A61K47/24 ,  B01J13/04 ,  C07K14/00

CPC分类号： A61K9/127 ,  A61K38/00 ,  A61K47/42 ,  C07K14/00

摘要： It is intended to provide a positively charged liposome, particularly having a polyarginine peptide on a surface thereof, which is capable of increasing the resistance to a negatively charged biological component such as a protein in the blood and maintaining a high ability to deliver a substance even in the blood. An agent for enhancing the resistance of liposome against biological component comprising a peptide having at least one of the following characteristics (a) and (b) as an active ingredient:
(a) A peptide comprising an amino acid sequence represented by SEQ ID No: 1 or 2; and
(b) A peptide comprising an amino acid sequence represented by SEQ ID No: 1 or 2, in which one or more amino acids are deleted, substituted or added, and having an activity for promoting lipid membrane fusion under acidic condition. An agent for enhancing the resistance of liposome against biological component in this invention, being included in a liposome, is capable of increasing the resistance to a negatively charged biological component such as a protein in the blood and maintaining a high ability to deliver a substance even in the blood.

摘要翻译： 它的目的是提供一个带正电荷的脂质体，特别是具有在其表面，在所有其能够电阻增加至带负电荷的生物成分的在聚精氨酸的肽：如在血液中的蛋白质和维护，即使传递的物质的能力高 在血液中。 用于增强脂质体的抵抗生物组分，其包含具有至少一个下列特征的肽的试剂（a）和（b）中作为活性成分的：（a）一个肽，其包含由SEQ ID NO所示的氨基酸序列组成： 1或2; 和（b）的氨基酸序列的肽，其包含由SEQ ID NO：1或2，在其中一个或多个氨基酸被缺失，substituiertem奥德加入，并且具有用于在酸性条件下促进脂质膜融合的活性。 为增强抗生物成分的脂质体的电阻在本发明中，被包括在脂质体中的药剂，能够将电阻增加带负电荷的生物成分的：如在血液中的蛋白质和维护，即使传递的物质的能力高 在血液中。