Nof Corporation

Daiichi Pharmaceutical Co., Ltd.

Hokkaido University

Osaka Prefecture University Public Corporation

Teruyuki Nagamune

The University of Tokushima

Nagamune, Teruyuki

Kazuhiro Kubo

Chika Itoh

Tohru Yasukohchi

Syunsuke Ohhashi

Hiroshi Kikuchi

Norio Suzuki

Hitoshi Yamauchi

Kota Tange

Miho Takahashi

Hideyoshi Harashima

Masaya Arai

Hidetaka Akita

Hiroto Hatakeyama

Tatsuhiro Ishida

Kenji Sakanoue

Yuta Nakai

Shoichi Yokoyama

Shigeru Kitano

Syunsuke Ohashi

Hiroki Tanaka

Masaki Ota

Shota Sasaki

Yusuke Ohkawa

Masaki Ohta

Miho Kurosawa

Kenji Kono

Nayuta Shimizu

Chika Ito

Ryohei Ishiba

Masami Ukawa

Yuki Noguchi

Hiroshi Daiichi Pharmaceutical Co Ltd Kikuchi

Hitoshi Daiichi Pharmaceutical Co Ltd Yamauchi

Miho Daiichi Pharmaceutical Co Ltd Takahashi

Norio Daiichi Pharmaceutical Co Ltd Suzuki

Hiroshi Kiwada

The invention provides 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. The cationic lipid is represented by the formula (1): 

Cationic lipid for nucleic acid delivery

The present invention relates to a compound represented by the formula (1) wherein Xand Xare each independently Xor X; s is 1 or 2,Ris an alkyl group having 1-6 carbon atoms,nand nare each independently 0 or 1,Rand Rare each independently an alkylene group having 1-6 carbon atoms,Rand Rare each independently an alkylene group having 1-6 carbon atoms,Yand Yare each independently an ester bond, an amide bond, a carbamate bond, an ether bond or a urea bond, andRand Rare each independently a sterol residue, a liposoluble vitamin residue or an aliphatic hydrocarbon group having 12-22 carbon atoms,and use thereof.

Cationic lipid having improved intracellular kinetics

In production of a cationic lipid having at least one methylene group sandwiched between adjacent two cis form double bonds in the molecule, isomerization from a cis form to a trans form is suppressed. A compound represented by the following formula (I):R&#x2014;X&#x2003;&#x2003;(I)(in Formula, Rrepresents a hydrocarbon group having at least one methylene group sandwiched between adjacent two cis form double bonds in the molecule and having the carbon number of 8 to 24 and X represents a releasing group) is reacted with (B) a compound having at least one of each of tertiary amino group and hydroxyl group in the molecule in a saturated hydrocarbon solvent having the carbon number of 5 to 10 in the presence of an alkali catalyst.

Method for manufacturing tertiary amino group-containing lipid

A method for producing a biodegradable polyoxyalkylene derivative, includes: reacting a biodegradable polyoxyalkylene compound represented by the formula (1) as defined herein with a compound represented by one of the formulae (I) to (IV) as defined herein in a presence of an alkaline solid salt, the biodegradable polyoxyalkylene derivative being represented by the formula (2) as defined herein.

Method for producing biodegradable polyoxyalkylene derivative

A phospholipid derivative represented by the following formula (1) wherein each symbol is as described in the specification; a liposome containing the phospholipid derivative, and the like.

Phospholipid derivative and pH-responsive liposomes

A phospholipid derivative, utilizable for modification of liposomes and the like, which is a copolymer containing, as essential component units, a component unit A represented by the formula (1), a component unit B represented by the formula (2A) and/or the formula (2B), and a component unit C represented by the formula (3) [Rand Rrepresent hydrogen atom or methyl group, provided that Rand Rdo not simultaneously represent methyl group; Rrepresents a divalent hydrocarbon group having 1 to 3 carbon atoms; AO represents an oxyalkylene group having 2 to 4 carbon atoms; m represents an average molar number of the added oxyalkylene groups and is a number in the range represented as 4&#x2266;m&#x2266;100; Rrepresents hydrogen atom, a hydrocarbon group or acyl group having 1 to 20 carbon atoms; RCO and RCO represent an acyl group having 8 to 24 carbon atoms; Rrepresents a divalent hydrocarbon group having 2 to 4 carbon atoms; and X and Y represent hydrogen atom, an alkali metal atom, ammonium or an organic ammonium] wherein a molar ratio of the component unit A relative to a total of the component unit B and the component unit C is from 7/3 to 3/7, and the component unit C is contained at a ratio of from 1 to 4 moles per 1 mole of the copolymer. 

Phospholipid derivative

A phospholipid derivative represented by the following formula (1): wherein [PG]k represents a residue of polyglycerin having a polymerization degree of k, wherein k is 2 to 50, RCO and RCO independently represent an acyl group having 8 to 22 carbon atoms, symbol 'a' independently represents an integer of 0 to 5, symbol 'b' independently represents 0 or 1, M represents hydrogen atom, an alkali metal atom, an ammonium, or an organic ammonium, and k1, k2, and k3 represent numbers satisfying the following conditions: 1&#x2266;k1&#x2266;(k+2)/2, 0&#x2266;k2, and k1+k2+k3=k+2. The phospholipid derivative is highly safe for living bodies and can be suitably utilized in drug delivery systems such as liposome, and the like.

Phospholipid derivatives and process for the production there

A phospholipid derivative represented by the formula (1) (Z represents a residue of a compound having 3 to 10 hydroxyl groups; AO represents an oxyalkylene group having 2 to 4 carbon atoms; RCO and RCO represent an acyl group having 8 to 22 carbon atoms; X represents hydrogen atom, an alkali metal atom, ammonium or an organic ammonium; 'a' represents an integer of 0 to 4; 'b' represents 0 or 1; Q represents hydrogen atom or methyl group; m represents an average number of moles of the oxyalkylene group added; and m, k1, k2, and k3 are numbers satisfying the following conditions: 3&#x2266;m&#x2266;200, 9&#x2266;m&#xd7;(k1+k2+k3)&#x2266;1000, 1&#x2266;k1&#x2266;2, 0&#x2266;k2&#x2266;9 and 0&#x2266;k3&#x2266;9, and 3&#x2266;k1+k2+k3&#x2266;10), which is highly safe for living bodies, and is suitably used for solubilization and dispersion of physiologically active substances and the like, or in the fields of drug delivery systems such as liposomes and cosmetics. 

A phospholipid derivative represented by the following formula (I) wherein RCO and RCO independently represent an acyl group; Rrepresents hydrogen atom, or a hydrocarbon group; symbol 'a' represents an integer of 0 to 4; symbol 'b' represents 0 or 1, provided that when a is 0, b is 0; X represents hydrogen atom, an alkali metal atom, an ammonium, or an organic ammonium; AO and AO represent an oxyalkylene group containing oxyethylene group, wherein the ratio of the oxyethylene group to the oxyalkylene group in AO and AO is 0.5 or larger in terms of a weight ratio; AO represents an oxyalkylene group; symbols &#x201c;m&#x201d; and &#x201c;q&#x201d; represent an average molar number of added oxyalkylene groups; and symbol &#x201c;n&#x201d; represent an average molar number of added oxyalkylene groups; provided that m, n and q satisfy the following conditions: 5&#x2266;m&#x2266;600, 1&#x2266;n&#x2266;45, 0&#x2266;q&#x2266;200, 10&#x2266;m+n+q&#x2266;600, 0.04&#x2266;n/(m+n+q), and q/(m+n+q)&#x2266;0.8, which can thicken the water shell of liposome surface by suppressing the spreading of the polyalkylene oxide structure on the surface and thus increase stability of the liposome 

A cell in which a reaction product of a substance to be modified and an amphipathic compound is non-covalently bound to a cell membrane, wherein said compound has the following features:

Cell having modified cell membrane

A polyoxyalkylene derivative is represented by formula (I):wherein Z represents a residue of a compound having 2 to 8 hydroxyl groups; AO represents an oxyalkylene group having 2 to 18 carbon atoms; n and m each represent an integer of 0 to 2000 provided that both n and m do not represent 0; a and b each represent an integer satisfying the relationships: 2&#x2266;a+b&#x2266;8 and 1&#x2266;b; R represents a hydrocarbon group having 1 to 30 carbon atoms; and X represents a divalent hydrocarbon group having 3 to 10 carbon atoms.

Polyoxyalkylene derivative and process of producing the same

A polyalkylene oxide-modified phospholipid represented by formula (1) defined in the specification, has a monoacyl phospholipid content of not more than 3% by weight and a content of a base having a nitrogen atom of not more than 0.02% by weight.

Polyalkylene oxide-modified phospholipid and production method thereof

Growing community of inventors

Kawasaki, Japan

Kazuhiro Kubo