Nof Corporation

Daiichi Pharmaceutical Co., Ltd.

Other

Teruyuki Nagamune

Nagamune, Teruyuki

Syunsuke Ohhashi

Yuji Yamamoto

Tohru Yasukohchi

Chika Itoh

Kazuhiro Kubo

Norio Suzuki

Hiroshi Kikuchi

Hitoshi Yamauchi

Miho Takahashi

Kei-ichi Maruyama

Kouzoh Sanchika

Tomomi Suzuki

Kenji Sakanoue

Yusuke Ohkawa

Miho Kurosawa

Satoshi Nanba

Ken-Ichiro Nakamoto

Hiroshi Daiichi Pharmaceutical Co Ltd Kikuchi

Hitoshi Daiichi Pharmaceutical Co Ltd Yamauchi

Miho Daiichi Pharmaceutical Co Ltd Takahashi

Norio Daiichi Pharmaceutical Co Ltd Suzuki

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 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

A composition is provided which comprises catalase modified with a copolymer (A) and a second copolymer, i.e., copolymer (B). The copolymer (A) comprises an alkenyl ether, maleic anhydride, and at least one monomer selected from the group consisting of unsaturated carboxylic acid, vinyl compound and olefin, and copolymer (B) consists of an ethylenically unsaturated monomer and a monomer selected from the group consisting of a monomer having a carboxyl group and a monomer having an acid anhydride group, or a salt of the copolymer (B).

Modified catalase, a composition thereof and process for preparing the catalase

A process for producing a polyoxyalkylene derivative substituted with succinimidyl group which comprises reacting a polyoxyalkylene compound having carboxyl group at ends with N-hydroxysuccinimide in an inert solvent in the presence of dicyclohexylcarbodiimide; dissolving an obtained reaction product into chloroform, an amount by weight of chloroform being 0.5 to 10 times as much as an amount by weight of the polyoxyalkylene compound having carboxyl group at ends; and crystallizing the polyoxyalkylene derivative substituted with succinimidyl group by adding an aliphatic hydrocarbon having 5 to 8 carbon atoms to a resultant solution, an amount by weight of the aliphatic hydrocarbon being 2 to 10 times as much as an amount by weight of chloroform. Materials can be handled with safety, and a highly pure polyoxyalkylene derivative substituted with succinimidyl group which does not cause turbidity in an aqueous solution and has an excellent quality as a material for drugs can be produced.

Process for producing a polyoxyalkylene derivatives substituted with

A process for producing a polyoxyalkylene derivative substituted with succinimidyl group which comprises reacting a polyoxyalkylene compound having carboxyl group at ends with N-hydroxysuccinimide in an inert solvent in the presence of dicyclohexylcarbodiimide; filtering an obtained reaction product; and crystallizing the polyoxyalkylene derivative substituted with succinimidyl group by adding isopropyl alcohol to a filtrate obtained by the filtration, an amount by weight of isopropyl alcohol being 1 to 100 times as much as an amount by weight of the polyoxyalkylene compound having carboxyl group at ends. Materials can be handled with safety in the process of the present invention, and a highly pure polyoxyalkylene derivative substituted with succinimidyl group which does not cause turbidity in an aqueous solution and has an excellent quality as a material for drugs can be produced.

Growing community of inventors

Kanagawa, Japan

Syunsuke Ohhashi