Daiichi Pharmaceutical Co., Ltd.

Nof Corporation

Daiichi Seiyaku Co., Ltd.

Nomura Micro Science Co., Ltd.

Drug Delivery System Institute, Ltd.

Hitoshi Yamauchi

Hiroshi Kikuchi

Norio Suzuki

Tohru Yasukohchi

Chika Itoh

Kazuhiro Kubo

Syunsuke Ohhashi

Sadao Hirota

Miho Takahashi

Munehiro Tomikawa

Shiro Miyoshi

Satoru Nakabayashi

Kiyoto Yachi

Yusuke Ohkawa

Takazo Hirose

Miho Kurosawa

Akinori Hoshio

Hiroshi Honda

Yasuyoshi Kawato

Kunio Higashi

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 filter unit comprises a metallic supporting plate possessed of stepped through holes opening with a larger diameter in one main surface and with a smaller diameter in the other main surface (wherein the diameter ratio of larger-diameter openings to smaller-diameter openings is desired to be in the range of 1:0.01 to 1:0.5) or a pressureproof supporting plate having in one surface thereof inclined liquid flow grooves arranged in a radial pattern and concentric circular liquid flow grooves adapted to intersect the radially arranged liquid flow grooves and a membrane filter disposed on the surface of the supporting plate containing larger-diameter openings or liquid flow grooves. This filter unit is ideally used for finely dividing and uniformly sizing suspended lipid particles assuming a definite average particle size and a specific particle size distribution. The high-pressure sizing apparatus and the method for production of suspended lipid particles utilize the filter unit constructed as described above and rely essentially for their operation on effecting fine division of lipid particles in the suspension by supplying the suspension of lipid particles from the membrane filter side under pressure and causing the suspension to pass through the membrane filter. Thus, they constitute themselves effective measures for pharmacological products and cosmetic products which are in need of lipid particles assuming a definite average particle size and a specific particle size distribution.

Filter unit and high-pressure sizing apparatus

Sialic acid-containing glycolipid derivatives

Lipid membrane structures containing, in the lipid membrane thereof, a compound represented by formula (I): ##STR1## wherein R.sub.1 represents a hydrogen atom or a fatty acid residue; R.sub.2 represents a hydrogen atom or an acyclic hydrocarbon residue; R.sub.3 represents an amino group, a guanidino group or an amidino group; and n represents an integer of from 1 to 6; provided that R.sub.1 and R.sub.2 do not represent hydrogen atoms at the same time, or a salt thereof. The lipid membrane structures exhibit excellent specific affinity for tumor cells and can be delivered preferentially to tumor cells.

Lipid membrane structures

An ointment comprising an adenosine 3',5'-cyclic phosphate derivative as an active ingrediment, an ointment base having water-absorbing and drying properties, a saccharide and/or inorganic high polymer is disclosed. The ointment exhibits improved stability of the adenosine 3',5'-cyclic phosphate derivative.

Cyclic amp derivative ointments

Lipid membrane structures containing a lactose monofatty acid ester or amide are disclosed. The lipid membrane structures are delivered preferentially to the liver parenchymal cells and are useful as carriers of drugs.

A method for producing liposomes which comprises mixing liposome membrane components with a water-soluble non-volatile solvent and, then, dispersing the mixture in an aqueous medium. The pharmaceutically acceptable liposome preparation as a drug delivery system can thus be produced with efficiency on an industrial scale.

Growing community of inventors

Tokyo, Japan

Hitoshi Yamauchi