Block copolymer, micelle preparation, and anticancer agent containing the same as active ingredient

Patent metadata

Field	Value
Publication number	US-9434822-B2
Application number	US-201313971036-A
Country	US
Kind code	B2
Filing date	Aug 20, 2013
Priority date	Sep 22, 2004
Publication date	Sep 6, 2016
Grant date	Sep 6, 2016

Abstract

A medicinal preparation is desired which has no harmful side effects such as hypersensitive reaction, heightens the water solubility of a sparingly water-soluble anticancer agent, maintains a high drug concentration in the blood, accumulates a drug in a tumor tissue at a high concentration, heightens the pharmacological effect of the sparingly water-soluble anticancer agent, and diminishes the side effects of the anticancer agent. Provided are: a novel block copolymer which can be a drug carrier having no harmful side effects such as hypersensitive reaction; a micelle preparation in which micelles are formed and which contains a sparingly water-soluble anticancer agent, especially paclitaxel, incorporated in the micelles in an amount necessary for a disease treatment without bonding it to the block copolymer and which can heighten the solubility of the drug in water; and an anticancer agent which comprises the micelle preparation as a medical ingredient, maintains a high concentration in the blood, has more potent drug activity, and is reduced in toxicity.

First claim

What is claimed is:

1. A block copolymer represented by the following general formula (3):

wherein R1 represents a hydrogen atom or a (C1 to C5) alkyl group, R2 represents a (C1 to C5) alkylene group, R3 represents a methylene group or an ethylene group, R4 represents a hydrogen atom or a (C1 to C4) acyl group, R5 represents a hydroxyl group, an optionally substituted aryl (C1 to C8) alkoxy group or —N(R6)-CO—NHR7, R6 and R7 may be the same or different and each represents a (C3 to C6) cyclic alkyl group or a (C1 to C5) alkyl group optionally substituted with a tertiary amino group; n represents 5 to 1000, m represents 2 to 300, x′ represents 0 to 300 and y′ represents 0 to 300, provided that the sum of x′ and y′ is 1 or and less than m; and R5 is a hydroxyl group at a ratio 0% relative to m, an optionally substituted aryl (C1 to C8) alkoxy group at a ratio of 10-80% relative to m, and —N(R6)-CO—NHR7 at a ratio of 11-30% relative to m.

2. The block copolymer according to claim 1 , wherein R1 is a methyl group, R2 is a trimethylene group, R3 is a methylene group, R4 is an acetyl group, the optionally substituted aryl (C1 to C8) alkoxy group represented by R5 is a benzyloxy group or a 4-phenyl-1-butoxy group, each of R6 and R7 is an isopropyl group, n is 20 to 500, m is 10 to 100, x′ is 0 to 100, and y′ is 0 to 100.

3. A micelle preparation formed from the block copolymer of claim 1 or 2 and a sparingly water-soluble anticancer agent.

4. The micelle preparation according to claim 3 , wherein the sparingly water-soluble anticancer agent is a taxane-based anticancer agent.

5. The micelle preparation according to claim 4 , wherein the taxane-based anticancer agent is paclitaxel.

6. An anticancer agent comprising the micelle preparation of claim 3 as an active ingredient and a pharmacologically acceptable additive.

7. An anticancer agent comprising the micelle preparation of claim 4 as an active ingredient and a pharmacologically acceptable additive.

8. An anticancer agent comprising the micelle preparation of claim 5 as an active ingredient and a pharmacologically acceptable additive.

Assignees

• Nippon Kayaku Kk

Inventors

• Shimizu Kazuhisa
• Ishikawa Keizou
• Nakanishi Takeshi

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K31/337

  having four-membered rings, e.g. taxol · CPC title

• C08G81/00 Primary

  Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers (involving only carbon-to-carbon unsaturated bond reactions C08F299/00 {; polyester-amides C08G69/44; polyester-imides C08G73/16; polyamides-imides C08G73/14; block- or graft polymers containing polysiloxane sequences C08G77/42}) · CPC title

• A61K9/1075 Primary

  Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers (A61K9/0026 takes precedence) · CPC title

• A61K47/34

  Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers (A61K47/10 takes precedence) · CPC title