Process for producing block copolymer/drug composite

• US 20050214375A1
• Filed: 06/18/2003
• Published: 09/29/2005
• Est. Priority Date: 06/19/2002
• Status: Abandoned Application

• Current Assignee: Nippon Kayaku Company Limited, Yasuhisa Sakurai
• Original Assignee: Nippon Kayaku Company Limited, Yasuhisa Sakurai
• Inventors: Nakanishi, Takeshi, Shimizu, Kazuhisa
• Application Number:
  US10/517,729
• Publication Number:
  US 20050214375A1
• Time in Patent Office: Days
• US Class Current: 424/486
• CPC Class Codes: A61K 31/785 Polymers containing nitrogen
• CPC Class Codes: A61K 47/34 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 Class Codes: A61K 47/6907 the form being a microemulsion, nanoemulsion or micelle
• CPC Class Codes: A61K 9/19 lyophilised , i.e. freeze-dried, solutions or dispersions lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C08G 73/1092 Polysuccinimides
• CPC Class Codes: C08L 2666/20 Macromolecular compounds having nitrogen in the main chain according to C08L75/00 - C08L79/00; Derivatives thereof
• CPC Class Codes: C08L 71/10 from phenols

Abstract

A process for producing a block copolymer-drug composite that can be industrialized, wherein neither dialysis nor ultrafiltration is performed and wherein halogenated hydrocarbons are not used. The process for producing a block copolymer-drug composite is characterized by comprising the steps of dissolving an AB type block copolymer composed of hydrophilic polymer structure moiety and hydrophobic polyamino aid structure moiety together with a drug in water or a mixed solvent of water and a low-boiling-point organic solvent miscible with water and concentrating the resultant solution.

Claims

1. A process for producing a block copolymer-drug composite, comprising the steps of dissolving an AB type block copolymer composed of hydrophilic polymer structure moiety and hydrophobic polyamino acid structure moiety together with a drug in water or a mixed solvent of water and a low-boiling-point organic solvent miscible with water, and concentrating the resultant solution.

2. The process for producing a block copolymer-drug composite according to claim 1, wherein neither dialysis nor ultrafiltration process is included in the production process.

3. The process for producing a block copolymer-drug composite according to claim 1 or 2, wherein the hydrophilic polymer structure moiety in the AB type block copolymer is a polyethylene oxide derivative, and the hydrophobic polyamino acid structure moiety in the AB type block copolymer is polyaspartic acid containing aspartic acid having a side chain carboxyl group bonded by an anthracycline-based anticancer agent.

4. The process for producing a block copolymer-drug composite according to claim 1 or 2, wherein the hydrophilic polymer structure moiety in the AB type block copolymer is a polyethylene oxide derivative, and the hydrophobic polyamino acid structure moiety in the AB type block copolymer is polyglutamic acid containing glutamic acid having a side chain carboxyl group bonded by an anthracycline-based anticancer agent.

5. The process for producing a block copolymer-drug composite according to claim 3 or 4, wherein the anthracycline-based anticancer agent bonded to a side chain carboxyl group on the hydrophobic polyamino acid structure moiety is doxorubicin.

6. The process for producing a block copolymer-drug composite according to any one of claims 1 to 5, wherein the drug is an anthracycline-based anticancer agent.

7. The process for producing a block copolymer-drug composite according to claim 6, wherein the anthracycline-based anticancer agent is doxorubicin or a salt thereof.

8. A process for producing a lyophilization preparation containing a block copolymer-drug composite, comprising the steps of dissolving an AB type block copolymer composed of hydrophilic polymer structure moiety and hydrophobic polyamino acid structure moiety together with a drug in water or a mixed solvent of water and a low-boiling-point organic solvent miscible with water, concentrating the resultant solution, and further lyophilizing this.