Amphiphilic diblock, triblock and star-block copolymers and their pharmaceutical compositions

• US 7,018,655 B2
• Filed: 03/18/2002
• Issued: 03/28/2006
• Est. Priority Date: 03/18/2002
• Status: Expired due to Term

• Current Assignee: Paladin Pharma Incorporated
• Original Assignee: Labopharm Incorporated (Endo International PLC)
• Inventors: Leroux, Jean-Christophe, Lele, Bhalchandra Shripad
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): FUBARA, BLESSING M
• Application Number:
  US10/101,093
• Publication Number:
  US 20030181613A1
• Time in Patent Office: 1,471 Days
• Field of Search: 424/486, 424/489, 424/450, 514/772.3, 526/222
• US Class Current: 424/486
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: C08F 293/00 Macromolecular compounds obtained by polymerisation on to a macromolecule having groups capable of inducing the formation of new polymer chains bound exclusively at one or both ends of the starting macromolecule on to polymers modified by introduction of unsaturated end groups C08F290/02

Abstract

This invention relates to novel amphiphilic diblock, triblock copolymers and star-shaped block copolymers comprising a biodegradable polymer covalently attached at the polymer ends, to a hydrophilic vinyl polymer, via divalent sulfur atom; to a process for producing the block polymers; to a polymerization process which comprises subjecting the monomers capable of radical polymerization to radical polymerization in the presence of a macromolecular biodegradable chain-transfer agent; and to pharmaceutical compositions comprising the block copolymers loaded with therapeutic agents.

Claims

1. A therapeutic composition consisting of:

an amphiphilic diblock, triblock or star-shaped block copolymer formed by a biodegradable polymer selected from the group consisting of a polyester, a polyamide, a poly(ester-amide), a polyanhydride and combinations thereof, being covalently attached at the polymer ends to at least one hydrophilic vinyl polymer by way of a divalent sulfur atom; and

an effective amount of at least one therapeutic agent;

wherein said therapeutic composition is characterized by its ability to form a nanodispersion or micelle in aqueous media.

2. The therapeutic composition accordance with claim 1 wherein said hydrophilic vinyl polymer is at least one member selected from the group consisting of poly(N-2-hydroxypropylmethacrylamide), poly(N-vinylpyrrolidone), poly(ethylene glycol)methacrylate, poly(N-isopropyl acrylamide), polyacrylic acid, polymethacrylic acid, poly(2-aminoethylmethacrylate), poly(3-aminopropylmethacrylamide), poly(2-N,N-dimethylaminoethylmethacrylate) and copolymers thereof.

5. The therapeutic composition in accordance with claim 1 wherein:

said at least one therapeutic agent is poorly water-soluble and is at least one member selected from the group consisting of anticancer drugs, antifungal drugs, antiviral drugs, antibacterials, immunomodulators, central nervous system agents, anti-inflammatory drugs, or combinations thereof.

6. The therapeutic composition in accordance with claim 5 wherein:

said anticancer drug is at least one member selected from the group consisting of aluminium chloride phthalocyanines, doxorubicin, vinbiastine, paclitaxel, docetaxel, melphalan, teniposide, etiposide, and combinations thereof.

8. The therapeutic composition accordance with claim 1 wherein said biodegradable polyester is at least one member selected from the group consisting of hydroxyl or carboxyl end-functionalized linear and star shaped poly(ε

-caprolactone), poly(L-lactide), poly(D-lactide), poly(D,L-lactide), poly(glycolic acid), poly(lactide-co-glycolide), poly(3-hydroxybutyrate) and derivatives thereof.

3. A therapeutic composition consisting of:

an amphiphilic diblock, triblock or star-shaped block copolymer formed by a biodegradable polymer selected from the group consisting of a polyester, a polyamide, a poly(ester-amide), a polyanhydride and combinations thereof, being covalently attached at the polymer ends to at least one hydrophilic vinyl polymer by way of a divalent sulfur atom;

and an effective amount of at least one therapeutic agent; and

at least one targeting moiety conjugated to pendant functional groups in said at least one hydrophilic vinyl polymer;

wherein said therapeutic composition is characterized by its ability to form a nanodispersion or micelle in aqueous media.

4. The therapeutic composition accordance with claim 3 wherein said targeting moiety is at least one member selected from the group consisting of vitamins, sugars, antibodies, lectins, peptides and combinations thereof.

7. The therapeutic composition in accordance with claim 3 wherein said targeting moiety is provided in an amount effective to provide site-specific delivery of said therapeutic agent.