Amphiphilic block copolymer and polymeric composition comprising the same for drug delivery

• US 7,311,901 B2
• Filed: 10/07/2004
• Issued: 12/25/2007
• Est. Priority Date: 10/10/2003
• Status: Active Grant

• Current Assignee: Samyang Holdings Corporation
• Original Assignee: Samyang Corporation (Samyang Holdings Corporation)
• Inventors: Seo, Min Hyo, Kim, Bong Oh, Choi, In Ja, Shim, Myung Seob
• Primary Examiner(s): Hartley, Michael G.
• Assistant Examiner(s): VU, JAKE MINH
• Application Number:
  US10/962,204
• Publication Number:
  US 20050201972A1
• Time in Patent Office: 1,174 Days
• Field of Search: None
• US Class Current: 424/78.27
• 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: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C08G 63/08 Lactones or lactides
• CPC Class Codes: C08L 2666/02 Organic macromolecular compounds, natural resins, waxes or and bituminous materials
• CPC Class Codes: C08L 2666/14 Macromolecular compounds according to C08L59/00 - C08L87/00; Derivatives thereof
• CPC Class Codes: C08L 53/00 Compositions of block copolymers containing at least one sequence of a polymer obtained by reactions only involving carbon-to-carbon unsaturated bonds; Compositions of derivatives of such polymers

Abstract

The present invention relates to an amphiphilic block copolymer of a hydrophilic block and a hydrophobic block with a terminal hydroxyl group wherein the terminal hydroxyl group of the hydrophobic bock is substituted with a tocopherol or cholesterol group. It also relates to polymeric compositions capable of forming stable micelles in an aqueous solution, comprising the amphiphilic block copolymer and a polylactic acid derivative wherein one or more ends of the polylactic acid are covalently bound to at least one carboxyl group.

Claims

1. A block copolymer comprising hydrophilic A blocks and hydrophobic B blocks with a terminal hydroxyl group, wherein said terminal hydroxyl group of the hydrophobic block is substituted with tocopherol or cholesterol, wherein the hydrophilic A block is a member selected from the group consisting of polyalkylene glycols, polyvinyl alcohols, polyvinyl pyrrolidones, and polyacryl amides wherein the hydrophobic B block is a member selected from the group consisting of polylactides, polyglycolides, polycaprolactone, polydioxan-2-one, polylactic-co-glycolide, polylactic-co-dioxan-2-one, polylactic-co-caprolactone and polyglycolic-co-caprolacton.

2. The block copolymer according to claim 1, which is an A-B type diblock copolymer or a B-A-B type triblock copolymer.

3. The block copolymer according to claim 1, wherein the ratio of the hydrophilic A block to the hydrophobic B block is within the range of 30:

70 to 97;

3 by weight.

4. The block copolymer according to claim 1, wherein the hydrophilic A block has a number average molecular weight of 200 to 50,000 Daltons.

5. The block copolymer according to claim 1, wherein the hydrophobic B block has a weight average molecular weight of 50 to 50,000 Daltons.

7. A drug carrier comprised essentially of block copolymer according to claim 1.

6. A block copolymer, which is represented by the following formula:

R_1′

—

O—

[R_3′

]_x′

—

[R_4′

]_m′

—

[R_5′

]_n′

—

C(═

O)—

(CH₂)_x′

—

C(═

O)—

O—

R_2′

 

 

(I′

)

wherein R_1′

is CH₃—

, H—

[R_5′

]_n′

—

[R_4′

]_m′

—

, or R_2′

—

O—

C(═

O)—

(CH₂)_x′

—

C(═

O)—

[R_5′

]_n′

—

[R_4′

]_m′

—

;

R_2′

is tocopherol or cholesterol;

R_3′

is —

CH₂CH₂—

O—

, —

CH(OH)—

CH₂—

, —

CH(C(═

O)—

NH₂)—

CH₂—

, or