Amphiphilic polymer

Patent metadata

Field	Value
Publication number	US-10143651-B2
Application number	US-201615355225-A
Country	US
Kind code	B2
Filing date	Nov 18, 2016
Priority date	Nov 25, 2015
Publication date	Dec 4, 2018
Grant date	Dec 4, 2018

Abstract

The present application relates to a micelle comprising a drug encapsulated by an amphiphilic polymer and a composition comprising the same. The micelle of the present application has an excellent dispersion property on an aqueous solution and a superior percutaneous absorption characteristic on preparing a formulation.

First claim

What is claimed is:

1. A micelle comprising:
a drug; and
an amphiphilic polymer which encapsulates said drug, has a first block (A) and a second block (B) that is phase-separated with said first block (A) and comprises a polymerization unit (B1) of an acrylic monomer or a vinylic monomer having a solubility parameter of a single polymer of less than 10.0 (cal/cm 3 ) 1/2 and a polymerization unit (B2) of a polymerizable monomer having a functional group being capable of forming a hydrogen bond,
wherein the first block (A) comprises a polymer having a solubility parameter of 10 (cal/cm 3 ) 1/2 or more,
wherein a weight ratio (B1:B2) of the polymerization unit (B1) of an acrylic monomer or a vinylic monomer having a solubility parameter of a single polymer of less than 10.0 (cal/cm 3 ) 1/2 and the polymerization unit (B2) of a polymerizable monomer having a functional group being capable of forming a hydrogen bond, in the second block (B), is in a range of 1:9 to 9:1,
wherein the drug includes intramolecular —H, wherein the intramolecular —H forms a hydrogen bond with the functional group of polymerization unit (B2) in the second block (B) of the amphiphilic polymer.

2. The micelle according to claim 1 , wherein the drug comprises a physiologically active substance.

3. The micelle according to claim 2 , wherein the physiologically active substance is sparingly soluble.

4. The micelle according to claim 3 , wherein the sparingly soluble and physiologically active substance is any one selected from the group consisting of genistein, daidzein, cucurbitasin, prangenidin or a derivative thereof; a polyphenol; or a mixture thereof.

5. The micelle according to claim 4 , wherein the sparingly soluble and physiologically active substance is genistein or a glycoside of said genistein.

6. The micelle according to claim 1 , wherein the first block (A) is any one selected from the group consisting of polyethylene glycol, a polyethylene glycol-propylene glycol copolymer, polyvinyl pyrrolidone and polyethyleneimine.

7. The micelle according to claim 1 , wherein
the acrylic monomer is represented by Formula 1 or Formula 2 below:

where, Q in Formula 1 and 2 is hydrogen or an alkyl group, B in Formula 1 is a straight or branched alkyl group having at least one carbon atom, an alicyclic hydrocarbon group, an aromatic substituent or a carboxyl group, and R 1 and R 2 in Formula 2 are each independently hydrogen, a straight or branched alkyl group having at least one carbon atom, an alicyclic hydrocarbon group, or an aromatic substituent.

8. The micelle according to claim 7 , wherein
Q in Formula 1 is hydrogen or an alkyl group having 1 to 4 carbon atoms, B is an alkyl group having at least one carbon atom or an alicyclic hydrocarbon group having 6 to 12 carbon atoms.

9. The micelle according to claim 1 , wherein
the vinylic monomer is represented by Formula 3 or Formula 4 below:

where, X is a nitrogen atom or an oxygen atom, Y is a carbonyl group or a single bond, R 3 and R 5 are each independently hydrogen or an alkyl group, or R 3 and R 5 are linked together to form an alkylene group, and R 4 is an alkenyl group (provided that R 3 is not present, if X is an oxygen atom);

where, R 6 , R 7 and R 8 are each independently hydrogen or an alkyl group, and R 9 is a cyano group or an aromatic substituent.

10. The micelle according to claim 1 , wherein
the functional group is a hydroxyl group, an amine group, a nitro group, an amino group, an imide group, an alkoxysilane group or a cyano group.

11. The micelle according to claim 1 , wherein
the amphiphilic polymer has a block ratio (A:B) of the first block (A) and the second block (B) different from each other.

12. The micelle according to claim 11 , wherein
the block ratio (A:B) of the first block (A) and the second block (B) in the amphiphilic polymer is 1:9 to 9:1.

13. The micelle according to claim 1 , wherein
the block ratio (A:B) of the first block (A) and the second block (B) in the amphiphilic polymer is 3:7 to 7:3.

14. The micelle according to claim 1 , wherein
the second block of the amphiphilic polymer is adjacent to the drug.

15. The micelle according to claim 1 , wherein
the average particle diameter is in a range of 1 to 10,000 nm.

16. A composition for preparing particles comprising the micelle of claim 1 .

17. A pharmaceutical or cosmetic composition comprising the micelle of claim 1 .

18. The pharmaceutical or cosmetic composition according to claim 17 , wherein the composition is in a water-in-oil type emulsion form or an oil-in-water type emulsion form.

19. A process for preparing the micelle of claim 1 comprising:
a step of polymerizing a polymer forming a first block (A) and an acrylic monomer or a vinylic monomer having a solubility parameter of a single polymer of less than 10.0 (cal/cm 3 ) 1/2 to prepare an amphiphilic polymer; and
a step of mixing said amphiphilic polymer and a drug.

Assignees

• Lg Chemical Ltd
• Lg Household & Health Care Ltd

Inventors

• Kim Su Jeong
• Yoon Jeong Ae
• Lee Sun Hwa
• Shim Woo Sun
• Yoon Sung Soo
• Ju Chang Hwan
• Kim Jung A
• Kang Nae Gyu

Classifications

• 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

• A61K31/352

  condensed with carbocyclic rings, e.g. methantheline  {(cannabinoids A61K31/658)} · CPC title

• A61K47/32

  Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers {, poly(meth)acrylates, or polyvinyl pyrrolidone} · CPC title

• C08F220/14

  Methyl esters {, e.g. methyl (meth)acrylate} · CPC title

• C08F293/00

  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) · CPC title