Method of Producing Fine Particles Surface-Modified with Water-Soluble Substance

• US 20080145414A1
• Filed: 01/27/2006
• Published: 06/19/2008
• Est. Priority Date: 01/28/2005
• Status: Active Grant

• Current Assignee: Kyowa Hakko Kirin Company Limited (Kirin Holdings Company Limited)
• Original Assignee: Kyowa Hakko Kirin Company Limited (Kirin Holdings Company Limited)
• Inventors: Nakakura, Masashi, Sugishita, Hiroko, Kusano, Hiroko, Yagi, Nobuhiro
• Granted Patent: US 9,937,127 B2
• Time in Patent Office: Days
• US Class Current: 424/450
• CPC Class Codes: A61K 9/0019 Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner non-active ingredients are additionally classified in A61K47/00
• CPC Class Codes: A61K 9/107 Emulsions ; Emulsion preconcentrates; Micelles composition of emulsions A61K47/00
• CPC Class Codes: A61K 9/1271 Non-conventional liposomes, e.g. PEGylated liposomes, liposomes coated with polymers liposome as conjugate A61K47/6911
• CPC Class Codes: A61P 29/00 Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: B01J 13/02 Making microcapsules or microballoons for medical preparations A61K9/50

Abstract

An object of the present invention is to provide a method of easily producing fine particles comprising a lipid, a fatty acid, or a derivative thereof, surface-modified with a water-soluble substance, etc. There are provided a method of producing a fine particles, surface-modified with a water-soluble substance, which contains the process of dispersing fine particles comprising a lipid, a fatty acid, or a derivative thereof, and dissolving or dispersing a surface modifier which is a lipid derivative, a fatty acid derivative, or an aliphatic hydrocarbon derivative of a water-soluble substance, in a liquid containing a polar organic solvent, and the like.

Claims

1. A method of producing fine particles, surface-modified with a water-soluble substance, which comprises the Step A of dispersing fine particles comprising a lipid, a fatty acid, or a derivative thereof, and dissolving or dispersing a surface modifier which is a lipid derivative, a fatty acid derivative, or an aliphatic hydrocarbon derivative of the water-soluble substance, in a liquid containing a polar organic solvent.

2. The method according to claim 1, wherein a polar organic solvent in which the surface modifier is soluble is used as the polar organic solvent.

3. The method according to claim 1, wherein one or more solvent(s) selected from alcohols, glycols, and polyalkylene glycols is used as the polar organic solvent.

4. The method according to claim 1, wherein a liquid containing the polar organic solvent in which a concentration of the polar organic solvent is 80 vol % or less is used as the liquid containing a polar organic solvent.

5. The method according to claim 1, wherein the fine particles comprising a lipid, a fatty acid, or a derivative thereof are fine particles coated with the lipid, the fatty acid, or the derivative thereof.

6. The method according to claim 1, wherein in the Step A, an amphiphilic substance is dissolved or dispersed in the liquid comprising a polar organic solvent.

7. The method according to claim 6, wherein the weight ratio between the amphiphilic substance and the surface modifier is 10:

1 to 1;

100.

8. The method according to claim 6, wherein the amphiphilic substance is one or more substance(s) selected from phospholipids, glycoglycerolipids, glycosphingolipids, cholesterols, cationic lipids, anionic lipids, surfactants, and lipid or fatty acid derivatives of water-soluble polymers.

9. The method according to claim 1, wherein the fine particles comprising a lipid, a fatty acid, or a derivative thereof are fine particles comprising one or more component(s) selected from a lipid assembly, liposome, and emulsion particles as a constituent component.

10. The method according to claim 1, wherein the surface modifier is one or more component(s) selected from polyethylene glycolated lipids, polyglycerolated lipids, polyethylene glycol alkyl ethers, polyethylene glycol sorbitan fatty acid esters, polyethylene glycol fatty acid esters, and polyglycerol fatty acid esters.

11. The method according to claim 6, wherein the fine particles comprising a lipid, a fatty acid, or a derivative thereof are liposome, the polar organic solvent is ethanol, the amphiphilic substance is a phospholipid, and the surface modifier is a polyethylene glycolated lipid.

12. The method according to claim 6, wherein the fine particles comprising a lipid, a fatty acid, or a derivative thereof are liposome, the polar organic solvent is ethanol, the amphiphilic substance is a phospholipid, and the surface modifier is a polyethylene glycol fatty acid ester.

13. A kit for preparing the fine particles comprising a lipid, a fatty acid, or a derivative thereof surface-modified by the method described in claim 1, which comprises at least fine particles comprising the lipid, the fatty acid, or the derivative thereof, a surface modifier which is a lipid derivative, a fatty acid derivative, or an aliphatic hydrocarbon derivative of a water-soluble substance, and a liquid containing a polar organic solvent.

14. Fine particles comprising a lipid, a fatty acid, or a derivative thereof, surface-modified with a water-soluble substance, obtainable by the method described in claim 1.

15. A therapeutic agent for tumor, which comprises the fine particles comprising a lipid, a fatty acid, or a derivative thereof, surface-modified with a water-soluble substance, obtainable by the method described in claim 1, wherein the fine particles contain an antitumor drug.

16. A therapeutic agent for inflammation, which comprises the fine particles comprising a lipid, a fatty acid, or a derivative thereof, surface-modified with a water-soluble substance, obtainable by the method described in claim 1, wherein the fine particles contain an anti-inflammatory drug.

17. A carrier comprising drug for a tumor site or an inflammation site, which comprises the fine particles comprising a lipid, a fatty acid, or a derivative thereof, surface-modified with a water-soluble substance, obtainable by the method described in claim 1, wherein the fine particles contain the drug.