Emulsion vehicle for poorly soluble drugs

• US 6,667,048 B1
• Filed: 07/27/1999
• Issued: 12/23/2003
• Est. Priority Date: 01/07/1997
• Status: Expired due to Fees

• Current Assignee: Sonus Pharmaceuticals Inc. (Achieve Life Sciences, Inc.)
• Original Assignee: Sonus Pharmaceuticals Inc. (Achieve Life Sciences, Inc.)
• Inventors: Quay, Steven C., Constantinides, Panayiotis P., Lambert, Karel J.
• Primary Examiner(s): Webman, Edward J.
• Application Number:
  US09/361,935
• Time in Patent Office: 1,610 Days
• Field of Search: 424/486, 424/422-23, 514/938, 514/975
• US Class Current: 424/405
• CPC Class Codes: A61K 47/22 Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
• 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 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: Y10S 977/775 Nanosized powder or flake, e.g. nanosized catalyst
• CPC Class Codes: Y10S 977/801 Drug
• CPC Class Codes: Y10S 977/907 Liposome
• CPC Class Codes: Y10S 977/915 Therapeutic or pharmaceutical composition

Abstract

An emulsion of α-tocopherol, stabilized by biocompatible surfactants, as a vehicle or carrier for therapeutic drugs, which is substantially ethanol free and which can be administered to animals or humans various routes is disclosed. Also included in the emulsion is PEGylated vitamin E. PEGylated α-tocopherol includes polyethylene glycol subunits attached by a succinic acid diester at the ring hydroxyl of vitamin E and serves as a primary surfactant, stabilizer and a secondary solvent in emulsions of α-tocopherol.

Claims

1. A pharmaceutical composition, comprising a chemotherapeutic agent, wherein the chemotherapeutic agent is at least one of a taxoid, a taxane, or a taxine;

α

-tocopherol;

a tocopherol polyethylene glycol succinate; and

an aqueous phase;

wherein the composition is an emulsion or a microemulsion having an oil and a water phase, and wherein all of the chemotherapeutic agent is in the oil phase.

2. The composition of claim 1 further comprising a cosolvent.

3. The composition of claim 2 wherein said cosolvent is polyethylene glycol, ethanol, methanol, propanol, chloroform, isopropanol, butanol or pentanol.

4. The composition of claim 2 wherein said cosolvent is polyethylene glycol.

5. The composition of claim 4 wherein said polyethylene glycol has an average molecular weight of 100 to 600.

6. The composition of claim 4 wherein said polyethylene glycol has an averae molecular weight of 400.

7. The composition of claim 1, wherein the ratio of α

-tocopherol to the tocopherol polyethylene glycol succinate is from 1;

1 to 10;

1 w/w.

8. The composition of claim 1 further comprising a surfactant.

9. The composition of claim 8, wherein said surfactant has an HLB of at least 10.

10. The composition of claim 8, wherein said surfactant is at least one of an anionic, a cationic, a nonionic, or a zwitterionic surfactant.

11. The composition of claim 8, wherein said surfactant is at least one of a polyoxypropylene-polyoxyethylene glycol nonionic block co-polymer, ascorbyl-6-palmitate, vitamin E polyglutamate, stearylamine, or a sucrose fatty ester.

12. The composition of claim 8, wherein said surfactant is ascorbyl-6-palmitate.

13. The composition of claim 8, wherein said surfactant is a polyoxypropylene-polyoxyethylene glycol nonionic block co-polymer.

14. The composition of claim 13, wherein said block co-polymer has the structure:

15. The composition of claim 1, wherein said chemotherpeutic agent is paclitaxel.

16. The composition of claim 15, wherein the concentration of said paclitaxel in said composition is 1 to 20 mg/ml.

17. The composition of claim 16 wherein the cocentration of said paclitaxel in said composition is 5 to 10 mg/ml.

18. The composition of claim 1 that is substantially ethanol-free.

19. The composition of claim 1, wherein the emulsion or microemulsion has a particle size from about 10 nm to about 500 nm.

20. The composition of claim 19, wherein the emulsion or microemulsion has a particle size from about 10 nm to about 200 nm.

21. The composition of claim 19, wherein the emulsion or microemulsion has a particle size from about 10 nm to about 100 nm.