Encapsulation of lipophilic or amphiphilic therapeutic agents in nano-emulsion

Patent metadata

Field	Value
Publication number	US-10092506-B2
Application number	US-200913058850-A
Country	US
Kind code	B2
Filing date	Aug 14, 2009
Priority date	Aug 14, 2008
Publication date	Oct 9, 2018
Grant date	Oct 9, 2018

Abstract

The invention also relates to a preparation method and use of this formulation.

First claim

The invention claimed is:

1. Therapeutic agent formulation in the form of a stable nano-emulsion, comprising a continuous aqueous phase and at least one dispersed oily phase, wherein the surface of the dispersed phase has a zeta potential in a range of from more than −20 mV to less than 20 mV,
wherein the aqueous phase comprises a polyalkoxylated cosurfactant comprising at least one chain composed of ethylene oxide units or ethylene oxide and propylene oxide units,
wherein the oily phase also comprises (i) a therapeutic agent, and (ii) at least one phospholipid and at least one solubilising lipid consisting of a mixture of saturated fatty acid glycerides comprising:
0% to 20% by weight C8 fatty acids
0% to 20% by weight C10 fatty acids,
10% to 70% by weight C12 fatty acids,
5% to 30% by weight C14 fatty acids,
5% to 30% by weight C16 fatty acids, and
5% to 30% by weight C18 fatty acids,
and wherein the dispersed oily phase has an average droplet size of from 10 to 200 nm, so that the therapeutic agent formulation exhibits colloidal stability during storage over a period of at least about 170 days at 40° C. and stealthy character upon administration.

2. Therapeutic agent formulation according to claim 1 , wherein the oily phase further comprises at least one oil.

3. Therapeutic agent formulation according to claim 2 , wherein the oil has a hydrophilic-lipophilic balance (HLB) of between 3 and 6.

4. Therapeutic agent formulation according to claim 1 , wherein the cosurfactant is selected from the conjugated compounds polyethylene glycol/phosphatidylethanolamine (PEG-PE), fatty acid and polyethylene glycol ethers, fatty acid and polyethylene glycol esters, and ethylene oxide and propylene oxide block copolymers.

5. Therapeutic agent formulation according to claim 1 , wherein the therapeutic agent is a pharmaceutical ingredient.

6. Therapeutic agent formulation according to claim 1 , wherein the therapeutic agent is a photosensitizer.

7. Therapeutic agent formulation according to claim 1 , characterised in that it is functionalised.

8. Method for preparing a therapeutic agent formulation in the form of a nano-emulsion comprising at least one continuous aqueous phase and at least one dispersed oily phase, said method comprising the steps of:
(i) preparing the oily phase comprising the therapeutic agent, a phospholipid and at least one solubilising lipid consisting of a mixture of saturated fatty acid glycerides comprising:
0% to 20% by weight C8 fatty acids
0% to 20% by weight C10 fatty acids,
10% to 70% by weight C12 fatty acids,
5% to 30% by weight C14 fatty acids,
5% to 30% by weight C16 fatty acids, and
5% to 30% by weight C18 fatty acids;
(ii) preparing an aqueous phase comprising a polyalkoxylated cosurfactant comprising at least one chain composed of ethylene oxide units or ethylene oxide and propylene oxide units;
(iii) dispersing the oily phase in the aqueous phase under the effect of sufficient shear force to form a nano-emulsion; and
(iv) recovering the nano-emulsion thus formed, wherein the nano-emulsion is a therapeutic agent formulation according to claim 1 .

9. Preparation method according to claim 8 , wherein the shear force effect is produced by sonication.

10. Preparation method according to claim 8 , wherein the oily phase is prepared by placing all or some of the constituents in solution in an appropriate solvent and subsequently evaporating the solvent.

11. Therapeutic treatment method comprising administration of an effective therapeutic amount of the formulation according to claim 1 to a mammal in need, thereof.

12. Therapeutic agent formulation according to claim 1 , wherein the polyalkoxylated cosurfactant of the aqueous phase is the only polyalkoxylated cosurfactant in the therapeutic agent formulation.

13. Preparation method according to claim 8 , wherein the polyalkoxylated cosurfactant of the aqueous phase is the only polyalkoxylated cosurfactant in the therapeutic agent formulation.

Assignees

• Mourier Robert Veronique
• Bibette Jerome
• Goutayer Mathieu
• Navarro Y Garcia Fabrice
• Texier Nogues Isabelle
• Commissariat Energie Atomique

Inventors

• Mourier-Robert Veronique
• Bibette Jerome
• Goutayer Mathieu
• Navarro Y Garcia Fabrice
• Texier-Nogues Isabelle

Classifications

• A61K41/0071

  PDT with porphyrins having exactly 20 ring atoms, i.e. based on the non-expanded tetrapyrrolic ring system, e.g. bacteriochlorin, chlorin-e6, or phthalocyanines · CPC title

• B82Y5/00

  Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery · CPC title

• A61K9/0019 Primary

  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 title

• A61K47/6907

  the form being a microemulsion, nanoemulsion or micelle · CPC title

• A61K9/1075

  Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers (A61K9/0026 takes precedence) · CPC title