Dispersion of poloxamer-protein particles, methods of manufacturing and uses thereof

Patent metadata

Field	Value
Publication number	US-10123976-B2
Application number	US-68122508-A
Country	US
Kind code	B2
Filing date	Oct 1, 2008
Priority date	Oct 1, 2007
Publication date	Nov 13, 2018
Grant date	Nov 13, 2018

Abstract

The present invention relates to a method for preparing poloxamer-protein particles. It also relates to poloxamer-protein particles obtainable by this method, dispersion thereof, and their use in methods of encapsulation, in particular of microencapsulation.

First claim

The invention claimed is:

1. A method for preparing a dispersion of poloxamer-protein particles, said method comprising the steps of:
i) preparing an aqueous solution comprising a protein and a poloxamer; and
ii) contacting the obtained solution with a water-miscible protein non-solvent in a sufficient amount to form a dispersion of poloxamer-protein particles,

wherein the water-miscible protein non-solvent is glycofurol and wherein said poloxamer-protein particles are solid.

2. The method of claim 1 , wherein the poloxamer is selected from the group consisting of poloxamer 188, 407, 338 and 237.

3. The method of claim 1 , wherein the aqueous solution further contains a salt.

4. The method of claim 3 , wherein the salt is present in a concentration ranging from 0.01 to 3M.

5. The method of claim 3 , wherein the salt is NaCl.

6. The method of claim 1 , wherein the protein is a therapeutic protein.

7. The method of claim 6 , wherein the protein is an enzyme, a growth factor, a cytokine, a hormone, an antibody, an antibody fragment or a coagulation factor.

8. The method of claim 1 , wherein the poloxamer-protein particles are recovered after centrifugation.

9. The method of claim 1 , wherein the water-miscible protein non-solvent further contains a dissolved wall-forming polymer.

10. The method of claim 1 , further comprising the step of iii) recovering the obtained poloxamer-protein particles.

11. A dispersion of poloxamer-protein particles obtainable according to claim 1 .

12. The dispersion according to claim 11 , wherein the water-miscible protein non-solvent, further contains a dissolved wall-forming polymer.

13. Poloxamer-protein particles obtainable according to claim 1 .

14. The protein particles according to claim 13 , of which median diameter ranges from 50 to 200 nm.

15. A method for encapsulating poloxamer-protein particles comprising:
i) preparing a s/o/w emulsion containing:
as a continuous phase, an aqueous phase, and
as a discontinuous phase, an organic solvent containing dispersed poloxamer-protein particles according to claim 13 and a wall-forming polymer, said wall-forming polymer being soluble in said organic solvent, and insoluble in said continuous phase, and

ii) solidifying said discontinuous phase, thereby forming encapsulated poloxamer-protein particles.

16. The method of claim 15 , wherein the wall-forming polymer is a polymer of lactic acid, a copolymer of lactic acid and glycolic acid or a polyethylene glycol conjugated with a copolymer of lactic acid and glycolic acid or with a polymer of lactic acid.

17. The method of claim 16 , wherein the wall-forming polymer is poly(D,L-lactide-co-glycolide) (PLGA) or PLGA-PEG-PLGA.

18. The method of claim 15 , further comprising the step of iii) recovering the obtained encapsulated poloxamer-protein particles.

19. A method for encapsulating poloxamer-protein particles comprising:
i) providing a dispersion of poloxamer-protein particles obtainable according to claim 1 , wherein the water-miscible protein non-solvent further contains a dissolved wall-forming polymer or dispersing poloxamer-protein particles obtainable according to claim 1 in a solution of a wall-forming polymer dissolved in a solvent;
ii) forming droplets of the dispersion of step i); and
iii) solidifying said droplets.

20. The method of claim 19 , wherein the droplets are solidified by extracting the solvent of the dispersion.

21. The method of claim 19 , further comprising the step of iv) recovering the obtained encapsulated poloxamer-protein particles.

22. Encapsulated poloxamer-protein particles obtainable according to claim 15 .

23. A pharmaceutical composition comprising encapsulated poloxamer-protein according to claim 22 .

Assignees

• Paillard Alexandra
• Venier Marie Claire
• Benoit Jean Pierre
• Institut National De La Sante Etde La Rech Medicale Inserm
• Univ Angers

Inventors

• Paillard Alexandra
• Venier Marie-Claire
• Benoit Jean-Pierre

Classifications

• A61K9/5089

  Processes · CPC title

• A61K9/5031

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide) · CPC title

• A61K9/5146 Primary

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides · CPC title

• A61K9/1641

  obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers · CPC title

• A61K9/5192

  Processes · CPC title