Method for the production of polymerized nanoparticles and microparticles by ternary agent concentration and temperature alteration induced immiscibility

• US 7,495,052 B2
• Filed: 09/15/2004
• Issued: 02/24/2009
• Est. Priority Date: 09/15/2004
• Status: Expired due to Fees

• Current Assignee: Bausch & Lomb Incorporated (Bausch Health Cos., Inc.)
• Original Assignee: Bausch & Lomb Incorporated (Bausch Health Cos., Inc.)
• Inventors: Raiche, Adrian T., Linhardt, Jeffrey, Salamone, Joseph C.
• Primary Examiner(s): Cain; Edward J
• Application Number:
  US10/941,163
• Publication Number:
  US 20060057222A1
• Time in Patent Office: 1,623 Days
• Field of Search: 524/457, 524/458, 524/725, 524/765
• US Class Current: 524/457
• CPC Class Codes: A61K 9/1682 Processes
• CPC Class Codes: A61K 9/5089 Processes
• CPC Class Codes: C08F 2/22 Emulsion polymerisation

Abstract

Polymerized drug delivery devices are described. Additionally, methods are described for producing and for using polymerized particles for use as drug delivery devices.

Claims

1. A method for the production of polymer-containing particles comprising:

combining (a) a non-solvent;

(b) a ternary agent;

(c) a surfactant;

(d) a monomer, macromonomer, or a combination thereof; and

(e) an initiator to produce a non-solvent solution;

combining a solvent that is miscible with said non-solvent, and a polymer that is soluble in said solvent to produce a solvent solution; and

combining said non-solvent solution and said solvent solution to produce polymer-containing particles as a result of a phase separation between a non-solvent phase and a solvent phase induced by an amount of said ternary agent.

3. The method of claim 1 or 2 wherein said monomer or macromonomer is selected from the group consisting of poly(ethylene glycol) diamethacrylate, methylene bisacrylamide, 2-hydroxyethyl methacrylate, methyl methacrylate, acrylic acid, methacrylic acid2-ethylhexyl methacrylate, 3-methacryloyloxypropyldiphenylmethylsilane, 3-methacryloyloxypropyltris (trimethylsiloxy)silane, 2-phenyoxyethyl methacrylate, poly(proprionic acid) and copolymers containing poly(proprionic acid), polycaprolactone dimethacrylate and other methacrylate, glycidyl and cyanoacrylate end-capped macromonomers.

4. The method of claim 1 or 2 wherein said initiator is selected from the group consisting of azobis-isobutyronitrile, acetyl peroxide, lauroyl peroxide, decanoyl peroxide, stearoyl peroxide, benzoyl peroxide, tert-butyl peroxypivalate, peroxydicarbonate, benzoin methyl ether, benzoin ethyl ether.

5. The method of claim 1 or 2 wherein said initiator is selected from the group consisting of free radical thermal polymerization initiators, ultraviolet light initiators, and blue light initiators.

6. The method of claim 1 or 2 wherein size of said polymer-containing particles is controlled through temperature variation.

7. The method of claim 1 or 2 wherein size of said polymer-containing particles are about 1 mm to about 0.10 nm in size.

8. The method of claim 1 or 2 wherein size of said polymer-containing particles are about 400 nm to about 0.10 nm in size.

9. The method of claim 1 or 2 wherein size of said polymer-containing particles are about 350 nm to about 0.50 nm in size.

10. The method of claim 1 or 2 wherein said solvent is selected from the group consisting of acetone, acetonitrile, ethanol, isopropyl alcohol, dimethyl sulfoxide, dimethyl formamide, tetrahydrofuran and dioxane.

11. The method of claim 1 wherein solvent is acetone, acetonitrile or a combination thereof.

12. The method of claim 1 wherein said non-solvent is selected from the group consisting of water, alcohols, ethers, amine-containing solvents, carboxyl-containing solvents and organic solvents.

13. The method of claim 1 wherein non-solvent is water, methanol, ethanol or a combination thereof.

14. The method of claim 1 wherein said ternary agent is selected from the group consisting of ammonium azide, ammonium bisulfite, barium acetate hydrate, barium hypophosphate, cadmium chloride, calcium acetate dihydrate, calcium chromate, calcium ethyl methyl acetate, cobalt perchiorate, iron perchiorate hexahydrate, lead chlorate hydrate, lithium hydroxide monohydrate, lithium sulfate, lithium sulfite monohydrate, potassium carbonate, potassium chloride, sodium selenate, sodium stannate (hydroxo), strontium acetate and yttrium chloride.

15. The method of claim 1 wherein said ternary agent is sodium chloride, sodium bromide or a combination thereof.

16. The method of claim 1 wherein said polymer is selected from the group consisting of polyesters, polyanhydrides, polyorthoesters, polyurethanes, polyethylene and its derivatives, all acrylate-based polymers including poly(acrylic acid), poly(methyl methacrylate) and poly(2-hydroxyethyl methacrylate), poly(N-vinylpyrrolidone) and polyethylenimine.

17. The method of claim 1 wherein said solvent solution further comprising a material selected from the group consisting of trehalose, dextrose, triethanolamine, and calcium carbonate.

18. The method of claim 1 wherein said surfactant is selected from the group consisting of poly(N-vinylpyrrolidone), poly(ethylene oxide)/poly(propylene oxide) triblock copolymers, Tweens, Sorbitans and triacyl glycerols.

19. The method of claim 1 or 2 wherein said polymer-containing particles are useful as drug delivery agents.

20. The method of claim 1 or 2 wherein said polymer-containing particles are useful as ophthalmic drug delivery agents.

2. A method for the production of polymer-containing particles, the method comprising:

combining;

(a) water;

(b) sodium chloride;

(c) sodium bromide;

(d) poly(ethylene oxide)/poly(propylene oxide) triblock copolymers;

one or more monomers, macromonomers or a combination thereof; and

one or more initiators to produce a non-solvent solution;

combining;

(a) acetone;

(b) acetonitrile; and

one or more (c) (i) polysaccharide and polyurethane polymers, or (ii) trehalose, dextrose and triethanolamine, or (iii) a combination thereof to produce a solvent solution; and

combining said non-solvent solution with said solvent solution to produce polymerized particles ranging in size from about 0.10 nm to about 1 mm.