Injectable fillers for aesthetic medical enhancement and for therapeutic applications

• US 9,561,961 B2
• Filed: 08/17/2012
• Issued: 02/07/2017
• Est. Priority Date: 08/19/2011
• Status: Active Grant

• Current Assignee: Xtant Medical Holdings, Inc. (OrbiMed Advisors LLC (China))
• Original Assignee: Pioneer Surgical Technology Incorporated (Surgalign Holdings, Inc.)
• Inventors: Capistron, Stephen M., Ahn, Edward S.
• Primary Examiner(s): Javier, Melissa
• Application Number:
  US13/588,809
• Publication Number:
  US 20130060230A1
• Time in Patent Office: 1,635 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: A61K 2800/594 Mixtures of polymers
• CPC Class Codes: A61K 2800/91 Injection
• CPC Class Codes: A61K 8/0279 Porous; Hollow
• CPC Class Codes: A61K 8/042 Gels
• CPC Class Codes: A61K 8/24 Phosphorous; Compounds thereof
• CPC Class Codes: A61K 8/73 Polysaccharides
• CPC Class Codes: A61K 8/90 Block copolymers A61K8/89 takes precedence
• CPC Class Codes: A61Q 19/08 Anti-ageing preparations
• CPC Class Codes: C01B 25/32 Phosphates of magnesium, calcium, strontium, or barium
• CPC Class Codes: C01B 25/327 After-treatment increasing the phosphate content of ores C01B25/32
• CPC Class Codes: C01P 2004/61 Micrometer sized, i.e. from 1-100 micrometer
• CPC Class Codes: C01P 2006/12 Surface area

Abstract

The present invention relates to a biocompatible injectable filler composition comprising calcium phosphate particles having a porosity of about 10% to about 90%, a BET surface area of about 1 m²/g to about 100 m²/g, and a mean particle size of about 1 micron to about 30 microns, a thermoreversible hydrophilic gelling agent, a carrier comprising water and an optional persistence enhancer and/or volumizing agent, and methods of its use to restore tissue volume and/or to smooth out tissue defects as in soft tissue or deep tissue augmentation.

Claims

1. An injectable soft tissue filler composition comprising

(a) about 40% calcium phosphate particles, based on the weight of the filler composition, wherein the calcium phosphate particles have a porosity of about 10% to about 90%, a surface area of about 1 m²/g to about 100 m²/g, and a mean particle size of about 2 microns to about 10 microns, and are acid etched,

(b) about 5% to about 15% poloxamer, based on the weight of the filler composition, wherein the poloxamer is a hydrogel that is in the form of a liquid at 25°

C. and in the form of a gel having a viscosity of about 2000 cP or more at 35°

C.,

(c) a persistence enhancer selected from the group consisting of dextran and agarose, and

(d) aqueous carrier,

wherein the soft tissue filler composition has a pH of about 6.5 to about 7.5,

wherein the soft tissue filler composition can be injected through a 27 gauge or smaller opening needle, and

wherein the soft tissue filler composition is pliable, moldable, flexible, and has a viscosity of about 100,000 cP to about 200,000 cP after injection into the soft tissue.

2. The filler composition of claim 1, wherein the calcium phosphate particles are selected from the group consisting of hydroxyapatite, tricalcium phosphate, octacalcium phosphate, and combinations thereof.

3. The filler composition of claim 1, wherein the calcium phosphate particles comprise hydroxyapatite.

4. The filler composition of claim 1, wherein the calcium phosphate particles have an average crystal size of about 300 nm or less.

5. The filler composition of claim 1, wherein the poloxamer contains a block copolymer having a middle block of poly(propylene oxide) with a molecular weight of from about 1450 g/mol to about 6000 g/mol, and end blocks of poly(ethylene oxide) that comprise about 50% to about 90% by weight of the copolymer.

6. The filler composition of claim 5, wherein the poloxamer has a polyoxypropylene molecular mass of 4,000 g/mol and a 70% polyoxyethylene content.

7. The filler composition of claim 1, wherein the persistence enhancer is a dextran having an average molecular weight of about 500,000 g/mol or greater.

8. The filler composition of claim 1, wherein the composition comprises about 0.1% to about 25% persistence enhancer, by weight of the filler composition.

9. The filler composition of claim 1, wherein the calcium phosphate particles have a rounded morphology.

10. The filler composition of claim 1, wherein the calcium phosphate particles comprise about 95% or more hydroxyapatite, wherein poloxamer is poloxamer 407, and wherein the persistence enhancer is dextran having an average molecular weight of about 500,000 g/mol or greater, glycerol, and a phosphate buffer.

11. The filler composition of claim 10, wherein the amount of dextran is about 2% to about 8%, the amount of glycerol is about 2% to about 6%, and the amount of aqueous carrier is about 40% to about 50%, based on the weight of the filler composition.

12. The filler composition of claim 1, wherein the amount of poloxamer is about 5% to about 10%.

13. The filler composition of claim 11, wherein the amount of poloxamer is about 5% to about 10%.

14. The filler composition of claim 12, wherein the poloxamer is poloxamer 407.