	US 12,220,427 B2
	Continuous release compositions made from hyaluronic acid, and therapeutic applications of same
Yannis Guillemin, Villeneune Loubet (FR); and Jean-Noël Gouze, Vallauris (FR)
Assigned to IBSA PHARMA SAS, Antibes (FR)
Filed by IBSA PHARMA SAS, Antibes (FR)
Filed on Feb. 14, 2023, as Appl. No. 18/169,051.
Application 18/169,051 is a division of application No. 17/067,297, filed on Oct. 9, 2020, granted, now 11,738,039.
Application 17/067,297 is a continuation of application No. 14/909,909, granted, now 10,842,810, issued on Nov. 24, 2020, previously published as PCT/IB2014/063744, filed on Aug. 6, 2014.
Prior Publication US 2023/0190786 A1, Jun. 22, 2023
Int. Cl. A61K 9/00 (2006.01); A61K 8/73 (2006.01); A61K 8/86 (2006.01); A61K 9/16 (2006.01); A61K 9/50 (2006.01); A61K 31/728 (2006.01); A61Q 19/08 (2006.01)

CPC A61K 31/728 (2013.01) [A61K 8/735 (2013.01); A61K 8/86 (2013.01); A61K 9/0019 (2013.01); A61K 9/0024 (2013.01); A61K 9/1641 (2013.01); A61K 9/5084 (2013.01); A61K 9/5089 (2013.01); A61Q 19/08 (2013.01); A61K 2800/91 (2013.01)]

28 Claims

1. A process for the preparation of polymer particles consisting essentially of at least a poly (lactic-co-glycolic acid)-polyethylene glycol-poly (lactic-co-glycolic acid) (PLGA-PEG-PLGA) copolymer or a mixture of a poly (lactic-co-glycolic acid) (PLGA) polymer and a poly (lactic-co-glycolic acid)-polyethylene glycol-poly (lactic-co-glycolic acid) (PLGA-PEG-PLGA) copolymer, combined with hyaluronic acid molecules or hyaluronic acid salts without formation of covalent bonds between the hyaluronic acid molecules or hyaluronic acid salts and the polymer, wherein said polymer particles continuously release the hyaluronic acid molecules or hyaluronic acid salts, and have a size ranging from 10 to 130 μm, wherein the continuous release of the hyaluronic acid or hyaluronic acid salts continues to occur for between 8 to 12 weeks when the polymer particles are in synovial fluid, and wherein the content by weight of hyaluronic acid or of hyaluronic acid salts combined with the polymer particles is in a range from 1 to 50 μg·mg⁻¹, comprising:

(i) with stirring, emulsifying an aqueous solution of hyaluronic acid or of hyaluronic acid salts in an organic solution comprising at least a poly (lactic-co-glycolic acid)-polyethylene glycol-poly (lactic-co-glycolic acid) (PLGA-PEG-PLGA) copolymer or a mixture of a poly (lactic-co-glycolic acid) (PLGA) polymer and of a poly (lactic-co-glycolic acid)-polyethylene glycol-poly (lactic-co-glycolic acid) (PLGA-PEG-PLGA) copolymer, wherein the poly (lactic-co-glycolic acid)-polyethylene glycol-poly (lactic-co-glycolic acid) (PLGA-PEG-PLGA) copolymer has a molecular weight ranging from 50 000 to 70 000 g·mol⁻¹

(ii) with stirring, mixing the emulsion obtained from stage (i) with an aqueous solution of polyvinyl alcohol (PVA),

(iii) with stirring, adding an aqueous solvent to the emulsion obtained from stage (ii), said aqueous solvent preferably being purified water,

(iv) filtering the emulsion obtained from stage (iii), and

(v) freeze-drying the polymer particles obtained from stage (iv), and

(vi) optionally sterilizing the freeze-dried polymer particles obtained from stage (v).