US 11,939,409 B2
Cross-linked polycarboxylated polysaccharides and methods of use thereof
Stephane Meunier, Herzliya (IL); Svetlana Shneider, Haifa (IL); and Elena Ragozin, Ashqelon (IL)
Assigned to HALLURA LTD., Yokneam (IL)
Appl. No. 17/256,182
Filed by HALLURA LTD., Yokneam (IL)
PCT Filed Jun. 11, 2019, PCT No. PCT/IL2019/050663
§ 371(c)(1), (2) Date Dec. 25, 2020,
PCT Pub. No. WO2020/003298, PCT Pub. Date Jan. 2, 2020.
Claims priority of provisional application 62/691,035, filed on Jun. 28, 2018.
Prior Publication US 2021/0261693 A1, Aug. 26, 2021
Int. Cl. C08B 37/08 (2006.01); A61L 27/20 (2006.01); A61L 27/52 (2006.01); C07D 237/26 (2006.01); C07D 257/08 (2006.01)
CPC C08B 37/0072 (2013.01) [A61L 27/20 (2013.01); A61L 27/52 (2013.01); C07D 237/26 (2013.01); C07D 257/08 (2013.01); A61L 2300/402 (2013.01); A61L 2300/428 (2013.01); A61L 2400/06 (2013.01)] 15 Claims
 
1. A polymer comprising a first hyaluronic acid (HA) chain and a second HA chain, wherein said first HA chain and said second HA chain are crosslinked via one or more linkers, wherein said one or more linkers are represented by formula (C):

OG Complex Work Unit Chemistry
or by formula (D):

OG Complex Work Unit Chemistry
or a combination thereof; wherein:
- - - represents a single or a double bond;
R1 is selected from the group consisting of: a bond, alkyl, alkenyl, cycloalkyl, aryl, heteroaryl, heteroalicyclic, C(O)—NH-alkyl-NH, and —C0-C6alkyl-ZN— wherein Z is a bond, aryl, or heteroaryl, wherein said aryl or said heteroaryl is optionally substituted with halogen, hydroxy, C1-C6alkyl, C1-C6alkoxy, (C1-C6alkyl) amino, and di(C1-C6alkyl)amino;
R2 is C(O)—NH-alkyl-NH;
Q1, Q2 or both represent hydrogen, or are absent;
R3 is selected from the group consisting of: hydrogen, alkyl, aryl, or heteroaryl substituted or non-substituted, and wherein said polymer is characterized by a crosslinking degree of 0.2 to 4% and
wherein said polymer is characterized by at least one of: a phase angle (δ) of 0.1 to 10°, an elastic modulus (G′) of 10 to 1,000 Pa.