US 12,011,487 B2
Salvianolic acid-gelatin conjugate hydrogel particles
Chun Hay Ko, Hong Kong (CN); Joo Ann Ewe, Hong Kong (CN); Guang Rong Tan, Singapore (SG); Hok Him Pan, Hong Kong (CN); and Tsz Wai Ng, Hong Kong (CN)
Assigned to Nano and Advanced Materials Institute Limited, Hong Kong (CN)
Filed by Nano and Advanced Materials Institute Limited, Hong Kong (CN)
Filed on Mar. 19, 2021, as Appl. No. 17/206,273.
Claims priority of provisional application 63/006,137, filed on Apr. 7, 2020.
Prior Publication US 2021/0308279 A1, Oct. 7, 2021
Int. Cl. A61K 47/69 (2017.01); A61K 9/00 (2006.01); A61K 31/216 (2006.01); A61K 31/343 (2006.01); A61K 47/18 (2017.01); A61K 47/22 (2006.01); B82Y 5/00 (2011.01); B82Y 30/00 (2011.01); B82Y 40/00 (2011.01)
CPC A61K 47/6939 (2017.08) [A61K 9/0053 (2013.01); A61K 31/216 (2013.01); A61K 31/343 (2013.01); A61K 47/18 (2013.01); A61K 47/22 (2013.01); B82Y 5/00 (2013.01); B82Y 30/00 (2013.01); B82Y 40/00 (2013.01)] 8 Claims
 
1. A method of preparing a nanoparticle comprising: a core and a polymer shell coating the core, wherein the polymer shell comprises an inner shell comprising at least one polysaccharide and optionally an outer shell comprising chitosan, shellac, or an enteric coating material, wherein the core comprises a salvianolic acid B-gelatin conjugate (SAB-gelatin conjugate) comprising gelatin covalently bonded to salvianolic acid B (SAB), the method comprising:
contacting gelatin, SAB, a coupling agent, and optionally a coupling additive thereby forming the SAB-gelatin conjugate; coating the SAB-gelatin conjugate with the at least one polysaccharide thereby forming an inner shell coated gelatin conjugate; and optionally coating the inner shell coated gelatin conjugate with chitosan, shellac, or an enteric coating material thereby forming the nanoparticle, wherein the SAB-gelatin conjugate is represented by Formula 1:

OG Complex Work Unit Chemistry
or a pharmaceutically acceptable salt thereof, wherein
R1 and R2 are independently selected from the group consisting of OH and —NHR3; and
R3 for each instance is independently an amine containing amino acid side chain of the gelatin or a N-terminal amine of the gelatin, with the proviso that at least one of R1 or R2 is —NHR3;
the at least one polysaccharide is selected from the group consisting of alginate, agarose, hyaluronic acid, carboxymethyl cellulose, hydroxypropyl methylcellulose, and combinations thereof; and
the enteric coating material is selected from the group consisting of an anionic copolymer derived from methacrylic acid and ethyl acrylate, hydroxypropyl methylcellulose phthalate, polyvinyl acetate phthalate, polyvinyl acetate phthalate, cellulose acetate phthalate, or a combination thereof.