Salvianolic acid-gelatin conjugate hydrogel particles
Inventors
KO, Chun Hay • EWE, Joo Ann • TAN, Guang Rong • PAN, Hok Him • NG, Tsz Wai
Assignees
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Publication Number
US-12011487-B2
Publication Date
2024-06-18
Expiration Date
Abstract
The present disclosure relates to salvianolic acid-gelatin conjugate load retentive hydrogel nanoparticles useful for oral delivery of salvianolic acid, pharmaceutical compositions comprising the same, and methods of use and preparation thereof.
Core Innovation
The invention relates to salvianolic acid-gelatin conjugate (SAB-gelatin) loaded, load-retentive oral hydrogel nanoparticles having a core and a polymer shell coating the core. The core comprises a covalently bonded gelatin-salvianolic acid conjugate, where gelatin is covalently bonded to salvianolic acid B (SAB).
The polymer shell comprises at least one polysaccharide and optionally an outer shell. The inner shell is formed from polysaccharides selected from alginate, agarose, hyaluronic acid, carboxymethyl cellulose, and hydroxypropyl methylcellulose, with combinations contemplated. The optional outer shell comprises chitosan, shellac, or an enteric coating material such as an anionic copolymer derived from methacrylic acid and ethyl acrylate, hydroxypropyl methylcellulose phthalate, polyvinyl acetate phthalate, or cellulose acetate phthalate.
The SAB-gelatin conjugate is formed by contacting gelatin, SAB, a coupling agent, and optionally a coupling additive, thereby forming a gelatin covalently bonded to SAB. The resulting conjugate is coated with the at least one polysaccharide to form an inner shell coated gelatin conjugate, followed by optional outer coating with chitosan, shellac, or an enteric coating material.
Comparative results are reported showing higher SAB B retention from SAB-gelatin conjugate-loaded particles than particles loaded with unmodified SAB/gelatin admixture, together with stability and release behavior under simulated gastric versus intestinal conditions. The document further states therapeutic use of the oral nanoparticle formulations for treating cancer, inflammatory disease, or cardiac disease via oral administration.
Claims Coverage
The independently claimed subject matter includes one independent method claim covering nanoparticle preparation with a SAB-gelatin conjugate core and a polymer shell comprising an inner polysaccharide shell and optionally an outer enteric or mucoadhesive shell. The claim includes formation of the SAB-gelatin conjugate using a coupling agent, followed by sequential coating to form the inner shell and the optional outer shell, with defined selections for polysaccharides and enteric coating materials.
SAB-gelatin conjugate core with covalently bonded gelatin and SAB
The method comprises a core wherein the core comprises a salvianolic acid B-gelatin conjugate (SAB-gelatin conjugate) comprising gelatin covalently bonded to salvianolic acid B (SAB).
Inner polysaccharide shell coating of the SAB-gelatin conjugate
The method includes coating the SAB-gelatin conjugate with at least one polysaccharide thereby forming an inner shell coated gelatin conjugate, wherein the at least one polysaccharide is selected from alginate, agarose, hyaluronic acid, carboxymethyl cellulose, hydroxypropyl methylcellulose, and combinations thereof.
Optional outer shell using chitosan, shellac, or an enteric coating material
The method optionally coats the inner shell coated gelatin conjugate with chitosan, shellac, or an enteric coating material thereby forming the nanoparticle, wherein the enteric coating material is selected from an anionic copolymer derived from methacrylic acid and ethyl acrylate, hydroxypropyl methylcellulose phthalate, polyvinyl acetate phthalate, cellulose acetate phthalate, or a combination thereof.
Coupling of gelatin and SAB using a coupling agent and optionally a coupling additive
The method includes contacting gelatin, SAB, a coupling agent, and optionally a coupling additive thereby forming the SAB-gelatin conjugate.
Across the independently claimed method, the coverage is centered on preparing nanoparticles with a SAB-gelatin conjugate core formed by contacting gelatin and SAB with a coupling agent, followed by coating with at least one selected polysaccharide to form an inner shell, and optionally further coating with chitosan, shellac, or a specified enteric coating material.
Stated Advantages
Higher SAB B retention in SAB-gelatin conjugate-loaded particles than particles loaded with unmodified SAB/gelatin admixture.
Reported stability and release behavior under simulated gastric versus intestinal conditions.
Documented Applications
Therapeutic use for treating cancer via oral administration.
Therapeutic use for treating inflammatory disease via oral administration.
Therapeutic use for treating cardiac disease via oral administration.
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