Core-Shell Crosslinked Hyaluronic Acid Gel Particles, Production Method for Same, and Medical Material

Abstract

A core-shell gel particle of the invention contains a crosslinked hyaluronic acid, has a higher equilibrium swelling capacity at the surface than at the center, the equilibrium swelling capacity showing a change curve with an inflection point from the center to the surface, and has a probe pushing force of 20 nN or less from the surface to a depth of 800 nm.

1 . A core-shell gel particle comprising a crosslinked hyaluronic acid,
 the particle having a higher equilibrium swelling capacity at the surface than at the center, the equilibrium swelling capacity showing a change curve with an inflection point from the center to the surface,   and the particle having a probe pushing force of 20 nN or less from the surface to a depth of 800 nm.   
     
     
         2 . The core-shell gel particle according to  claim 1 , wherein the equilibrium swelling capacity is 40 or greater from the inflection point to the surface. 
     
     
         3 . A core-shell gel particle comprising a crosslinked hyaluronic acid,
 the particle having a higher equilibrium swelling capacity at the surface than at the center, the equilibrium swelling capacity showing a change curve with an inflection point from the center to the surface, and   the particle having the equilibrium swelling capacity of 65 or greater from the inflection point to the surface.   
     
     
         4 . The core-shell gel particle according to  claim 1 , wherein a distance from the inflection point to the surface is 5 μm or greater. 
     
     
         5 . A method for manufacturing the core-shell gel particle according to  claim 1 , the method comprising the step of contacting a gel particle containing a crosslinked hyaluronic acid with a basic substance to form a core-shell structure in the gel particle. 
     
     
         6 . A method for manufacturing the core-shell gel particle according to  claim 1 , the method comprising the step of forming a shell of a crosslinked hyaluronic acid gel on the surface of a gel particle containing a crosslinked hyaluronic acid, the crosslinked hyaluronic acid gel having a lower crosslink density of hyaluronic acid than the gel particle. 
     
     
         7 . A medical material comprising the core-shell gel particle according to  claim 1 . 
     
     
         8 . The medical material according to  claim 7 , wherein the medical material is selected from intraarticular infusions, pharmacologically active substance supports, wound coverings, tissue-replacing biological tissue repair agents, antiadhesive agents, hemostatic agents, artificial extracellular matrices and dermal fillers. 
     
     
         9 . The medical material according to  claim 7 , wherein the medical material is an intraarticular infusion. 
     
     
         10 . The core-shell gel particle according to  claim 3 , wherein a distance from the inflection point to the surface is 5 μm or greater. 
     
     
         11 . A method for manufacturing the core-shell gel particle according to  claim 3 , the method comprising the step of contacting a gel particle containing a crosslinked hyaluronic acid with a basic substance to form a core-shell structure in the gel particle. 
     
     
         12 . A method for manufacturing the core-shell gel particle according to  claim 3 , the method comprising the step of forming a shell of a crosslinked hyaluronic acid gel on the surface of a gel particle containing a crosslinked hyaluronic acid, the crosslinked hyaluronic acid gel having a lower crosslink density of hyaluronic acid than the gel particle. 
     
     
         13 . A medical material comprising the core-shell gel particle according to  claim 3 . 
     
     
         14 . The medical material according to  claim 13 , wherein the medical material is selected from intraarticular infusions, pharmacologically active substance supports, wound coverings, tissue-replacing biological tissue repair agents, antiadhesive agents, hemostatic agents, artificial extracellular matrices and dermal fillers.