Crosslinked hyaluronic acid in emulsion

Abstract

The present invention relates to methods of producing crosslinked hyaluronic acid microbeads, as well as the produced microbeads, said method comprising the steps of: (a) providing an aqueous alkaline solution comprising hyaluronic acid, or a salt thereof; (b) forming microdroplets having a desired size from the mixed solution of step (a) in an organic or oil phase to form a water in organic or water in oil (W/O) emulsion, wherein the amount of oil phase used is of from 20 to less than 50% by weight based on the sum of oil phase and water; (c) adding a solution comprising a crosslinking agent to the emulsion, whereby the reaction of hyaluronic acid with the crosslinking agent takes place to provide crosslinked hyaluronic acid microbeads; and (d) optionally working up the dispersion of crosslinked hyaluronic acid microbeads obtained in step (c).

1 . Microbeads comprising hyaluronic acid, or a salt thereof, crosslinked with a crosslinking agent, wherein said crosslinking agent is divinylsulfone, glycerol diclycidyl ether or 1,4-butanediyl diglycidyl ether, and wherein said microbeads have a polydispersity in which greater than 97% of the particles are less than or equal to a tenfold of a maximum of particle size distribution. 
     
     
         2 . The microbeads according to  claim 1 , wherein said crosslinking agent is divinylsulfone. 
     
     
         3 . The microbeads according to  claim 1 , wherein said microbeads have an average diameter in a range of about 1 nanometre to 1 millimetre. 
     
     
         4 . The microbeads according to  claim 1 , wherein said salt of hyaluronic acid is selected from the group consisting of sodium hyaluronate, potassium hyaluronate, ammonium hyaluronate, calcium hyaluronate, magnesium hyaluronate, zinc hyaluronate, and cobalt hyaluronate. 
     
     
         5 . The microbeads according to  claim 1 , wherein said hyaluronic acid, or the salt thereof has a number average molecular weight of about 10,000 to about 10,000,000 Daltons. 
     
     
         6 . The microbeads according to  claim 1 , wherein said microbeads have a degree of crosslinking in a range from 0.001 to 1. 
     
     
         7 . The microbeads according to  claim 1 , wherein said microbeads contain an emollient, said emollient is other than a hydrocarbon or an aromatic hydrocarbon. 
     
     
         8 . The microbeads according to  claim 1 , wherein said microbeads have a maximum particle size distribution in a range from 0.1 to 100 μm. 
     
     
         9 . The microbeads according to  claim 1 , further comprising less than 10 parts by weight of a non-crosslinked portion of said crosslinking agent. 
     
     
         10 . The microbeads according to  claim 1 , wherein said microbeads are spherical. 
     
     
         11 . The microbeads according to  claim 1 , wherein said microbeads further comprise an active ingredient, a water-soluble excipient, a preservative or any mixture thereof. 
     
     
         12 . The microbeads according to  claim 11 , wherein the active ingredient is a personal care active substance. 
     
     
         13 . A composition comprising microbeads comprising hyaluronic acid, or a salt thereof, crosslinked with a crosslinking agent, wherein said crosslinking agent is divinylsulfone, glycerol diclycidyl ether or 1,4-butanediyl diglycidyl ether, and wherein said microbeads have a polydispersity in which greater than 97% of the particles are less than or equal to a tenfold of a maximum of particle size distribution. 
     
     
         14 . The composition according to  claim 13 , wherein said crosslinking agent is divinylsulfone. 
     
     
         15 . The composition according to  claim 13 , further comprising at least one additional component selected from the group consisting of emollients, emulsifiers and surfactants, thickeners/viscosity regulators/stabilizers, UV light protection filters, antioxidants, hydrotropic agents, solids and fillers, film-forming agents, pearlescent additives, deodorant and antiperspirant active compounds, insect repellents, self-tanning agents, preservatives, conditioning agents, perfumes, dyestuffs, biogenic active compounds, care additives, super-oiling agents and solvents. 
     
     
         16 . The composition according to  claim 15 , wherein said at least one additional component is present inside the microbeads. 
     
     
         17 . The composition according to  claim 15 , wherein said at least one additional component is present outside the microbeads. 
     
     
         18 . The composition according to  claim 15 , wherein said at least one additional component is present inside and outside the microbeads. 
     
     
         19 . The composition according to  claim 13 , wherein the composition is a personal care or cosmetic composition selected from the group consisting of a skin care, face care, head care, body care, intimate care, foot care, hair care, nail care, dental care and oral care compositions. 
     
     
         20 . The composition according to  claim 13  wherein the composition is an emulsion, a suspension, a solution, a cream, an ointment, a paste, a gel, an oil, a powder, an aerosol, a stick, a spray, a cleansing product, a make-up or sunscreen preparation or a face lotion. 
     
     
         21 . A method for moisturizing human hair or skin comprising:
 applying a composition comprising microbeads of hyaluronic acid, or a salt thereof, crosslinked with a crosslinking agent to human hair or skin requiring moisturizing, wherein said crosslinking agent is divinylsulfone, glycerol diclycidyl ether or 1,4-butanediyl diglycidyl ether, and wherein said microbeads have a polydispersity in which greater than 97% of the particles are less than or equal to a tenfold of a maximum of particle size distribution.   
     
     
         22 . The method according to  claim 21 , wherein said crosslinking agent is divinylsulfone. 
     
     
         23 . The method according to  claim 21 , wherein said microbeads are present in said composition in an amount from 0.1 to 60%. 
     
     
         24 . A method the treatment of wrinkles and rough skin comprising:
 applying a composition comprising microbeads of hyaluronic acid, or a salt thereof, crosslinked with a crosslinking agent to said human skin for a time period sufficient to reduce wrinkles or skin roughness of said human skin, wherein said crosslinking agent is divinylsulfone, glycerol diclycidyl ether or 1,4-butanediyl diglycidyl ether, wherein said microbeads have a polydispersity in which greater than 97% of the particles are less than or equal to a tenfold of a maximum of particle size distribution.   
     
     
         25 . The method according to  claim 24 , wherein said crosslinking agent is divinylsulfone. 
     
     
         26 . The method according to  claim 24 , wherein said microbeads are present in said composition in an amount from 0.1 to 60%.