Preparation for Attaching to Teeth or Surrounding Part of Teeth

Abstract

The present invention provides a preparation for attaching to teeth or tooth peripheries, which comprises a malleable oral composition and an active ingredient for intra-oral delivery. Further, the present invention provides a preparation for attaching to teeth or tooth peripheries, which comprises an oral composition in a hardening ointment-phase and an active ingredient for intra-oral delivery. The preparation of the present invention may give high adhesive force to the desired site in spite of gaps between teeth or curves of teeth. The preparation of the present invention having high adhesive force increases the time of adhesion to a target site in the oral cavity, and thus may be advantageous in achieving an intended effect.

1 . A preparation for attaching to teeth or tooth peripheries, which comprises: an oral composition in a hardening ointment-phase; and an active ingredient for intra-oral delivery,
 wherein the oral composition in the hardening ointment-phase comprises a phase transition material, a phase transition auxiliary material, and an attachment-enhancing material of a phase transition composition,   wherein the phase transition material includes carrageenan, pectin, xyloglucan, gellan gum, ammonium alginate, magnesium alginate, potassium alginate, sodium alginate, lithium alginate, chitosan, poly-lactic acid (poly(D,L-lactic acid)), polylactide-co-glycolide (poly(DL-lactide-co-glycolide)), poly-caprolactone, polyacrylic acid (carbopol), polyvinylacetal diethyl aminoacetate (AEA), hydroxypropylmethyl cellulose, poly(methacrylic acid)-poly(ethylene glycol), poly(D,L-lactide)-block-poly(ethylene glycol)-block-poly(D,L-lactide), PEG-oligoglycolyl-acrylate, poly(N-isopropyl acrylamide), sucrose acetate isobutyrate, polyvinyl alcohol, glyceryl monooleate, glyceryl monolinoleate, glyceryl monoarachidonate, glyceryl monostearate, or a mixture thereof,   wherein the phase transition auxiliary material includes a calcium ion source of calcium sulfate, calcium carbonate, calcium phosphate dibasic (CaHPO 4 ), barium carbonate, zinc carbonate, calcium chloride, calcium lactate, calcium citrate, calcium aspartate, calcium saccharate, calcium oxovalerate, calcium gluconate, calcium lactobionate or calcium lactogluconate; a chelating agent of barium carbonate, zinc carbonate, sodium bicarbonate, sodium carbonate, tetraborate or tripolyphosphate; acetic acid, malic acid, lactic acid, gluconic acid, ascorbic acid, boric acid or a mixture or a salt thereof; or NaOH, KOH or a mixture thereof,   wherein the attachment-enhancing material of the phase transition composition includes precipitated silica for thickening, colloidal silicone dioxide, polyvinyl pyrrolidone, poly methyl vinyl ether and maleic acid copolymer, shellac, rosin, poloxamer, hyaluronic acid, acrylate copolymer, hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC), polyacrylic acid, polyethylene glycol, ethyl cellulose or a mixture thereof, or a crosslinked body thereof,   wherein the active ingredient is sodium fluoride, stannous fluoride, indium fluoride, amine fluoride, sodium monofluorophosphate, tetrasodium pyrophosphate (TSPP), sodium acid pyrophosphate (SAPP), sodium tripolyphosphate (STP), sodium potassium pyrophosphate, tetrapotassium pyrophosphate, acidic sodium metaphosphate, acidic sodium polyphosphate, triclosan, chlorhexidine, alexidine, hexetidine, sanguinarine, benzalkonium chloride, salicylanilide, domiphen bromide, cetylpyridinium chloride (CPC), tetradecylpyridinium chloride (TPC), aspirin, ketorolac, flurbiprofen, piroxicam, meclofenamic acid, thiamine, riboflavin, nicotinic acid, pantothenic acid, pyridoxine, biotin, folic acid, vitamin B12, lipoic acid, ascorbic acid, vitamin A, vitamin D, vitamin E, vitamin K, titrated extract of  Zea Mays  L. unsaponifiable fraction,  Magnoliae  Cortex, Myrrha, Rhatany, Chamomile, policresulen, titrated extract of Centella  Asiatica , nutmeg extract, dexpanthenol, β-sitosterol, acetyl salicylic acid, zinc chloride, potassium phosphate, potassium diphosphate, calcium chloride, oxalic acid, potassium oxalate, ferric oxalate, vitamin E, or a mixture thereof, and   wherein the preparation has the initial hardness of from 0.1 g to 20,000 g, measured at Compression mode of Texture Analyzer (TA), at the time of attachment; and has the final hardness of 40,000 g or less, measured at Compression mode of Texture Analyzer (TA), at the time of removal.   
     
     
         2 . The preparation of  claim 1 , wherein the active ingredient is mixed with the oral composition in a hardening ointment-phase and contained in the preparation. 
     
     
         3 . The preparation of  claim 1 , wherein the preparation becomes hardened and substantially loses its moldability in 5 minutes to 3 hours after the preparation is attached to teeth or tooth peripheries under the humidity and temperature conditions of the oral cavity. 
     
     
         4 . The preparation of  claim 3 , wherein the becoming hardened and losing its moldability means that the preparation becomes to have a viscosity of 5000 cps or higher, which is measured by using Brookfield viscometer equipped with No. 6, 7 spindles at 20° C., 5 to 20 rpm, in 5 minutes to 3 hours after the preparation is attached to teeth or tooth peripheries. 
     
     
         5 . The preparation of  claim 1 , wherein the time of removal is when the amount of the active ingredient released into the oral cavity is 60 wt % or more, based on the amount of the active ingredient contained in the initial preparation, after 30 minutes from the attachment of the preparation to teeth or tooth peripheries. 
     
     
         6 . The preparation of  claim 1 , wherein the preparation increases its area when the preparation is pressed by applying force at the beginning of attachment. 
     
     
         7 . The preparation of  claim 1 , wherein the preparation is one-formulation type; or two-formulation type consisting of the first formulation and the second formulation. 
     
     
         8 . The preparation of  claim 1 , wherein the oral composition in a hardening ointment-phase further comprises a material for helping drug release, and
 wherein the material for helping drug release includes at least one acid and at least one base, and wherein the preparation is a two-formulation type consisting of a first formulation containing the at least acid and a second formulation containing the at least one base.   
     
     
         9 . The preparation of  claim 1 , wherein water-solubility of the preparation, measured at 32° C., 1 atm after 5 minutes to 3 hours from attachment of the preparation to teeth or tooth peripheries, is 20 wt % or less. 
     
     
         10 . The preparation of  claim 1 , wherein the preparation further comprises a backing layer. 
     
     
         11 . A preparation for attaching to teeth or tooth peripheries, which comprises: a malleable oral composition; and an active ingredient for intra-oral delivery,
 wherein the malleable oral composition comprises a phase transition material, a phase transition auxiliary material, and an attachment-enhancing material of a phase transition composition,   wherein the phase transition material includes carrageenan, pectin, xyloglucan, gellan gum, ammonium alginate, magnesium alginate, potassium alginate, sodium alginate, lithium alginate, chitosan, poly-lactic acid (poly(D,L-lactic acid)), polylactide-co-glycolide (poly(DL-lactide-co-glycolide)), poly-caprolactone, polyacrylic acid (carbopol), polyvinylacetal diethyl aminoacetate (AEA), hydroxypropylmethyl cellulose, poly(methacrylic acid)-poly(ethylene glycol), poly(D,L-lactide)-block-poly(ethylene glycol)-block-poly(D,L-lactide), PEG-oligoglycolyl-acrylate, poly(N-isopropyl acrylamide), sucrose acetate isobutyrate, polyvinyl alcohol, glyceryl monooleate, glyceryl monolinoleate, glyceryl monoarachidonate, glyceryl monostearate, or a mixture thereof,   wherein the phase transition auxiliary material includes a calcium ion source of calcium sulfate, calcium carbonate, calcium phosphate dibasic (CaHPO 4 ), barium carbonate, zinc carbonate, calcium chloride, calcium lactate, calcium citrate, calcium aspartate, calcium saccharate, calcium oxovalerate, calcium gluconate, calcium lactobionate or calcium lactogluconate; a chelating agent of barium carbonate, zinc carbonate, sodium bicarbonate, sodium carbonate, tetraborate or tripolyphosphate; acetic acid, malic acid, lactic acid, gluconic acid, ascorbic acid, boric acid or a mixture or a salt thereof; or NaOH, KOH or a mixture thereof,   wherein the attachment-enhancing material of the phase transition composition includes precipitated silica for thickening, colloidal silicone dioxide, polyvinyl pyrrolidone, poly methyl vinyl ether and maleic acid copolymer, shellac, rosin, poloxamer, hyaluronic acid, acrylate copolymer, hydroxypropyl methyl cellulose (HPMC), hydroxypropyl cellulose (HPC), polyacrylic acid, polyethylene glycol, ethyl cellulose or a mixture thereof, or a crosslinked body thereof,   wherein the active ingredient is sodium fluoride, stannous fluoride, indium fluoride, amine fluoride, sodium monofluorophosphate, tetrasodium pyrophosphate (TSPP), sodium acid pyrophosphate (SAPP), sodium tripolyphosphate (STP), sodium potassium pyrophosphate, tetrapotassium pyrophosphate, acidic sodium metaphosphate, acidic sodium polyphosphate, triclosan, chlorhexidine, alexidine, hexetidine, sanguinarine, benzalkonium chloride, salicylanilide, domiphen bromide, cetylpyridinium chloride (CPC), tetradecylpyridinium chloride (TPC), aspirin, ketorolac, flurbiprofen, piroxicam, meclofenamic acid, thiamine, riboflavin, nicotinic acid, pantothenic acid, pyridoxine, biotin, folic acid, vitamin B12, lipoic acid, ascorbic acid, vitamin A, vitamin D, vitamin E, vitamin K, titrated extract of  Zea Mays  L. unsaponifiable fraction,  Magnoliae  Cortex, Myrrha, Rhatany, Chamomile, policresulen, titrated extract of Centella  Asiatica , nutmeg extract, dexpanthenol, β-sitosterol, acetyl salicylic acid, zinc chloride, potassium phosphate, potassium diphosphate, calcium chloride, oxalic acid, potassium oxalate, ferric oxalate, vitamin E, or a mixture thereof, and   wherein the preparation has the initial compressibility of 0.1 to 30,000 gs, measured at Compression mode of Texture Analyzer (TA); and has the final compressibility of 50,000 gs or less, measured at Compression mode of Texture Analyzer (TA).   
     
     
         12 . The preparation of  claim 11 , wherein the active ingredient is mixed with the malleable oral composition and dispersed in the preparation. 
     
     
         13 . The preparation of  claim 11 , wherein the time of removal is when the amount of the active ingredient released into the oral cavity is 60 wt % or more, based on the amount of the active ingredient contained in the initial preparation, after 30 minutes from the attachment of the preparation to teeth or tooth peripheries. 
     
     
         14 . The preparation of  claim 11 , wherein the preparation increases its area when the preparation is pressed by applying force at the beginning of attachment. 
     
     
         15 . The preparation of  claim 11 , wherein the malleable oral composition further comprises a material for helping drug release, and
 wherein the material for helping drug release includes at least one acid and at least one base, and wherein the preparation is a two-formulation type consisting of a first formulation containing the at least acid and a second formulation containing the at least one base.   
     
     
         16 . The preparation of  claim 11 , wherein the preparation is one-formulation type; or two-formulation type consisting of the first formulation and the second formulation. 
     
     
         17 . The preparation of  claim 11 , wherein the preparation becomes hardened and substantially loses its moldability in 5 minutes to 3 hours after the preparation is attached to teeth or tooth peripheries under the humidity and temperature conditions of the oral cavity. 
     
     
         18 . The preparation of  claim 17 , wherein the becoming hardened and losing its moldability means that the preparation becomes to have a viscosity of 5000 cps or higher, which is measured by using Brookfield viscometer equipped with No. 6, 7 spindles at 20° C., 5 to 20 rpm, in 5 minutes to 3 hours after the preparation is attached to teeth or tooth peripheries. 
     
     
         19 . The preparation of  claim 11 , wherein water-solubility of the preparation, measured at 32° C., 1 atm after 5 minutes to 3 hours from attachment of the preparation to teeth or tooth peripheries, is 20 wt % or less. 
     
     
         20 . The preparation of  claim 11 , wherein the preparation further comprises a backing layer.