Casein formulations for the delivery of bioactive constituents

Abstract

The present invention provides a formulation for the delivery of bioactive constituents to biological surfaces, wherein said formulation comprises a suspension or solution of at least one isolated and purified casein protein or salt thereof, in water, together with at least one bioactive constituent.

1 . A formulation for the delivery of bioactive constituents to biological surfaces, wherein said formulation comprises a suspension or solution of at least one isolated and purified casein protein, or salt thereof, in water, together with at least one bioactive constituent.  
     
     
         2 . The formulation of  claim 1 , wherein said casein protein is selected from the group consisting of: α-casein, β-casein, κ-casein, and mixtures thereof.  
     
     
         3 . The formulation of  claim 1  or  2 , wherein said casein protein is in the form of casein phosphoprotein.  
     
     
         4 . The formulation of  claim 3 , wherein said casein phosphoprotein is in the form of caseinate calcium phosphate or caseinate calcium fluorophosphate.  
     
     
         5 . The formulation of  claim 4 , wherein the amount of casein calcium phosphate present in the formulation is between about 1 and 20% by weight.  
     
     
         6 . The formulation of any one of claims  1 - 5 , wherein said bioactive constituents comprise ions selected from the group consisting of: calcium, phosphate, fluorophosphate, fluoride, magnesium, barium, strontium, zinc, iron, copper, aluminium, tin; and salts of said bioactive constituents selected from the group consisting of: titanium dioxide, zinc oxide, zirconia, calcium fluoride, sodium fluoride, stannous fluoride, sodium monofluorophosphate, zinc ammonium fluoride, tin ammonium fluoride, cobalt ammonium fluoride calcium phosphate, calcium fluorophosphate and calcium oxide.  
     
     
         7 . The formulation of any one of claims  1 - 6 , wherein said bioactive constituent is an antimicrobial agent.  
     
     
         8 . The formulation of  claim 7 , wherein the antimicrobial agent is selected from the group consisting of: halogenated diphenyl ethers, such as: 2′,4,4′-trichloro-2-hydroxy-diphenyl ether (Triclosan); phenolic compounds, including phenol and its homologues, such as: 2-methyl-phenol, 3-methyl-phenol, 4-methyl-phenol, 4-ethyl-phenol, 2,4-dimethyl-phenol, 34-dimethyl-phenol, 2,6-dimethyl-phenol, 2,2-methylene bis (4-chloro-6-bromo-phenol); mono- and poly-alkyl and aromatic halophenols, including p-chlorophenols such as: methyl-p-chlorophenol, ethyl-p-chlorophenol, n-propyl-p-chlorophenol, n-butyl-chlorophenol; -o-chlorophenols; p-bromophenols; -o-bromophenols; resorcinol; n-methyl hexyl resorcinol; bisphenolic compounds and halogenated carbanilides.  
     
     
         9 . The formulation of  claim 8 , wherein the antimicrobial agent is selected from the group consisting of: glycerol, ethanol sorbitol, mannitol, sodium benzoate, methyl-p-hydroxybenzoate, ethyl-p-hydroxybenzoate, N-propyl p-hydroxybenzoate, butyl-p-hydroxybenzoate, phenoxy ethanol and quaternary ammonium salts, benzethonium chloride, and diisobutyl-phenoxyethoxyethyl dimethyl benzyl ammonium chloride.  
     
     
         10 . The formulation of  claim 8  or  9 , wherein said antimicrobial agent is sodium benzoate or ethanol.  
     
     
         11 . The formulation of  claim 10 , wherein the amount of sodium benzoate present in the formulation is between 0.001 and 0.1% by weight.  
     
     
         12 . The formulation of  claim 11 , wherein the amount of ethanol present in the formulation is between about 2 and 6% by weight.  
     
     
         13 . The formulation of any one of claims  1 - 12 , wherein said formulation is incorporated into a formulation selected from the group consisting of: toothpaste creams or gels, mouthwashes, lozenges, food-stuffs, and confectionary.  
     
     
         14 . The formulation of any one of claims  1 - 13 , wherein said formulation also includes a thickening agent.  
     
     
         15 . The formulation of  claim 14 , wherein said thickening agent is selected from the is group consisting of: clay, polymer, or a combination thereof.  
     
     
         16 . The formulation of  claim 15 , wherein said clay is selected from the group consisting of laponite, laponite DF, hectorite, calcium montmorillonite, sodium montmorillonite (bentonite), sodium exchanged montmorillonite, acid activated bleaching earth and palygorskite.  
     
     
         17 . The formulation of  claim 15 , wherein said polymer is selected from the group consisting of: alginate, cellulose and cellulose derivatives, carboxymethyl cellulose, Irish moss, gum tragacanth, starch polyvinylpyrrolidone, hydroxyethylpropylcellulose, hydroxybutyl methyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl cellulose, sodium carboxymethyl cellulose, and colloidal silica.  
     
     
         18 . The formulation of any one of claims  14 - 17 , wherein the amount of thickening agent present in the formulation is up to about 20% by weight.  
     
     
         19 . A method for treating and/or preventing dental caries and/or tooth erosion in humans or animals in need of said treatment and/or prevention, said method comprising administering a therapeutically effective amount of the formulation of any one of claims  1 - 18 , wherein said formulation is capable of controlling or preventing dental caries and/or tooth erosion in humans or animals.  
     
     
         20 . The method of  claim 19 , wherein said bioactive constituents of the formulation are selected from the group consisting of: tetrasodium pyrophosphate; N-methylpyrrolidone or 2-pyrrolidone-5,5-diethyl phosphoric acid.  
     
     
         21 . A method of treating and/or preventing dental sensitivity in humans or animals in need of said treatment and/or prevention, said method comprising administering a therapeutically effective amount of the formulation of any one of claims  1 - 18 , wherein said formulation is capable of controlling and/or preventing dental sensitivity in humans or animals.  
     
     
         22 . The method of  claim 21 , wherein said bioactive constituents are selected from the group consisting of: glycerine, strontium chloride, sodium citrate, potassium nitrate and dicalcium phosphate.  
     
     
         23 . A method of treating and/or preventing gingivitis in humans or animals in need of said treatment and/or prevention, said method comprising administering a therapeutically effective amount of the formulation of any one of claims  1 - 18 , wherein said formulation is capable of controlling and/or preventing gingivitis in humans or animals.  
     
     
         24 . A method of treating or preventing mouth odour in humans or animals in need of said treatment and/or prevention, said method comprising administering a therapeutically effective amount of the formulation of any one of claims  1 - 18 , wherein said formulation is capable of controlling or preventing mouth odour in humans or animals.  
     
     
         25 . The method of  claim 23  or  24 , wherein said bioactive constituent include an antimicrobial agent.  
     
     
         26 . The method of  claim 25 , wherein said antimicrobial agent is selected from the group consisting of: halogenated diphenyl ethers, such as: 2′,4,4′-trichloro-2-hydroxy-diphenyl ether (Triclosan); phenolic compounds, including phenol and its homologues, such as: 2-methyl-phenol, 3-methyl-phenol, 4-methyl-phenol, 4-ethyl-phenol, 2,4-dimethyl-phenol, 3,4-dimethyl-phenol, 2,6-dimethyl-phenol, 2,2-methylene bis (4-chloro-6-bromo-phenol); mono- and poly-alkyl and aromatic halophenols, including -p-chlorophenols such as: methyl-p-chlorophenol, ethyl-p-chlorophenol, n-propyl-p-chlorophenol, n-butyl-chlorophenol; -o-chlorophenols; p-bromophenols; -o-bromophenols; resorcinol; n-methyl hexyl resorcinol; bisphenolic compounds and halogenated carbanilides.  
     
     
         27 . A method of recrystallising and/or remineralising enamel and/or dentine in humans or animals in need of said recrystallising and/or remineralising, said method comprising administering an effective amount of the formulation of any one of claims  1 - 18 , wherein said formulation is capable of recrystallising and remineralising enamel and/or dentine in humans or animals.  
     
     
         28 . The method of  claim 27 , wherein said the bioactive constituents are selected from the group consisting of: fluoride, a calcium phosphate complex and a calcium fluorophosphate complex.  
     
     
         29 . A method of buffering plaque against a decrease in pH in humans or animals in need of said buffering, said method comprising administering an effective amount of the formulation of any one of claims  1 - 18 , wherein said formulation is capable of buffering plaque against a fall in pH in humans or animals.  
     
     
         30 . A method of treating and/or preventing osteoporosis in humans or animals in need of said treatment and/or prevention, said method comprising administering a therapeutically effective amount of the formulation of any one of claims  1 - 18 , wherein said formulation is capable of controlling or preventing osteoporosis in humans or animals.  
     
     
         31 . The method of  claim 30 , wherein said bioactive constituents are selected from the group consisting of: vitamin D, calcium phosphate complex and/or calcium fluorophosphate complex, wherein said calcium phosphate complex and/or calcium fluorophosphate complex provides a soluble (bioavailable) source of calcium.  
     
     
         32 . A method of treating and/or preventing calculus formation in the oral cavity of humans or animals in need of said treatment and/or prevention, wherein said method comprising administering a therapeutically effective amount of the formulation of any one of claims  1 - 18 , wherein said formulation is capable of controlling and/or preventing calculus formation in the oral cavity of humans or animals.  
     
     
         33 . The method of  claim 32 , wherein said bioactive constituents are selected from the group consisting of: casein phosphoprotein, tetrasodium pyrophosphate, tetrapotassium pyrophosphate, and mixtures thereof.  
     
     
         34 . A glass ionomer cement comprising the formulation of any one of claims  1 - 18 , together a glass powder that can react with a polymeric or polymerisable monomer acid to form a glass ionomer cement.  
     
     
         35 . The formulation of any one of claims  1 - 18 , wherein said formulation additionally comprises a dispersing agent.  
     
     
         36 . The formulation of  claim 35 , wherein said dispersing agent is selected from the group consisting of: sugars, carbohydrates, proteins, peptides, amino acids, lipids, urea, uric acid, and mixtures thereof.  
     
     
         37 . The formulation of  claim 35  or  36 , wherein said carbohydrate is selected from the group consisting of: sugar, monosaccharides, disaccharides, oligosaccharides, polysaccharides and derivatives thereof.  
     
     
         38 . The formulation of  claim 35  or  36 , wherein said protein is selected from the group consisting of: whey protein, glycoproteins, hydrolysed proteins and hydrolysed dephosphorylated proteins.  
     
     
         39 . The formulation of  claim 35  or  36 , wherein said peptide is selected from the group consisting of: adrenocorticotropic hormone and fragments, angiotensin and related peptides, atrial natriurertic peptides, bradykinin and related peptides, chemotactic peptides, dynorphin and related peptides endorphins and β-lipotropin fragments, enkephalin and related peptides, enzyme inhibitors, fibronectin fragments and related peptides, gastrointestinal peptides, growth hormone releasing peptides, luteinizing hormone releasing and related peptides, melanocyte stimulating hormone and related peptides, neurotensin and related peptides, opioid peptides, oxytocin, vasopressin, vasotocin and related peptides, parathyroid hormone and fragments, protein kinase related peptides, somatostatin and related peptides, substance p and related peptides, and mixtures thereof.  
     
     
         40 . The formulation of  claim 35  or  36 , wherein said amino acid is selected from the group consisting of: alanine, arginine, asparagine, aspartic acid, α-aminobuberic acid, cysteine, glutamine, glutamic acid, glycine, histidine, homoserine, hydroxyproline, isolcucine, lecine, lysine, methionine, norleucine, norvalineornithine, pencillamine, proglutamic acid, phenylalanine, proline, sarcosine, serine, staline, threonine, tyrptophan, tyrosine, valine and analogues and mixtures thereof.  
     
     
         41 . The formulation of any one of claims  1 - 18 , further comprising a salivary stimulator, wherein said formulation acts as a salivary substitute in humans or animals.  
     
     
         42 . The formulation of  claim 41 , wherein said salivary stimulator is pilocarpine.  
     
     
         43 . The formulation of any one of claims  1 - 42 , wherein said formulation is pre-dried prior to use in solid form.  
     
     
         44 . The formulation of any one of claims  1 - 42 , wherein said formulation is pre-dried prior to resuspension in aqueous form.