United States Patent (19. 11) Patent Number: 5,089,255 Gaffar Et Al
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IIIIUS0050892.55A United States Patent (19. 11) Patent Number: 5,089,255 Gaffar et al. 45 Date of Patent: Feb. 18, 1992 DENTAL REMNERALIZATION 4,701,319 10/1987 Woo ...................................... 424/52 (54) 4,806,339 2/1989 Parran et al. ......................... 424/52 75 Inventors: Abdul Gaffar, Princeton; James 4,822,599 4/1989 Mitra .......... ... 424/52 Mellberg, Pottersville; John 4,842,847 6/1989 Amjad ................................... 424/52 Blake-Haskins, Piscataway, all of 4,885,155 12/1989 Parran et al. ......................... 424/52 N.J. FOREIGN PATENT DOCUMENTS (73) Assignee: Colgate-Palmolive Company, 0138705 4/1985 European Pat. Off. Piscataway, N.J. 0251146 1/1988 European Pat. Off. 30776 9/1976 United Kingdom. (21) Appl. No.: 649,208 2204487A 11/1988 United Kingdom . 22 Filed: Jan. 25, 1991 OTHER PUBLICATIONS Vissink et al., C.A.102; 160408s (1985) of Caries Res. Related U.S. Application Data 19(3); 212-218 (1985), "Rehardening properties . on 63 Continuation of Ser. No. 37,145, Jun. 26, 1989, aban Softened Human Enamel Effects of Sorbitol, Xylitol . doned. (51) Int, C. .......................... A61K 7/16; A61K 7/18 Rolla et al., C.A. 108; 8.1860d (1988) of EP251146, Jan. (52) U.S. Cl. ...................................... 424/52; 424/673; 7, 1988. 424/676 Primary Examiner-Shep K. Rose 58) Field of Search .................................... 424/49-58, Attorney, Agent, or Firm-Robert L. Stone; Murray M. 424/673, 676 Grill; Robert C. Sullivan (56) References Cited 57 ABSTRACT U.S. PATENT DOCUMENTS A method is disclosed for remineralizing demineralized 3,932,604 1/1976 Barth ..................................... 424/49 portions of teeth by treatment with a non-astringent 3,970,747 7/1976 Barth. ... 424/52 composition containing about 10-20% xylitol, and at 4,233,288 11/1980 Cornell. ... 424/52 least one fluoride ion-providing compound in a total 4,254,101 3/1981 Denny .. ... 424/52 amount sufficient to provide about 150 ppm to about 4,284,650 8/1981 Goupil ...... ... 424/49 1800 ppm of fluoride ions, with sodium fluoride provid 4,314,990 2/1982 Denny et al. ... 424/52 ing a predominant proportion of such fluoride ions. 4,340,583 7/1982 Wason ............... ... 424/52 4,515,772 5/1985 Parranet al. ..... ... 424/57 4,590,066 5/1986 Parran et al. ......................... 424/52 6 Claims, No Drawings 5,089,255 1 2 non-astringent oral composition in the form of a denti frice or mouthwash containing approximately by DENTAL REMINERALIZATION weight, 10% to 20% of xylitol and at least one fluoride This application is a continuation of application Ser. ion-providing compound in a total amount sufficient to No. 07/371,145, filed June 26, 1989, now abandoned. 5 provide 150 ppm to 1800 ppm, preferably 200 to 1200 ppm, of fluoride ions, with sodium fluoride providing a FIELD OF THE INVENTION predominant proportion of such fluoride ions. The present invention relates to oral compositions in DETAILED DESCRIPTION OF THE the form of dentrifices and mouthwashes providing INVENTION improved remineralization effects. O As indicated above, the compositions employed in BACKGROUND OF THE INVENTION the present invention are non-astringent, i.e. they are In the mouth, there is a natural equilibrium between devoid of zinc salts which introduce problems of mouth hydroxyapatite being dissolved from the enamel of feel and taste and tend to interfere with the desired teeth, on the one hand, and hydroxyapatite being 15 remineralizing mechanism, for example by reacting formed on or in the teeth from substances occurring with, complexing, precipitating or otherwise modifying naturally in the saliva, on the other. This equilibrium is the essential xylitol and sodium fluoride in the presently . shifting continuously. Among other factors, it is deter employed compositions. mined by diet and physical condition. If the equilibrium In the method of the present invention, the defined is such that hydroxyapatite is dissolved, a cariogenic 20 combination of xylitol and fluoride ion-providing com condition arises which is referred to as demineraliza pounds, employed in amounts within the indicated tion. If the equilibrium is such that hydroxyapatite is weight ranges and in relative proportions or ratios pre being formed in demineralized enamel, this is referred determined to achieve optimum remineralization ef. to as remineralization. By remineralization, pre-existing fects, have been unexpectedly found to coact synergisti tooth decay and caries can be reduced or eliminated by 25 cally to yield substantially better remineralization re natural means. sults than those obtainable with compositions contain It has long been known that fluoride-providing com ing the individual xylitol and fluoride ion-providing pounds, even in low concentrations, promote the remin compounds. eralization process and thereby reduce pre-existing cari The fluoride ion-providing compounds optionally ous conditions in the tooth structure. 30 present singly or in any mixtures thereof in the composi Xylitol has been disclosed in patent and literature tions employed in the present invention in addition to publications for the treatment of dental structures to the essential sodium fluoride are well known as anti-car provide sweetened non-cariogenic compositions, con ies agents. They may be fully or at least slightly but trol dental plaque, prophylactic prevention of occur sufficiently water soluble to provide the required fluo rence of carious conditions, and/or remineralization of 35 ride ions, organic or inorganic, and are characterized by pre-existing carious conditions. Barth U.S. Pat, No. their ability to release fluoride ions in water or saliva 3,932,604 and its divisional U.S. Pat. No. 3,970,747, are and by their freedom from undesired reaction with the directed to dentifrices containing substantial amounts of other components of the oral compositions employed xylitol as a non-cariogenic sweetenerahumectant, and herein. discloses formulations also containing sodium mono- 40 Inorganic fluoride ion-providing compounds include fluorophosphate; no remineralizing effect is disclosed. metal, alkali metal, alkaline earth metal and ammonium Hoffman-LaRoche Irish Patent Application 307/76, salts, as for example potassium fluoride, ammonium filed Feb. 16, 1976 and opened to public inspection Sept. bifluoride, calcium fluoride, a copper fluoride such as 1, 1976 (based on Swiss Application 2158/75), discloses cuprous fluoride, barium fluoride, sodium fluorosilicate, oral compositions containing xylitol, but no fluoride, for 45 ammonium fluorosilicate, sodium fluorozirconate, so remineralizing dental caries. EP Publication No. dium monofluorophosphate, aluminum mono- and di 0138705, published in Patent Bulletin 85/17, discloses fluorophosphate, fluorinated sodium calcium pyrophos anti-caries compositions containing xylitol and mixtures phate, stannous fluoride, lithium fluoride, cesium fluo of at least two fluoride salts providing at least 2,000 up ride, aluminum fluoride, cupric fluoride, indium fluo to 20,000 ppm total fluoride ion. EP Publication No. ride, stannous fluorozirconate, ferric fluoride, nickel 0251146, published Jan. 7, 1988 in Patent Bulletin 88/01, fluoride, palladium fluoride, silver fluoride, zirconium discloses oral compositions having a dental plaque pre fluoride, and the like and mixtures thereof. venting, and thus caries-prophylactic, activity contain Organic fluoride ion-providing compounds include ing a synergistic mixture of at least one fluorine com hexylamine hydrofluoride, laurylamine hydrofluoride, pound, at least one zinc ion releasing compound (astrin 55 myristylamine hydrofluoride, decanolamine hydroflu gent), and xylitol. oride, octadecenylamine hydrofluoride, myristoxya It is an object of this invention to provide a new and mine hydrofluoride, diethylaminoethyloctoylamide hy improved method of remineralizing demineralized por drofluoride, diethanolamineoethyloleylamide hydroflu tions of tooth structures. Another object of the inven oride, diethanolaminopropyl-N'-octadecenylamine tion is to provide such a process yielding unexpectedly 60 dihydrofluoride, 1-ethanol-2-hexadecylimidazoline improved remineralization effects. Other objects and dihydrofluoride, octoylethanolamine hydrofluoride, advantages will appear as the description proceeds. octyltrimethylammonium fluoride, dodecylethyldime thylammonium fluoride, tetraethylammonium fluoride, SUMMARY OF THE INVENTON dilauryldimethylammonium fluoride, The attainment of one or more of the above objects is 65 A-'octadecenylbenzyldimethylammonium fluoride, made possible by the present invention which includes a dioctyldiethylammonium fluoride, cyclohexylcetyl method for remineralizing demineralized portions of dimethylammonium fluoride, furfuryllauryldime tooth structures comprising applying to such portions a thylammonium fluoride, phenoxyethylcetyldine 5,089,255 3 4. thylammonium fluoride, N:N'-tetramethyl-N:N:- trademark SYLOID as Syloid 72 and Syloid 74 or dilaurylethylenediammonium difluoride, N-cetyl under the trademark SANTOCEL as Santocel 100 and pyridinium fluoride, N:N-dilauryl-morpholinium fluo alkali metal aluminosilicate complexes are particularly ride, N-myristyl-N-ethylmorpholinium fluoride, N-(oc useful, since they have refractive indices close to the tylaminocarbonylethyl)-N-benzyldimethylammonium refractive indices of gelling agent-liquid (including fluoride, N-(B-hydroxydodecyl)trimethylammonium water and/or humectant) systems commonly used in fluoride, N-phenyl-N-hexadecyldiethylammonium