CA1060346A - Method for remineralizing tooth enamel - Google Patents
Method for remineralizing tooth enamelInfo
- Publication number
- CA1060346A CA1060346A CA213,487A CA213487A CA1060346A CA 1060346 A CA1060346 A CA 1060346A CA 213487 A CA213487 A CA 213487A CA 1060346 A CA1060346 A CA 1060346A
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- Canada
- Prior art keywords
- solution
- calcium
- pack
- heavy metal
- ions
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
- A61K8/24—Phosphorous; Compounds thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/80—Process related aspects concerning the preparation of the cosmetic composition or the storage or application thereof
- A61K2800/88—Two- or multipart kits
Abstract
METHOD FOR REMINERALIZING TOOTH ENAMEL
David N. DiGiulio Robert J. Grabenstetter ABSTRACT OF THE DISCLOSURE
Demineralized tooth enamel is remineralized by first forming a metastable mixture by mixing a solution containing a soluble calcium salt with a solution containing a soluble phosphate salt, the mixture having a pH of from about 2 to about 5 and a ratio of calcium ions to phosphate ions of from .01 to 100; and second, applying the metastable mixture to the tooth surface. Preferably, the first solution additionally con-tains a soluble indium salt and has a pH of less than about 5, the second solution contains a soluble fluoride salt, and the metastable mixture has a pH of from about 2.5 to about 4.
David N. DiGiulio Robert J. Grabenstetter ABSTRACT OF THE DISCLOSURE
Demineralized tooth enamel is remineralized by first forming a metastable mixture by mixing a solution containing a soluble calcium salt with a solution containing a soluble phosphate salt, the mixture having a pH of from about 2 to about 5 and a ratio of calcium ions to phosphate ions of from .01 to 100; and second, applying the metastable mixture to the tooth surface. Preferably, the first solution additionally con-tains a soluble indium salt and has a pH of less than about 5, the second solution contains a soluble fluoride salt, and the metastable mixture has a pH of from about 2.5 to about 4.
Description
BACKGROJND OF THE INVENTION
Field of the Invention This invention relates to a process for remineralizing dental enamel in which solutions containing calcium and phosphate ions are mixed and applied to dental enamel, re-sulting in remineralization of the dental enamel and efficacyagainst caries~
The Prior ~rt It is well kno~n in the dental art that dental caries begins as a subsurface demineralization ("white spots") of the dental enamel and that remineralization or recalci-fication may be of importancè in retarding or arresting dental q~
c~_ies. However, heretofore no method was known by which a member of the general public could conveniently effect reminer-alization of subsurface dental enamel. U. S. Patent 1,222,144, April 10, 1917, to Ruthrauff, teaches acidic dentifrice compo-sitions for remineralizing tooth enamel comprising a soluble calcium salt, and an agent for more effectively causing the solution to permeate and completely fill up the minute spaces in the tooth surface. U. S. Patent 2,154,168, April 11, 1939, to Klein et al, discloses denti ~ces ^ontaining calcium and phos-phate ions and having a pH of from about ~ to about 10. U. S.
Patent 3,679,~360, July 25, 1972, to Rubin et al, discloses a method, the purpose of which is to deposit calcium phosphate from a gel medium onto the tooth surface. The surface on which calcium phosphate growth is desired is prepared (as by roughening) and the tooth and coatings are covered by a suitable cap for several days while the remineralization takes place.
Although the prior art does not teach either compositions or methods by which remineralization can be conveniently and effectively accomplished, copending Canadian Application Ser. No.
20 183,295 of Robert John Grabenstetter and John Augustus Gray, III, filed OctGber 12, 1973, said application being entitled "PROCESSES
AND COMPOSITIONS FOR REMINERALIZATION OF DENTAL ENAMEL" teaches a method of remineralizing subsurface dental enamel in which two compositions containing, respectively, a cation and an anion, such as calcium ion and phosphate ion, are sequentially applied to the dental enamel. This method, while successful, requires sequential application of the respective solutions. The present invention, on the other hand, provides a method by which subsurface dental enamel may be remineralized by the application of one solution to the tooth surface.
`` 10~;0346 SUMMARY OF THE INVENTIONIn accordance with one aspect of the present invention, demineralized tooth enamel is remineralized by:
(A) first, mixing a first solution containing a soluble calcium salt yielding from about .005% to about 5% of calcium ions with a second solution containing a soluble phosphate salt yielding from about .005% to about 5% phosphate ions, said mixture having a pH of from about 2.0 to about 5.0 and a molar ratio of calcium ions to phosphate ions of from about .01 to about 100; and (B) second, within 5 minutes after forming said mixture, applying a therapeutic amount of said mixture to a tooth surface for a period of time of from about 10 seconds to about 3 minutes.
The present invention, in another aspect, resides in a composition for remineralizing dental enamel which takes the form of a two-pack system wherein one pack contains a solution con-taining a water-soluble calcium salt yielding from about 0.005%
to about 5~ by weight of calcium ions, and the other pack contains a solution containing a water-soluble phosphate salt yielding from about 0.005% to about 5% by weight of phosphate ions, said solu-tion having individual pH's such that when mixed to form a mixture having a molar ratio of calcium ions to phosphate ions of from 0.01:1 to 100:1, said mixture has a pH of from about 2.0 to about 5.0; said system being adapted and arranges such that the contents of the packs, when ~ - 3 -combined and admixed, provide a metastable solution of calcium and phosphate ions having the aforesaid molar ratio of calcium ions to phosphate ions of from 0.01:1 to 100:1 and a pH ranging from about 2.0 to about 5.0, which meta-stable solution when applied to a tooth surface for a period of time ranging from about 10 seconds to about 3 minutes, within five minutes after formation of said solution, ; effects remineralization of subsurface dental enamel.
In a further aspect, this invention resides in a process for preparing a metastable solution for remineral-izing tooth enamel, said process comprising: mixing a first solution containing a water-soluble calcium salt yielding from about 0.005% to about 5% by weight of calcium ions with a second solution containing a water-soluble phosphate salt yielding from about 0.005% to about 5% by weight of phosphate ions, the proportions of said first and second solutions being such as to provide a mixture having a molar ratio of calcium ions to phosphate ions of from ` 0.01:1 to 100:1, and said first and second solutions having individual pH's such that when they are mixed as aforesaid, the metastable solution so formed has a pH of from about
Field of the Invention This invention relates to a process for remineralizing dental enamel in which solutions containing calcium and phosphate ions are mixed and applied to dental enamel, re-sulting in remineralization of the dental enamel and efficacyagainst caries~
The Prior ~rt It is well kno~n in the dental art that dental caries begins as a subsurface demineralization ("white spots") of the dental enamel and that remineralization or recalci-fication may be of importancè in retarding or arresting dental q~
c~_ies. However, heretofore no method was known by which a member of the general public could conveniently effect reminer-alization of subsurface dental enamel. U. S. Patent 1,222,144, April 10, 1917, to Ruthrauff, teaches acidic dentifrice compo-sitions for remineralizing tooth enamel comprising a soluble calcium salt, and an agent for more effectively causing the solution to permeate and completely fill up the minute spaces in the tooth surface. U. S. Patent 2,154,168, April 11, 1939, to Klein et al, discloses denti ~ces ^ontaining calcium and phos-phate ions and having a pH of from about ~ to about 10. U. S.
Patent 3,679,~360, July 25, 1972, to Rubin et al, discloses a method, the purpose of which is to deposit calcium phosphate from a gel medium onto the tooth surface. The surface on which calcium phosphate growth is desired is prepared (as by roughening) and the tooth and coatings are covered by a suitable cap for several days while the remineralization takes place.
Although the prior art does not teach either compositions or methods by which remineralization can be conveniently and effectively accomplished, copending Canadian Application Ser. No.
20 183,295 of Robert John Grabenstetter and John Augustus Gray, III, filed OctGber 12, 1973, said application being entitled "PROCESSES
AND COMPOSITIONS FOR REMINERALIZATION OF DENTAL ENAMEL" teaches a method of remineralizing subsurface dental enamel in which two compositions containing, respectively, a cation and an anion, such as calcium ion and phosphate ion, are sequentially applied to the dental enamel. This method, while successful, requires sequential application of the respective solutions. The present invention, on the other hand, provides a method by which subsurface dental enamel may be remineralized by the application of one solution to the tooth surface.
`` 10~;0346 SUMMARY OF THE INVENTIONIn accordance with one aspect of the present invention, demineralized tooth enamel is remineralized by:
(A) first, mixing a first solution containing a soluble calcium salt yielding from about .005% to about 5% of calcium ions with a second solution containing a soluble phosphate salt yielding from about .005% to about 5% phosphate ions, said mixture having a pH of from about 2.0 to about 5.0 and a molar ratio of calcium ions to phosphate ions of from about .01 to about 100; and (B) second, within 5 minutes after forming said mixture, applying a therapeutic amount of said mixture to a tooth surface for a period of time of from about 10 seconds to about 3 minutes.
The present invention, in another aspect, resides in a composition for remineralizing dental enamel which takes the form of a two-pack system wherein one pack contains a solution con-taining a water-soluble calcium salt yielding from about 0.005%
to about 5~ by weight of calcium ions, and the other pack contains a solution containing a water-soluble phosphate salt yielding from about 0.005% to about 5% by weight of phosphate ions, said solu-tion having individual pH's such that when mixed to form a mixture having a molar ratio of calcium ions to phosphate ions of from 0.01:1 to 100:1, said mixture has a pH of from about 2.0 to about 5.0; said system being adapted and arranges such that the contents of the packs, when ~ - 3 -combined and admixed, provide a metastable solution of calcium and phosphate ions having the aforesaid molar ratio of calcium ions to phosphate ions of from 0.01:1 to 100:1 and a pH ranging from about 2.0 to about 5.0, which meta-stable solution when applied to a tooth surface for a period of time ranging from about 10 seconds to about 3 minutes, within five minutes after formation of said solution, ; effects remineralization of subsurface dental enamel.
In a further aspect, this invention resides in a process for preparing a metastable solution for remineral-izing tooth enamel, said process comprising: mixing a first solution containing a water-soluble calcium salt yielding from about 0.005% to about 5% by weight of calcium ions with a second solution containing a water-soluble phosphate salt yielding from about 0.005% to about 5% by weight of phosphate ions, the proportions of said first and second solutions being such as to provide a mixture having a molar ratio of calcium ions to phosphate ions of from ` 0.01:1 to 100:1, and said first and second solutions having individual pH's such that when they are mixed as aforesaid, the metastable solution so formed has a pH of from about
2.0 to about 5Ø
In still another aspect, the present invention resides in a metastable solution containing both calcium ions and phosphate ions, in a molar ratio of said calcium ions to said phosphate ions ranging from 0.01:1 to 100:1, and having a pH ranging from about 2.0 to about 5.0, said metastable solution being suitable for use in remineralizing demineralized dental enamel when applied to a tooth surface within 5 minutes after its formation.
-3a-~`'1 In a preferred embodiment of the present invention, the first solution additionally contains a soluble salt of magnesium or a heavy metal yielding from about .005% to about 5%, preferably from .005~ to aboùt 0.1% of magnesium or heavy metal cations and has a ^pH of less than about 5, and the second solution additionally contains a soluble salt of an anion capable of forming an insoluble precipitate with calcium, magnesium or heavy metal cations, said soluble salt yielding from about .005% to about 5%, preferably from about .005%
to about O.S~ of said anions. Preferred cations, in thè preferred embodiment, are tin, aluminum, indium, and the rare earth metals. Indium is most preferred. Preferred anions are . ~ . .
..:
1~60346 fluoride, fluorophosphate, fatty acid radicals having from 8 to 18 carbon atoms and carbonate. Fluoride is most preferred. Most preferably, the hea~y metal ion is indium, the anion is fluoride, and the mixture has a pH of from about 2~5 to about 4. If the remineralization contemplated by this invention is carried out in accordance with this preferred embodiment, an antisolubility effect results, i.e., the remineralized enamel is more resistant to demineralization than was the original enamel.
DESC~I~TION OF THE INVENTION
The present invention lies in the discovery that demineralized dental enamel may be remineralized by applying to the teeth a metastable solution of calcium and phosphate ions which will diffuse through the tooth surface to the de-mineralized subsurface and precipitate, resulting in reminerali-zation or recalcification of subsurface dental enamel. The metastable solution is made by mixing a first solution, also referred to herein as the cationic solution, containing a water-soluble calcium salt yielding from about .005% to about ~0 5~ of calcium cations, with a second solùtion, also referred to herein as the anionic solution, containing a water-soluble phosphate salt yielding from about .005% to about 5% phosphate anions, said mixture having a pH of from about 2.0 to about 5, and a molar ratio of calcium cations to phosphate anions of from about ~01 to 100 ~i.e., .01:1 to 100:1). Unless speci-fied othe~ise, all percentages referred to herein are per-centages by weight.
The water-soluble calcium salts suitable for use in the present invention can be any water-soluble calcium salt which is safe for use in the oral cavity. ~he solu-bility should preferably be at least about 0.07% in water at 100C. Examp,les of suitable calcium salts are calcium chloride, calcium acetate, calcium formate, calcium lactate and calcium nitrate. Likewise, the phosphate salts suitable for USQ can be any of the water-soluble phosphate salts which are suitable for use in the oral cavity and having a solu-bility of at least 0.07~ in water at 100C. Phosphoric acid is also suitable for use, and for purposes of brevity, it will be understood that when the term "phosphate salts" is used herein, it is intended to also include phosphoric acid.
Examplès of suitable water-soluble phosphate salts are di-sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate and trisodium phosphate.
It is preferred to remineralize the tooth strùcture with a precipitate which has antisolubility characteristics, i.e., with a precipitate which is more resistant to deminerali-zation than was the original enamel. Thus, it is preferredth~t the first solution have a pH of less than about 5 and ~ontain a soluble salt of magnesium or a heavy metal yielding from about .005% to about 5~, preferably from about .005%
to about 0.1% of magnesium or heavy metal cations in addition to the calcium salt, that the second solution additionall~
contain a soluble salt of an anion capable of forming an insoluble precipitate with calcium, màgnesium or heavy metal cation, said salt yielding from about .005% to about 5%, preferably from about .005% to about 0.1~ of said anions, and that the metasta~le mixture have a pH of from about 2.5 to aboùt 4.
While applicants do not wish the scope Or the present invention to be limited by theory, it is believed that the calcium and phosphate ions diffuse through the tooth surface to the demineralized subsurface while the mixture is in the metastable state and precipitate in the demineralized subsurface where they remineralize the tooth structure. This is accom-plished by employing à metastable solution in which the calciumand phosphate ions remain soluble for a period of time sufficient to permit their diffusion into the demineralized subsurface of the dental enamel. More specifically, this is accomplished by combining the particular ions just prior to thèir application ~0 to the tooth in a solution having a pH of from about 2 to about 5, at which pH the calcium and phosphate ions remain soluble ~or the period of time re~uired. The calcium and phosphate ions are stored separately to avoid the premature precipita-tion of calcium phosphate.
` Chemically equiva'ent concentration~ of the first and second solutions are not necessary so long as the molar ratio of calcium and phosphate ions in the mixture is from .01 to 100.
It is preferred that the ratio is from about .2 to about 5 and it is most preferred that the ratio is about 1.67, the ratio of calcium to phosphate in natural teeth enamel (hydroxyapatite).
While completely aqueous solutions are preferred in the present invention, non-aqueous solvents may be em-ployed in combination with water. For example, suitable non-a~ueous solvents include ethyi alcohol, glycerine and propylene glycol. Solvent systems suitable for use in the present invention are those which are capable of dissolving the salts employed in the invention and which are safe for use in the mouth.
~ n considering the period of time of exposure of the metastable solution to the tooth, it is necessary that the length of time be great enough to allow diffusion of the ions into the demineralized subsurface. At least about ten seconds are required for this diffusion. The solution is preferably applied to the teeth for from about 10 seconds to about 3 minutes. The pH of the solution will rise due to natural factors after its introduction into the oral cavity.
Calcium phosphate prec;pitates during this rise in pH, but after calcium ions and phosphate ions have diffused in~o the demineralized tooth enamel. It is believed that the ability of the metastable solution to provide ions for remineralization 2~ is greatest upon its first introduction into the oral cavity, thereafter decreasing.
1~60346 .
The time period between the mixing of the first and second solutions and the application of the mixture to the teeth should not exceed 5 minutes, and preferably is less than 1 minute. The essence of the present invention lies in the creation of a metastable solution which will precipitate calcium phosphate and, in the most preferred embodiment, also indium phosphate and calcium fluoride, in the subsurface enamel of the teeth~ Before such precipitation occurs, the solution is applied to the teeth. The solution msut have a pH of about 5 or below to achieve this result. At a pH above about 5, precipitation'occurs too rapidly. A pH below 2 is generally undesirable from a safety standpoint and ad~s nothing to the invention. Although one would expect an acidic solution to demineralize the teeth, the use of the metastable solution of the present invention, which is saturated or supersaturated with respect to calcium phosphate, results in remineralization instead o demineralization.
The pH of the solutions of the present invention may be adjusted to the pH desired by methods well known in ~0 the art. The p~ may be lowered by the addition of any acid which is safe for use in the oral cavity and which yields t~e desired pH at the amount employed. Examples of suitable acids are hydroEluoric acid, phosphoric acid, hydrochloric acid, citric acid and malic acid. Should the pH be lower ~5 than desired, an appropriate amount of sodium hydroxide may be added to raise it. The appropriate acid can be added to the mixture of the first and second solutions immediately upon mixing or, preferably, the acid can be incorporated into one or both of the solutions before mixing in amount such that the two solutions have the required pH after mixing.
In order to effect remineralization of the dental enamel, a therapeutic amount of a solution of calcium and phosphate ions must be employed in the mouth. The amount of solution placed in the mouth must contain at least .001 g.
of calcium phosphate, and preferably contains more than .1 g.
of calcium phosphate ~calculated as Ca3(PO4)2].
If the deminexalized subsurface dent::l enamel is remineralized with a precipitate which is less soluble than-the original enamel, the remineralized subsurface is more resistant to demineralization than was the original enamel.
If the remineralization contemplated by this invention is carried out in accordance with the preferred embodiments, the remineralized enamel is more resistant to demineralization than was the original enamel because magnesium or heavy metal cations and/or certain anions such as fluoride ions, which are capable of forming insoluble precipitates with calcium, magnesium or heavy metal catio:~s (hereinafter also referred to as secondary anions) are incorporated into the remineralized tooth structure. If both types of ions are so incorporated, the remineralized enamel is even more resistant to deminerali-zation than if only one type of ion is incorporated. The concentration of magnesium or heavy metal cation and s~condary anion in the respective solutions may be from about .005%
to about 5~, and is preferably from about .005% to about 1%.
Examples of hea~-y ~,etal cations suitable for incor-poration into the first, or cationic solution, herein include soluble salts of mangan~se, tin, zinc, indium, zirconium, iron, titanium, vanadium, rare earth metals such as lantl-anum and ceriùm, and aluminum. Tin, indium, thè rare earth metals and aluminum are preferred; indium is most preferrea. Suitable soluble salts of these cations include the halide (e.g., chloride), nitrate, sulfate, acetate and gluconate salts of the desired cation. For example, suita~le soluble indium salts include indium chloride, indium sulfate, and indium nitrate.
Examples of anions which ~`ill react with cations to give desirable insoluble preci~itates, and are therefore suitable for incorporation into the second, or anionic solution herein include fatty acid groups having from 8 to 18 carbon--atoms, fluoride, fluorophosphate, silica fluoride, molybdate,sulfate, tungstate, tartrate, sorbate, alkyl sulfonates having ~rom 6 to 18 carbon atoms, carbonates, and ioaates. Fluoride, iluorophosphate, fatty acids having from 8 to 18 carbon atoms, e.g., laurate and stearate, and carbonates are preferred. Suitable soluble salts of these secondary anions include the sodium, rotassium, ammonium and substitutèd ammonium salts. The most A~ lo-preferred secondary anion is fluoride ion. Examples of soluble fluoride salts which are suitable for use in the second solution - of the present invention include sodium fluoride, ~.inc fluoride, betaine fluoride, alanine stannous fluoride, and hexylamine fluoride. Hydrofluoric acid can also be used.
It will be recognized by those skilled in the art that many different precipitates can be formed by a solution made in ac~ordance with the present invention. It is preferred that the precipitate be white in color. Some of these precipitates may be formed by first forming an original precipitate which then further reacts to form the indicated precipitate. For example, a hydroxide may form first and then react further to form the corresponding oxide. It is most preferred that the ingredients of the present invention are selected so that most precipitates are calcium phosphate compounds with small amounts of indium and fluoride incorporated therein. This results in a remineralized tooth structure which is similar to the natural tooth structure with small amounts o~ indium and fluoride incorporated therein, resulting in increased resistance to solubility. Thus, the reminerali~ed tooth structure will be more resistant to dental caries than was the ori~inal structure.
By employing suitable ions in the present composi-tion, the following insoluble precipitates in addition to calcium phosphate may be formed: CaF2, ZnN1~4PO4, InPO4, rare earth phos-phates such as lanthanum, cerium, and samarium phosphate, rare earth fluorides such as lanthanum, cerium, praseodymium, 10~0346 neodynium, and samarium fluorides, magnesium alkyl sulfonate wherein the alkyl group has from 10 to 22 carbon atoms, magnesium stearate, calcium stearate, zinc stearate, and aluminum phosphate.
Other precipitates contemplated by this invention - -are: Aluminum oxide; aluminum hydroxide; indium hydroxidej--indium phosphate; lanthanum tartrate; lanthanum sorbate;
lanthanum oxalate; lanthanum oxide; lanthanum tungstate;
lanthanum phosphate; magnesium alkyl sulfonates such as ~0 magnesium n-decyl sulfonate, magnesium lauryl sulfonate, magnesium myristyl sulfonate, magnesium cetyl sulfonate, and magnesium n-octadecyl sulfonate; magnesium oleate; magnesium myristate; magnesium palmitate; magnesium stearate; magnesium laura'e; magnesium carbonate; magnesium fl~oride; magnesium phosphates; magnesium hydroxide; magnesium ammonium phosphate;
manganese carbonate: manganess hydroxide; manganese ammonium phosphate; nickel hydroxide; manganese laurate; manganese myristate; manganese palmitate; manganese stearate;
stannous oxalate; zinc tartrate; zinc carbonate;
zinc oxalate; zinc hydroxide; zinc phosphate (usually complex mixtures); zinc ammonium phosphate; zirconium hydroxide;
zirconium phosphate; calcium carbonate; calcium molybdate;
calcium silicate; calcium tunqstate; calcium lauryl sulfonate;
calcium m~ristyl sulfonate; ca.cium n-hexadecyl sulfonate;
calcium n-octadecyl sulfonate; calcium oleate; calcium stearate; calcium tartrate; calcium aluminates; calcium ~ydroxide; calcium ammonium phosphate; tricalcium phosphate;
~`` ~` .
10~0346 dicalcium phosphate; calcium ~onofluorophosphate; Mg~PO4;
Mg3(PO4)2; MgNH4PO4; aluminum phosphates; aluminum ortho-phosphate, calcium phosphates, zinc phosphates; strontium phosphate; indium phosphate; tin phosphate; ceric phosphate;
MoO3; SiO2; SiO2 xH2O; Sn(OH)2; SnO ~ xH2O; Ti(oH)4; TiO2; V2O5;
and W03. These precipitates are formed by using the appropriate cations ~n the first solution and the appropriate anions in ~he second solution as described above.`
For commercial exploitation of the present invention, it is contemplated that "kits" will be made which will enable the consumer to make a metastable solution and apply lt to the teeth. Suitable kits can comprise two separately packaged solutions of the respective cations and anions, but more preferably, the kits are in the form of a two-part tooth-paste or mouthwash composition. The two parts, a cationicportion and an anionic portion, should be packaged to facilitate mixing the two parts and then applying the mixture to the teeth~ The term "cationic part" refers to the solution containin~ from ~005~ to 5% calcium cations, and the term `'anionic part" refers to the solution containing from .005~
to 5~ phosphate anions. The solutions in the kit are compounds with respect to acidity and ionic concentration such that mixing of the solutions in proper proportions for use in the process of the present invention will give a pH of from about 2.0 to abont 5.0 and a calcium to phosphate molar ratio of from about 0~01 to 100.
10~0346 Both the cationic and anionic parts of mouthwashes may be made in accordance with the following. Mouthwashes generally comprise an aqueous solution of ethyl alcohol and flavoxing materials. The alcohol provides an antibacterial 5 effect and also solubilizes the flavoring materials. Op-tionally, mouthwashes also contain additional antibacterial agents such as cetyl pyridinium chloride and domiphen bromide, and humectants such as glycerine and sorbitol which give a moist feeling to the mouth.
Typically, mouthwashes contain 3%-60% ethyl alcohol, 30~-90~ water, 5~-20~ glycerine or other humectant, 0.01~-0.1%
~ ~0~0346 of an antibacterial agent, 0.01~-0.5% of a sweetening agent, 0.01~-2.0% of a fLavoring agent, and from 0.1%-1% of an emulsifier-surfactant such as polyoxyethylene (20) sorbitan monoisostearate. Examples of suitable flavoring agents include heliotropyl ni~rile, wi`ntergreen oil tmethyl salicylate) oil of peppermint, oil of cassia, oil of anise, oil of cinnamon, and mixtures thereof. Suitable sweetening agents include sàccharin, g~ycerine, sorbitol, levulose, and 6-~trifluoro-methyl)-tryptophane, aspartyl phenylalanine methyl ester~
The present invention may be embodied in a tooth-paste composition and packaged in a codispensing toothpaste tube such as tbat disclosed~in U.S. Patent 3,290,422, Dec. 6, 1966, t Kenneth George Michel, or Canadian Patent 1,016,131 of Charles R. Hood and Stephen F. Evans, granted August 23, 1977, said patent being entitled "COLLAPSIBLE, LONGITUDINALLY
PARTITIONED TVBULAR DISPENSING CO~TAINER".
Suitable toothpastes may be made by employing in both the anionic and cationic portions of the toothpaste, ~rom about 0.5~ to about 50~, preferably from 5% to 25%, of an abrasive, from about 0.2% to about 5% of a sudsing agent, from about 0.1~ to about 5~ of a binding a~ent, from 0~ to about 50~ of a humectant, and balance, water and minors.
The pH of the toothpaste containing the active cationic ingredients has a pH of less than about 5. The mixture of the t~o portions which is placed in the mouth must have a pH of from about 2.0 to about 5. The pl~'s of the cationic portion and the anionic portion may be adjusted so long as the above parameters are not exceeded. Should the anionic portion of the toothpaste contain fluoride ions and have a pH of less than 5, the active f luoride might etch the teeth should it be placed in the mouth alone.
' Suitable abrasives include silica xerogels such -as those disclosed in U. S. Patent 3,538,230, dated Nov. 3, 1970, to Pader et al. Other conventional toothpaste abrasives can be used in the compositions of this invention, and include ~e~a-phase calcium pyrophosphate, zirconium silicate, the thermosetting polymerized resins described by Cooley et al.
in U. S. Patent 3,070,510, dated Dec. 25, 1962. Silica aerogels and the insoluble metaphosphates such as insoluble sodium metaphosphatc. Mixtures of abrasives can also be used.
Silica xerogel abrasives are preferred.
.
Suitable sudsing agents are those which are rea-sonably stable and form suds throughout an acidic pH range.
Preferably, non-soap anionic or nonionic oraanic synthetic detergents. Examples of such agents are water-soluble salts ~0 o~ alkyl sulfate having from 10 to 18 carl~on atoms in the alkyl radical, such as sodium lauryl sulfate, water-soluble salts of sulfonated monoglycerides of fatty acids having from 10 to 18 carbon atoms, such as sodium monoglyceride sulfonate, salts of ~10-C18 fatty acid amides of taurine, such as sodium ~-methyl,N-palmitoyl tauride, sodium N-coconut-acid-N-meth taurate, salts of ClO-C18 fatty acid esters of isothionic acid, and substantially saturated aliphatic acyl amides of ,, - 16 -1~60346 saturated monoaminocarboxylic acids having 2 to 6 carbon atoms, and in which the acyl radical contains 12 to 16 carbon atoms, such as sodium-N-lauryl sarcoside. Mixtures of two or more sudsing agents can be used.
~ binding material is added to thicken and provide a desirable consistency for the present compositions. Suit-able thickening agents are water-soluble salts of cellulose ethers, such as sodium carboxymethyl cellulose, hydroxypropyl cellulose, and hydroxyethyl cellulose. Natural gums such as gum karaya! gum arabic, and gum tragacanth, can also be used.
Colloidal magnesium aluminum silicate, silica aerogels, silica xerogels~ fumed silica, or other finely divided silica can be used as part of the thickening agent for further improved texture. A preferred thickening agent is xanthan gum, avail-able from the Kelco Company.
It is also desirable to include scine humectantmaterial in a toothpaste to keep i~ from hardening. Suitable humectants include glycerine, sorbitol, propylene glycol, and other edLble polyhydric alcohols.
2~` Toothpaste compositions may also contain flavoring agents such as oil of wintexgreen, oil of peppermint, oil of spearmint, oil of sassafras r and oil of clove. Toothpaste compositions may also contain sweetening agents such as saccharin, dextrose, levulose, and sodium cyclamate. A
toothpaste and mouthwash illustrating the present invention are set forth in the following examples, which are intended to illustrate, but not to act as a limitation, upon the present invention.
1~60346 EXAMPLE I
A s~__able two-part toothpaste for use in accordance with the present invention was made of the following ingredients and stored with the anionic and cationic portions separate.d:
`` ` . ' 1(~0346 ~. ~
0~ ~o 1-- o o o o o o o u'l In o o U Q~I I u~ ~ o o ~ O ~ O O I ~ ~ I ~ O
3I I ..... . ... I I
o ~ ~ ~ ~ ~ o o o ,1 o ~
R _~ ~ R
d~
,.
U ~3c~ o I ~ Oo o ~~ ~ ~ o .~; o o ~ C5~ ~ O -i i a s ~U o .~
s o B ~ ~ Z o . ~ --o ^ 3 ^ ~ ~ ~ x ~ ~ ~ `
o ~ ~ S ~ ~o ~o o3 ~ 3 n~ E~ 3 ~ n ~
~ r o n5 O ~ O ~ O ~ Q~
O O s~ s c~ a Qo) ~ 3 ~ ~ U O ~ O ~ ~ X X~ X
_I U h ~ ~ U h ~
D ¦ E `' ~3 V j C7 ~ ~' g o ~ h C V E C O h -- ~ h h O 1:: - - H ~ 'I O C ~ O O ~ ~ 3 3 ,~
o "^, o U~ `
The anionic paste had a pH of about 5.2. The cationic paste had a pH of about 3Ø One gram portions of each of the above pastes were simultaneously placed in the mouth whereupon the teeth were brushed in the usual manner three times per day for four weeks. The pH of the mixture was about 3.3. Observation indicatec~ that remineralization of demineralized enamel had occurred. The remineralized enamel was more resistant to demineralization than was the original enamel.
EXAMPLE II
A suitable two-part mouthwash for use in accordance with the present invention was made of the following ingre-dients and stored with the anionic and cationic parts separated:
h ~.C ~Uo~
~rl N ~D O O U) O ~ 1 - U ~ I I N O O 10 ~ N O ~i ~1 0 Id N 0 01` 0 o O O O O 1~ --O ~
P
~. ` ' ' .
~ ~ ~ . .
` al O
0 1`
~,1 ~ ~` O O O CO ~ 11'1 ' U~ ~ -U ~ ~D O I I O In N I O ` O O O 115 N
~,~ æ . . I I ~ . . I . . . . .~
~ O O 1~ 0 O O O O
o ~ ~I
dP
o o N
rl O
O ~ O .t: o ` ~ rl O
,~ O ~1 U ,~
P~ rl O ~
~:: ~1 U ~ ~ t.) ~ U
~O .1 E ~ X U h O ~ h u~
o .~ u ~ u ~ o a.)~
~ o r~ t~ ~ ~ O U O ~1 0 3 td, ~a m ~ C~
- 21 ~
r~
1~60346 Ten ml. portions of each of the above solutions were mixed and immed~ately (within ten seconds) placed in the mouth whereupon the 20 ml. mixture was held in contact with the teeth for from 15 to 30 seconds. The mixture had a pH of about 2.7. This procedure was repeated twice a day for three weeks. Observation indicated that remineralization of de-mineralizèd enamel had occurred. The re:~ineralized enamel was more resistant to demineralization than was the original enamel.
lt~
In still another aspect, the present invention resides in a metastable solution containing both calcium ions and phosphate ions, in a molar ratio of said calcium ions to said phosphate ions ranging from 0.01:1 to 100:1, and having a pH ranging from about 2.0 to about 5.0, said metastable solution being suitable for use in remineralizing demineralized dental enamel when applied to a tooth surface within 5 minutes after its formation.
-3a-~`'1 In a preferred embodiment of the present invention, the first solution additionally contains a soluble salt of magnesium or a heavy metal yielding from about .005% to about 5%, preferably from .005~ to aboùt 0.1% of magnesium or heavy metal cations and has a ^pH of less than about 5, and the second solution additionally contains a soluble salt of an anion capable of forming an insoluble precipitate with calcium, magnesium or heavy metal cations, said soluble salt yielding from about .005% to about 5%, preferably from about .005%
to about O.S~ of said anions. Preferred cations, in thè preferred embodiment, are tin, aluminum, indium, and the rare earth metals. Indium is most preferred. Preferred anions are . ~ . .
..:
1~60346 fluoride, fluorophosphate, fatty acid radicals having from 8 to 18 carbon atoms and carbonate. Fluoride is most preferred. Most preferably, the hea~y metal ion is indium, the anion is fluoride, and the mixture has a pH of from about 2~5 to about 4. If the remineralization contemplated by this invention is carried out in accordance with this preferred embodiment, an antisolubility effect results, i.e., the remineralized enamel is more resistant to demineralization than was the original enamel.
DESC~I~TION OF THE INVENTION
The present invention lies in the discovery that demineralized dental enamel may be remineralized by applying to the teeth a metastable solution of calcium and phosphate ions which will diffuse through the tooth surface to the de-mineralized subsurface and precipitate, resulting in reminerali-zation or recalcification of subsurface dental enamel. The metastable solution is made by mixing a first solution, also referred to herein as the cationic solution, containing a water-soluble calcium salt yielding from about .005% to about ~0 5~ of calcium cations, with a second solùtion, also referred to herein as the anionic solution, containing a water-soluble phosphate salt yielding from about .005% to about 5% phosphate anions, said mixture having a pH of from about 2.0 to about 5, and a molar ratio of calcium cations to phosphate anions of from about ~01 to 100 ~i.e., .01:1 to 100:1). Unless speci-fied othe~ise, all percentages referred to herein are per-centages by weight.
The water-soluble calcium salts suitable for use in the present invention can be any water-soluble calcium salt which is safe for use in the oral cavity. ~he solu-bility should preferably be at least about 0.07% in water at 100C. Examp,les of suitable calcium salts are calcium chloride, calcium acetate, calcium formate, calcium lactate and calcium nitrate. Likewise, the phosphate salts suitable for USQ can be any of the water-soluble phosphate salts which are suitable for use in the oral cavity and having a solu-bility of at least 0.07~ in water at 100C. Phosphoric acid is also suitable for use, and for purposes of brevity, it will be understood that when the term "phosphate salts" is used herein, it is intended to also include phosphoric acid.
Examplès of suitable water-soluble phosphate salts are di-sodium hydrogen phosphate, sodium dihydrogen phosphate, potassium dihydrogen phosphate and trisodium phosphate.
It is preferred to remineralize the tooth strùcture with a precipitate which has antisolubility characteristics, i.e., with a precipitate which is more resistant to deminerali-zation than was the original enamel. Thus, it is preferredth~t the first solution have a pH of less than about 5 and ~ontain a soluble salt of magnesium or a heavy metal yielding from about .005% to about 5~, preferably from about .005%
to about 0.1% of magnesium or heavy metal cations in addition to the calcium salt, that the second solution additionall~
contain a soluble salt of an anion capable of forming an insoluble precipitate with calcium, màgnesium or heavy metal cation, said salt yielding from about .005% to about 5%, preferably from about .005% to about 0.1~ of said anions, and that the metasta~le mixture have a pH of from about 2.5 to aboùt 4.
While applicants do not wish the scope Or the present invention to be limited by theory, it is believed that the calcium and phosphate ions diffuse through the tooth surface to the demineralized subsurface while the mixture is in the metastable state and precipitate in the demineralized subsurface where they remineralize the tooth structure. This is accom-plished by employing à metastable solution in which the calciumand phosphate ions remain soluble for a period of time sufficient to permit their diffusion into the demineralized subsurface of the dental enamel. More specifically, this is accomplished by combining the particular ions just prior to thèir application ~0 to the tooth in a solution having a pH of from about 2 to about 5, at which pH the calcium and phosphate ions remain soluble ~or the period of time re~uired. The calcium and phosphate ions are stored separately to avoid the premature precipita-tion of calcium phosphate.
` Chemically equiva'ent concentration~ of the first and second solutions are not necessary so long as the molar ratio of calcium and phosphate ions in the mixture is from .01 to 100.
It is preferred that the ratio is from about .2 to about 5 and it is most preferred that the ratio is about 1.67, the ratio of calcium to phosphate in natural teeth enamel (hydroxyapatite).
While completely aqueous solutions are preferred in the present invention, non-aqueous solvents may be em-ployed in combination with water. For example, suitable non-a~ueous solvents include ethyi alcohol, glycerine and propylene glycol. Solvent systems suitable for use in the present invention are those which are capable of dissolving the salts employed in the invention and which are safe for use in the mouth.
~ n considering the period of time of exposure of the metastable solution to the tooth, it is necessary that the length of time be great enough to allow diffusion of the ions into the demineralized subsurface. At least about ten seconds are required for this diffusion. The solution is preferably applied to the teeth for from about 10 seconds to about 3 minutes. The pH of the solution will rise due to natural factors after its introduction into the oral cavity.
Calcium phosphate prec;pitates during this rise in pH, but after calcium ions and phosphate ions have diffused in~o the demineralized tooth enamel. It is believed that the ability of the metastable solution to provide ions for remineralization 2~ is greatest upon its first introduction into the oral cavity, thereafter decreasing.
1~60346 .
The time period between the mixing of the first and second solutions and the application of the mixture to the teeth should not exceed 5 minutes, and preferably is less than 1 minute. The essence of the present invention lies in the creation of a metastable solution which will precipitate calcium phosphate and, in the most preferred embodiment, also indium phosphate and calcium fluoride, in the subsurface enamel of the teeth~ Before such precipitation occurs, the solution is applied to the teeth. The solution msut have a pH of about 5 or below to achieve this result. At a pH above about 5, precipitation'occurs too rapidly. A pH below 2 is generally undesirable from a safety standpoint and ad~s nothing to the invention. Although one would expect an acidic solution to demineralize the teeth, the use of the metastable solution of the present invention, which is saturated or supersaturated with respect to calcium phosphate, results in remineralization instead o demineralization.
The pH of the solutions of the present invention may be adjusted to the pH desired by methods well known in ~0 the art. The p~ may be lowered by the addition of any acid which is safe for use in the oral cavity and which yields t~e desired pH at the amount employed. Examples of suitable acids are hydroEluoric acid, phosphoric acid, hydrochloric acid, citric acid and malic acid. Should the pH be lower ~5 than desired, an appropriate amount of sodium hydroxide may be added to raise it. The appropriate acid can be added to the mixture of the first and second solutions immediately upon mixing or, preferably, the acid can be incorporated into one or both of the solutions before mixing in amount such that the two solutions have the required pH after mixing.
In order to effect remineralization of the dental enamel, a therapeutic amount of a solution of calcium and phosphate ions must be employed in the mouth. The amount of solution placed in the mouth must contain at least .001 g.
of calcium phosphate, and preferably contains more than .1 g.
of calcium phosphate ~calculated as Ca3(PO4)2].
If the deminexalized subsurface dent::l enamel is remineralized with a precipitate which is less soluble than-the original enamel, the remineralized subsurface is more resistant to demineralization than was the original enamel.
If the remineralization contemplated by this invention is carried out in accordance with the preferred embodiments, the remineralized enamel is more resistant to demineralization than was the original enamel because magnesium or heavy metal cations and/or certain anions such as fluoride ions, which are capable of forming insoluble precipitates with calcium, magnesium or heavy metal catio:~s (hereinafter also referred to as secondary anions) are incorporated into the remineralized tooth structure. If both types of ions are so incorporated, the remineralized enamel is even more resistant to deminerali-zation than if only one type of ion is incorporated. The concentration of magnesium or heavy metal cation and s~condary anion in the respective solutions may be from about .005%
to about 5~, and is preferably from about .005% to about 1%.
Examples of hea~-y ~,etal cations suitable for incor-poration into the first, or cationic solution, herein include soluble salts of mangan~se, tin, zinc, indium, zirconium, iron, titanium, vanadium, rare earth metals such as lantl-anum and ceriùm, and aluminum. Tin, indium, thè rare earth metals and aluminum are preferred; indium is most preferrea. Suitable soluble salts of these cations include the halide (e.g., chloride), nitrate, sulfate, acetate and gluconate salts of the desired cation. For example, suita~le soluble indium salts include indium chloride, indium sulfate, and indium nitrate.
Examples of anions which ~`ill react with cations to give desirable insoluble preci~itates, and are therefore suitable for incorporation into the second, or anionic solution herein include fatty acid groups having from 8 to 18 carbon--atoms, fluoride, fluorophosphate, silica fluoride, molybdate,sulfate, tungstate, tartrate, sorbate, alkyl sulfonates having ~rom 6 to 18 carbon atoms, carbonates, and ioaates. Fluoride, iluorophosphate, fatty acids having from 8 to 18 carbon atoms, e.g., laurate and stearate, and carbonates are preferred. Suitable soluble salts of these secondary anions include the sodium, rotassium, ammonium and substitutèd ammonium salts. The most A~ lo-preferred secondary anion is fluoride ion. Examples of soluble fluoride salts which are suitable for use in the second solution - of the present invention include sodium fluoride, ~.inc fluoride, betaine fluoride, alanine stannous fluoride, and hexylamine fluoride. Hydrofluoric acid can also be used.
It will be recognized by those skilled in the art that many different precipitates can be formed by a solution made in ac~ordance with the present invention. It is preferred that the precipitate be white in color. Some of these precipitates may be formed by first forming an original precipitate which then further reacts to form the indicated precipitate. For example, a hydroxide may form first and then react further to form the corresponding oxide. It is most preferred that the ingredients of the present invention are selected so that most precipitates are calcium phosphate compounds with small amounts of indium and fluoride incorporated therein. This results in a remineralized tooth structure which is similar to the natural tooth structure with small amounts o~ indium and fluoride incorporated therein, resulting in increased resistance to solubility. Thus, the reminerali~ed tooth structure will be more resistant to dental caries than was the ori~inal structure.
By employing suitable ions in the present composi-tion, the following insoluble precipitates in addition to calcium phosphate may be formed: CaF2, ZnN1~4PO4, InPO4, rare earth phos-phates such as lanthanum, cerium, and samarium phosphate, rare earth fluorides such as lanthanum, cerium, praseodymium, 10~0346 neodynium, and samarium fluorides, magnesium alkyl sulfonate wherein the alkyl group has from 10 to 22 carbon atoms, magnesium stearate, calcium stearate, zinc stearate, and aluminum phosphate.
Other precipitates contemplated by this invention - -are: Aluminum oxide; aluminum hydroxide; indium hydroxidej--indium phosphate; lanthanum tartrate; lanthanum sorbate;
lanthanum oxalate; lanthanum oxide; lanthanum tungstate;
lanthanum phosphate; magnesium alkyl sulfonates such as ~0 magnesium n-decyl sulfonate, magnesium lauryl sulfonate, magnesium myristyl sulfonate, magnesium cetyl sulfonate, and magnesium n-octadecyl sulfonate; magnesium oleate; magnesium myristate; magnesium palmitate; magnesium stearate; magnesium laura'e; magnesium carbonate; magnesium fl~oride; magnesium phosphates; magnesium hydroxide; magnesium ammonium phosphate;
manganese carbonate: manganess hydroxide; manganese ammonium phosphate; nickel hydroxide; manganese laurate; manganese myristate; manganese palmitate; manganese stearate;
stannous oxalate; zinc tartrate; zinc carbonate;
zinc oxalate; zinc hydroxide; zinc phosphate (usually complex mixtures); zinc ammonium phosphate; zirconium hydroxide;
zirconium phosphate; calcium carbonate; calcium molybdate;
calcium silicate; calcium tunqstate; calcium lauryl sulfonate;
calcium m~ristyl sulfonate; ca.cium n-hexadecyl sulfonate;
calcium n-octadecyl sulfonate; calcium oleate; calcium stearate; calcium tartrate; calcium aluminates; calcium ~ydroxide; calcium ammonium phosphate; tricalcium phosphate;
~`` ~` .
10~0346 dicalcium phosphate; calcium ~onofluorophosphate; Mg~PO4;
Mg3(PO4)2; MgNH4PO4; aluminum phosphates; aluminum ortho-phosphate, calcium phosphates, zinc phosphates; strontium phosphate; indium phosphate; tin phosphate; ceric phosphate;
MoO3; SiO2; SiO2 xH2O; Sn(OH)2; SnO ~ xH2O; Ti(oH)4; TiO2; V2O5;
and W03. These precipitates are formed by using the appropriate cations ~n the first solution and the appropriate anions in ~he second solution as described above.`
For commercial exploitation of the present invention, it is contemplated that "kits" will be made which will enable the consumer to make a metastable solution and apply lt to the teeth. Suitable kits can comprise two separately packaged solutions of the respective cations and anions, but more preferably, the kits are in the form of a two-part tooth-paste or mouthwash composition. The two parts, a cationicportion and an anionic portion, should be packaged to facilitate mixing the two parts and then applying the mixture to the teeth~ The term "cationic part" refers to the solution containin~ from ~005~ to 5% calcium cations, and the term `'anionic part" refers to the solution containing from .005~
to 5~ phosphate anions. The solutions in the kit are compounds with respect to acidity and ionic concentration such that mixing of the solutions in proper proportions for use in the process of the present invention will give a pH of from about 2.0 to abont 5.0 and a calcium to phosphate molar ratio of from about 0~01 to 100.
10~0346 Both the cationic and anionic parts of mouthwashes may be made in accordance with the following. Mouthwashes generally comprise an aqueous solution of ethyl alcohol and flavoxing materials. The alcohol provides an antibacterial 5 effect and also solubilizes the flavoring materials. Op-tionally, mouthwashes also contain additional antibacterial agents such as cetyl pyridinium chloride and domiphen bromide, and humectants such as glycerine and sorbitol which give a moist feeling to the mouth.
Typically, mouthwashes contain 3%-60% ethyl alcohol, 30~-90~ water, 5~-20~ glycerine or other humectant, 0.01~-0.1%
~ ~0~0346 of an antibacterial agent, 0.01~-0.5% of a sweetening agent, 0.01~-2.0% of a fLavoring agent, and from 0.1%-1% of an emulsifier-surfactant such as polyoxyethylene (20) sorbitan monoisostearate. Examples of suitable flavoring agents include heliotropyl ni~rile, wi`ntergreen oil tmethyl salicylate) oil of peppermint, oil of cassia, oil of anise, oil of cinnamon, and mixtures thereof. Suitable sweetening agents include sàccharin, g~ycerine, sorbitol, levulose, and 6-~trifluoro-methyl)-tryptophane, aspartyl phenylalanine methyl ester~
The present invention may be embodied in a tooth-paste composition and packaged in a codispensing toothpaste tube such as tbat disclosed~in U.S. Patent 3,290,422, Dec. 6, 1966, t Kenneth George Michel, or Canadian Patent 1,016,131 of Charles R. Hood and Stephen F. Evans, granted August 23, 1977, said patent being entitled "COLLAPSIBLE, LONGITUDINALLY
PARTITIONED TVBULAR DISPENSING CO~TAINER".
Suitable toothpastes may be made by employing in both the anionic and cationic portions of the toothpaste, ~rom about 0.5~ to about 50~, preferably from 5% to 25%, of an abrasive, from about 0.2% to about 5% of a sudsing agent, from about 0.1~ to about 5~ of a binding a~ent, from 0~ to about 50~ of a humectant, and balance, water and minors.
The pH of the toothpaste containing the active cationic ingredients has a pH of less than about 5. The mixture of the t~o portions which is placed in the mouth must have a pH of from about 2.0 to about 5. The pl~'s of the cationic portion and the anionic portion may be adjusted so long as the above parameters are not exceeded. Should the anionic portion of the toothpaste contain fluoride ions and have a pH of less than 5, the active f luoride might etch the teeth should it be placed in the mouth alone.
' Suitable abrasives include silica xerogels such -as those disclosed in U. S. Patent 3,538,230, dated Nov. 3, 1970, to Pader et al. Other conventional toothpaste abrasives can be used in the compositions of this invention, and include ~e~a-phase calcium pyrophosphate, zirconium silicate, the thermosetting polymerized resins described by Cooley et al.
in U. S. Patent 3,070,510, dated Dec. 25, 1962. Silica aerogels and the insoluble metaphosphates such as insoluble sodium metaphosphatc. Mixtures of abrasives can also be used.
Silica xerogel abrasives are preferred.
.
Suitable sudsing agents are those which are rea-sonably stable and form suds throughout an acidic pH range.
Preferably, non-soap anionic or nonionic oraanic synthetic detergents. Examples of such agents are water-soluble salts ~0 o~ alkyl sulfate having from 10 to 18 carl~on atoms in the alkyl radical, such as sodium lauryl sulfate, water-soluble salts of sulfonated monoglycerides of fatty acids having from 10 to 18 carbon atoms, such as sodium monoglyceride sulfonate, salts of ~10-C18 fatty acid amides of taurine, such as sodium ~-methyl,N-palmitoyl tauride, sodium N-coconut-acid-N-meth taurate, salts of ClO-C18 fatty acid esters of isothionic acid, and substantially saturated aliphatic acyl amides of ,, - 16 -1~60346 saturated monoaminocarboxylic acids having 2 to 6 carbon atoms, and in which the acyl radical contains 12 to 16 carbon atoms, such as sodium-N-lauryl sarcoside. Mixtures of two or more sudsing agents can be used.
~ binding material is added to thicken and provide a desirable consistency for the present compositions. Suit-able thickening agents are water-soluble salts of cellulose ethers, such as sodium carboxymethyl cellulose, hydroxypropyl cellulose, and hydroxyethyl cellulose. Natural gums such as gum karaya! gum arabic, and gum tragacanth, can also be used.
Colloidal magnesium aluminum silicate, silica aerogels, silica xerogels~ fumed silica, or other finely divided silica can be used as part of the thickening agent for further improved texture. A preferred thickening agent is xanthan gum, avail-able from the Kelco Company.
It is also desirable to include scine humectantmaterial in a toothpaste to keep i~ from hardening. Suitable humectants include glycerine, sorbitol, propylene glycol, and other edLble polyhydric alcohols.
2~` Toothpaste compositions may also contain flavoring agents such as oil of wintexgreen, oil of peppermint, oil of spearmint, oil of sassafras r and oil of clove. Toothpaste compositions may also contain sweetening agents such as saccharin, dextrose, levulose, and sodium cyclamate. A
toothpaste and mouthwash illustrating the present invention are set forth in the following examples, which are intended to illustrate, but not to act as a limitation, upon the present invention.
1~60346 EXAMPLE I
A s~__able two-part toothpaste for use in accordance with the present invention was made of the following ingredients and stored with the anionic and cationic portions separate.d:
`` ` . ' 1(~0346 ~. ~
0~ ~o 1-- o o o o o o o u'l In o o U Q~I I u~ ~ o o ~ O ~ O O I ~ ~ I ~ O
3I I ..... . ... I I
o ~ ~ ~ ~ ~ o o o ,1 o ~
R _~ ~ R
d~
,.
U ~3c~ o I ~ Oo o ~~ ~ ~ o .~; o o ~ C5~ ~ O -i i a s ~U o .~
s o B ~ ~ Z o . ~ --o ^ 3 ^ ~ ~ ~ x ~ ~ ~ `
o ~ ~ S ~ ~o ~o o3 ~ 3 n~ E~ 3 ~ n ~
~ r o n5 O ~ O ~ O ~ Q~
O O s~ s c~ a Qo) ~ 3 ~ ~ U O ~ O ~ ~ X X~ X
_I U h ~ ~ U h ~
D ¦ E `' ~3 V j C7 ~ ~' g o ~ h C V E C O h -- ~ h h O 1:: - - H ~ 'I O C ~ O O ~ ~ 3 3 ,~
o "^, o U~ `
The anionic paste had a pH of about 5.2. The cationic paste had a pH of about 3Ø One gram portions of each of the above pastes were simultaneously placed in the mouth whereupon the teeth were brushed in the usual manner three times per day for four weeks. The pH of the mixture was about 3.3. Observation indicatec~ that remineralization of demineralized enamel had occurred. The remineralized enamel was more resistant to demineralization than was the original enamel.
EXAMPLE II
A suitable two-part mouthwash for use in accordance with the present invention was made of the following ingre-dients and stored with the anionic and cationic parts separated:
h ~.C ~Uo~
~rl N ~D O O U) O ~ 1 - U ~ I I N O O 10 ~ N O ~i ~1 0 Id N 0 01` 0 o O O O O 1~ --O ~
P
~. ` ' ' .
~ ~ ~ . .
` al O
0 1`
~,1 ~ ~` O O O CO ~ 11'1 ' U~ ~ -U ~ ~D O I I O In N I O ` O O O 115 N
~,~ æ . . I I ~ . . I . . . . .~
~ O O 1~ 0 O O O O
o ~ ~I
dP
o o N
rl O
O ~ O .t: o ` ~ rl O
,~ O ~1 U ,~
P~ rl O ~
~:: ~1 U ~ ~ t.) ~ U
~O .1 E ~ X U h O ~ h u~
o .~ u ~ u ~ o a.)~
~ o r~ t~ ~ ~ O U O ~1 0 3 td, ~a m ~ C~
- 21 ~
r~
1~60346 Ten ml. portions of each of the above solutions were mixed and immed~ately (within ten seconds) placed in the mouth whereupon the 20 ml. mixture was held in contact with the teeth for from 15 to 30 seconds. The mixture had a pH of about 2.7. This procedure was repeated twice a day for three weeks. Observation indicated that remineralization of de-mineralizèd enamel had occurred. The re:~ineralized enamel was more resistant to demineralization than was the original enamel.
lt~
Claims (19)
1. A composition for remineralizing dental enamel which takes the form of a two-pack system wherein one pack contains a solution containing a water-soluble calcium salt yielding from about 0.005% to about 5% by weight of calcium ions, and the other pack contains a solution containing a water-soluble phosphate salt yielding from about 0.005% to about 5% by weight of phosphate ions, said solution having individual pH's such that when mixed to form a mixture having a molar ratio of calcium ions to phosphate ions of from 0.01:1 to 100:1, said mixture has a pH of from about 2.0 to about 5.0; said system being adapted and arranged such that the contents of the packs, when combined and admixed, provide a metastable solution of calcium and phosphate ions having the aforesaid molar ratio of calcium ions to phosphate ions of from 0.01:1 to 100:1 and a pH ranging from about 2.0 to about 5.0, which metastable solution when applied to a tooth surface for a period of time ranging from about 10 seconds to about 3 minutes, within five minutes after formation of said solution, effects remineralization of subsurface dental enamel.
2. A composition according to claim 1 wherein the solution contained in the first pack additionally contains a water-soluble salt of magnesium or a heavy metal yielding from about .005% to about 5% by weight of magnesium or heavy metal cations, and has a pH of less than about 5, and the solution contained in the second pack additionally contains a water-soluble salt of an anion capable of forming an insoluble precipitate with calcium, magnesium or said heavy metal cation.
3. The composition of claim 2 wherein the additional soluble salt in the solution contained in the first pack is a water-soluble salt of a heavy metal selected from the group consisting of tin, indium, rare earth metals, and aluminum, and wherein the additional soluble salt in the solution contained in the second pack is a water-soluble salt of an anion selected from the group consisting of fluorophosphates, fatty acid radicals containing from 8 to 18 carbon atoms, carbonate and fluoride.
4. A composition according to claim 1 wherein the additional soluble salt in the solution contained in the first pack is a water-soluble salt of indium which yields from about .005% to about .1% of indium cation and wherein the additional soluble salt in the solution contained in the second pack is a water-soluble salt of fluoride yielding from about .005% to about .1% of fluoride anions, and wherein a mixture of an equal portion of each of said solution contained in the first and second packs has a molar ratio of calcium ions to phosphate ions of from 0.2 to 5.0 and has a pH of from about 2.5 to about 4.
5. A composition as recited in claim 2 in the form of a toothpaste wherein said solution contained in the first pack and said solution contained in the second pack each contain, in addition:
(1) from about 0.5% to about 50% of an abrasive;
(2) from about 0.2% to about 5% of a sudsing agent;
(3) from about 0.1% to about 5% of a binding agent;
and (4) from 0% to about 50% of a humectant.
(1) from about 0.5% to about 50% of an abrasive;
(2) from about 0.2% to about 5% of a sudsing agent;
(3) from about 0.1% to about 5% of a binding agent;
and (4) from 0% to about 50% of a humectant.
6. A composition as recited in claim 2 in the form of a mouthwash wherein said solution contained in the first pack and said solution contained in the second pack each contain, in addi-tion:
(1) from about 3% to about 60% of ethyl alcohol;
(2) from about .01% to about .5% of a sweetening agent;
and (3) from about .01% to about 2.0% of a flavoring agent.
(1) from about 3% to about 60% of ethyl alcohol;
(2) from about .01% to about .5% of a sweetening agent;
and (3) from about .01% to about 2.0% of a flavoring agent.
7. A composition as recited in claim 4 in the form of a toothpaste wherein said solution contained in the first pack and said solution contained in the second pack each contain, in addition:
(1) from about 0.5% to about 50% of an abrasive;
(2) from about 0.2% to about 5% of a sudsing agent;
(3) from about 0.1% to about 5% of a binding agent;
and (4) from 0% to about 50% of a humectant.
(1) from about 0.5% to about 50% of an abrasive;
(2) from about 0.2% to about 5% of a sudsing agent;
(3) from about 0.1% to about 5% of a binding agent;
and (4) from 0% to about 50% of a humectant.
8. A composition as recited in claim 4 in the form of a mouthwash wherein said solution contained in the first pack and said solution contained in the second pack each contain, in addi-tion:
(l) from about 3% to about 60% of ethyl alcohol;
(2) from about .01% to about .5% of a sweetening agent;
and (3) from about .01% to about 2.0% of a flavoring agent.
(l) from about 3% to about 60% of ethyl alcohol;
(2) from about .01% to about .5% of a sweetening agent;
and (3) from about .01% to about 2.0% of a flavoring agent.
9. A process for preparing a metastable solution for remineralizing tooth enamel, said process comprising:
mixing a first solution containing a water-soluble calcium salt yielding from about 0.005% to about 5% by weight of calcium ions with a second solution containing a water-soluble phosphate salt yielding from about 0.005% to about 5% by weight of phosphate ions, the proportions of said first and second solutions being such as to provide a mixture having a molar ratio of calcium ions to phosphate ions of from 0.01:1 to 100:1, and said first and second solutions having individual pH's such that when they are mixed as aforesaid, the metastable solution so formed has a pH of from about 2.0 to about 5Ø
mixing a first solution containing a water-soluble calcium salt yielding from about 0.005% to about 5% by weight of calcium ions with a second solution containing a water-soluble phosphate salt yielding from about 0.005% to about 5% by weight of phosphate ions, the proportions of said first and second solutions being such as to provide a mixture having a molar ratio of calcium ions to phosphate ions of from 0.01:1 to 100:1, and said first and second solutions having individual pH's such that when they are mixed as aforesaid, the metastable solution so formed has a pH of from about 2.0 to about 5Ø
10. The process of claim 9 wherein said first solution additionally contains a water-soluble salt of magnesium or a heavy metal yielding from about .005% to about 5% of magnesium or heavy metal cations and has a pH of less than about 5, and said second solution additionally contains a water-soluble salt of an anion capable of forming an insoluble precipitate with calcium, magnesium or said heavy metal cation, said salt yielding from about .005% to about 5% of said anions.
11. The process of claim 10 wherein the additional salt in said first solution is a water-soluble salt of a heavy metal selected from the group consisting of tin, indium, rare earth metals, and aluminum, and the additional salt in said second solution is a water-soluble salt of an anion selected from the group consisting of fluorophosphates, fatty acid radicals having from 8 to 18 carbon atoms, carbonate, and fluoride.
12. The process of claim 11 wherein the additional salt of said heavy metal yields from about .005% to about 0.1% of heavy metal cation in said first solution and wherein the additional salt of said anion yields from about .005% to about 0.1% of said anion in said second solution.
13. The process of claim 12, wherein said heavy metal cation is indium, said anion is fluoride, and said metastable solution has a pH of from 2.5 to 4.
14. The process of claim 9 wherein said molar ratio of calcium ions to phosphate ions is from about 0.2 to about 5Ø
15. A metastable solution containing both calcium ions and phosphate ions, in a molar ratio of said calcium ions to said phosphate ions ranging from 0.01:1 to 100:1, and having a pH
ranging from about 2.0 to about 5.0, said metastable solution being suitable for use in remineralizing demineralized dental enamel when applied to a tooth surface within 5 minutes after its formation, and having been prepared by the process of claim 9.
ranging from about 2.0 to about 5.0, said metastable solution being suitable for use in remineralizing demineralized dental enamel when applied to a tooth surface within 5 minutes after its formation, and having been prepared by the process of claim 9.
16. A metastable solution containing both calcium ions and phosphate ions, in a molar ratio of said calcium ions to said phosphate ions ranging from 0.01:1 to 100:1, and having a pH
ranging from about 2.0 to about 5.0, said solution additionally containing from about 0.005% to about 5% by weight of magnesium or heavy metal cations, and from about 0.005% to about 5% by weight of anions capable of forming and insoluble precipitate with cal-cium, magnesium or said heavy metal cations, said metastable solu-tion being suitable for use in remineralizing demineralized dental enamel when applied to a tooth surface within 5 minutes after its formation, and having been prepared by the process of claim 10.
ranging from about 2.0 to about 5.0, said solution additionally containing from about 0.005% to about 5% by weight of magnesium or heavy metal cations, and from about 0.005% to about 5% by weight of anions capable of forming and insoluble precipitate with cal-cium, magnesium or said heavy metal cations, said metastable solu-tion being suitable for use in remineralizing demineralized dental enamel when applied to a tooth surface within 5 minutes after its formation, and having been prepared by the process of claim 10.
17. A metastable solution containing both calcium ions and phosphate ions, in a molar ratio of said calcium ions to said phosphate ions ranging from 0.01:1 to 100:1, and having a pH
ranging from about 2.0 to about 5.0, said solution additionally containing from about 0.005% to about 5.0% by weight of cations of a heavy metal selected from the group consisting of tin, indium, rare earth metals, and aluminum, and from about 0.005% to about 5.0% by weight of anions capable of forming an insoluble precipi-tate with calcium, magnesium or said heavy metal cations, selected from the group consisting of fluorophosphates, fatty acid radicals having from 8 to 18 carbon atoms, carbonate, and fluoride, said metastable solution being suitable for use in remineralizing demineralized dental enamel when applied to a tooth surface within 5 minutes after its formation, and having been prepared by the process of claim 11.
ranging from about 2.0 to about 5.0, said solution additionally containing from about 0.005% to about 5.0% by weight of cations of a heavy metal selected from the group consisting of tin, indium, rare earth metals, and aluminum, and from about 0.005% to about 5.0% by weight of anions capable of forming an insoluble precipi-tate with calcium, magnesium or said heavy metal cations, selected from the group consisting of fluorophosphates, fatty acid radicals having from 8 to 18 carbon atoms, carbonate, and fluoride, said metastable solution being suitable for use in remineralizing demineralized dental enamel when applied to a tooth surface within 5 minutes after its formation, and having been prepared by the process of claim 11.
18. A metastable solution according to claim 17 wherein said heavy metal cation is indium, said anion is fluoride, and said metastable solution has a pH of from 2.5 to 4, said metastable solution having been prepared by the process of claim 13.
19. A metastable solution according to claim 15 wherein said molar ratio of calcium ions to phosphate ions is from about 0.2 to about 5.0, when prepared by the process of claim 14.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US41548473A | 1973-11-13 | 1973-11-13 | |
| US51321174A | 1974-10-10 | 1974-10-10 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA1060346A true CA1060346A (en) | 1979-08-14 |
Family
ID=27022991
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA213,487A Expired CA1060346A (en) | 1973-11-13 | 1974-11-12 | Method for remineralizing tooth enamel |
Country Status (12)
| Country | Link |
|---|---|
| JP (1) | JPS5090192A (en) |
| CA (1) | CA1060346A (en) |
| CH (1) | CH604712A5 (en) |
| DE (1) | DE2452969A1 (en) |
| ES (1) | ES431896A1 (en) |
| FR (1) | FR2250537B1 (en) |
| GB (1) | GB1488859A (en) |
| IE (1) | IE40115B1 (en) |
| IT (1) | IT1050258B (en) |
| NL (1) | NL7414716A (en) |
| PH (1) | PH11187A (en) |
| SE (1) | SE429194B (en) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA1226525A (en) * | 1977-06-23 | 1987-09-08 | Gunnar Rolla | Lanthanum cation for cleaning teeth |
| CA2032556C (en) * | 1989-12-28 | 1995-10-24 | Yohji Imai | Odontotherapeutical materials |
| GB2329836B (en) * | 1996-09-18 | 1999-07-21 | Erling Johansen | Mouthwash compositions |
| ES2197364T3 (en) * | 1996-09-18 | 2004-01-01 | Erling Johansen | ORAL BATHROOM UNDERSTANDING CALCIUM AND PHOSPHATE IONS IN OVERRESTED SOLUTION. |
| JP2003104821A (en) * | 2001-09-28 | 2003-04-09 | Gc Corp | Tooth treatment material |
| JP2005245800A (en) * | 2004-03-05 | 2005-09-15 | Hosoda Denki:Kk | Acidic water containing promotion agent, acidic water containing implant, and mouth wash liquid |
| CN111135104B (en) * | 2020-02-13 | 2022-07-08 | 云南白药集团健康产品有限公司 | Preparation method of toothpaste capable of repairing enamel |
| CN111265413B (en) * | 2020-02-13 | 2022-11-29 | 西安科技大学 | Preparation method of toothpaste containing water and bioactive glass components |
| CN111249165B (en) * | 2020-02-13 | 2022-08-30 | 云南白药集团健康产品有限公司 | Lipophilic colloid stable water-in-oil emulsion and preparation method of product for repairing tooth enamel by using same |
| CN111281817B (en) * | 2020-02-13 | 2022-08-30 | 云南白药集团健康产品有限公司 | Preparation method of water-containing bioactive glass toothpaste |
| CN111110576B (en) * | 2020-02-13 | 2022-04-19 | 西安科技大学 | Preparation method of dental enamel regeneration composition |
| CN116270254B (en) * | 2022-11-28 | 2024-03-19 | 昆明理工大学 | Preparation method and application of amorphous calcium phosphate-cerium phosphate composite material |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB1408922A (en) * | 1972-02-02 | 1975-10-08 | Blendax Werke Schneider Co | Process and composition for the remineralisation and prevention of demineralisation of human teeth |
-
1974
- 1974-11-08 DE DE19742452969 patent/DE2452969A1/en not_active Withdrawn
- 1974-11-11 PH PH16502A patent/PH11187A/en unknown
- 1974-11-12 IT IT53988/74A patent/IT1050258B/en active
- 1974-11-12 FR FR7437318A patent/FR2250537B1/fr not_active Expired
- 1974-11-12 IE IE2329/74A patent/IE40115B1/en unknown
- 1974-11-12 NL NL7414716A patent/NL7414716A/en not_active Application Discontinuation
- 1974-11-12 CA CA213,487A patent/CA1060346A/en not_active Expired
- 1974-11-12 CH CH1511474A patent/CH604712A5/xx not_active IP Right Cessation
- 1974-11-13 JP JP49130942A patent/JPS5090192A/ja active Pending
- 1974-11-13 ES ES431896A patent/ES431896A1/en not_active Expired
- 1974-11-13 GB GB49120/74A patent/GB1488859A/en not_active Expired
- 1974-11-13 SE SE7414251A patent/SE429194B/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| IE40115L (en) | 1975-05-13 |
| FR2250537B1 (en) | 1978-07-28 |
| SE429194B (en) | 1983-08-22 |
| CH604712A5 (en) | 1978-09-15 |
| NL7414716A (en) | 1975-05-15 |
| IT1050258B (en) | 1981-03-10 |
| SE7414251L (en) | 1975-05-14 |
| IE40115B1 (en) | 1979-03-14 |
| DE2452969A1 (en) | 1975-05-15 |
| GB1488859A (en) | 1977-10-12 |
| PH11187A (en) | 1977-10-28 |
| FR2250537A1 (en) | 1975-06-06 |
| ES431896A1 (en) | 1977-02-01 |
| JPS5090192A (en) | 1975-07-19 |
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