Note: Descriptions are shown in the official language in which they were submitted.
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CARBONATED SOLUTIONS FOR TREATIl~G,
MINERALIZING AND FLUORIDATING CALCIFIED
TISSUES AND METHODS FOR THETR USE
This invention was made in the course of research, supported partially by
the Government under grant DE 08916, awarded by the National Institute of DentalResearch. The Government may have certain rights in the invention.
BACKGROUND OF THE INVENTION
1. Field of the Invention
This invention relates to certain carbonated calcium phosphate solutions that are
unique in their applications as remineralizers of caries lesions, cavities and root
erosions of the tooth, as mouth rinses and saliva substitutes. These solutions whcn
further containing a fluoride compound can also be used for topical fluoridation of
the teeth. When used for either fluoridation or mineralization these solutions
prevent further tooth decay and actually restore the lesions caused by dental caries.
2. DescriDtion of the Prior Art
Dental lesions, cavities, exposed roots and dentin sensitivity all develop due
to the loss of minerals from the dental tissue. In recent years, a large amount of
research has been done in the field of mineralization and fluoridation to prevent
and counteract such mineral loss. -Tooth minerals are generally impure forms of
hydroxyapatite, Ca5(PO,~)OH. Therefore, the objectives of the research has been to
deposit fluoride and apatite on and into the tooth, thus preventing further tooth
decay, restoring the tooth and/or obturating the dentinal tubules.
U.S. Patent No. 5,037,639 discloses the use of a carbonated solution for
mineralizing and fluoridating calcified tissues. A continuation-in-part application
(Serial No. 07/936,068) filed August 26, 1992 further discloses the use of a
carbonated calcium phosphate solution under pressurized carbonated solutions formineralizing and fluoridating calcified tissues. The carbonated solution under
pressurized carbon dioxide atmosphere offers a novel and useful method and
composition to mineralize and fluoridate the tooth at the sites needed by controlling
the pH and stability of the calcium phosphate fluoride solutions. However, the prior
carbonated solutions needed to be maintained in a pressurized carbon dioxide
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atmosphere prior to application to sustain its beneficial effects. The present
invention encompasses simple methods to prepare carbonated remineralizing
solutions without the need to use a pressurized aerosol.
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SU M MARY OF THE INVENTION
The potential for application of dental remineralization is vast. Dentists fill
millions of cavities each year. If these cavities where remineralized rather than
filled the general dental health of the public would be increased substantially, since
remineralization results in a whole tooth. The present invention seeks to provide
remineralization compositions and methods that can practically be applied under a
dentist's care and virtually replace the need for filling of the teeth.
This invention involves methods and compositions for preparation Or
unstable carbonated calcium phosphate solutions, which are supersaturated with
respect to calcium phosphate solids and carbon dioxide. The invention takes
advantage of the fact that at alkaline pH aqueous solutions are capable of
maintaining a greater amount of phosphate ions and carbonate ions in solution
under atmospheric conditions. These alkaline solutions can then be mixed with
acidic calcium solutions to create carbonated solutions useful for treating dental
1 5 tissue.
When used to treat dental tissue the carbonated solutions of the present
invention will deposit calcium phosphate compounds with or without fluoride on
and in the tooth when applied for the prevention and/or repair of tooth weaknesses
such as dental caries, exposed root, or dentin sensitivity. The deposition of the
calcium phosphate compounds is controlled by the pH of the carbonated solutions.The pH of the solutions increases as carbon dioxide escapes and this facilitates the
precipitation of the calcium phosphates over a range of time as needed.
In addition, it has been discovered that high pH and relatively high pH
carbonated solutions are useful as mouth rinses for preventing cavities. Such mouth
rinses create a basic oral environment, thus removing acid from the teeth and
preventing the resulting cavities.
The advantages of the use of the calcium phosphate solution of the present
invention as compared to the solutions and slurries of the prior art are many. Most
importantly, the use of the compounds and methods of the invention allows for
rapid formation of apatite upon dental tissues. Therefore, remineralization of the
teeth can be achieved more quickly. In addition, the present invention provides for
~, remineralization and fluoridation simultaneously when the carbonated solutions
contain a fluorine compounds.
Another significant advantage is that the present invention will not damage
the teeth due to a large change in pH during the remineralization process.
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Yet another advantage of the present invention is the provision of a
composition for remineralization of teeth which can be easily formulated and easily
applied to the teeth.
Still another advantage of the present invention is the easy formulation of
S remineralizing carbonated solutions from solid powders.
And still a further advantage of the present invention is the provision of a
composition which can be easily prepared and easily taken as an artificial saliva for
individuals suffering from hyposalivation.
Thus, the present invention provides compositions and methods for
remineralization of caries lesions that are practical for the use in a clinic
environment. The invention also provides compositions and methods for the rapid
fluoridation of teeth by the use of fluoride containing carbonated calcium
phosphate solutions.
Further objects of the inventions will become apparent with the following
1~ description of the preferred embodiments and claims.
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DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
The present invention provides the compositions and methods that can
remineralize and/or fluoridate the tooth and, in the ease of exposed root and dentin
sensitivity, obstruct the dentinal tubules. The solution can be used as mouth rinse.
When properly formulated, ~his carbonated calcium phosphate solution can be usedas an artificial saliva to serve as a replaeement modality for individuals exhibiting
hyposalivation. The solutions may further contain other beneficial ions such as
fluorides, hydrogen peroxidle and strontium.
The inventor has found that under atmospheric eonditions, in an aqueous
solution the maximum concentration of carbonate ions in equilibrium with the
carbon dioxide in the air increases dramatically with the increase in the pH of the
solution. The data is shown in the Table I below.
TABLE I
CONCENTRATION OF TOTAL CARBONATE IN THE 30 mM
POTASSIUM DIHYDROGEN PHOSPHATE SOLUTION UNDER
0.00033 ATM
CO2 PRESSURE. THE pH WAS ADJUSTED BY ADDITION OF KOH.
TOTAL KOH
CARBONATE ADDED
DH (m M) (~ M)
4.59 0.0116 0
6.62 0.0373 10
7.19 0.109 - 20
8.25 1.18 30
9.09 9.09 40
9.32 16.9 50
9.45 24.3 60
9.53 31.3 70
9.64 44.7 90
9.74 63.9 120
9.81 82.4 150
9.84 94.5 170
9.89 112 200
This property makes it possible to prepare stable alkaline carbonated solutions that
contain a large quantity of carbonate ions. Therefore, by increasing the pH, a
solution containing a high concentration of carbonate can be maintained without
the need for maintaining the solution under a pressurized carbon dioxide
atmosphere to keep the carbon dioxide from escaping the solution.
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These stable alkaline carbonated solutions are usef ul unto themselves as
mouth rinses. The solutions act as buffers to create an oral environment with a
basic pH. This basic environment will remove acid from the dental surface and
thereby prevent the formation of cavities.
In a particularly preferred embodiment, the alkaline carbonated solutions of
the present invention contain phosphate. Such solutions are stable with respect to
both carbonate and phosphate. These alkaline carbonated phosphate solutions can
be mixed with stable aqueous solutions containing high concentration of calcium
ions at acidic pH. The resulting mixed solutions are supersaturated with respect to
calcium phosphate and carbon dioxide. These mixed calcium phosphate solutions
thus contain high calcium and phosphate concentrations at lower pH (preferably 5to 7.5). Because of the supersatu}ated nature of the mixed solutions, calcium
phosphate compounds will precipitate out of the mixed solution as the pH of the
solution increases due to the release of carbon dioxide to the air. Therefore, when
the mixed solution is put in the mouth, carbon dioxide will be released and calcium
phosphate will precipitate on and in the teeth. The calcium phosphate then reacts
with the dental tissue and forms apatite.
The pH of the alkaline carbonated solutions is preferably between 8 and 12
and more preferably between 9 and 10. The desired pH and concentrations of the
mixed carbonated calcium phosphate solution will determine what the acid
concentration of the acidic calcium solution should be; the acid concentration is
such as to make the pH of the mixed carbonated calcium phosphate solutions in the
preferred range of 5 to 7.5.
The mixed solutions with the same compositions and properties as the above
solutions can also be obtained by mixing a stable alkaline carbonated solution that
contains a large quantity of carbonate under atmospheric conditions with a stable
acidic calcium phosphate solution. In this system, the phosphate originates from the
acidic solution, rather than the alkaline solution. The phosphate ions may also
originate from both solutions, i.e., both the alkaline carbonated solution and the
acidic calcium solution may include phosphate ions.
The mixed solution can also be obtained from the dissolution of solids in
water. Stable solid powders containing all the ingredients in the mixed solutions can
be created. These powders contain a mixture of calcium salts, phosphate salts, solid
acid (such as acetic acid and/or citric acid) and carbonate salts with or without
fluoride. When water is added to these powders, the solids will dissolve rapidly and
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the same carbonated calcium phosphate solutions as the mixed solutions can be
obtained. These solutions can similarly be applied to dental surfaces for the
prevention and repair of caries lesions, cavities, exposed roots and dentin sensitivity.
The final mixed car~onated solutions of the present invention may further
include other beneficial components including: complex fluorides, such as
monofluorophosphate, fluorosilicates and fluorostannates; antiseptic agents, such as
chlorhexidine; and further mineralizing materials, such as strontium. When used as
artificial saliva, the final mixed carbonated solution of the present invention may
further contain mucins, carboxymethylcellulose (CMC), and a sweetner, such as
sorbitol or xylitol. The final mixed solution may also include hydrogen peroxide as
an antiseptic agent. However, hydrogen peroxide is particularly preferred when the
final mixed carbonated solution is created by dissolving powder in water. While
hydrogen peroxide can be included in the alkaline carbonated solution and acidicsolution mixture, under some conditions, it may render those solutions unstable.lS The following examples serve to illustrate the composition and method of
invention, but are in no way limiting thereto.
EXAMPLE 1
A first carbonated solution contains 50.6 mM of KzCO3~ 7.4 mM of KH2PO4
and 12.6 mM of H3PO4 with pH of 9.69 and a second solution contains 33 mM of
Ca(NO3)2 and 50.6 mM of acetic acid with pH of 2.5. Both solutions are stable under
atmospheric pressure. When the two solutions are mixed, the mixed solution has the
pH of 6.4 and is supersaturated with respect to calcium phosphate and carbon
dioxide under atmospheric p}essure. As the carbon dioxide evaporates the pH of the
solution increases and calcium phosphate precipitates out of solution.
EXAMPLE 2
The procedure of EXAMPLE I is repeated, except that phosphate compounds
are added to the acidic calcium solution, instead of the alkaline solution. A first
solution contains 50.6 mM K2CO3 with a pH of 11.24, and a second stable calcium
phosphate solution contains 7.4 mM KH2PO4, 12.6 mM H3PO4, 33 mM Ca(NO3)2 and
50.6 mM acetic acid with a pH of 2.29. Both solutions are stable under atmospheric
pressure. When the two solutions are mixed, the mixed solution has the pH of 6.4and is supersaturated with respect to calcium phosphate and carbon dioxide underatmospheric pressure. As the carbon dioxide evaporates, the pH of the solution
increases and calcium phosphate precipitates out of the solution.
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EXAMPLE 3
A solid powder containing 54 mg calcium nitrate, 38 mg tripotassium
phosphate, 3.5 mg potassium monohydrogen phosphate, 30.4 mg acetic acid and 50.7mg potassium bicarbonate is created. 20 mL of water is added to the solid powder,
the powders dissolve quickly and creates a solution having the same properties as
the mixed solution in EXAMPLE I, i.e. the solution has the pH of 6.4 and is
supersaturated with respect to calcium phosphate and carbon dioxide under
atmospheric pressure. As the carbon dioxide evaporates the pH of solution increases
and calcium phosphate precipitates. Therefore, this solution can be applied directly
to the tooth as a mineralizing solution.
EXAMPLE 4
A carbonated solution is prepared according to the procedure of EXAMPLE
1. The mixed solution is promptly applied directly to the dental tissue. Carbon
dioxide escapes from the solution and calcium phosphate precipitates out of solution
and is deposited on and into the dental tissue.
EXAMPLE 5
A carbonated solution is prepared according to the procedure of EXAMPLE
3. The solution is then promptly applied directly to the dental tissue. Carbon
dioxide escapes from solution and calcium phosphate precipitates out of solutionand is deposited on and into the dental tissue.
EXAMPLE 6
A carbonated solution is prepared according to the procedure of EXAMPLE
1, except that the acidic calcium solution also includes I mM fluorosilicate ions.
EXAMPLE 7
A carbonated solution is prepared according to the procedure of EXAMPLE
1, except that the acidic calcium solution also includes I mM fluorostannate ions.
EXAMPLE 8 ~ ~
A carbonated solution is prepared according to the procedure of EXAMPLE
1, except that the carbonated phosphate solution also contains 5 mM fluoride ions.
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EXAMPLE 9
A carbonated solution is prepared according to the procedure of EXAMPLE
1, except that the acidic calcium solution also contains 33 mM strontium ions.
EXAMPLE 10
A carbonated solution is prepared according to the procedure of EXAMPLE
3, except that the solid mixture also includes 2.5 mM fluorine compound.
EXAMPLE 11
A carbonated solution is prepared according to the procedure of EXAMPLE
3, except that the solid mixture also includes 0.33 mM strontium compound.
10 EXAMPLE 12
A stable alkaline carbonated solution is created, containing 30 mM K2CO3
and ~0 mM K2HPO4 at a pH of 10.6. This alkaline carbonated solution is used as amouth rinse and removes acidic residue from the teeth thereby preventing cavities
which might have resulted from the acidic residue.
The preferred embodiment of the present invention is now fully described.
The above description, however, is only illustrative of the invention and is notintended to limit the invention in spirit or scope. Only the following claims and
their equivalents limit the scope of the invention.
