MXPA97006443A - Carbonated solutions to treat, mineralize and fluorinate calcified tissues and methods for your - Google Patents

Abstract

The present invention relates to the use of a supersaturated solution with calcium phosphate and carbon dioxide, formed from the mixture of: a) an alkaline stable non-pressurized solution containing carbonate and b) a stable non-pressurized solution containing ions of calcium, wherein one or both solutions contain phosphate ions, to prepare a dental composition for treating dental tissue, wherein said solution when applied to dental tissue provides a deposit of calcium phosphate to said tissue upon escape of carbon dioxide from said solution

Description

CARBONATED SOLUTIONS TO TREAT, MINERALIZE AND FLUORINATARIZED TISSUES AND METHODS FOR USE This invention was made in the course of research, partially supported by the government under the permission DE 08916, granted by the National Institute of Dental Research. The government may have certain rights in the invention.

Background of the Invention 1. Field of the Invention This invention relates to certain solutions of calcium phosphate that are unique in their applications as mineralizers of caries lesions and erosions in the root of the teeth, as substitutes for mouth rinses and saliva. These solutions when they also contain a fluoride compound can also be used for the fluorination of the teeth. When used for either fluoridation or mineralization these solutions also prevent the deterioration of the teeth and actually restore the lesions caused by dental caries. 2. Description of the Prior Art Dental lesions, cavities, exposed roots and dental 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 fluorination to prevent and counteract such loss of minerals. Dental minerals are usually impure forms of hydroxyapatite, Ca5 (P0) OH. Therefore, the objectives of the research have been to deposit fluoride and apatite on and inside the tooth, thus preventing further deterioration in the teeth, restoring the tooth and / or sealing the dentinal tubules.

U.S. Patent No. 5,037,639 discloses the use of a carbonated solution to mineralize and fluorinate calcified tissues. A continuation application in part (Serial No. 07 / 936,068) filed on August 26, 1992 further presents the use of a solution of calcium carbonate phosphate under pressurized carbonated solutions to mineralize and fluorinate calcified tissues. The carbonated solution under pressurized carbon dioxide atmosphere offers a novel and useful method and composition for mineralizing and fluorinating the tooth at the necessary sites by controlling the pH and stability of the calcium phosphate fluoride solutions. However, previous carbonated solutions needed to be maintained in a pressurized carbon dioxide atmosphere prior to application to maintain their beneficial effects. The present invention encompasses simple methods for preparing remineralizing solutions without the need to use a pressurized aerosol.

Summary of the Invention The potential for the application of dental remineralization is vast. Dentists fill millions of cavities every year. If these cavities are remineralized instead of filling the general dental health of the public would increase substantially, since remineralization results in a complete tooth. The present invention seeks to provide remineralizing compositions and methods that can be practically applied under the dentist's care and virtually replace the need to bind the teeth.

This invention involves methods and compositions for the preparation of unstable calcium carbonate phosphate solutions, which are supersaturated with respect to the calcium phosphate and carbon dioxide solids. The invention takes advantage of the fact that at alkaline pH the aqueous solutions are capable of maintaining a greater amount of phosphate ions and carbonate ions in solution under atmospheric conditions. These alkaline solutions can be mixed with acidic calcium solutions to create carbonated solutions useful for the treatment of dental 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 within the tooth when applied for the prevention and / or repair of dental weaknesses such as tooth decay, exposed roots or dentin sensitivity. The deposition of calcium phosphate compounds is controlled by the pH of the carbonated solutions. The pH of the solutions increases as the carbon dioxide escapes and this facilitates the precipitation of the calcium phosphates for a necessary time range.

In addition, it has been found that high pH and relatively high pH carbonated solutions are useful as mouth rinses to prevent caries. These mouth rinses create a basic environment, thus eliminating acid from the teeth and preventing the resulting decay.

The advantages of the use of the calcium phosphate solution of the present invention compared to the solutions and slurries of the prior art are many. More importantly, the use of the compounds and methods of the invention allows the rapid formation of apatite on dental tissues. Therefore, remineralization of the teeth can be achieved more quickly. In addition, the present invention provides remineralization and fluorination simultaneously when the carbonated solutions contain a fluorine compound.

Another significant advantage is that the present invention will not damage the teeth due to a large change in pH during the remineralization process.

Yet another advantage of the present invention is the provision of a composition for the remineralization of the teeth that can be easily formulated and easily applied to the teeth.

Still another advantage of the present invention is the simple formula of the remineralizing carbonated solutions from solid powders. And still another advantage of the present invention is the provision of a composition that can be easily prepared and can be easily taken as an artificial saliva for individuals suffering from hyposalivation.

Thus, the present invention provides compositions and methods for the remineralization of caries that are practical for use in a clinical setting. The invention also provides compositions and methods for rapid fluorination of the teeth by the use of carbonated calcium phosphate solutions containing fluoride.

Other objects of the inventions will be apparent with the following description of the preferred specimens and the claims.

Detailed Description of the Preferred Specimens The present invention provides the compositions and methods that can be remineralize and / or fluorinate the tooth and, in the case of exposed roots and dentine sensitivity, clog the dentinal tubules. The solution can be used as a mouthwash.

When properly formulated, this calcium carbonate phosphate solution can be used as an artificial saliva as a replacement modality for individuals who exhibit hyposalivation The solutions may also contain other beneficial ions such as fluorides, hydrogen peroxide and strontium.

The inventor has found that under atmospheric conditions, in an aqueous solution the maximum concentration of carbonate ions in equilibrium with carbon dioxide in the air increases dramatically with the pH increase of the solution. The data is shown in Table I below.

TABLE I Total carbonate concentration in the solution of 30 mM dihydrogen phosphate Potassium under pressure of C02 0.00033 ATM. The pH was adjusted by the addition of KOH. pH Total carbonate (mM) added KOH (mM) 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 containing a large amount of carbonate ions. Therefore, by increasing the pH, a solution containing a high concentration of carbonate can be maintained without the need to keep the solution under a pressurized carbon dioxide atmosphere to prevent the carbon dioxide from escaping from the solution.

These stable alkaline carbonated solutions are useful by themselves as mouth rinses. The solutions act as regulators to create an oral environment with a basic pH. This basic environment will remove the acid from the tooth surface and therefore prevent the formation of cavities.

In a particularly preferred example, the alkaline carbonated solutions of the present invention contain phosphate. These carbonated phosphate solutions can be mixed with stable aqueous solutions containing a 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 concentrations of calcium and phosphate with lower pH (preferably 5 to 7.5). Due to the supersaturated nature of the mixed solutions, the calcium phosphate compounds will precipitate out of the mixed solution as the pH of the solution increases due to the release of carbon dioxide into the air. Therefore, when the mixed solution is put in the mouth, the carbon dioxide will be released and the calcium phosphate will precipitate on and in the teeth. Calcium phosphate then reacts with 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 pH and the desired concentrations of the mixed carbonate 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 carbonate calcium phosphate solutions in the preferred range of 5 to 7.5.

The solutions mixed with the same compositions and properties as the above solutions can also be obtained by mixing a stable alkaline carbonated solution containing a large amount of carbonate under atmospheric conditions with a stable acidic calcium phosphate solution. In this system, the phosphate originates from the acidic solution, instead of the alkaline solution. Phosphate ions can also originate from both solutions, that is, both the alkaline carbonate solution and the acidic calcium solution can 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 the same carbonated calcium phosphate solutions can be obtained in the mixed solutions. These solutions can be applied similarly to dental surfaces for the prevention and repair of caries, exposed roots and dentinal sensitivity.

The final blended carbonated solutions of the present invention may further include other beneficial components including; complex fluorides, such as monofluorophosphate, fluorosilicates and fluorostearates; antiseptic agents, such as chlorhexidine; and also mineralizing materials such as strontium. When used as artificial saliva, the final mixed carbonated solution of the present invention may also contain mucins, carboxymethylcellulose (CMC) and a sweetener, such as sorbitol or silitol. 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 the powder in water. While hydrogen peroxide can be included in the alkaline carbonated solution and the acidic solution mixture, under some conditions, it can make those solutions unstable. The following examples serve to illustrate the composition and method of the invention, but are not in any way limiting thereof.

EXAMPLE 1 A first carbonated solution contains 50.6 mm of K2C03, 7.4 mm of KH2P0 and 12.6 mm of HsP04 with a pH of 9.69 and a second solution contains 33 mm of Ca (N03) 2 and 50.6 mm of acetic acid with a pH of 2.5. Both solutions are stable under atmospheric pressure. When the two solutions are mixed, the mixed solution has a 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 the solution increases and the calcium phosphate precipitates out of the solution.

EXAMPLE 2 The procedure of Example 1 is repeated, except that the phosphate compounds are added to the acidic calcium solution, instead of the alkaline solution. A first solution contains 50.6 mm of K2C? 3 with a pH of 11.24 and a second stable calcium phosphate solution contains 7.4 mm of KH2P0, 12.6 mm of HsP0, 33 mm of Ca (NOs) and 50.6 mm of 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 a 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 the solution increases and the calcium phosphate precipitates out of the solution.

EXAMPLE 3 A solid powder containing 54 mg of calcium nitrate, 38 mg of tripotassium phosphate, 3.5 mg of potassium monohydrogen phosphate, 30.4 mg of acetic acid and 50.7 mg of potassium bicarbonate is created. 20 ml of water are added to the solid powder, the powder dissolves rapidly and creates a solution having the same properties as the mixed solution of Example 1, ie, the solution has a pH of 6.4 and is supersaturated with respect to the phosphate of calcium and carbon dioxide under atmospheric pressure. As the carbon dioxide evaporates the pH of the solution increases and the 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 Examples 1. The mixed solution is rapidly and directly applied to the dental tissue. Carbon dioxide escapes from the solution. Calcium phosphate precipitates out of the solution and is deposited on and inside the dental tissue.

EXAMPLE 5 A carbonated solution is prepared according to the procedure of Example 3. The solution is applied quickly and directly to the dental tissue. Carbon dioxide escapes from the solution. Calcium phosphate precipitates out of the solution and is deposited on and inside 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 1 mm of fluorosilicate ions.

EXAMPLE 7 A carbonated solution is prepared according to the procedure of Example 1, except that the acidic calcium solution also includes 1 mm of fluorostated 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 of fluoride ions.

EXAMPLE 9 A carbonated solution is prepared according to the procedure of Example 1, except that the acidic calcium solution also includes 33 mm of 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 of 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 of strontium compound.

EXAMPLE 12 A stable alkaline carbonate solution is created, containing 30 mm of K2CÜ3 and 50 mm of K2HP04 at a pH of 10.6. This alkaline carbonated solution is used as a mouthwash and removes the acidic residue from the teeth thus preventing cavities that may have resulted from the acidic residue.

The preferred specimen of the present invention is now fully described. The foregoing description, however, is only illustrative of the invention and is not intended to limit the invention in spirit or scope. Only the following claims and their equivalents limit the scope of the invention.

Claims (30)

1. CLAIMS: 1. A method for preparing a solution of supersaturated aqueous calcium carbonate phosphate with respect to calcium phosphates and carbon dioxide under atmospheric conditions for use in dental tissue treatment, comprising, mixing a stable alkaline solution containing carbonate with a stable acidic solution containing calcium ions and either or both solutions also contain phosphate ions.
2. 2. The method of Claim 1 wherein either or both of the solutions further contains fluoride ions.
3. 3. The method of Claim 2 wherein the fluoride is monofluorophosphate.
4. 4. The method of Claim 1 wherein the stable acidic solution further contains the complex fluoride ions.
5. 5. The method of Claim 4 wherein the complex fluoride is fluorosilicate.
6. 6. The method of Claim 4 wherein the complex fluoride is fluoro stannate.
7. 7. The method of Claim 1 wherein the acidic solution further contains strontium ions.
8. 8. The method of Claim 1 wherein either or both of the solutions further contains chlorhexidine compounds.
9. 9. A method for preparing a solution of aqueous calcium carbonate phosphate capable of mineralizing the teeth comprising adding water to a solid containing calcium salt, phosphate salt and carbonate salt.
10. 10. The method of Claim 9 wherein the water further contains hydrogen peroxide.
11. 11. The method of Claim 9 wherein the water further contains chlorhexidine compound.
12. 12. A method of Claim 9 wherein the solid further contains fluorine compound.
13. 13. A method of Claim 9 wherein the solid further contains strontium compound.
14. 14. A method for treating dental tissue comprising. (a) mixing a stable non-pressurized alkaline carbonated solution containing carbonate with a stable non-pressurized acidic solution containing calcium ions where either or both solutions contain phosphate ions, to create a supersaturated mixed solution with calcium phosphate and carbon dioxide; and (b) rapidly applying the mixed solution to the dental tissue whereby the carbon dioxide escapes and the calcium phosphate is deposited on and in the dental tissue.
15. 15. The method of Claim 14 wherein either or both alkaline solutions further contain fluoride ions.
16. 16. The method of Claim 14 wherein the stable acidic solution further contains complex fluoride ions.
17. . 17. The method of Claim 16 wherein the complex fluoride is fluorosilicate.
18. 18. The method of Claim 16 wherein the fluoride complex is fluoro stanate.
19. 19. The method of Claim 14 wherein the stable acidic solution further contains strontium ions.
20. 20. The method of Claim 14 wherein either or both solutions further contain chlorhexidine compounds.
21. 21. The method of Claim 14 wherein the pH of the stable alkaline solution is at least 8.
22. 22. A method for treating dental tissue comprising: (1) adding water to a solid mixture containing calcium salt, phosphate salt and carbonate salt to create a supersaturated unstable carbonated solution with respect to calcium phosphate and carbon dioxide; and (2) promptly apply the solution to the dental tissue whereby the carbon dioxide escapes and the calcium phosphate is deposited in and on the dental tissue.
23. 23. A method of Claim 22 wherein the water further contains hydrogen peroxide.
24. 24. A method of Claim 22 wherein the water further contains chlorhexidine compounds.
25. 25. A method of Claim 22 wherein the solid further contains fluorine compound.
26. 26. A method of Claim 22 wherein the solid further contains strontium compound.
27. 27. A method for treating dental tissue comprising contacting the dental tissue with a non-pressurized alkaline carbonated mouthwash by means of which the alkaline carbonated mouthwash interacts with the dental tissue to remove acidic materials.
28. 28. The method of Claim 27 wherein the alkaline carbonated mouth rinse further contains phosphate.
29. 29. The method of Claim 27 wherein the alkaline mouthwash further contains chlorhexidine.
30. 30. The method of Claim 27 wherein the alkaline mouth rinse further contains fluoride. EXTRACT OF THE INVENTION This invention involves methods and compositions for the preparation of unstable carbonated calcium phosphate solutions, which are supersaturated with respect to the calcium phosphate and carbon dioxide solids and the use of said solutions for the treatment of dental tissue. and hyposalivation. Specifically, the methods include mixing a stable alkaline carbonated solution with a stable acidic calcium solution, either or both solutions also contain phosphate to create an unstable carbonate solution with respect to calcium phosphate and carbon dioxide. Also, the methods include adding aqueous solution to the solids containing calcium salts, phosphate salts and carbonate salts to create a supersaturated unstable carbonated solution with respect to the calcium phosphate solids and carbon dioxide. The methods also include using alkaline solutions to remove the aqueous residue from the dental tissue and maintain cariostatic conditions.