CA2213689A1 - Carbonated solutions for treating, mineralizing and fluoridating calcified tissues and methods for their use - Google Patents
Carbonated solutions for treating, mineralizing and fluoridating calcified tissues and methods for their useInfo
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- CA2213689A1 CA2213689A1 CA002213689A CA2213689A CA2213689A1 CA 2213689 A1 CA2213689 A1 CA 2213689A1 CA 002213689 A CA002213689 A CA 002213689A CA 2213689 A CA2213689 A CA 2213689A CA 2213689 A1 CA2213689 A1 CA 2213689A1
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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
- A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
- A61C19/00—Dental auxiliary appliances
- A61C19/06—Implements for therapeutic treatment
- A61C19/063—Medicament applicators for teeth or gums, e.g. treatment with fluorides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K6/00—Preparations for dentistry
- A61K6/20—Protective coatings for natural or artificial teeth, e.g. sealings, dye coatings or varnish
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K6/00—Preparations for dentistry
- A61K6/80—Preparations for artificial teeth, for filling teeth or for capping teeth
- A61K6/849—Preparations for artificial teeth, for filling teeth or for capping teeth comprising inorganic cements
- A61K6/864—Phosphate cements
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- 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
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- 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
- A61K8/20—Halogens; Compounds thereof
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- 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
- A61K8/20—Halogens; Compounds thereof
- A61K8/21—Fluorides; Derivatives thereof
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- 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
- A61K8/22—Peroxides; Oxygen; Ozone
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- 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
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- 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
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- Inorganic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Birds (AREA)
- Oral & Maxillofacial Surgery (AREA)
- Plastic & Reconstructive Surgery (AREA)
- Dentistry (AREA)
- Emergency Medicine (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
This invention involves methods and compositions for preparation of unstable carbonated calcium phosphate solutions, which are supersaturated with respect to calcium phosphate solids and carbon dioxide and the use of such solutions for the treatment of dental tissue and hyposalivation. Specifically the methods include mixing a stable alkaline carbonated solution containing carbonate with a stable acidic calcium solution, either or both solutions also containing phosphate to create an unstable carbonated 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 an unstable carbonated solution supersaturated with respect to calcium phosphate solids and carbon dioxide. The methods further include using alkaline solutions to remove the acidic residue from dental tissue and maintain cariostatic conditions.
Description
CA 022l3689 l997-08-22 W O96J25914 PCT~US95/02364 I -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.
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 W O 96/25914 PCTrUS95/02364 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.
W ~96125914 PCT~US95/02364 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.
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.
W O96/25914 PCT~US95/0236 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.
W O 96/25914 PCTrUS95/02364 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 W O 96125914 PCT~US9S102364 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.
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.
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.
W O96/25914 PCTrUS95/02364 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.
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.
A carbonated solution is prepared according to the procedure of EXAMPLE
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 W O 96/25914 PCTrUS95/02364 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.
W ~96125914 PCT~US95/02364 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.
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.
W O96/25914 PCT~US95/0236 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.
W O 96/25914 PCTrUS95/02364 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 W O 96125914 PCT~US9S102364 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.
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.
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.
W O96/25914 PCTrUS95/02364 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.
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.
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.
A carbonated solution is prepared according to the procedure of EXAMPLE
1, except that the acidic calcium solution also includes I mM fluorosilicate ions.
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.
W O~6J25914 PCT~US95/02364 g A carbonated solution is prepared according to the procedure of EXAMPLE
1, except that the acidic calcium solution also contains 33 mM strontium ions.
A carbonated solution is prepared according to the procedure of EXAMPLE
3, except that the solid mixture also includes 2.5 mM fluorine compound.
A carbonated solution is prepared according to the procedure of EXAMPLE
3, except that the solid mixture also includes 0.33 mM strontium compound.
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.
A carbonated solution is prepared according to the procedure of EXAMPLE
1, except that the acidic calcium solution also includes I mM fluorosilicate ions.
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.
W O~6J25914 PCT~US95/02364 g A carbonated solution is prepared according to the procedure of EXAMPLE
1, except that the acidic calcium solution also contains 33 mM strontium ions.
A carbonated solution is prepared according to the procedure of EXAMPLE
3, except that the solid mixture also includes 2.5 mM fluorine compound.
A carbonated solution is prepared according to the procedure of EXAMPLE
3, except that the solid mixture also includes 0.33 mM strontium compound.
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.
Claims (30)
1. A -method of preparing an aqueous carbonated calcium phosphate solution supersaturated with respect to calcium phosphates and carbon dioxide under atmospheric conditions for use in treatment of dental tissue, comprising, mixing a stable alkaline solution containing carbonate with a stable acidic solution containing calcium ions and either or both solutions further contain phosphate ions.
2. The method of Claim 1 wherein either or both solutions further contain fluoride ions.
3. The method of Claim 2 wherein the fluoride is monofluorophosphate.
4. The method of Claim 1 wherein the stable acidic solution further contains the complex fluoride ions.
5. The method of Claim 4 wherein the complex fluoride is fluorosilicate.
6. The method of Claim 4 wherein the complex fluoride is fluorostannate.
7. The method of Claim 1 wherein the acidic solution further contains strontium ions.
8. The method of Claim 1 wherein either or both solutions further contain chlorhexidine compounds.
9. A method of preparing an aqueous carbonated calcium phosphate solution capable of remineralization of the teeth comprising adding water to solid containing calcium salt, phosphate salt and carbonate salt.
10. The method of Claim 9 wherein the water further contains hydrogen peroxide.
11. The method of Claim 9 wherein the water further contains chlorhexidine compound.
12. A method of Claim 9 wherein the solid further contains fluorine compound.
13. A method of Claim 9 wherein the solid further contains strontium compound.
14. A method of treating dental tissue comprising:
(1) mixing a stable nonpressurized alkaline carbonated solution containing carbonate with a stable nonpressurized acidic solution containing calcium ions where either or both said solutions contain phosphate ions, to create a mixed solution supersaturated with calcium phosphate and carbon dioxide; and (2) promptly applying the mixed solution to the dental tissue whereby the carbon dioxide escapes and calcium phosphate is deposited on and in the dental tissue.
(1) mixing a stable nonpressurized alkaline carbonated solution containing carbonate with a stable nonpressurized acidic solution containing calcium ions where either or both said solutions contain phosphate ions, to create a mixed solution supersaturated with calcium phosphate and carbon dioxide; and (2) promptly applying the mixed solution to the dental tissue whereby the carbon dioxide escapes and calcium phosphate is deposited on and in the dental tissue.
15. The method of Claim 14 wherein either or both alkaline solutions further contain fluoride ions.
16. The method of Claim 14 wherein the stable acidic solution further contains complex fluoride ions.
17. The method of Claim 16 wherein the complex fluoride is fluosilicate.
18. The method of Claim 16 wherein the complex fluoride is fluorostannate.
19. The method of Claim 14 wherein the stable acidic solution further contains strontium ions.
20. The method of Claim 14 wherein either or both solutions further contain chlorhexidine compounds.
21. The method of Claim 14 wherein the pH of the stable alkaline solution is at least about 8.
22. A method of treating dental tissue comprising:
(1) adding water to a solid mixture containing calcium salt, phosphate salt and carbonate salt to create an unstable carbonated solution supersaturated with respect to calcium phosphate and carbon dioxide; and (2) promptly applying the solution to the dental tissue whereby the carbon dioxide escapes and calcium phosphate is deposited on and in the dental tissue.
(1) adding water to a solid mixture containing calcium salt, phosphate salt and carbonate salt to create an unstable carbonated solution supersaturated with respect to calcium phosphate and carbon dioxide; and (2) promptly applying the solution to the dental tissue whereby the carbon dioxide escapes and calcium phosphate is deposited on and in the dental tissue.
23. A method of Claim 22 wherein the water further contains hydrogen peroxide.
24. A method of Claim 22 wherein the water further contains chlorhexidine compounds.
25. A method of Claim 22 wherein the solid further contains fluorine compound.
26. A method of Claim 22 wherein the solid further contains strontium compound.
27. A method of treating dental tissue comprising contacting the dental tissue with a nonpressurized alkaline carbonated mouth rinse whereby the alkaline carbonated mouth rinse interacts with the dental tissue to remove acidic materials.
28. The method of Claim 27 wherein the alkaline carbonated mouth rinse further contains phosphate.
29. The method of Claim 27 wherein the alkaline mouth rinse further contains chlorhexidine.
30. The method of Claim 27 wherein the alkaline mouth rinse further contains fluoride.
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002213689A CA2213689A1 (en) | 1995-02-24 | 1995-02-24 | Carbonated solutions for treating, mineralizing and fluoridating calcified tissues and methods for their use |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CA002213689A CA2213689A1 (en) | 1995-02-24 | 1995-02-24 | Carbonated solutions for treating, mineralizing and fluoridating calcified tissues and methods for their use |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2213689A1 true CA2213689A1 (en) | 1996-08-29 |
Family
ID=4161322
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002213689A Abandoned CA2213689A1 (en) | 1995-02-24 | 1995-02-24 | Carbonated solutions for treating, mineralizing and fluoridating calcified tissues and methods for their use |
Country Status (1)
Country | Link |
---|---|
CA (1) | CA2213689A1 (en) |
-
1995
- 1995-02-24 CA CA002213689A patent/CA2213689A1/en not_active Abandoned
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