Drug – bio-affecting and body treating compositions – Dentifrices
Reexamination Certificate
1999-07-09
2002-05-14
Rose, Shep K. (Department: 1614)
Drug, bio-affecting and body treating compositions
Dentifrices
C424S052000, C424S057000
Reexamination Certificate
active
06387352
ABSTRACT:
FIELD OF THE INVENTION
The present invention relates to calcium- and phosphate-containing compositions for use as mouthwashes or dental rinses. In particular, it relates to solutions supersaturated with calcium and phosphate, their preparation and use.
BACKGROUND OF THE INVENTION
By “supersaturated” with calcium and phosphate is herein meant that higher concentrations of calcium ions and orthophosphate ions are present in the solution than would be present in a saturated solution of those ions.
British patent specification no. GB 1 090 340, published in 1967, discloses compositions for rehardening dental enamel comprising fluoride, calcium, phosphate and sodium chloride which yield, on contact with saliva, supersaturated solutions to form hydroxyapatite. Because saliva is required to form the supersaturated solution, the preferred compositions are in the form of confectionery such as chewing gum. However, it is known that, under most circumstances, saliva is already supersaturated with calcium and phosphate. No disclosure is given of how to make a supersaturated solution ab initio which can then be used effectively in the form of a mouthwash or dental rinse. Furthermore, no mention is made of the possibility of excluding fluoride; or of the formation of octacalcium phosphate by the supersaturated solution in the saliva. In any case, in the absence of or where there is a significantly reduced mount of saliva, these compositions would not work as described.
A supersaturated solution is disclosed in U.S. Pat. No. 5,427,768 which is supersaturated with calcium phosphate and carbon dioxide and used to deposit apatite on the teeth. However, in this case, the supersaturation is caused by release of carbon dioxide, and carbonate is absorbed by the teeth which results in a deposited mineral phase with decreased resistance to dental caries.
British patent specification no. GB 1 408 922, published in 1975, discloses an oral treatment pack which comprises two phases for sequential application to teeth, the isolated phases comprising calcium (50 to 35000 ppm) and phosphate (50 to 40000 ppm) compounds, respectively. However, there is no disclosure or teaching regarding how to make a single phase, supersaturated solution within these concentration ranges which cover four orders of magnitude. Indeed, Example 3 thereof teaches two phases which, if mixed, would result in immediate precipitation of calcium phosphates.
A further solution containing calcium and phosphate is disclosed in British patent specification no. GB 1 509 977, published in 1978. This solution comprises one component containing calcium ions (at least 30 ppm) and another component containing at least 100 ppm fluoride, one or both components also containing phosphate ions (at least 0.1M) such that on mixing the components hydroxyapatite can be deposited therefrom on teeth. However, such solutions are not stably supersaturated (indeed, this patent teaches that the phosphate ions can be incorporated only in the solution containing calcium ions (at low concentration) which would not allow for the preparation of a stable, non-precipitating, supersaturated solution), and contains greater fluoride than considered to be clinically safe if accidentally swallowed. Again, no reference is made to producing octacalcium phosphate deposits.
BRIEF DESCRIPTION OF THE INVENTION
On the other hand, the present invention relates to an aqueous solution suitable for use as a dental rinse or mouthwash, which solution is supersaturated with respect to calcium phosphate(s) and which solution further comprises a stabilising agent such as sodium chloride (NaCl).
Although, as previously mentioned, it is known that, normally, saliva is supersaturated with respect to calcium and phosphates, the supersaturated solutions of the present invention contain significantly higher concentrations of those ions. Since the degree of supersaturation of saliva is variable from individual to individual, it is not possible to state definitively how much more supersaturated are the solutions of the present invention, but they may in many cases contain of the order of from 5 to 10 times the concentrations of calcium and phosphate ions than normal saliva.
The present inventors have disclosed (Gerodontics 3, 47-50 (1987)) the remineralisation of carious lesions in elderly patients using an experimental regimen which included mouthwashing with a solution comprising 5 mM Ca, 3 mM PO
4
and 0.25 mM (5 ppm) fluoride, stabilised by NaCl, at pH 7.0. No other uses of the solution were mentioned and no details concerning the preparation of the solution were given other than that “two stock solutions were stored separately and mixed in proper volumes immediately before use”.
The supersaturated solutions of the present invention are required to be prepared just prior to use due to the degree of supersaturation thereof and the risk of precipitation of calcium phosphate (mineral) therefrom.
DETAILED DESCRIPTION OF THE INVENTION
Accordingly, the present invention provides a formulation suitable for use as a dental rinse or mouthwash, which formulation comprises:
(a) a calcium component (calcium stock solution) which itself comprises an aqueous solution of calcium ions and stabiliser; and, associated therewith but separate therefrom,
(b) a phosphate component (phosphate stock solution) which itself comprises an aqueous solution of phosphate ions and stabiliser wherein the calcium and phosphate are present in amounts sufficient to form, on mixing, a supersaturated solution thereof, as described hereinbelow.
The present invention therefore specifically provides a multi-component formulation suitable for use as a dental rinse or mouthwash, which formulation comprises:
(a) a calcium component (calcium stock solution) which itself comprises an aqueous solution of calcium ions having a concentration in the range of from about 4 to about 80 mM and from about 40 to about 400 mM stabiliser; and, associated therewith but separate therefrom,
(b) a phospate component (phosphate stock solution) which itself comprises an aqueous solution of (ortho)phosphate ions having a concentration in the range of from about 1 to about 64 mM and from about 40 to about 400 mM stabiliser
whereby, on mixing, the components form a solution supersaturated with respect to calcium phosphate(s).
The supersaturated solutions of the present invention remain stable at least for the length of time and under normal conditions of their use. By this is meant that the supersaturated solution remains substantially supersaturated with respect to calcium and orthophosphate ions for the normal time the solution is rinsed or washed around the oral cavity. After this time, the solution may begin to contain some precipitate of calcium phosphates which would reduce its therapeutic effectiveness. Therefore, conveniently, the solution may remain supersaturated in the oral cavity for up to about five minutes, especially up to 2-3 minutes and necessarily up to about 1 minute, all measurements therefore taken at body temperature. It will be understood that, at lower temperatures such as room or ambient temperature, the supersaturated solution will remain so for significantly longer periods such as of the order of up to 2 hours, especially up to 1 hour and necessarily for the length of time taken to use the supersaturated solution just mixed as a dental rinse or mouthwash which may be in the range of from about 3 minutes to about 15 minutes.
Preferably components (a) and (b) do not, respectively, contain any phosphate or calcium, although minor amounts (up to 10-20% either way—less at higher pH and vice versa) could be tolerated.
Preferably, the supersaturated solution has a pH of from about 5 to about 8.0, more preferably of from about 6 to about 7.5, such as about 6.5 to about 7.5; especially preferred is when the pH is about neutral such as 7.0±0.2. The pH of each stock solution component may vary widely: for component (a), it is in the range 1 to 12.5, preferably 3.5 to 8, more preferably 4 to 7.5; for component (b), it is in the range
Johansen Erling
Olsen Thor
Papas Athena
Erling Johansen
Rose Shep K.
Synnestvedt & Lechner LLP
LandOfFree
Mouthwash compositions does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Mouthwash compositions, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Mouthwash compositions will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2845795