U.S. patent application number 15/664875 was filed with the patent office on 2018-01-18 for composition for preventing or treating dental erosion.
The applicant listed for this patent is MEDA OTC AB. Invention is credited to Thomas BERGLUND, Gunilla JOHANSSON-RUDEN.
Application Number | 20180015011 15/664875 |
Document ID | / |
Family ID | 53476865 |
Filed Date | 2018-01-18 |
United States Patent
Application |
20180015011 |
Kind Code |
A1 |
BERGLUND; Thomas ; et
al. |
January 18, 2018 |
COMPOSITION FOR PREVENTING OR TREATING DENTAL EROSION
Abstract
The present invention related to a composition of pH in the
range 2.0 to 4.5 comprising at least one fluoride source and at
least one other agent for use in prevention and/or treatment of
dental erosion.
Inventors: |
BERGLUND; Thomas; (Jar,
NO) ; JOHANSSON-RUDEN; Gunilla; (Askim, SE) |
|
Applicant: |
Name |
City |
State |
Country |
Type |
MEDA OTC AB |
Solna |
|
SE |
|
|
Family ID: |
53476865 |
Appl. No.: |
15/664875 |
Filed: |
July 31, 2017 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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15315982 |
Dec 2, 2016 |
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PCT/EP2015/063693 |
Jun 18, 2015 |
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15664875 |
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Current U.S.
Class: |
1/1 |
Current CPC
Class: |
A61K 8/368 20130101;
A61K 8/362 20130101; A61K 8/44 20130101; A61Q 11/00 20130101; A61K
8/365 20130101; A61P 1/02 20180101; A61P 43/00 20180101; A61K 8/36
20130101; A61K 8/21 20130101; A61K 8/37 20130101 |
International
Class: |
A61K 8/21 20060101
A61K008/21; A61K 8/44 20060101 A61K008/44; A61K 8/368 20060101
A61K008/368; A61K 8/36 20060101 A61K008/36; A61K 8/365 20060101
A61K008/365; A61K 8/362 20060101 A61K008/362; A61Q 11/00 20060101
A61Q011/00; A61K 8/37 20060101 A61K008/37 |
Foreign Application Data
Date |
Code |
Application Number |
Jun 18, 2014 |
NO |
20140766 |
Claims
1-10. (canceled)
11. A method for preventing and/or treating dental erosion;
preventing demineralization or subsurface demineralization of the
dental enamel; and/or enhancing remineralization of the dental
enamel or the subsurface dental enamel, comprising administering to
a subject in need thereof a composition comprising, at least one
fluoride source selected from hydrofluoric acid (HF), one or more
bifluoride(s) or a mixture thereof; and at least one organic acid
or salt thereof, wherein at least one pKa of the organic acid is in
the range from 2 to 6; wherein the pH of the composition is in the
range from 2.0 to 4.5, for use in.
12. The method of claim 11, wherein the pH of the composition is in
the range from 2.5 to 4.0.
13. The method of claim 11, wherein the pH of the composition is in
the range from 3.0 to 3.5.
14. The method of claim 11, wherein the pH of the composition is
about 3.5.
15. The method of claim 11, wherein the total amount of fluoride
present in the composition is from about 0.01% to about 4.0% by
weight.
16. The method of claim 11, wherein the total amount of fluoride
present in the composition is from about 0.01% to about 2.0% by
weight.
17. The method of claim 11, wherein the total amount of fluoride
present in the composition is from about 0.01% to about 1.0% by
weight.
18. The method of claim 11, wherein the total amount of fluoride
present in the composition is from about 0.01% to about 0.5% by
weight.
19. The method of claim 11, wherein the total amount of fluoride
present in the composition is from about 0.01% to about 0.05% by
weight.
20. The method of claim 11, wherein the total amount of fluoride
present in the composition is less than 0.05% by weight.
21. The method of claim 11, wherein the fluoride source is HF.
22. The method of claim 11, wherein the fluoride source is a
bifluoride selected from the group consisting of NaHF2, KHF2,
NH4HF2, and any mixtures thereof.
23. The method of claim 11, wherein the organic acid or salt
thereof is selected from the group consisting of benzoic acid,
sodium benzoate, glycine, glycolic acid, glutamic acid, lactic
acid, and any mixtures thereof.
24. The method of claim 11, wherein the organic acid or salt
thereof is selected from the group consisting of benzoic acid,
sodium benzoate, glycine, and any mixtures thereof.
25. The method of claim 11, wherein the fluoride source is HF and
the organic acid or salt thereof is a mixture of sodium benzoate
and glycine.
26. The method of claim 11, wherein the fluoride source is a
bifluoride and the organic acid or salt thereof is a mixture of
sodium benzoate and glycine.
27. The method of claim 11, wherein the composition is in the form
of an aqueous solution, a gel, a foam, a dentifrice, a dental
varnish, or a toothpaste.
Description
FIELD OF THE INVENTION
[0001] The present invention relates to a composition of pH in the
range 2.0 to 4.5 comprising at least one fluoride source and at
least one organic acid or salt thereof for use in prevention and/or
treatment of dental erosion, prevention of demineralisation of the
dental enamel and/or enhancement of remineralisation of the dental
enamel, prevention of subsurface demineralisation of the dental
enamel and/or enhancement of remineralisation of the subsurface
dental enamel.
BACKGROUND OF THE INVENTION
[0002] Tooth enamel mainly consists of minerals and the primary
mineral is hydroxyl apatite (HA), which is a crystalline calcium
phosphate with the formula Ca.sub.5(PO.sub.4).sub.3(OH).
[0003] Demineralisation of HA starts when the local pH goes below
5.5. The saliva is supersaturated with various ions (see M. J.
Larsen et al., "Saturation of human saliva with respect to calcium
salts", Archives of Oral Biology (2003) 48, 317-322). These ions
act as a buffer, keeping the acidity of the mouth within a certain
range, typically pH 6.2 to 7.4. This normally prevents the minerals
from dissolving. Some of the mineral loss can be
recovered/remineralised from the ions in the saliva if the pH is
buffered and stay above 5.5.
[0004] Dental/acidic erosion is defined as the irreversible loss of
tooth structure (enamel, dentine and cementum) due to chemical
dissolution by acids not of bacterial origin. Dental erosion is
thus different in both ethology and pathogenesis from dental caries
that is an infectious disease caused by certain bacteria in the
dental plaque (biofilm). The most common cause of dental erosion is
by acidic foods and drinks but can sometimes be caused by
gastro-oesophageal reflux. It is the most common chronic disease of
children aged 5-17 years according to the US Department of health
and Human services (8. Aug. 2007).
[0005] Dentists have no established good ways to mend already
eroded enamel. The best way is to prevent erosion but there are no
effective products on the market today.
[0006] The use of topical products containing fluoride will result
in formation of calcium fluoride (CaF.sub.2) precipitate in contact
with the enamel. The calcium (Ca) originates from salvia and teeth.
CaF.sub.2 formation on dental hard tissues during topical fluoride
treatment depends on many factors such as the solubility of the
tooth, sound or demineralised surface, length of fluoride exposure
time, the fluoride concentration and the pH of the topical agent
(see Bjorn Ogaard, <<CaF.sub.2 Formation: Cariostatic
Properties and Factors of Enhancing the Effect>>, Caries
Research 2001; 35(suppl 1):40-44.).
[0007] Fluorapatite formation following the CaF.sub.2 material has
been suggested. Fluorapatite Ca.sub.5(PO.sub.4).sub.3F can be
formed in neutral or acidic conditions above pH 4.5 and will
dissolve and thus not protect from acidic situations below pH 4.5
such as fruit juices, energy drinks and sodas etc. resulting in
erosion of enamel.
[0008] An acidic topical product (i.e. below pH of 4.5) containing
a small amount of fluoride will after a minor etch release Ca from
HA and then instantly be followed by deposition of a thin
protective layer of CaF.sub.2 on the teeth. The formed low
phosphate contaminated CaF.sub.2 is only slightly soluble in water
and in acidic solutions and much less in saliva (as saliva normally
already contains at least 100 mg Calcium/L). CaF.sub.2 is much less
soluble in acids such as citric acid than the normal enamel
hydroxyapatite or fluorapatite. Thus, said low phosphate
contaminated CaF.sub.2 forms a mechanical barrier that protects
dental enamel from acidic erosion.
[0009] International patent application with publication no. WO
2005/110347 relates to a composition for inhibiting dental erosion
comprising an aqueous solution of hydrofluoric acid (HF) in a
concentration of 0.05 to 2.00% in which the pH of the aqueous
solution is between 2.5 and 4.5.
[0010] C. Hjortsjo et al., "Effect of Stannous Fluoride and Dilute
Hydrofluoric Acid on Early Enamel Erosion over Time in vivo",
Caries Research 2009; 43:449-454, reports a study made in order to
evaluate the longer-term protective effect of aqueous solutions of
HF (0.2%, pH 2.0) and stannous fluoride (SnF.sub.2) (0.78%, pH 2.9)
(both--0.1 mol/l F) on enamel solubility. It was concluded from
this study that treatment of sound enamel with a 0.2% HF solution
had a protective effect against citric acid attack that lasted for
at least 1 week. In contrast, the SnF.sub.2 solution containing the
same low fluoride concentration had no effect after only 1 day.
SUMMARY OF THE INVENTION
[0011] The present invention has surprisingly shown improved
results against dental erosion by adding at least one organic acid
or salt thereof to a composition of at least one fluoride
source.
[0012] A main object of the present invention is to provide
compositions useful in inhibition of dental erosion which is more
effective than those known in the art.
[0013] This and other objects are achieved by a composition
comprising at least one fluoride source selected from HF, one or
more bifluoride(s) or a mixture thereof; and at least one organic
acid or salt thereof, wherein at least one pKa of the organic acid
is in the range from 2 to 6;
wherein the pH of the composition is in the range from 2.0 to
4.5.
[0014] According to a preferred embodiment of the present
invention, the pH of the composition is in the range from 2.5 to
4.0, more preferable in the range from 3.0 to 3.5, and most
preferable about 3.5.
[0015] The amount of fluoride in the composition of the present
invention is selected from the group consisting of from about 0.01%
to about 4.0% by weight, from about 0.01% to about 2.0% by weight,
from about 0.01% to about 1.0% by weight, from about 0.01% to about
0.5% by weight, from about 0.01% to about 0.05% by weight and less
than 0.05% by weight.
[0016] According to a preferred embodiment of the present
invention, the amount of fluoride in the composition is from about
0.01% to about 1.0% by weight, more preferable from about 0.01% to
about 0.5% by weight, most preferable about 0.15% by weight.
[0017] According to one aspect of the present invention, the at
least one fluoride source is selected from the group consisting of
HF, NaHF.sub.2, KHF.sub.2, NH.sub.4HF.sub.2 and any mixtures
thereof.
[0018] According to a preferred embodiment of the present
invention, the at least one fluoride source is HF.
[0019] According to another preferred embodiment of the present
invention, the at least one fluoride source is a bifluoride. The
bifluoride is preferably selected from the group consisting of
NaHF.sub.2, KHF.sub.2, NH.sub.4HF.sub.2 and any mixtures
thereof.
[0020] In addition to the at least one fluoride source defined
above, the composition of the invention may include a further
fluoride source, for example selected from the group consisting of
NaF, KF, NH.sub.4F and mixtures thereof.
[0021] According to one embodiment of the invention, the fluoride
source is a mixture of HF and one or more bifuoride(s).
[0022] According to another embodiment of the invention, the
fluoride source is a mixture of HF and another fluoride, for
example selected from the group consisting of NaF, KF, NH.sub.4F
and mixtures thereof.
[0023] According to further embodiment of the invention, the
fluoride source is a mixture of one or more bifluoride(s) and a
further fluoride, for example selected from the group consisting of
NaF, KF, NH.sub.4F and mixtures thereof.
[0024] According to yet another embodiment of the invention, the
fluoride source is a mixture of HF, one or more bifluoride(s), and
a further fluoride, for example selected from the group consisting
of NaF, KF, NH.sub.4F and mixtures thereof.
[0025] According to another aspect of the present invention it is a
proviso that the composition does not comprise acidulated phosphate
fluorides.
[0026] According to a preferred embodiment of the present
invention, the at least one organic acid or salt thereof is
physiologically acceptable.
[0027] In another preferred embodiment of the invention, the at
least one organic acid or salt thereof of the composition is
selected from the group consisting of benzoic acid, sodium
benzoate, glycine, glycolic acid, glutamic acid, lactic acid and
any mixtures thereof.
[0028] The amount of organic acid(s) or salts thereof in the
composition of the present invention is selected from the group
consisting of from about 0.01% to about 10.0% by weight, from about
0.01% to about 7.0% by weight, from about 0.01% to about 3.0% by
weight, from about 0.01% to about 2.0% by weight, from about 0.10%
to about 2.0% by weight, from about 0.01% to about 1.0% by weight,
from about 0.10% to about 1.0% by weight, and from about 0.10% to
about 0.5% by weight.
[0029] In a preferred embodiment of the present invention, each of
the organic acids or salts thereof present in the composition is in
an amount of from about 0.10% to about 2.0 by weight, more
preferably from about 0.10% to about 1.0% by weight, and most
preferably from about 0.10% to about 0.5% by weight.
[0030] In a preferred embodiment of the present invention, glycine
is present in the composition in an amount of from about 0.10% to
about 10.0% by weight, from about 0.10% to about 7.0% by weight,
from about 0.10% to about 5.0% by weight, from about 0.10% to about
3.0% by weight, from about 0.10% to about 2.0% by weight, from
about 0.10% to about 1.0% by weight, from about 0.10% to about 0.5%
by weight or from about 0.10% to about 0.3% by weight. One or more
other organic acid(s) or salt thereof may be present in the
composition in addition to the glycine.
[0031] In another preferred embodiment of the present invention,
benzoic acid is present in the composition in an amount of from
about 0.05% to about 2.0% by weight, from about 0.10% to about 1.0%
by weight, or from about 0.10% to about 0.5% by weight. One or more
other organic acid(s) or salt thereof may be present in the
composition in addition to the benzoic acid.
[0032] In a further preferred embodiment of the present invention,
sodium benzoate is present in the composition in an amount of from
about 0.05% to about 2.0% by weight, from about 0.10% to about 1.0%
by weight, or from about 0.10% to about 0.5% by weight. One or more
other organic acid(s) or salt thereof may be present in the
composition in addition to the sodium benzoate.
[0033] In yet another preferred embodiment of the present
invention, glycine and benzoic acid, or glycine and sodium benzoate
are present in the composition. The amount of each of organic acid
or salt is in the amount from about 0.05% to about 2.0% by weight,
from about 0.10% to about 1.0% by weight, or from about 0.10% to
about 0.5% by weight of the composition.
[0034] According to still another embodiment of the invention,
glycine and glycolic acid, glycine and glutamic acid, or glycine
and lactic acid are present in the composition. The amount of each
of organic acid or salt is in the amount from about 0.05% to about
2.0% by weight, from about 0.10% to about 1.0% by weight, or from
about 0.10% to about 0.5% by weight of the composition.
[0035] According to one aspect of the present invention, at least
part of the fluoride source is in particulate form.
[0036] According to another aspect of the present invention, the
composition is in the form of an aqueous solution, a gel, a foam, a
dentifrice, a dental varnish or a toothpaste.
[0037] According to another aspect of the present invention, the
composition is in form of a fluid on application and sets as a
varnish on the teeth in temperatures above 30.degree. C.
[0038] According to a preferred embodiment of the present
invention, the composition is in the form of a toothpaste
comprising a bifluoride in particulate form.
[0039] According to another preferred embodiment, the composition
is in a form of an aqueous solution that is used in the same way as
a mouth rinse.
[0040] In one embodiment of the present invention, the composition
may comprise a further agent being a water soluble polymer. The
polymer may be selected from the group consisting of a
polysaccharide, a polysaccharide derivative, a poloxamer and a
polyethylene glycol (PEG). The polymer may be present in the
composition in an amount of 0.1% to 10% by weight.
[0041] According to one embodiment of the present invention,
polymer is a chitosan and a chitosan derivative.
[0042] In one embodiment of the present invention, the composition
may further comprise a divalent metal ion. The divalent metal ion
may be present in the composition in an amount of 0.01% to 0.5% by
weight. The divalent metal ion is selected from the group
consisting of Ca, Zn, Cu and Sn.
[0043] In one embodiment of the present invention, the composition
may further comprise an antibacterial agent. The antibacterial
agent may be selected from bis-biguanide and quaternary ammonium
compounds or any combination thereof. Zn and Cu as mentioned above
are antibacterial agents as well. According to one embodiment, the
antibacterial agent is chlorhexidine and the chlorhexidine is
present in the composition in an amount of 0.001% to 1% by
weight.
[0044] The present composition according to the invention is for
use in prevention and/or treatment of dental erosion.
[0045] In another aspect the present invention the composition as
defined above is for use in preventing demineralisation of the
dental enamel and/or enhancing remineralisation of the dental
enamel.
[0046] In yet another aspect the present invention the composition
as defined above is for use in preventing subsurface
demineralisation of the dental enamel and/or enhancing
remineralisation of the subsurface dental enamel.
DESCRIPTION OF THE FIGURES
[0047] Preferred embodiments of the present invention will now be
illustrated in more detail with reference to the accompanying
figures.
[0048] FIG. 1 illustrates SEM pictures of an untreated HA disc
before and after etching.
[0049] FIG. 2 shows an EDS spectra of an untreated HA disc.
[0050] FIG. 3 illustrates SEM pictures of a HA disc treated with a
solution of Table 1 before and after etching, and compared to FIG.
1 this HA disc is protected from the etching.
[0051] FIG. 4 shows an EDS spectra of the HA disc after treatment
with the solution of Table 1.
DETAILED DESCRIPTION OF THE INVENTION
[0052] Experiments were performed to study the compositions' effect
on dental erosion.
[0053] A Comparison Example was performed to show that polished HA
discs are an appropriate in vitro model for studying effects of
fluoride solutions and etching on enamel.
[0054] Reference Example 1 shows SEM pictures of an untreated HA
disc before and after etching (see FIG. 1), and EDS spectrum of the
presence of oxygen (O), phosphor (P) and calcium (Ca) proving that
hydroxyl apatite Ca.sub.5(PO.sub.4).sub.3(OH) is formed on the
surface of the untreated HA disc (see FIG. 2).
[0055] Example 1 shows corresponding date as presented in Reference
Example 1 for a HA disc treated with a composition of the invention
(see FIGS. 3 and 4).
[0056] Reference Example 2 shows an experiment with a composition
according to the prior art (WO 2005/110347) wherein the fluoride
source is hydrogen fluoride (HF). No organic acids or salts thereof
are added.
[0057] Examples 1 to 10 show experiments with compositions of the
invention wherein the fluoride source is HF. Different organic
acids or salts thereof are present in the various compositions. The
amounts of HF and organic acid(s)/salt(s) are varied, as well as
the pH value.
[0058] As can be seen from Examples 1 to 10, as shown by ICP-AES
analysis, all compositions according to the invention are more
effective in inhibiting dental erosion than the composition of
Reference Example 2.
[0059] Reference Example 3 shows an experiment with a composition
wherein the fluoride source is a bifluoride (i.e. NaHF.sub.2). No
organic acids or salts thereof are added.
[0060] Examples 11 to 12 show experiments with compositions of the
invention wherein the fluoride source is a bifluoride (i.e.
NaHF.sub.2). Different organic acids are present in the various
compositions.
[0061] As can be seen from Examples 11 and 12, as shown by ICP-AES
analysis, the compositions according to the invention are more
effective in inhibition of dental erosion than the composition of
Reference Example 2 not comprising an organic acid or salt
thereof.
Experimental Model
[0062] The method used is an in vitro model consisting of hydroxyl
apatite (HA) discs which serve as a model for tooth enamel. The
model enables testing the effect on preventing enamel erosion after
acid etching by using different solutions containing fluoride (F).
As shown by the Comparison Example below, this is a good in vitro
model for studying effects of aqueous fluoride solutions and
etching on enamel.
Analytical Methods
[0063] Analyses were carried out by using low vacuum scanning
electron microscopy (SEM) equipped with energy-dispersive X-ray
spectroscopy (EDS) detectors for elemental analysis of disc
surfaces and inductively coupled plasma atomic emission
spectroscopy (ICP-AES) analysis of the etching solution.
SEM
[0064] In general, SEM produces images of a sample by scanning it
with a focused beam of electrons. The electrons interact with atoms
in the sample, producing various signals that can be detected and
that contain information about the sample's surface topography and
composition. Specimens can be observed in high vacuum, in low
vacuum, in wet conditions. In the present analyses, low vacuum
conditions have been used.
[0065] EDS detectors as used in the present SEM, have analytical
capabilities, and can provide several items of data at each
pixel.
[0066] In the examples below, SEM analysis enables a visual
comparison of the surface layers, i.e. CaF.sub.2 layer formed upon
fluoride treatment of the HA discs, as well as elemental analysis
and comparison of the layer thickness. EDS is preferably run to
compare the amount of fluoride (F), phosphor (P) and calcium (Ca)
on the disc surface. An increase in Ca and F in combination with a
decrease in P after fluoride treatment means that a CaF.sub.2 layer
has been formed on the surface. After etching, peaks of Ca and F
usually decrease and P increases.
ICP-AES
[0067] In general, ICP-AES is an analytical technique used for the
detection of trace metals. It is a type of emission spectroscopy
that uses the inductively coupled plasma to produce excited atoms
and ions that emit electromagnetic radiation at wavelengths
characteristic of a particular element. The intensity of this
emission is indicative of the concentration of the element within
the sample.
[0068] In the examples below, erosion corresponds to surface
dissolution and when HA is dissolved there are ions released into
the acid. Difference in amount dissolved HA as Ca and P (mg/L) are
found. The interpretation of the data is; when there is less Ca and
P found in the citric acid after fluoride treatment compared to a
citric acid etched control HA-disc, then the fluoride treatment has
proven to protect the disc. That is, ICP-AES analysis measures the
amount of Ca and P ions in the etching solutions. Ca and P
concentration in mg/l or .mu.g/l of etching solutions are compared
to results of etching solution of an untreated reference HA disc
and the percentage reduction of Ca and P is calculated. This
percentages indicate how well the HA discs are protected from
etching. The lower concentrations of Ca and P ions, the higher
resistance against etching/erosion.
Comparison Example
Equipment
[0069] A low vacuum scanning electron microscope, JEOL JSM 6610 LV,
was used for studying surfaces.
[0070] SEM pictures were taken with 5000 times magnification (SEM
.times.5000).
Hydroxyl Apatite (HA) Discs
[0071] HA discs were prepared. The discs had one polished side and
one unpolished. The discs were stored at room temperature and kept
dry.
[0072] 3 drops of 2% citric acid were placed on a HA disc using a
pipette. The 3 drops were allowed to etch the HA disc for 15
minutes at room temperature. The contours of the drops were clearly
defined and there was obviously a surface tension. The HA disc was
then rinsed in distilled water and then left to dry on tissue
paper. SEM pictures (.times.5000) (FIGS. 5-6) were taken to analyse
the HA surface before and after etching with citric acid.
[0073] A HA disc were immersed in a solution comprising 0.15%
hydrogen fluoride (HF) at pH 2.58 for 5 minutes in 37.degree. C.
during gentle agitation (50 ml plastic bottle was used). The disc
was rinsed in distilled water and left to dry on tissue paper for a
few minutes. 3 droplets of 2% citric acid were placed on the
surface by using a syringe, and the etching was allowed for 15
minutes. Visual inspection of the disc surface showed that after
treatment with HF solution, the surface tension had decreased and
the droplets of acid floated out compared to the disc that was not
HF treated. The disc was then rinsed in distilled water. SEM
picture (.times.5000) (FIG. 7) was taken to analyse the HA surface
after HF treatment.
Ex Vivo Human Tooth
[0074] A human ex vivo tooth (premolar) was received from a dentist
practice. The tooth was stored in Ringer solution and kept in
refrigerator.
[0075] The effect of the HF treatment on HA surfaces was verified
using an ex vivo human premolar tooth. The tooth had been split
into two halves before the experiment (tooth 1:1 and tooth 1:2).
The two tooth halves were rinsed with distilled water. One tooth
half was placed in a 50 ml plastic bottle containing 2% citric acid
and then allowed to incubate at 37.degree. C. for 15 minutes under
gentle agitation. The tooth was then rinsed with distilled water
for a few minutes and then put on tissue paper to dry. The other
tooth half was immersed in a solution comprising 0.15% hydrogen
fluoride (HF) at pH 2.58 for 5 minutes at 37.degree. C. under
gentle agitation (50 ml plastic bottle). The tooth half was rinsed
with distilled water and then immersed in 2% citric acid and then
allowed to incubate at 37.degree. C. for 15 minutes under gentle
agitation. The tooth was then rinsed with distilled water and left
to dry on tissue paper for a few minutes.
[0076] SEM pictures (.times.5000) were taken to study the effect of
HF treatment and subsequent citric acid etching on the enamel
surface.
[0077] The SEM pictures (FIGS. 8-11) show that the enamel is
clearly protected from etching by the CaF.sub.2 layer formed during
HF treatment.
Conclusion of Comparison Example
[0078] Polished HA discs appear to be a good in vitro model for
studying effects of fluoride solutions and etching on enamel.
Materials, Conditions and Routines used in the following Reference
Examples and Examples
[0079] 2% citric acid (pH 2.2) was used as etching solution.
[0080] Distilled water or tap water was used for rinsing.
[0081] All steps of the experiments were performed at 20 to
25.degree. C.
[0082] Fluoride solutions were weighed into plastic beakers and one
or more HA discs were placed into each beaker for 5 minutes. Then
the discs were moved to a container with water to be rinsed for at
least 5-10 seconds.
[0083] Etching solution was weighed into plastic bottles and one
fluoride treated HA discs were placed in each bottle for 15
minutes. Then the discs were moved to a container with water to be
rinsed for at least 5-10 seconds.
[0084] The disc surface after etching were analysed with SEM.
[0085] The citric acid solution used in the studies was subjected
to ICP-AES analysis.
Reference Example 1
[0086] A low vacuum scanning electron microscope, JEOL JSM 6610 LV,
was used for studying surfaces and equipped with EDS for elemental
analysis.
[0087] SEM pictures (SEM .times.1000) of an untreated HA disc
before (on the left) and after etching (on the right) are shown in
FIG. 1.
[0088] In FIG. 2 an EDS spectrum of an untreated HA disc showing
the presence of oxygen (O), phosphor (P) and calcium (Ca) in
proportions telling that it is hydroxyl apatite
Ca.sub.5(PO.sub.4).sub.3(OH) on the surface.
Reference Example 2
[0089] A solution consisting of the ingredients shown in the table
below was prepared:
TABLE-US-00001 TABLE (Reference solution 2) Ingredient Amount in %
(w/w) Hydrogen fluoride 0.15 Purified water up to 100 NaOH
Adjustment of pH to 3.5
[0090] The following results were obtained.
TABLE-US-00002 ICP Citric acid etch 15 min 2% citric acid etch
(room temp) Product Reduction Ca % Reduction P Reference solution 2
60 66
Example 1
[0091] A solution consisting of the ingredients shown in table 1
was prepared:
TABLE-US-00003 TABLE 1 Ingredient Amount in % (w/w) Hydrogen
fluoride 0.15 Glycine 0.20 Sodium benzoate 0.15 Sweetener,
viscosity improver, 36 taste etc. Purified water 63 HCl or NaOH
Adjustment of pH to 3.5
[0092] The total amount of fluoride in the composition was
0.14%.
[0093] A low vacuum scanning electron microscope, JEOL JSM 6610 LV,
was used for studying surfaces and equipped with EDS for elemental
analysis.
[0094] SEM pictures of a HA disc treated with the solution of Table
1 before (on the left, SEM .times.200) and after etching (on the
right, SEM .times.1000)) are shown in FIG. 3. The protective layer
is somewhat affected after 15 min etching but mainly intact and the
tooth beneath is protected.
[0095] EDS spectrum of the HA disc after treatment with the
solution of Table 1 showing the presence of F and Ca in proportions
telling that it is CaF.sub.2 is shown in FIG. 4. The amounts of 0
and P are supressed due to the covering layer of is CaF.sub.2 but
still visible in the spectra because EDS penetrates deeper into the
specimen than the layer. The spectrum also shows that the layer
does not consist of fluorapatite Ca.sub.5(PO.sub.4).sub.3F due to
the proportions in the spectrum.
[0096] Amount released P and Ca compared to control (untreated) was
noted and the treatment with the solution of Table 1 had a major
protective impact as showed by the reduction of amount eroded
ions:
% reduction = ( release from Control ( untreated ) release from
Control - treated ) .times. 100 ##EQU00001##
TABLE-US-00004 ICP Citric acid etch 15 min 2% citric acid etch
(room temp) Product Reduction Ca % Reduction P Solution of Table 1
73 79
Example 2
[0097] A solution consisting of the ingredients shown in table 1
except that the amount of sodium benzoate was increased to 0.30%
and the amount of purified water was decreased accordingly, was
prepared and tested. The total amount of fluoride in the
composition was 0.14%, and the acidity was adjusted to pH 3.5.
[0098] The surfaces of the HA discs treated with the present
solution before and after etching were significantly improved over
that treated by the solution of Table 1.
[0099] The following results were obtained.
TABLE-US-00005 ICP Citric acid etch 15 min 2% citric acid etch
(room temp) Product Reduction Ca % Reduction P Solution of Table 2
79 85
Example 3
[0100] A solution consisting of the ingredients shown in table 3
was prepared:
TABLE-US-00006 TABLE 3 Ingredient Amount in % (w/w) Hydrogen
fluoride 0.15 Glycine 0.90 Purified water up to 100 HCl or NaOH
Adjustment of pH to 3.5
[0101] The total amount of fluoride in the composition was
0.14%.
[0102] The following results were obtained.
TABLE-US-00007 ICP Citric acid etch 15 min 2% citric acid etch
(room temp) Product Reduction Ca % Reduction P Solution of Table 3
72 61
Example 4
[0103] A solution consisting of the ingredients shown in table 4
was prepared:
TABLE-US-00008 TABLE 4 Ingredient Amount in % (w/w) Hydrogen
fluoride 0.48 Glycine 0.56 Purified water up to 100 HCl or NaOH
Adjustment of pH to 3.51
[0104] The total amount of fluoride in the composition was
0.5%.
[0105] The following results were obtained.
TABLE-US-00009 ICP Citric acid etch 15 min 2% citric acid etch
(room temp) Product Reduction Ca % Reduction P Solution of Example
12 89 86
Example 5
[0106] A solution consisting of the ingredients shown in table 5
was prepared:
TABLE-US-00010 TABLE 5 Ingredient Amount in % (w/w) Hydrogen
fluoride 0.15 Glycine 0.20 Purified water up to 100 HCl or NaOH
Adjustment of pH to 2.58
[0107] The total amount of fluoride in the composition was
0.14%.
[0108] The following results were obtained.
TABLE-US-00011 ICP Citric acid etch 15 min 2% citric acid etch
(room temp) Product Reduction Ca % Reduction P Solution of Table 5
61 83
Example 6
[0109] A solution consisting of the ingredients shown in table 6
was prepared:
TABLE-US-00012 TABLE 6 Ingredient Amount in % (w/w) Hydrogen
fluoride 0.95 Glycine 1.34 Purified water up to 100 HCl or NaOH
Adjustment of pH to 3.87
[0110] The total amount of fluoride in the composition was 1%.
[0111] The following results were obtained.
TABLE-US-00013 ICP Citric acid etch 15 min 2% citric acid etch
(room temp) Product Reduction Ca % Reduction P Solution of Table 6
65 71
Example 7
[0112] A solution consisting of the ingredients shown in table 7
was prepared:
TABLE-US-00014 TABLE 7 Ingredient Amount in % (w/w) Hydrogen
fluoride 0.95 Glycine 1.34 Sodium benzoate 0.30 Purified water up
to 100 HCl Adjustment of pH to 3.9
TABLE-US-00015 ICP Citric acid etch 15 min 2% citric acid etch
(room temp) Product Reduction Ca % Reduction P Solution of Table 7
67 81
Example 8
[0113] A solution consisting of the ingredients shown in table 8
was prepared:
TABLE-US-00016 TABLE 8 Ingredient Amount in % (w/w) Hydrogen
fluoride 0.15 Glycine 0.20 Glycolic acid 0.30 Purified water up to
100 NaOH Adjustment of pH to 3.5
[0114] The following results were obtained.
TABLE-US-00017 ICP Citric acid etch 15 min 2% citric acid etch
(room temp) Product Reduction Ca % Reduction P Solution of Table 8
76 77
Example 9
[0115] A solution consisting of the ingredients shown in table 9
was prepared:
TABLE-US-00018 TABLE 9 Ingredient Amount in % (w/w) Hydrogen
fluoride 0.15 Glutamic acid 0.30 Purified water up to 100 NaOH
Adjustment of pH to 3.5
[0116] The following results were obtained.
TABLE-US-00019 ICP Citric acid etch 15 min 2% citric acid etch
(room temp) Product Reduction Ca % Reduction P Solution of Table 9
69 70
Example 10
[0117] A solution consisting of the ingredients shown in table 10
was prepared:
TABLE-US-00020 TABLE 10 Ingredient Amount in % (w/w) Hydrogen
fluoride 0.15 Glycine 0.20 Lactic acid 0.30 Purified water up to
100 NaOH Adjustment of pH to 3.5
[0118] The following results were obtained.
TABLE-US-00021 ICP Citric acid etch 15 min 2% citric acid etch
(room temp) Product Reduction Ca % Reduction P Solution of Table 11
69 70
Reference Example 3
[0119] A solution consisting of the ingredients shown in the table
below was prepared:
TABLE-US-00022 TABLE (Reference solution 3) Ingredient Amount in %
(w/w) NaHF.sub.2 corr. to 0.14% F Purified water up to 100 HCl
Adjustment of pH to 3.5
[0120] The total amount of fluoride in the composition was
0.14%.
[0121] The following results were obtained.
TABLE-US-00023 ICP Citric acid etch 15 min 2% citric acid etch
(room temp) Product Reduction Ca % Reduction P Reference solution 3
47 56
Example 11
[0122] A solution consisting of the ingredients shown in table 11
was prepared:
TABLE-US-00024 TABLE 11 Ingredient Amount in % (w/w) NaHF.sub.2
corr. to 0.14% F Glycine 0.20 Purified water up to 100 HCl or NaOH
Adjustment of pH to 3.5
[0123] The following results were obtained.
TABLE-US-00025 ICP Citric acid etch 15 min 2% citric acid etch
(room temp) Product Reduction Ca % Reduction P Solution of Table 11
55 66
Example 12
[0124] A solution consisting of the ingredients shown in table 12
was prepared:
TABLE-US-00026 TABLE 12 Ingredient Amount in % (w/w) NaHF.sub.2
corr. to 0.14% F Benzoic acid 0.30 Purified water up to 100 HCl or
NaOH Adjustment of pH to 3.5
[0125] The following results were obtained.
TABLE-US-00027 ICP Citric acid etch 15 min 2% citric acid etch
(room temp) Product Reduction Ca % Reduction P Solution of Table 12
73 81
* * * * *