Remineralisation of calcified tissue

Abstract

A cosmetic and/or therapeutic treatment of tissue, such as tooth, is disclosed that effects, for instance, whitening and tissue re-building through mineralization. Further, a method of performing iontophoresis utilizing an aqueous composition of a remineralizing agent to achieve mineralization is disclosed, as well as a kit for performing the mineralization or remineralization.

Claims

1. A method of remineralising enamel comprising: pre-conditioning the enamel to remove protein and/or lipids; applying a remineralising agent including a first component and a second component whilst separately, sequentially or simultaneously applying iontophoresis with a first electrode having a first polarity and a second electrode having a second polarity, or applying iontophoresis with the first electrode having the first polarity for a predetermined period of time and subsequently reversing the first polarity to the second polarity; driving the first component of the remineralising agent into the enamel with the first polarity and driving the second component of the remineralising agent into the enamel with the second polarity; and, depositing the remineralising agent within the enamel, wherein the first component is a source of calcium ions and the second component is a source of phosphate ions, wherein the remineralising agent is selected from the group consisting of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), casein phosphopeptide-amorphous calcium fluoride phosphate (CPP-ACFP), fluoroapatite, monetite, brushite, amorphous calcium phosphate, hydroxyapatite, calcium-deficient hydroxyapatite, and hilgenstockite, or a mixture thereof, and wherein the first polarity is positive and the second polarity is negative or the first polarity is negative and the second polarity is positive.

2. The method according to claim 1, further comprising: remineralisation of a hypo-mineralised or a de-mineralised tooth.

3. The method according to claim 2, further comprising: performing a cosmetic treatment of the tooth.

4. The method according to claim 3, further comprising: performing tooth lightening or whitening.

5. The method according to claim 1, further comprising: performing a preventive treatment of tooth erosion.

6. The method according to claim 1, wherein the remineralising agent comprises casein phosphopeptide-amorphous calcium phosphate (CPP-ACP).

7. The method according to claim 1, wherein the remineralising agent is a fluoride-containing remineralising agent.

8. The method according to claim 7, wherein the fluoride-containing agent is casein phosphopeptide-amorphous calcium fluoride phosphate (CPP-ACFP).

9. The method according to claim 1, wherein the remineralising agent includes one or more remineralisation enhancers.

10. The method according to claim 9, wherein the remineralisation enhancer is strontium.

11. The method according to claim 1, wherein the pre-conditioning comprises treatment with an acid.

12. The method according to claim 11, wherein the acid is phosphoric acid.

13. The method according to claim 1, wherein the pre-conditioning comprises treatment with a hypochlorite.

14. The method according to claim 1, wherein the method further comprises the treatment or alleviation of dental caries and/or dental fluorosis in a mammal.

15. The method according to claim 1, wherein the method further comprises the remineralising of hypo-mineralised or de-mineralised (carious) dentine.

16. The method according to claim 1, wherein a counterelectrode is provided within a mouth of a mammal.

17. The method according to claim 16, further comprising: remineralising a lesion of the tooth.

18. The method according to claim 1, further comprising: driving at least one of the first component or the second component of the remineralising agent into the tissue by applying iontophoresis at a constant voltage or a constant current.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The invention will now be described by way of examples only and with reference to the accompanying figures:

(2) FIG. 1 is a graph showing the effect of pre-conditioning on iontophoretic treatment of a tooth. This figure shows current-time responses of a tooth obtained using a saline pad to complete the circuit between the working and reference of the counter-electrodes;

(3) FIG. 2 shows a comparison of two lesions in one tooth before and after treatment using CPP-ACP as the remineralising agent; and

(4) FIG. 3 shows (a) an incisor tooth before any treatment, (b) after pre-conditioning and (c) after the iontophoresis-remineralising method has been applied.

EXAMPLES

Example 1

(5) In this experiment the current-time responses of an extracted tooth after the application of 1 V at the working electrode were recorded. One electrode the shorted reference/counter electrode) was a 0.5 mm stainless steel wire inserted into the tooth root. The other electrode (the working electrode) was a Pt sheet electrode of area ca 0.25 cm.sup.2 held in contact with a saline-soaked tissue pad, which in turn was held in contact with the tooth surface close to the enamel lesion.

(6) FIG. 1 shows the saline response (upper dotted line) measured after the tooth was previously held in contact with a hypochlorite-soaked pad for 3 mins. The initial current after this topical hypochlorite pre-treatment was 18 A, over 20% higher than that of the tooth before pre treatment, and the extended-time current was similar. The lower, solid trace shows the saline tooth response for the same tooth measured after being held in contact with a hypochlorite pad under electrically-assisted (EA) pre-treatment for 3 mins at 1 V applied at the working electrode. The initial current is similar, but the extended-time current is over five times larger (i.e. the current is more negative, being lower down the negative current scale) after EA hypochlorite pre-treatment.

Example 2

(7) FIG. 2 shows a comparison of two lesions in one tooth before and after treatment using CPP-ACP (Tooth Mousse) as the remineralising agent. Analysis of the mean mineral density of the lesions resulted in Demineralisation Parameters of 0.76 (left side) and 0.83 (right side) prior to treatment and 0.92 (left) and 0.83 (right) after treatment. This Demineralisation Parameter was derived by as comparison of average grey-scale levels within the Micro-CT image of: a) the lesion and b) the healthy tissue.

(8) This in vitro demonstration indicates that, applying a current at a level safe and not perceived by patients at a fixed voltage to a pre-conditioned natural caries lesion, in combination with CPP-ACP in the form of Tooth Mousse resulted in significant (approximately 67%) remineralisation of the lesion (as measured by Image Analysis of Micro-CT images of the tooth before and after treatment) after 3 hours electrophoresis/iontophoresis application. The passive application of the agent Tooth Mousse-Plus (also known as MI paste) to the other natural caries lesion on the same tooth for 3 hours resulted in minimal remineralisation (measured on Micro-CT images).

(9) The comparison in FIG. 2 is of two lesions in one tooth before and after treatment.

(10) The images represent an approximately 10 micron thickness horizontal Micro-CT

(11) (XCT slice) through the same path of the tooth with separate mesial and distal lesions. The XCT image on the left shows the lesions prior to any treatment. The image on the right shows the lesions after the lesions were pre-treated to remove protein and lipids. The lesion on the left was treated with CPP-ACP and iontophoresis for three hours, whilst the lesion on the right was treated only with CPP-ACP plus Fluoride

(12) (MI paste) for three hours.

Example 3

(13) FIG. 3 shows an incisor tooth before any treatment, after pre-conditioning and after the iontophoresis-remineralising method has been applied.

(14) The uppermost image shows an extracted incisor tooth which exhibits both a large carious cavity (caused by tooth decay), which is significantly discoloured, and areas of dark discolouration on the labial (flat) facing surface of the crown of the tooth, adjacent to the canons cavity in the direction of the incisal (lower) edge of the tooth. This image was taken prior to any treatment being carried out.

(15) The middle image shows the same tooth after 2 minutes of pre-conditioning with sodium hypochlorite solution. There is very little difference between the uppermost and middle images in terms of tooth discolouration.

(16) The lowermost image shows the tooth after the iontophoresis-remineralisation has been carried out using Tooth Mousse (CPP-ACP) as the re-mineralising agent for 1 hour. It is clear that the cavity has now lost its dark discolouration completely. The dark discolourations in the enamel of the crown of the tooth adjacent to the cavity have also disappeared. There is some increased whitening of the edges of the carious cavity at both the upper and lower margins of the cavity.

(17) These images demonstrate the tooth-whitening effect of the iontophoresis-remineralising method.