This invention relates to the use of ozone in he treatment of dental and oral conditions.

The great destructive disease of teeth is dental caries which may be defined as the acid dissolution of enamel, dentine or cementum as a consequence of the metabolism of micro-organisms living within deposits on the teeth known as plaque. Dental caries is believed to be associated with specific micro-organisms, the principal ones being Streptococcus Mutans, Lactobacilli, Actinomyces Visosus Serovar 2, Actinomyces Naesludii and "Intermediate" Actinomyces, other Streptococci and yeasts. These are acid producing micro-organisms which produce acids such as acetic and lactic acids from the dietary carbohydrates. The micro-organisms associated with dental caries are unique and are ecologically very different from those associated with, for example, infected root canals.

Dental caries is currently managed by one or more of the following:

(i) preventive treatment by, for example, dietary and oral hygiene measure and may include the topical application of chemotherapeutic agents;

(ii) the removal of dentine exhibiting the signs of active caries;

(iii) the protection of any newly exposed non-carious dentine with restorative material.

Measures aimed at the prevention or the arrest of dental caries are mainly based on the elimination of dental plaque from the surfaces of roots and the institution of dietary controls to reduce the frequency and quantity of readily fermentable carbohydrate ingestion. The mechanical removal of plaque has been a major platform for the prevention of dental caries for some time. However, this poses special problems in the case of primary root caries due to access problems. Because dentine has a Knoop hardness of 68 in contrast to enamel at 11, the mechanical removal of plaque from its surface inevitably results in some loss of tissue also. Toothbrush abrasion is now a very common phenomenon and invariably leads to the loss of root dentine from the facial aspects of teeth. Consequently, the traditional methods of plaque control in the prevention of dental caries create further problems even when access permits it to be used effectively.

Conventional caries removal and cavity preparation entail the use of high and low speed handpieces. However, disadvantages of this system include the perception that drilling is unpleasant for patients and local anesthetic is frequently required. Furthermore, handpieces are expensive to purchase and maintain and their use may lead to the removal of softened but uninfected dentine resulting in the excessive loss of tooth tissue.

Where restoration is required, all materials used to restore carious lesions have their limitations. For example, gold and ceramic are expensive and present a technical challenge for the practitioner. While amalgam is durable, predictable material, it has poor aesthetic qualities, is potentially toxic and may cause allergic reactions in some people.

It is an object of the invention to alleviate the disadvantages of the prior art.

It has now unexpectedly been found that ozone can penetrate carious tissue and can therefore be used in the treatment of dental caries.

According to the present invention there is provided the use of ozone in the preparation of a therapeutic system for the treatment of dental caries.

As used herein, the term "ozone" is intended to embrace pure ozone, oxonised air and ozonized aqueous media, such as water optionally containing a reductant, such as thiocyanate or peppermint.

The ozone is delivered at a pressure sufficient to penetrate the carious tissue and at a concentration and for a period of time sufficient to kill substantially all of the micro-organisms within the carious lesion.

Preferably, a needle-sized jet of pure ozone or ozonized air in a shroud of micro-organism-free aqueous medium, e.g. water optionally containing a reductant, is injected at the desired location.

If desired, a sealant of the type known in the art may be applied to a carious lesion following ozone treatment.

The advantages using ozone in the treatment of dental caries include the following:

1. It eliminates drilling and its attendant problems;

2. It is rapid and painless;

3. It does not require sophisticated methods of isolating the tooth;

4. No local anesthetic is required.

The invention is illustrated in the following Examples. Unless otherwise stated, the ozone delivered in the following Examples is present in air at a concentration of 5.2%,

EXAMPLE 1

Many studies concerning the clinical evaluation of ozone have been based on assessments of its harmful effects rather than demonstrating any therapeutic benefits it may offer. Ozone is one of nature's most powerful oxidants which accounts for its ability to kill bacteria, spores and viruses. Uniquely, ozone decomposes to a harmless, non-toxic and environmentally safe material (oxygen). In this investigation, a multicomponent evaluation of the oxidative consumption of salivary biomolecules by ozone (O.sub.3) has been performed using high resolution proton (.sup.1 H) nuclear magnetic resonance (NMR) spectroscopy. The ozone-generating equipment employed in this study was designed by Purezone Ltd. (Ipswich, U.K.). Unstimulated human saliva samples were collected from 8 patients and each of them was divided into two equivalent portions (0.60 ml). The first of these was treated with O.sub.3 generated from the above device for a period of 30 seconds; the second group of portions served as controls. Samples were subjected to .sup.1 H NMR analysis at an operating frequency of 600 MHz. Results acquired revealed that O.sub.3 treatment gave rise to (1) the oxidative decarboxylation of the salivary electron-donor pyruvate (generating acetate and CO.sub.2, as products), (2) oxidation of the volatile sulphur compound precursor methionine to its corresponding sulphoxide and (3) the oxidative consumption of salivary polyunsaturated fatty acids. Moreover, evidence for the O.sub.3 -mediated oxidation of salivary 3-D-hydroxybutyrate was also obtained. High field .sup.1 H NMR spectroscopy provides much useful analytical data regarding the fate of O.sub.3 in human saliva, information which is of much relevance to its potential therapeutic actions in vivo.

EXAMPLE 2

Ozone Effect on Microflora from Primary Root Caries Ex-vivo

Primary root carious lesions (PRCL) are a major clinical problem. The aim of this study was to establish if ozone could achieve effective microbial killing in PRCL. An ozone producing generator (Purezone Ltd., Ipswich, U.K.) was used in this ex-vivo study assessing the use of ozone on PRCL. In this study, soft PRCL requiring restoration were used as these are the most severe type of lesion found in humans. 20 freshly extracted teeth with PRCL requiring restoration were used. After plaque removal using a hand held standard fine nylon fiber sterile toothbrush with sterile water as a lubricant to cleanse the surface, each tooth was then isolated using sterile cotton wool rolls and dried using a dry sterile cotton wool roll. A sample of PRCL was taken using a sterile excavator from half of the most active part of the lesion. Subsequently, 10 seconds of the ozonized water was applied to the lesion and another sample was taken from the other half of the most active part of the lesion. Each sample was weighed and immediately placed in 1 ml of Fastidious Anaerobe Broth (FAB). To each 1 ml of FAB containing a biopsy o carious or ozone treated carious dentine, sterile glass beads were added. They were vortexed for 30 seconds to facilitate the extraction of any micro-organisms from the carious dentine and disperse any aggregates. After decimal dilution with FAB, 100 ml aliquots of these was spread on Fastidious Anaerobe Agar (LabM, Bury, Lancs., U.K.) supplemented with 5% (V/V) horse blood in an anaerobic chamber at 37.degree. C. for four days. The mean.+-.SE number of each colony type was counted and calculated.

                           Before Ozone     After 10 Seconds
                             Treatment     of Ozone Treatment
        Mean .+-. SE of    5.9 .+-. 0.15     3.57 .+-. 0.37
        Total cfu (Log.sub.10)

        Adhesive                       Control       Carious
        OptiBond FL Prime/Optibond   5.31 (1.03)   5.58 (1.05)
        FL Adhesive/OptiGuard
        Optibond FL Prime/OptiGuard  2.01 (0.59)   1.63 (0.40)
        OptiGuard                    0.73 (0.24)   1.45 (0.52)
        ChemFil II                   1.42 (0.28)   1.01 (0.26)

FIG. 8 illustrates the use of the cup shown in FIG. 7 as it may be applied to adjacent teeth.

DETAILED DESCRIPTION

With reference to FIGS. 1-4, there is shown apparatus 10 in accordance with the present invention for the treatment of dental caries which includes a source 12 of oxidizing gas, preferably ozone, and a handpiece 16 (see FIG. 2) for delivering the gas to a tooth, not shown in FIGS. 1-3. The effectiveness of an oxidizing gas such as ozone is set forth in co-pending International Patent Application PCT/EP99/04035 now U.S. Ser. No. 09/700,275 entitled "Use Of Ozone For The Preparation Of Medicaments For The Treatment of Dental Caries" by Edward Lynch. This application is incorporated herewith in its entirety including all specification and drawings by this specific reference thereto.

As illustrated in FIG. 1, the ozone source 12 includes an ozone generator 20 and an ozone pump 22 for supplying ozone through a line 24, a connector 28 and lines 30 to the handpiece 16. As used herein, the term "ozone" is intended to embrace any suitable oxidizing gas, pure ozone, ionized air and other ozone gaseous mixtures.

As noted in the referenced international patent application, ozone is delivered at a pressure, concentration and for a period of time sufficient to penetrate the carious tissue and kill substantial all of the micro-organism within a carious lesion. Specific examples of the use of ozone are set forth in the referenced patent application and are incorporated herewith by the specific reference thereto.

As shown in FIGS. 2-3, cups 3436 attached to the handpiece 16 are provided for receiving the gas and exposing a selected area 38 on a tooth 40, see FIG. 3. The cup 34 may be attached to the handpiece 16 in any conventional manner and include a resilient edge, or sidewall, 44 for sealable engaging the tooth 40 to prevent the escape of gas therepast.

Many different sized and shaped cups may be utilized, as for example shown in FIG. 3 the cup 36 includes an arcuate trunk 50 to facilitate the placement of the cup 36 over the selected area 38 as shown in FIG. 4. The cups 34, 36 may have relatively uniform perimeters 52, 54 for sealably engaging the tooth 40 between a cusp 58 and a gingiva 60 as shown in FIG. 4.

A further cup embodiment 64 is shown in cross-section in FIG. 6 includes a tapered sidewall 66 that may be used for application of oxidizing gas to a smaller selected area (not shown) on the tooth 40.

While a resilient edge or sidewall may be used to couple the cup to the selected area 38 on the tooth 40, it should be appreciated that a separate sealant 68 (See FIG. 6) may be utilized for providing a sealable engagement between the cup 64 and the tooth 40. In this instance, the sidewall 66 need not be resilient.

Another embodiment of a cup 70 is shown in cross-section in FIG. 7 which includes walls 72 which are contoured for enabling the sealable engagement with adjacent teeth 74, 76 as shown in FIG. 8. As shown in FIG. 8, a cup edge 80 has a perimeter contour 82 for providing a sealable engagement with cups 86, 88 of adjacent teeth 74, 76.

All of the cups 34, 64, 70, cross-sectionally illustrated in FIGS. 5-7. include cup chambers 92, 94, 96 that subtend cup edges 98, 100, 102. As shown each of the cups 34, 64, 70 include walls 44, 66, 72 that define the chambers 92, 94, 96 and include first perimeters 106, 108, 110 for sealably coupling the walls 44,66, 72 to the handpiece 16. Second perimeters 112, 114, 116 provide for coupling the walls 44,6672 to the tooth 40 and exposing the selected areas 38 to gas circulated in the chambers 92, 94, 96.

As shown in FIG. 6, the embodiment 64 the first perimeter 108 may be larger than the second perimeter 115 or, as shown in FIG. 7, the first perimeter 110 may be smaller than the second perimeter 116. Accordingly this variation in cup 64, 70 design enables the application of oxidizing gas the any number of tooth contours and to the application of oxidizing gas to a plurality of teeth has hereinabove described.

With reference again to FIG. 1, the apparatus 12 includes an aspiration pump 120 and lines 30, 122, 124 connected to the handpiece 16 for enabling circulation of the ozone into and out of the cup chambers 92, 94, 96.

A controller 126, which may be of any conventional circuit design, is provided for regulating the ozone and aspiration pumps 22, 120 in order to circulate the gas into and out of the cup chambers 92, 94, 96 at a pressure insufficient to permit escape of the gas past a sealed engagement between the cups 34, 64, 70 and teeth 40, 86, 88. Control of the gas flows may also be effected through valves 127, 127 regulated by the controller 126.

Additionally, the apparatus 10 may include a reductant source 128, which is in fluid communication with the cup chambers 92, 94, 96 through lines 30, 130 and a parastalic pump 131. The reductant, which may be a solution of thiocyanate or peppermint, is utilized to flush the cup chambers 92, 94, 96 of oxidizing gas. The oxidizing gas is flushed into the aspiration line 122 following ozone treatment of the tooth 40, 86, 88. The reductant is then aspirated through line 122 and into a waste accumulator 132.

Any residual ozone is then aspirated from the accumulator 132 through the line 124 and into a canister 134 through line 136 for final elimination of the ozone. Thus, the apparatus 12 provides for a totally closed system for the application and removal of ozone to and from teeth 40, 86, 88.

It should also be appreciate that when the cups 34, 36, 64 are utilized between teeth 40, 138 (not shown in FIG. 4) a separate dam 140 maybe utilized as necessary to enable the cups 34, 36, 64 (not shown in FIG. 4) to sealably enclose a selected area for treatment between the teeth 40, 138.

EXAMPLE 1

Ozone Detection (ppm) Around the Cup Using a Ozone Analyzer After Either 10 or 20 s of Ozone Application in vivo

Study or Test: Ozone Detection (ppm) Around the Cup 34 Using a Ozone Analyzer After Either 10 or 20 s of Ozone Application in vivo

Purpose: To assess the maximum ozone detectable level (ppm) around the cup 34 after either 10 s or 20 s of ozone application in vivo.

Study or Test Protocol: 20 primary root carious lesions (PRCLs) were randomly selected when the cross-sectional study was conducted. The tip of the sensor was always held within 2 mm of the edge of the cup, positioned half way between the mesial and occlusal sides of the cup. The maximum ozone detectable level (ppm) around the cup from the extracted teeth using an ozone analyzer after 10 s of ozone application. The ozone analyzer used was an API 450 model available from ENVIRO Technologies, UK, and was calibrated by the supplier within the previous week of delivery and this device was not used for any other purpose other than this study in the interim.

Overlying plaque was then removed using a hand held standard fine nylon fiber sterile toothbrush with water as a lubricant. Each tooth was dried using dry sterile cotton wool rolls and a dental 3 in 1-air syringe. The excavator blade was used to traverse the lesion in line with long axis of the tooth across the maximum gingival/occlusal dimension. Half of each lesion was removed using a sterile excavator. Subsequently, the remaining lesion was exposed to the ozone gas for a period of either 10 s or 20 s at room temperature (23.degree. C.) and maximum detectable ozone level was also measured using this ozone analyzer.

Test Results

The maximum ozone detectable level (ppm) around the cup from lesions for a period of either 10 s (Table 1 and FIG. 1) or 20 s (Table 2 and FIG. 2) ozone application during the treatment of root carious lesions were as follows:

                             TABLE 1
            Maximum ozone detectable level (ppm) after a 10 s of
                             ozone application
                                            Ozone detection
            Teeth types           Sites          (10 s)
         Upper left incisor      Mesial            0.066
      Upper right 1. premolar    Buccal            0.001
         Upper right canine      Distal            0.002
        Upper right 1. molar     Buccal            0.006
       Upper left 2. premolar    Buccal            0.076
      Lower right 2. premolar    Mesial            0.058
       Lower left 1. premolar    Buccal            0.169
         Lower left lateral      Buccal            0.106
        Upper right lateral      Distal            0.001
         Lower left canine       Labial            0.147


                         TABLE 2
            Maximum ozone detectable level (ppm) after a 20 s of
                          ozone application
                                            Ozone detection
            Teeth types           Sites          (20 s)
               Lower left lateral Labial            0.137
       Lower left 1. premolar    Buccal            0.177
        Lower right incisor      Labial            0.069
         Upper right canine      Labial            0.033
        Upper right lateral      Labial            0.079
       Lower left 2. premolar    Buccal            0.002
        Lower right 1. molar     Buccal            0.083
         Upper left lateral      Labial            0.004
         Lower left canine       Labial            0.056
       Upper left 1. premolar    Mesial            0.001

                             TABLE 3
                         Maximum ozone detectable level (ppm)
           Teeth types          Sites      Ozone detection
          Upper incisor        Mesial             0.005
      Upper lateral incisor    Labial             0.004
           Upper canine        Labial             0.003
        Upper 1. premolar      Mesial             0.006
        Upper 2. premolar      Distal             0.002
          Upper 1. molar       Buccal             0.003
          Upper 2. molar       Mesial             0
          Lower incisor        Lingual            0.007
      Lower lateral incisor    Distal             0.001
           Lower canine        Mesial             0
        Lower 1. premolar      Distal             0.009
        Lower 2. premolar      Lingual            0.018
          Lower 1. molar       Lingual            0.016
          Lower 2. molar       Mesial             0.005

    Duration  Reading 1 Reading 2 Reading 3 Reading 4 Reading 5 Reading 6
     Average
    (seconds) (g/Nm.sup.3) (g/Nm.sup.3) (g/Nm.sup.3) (g/Nm.sup.3) (g/Nm.sup.3)
     (g/Nm.sup.3) (g/Nm.sup.3)
        5         5.4       5.3       5.4       4.3       5.2       5.2
     5.1
       10         4.7       4.8       4.6       3.5       4.4       4.5
     4.4
       20         4.9       5.9       6.3       6.3
     5.9
       30         6.3       6.5       6.3       6.6
     6.4
       60         6.6       7.0       7.0       6.7
     6.8

    Duration  Reading 1 Reading 2 Reading 3 Reading 4 Reading 5 Reading 6
     Average
    (seconds)   (ppm)     (ppm)     (ppm)     (ppm)     (ppm)     (ppm)
     (ppm)
        5       2522      2475      2522      2008      2428      2428     2397
       10       2195      2242      2148      1635      2055      2102     2063
       20       2288      2755      2942      2942                         2732
       30       2942      3036      2942      3082                         3000
       60       3082      3269      3269      3129                         3187

              .lambda..sub.max  .lambda..sub.max  .lambda..sub.max
     .lambda..sub.max
    Duration   (351 nm)    (351 nm)    (351 nm)   (351 nm) average
    (seconds) absorbance  absorbance  absorbance    absorbance
        1          0.06        0.08        0.11          0.08
        2          0.50        0.44        0.26          0.40
        3          0.70        0.56        0.42          0.56
        4          0.77        0.69        0.50          0.65
        5          0.90        0.84        0.51          0.75
        6          1.08        0.99        0.68          0.92
        7          1.17        1.11        0.75          1.01
        8          1.30        1.27        0.95          1.17
        9          1.40        1.40        1.19          1.33
       10          1.57        1.43        1.38          1.46

                                            Total           Volume of   Ozone
              .lambda..sub.max                dissolved         air/ozone  in
     air    Ozone
    Duration   absorbance   Concentration   ozone    Ozone   mixture  (.mu.g/ml
     = in air
    (seconds) (average of 3)  (.mu.mol/l)  (.mu.mol) (.mu.g)   (ml)
     g/m.sup.3)  (ppm)
        1           0.08          2.69        0.269   13        8         1.625
       759
        2           0.40         13.47        1.347   65       16         4.063
      1897
        3           0.50         18.86        1.886   91       24         3.792
      1771
        4           0.65         21.89        2.189   105      32         3.281
      1532
        5           0.75         25.25        2.525   121      40         3.025
      1413
        6           0.92         30.98        3.098   149      48         3.104
      1450
        7           1.01         34.39        3.439   165      56         2.946
      1376
        8           1.17         39.39        3.939   189      64         2.953
      1379
        9           1.33         44.79        4.479   215      72         2.986
      1394
       10           1.46         49.16        4.916   236      80         2.950
      1378

            Iodine Concentration       Absorbance at 351 nm
                  4 .mu.M                   0.1144
                  5 .mu.M                   0.1410
                  7 .mu.M                   0.1690
                 10 .mu.M                   0.2002