CA2752469A1 - Optical apparatus and methods - Google Patents
Optical apparatus and methods Download PDFInfo
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- CA2752469A1 CA2752469A1 CA2752469A CA2752469A CA2752469A1 CA 2752469 A1 CA2752469 A1 CA 2752469A1 CA 2752469 A CA2752469 A CA 2752469A CA 2752469 A CA2752469 A CA 2752469A CA 2752469 A1 CA2752469 A1 CA 2752469A1
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- photosensitiser
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/0613—Apparatus adapted for a specific treatment
- A61N5/0624—Apparatus adapted for a specific treatment for eliminating microbes, germs, bacteria on or in the body
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/0601—Apparatus for use inside the body
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N5/0613—Apparatus adapted for a specific treatment
- A61N5/062—Photodynamic therapy, i.e. excitation of an agent
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61C—DENTISTRY; APPARATUS OR METHODS FOR ORAL OR DENTAL HYGIENE
- A61C1/00—Dental machines for boring or cutting ; General features of dental machines or apparatus, e.g. hand-piece design
- A61C1/08—Machine parts specially adapted for dentistry
- A61C1/088—Illuminating devices or attachments
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- 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N5/00—Radiation therapy
- A61N5/06—Radiation therapy using light
- A61N2005/065—Light sources therefor
- A61N2005/0651—Diodes
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- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Life Sciences & Earth Sciences (AREA)
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- Radiology & Medical Imaging (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Biophysics (AREA)
- Dental Tools And Instruments Or Auxiliary Dental Instruments (AREA)
Abstract
The present invention relates to optical apparatus. In particular it relates to optical apparatus having utility in medical procedures, more particularly dental procedures and especially disinfection procedures. In particular, we describe an optical apparatus comprising a handpiece (10) housing a light emitting diode light source (21) and a light delivery system comprising a light guide (14) having a proximal end mountable to the light delivery system to receive light from the light source (21) and a distal end (15) from which light is emitted from the apparatus. Preferably, the light- emitting diode light source (21) is a single light-emitting diode and preferably the handpiece comprises cooling means (23, 24, 25) adapted to cool the light- emitting diode light-source (21).
Description
OPTICAL APPARATUS AND METHODS
The present invention relates to optical apparatus and methods. In particular it relates to optical apparatus having utility in medical procedures, more particularly dental procedures and especially disinfection procedures and to reduce the need for or extent of surgery and to promote healing.
In our earlier applications, WO00/62701 and WO00/74587 we describe apparatus for use in disinfection of dental cavities, including root canals. The apparatus described includes a source of laser light and a light guide for directing the laser light to the treatment site.
We described light guides terminating in a tip adapted to be inserted into a tooth and to spread light either substantially uniformly around a carious lesion or to spread light along and around a root canal. We developed this further in W02004/103471 in which we described an apparatus adapted to disinfect by external illumination of the tooth area. The apparatus described comprises a pair of light guides to direct light generated from a light emitting diode onto opposite sides of a tooth.
However, although these prior developments provide reliable and reproducible bacterial kills, the apparatus is not suitable for broad spectrum photodynamic procedures other than for small area or small volume disinfections. The present invention seeks to overcome that deficiency.
In its broadest sense, the present invention provides an optical apparatus comprising a handpiece housing a light emitting diode light source and a light delivery system comprising a demountable light guide having a proximal end mountable to the light delivery system to receive light from the light source and a distal end from which light is emitted from the apparatus.
Preferably, the light-emitting diode light source is a single light-emitting diode. Alternatively, the light source is an array or a multiplexed array of light-emitting diodes.
Advantageously, the light-emitting diode light source emits light having a wavelength in the region of 600-700nm, more advantageously 610-650nm or 670-680nm.
Preferably, the handpiece comprises cooling means adapted to reduce transmission of heat to the light guide. Typically, the handpiece cooling means is adapted to cool the light-emitting diode light-source.
In one embodiment, the handpiece cooling means comprises a heat pipe.
Preferably, the handpiece cooling means further comprises a heatsink.
Suitably, the optical apparatus further comprises a control console in communication with the handpiece. Suitably, the control console includes heat dissipation means in communication with the handpiece cooling means. Conveniently, the cooling means comprises water as a coolant.
Preferably, the light guide comprises an optical fibre.
In one embodiment, the light guide is of substantially uniform cross-section from a proximal end to a distal end. In an alternative embodiment, the light guide is shaped to taper between the proximal and distal ends. Said tapering may be substantially uniform along the length of the light guide or may be substantially in a distal portion of the light guide alone.
Advantageously, the distal portion of the light guide is shaped to suit the intended purpose of the apparatus. In certain embodiments, the distal portion has a rounded, cylindrical or tapered form. In alternative embodiments, the distal portion has a chisel or wedge form.
Preferably, the apparatus comprises a range of light guides each guide being adapted for a particular use.
Optionally, the light guide further includes a demountable reduction tip to reduce the area of the distal portion or an expansion tip spread light across an increased area or around an increased volume.
Preferably, the light delivery system comprises a reflector cone adjacent the light-source.
In a further aspect, the present invention provides a photodynamic therapy (PDT) apparatus comprising an optical apparatus as described above. Preferably, the PDT apparatus further comprises a photosensitiser.
Preferably, the photosensitiser is selected as having an uptake response appropriate to the target.
Suitably, the photosensitiser is capable of absorbing light towards the red end of the visible spectrum or at longer wavelengths.
The apparatus is suitable for use in PDT in disinfection and sterilisation techniques against bacteria, fungi and viruses.
Suitably, the photosensitiser is selected from dyes and other photosensitising compounds including azure blue cert, azure B chloride, azure 2, azure A chloride, azure B
tetrafluoroborate, thionin, azure A
eosinate, azure B eosinate, azure mix sicc, azure II eosinate, arianor steel blue, toluidine blue 0, tryptan blue, crystal violet, methylene blue, porphyrins, including haematoporphyrin HCl and haematoporphyrin ester and the porphyrins developed by Destiny Pharma Limited as their XF drugs, phthalocyanines, including aluminium disulphonated phthalocyanine, phenothiazines and chlorines;
conjugates, particularly conjugates of these materials, such as nanoparticle tiopronin gold nanoparticulate conjugates, or metabolic precursors of any of these materials.
One such metabolic precursor is 5-amino-levulinic acid (ALA) which is metabolised by eukaryotic cells to protoporphyrin IX, a very active endogenous sensitiser.
The present invention relates to optical apparatus and methods. In particular it relates to optical apparatus having utility in medical procedures, more particularly dental procedures and especially disinfection procedures and to reduce the need for or extent of surgery and to promote healing.
In our earlier applications, WO00/62701 and WO00/74587 we describe apparatus for use in disinfection of dental cavities, including root canals. The apparatus described includes a source of laser light and a light guide for directing the laser light to the treatment site.
We described light guides terminating in a tip adapted to be inserted into a tooth and to spread light either substantially uniformly around a carious lesion or to spread light along and around a root canal. We developed this further in W02004/103471 in which we described an apparatus adapted to disinfect by external illumination of the tooth area. The apparatus described comprises a pair of light guides to direct light generated from a light emitting diode onto opposite sides of a tooth.
However, although these prior developments provide reliable and reproducible bacterial kills, the apparatus is not suitable for broad spectrum photodynamic procedures other than for small area or small volume disinfections. The present invention seeks to overcome that deficiency.
In its broadest sense, the present invention provides an optical apparatus comprising a handpiece housing a light emitting diode light source and a light delivery system comprising a demountable light guide having a proximal end mountable to the light delivery system to receive light from the light source and a distal end from which light is emitted from the apparatus.
Preferably, the light-emitting diode light source is a single light-emitting diode. Alternatively, the light source is an array or a multiplexed array of light-emitting diodes.
Advantageously, the light-emitting diode light source emits light having a wavelength in the region of 600-700nm, more advantageously 610-650nm or 670-680nm.
Preferably, the handpiece comprises cooling means adapted to reduce transmission of heat to the light guide. Typically, the handpiece cooling means is adapted to cool the light-emitting diode light-source.
In one embodiment, the handpiece cooling means comprises a heat pipe.
Preferably, the handpiece cooling means further comprises a heatsink.
Suitably, the optical apparatus further comprises a control console in communication with the handpiece. Suitably, the control console includes heat dissipation means in communication with the handpiece cooling means. Conveniently, the cooling means comprises water as a coolant.
Preferably, the light guide comprises an optical fibre.
In one embodiment, the light guide is of substantially uniform cross-section from a proximal end to a distal end. In an alternative embodiment, the light guide is shaped to taper between the proximal and distal ends. Said tapering may be substantially uniform along the length of the light guide or may be substantially in a distal portion of the light guide alone.
Advantageously, the distal portion of the light guide is shaped to suit the intended purpose of the apparatus. In certain embodiments, the distal portion has a rounded, cylindrical or tapered form. In alternative embodiments, the distal portion has a chisel or wedge form.
Preferably, the apparatus comprises a range of light guides each guide being adapted for a particular use.
Optionally, the light guide further includes a demountable reduction tip to reduce the area of the distal portion or an expansion tip spread light across an increased area or around an increased volume.
Preferably, the light delivery system comprises a reflector cone adjacent the light-source.
In a further aspect, the present invention provides a photodynamic therapy (PDT) apparatus comprising an optical apparatus as described above. Preferably, the PDT apparatus further comprises a photosensitiser.
Preferably, the photosensitiser is selected as having an uptake response appropriate to the target.
Suitably, the photosensitiser is capable of absorbing light towards the red end of the visible spectrum or at longer wavelengths.
The apparatus is suitable for use in PDT in disinfection and sterilisation techniques against bacteria, fungi and viruses.
Suitably, the photosensitiser is selected from dyes and other photosensitising compounds including azure blue cert, azure B chloride, azure 2, azure A chloride, azure B
tetrafluoroborate, thionin, azure A
eosinate, azure B eosinate, azure mix sicc, azure II eosinate, arianor steel blue, toluidine blue 0, tryptan blue, crystal violet, methylene blue, porphyrins, including haematoporphyrin HCl and haematoporphyrin ester and the porphyrins developed by Destiny Pharma Limited as their XF drugs, phthalocyanines, including aluminium disulphonated phthalocyanine, phenothiazines and chlorines;
conjugates, particularly conjugates of these materials, such as nanoparticle tiopronin gold nanoparticulate conjugates, or metabolic precursors of any of these materials.
One such metabolic precursor is 5-amino-levulinic acid (ALA) which is metabolised by eukaryotic cells to protoporphyrin IX, a very active endogenous sensitiser.
Preferably, the photosensitising composition comprises at least one photosensitiser selected from toluidine blue 0, methylene blue, dimethylene blue or azure blue chloride.
More preferably the photosensitiser is toluidine blue O. Most preferably, the sensitiser is toluidine blue 0 in the form of `tolonium chloride', being the pharmaceutical grade of TBO wherein the purity and isometric ratios are maintained.
Advantageously, the photosensitiser is in a form adapted for the treatment site and is adapted to an appropriate method of delivery to maximise contact with the target species in the shortest possible time.
Suitably, the photosensitiser is in the form of a liquid, suitably a sprayable liquid, gel or paste, typically aqueous, or a varnish. A gel may be formed by including a gelling agent in an aqueous solution of the photosensitiser. Suitable gelling agents include hydrophilic polymers such as cellulose derivatives and polyvinyl pyrrolidone. Suitably, the gelling or thickening agent is hydroxypropyl methyl cellulose, typically in an amount of up to about 5% by weight. Alternatively, thickening agents such as colloidal silica (Cab-O-Sil) may be added, typically in amounts of up to 10% by weight.
The concentration of photosensitiser and the power of light source are selected to provide maximum tissue penetration and kill rates and will be dependent upon the treatment.
Suitably, the dye concentration is from 0.00001% to 2%, preferably from 0.00001% to 0.5% w/v, more preferably from 0.001 % to 0.1 % w/v.
Alternatively, the photosensitiser is supplied as a concentrate for application to the treatment site with dilution in situ to the desired concentration, for example, by addition of solvent or by dilution by tissue fluid, such as saliva.
In particular, the present invention provides apparatus for use against Gram positive and Gram negative bacteria, including strains of Peptostreptococcus, Streptococcus, Staphylococcus, Actinomyces, Bifidbacterium, Coorynebacterium, Eubacterium Lactobacillus, Propioibacterium, Pseudoramibacter, Nieserria, Veillonella, Actinobacilus, Campylobacter, Cantonella, Centipeda, Desulphovibrio, Enterococcus, Escheria, Fusobacterium, Haemophilus, Porphoromonas, Prevotella, Selenomonas, and Treponema; in particular bacteria selected from Staphylococcus aureus, Staphylococcus epidermidis;
Staphylococcus hominis, Staphylococcus haemolyticus, Staphylococcus pyogenes, Pseudomonas aeruginosa, Propioibacterium aches, Porphyromonas gingivalis, streptococcus intermedius and Streptococcus mutans; and against spore-forming bacteria such as Bacillus, Clostridium, Sporohalobacter, Anaerobacter and Heliobacterium.
The present invention also provides apparatus for use against a range of fungal and viral species including Candida species and dermatophytes which may be found on the skin or nail beds and fungal species associated with lesions in the mouth.
More preferably the photosensitiser is toluidine blue O. Most preferably, the sensitiser is toluidine blue 0 in the form of `tolonium chloride', being the pharmaceutical grade of TBO wherein the purity and isometric ratios are maintained.
Advantageously, the photosensitiser is in a form adapted for the treatment site and is adapted to an appropriate method of delivery to maximise contact with the target species in the shortest possible time.
Suitably, the photosensitiser is in the form of a liquid, suitably a sprayable liquid, gel or paste, typically aqueous, or a varnish. A gel may be formed by including a gelling agent in an aqueous solution of the photosensitiser. Suitable gelling agents include hydrophilic polymers such as cellulose derivatives and polyvinyl pyrrolidone. Suitably, the gelling or thickening agent is hydroxypropyl methyl cellulose, typically in an amount of up to about 5% by weight. Alternatively, thickening agents such as colloidal silica (Cab-O-Sil) may be added, typically in amounts of up to 10% by weight.
The concentration of photosensitiser and the power of light source are selected to provide maximum tissue penetration and kill rates and will be dependent upon the treatment.
Suitably, the dye concentration is from 0.00001% to 2%, preferably from 0.00001% to 0.5% w/v, more preferably from 0.001 % to 0.1 % w/v.
Alternatively, the photosensitiser is supplied as a concentrate for application to the treatment site with dilution in situ to the desired concentration, for example, by addition of solvent or by dilution by tissue fluid, such as saliva.
In particular, the present invention provides apparatus for use against Gram positive and Gram negative bacteria, including strains of Peptostreptococcus, Streptococcus, Staphylococcus, Actinomyces, Bifidbacterium, Coorynebacterium, Eubacterium Lactobacillus, Propioibacterium, Pseudoramibacter, Nieserria, Veillonella, Actinobacilus, Campylobacter, Cantonella, Centipeda, Desulphovibrio, Enterococcus, Escheria, Fusobacterium, Haemophilus, Porphoromonas, Prevotella, Selenomonas, and Treponema; in particular bacteria selected from Staphylococcus aureus, Staphylococcus epidermidis;
Staphylococcus hominis, Staphylococcus haemolyticus, Staphylococcus pyogenes, Pseudomonas aeruginosa, Propioibacterium aches, Porphyromonas gingivalis, streptococcus intermedius and Streptococcus mutans; and against spore-forming bacteria such as Bacillus, Clostridium, Sporohalobacter, Anaerobacter and Heliobacterium.
The present invention also provides apparatus for use against a range of fungal and viral species including Candida species and dermatophytes which may be found on the skin or nail beds and fungal species associated with lesions in the mouth.
The present invention also provides the treatment of bacterial, viral and fungal species using apparatus and photosensitisers as described above.
The above and other aspects of the present invention will now be described, by way of example only, with reference to the accompanying figures, in which:
Figure 1 is a perspective view of a handpiece and light delivery system of a first embodiment of an optical apparatus in accordance with the present invention;
Figure 2 is plan view of the apparatus to Figure 1 with light guide element detached;
Figure 3 is a side view of the apparatus to Figure 1 with light guide element detached;
Figure 4 is a cross-sectional view of a supplementary tip for attachment to the light guide element of the system of Figure 1;
Figure 5 is a longitudinal cross-section of the apparatus of Figure 1;
Figure 6 is a detailed part view of the cross-section of Figure 5;
Figure 7 is a longitudinal cross-section of a handpiece and light delivery system of a second embodiment of an optical apparatus in accordance with the present invention;
Figure 8 is a detailed part view of the cross-section of Figure 7;
Figure 9 is a side view of a third embodiment of a handpiece of an optical apparatus in accordance with the present invention;
Figure 10 is a longitudinal cross-sectional view of the handpiece of Figure 9;
Figure 11 is a perspective view of the handpiece of Figure 9 with outer sleeve removed; and Figure 12 is a plot showing light transmission through dentine.
Figure 1 shows a handpiece 10 coupled to a light delivery system 11. Handpiece 10 includes an umbilical cord 12 coupled to a control console, not shown. Light delivery system 11 includes a mounting base 13 for operative connection to handpiece 10 and a light guide element 14 for delivery of light to a chosen application site from a distal tip 15 of light guide element 14.
As indicated in Figures 2 and 3, the light guide element 14 is demountable from the body of handpiece 10. This enables alternative light guide elements having different lengths and different light focussing or dispersal characteristics to be used, having regard to the desired procedure.
The above and other aspects of the present invention will now be described, by way of example only, with reference to the accompanying figures, in which:
Figure 1 is a perspective view of a handpiece and light delivery system of a first embodiment of an optical apparatus in accordance with the present invention;
Figure 2 is plan view of the apparatus to Figure 1 with light guide element detached;
Figure 3 is a side view of the apparatus to Figure 1 with light guide element detached;
Figure 4 is a cross-sectional view of a supplementary tip for attachment to the light guide element of the system of Figure 1;
Figure 5 is a longitudinal cross-section of the apparatus of Figure 1;
Figure 6 is a detailed part view of the cross-section of Figure 5;
Figure 7 is a longitudinal cross-section of a handpiece and light delivery system of a second embodiment of an optical apparatus in accordance with the present invention;
Figure 8 is a detailed part view of the cross-section of Figure 7;
Figure 9 is a side view of a third embodiment of a handpiece of an optical apparatus in accordance with the present invention;
Figure 10 is a longitudinal cross-sectional view of the handpiece of Figure 9;
Figure 11 is a perspective view of the handpiece of Figure 9 with outer sleeve removed; and Figure 12 is a plot showing light transmission through dentine.
Figure 1 shows a handpiece 10 coupled to a light delivery system 11. Handpiece 10 includes an umbilical cord 12 coupled to a control console, not shown. Light delivery system 11 includes a mounting base 13 for operative connection to handpiece 10 and a light guide element 14 for delivery of light to a chosen application site from a distal tip 15 of light guide element 14.
As indicated in Figures 2 and 3, the light guide element 14 is demountable from the body of handpiece 10. This enables alternative light guide elements having different lengths and different light focussing or dispersal characteristics to be used, having regard to the desired procedure.
5 For example, a typical application may use a light guide element 14 having a distal tip 15 with a diameter in the region of 7mm to 9mm. Where a greater area is required to be treated, tip diameters of the order of 13mm or more may be more advantageous. Where access to the delivery site may be difficult, tip sizes of the order of 3mm have been found to be successful.
Additionally, light guide elements 14 are adapted to provide a range of different light dispersal characteristics. For example, the element can be designed such that light emission is substantially unidirectional or collimated from tip 15 or such that the light is substantially unidirectional but with a degree of off-axis light emission from the tip. Alternatively, the light guide element 14 can be adapted to `leak' light outwardly along a portion, optionally a substantial part of its length, optionally its entire length.
Furthermore, the demountability of the light guide element 14 allows light guide elements to be provided in a range of lengths to suit a range of procedures. For example, light guide elements in the range of 5-7 cm are suitable for intra-oral use, with longer light guide elements being more useful for orthopaedic procedures. Additionally, the light guide element can be changed during a procedure as the light requirements change during the procedure as the surface area of the treatment site changes in size.
The light guide element 14 itself may be manufactured according to any conventional process.
Typically, the light guide element is manufactured from a glass optical fibre.
The light guide element may be rigid or flexible as required in order to deliver light to the target site.
The light guide element 14 may also be shaped to suit the requirements of the procedure. In the embodiments shown, the light guide element is curved towards its distal end.
Straight elements (not shown) will be equally suitable in certain procedures. The light guide element 14 may be of substantially uniform diameter along its length or may taper towards a narrower diameter at its distal end.
In certain embodiments, depending upon application, the light guide element 14 may include a supplementary tip or piece to reduce the distal diameter yet further or a supplementary tip or piece to spread the light across an increased area or volume of the treatment site. An example of such a supplementary tip is shown in cross-section in Figure 4. The tip 17 comprises a cap 18 and a probe 19.
Cap 18 is adapted for operative coupling to distal tip 15 of light guide element 14. In the embodiment shown, an internal female thread engages a corresponding male thread formed on distal tip 15 or simply bites into a resilient surface formed around radially around the outside of distal tip 15.
Alternative arrangements are equally suitable, including simple frictional retention of supplementary tip 17 on light guide element 14. Probe 19 directs light to the target site and is adapted accordingly. In the embodiment shown, the tip 17 is intended for insertion into a dental root canal and so is elongate and tapering.
The construction of the handpiece is shown in more detail in Figures 5 and 6, in which the umbilical cord is omitted for clarity. The light guide element 14 is mounted at its proximal end within a light guide element clip 16 adapted to be received and retained by a corresponding engagement arrangement at a distal end of handpiece 10 having an external case 20.
Handpiece 10 includes a light source in the form of a light emitting diode (LED) 21 typically mounted on a heat-transmissive mounting block. LED 21 is positioned such that its light output is directed towards light guide element 14. LED 21 is typically spaced from the proximal end of the light guide element 14 by a reflector cone 22 which forms part of the light delivery system. Reflector cone 22 is adapted to maximise light passing into the light guide element 14, rather than allowing light to stray onto the body of the handpiece. Accordingly, reflector cone 22 acts to ensure high efficiency and reduce excessive heating of the distal portion of the handpiece. Reflector cone 22 is suitably formed by applying a reflective foil (3M) to a conically-shaped area adjacent LED 21.
Alternative arrangements such as vapour deposition of a reflective material are equally suitable.
Additionally, handpiece 10 includes electrical supply apparatus (not shown) to provide an electrical supply to the LED. Typically, this includes electrical wires to the umbilical cord 15 and thence to the control console, optionally also including switching apparatus within the handpiece itself to allow ready actuation of the LED by the user.
It is well known that substantial increases in temperature will cause damage to cellular tissue. The level at which this will occur varies with the tissue type. Skin can withstand more marked increases in temperature than other soft tissue as a result of the nature of the cellular component and also the copious blood supply which provides a means of dissipating the heat. During surgical intervention, there are some situations where the use of heat can be of benefit to the operator in causing coagulation of the tissue and reducing bleeding. This will however cause the tissue to be damaged. In most cases where heat is generated, it is essential to maintain vitality of the surrounding or underlying tissue.
The investigation of the level of tissue damage as a result of increasing temperature during treatment has been investigated most extensively in the field of dentistry since the treatment techniques used on both hard and soft tissue involved the generation of heat (hard tissue removal with high speed drills and scaling with ultrasonic devices). This has been followed up by studies in the medical arena as surgical intervention using lasers has become more common.
Additionally, light guide elements 14 are adapted to provide a range of different light dispersal characteristics. For example, the element can be designed such that light emission is substantially unidirectional or collimated from tip 15 or such that the light is substantially unidirectional but with a degree of off-axis light emission from the tip. Alternatively, the light guide element 14 can be adapted to `leak' light outwardly along a portion, optionally a substantial part of its length, optionally its entire length.
Furthermore, the demountability of the light guide element 14 allows light guide elements to be provided in a range of lengths to suit a range of procedures. For example, light guide elements in the range of 5-7 cm are suitable for intra-oral use, with longer light guide elements being more useful for orthopaedic procedures. Additionally, the light guide element can be changed during a procedure as the light requirements change during the procedure as the surface area of the treatment site changes in size.
The light guide element 14 itself may be manufactured according to any conventional process.
Typically, the light guide element is manufactured from a glass optical fibre.
The light guide element may be rigid or flexible as required in order to deliver light to the target site.
The light guide element 14 may also be shaped to suit the requirements of the procedure. In the embodiments shown, the light guide element is curved towards its distal end.
Straight elements (not shown) will be equally suitable in certain procedures. The light guide element 14 may be of substantially uniform diameter along its length or may taper towards a narrower diameter at its distal end.
In certain embodiments, depending upon application, the light guide element 14 may include a supplementary tip or piece to reduce the distal diameter yet further or a supplementary tip or piece to spread the light across an increased area or volume of the treatment site. An example of such a supplementary tip is shown in cross-section in Figure 4. The tip 17 comprises a cap 18 and a probe 19.
Cap 18 is adapted for operative coupling to distal tip 15 of light guide element 14. In the embodiment shown, an internal female thread engages a corresponding male thread formed on distal tip 15 or simply bites into a resilient surface formed around radially around the outside of distal tip 15.
Alternative arrangements are equally suitable, including simple frictional retention of supplementary tip 17 on light guide element 14. Probe 19 directs light to the target site and is adapted accordingly. In the embodiment shown, the tip 17 is intended for insertion into a dental root canal and so is elongate and tapering.
The construction of the handpiece is shown in more detail in Figures 5 and 6, in which the umbilical cord is omitted for clarity. The light guide element 14 is mounted at its proximal end within a light guide element clip 16 adapted to be received and retained by a corresponding engagement arrangement at a distal end of handpiece 10 having an external case 20.
Handpiece 10 includes a light source in the form of a light emitting diode (LED) 21 typically mounted on a heat-transmissive mounting block. LED 21 is positioned such that its light output is directed towards light guide element 14. LED 21 is typically spaced from the proximal end of the light guide element 14 by a reflector cone 22 which forms part of the light delivery system. Reflector cone 22 is adapted to maximise light passing into the light guide element 14, rather than allowing light to stray onto the body of the handpiece. Accordingly, reflector cone 22 acts to ensure high efficiency and reduce excessive heating of the distal portion of the handpiece. Reflector cone 22 is suitably formed by applying a reflective foil (3M) to a conically-shaped area adjacent LED 21.
Alternative arrangements such as vapour deposition of a reflective material are equally suitable.
Additionally, handpiece 10 includes electrical supply apparatus (not shown) to provide an electrical supply to the LED. Typically, this includes electrical wires to the umbilical cord 15 and thence to the control console, optionally also including switching apparatus within the handpiece itself to allow ready actuation of the LED by the user.
It is well known that substantial increases in temperature will cause damage to cellular tissue. The level at which this will occur varies with the tissue type. Skin can withstand more marked increases in temperature than other soft tissue as a result of the nature of the cellular component and also the copious blood supply which provides a means of dissipating the heat. During surgical intervention, there are some situations where the use of heat can be of benefit to the operator in causing coagulation of the tissue and reducing bleeding. This will however cause the tissue to be damaged. In most cases where heat is generated, it is essential to maintain vitality of the surrounding or underlying tissue.
The investigation of the level of tissue damage as a result of increasing temperature during treatment has been investigated most extensively in the field of dentistry since the treatment techniques used on both hard and soft tissue involved the generation of heat (hard tissue removal with high speed drills and scaling with ultrasonic devices). This has been followed up by studies in the medical arena as surgical intervention using lasers has become more common.
The evidence of the risk of trauma to pulpal tissue in cutting dental hard tissue has been extensively investigated. The general consensus is that the effects are a combination of temperature rise and exposure time but that a rise of 5.5 C will lead to critical changes in pulp tissue if extended for more than one minute. Zach and Cohen showed that rises in excess of 11-17 C caused pulpal necrosis in over 60% of cases [Zach L, Cohen G. Oral Surg, Oral Med, Oral Pathol (1965) 19: 515-5301. This is in part due to the limited ability of the blood supply to effectively dissipate the heat generated as the dentine surrounding the pulp has a low thermal diffusivity and the blood flow is low. Dentine has a composition which is regarded as relatively similar to bone.
Soft tissue temperature rises have again been extensively investigated in dental treatment with particular reference to damage to the periodontium by ultrasonic scaling and also a result of endodontic instrumentation beyond the apical foramen. The general consensus is that a threshold temperature of 7 C is the highest thermal change which is biologically acceptable to avoid periodontal damage.
[Machida et al., J Endod (1995), 21, 88-91; Sauk JJ et al., J Oral Pathol (1988), 17, 496-499;
Namnour S et al Lasers Med Sci (2004), 19, 27-32).
These values give an indication of the levels which should not be exceeded where long exposures, in excess of 30 seconds, occur with devices which may generate heat when treating both hard and soft tissue.
The embodiment shown in Figures 5 and 6 includes passive cooling to dissipate heat generated by LED
21. The passive cooling assembly comprises a heat exchanger 23, of a high thermal conductivity material such as copper, a heat-pipe 24 which conducts heat from copper heat exchange 23 to a heatsink 25. Insulating material 30 in the area of heat exchanger 23 reduces heat transmissions to that area of the handpiece which will be held by the user. A copper, silver or other thermal paste is used to ensure good thermal contact between heat exchanger 23 and LED 21.
Figures 7 and 8 show an alternative arrangement in which cooling of LED 21 is achieved by means of a water-cooling system. Water cooling tubes 31, 32 are in fluid communication with heat exchanger 23.
Inlet tube 31 delivers cooling water (which may include additional chemicals to improve its activity as a coolant) from a pump housed within the control console via umbilical cord 15. After removing heat dissipated from LED 21 into heat exchanger 23, the heated cooling water is returned to the control console via outlet tube 32. The control console includes a heat sink to dissipate the heat from the water and optionally may include supplementary electrical cooling elements such as Peltier or thermoelectric devices.
The power of LED 21 is matched to the photosensitiser to give practical clinical procedure times.
Soft tissue temperature rises have again been extensively investigated in dental treatment with particular reference to damage to the periodontium by ultrasonic scaling and also a result of endodontic instrumentation beyond the apical foramen. The general consensus is that a threshold temperature of 7 C is the highest thermal change which is biologically acceptable to avoid periodontal damage.
[Machida et al., J Endod (1995), 21, 88-91; Sauk JJ et al., J Oral Pathol (1988), 17, 496-499;
Namnour S et al Lasers Med Sci (2004), 19, 27-32).
These values give an indication of the levels which should not be exceeded where long exposures, in excess of 30 seconds, occur with devices which may generate heat when treating both hard and soft tissue.
The embodiment shown in Figures 5 and 6 includes passive cooling to dissipate heat generated by LED
21. The passive cooling assembly comprises a heat exchanger 23, of a high thermal conductivity material such as copper, a heat-pipe 24 which conducts heat from copper heat exchange 23 to a heatsink 25. Insulating material 30 in the area of heat exchanger 23 reduces heat transmissions to that area of the handpiece which will be held by the user. A copper, silver or other thermal paste is used to ensure good thermal contact between heat exchanger 23 and LED 21.
Figures 7 and 8 show an alternative arrangement in which cooling of LED 21 is achieved by means of a water-cooling system. Water cooling tubes 31, 32 are in fluid communication with heat exchanger 23.
Inlet tube 31 delivers cooling water (which may include additional chemicals to improve its activity as a coolant) from a pump housed within the control console via umbilical cord 15. After removing heat dissipated from LED 21 into heat exchanger 23, the heated cooling water is returned to the control console via outlet tube 32. The control console includes a heat sink to dissipate the heat from the water and optionally may include supplementary electrical cooling elements such as Peltier or thermoelectric devices.
The power of LED 21 is matched to the photosensitiser to give practical clinical procedure times.
Suitably, LED 21 is a high-output LED or array of LEDs or multiplexed array of LEDs. For example, W and 15 W LEDs obtainable from LedEngin, Inc have shown, in trials, to be suitable for operation at a range of output powers. For use with the photosensitiser tolonium chloride, LEDs having output wavelengths in the range of 610 to 650nm are preferred, especially in the range of 630 - 640nm. With 5 methylene blue as the photosensitiser, LEDs having an output in the range of 670-680nm are preferred.
With other photosensitisers, the output wavelengths of the LED source will be selected accordingly.
The control panel includes a power supply unit and electrical or electronic control circuit as necessary to control operation of the LED and of the cooling circuit as applicable. The control circuit may 10 provide for adjustment of the output power level of the LED and may include a timer circuit to limit the duration of activation of the LED.
In alternative embodiments, not shown, the handpiece 10 is a self-contained unit and includes cells or batteries to provide power for LED 21. Suitably, the cells are rechargeable cells, such as lithium ion batteries. Suitably, the cells are electrically coupled to LED 21 by means of a control circuit allowing adjustment of the output of LED 21.
Figures 9 to 11 show a further alternative embodiment of a handpiece, with the light guide omitted for clarity. In this embodiment, cooling of the LED 21 assembly is achieved by means of a copper heat exchanger 23 in contact with the LED assembly transferring heat by means of a heat pipe 24 to a heat sink 25. As shown in Figure 10, heat sink 25 has heat dissipating fins. Heat sink 23 is mounted within an external case 20 which also houses a fan 33 mounted with respect to heat sink 25 to draw cool air into the case 20 and other heat sink 25 and then expel the heated air away from the handpiece.
Experimental Data OPTICAL PROPERTIES
Air-cooling We measured the outputs obtained from a tip 15 of a 7mm effective optical diameter light guide element 14 with a 10 W air-cooled LED system as show in Figures 4 and 5. The LED output can be adjusted into the desired range of up to around 1W by adjusting the current applied to the LED. The outputs obtained are shown in Table 1.
Table 1 Input Current/mA Output power/mW
With other photosensitisers, the output wavelengths of the LED source will be selected accordingly.
The control panel includes a power supply unit and electrical or electronic control circuit as necessary to control operation of the LED and of the cooling circuit as applicable. The control circuit may 10 provide for adjustment of the output power level of the LED and may include a timer circuit to limit the duration of activation of the LED.
In alternative embodiments, not shown, the handpiece 10 is a self-contained unit and includes cells or batteries to provide power for LED 21. Suitably, the cells are rechargeable cells, such as lithium ion batteries. Suitably, the cells are electrically coupled to LED 21 by means of a control circuit allowing adjustment of the output of LED 21.
Figures 9 to 11 show a further alternative embodiment of a handpiece, with the light guide omitted for clarity. In this embodiment, cooling of the LED 21 assembly is achieved by means of a copper heat exchanger 23 in contact with the LED assembly transferring heat by means of a heat pipe 24 to a heat sink 25. As shown in Figure 10, heat sink 25 has heat dissipating fins. Heat sink 23 is mounted within an external case 20 which also houses a fan 33 mounted with respect to heat sink 25 to draw cool air into the case 20 and other heat sink 25 and then expel the heated air away from the handpiece.
Experimental Data OPTICAL PROPERTIES
Air-cooling We measured the outputs obtained from a tip 15 of a 7mm effective optical diameter light guide element 14 with a 10 W air-cooled LED system as show in Figures 4 and 5. The LED output can be adjusted into the desired range of up to around 1W by adjusting the current applied to the LED. The outputs obtained are shown in Table 1.
Table 1 Input Current/mA Output power/mW
In the absence of the light guide element 14 and the reflector cone 22, at a current of 700mA, the raw LED output was 1020 mW. Accordingly, at 700mA, we saw light efficiencies of around 70%. Over the course of a test period of 2.5 minutes, the voltage (at a constant current of 700mA) was observed to drop from 10.81 to 10.68 and the heatsink temperature rose from 22.1 C to 26.9 C. The output dropped from 720 to 700mW over that period, confirming that for the anticipated treatment times, air cooling of the LED would be adequate.
The output was then measured with a reflector cone formed from a reflective foil (3M) and optical guide elements in a range of dimensions. With the same input of 700mA, the output power from a 2.5mm distal diameter guide was 160mW and that of a 3mm distal diameter guide was 230mW.
Accordingly, it was observed that the output of the 3mm guide was approximately 32% of that of the 7mm guide, but the intensity of the light was greater, being 3.2W/cm2 compared with 1.7W/cm2 for the 7mm diameter guide.
Water-cooling We then investigated the corresponding outputs of a 15W LED device with water cooling, with a 7mm light guide. The data is shown in Table 2.
Table 2 Input Current/mA Output power/mW
The output at 1000mW input was stable over a 10 minute test period and the temperature of the optical assembly was steady throughout at 30 C. Accordingly, it was apparent that the water-cooled device could provide stable operation over a long period.
Temperature change within teeth at various delivered energies The temperature effect upon teeth was then examined to confirm that, in addition to thermally stable operation of the handpiece itself, the apparatus would not cause undue heating of the tooth itself. In a first trial, two lower molars were selected, one large and one small, and horizontal cavities prepared at the enamel/cementum junction passing to the centre of the tooth. A
thermocouple was passed down this cavity and the temperature of the tooth recorded. The thermocouple was removed and the tooth irradiated at 300mW and 450mW coronally for 150 seconds (45J and 67.5J). The probe was reinserted and the tooth core temperature was then re-recorded. Each measurement was repeated three times.
Each tooth was exposed in air and then the process repeated with the roots immersed in water at ambient temperature. The results are set out in Table 3.
5 Table 3 300mW/large 450mW/Large 450mW/Large 450mW/ 450mW/Large C C in water C small C in water C
Run 1 1.4 2.1 0.7 1.1 0.8 Run 2 1.35 1.7 1.1 1.3 0.7 Run 3 1.2 1.8 0.8 1.3 0.8 Run 4 1.4 2.0 1.0 1.2 0.9 The results show that heating of the tooth is well within the limits necessary to avoid tissue damage.
A second series of tests were carried out to compare temperature measurements within extracted teeth 10 both with or without a surrounding water bath. The water bath simulates the soft tissue support to a tooth in the mouth.
A 1.5mm diameter cavity was prepared in the side of two molar teeth at the crown root margin. This was large and deep enough to position a thermocouple in the centre of the tooth. The cavity was filled with lubricant. The light guide was then placed on the occlusal surface of the tooth. The temperature of the tooth was noted by placing the thermocouple in the cavity within the lubricant and allowing the reading to stabilise. The thermocouple was then withdrawn and the tooth irradiated for 150 seconds at 450mW (67.5J), immediately after the light was switched off the temperature of the tooth tissue was measured again in the same way. The operation was carried out with the tooth both in air and with the roots in a water bath at ambient temperature representing a heat sink as would be found in the mouth with the surrounding tissue. Using a 450mw output irradiation, a mean temperature rise of 1.6 C
( 0.6 C) was seen in the tooth kept in air and a 1.0 C ( 0.3 C) rise was seen in the tooth having its roots in water.
Temperatures within planktonic solutions before and after irradiation with various delivered energies.
Using a thermocouple, the temperature of the planktonic solution was taken immediately prior to the illumination of the suspension and then the temperature was taken again after the period of irradiation.
During the irradiation period the thermocouple was removed. The results of this study are set out in Table 4 and again show minimal temperature rises.
The output was then measured with a reflector cone formed from a reflective foil (3M) and optical guide elements in a range of dimensions. With the same input of 700mA, the output power from a 2.5mm distal diameter guide was 160mW and that of a 3mm distal diameter guide was 230mW.
Accordingly, it was observed that the output of the 3mm guide was approximately 32% of that of the 7mm guide, but the intensity of the light was greater, being 3.2W/cm2 compared with 1.7W/cm2 for the 7mm diameter guide.
Water-cooling We then investigated the corresponding outputs of a 15W LED device with water cooling, with a 7mm light guide. The data is shown in Table 2.
Table 2 Input Current/mA Output power/mW
The output at 1000mW input was stable over a 10 minute test period and the temperature of the optical assembly was steady throughout at 30 C. Accordingly, it was apparent that the water-cooled device could provide stable operation over a long period.
Temperature change within teeth at various delivered energies The temperature effect upon teeth was then examined to confirm that, in addition to thermally stable operation of the handpiece itself, the apparatus would not cause undue heating of the tooth itself. In a first trial, two lower molars were selected, one large and one small, and horizontal cavities prepared at the enamel/cementum junction passing to the centre of the tooth. A
thermocouple was passed down this cavity and the temperature of the tooth recorded. The thermocouple was removed and the tooth irradiated at 300mW and 450mW coronally for 150 seconds (45J and 67.5J). The probe was reinserted and the tooth core temperature was then re-recorded. Each measurement was repeated three times.
Each tooth was exposed in air and then the process repeated with the roots immersed in water at ambient temperature. The results are set out in Table 3.
5 Table 3 300mW/large 450mW/Large 450mW/Large 450mW/ 450mW/Large C C in water C small C in water C
Run 1 1.4 2.1 0.7 1.1 0.8 Run 2 1.35 1.7 1.1 1.3 0.7 Run 3 1.2 1.8 0.8 1.3 0.8 Run 4 1.4 2.0 1.0 1.2 0.9 The results show that heating of the tooth is well within the limits necessary to avoid tissue damage.
A second series of tests were carried out to compare temperature measurements within extracted teeth 10 both with or without a surrounding water bath. The water bath simulates the soft tissue support to a tooth in the mouth.
A 1.5mm diameter cavity was prepared in the side of two molar teeth at the crown root margin. This was large and deep enough to position a thermocouple in the centre of the tooth. The cavity was filled with lubricant. The light guide was then placed on the occlusal surface of the tooth. The temperature of the tooth was noted by placing the thermocouple in the cavity within the lubricant and allowing the reading to stabilise. The thermocouple was then withdrawn and the tooth irradiated for 150 seconds at 450mW (67.5J), immediately after the light was switched off the temperature of the tooth tissue was measured again in the same way. The operation was carried out with the tooth both in air and with the roots in a water bath at ambient temperature representing a heat sink as would be found in the mouth with the surrounding tissue. Using a 450mw output irradiation, a mean temperature rise of 1.6 C
( 0.6 C) was seen in the tooth kept in air and a 1.0 C ( 0.3 C) rise was seen in the tooth having its roots in water.
Temperatures within planktonic solutions before and after irradiation with various delivered energies.
Using a thermocouple, the temperature of the planktonic solution was taken immediately prior to the illumination of the suspension and then the temperature was taken again after the period of irradiation.
During the irradiation period the thermocouple was removed. The results of this study are set out in Table 4 and again show minimal temperature rises.
Table 4 Delivered Temperaturel/ C Temperature2/ C Increase/ C
Energy/J
2.94 22 23 1 2.4 22 23 1 0.9 23 23 0 4.4 22 24 2 3.6 22 23 1 1.35 23 23 0 5.88 22 25 3 4.8 23 25 2 1.8 23 24 1 3.75 22 24 2 2.94 23 24 1 1.5 23 24 1 7.5 23 25 2 5.88 23 24 1 3.0 23 24 1 13.8 23 27 4 11.76 23 26 3 6.0 23 24 1 7.05 21 24 3 5.85 23 25 2 3.15 23 24 1 14.1 22 25 3 11.7 23 26 3 6.3 23 24 1 The peak temperature noted was less than half that which would cause damage to the periodontal ligament.
Measurements of light transmission through dentine.
Dentine slices were interposed between the tip of the light guide of the apparatus described above and a light meter. It was then possible to measure the attenuation in the delivered energy through three thickness of dentine disc equivalent to 0.69mm of dentine with the meter 6mm from the interposed discs. These values are shown in Table 5.
Table 5 Tip out [mW] Measured output through 0.69 Energy delivered at 60 seconds dentine [mW] exposure 100 10 0.6J
250 40 2.4J
500 100 6.OJ
We then sought to investigate the effect of interposing soft tissue on light attenuation from the light guide of the apparatus described above. Varying thickness of porcine muscle were interposed between the end of the light guide and a light meter and the delivered energy measured at the under side of the tissue. Table 6 and Fig 12 show the results.
Energy/J
2.94 22 23 1 2.4 22 23 1 0.9 23 23 0 4.4 22 24 2 3.6 22 23 1 1.35 23 23 0 5.88 22 25 3 4.8 23 25 2 1.8 23 24 1 3.75 22 24 2 2.94 23 24 1 1.5 23 24 1 7.5 23 25 2 5.88 23 24 1 3.0 23 24 1 13.8 23 27 4 11.76 23 26 3 6.0 23 24 1 7.05 21 24 3 5.85 23 25 2 3.15 23 24 1 14.1 22 25 3 11.7 23 26 3 6.3 23 24 1 The peak temperature noted was less than half that which would cause damage to the periodontal ligament.
Measurements of light transmission through dentine.
Dentine slices were interposed between the tip of the light guide of the apparatus described above and a light meter. It was then possible to measure the attenuation in the delivered energy through three thickness of dentine disc equivalent to 0.69mm of dentine with the meter 6mm from the interposed discs. These values are shown in Table 5.
Table 5 Tip out [mW] Measured output through 0.69 Energy delivered at 60 seconds dentine [mW] exposure 100 10 0.6J
250 40 2.4J
500 100 6.OJ
We then sought to investigate the effect of interposing soft tissue on light attenuation from the light guide of the apparatus described above. Varying thickness of porcine muscle were interposed between the end of the light guide and a light meter and the delivered energy measured at the under side of the tissue. Table 6 and Fig 12 show the results.
Table 6 Values for light output after transmission through varying tissue thicknesses Interposed tissue thickness [ mm] Measured light output [mW]
0.4 470 0.8 400 0.9 370 1.0 330 1.5 200 MICROBIOLOGICAL PROPERTIES
We then investigated the use of the apparatus of the present invention for the purposes of disinfection, in combination with a photosensitiser, in particular tolonium chloride, selected as being exempliary of photosensitisers disclosed in the prior art. The bacteria selected were Streptococcus mutans (S mutans) and Porphyromonas gingivalis (P gingivalis), the most commonly occurring periodontal pathogen.
The concentration of photosensitiser and the power of light source are selected to provide maximum tissue penetration and kills rates and will be dependent upon the treatment.
Suitably, the dye concentration is from 0.00001% to 2%, preferably from 0.00001% to 0.5% w/v, more preferably from 0.001 % to 0.1 % w/v.
Cultures of S mutans and P gingivalis were prepared and grown to provide a source of bacteria at a concentration of 81og10 bacteria per ml. A flat ended aluminium well was used as the test vessel as the tip of the light guide was 7mm diameter and would irradiate the whole of the surface of the well. The light guide was set up to be positioned 6mm from the top of the bacterial suspension in the well. 80 l of the cell suspension of known cell concentration were added to the well. The well was positioned on a magnetic stirrer and the solution agitated. 80 l of the photosensitiser [Tolonium chloride] [TC]
(stock concentration 25.4mg/1) was then added to the well. After the contact time of 60 seconds for the photosensitiser during which time the solution was stirred with a magnetic stirrer, the tip of the light guide was positioned at 6mm from the surface of the solution and the solution irradiated with light for 60 seconds at 100mW, 250mW or 500mW. Each exposed well plate was then sampled and the suspension cultured for viable bacteria as described below.
After the treatment was completed, the treated suspension was transferred to an Eppendorf containing buffer to provide a 10-1 serial dilution. The mixture was then shaken vigorously and then serially diluted again. This sequence was carried out until a 10-7 dilution was obtained. Samples of solution from each dilution were then plated out on TSA plates. Counts of viable bacteria were obtained after incubating these plates for 3 days.
During each test procedure, a series of samples were pre-incubated with 80 l buffer instead of TC. A
further series were inoculated with the photosensitiser and the light guide positioned but not activated.
Similarly, controls were carried out. Here, the bacteria were pre-incubated with 8O l buffer instead of TC and the light guide positioned for 60 seconds but not activated. All experiments were carried out with a contact time for the photosensitiser of 60 seconds at a range of delivered energies of up to 21 J.
The results for P gingivalis are set out in Table 7 and S mutans in Table 8.
Table 7 P. Gingivalis Log reduction Delivered energy (mean of 3 tests) {Measured J}
3.89 2.94 4.2 4.41 5.39 5.88 3.14 1.47 4.42 3.45 4.73 6.9 4.85 10.35 4.935 13.8 5.67 7.05 6.11 14.1 6.35 21.15 8.99 28.2 Table 8 S mutans Log reduction Delivered energy (mean of 3 tests) {Measured J}
3.99 3 3.92 2.4 3.73 0.9 4.17 4.5 4.13 3.6 3.49 1.35 4.26 6 4.1 4.8 4.04 1.8 5.83 7.5 5.03 6.0 4.13 3.45 4.04 2.85 3.94 1.5 4.65 6.9 4.53 5.7 4.36 3.0 6.68 13.8 5.47 11.4 5.06 6.0 5.78 13.8 4.1 7.05 3.80 5.85 3.29 3.3 5.97 14.1 4.47 11.7 4.09 6.6 4.55 7.05 4.16 5.85 3.90 3.3 4.43 3.3 4.41 5.85 5.42 7.05 6.40 14.1 5.17 11.7 4.81 6 6.18 14.1 5.44 11.7 5.14 6 9.08 21.15 9.08 28.2 8.97 28.2 A further series of test were carried out to determine whether the light caused any reduction in bacterial load. In case of light alone to ensure uniform bacterial concentration, a 0.025m1 volume of buffer solution was added to the 0.025m1 of bacteria for the contact time of 60 seconds prior to irradiation at arrange of energies and distances as above. The results are set out in Table 9.
Table 9 Light alone Log reduction Delivered energy (mean of 3 tests) {Measured J}
0.07 3 0.10 2.4 0.02 0.9 0.05 4.5 0.01 3.6 0.09 1.35 0.12 6.0 0.11 4.8 0.07 1.8 0.08 3.75 0.05 2.85 0.05 1.5 0.09 6.9 0.06 5.7 0.02 3.0 0.10 13.8 0.08 11.4 0.02 6.0 0.08 7.05 0.04 5.85 0.01 3.3 0.04 14.1 0.06 11.7 0.06 6.6 Trials with photosensitiser alone had been carried out already in our previous applications to which further reference should be made and showed similar results of statistically no reduction.
No significant kill was achieved with either light or solution alone whereas both together and with the 10 apparatus of the present invention gave total bacterial kills based on loads of 7 log10 (S mutans) and 9 log10 (P gingivalis). These bacterial loads are much higher than would normally be experienced in typical clinical situations.
The results show that disinfection (a 4log reduction) occurs at delivered energies above about 3J to 8J
0.4 470 0.8 400 0.9 370 1.0 330 1.5 200 MICROBIOLOGICAL PROPERTIES
We then investigated the use of the apparatus of the present invention for the purposes of disinfection, in combination with a photosensitiser, in particular tolonium chloride, selected as being exempliary of photosensitisers disclosed in the prior art. The bacteria selected were Streptococcus mutans (S mutans) and Porphyromonas gingivalis (P gingivalis), the most commonly occurring periodontal pathogen.
The concentration of photosensitiser and the power of light source are selected to provide maximum tissue penetration and kills rates and will be dependent upon the treatment.
Suitably, the dye concentration is from 0.00001% to 2%, preferably from 0.00001% to 0.5% w/v, more preferably from 0.001 % to 0.1 % w/v.
Cultures of S mutans and P gingivalis were prepared and grown to provide a source of bacteria at a concentration of 81og10 bacteria per ml. A flat ended aluminium well was used as the test vessel as the tip of the light guide was 7mm diameter and would irradiate the whole of the surface of the well. The light guide was set up to be positioned 6mm from the top of the bacterial suspension in the well. 80 l of the cell suspension of known cell concentration were added to the well. The well was positioned on a magnetic stirrer and the solution agitated. 80 l of the photosensitiser [Tolonium chloride] [TC]
(stock concentration 25.4mg/1) was then added to the well. After the contact time of 60 seconds for the photosensitiser during which time the solution was stirred with a magnetic stirrer, the tip of the light guide was positioned at 6mm from the surface of the solution and the solution irradiated with light for 60 seconds at 100mW, 250mW or 500mW. Each exposed well plate was then sampled and the suspension cultured for viable bacteria as described below.
After the treatment was completed, the treated suspension was transferred to an Eppendorf containing buffer to provide a 10-1 serial dilution. The mixture was then shaken vigorously and then serially diluted again. This sequence was carried out until a 10-7 dilution was obtained. Samples of solution from each dilution were then plated out on TSA plates. Counts of viable bacteria were obtained after incubating these plates for 3 days.
During each test procedure, a series of samples were pre-incubated with 80 l buffer instead of TC. A
further series were inoculated with the photosensitiser and the light guide positioned but not activated.
Similarly, controls were carried out. Here, the bacteria were pre-incubated with 8O l buffer instead of TC and the light guide positioned for 60 seconds but not activated. All experiments were carried out with a contact time for the photosensitiser of 60 seconds at a range of delivered energies of up to 21 J.
The results for P gingivalis are set out in Table 7 and S mutans in Table 8.
Table 7 P. Gingivalis Log reduction Delivered energy (mean of 3 tests) {Measured J}
3.89 2.94 4.2 4.41 5.39 5.88 3.14 1.47 4.42 3.45 4.73 6.9 4.85 10.35 4.935 13.8 5.67 7.05 6.11 14.1 6.35 21.15 8.99 28.2 Table 8 S mutans Log reduction Delivered energy (mean of 3 tests) {Measured J}
3.99 3 3.92 2.4 3.73 0.9 4.17 4.5 4.13 3.6 3.49 1.35 4.26 6 4.1 4.8 4.04 1.8 5.83 7.5 5.03 6.0 4.13 3.45 4.04 2.85 3.94 1.5 4.65 6.9 4.53 5.7 4.36 3.0 6.68 13.8 5.47 11.4 5.06 6.0 5.78 13.8 4.1 7.05 3.80 5.85 3.29 3.3 5.97 14.1 4.47 11.7 4.09 6.6 4.55 7.05 4.16 5.85 3.90 3.3 4.43 3.3 4.41 5.85 5.42 7.05 6.40 14.1 5.17 11.7 4.81 6 6.18 14.1 5.44 11.7 5.14 6 9.08 21.15 9.08 28.2 8.97 28.2 A further series of test were carried out to determine whether the light caused any reduction in bacterial load. In case of light alone to ensure uniform bacterial concentration, a 0.025m1 volume of buffer solution was added to the 0.025m1 of bacteria for the contact time of 60 seconds prior to irradiation at arrange of energies and distances as above. The results are set out in Table 9.
Table 9 Light alone Log reduction Delivered energy (mean of 3 tests) {Measured J}
0.07 3 0.10 2.4 0.02 0.9 0.05 4.5 0.01 3.6 0.09 1.35 0.12 6.0 0.11 4.8 0.07 1.8 0.08 3.75 0.05 2.85 0.05 1.5 0.09 6.9 0.06 5.7 0.02 3.0 0.10 13.8 0.08 11.4 0.02 6.0 0.08 7.05 0.04 5.85 0.01 3.3 0.04 14.1 0.06 11.7 0.06 6.6 Trials with photosensitiser alone had been carried out already in our previous applications to which further reference should be made and showed similar results of statistically no reduction.
No significant kill was achieved with either light or solution alone whereas both together and with the 10 apparatus of the present invention gave total bacterial kills based on loads of 7 log10 (S mutans) and 9 log10 (P gingivalis). These bacterial loads are much higher than would normally be experienced in typical clinical situations.
The results show that disinfection (a 4log reduction) occurs at delivered energies above about 3J to 8J
15 and sterilization occurs at a delivered energy of from around 15J to 21J.
Thus taken together the various measurements cited demonstrate that the inventive process described herein is capable of providing bacterial and fungal disinfection on or within the tooth and oral soft tissue and soft tissue generally without any adverse effect to the normal tissue due to temperature rise.
A light guide element 14 having a diameter in the range of 7mm can be considered to be a general purpose guide, suitable for dental treatments such as carious lesions, surface treatments, fissure sealings and so on, as well as other medical indications. A narrower light guide element 14, such as one having a tip 15 in the range of 3mm diameter, can provide a more confined light at the tip than a wider tip.
The tip can be supplemented further by a reduction tip (not shown) demountably attachable to tip 15 to narrow the tip and reduce its area yet further. In alternative embodiments, the tip is supplementable with an expansion tip or element to increase the spread of light.
The flexibility of the invention apparatus is displayed yet further when considering its application in treatment of periodontal disease including gingivitis. A light guide element of the order of 7mm in diameter can deliver sufficient energy when placed above or at the side of the periodontal pocket to provide adequate activation of the photosensitiser. Alternatively, a small-tipped light guide element can be inserted directly into the periodontal pocket such that the infected area can be wholly disinfected.
Accordingly, the present invention provides an apparatus which is capable of a wide range of applications to localised or large areas of bacterial infections and provides a single apparatus which, with appropriate selection of light guide, allows a dentist to treat all bacterial and fungal infections of the oral cavity.
The apparatus is also, by similar selection, suitable for use in treating other bacterial infections, such as skin lesions and infections, infections of the epithelial tissue or ulceration such as mouth ulcers and ulcers those associated with diabetic conditions; soft and hard tissue, such as local or targeted treatment of muscle damage; and orthopaedic infections or other infections of the bone.
Indeed, the versatility of the apparatus is such that disinfection of any surface is possible with the present invention, such as disinfection of medical devices such as medical implants whether in vivo after placement into the body or ex vivo prior to placement; and disinfection of medical apparatus and instruments for example, disinfection of elongate apparatus such as indwelling catheters by means of `leaky' optical fibres which distribute light substantially along their entire length. This will be of great benefit for sterilisation of those materials which are not suitable for autoclaving sterilisation.
Satisfactory sterilisation of medical grade stainless steel and of acrylic materials (such as Perspex, a registered trade mark) has been demonstrated under similar conditions with tolonium chloride as the photosensitiser. The apparatus is also useful in treating and avoiding periimplantitis, in which bacterial infections develop post-operatively between soft tissue, the bone and an implant; and in apisectomy procedures. The apparatus is also useful in avoiding and treating infections in `dry sockets', the site remaining after a tooth extraction, which can readily become infected. The apparatus is also effective at treating deciduous teeth where a partial pulpectomy has been carried out.
ANTI FUNGAL PROPERTIES
Thus taken together the various measurements cited demonstrate that the inventive process described herein is capable of providing bacterial and fungal disinfection on or within the tooth and oral soft tissue and soft tissue generally without any adverse effect to the normal tissue due to temperature rise.
A light guide element 14 having a diameter in the range of 7mm can be considered to be a general purpose guide, suitable for dental treatments such as carious lesions, surface treatments, fissure sealings and so on, as well as other medical indications. A narrower light guide element 14, such as one having a tip 15 in the range of 3mm diameter, can provide a more confined light at the tip than a wider tip.
The tip can be supplemented further by a reduction tip (not shown) demountably attachable to tip 15 to narrow the tip and reduce its area yet further. In alternative embodiments, the tip is supplementable with an expansion tip or element to increase the spread of light.
The flexibility of the invention apparatus is displayed yet further when considering its application in treatment of periodontal disease including gingivitis. A light guide element of the order of 7mm in diameter can deliver sufficient energy when placed above or at the side of the periodontal pocket to provide adequate activation of the photosensitiser. Alternatively, a small-tipped light guide element can be inserted directly into the periodontal pocket such that the infected area can be wholly disinfected.
Accordingly, the present invention provides an apparatus which is capable of a wide range of applications to localised or large areas of bacterial infections and provides a single apparatus which, with appropriate selection of light guide, allows a dentist to treat all bacterial and fungal infections of the oral cavity.
The apparatus is also, by similar selection, suitable for use in treating other bacterial infections, such as skin lesions and infections, infections of the epithelial tissue or ulceration such as mouth ulcers and ulcers those associated with diabetic conditions; soft and hard tissue, such as local or targeted treatment of muscle damage; and orthopaedic infections or other infections of the bone.
Indeed, the versatility of the apparatus is such that disinfection of any surface is possible with the present invention, such as disinfection of medical devices such as medical implants whether in vivo after placement into the body or ex vivo prior to placement; and disinfection of medical apparatus and instruments for example, disinfection of elongate apparatus such as indwelling catheters by means of `leaky' optical fibres which distribute light substantially along their entire length. This will be of great benefit for sterilisation of those materials which are not suitable for autoclaving sterilisation.
Satisfactory sterilisation of medical grade stainless steel and of acrylic materials (such as Perspex, a registered trade mark) has been demonstrated under similar conditions with tolonium chloride as the photosensitiser. The apparatus is also useful in treating and avoiding periimplantitis, in which bacterial infections develop post-operatively between soft tissue, the bone and an implant; and in apisectomy procedures. The apparatus is also useful in avoiding and treating infections in `dry sockets', the site remaining after a tooth extraction, which can readily become infected. The apparatus is also effective at treating deciduous teeth where a partial pulpectomy has been carried out.
ANTI FUNGAL PROPERTIES
The apparatus can also be used in antifungal applications, such as treatment of fungal nail infection or denture sore mouth.
One and three day biofilms containing Candida albicans were produced on a polymer substrate. The biofilms were then exposed either to a saline solution or tolonium chloride photosensitiser for a pre-incubation period of 60 seconds. The biofilm was then exposed to LED light source at 20mm above the polymer substrate using the apparatus described above with a wavelength range 613-623nm. Varying exposure times and powers were evaluated and the results are shown in Tables 10 to 12.
Table 10 Log cfu reduction and percentage kill in 24 hour biofilm LED output[mW]/ exposure time Control [log cfu] Post exposure [log cfu] % kill [sec]
700mW/150secs 6.492 3.645 99.8 700mW/150secs 6.304 3.363 99.9 700mW/300secs 6.409 2.599 99.98 400mW/80 secs 6.304 5.768 70.93 400mW/150secs 6.409 4.315 99.2 400mW/150 secs 6.304 3.855 99.6 400mW/300 secs 6.409 2.700 99.98 In all cases the pre-incubation time was 60 sec Table 11 Log cfu reduction and percentage kill in 72 hour biofilm LED output[mW]/ exposure time Control [log cfu] Post exposure [log cfu] % kill [sec]
700mW/150secs 6.351 4.147 99.37 700mW/300secs 6.351 4.879 96.63 700mW/1200secs 6.049 3.217 99.85 400mW/80 secs 6.676 5.057 97.59 400mW/150secs 6.351 5.404 88.68 400mW/300 secs 6.351 4.511 98.56 In all cases the pre-incubation time was 60 sec Table 12 Effect of LED light alone on the bacterial biofilm with saline added in place of photosensitiser at 72 hours LED output[mW]/ exposure time Control [log cfu] Post exposure [log cfu] % kill [sec]
700mW/ 600sec 6.027 5.896 26.05 700mW/900secs 6.027 5.812 39 Fungal infections are conventionally generally treated by swabbing the infected area with the disinfectant and leaving for a period of time. The success requires that the disinfectant tracks through the infected area and the biofilm which supports the bacteria. This usually takes some time and often only the superficial infected areas are treated effectively such that the patient returns after a period of time with the infection again active. As results above show, tolonium chloride effectively affects an aged biofilm. In a clinical situation, typically the treatment will be to apply the photosensitiser for a conditioning period of about one minute with quite vigorous swabbing followed by irradiation for approximately 5 minutes at 700mw. In the mouth, the palate is the area normally affected by these fungi. The palate can be treated as described, as can the fit surface of dentures by spray application of the photosensitiser or by immersing the denture in a bath of the photosensitiser for the conditioning time and then irradiate as above.
For our initial experiments, comparing the sterilising and disinfecting properties of the inventive apparatus with the prior art devices, we used the photosensitisers known in the art, in particular, those described in our earlier applications, W00074587 and W00062701, more particularly, aqueous solutions of tolonium chloride. The photosensitiser will, however, be selected as having an uptake response appropriate to the target bacteria. Suitably, the photosensitiser is capable of absorbing light towards the red end of the visible spectrum or at longer wavelengths as these are typically better able to penetrate tissues at the treatment site.
For certain applications (particularly those involving surface treatments), it is advantageous to increase the viscosity of the photosensitiser, to avoid run off of the photosensitiser solution. Accordingly, in certain embodiments, we have used photosensitisers to which a thickening or gelling agent has been added. The thickening agent is selected having regard to the requirements of the procedure, in terms of biocompatibility etc. Suitable thickening agents include hydrophilic polymers such as cellulose derivatives and polyvinyl pyrrolidone. Cellulosic materials such as hydroxypropyl methyl cellulose or hydroxymethyl epoxy cellulose have shown to be particularly useful materials.
Alternatively, thickening agents such as colloidal silica (Cab-O-Sil) maybe added, typically in amounts of up to 10%
by weight.
The apparatus of the present invention allows illumination to be adjusted within a wide range of areas from, fundamentally, a single apparatus, ranging from localised coverage to wide-area illumination. As a result, the apparatus finds application in a much wider range of techniques than prior art devices and provides a means of treatment having reduced toxicity and/or contraindications. The apparatus is suitable for use in hard and soft tissues and for both human and animal uses.
One and three day biofilms containing Candida albicans were produced on a polymer substrate. The biofilms were then exposed either to a saline solution or tolonium chloride photosensitiser for a pre-incubation period of 60 seconds. The biofilm was then exposed to LED light source at 20mm above the polymer substrate using the apparatus described above with a wavelength range 613-623nm. Varying exposure times and powers were evaluated and the results are shown in Tables 10 to 12.
Table 10 Log cfu reduction and percentage kill in 24 hour biofilm LED output[mW]/ exposure time Control [log cfu] Post exposure [log cfu] % kill [sec]
700mW/150secs 6.492 3.645 99.8 700mW/150secs 6.304 3.363 99.9 700mW/300secs 6.409 2.599 99.98 400mW/80 secs 6.304 5.768 70.93 400mW/150secs 6.409 4.315 99.2 400mW/150 secs 6.304 3.855 99.6 400mW/300 secs 6.409 2.700 99.98 In all cases the pre-incubation time was 60 sec Table 11 Log cfu reduction and percentage kill in 72 hour biofilm LED output[mW]/ exposure time Control [log cfu] Post exposure [log cfu] % kill [sec]
700mW/150secs 6.351 4.147 99.37 700mW/300secs 6.351 4.879 96.63 700mW/1200secs 6.049 3.217 99.85 400mW/80 secs 6.676 5.057 97.59 400mW/150secs 6.351 5.404 88.68 400mW/300 secs 6.351 4.511 98.56 In all cases the pre-incubation time was 60 sec Table 12 Effect of LED light alone on the bacterial biofilm with saline added in place of photosensitiser at 72 hours LED output[mW]/ exposure time Control [log cfu] Post exposure [log cfu] % kill [sec]
700mW/ 600sec 6.027 5.896 26.05 700mW/900secs 6.027 5.812 39 Fungal infections are conventionally generally treated by swabbing the infected area with the disinfectant and leaving for a period of time. The success requires that the disinfectant tracks through the infected area and the biofilm which supports the bacteria. This usually takes some time and often only the superficial infected areas are treated effectively such that the patient returns after a period of time with the infection again active. As results above show, tolonium chloride effectively affects an aged biofilm. In a clinical situation, typically the treatment will be to apply the photosensitiser for a conditioning period of about one minute with quite vigorous swabbing followed by irradiation for approximately 5 minutes at 700mw. In the mouth, the palate is the area normally affected by these fungi. The palate can be treated as described, as can the fit surface of dentures by spray application of the photosensitiser or by immersing the denture in a bath of the photosensitiser for the conditioning time and then irradiate as above.
For our initial experiments, comparing the sterilising and disinfecting properties of the inventive apparatus with the prior art devices, we used the photosensitisers known in the art, in particular, those described in our earlier applications, W00074587 and W00062701, more particularly, aqueous solutions of tolonium chloride. The photosensitiser will, however, be selected as having an uptake response appropriate to the target bacteria. Suitably, the photosensitiser is capable of absorbing light towards the red end of the visible spectrum or at longer wavelengths as these are typically better able to penetrate tissues at the treatment site.
For certain applications (particularly those involving surface treatments), it is advantageous to increase the viscosity of the photosensitiser, to avoid run off of the photosensitiser solution. Accordingly, in certain embodiments, we have used photosensitisers to which a thickening or gelling agent has been added. The thickening agent is selected having regard to the requirements of the procedure, in terms of biocompatibility etc. Suitable thickening agents include hydrophilic polymers such as cellulose derivatives and polyvinyl pyrrolidone. Cellulosic materials such as hydroxypropyl methyl cellulose or hydroxymethyl epoxy cellulose have shown to be particularly useful materials.
Alternatively, thickening agents such as colloidal silica (Cab-O-Sil) maybe added, typically in amounts of up to 10%
by weight.
The apparatus of the present invention allows illumination to be adjusted within a wide range of areas from, fundamentally, a single apparatus, ranging from localised coverage to wide-area illumination. As a result, the apparatus finds application in a much wider range of techniques than prior art devices and provides a means of treatment having reduced toxicity and/or contraindications. The apparatus is suitable for use in hard and soft tissues and for both human and animal uses.
Claims (30)
1. An apparatus for activation of a photosensitiser for a tissue disinfection procedure, the apparatus comprising a handpiece (10), a light emitting diode light source (21) and a light delivery system comprising a light guide (14) having a proximal end mountable to the light delivery system to receive light from the light source (21) and a distal end from which light is emitted from the apparatus and further comprising cooling means adapted to reduce transmission of heat from the distal end (15) of the light guide (21).
2. An apparatus as claimed in claim 1 wherein the light emitting diode light source (21) is adapted to deliver a sufficient energy to activate the photosensitiser to disinfect tissue and wherein the cooling means (23, 24, 25) is adapted to provide a temperature rise to the tissue of less than that which causes tissue damage.
3. An apparatus as claimed in claim 2 wherein the light emitting diode light source delivers an energy of up to 15J and the temperature rise is less than or equal to 3°C.
4. An apparatus as claimed in any one of claims 1 to 3 wherein the cooling means is provided in the handpiece.
5. An apparatus as claimed in any preceding claim wherein the cooling means comprises a heat pipe.
6. An apparatus as claimed in any preceding claim wherein the cooling means comprises a heatsink.
7. An apparatus as claimed in any preceding claim wherein the optical apparatus further comprises a control console in communication with the handpiece.
8. An apparatus as claimed in claim 7 wherein the control console includes heat dissipation means in communication with the handpiece cooling means.
9. An apparatus as claimed in claim 8 wherein the cooling means comprises water as a coolant.
10. An optical apparatus as claimed in any preceding claim wherein the light emitting diode light source is housed within the handpiece.
11. An apparatus as claimed in any preceding claim wherein the light guide comprises an optical fibre.
12. An apparatus as claimed in any preceding claim wherein the light guide is of substantially uniform cross-section from a proximal end to a distal end.
13. An apparatus as claimed in claim 12 wherein the light guide is shaped to taper between the proximal and distal ends.
14. An apparatus as claimed in any preceding claim wherein the light guide further includes a demountable reduction tip to reduce the area of the distal portion of the tip.
15. An apparatus as claimed in any preceding claim wherein the light guide comprises a leaky fibre.
16. An apparatus as claimed in any preceding claim wherein the light delivery system comprises a reflector cone adjacent the light-source.
17. An apparatus as claimed in any preceding claim, wherein the light emitting diode light source is powered by means of a battery; preferably a rechargeable battery; more preferably a Li-ion battery.
18. A photodynamic therapy system comprising an apparatus as claimed in any one of claims 1 to 17.
19. A photodynamic therapy system as claimed in claim 18 further comprising a photosensitiser.
20. A photodynamic therapy apparatus as claimed in claim 19 wherein the photosensitiser is selected from photoactivatable dyes and other compounds; including azure blue cert, azure B chloride, azure 2, azure A chloride, azure B tetrafluoroborate, thionin, azure A eosinate, azure B eosinate, azure mix sicc, azure II eosinate, arianor steel blue, toluidine blue O, tryptan blue, crystal violet, methylene blue, porhyrins, including haematoporphyrin HCl and haematoporphyrin ester, phthalocyanines, including aluminium disulphonated phthalocyanine, phenothiazines and chlorines; or metabolic precursors thereof.
21. A photodynamic therapy apparatus as claimed in claim 19 or claim 20 wherein the photosensitiser is in the form of a liquid, a sprayable liquid, paste, gel or varnish.
22. An apparatus as claimed in claim 21 wherein the photosensitiser is in the form of a photosensitiser composition comprising the photosensitiser and a thickening agent.
23. An apparatus as claimed in claim 22 wherein the thickening agent is selected from cellulose derivatives and polyvinyl pyrrolidoine.
24. An apparatus as claimed in claim 23 wherein the cellulose derivative is hydroxypropyl methyl cellulose or hydroxmethyl epoxy cellulose.
25. An apparatus as claimed in any one of claims 19 to 24 for use against Gram positive and Gram negative bacteria, including strains of Peptostreptococcus, Streptococcus, Staphylococcus, Actinomyces, Bifidbacterium, Coorynebacterium, Eubacterium Lactobacillus, Propioibacterium, Pseudoramibacter, Nieserria, Veillonella, Actinobacilus, Campylobacter, Cantonella, Centipeda, Desulphovibrio, Enterococcus, Escheria, Fusobacterium, Haemophilus, Porphoromonas, Prevotella, Selenomonas, and Treponema; in particular bacteria selected from Staphylococcus aureus, Staphylococcus epidermidis; Staphylococcus hominis, Staphylococcus haemolyticus, Staphylococcus pyogenes, Pseudomonas aeruginosa, Propioibacterium acnes, Porphyromonas gingivalis, Streptococcus intermedius and Streptococcus mutans and against spore-forming bacteria such as Bacillus, Clostridium, Sporohalobacter, Anaerobacter and Heliobacterium, or against fungal or viral species.
26. Use of an apparatus as claimed in any one of claims 1 to 24 against Gram positive and Gram negative bacteria, including strains of Peptostreptococcus, Streptococcus, Staphylococcus, Actinomyces, Bifidbacterium, Coorynebacterium, Eubacterium Lactobacillus, Propioibacterium, Pseudoramibacter, Nieserria, Veillonella, Actinobacilus, Campylobacter, Cantonella, Centipeda, Desulphovibrio, Enterococcus, Escheria, Fusobacterium, Haemophilus, Porphoromonas, Prevotella, Selenomonas, and Treponema; in particular bacteria selected from Staphylococcus aureus, Staphylococcus epidermidis; Staphylococcus hominis, Staphylococcus haemolyticus, Staphylococcus pyogenes, Pseudomonas aeruginosa, Propioibacterium acnes, Porphyromonas gingivalis, Streptococcus intermedius and Streptococcus mutans; and against spore-forming bacteria such as Bacillus, Clostridium, Sporohalobacter, Anaerobacter and Heliobacterium.
27. Use of an apparatus as claimed in any one of claims 1 to 24 against fungal and viral species.
28. A method of tissue disinfection, the method comprising gaining access to an infected tissue site; applying a photosensitiser to the site; and irradiating the site by means of an apparatus as claimed in any one of claims 1 to 17.
29. A method as claimed in claim 28 wherein the site is a dental site.
30. A method as claimed in claim 28 or claim 29 wherein the tissue disinfection is of a bacterial, viral or fungal infection.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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GB0802822A GB0802822D0 (en) | 2008-02-15 | 2008-02-15 | Optical apparatus and methods |
GB0802822.7 | 2008-02-15 | ||
PCT/GB2009/050149 WO2009101452A1 (en) | 2008-02-15 | 2009-02-16 | Optical apparatus and methods |
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CA2752469A1 true CA2752469A1 (en) | 2009-08-20 |
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CA2752469A Abandoned CA2752469A1 (en) | 2008-02-15 | 2009-02-16 | Optical apparatus and methods |
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EP (1) | EP2326278A1 (en) |
CA (1) | CA2752469A1 (en) |
GB (1) | GB0802822D0 (en) |
WO (1) | WO2009101452A1 (en) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2020102134A1 (en) * | 2018-11-13 | 2020-05-22 | Conmed Corporation | Method for remotely cooling a scope-mounted (distal) arthroscopic light source |
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US20100330523A1 (en) * | 2007-03-30 | 2010-12-30 | Cms Dental Aps | Optical tip for photosynthesis |
WO2023250273A2 (en) * | 2022-06-22 | 2023-12-28 | Izadi Dr Mohammad | Heat scaler for orthodontics or dentistry |
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US5373571A (en) * | 1993-03-16 | 1994-12-13 | Spectran Specialty Optics Company | Fiber optic diffuser tip |
US5728090A (en) * | 1995-02-09 | 1998-03-17 | Quantum Devices, Inc. | Apparatus for irradiating living cells |
WO2001010327A1 (en) * | 1999-08-11 | 2001-02-15 | Ceramoptec Industries, Inc. | Dental laser scaling device and method |
DE10138071A1 (en) * | 2001-08-03 | 2003-02-27 | Georg Knott | irradiator |
EP1768745A1 (en) * | 2004-07-22 | 2007-04-04 | Ondine International Ltd. | Sonophotodynamic therapy for dental applications |
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2008
- 2008-02-15 GB GB0802822A patent/GB0802822D0/en not_active Ceased
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2009
- 2009-02-16 WO PCT/GB2009/050149 patent/WO2009101452A1/en active Application Filing
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Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
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WO2020102134A1 (en) * | 2018-11-13 | 2020-05-22 | Conmed Corporation | Method for remotely cooling a scope-mounted (distal) arthroscopic light source |
CN113038866A (en) * | 2018-11-13 | 2021-06-25 | 康曼德公司 | Method for remotely cooling a mirror-mounted (distal) arthroscopic light source |
US11421869B2 (en) | 2018-11-13 | 2022-08-23 | Conmed Corporation | Method for remotely cooling a scope-mounted (distal) arthroscopic light source |
AU2019381680B2 (en) * | 2018-11-13 | 2022-09-29 | Conmed Corporation | Method for remotely cooling a scope-mounted (distal) arthroscopic light source |
Also Published As
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WO2009101452A1 (en) | 2009-08-20 |
EP2326278A1 (en) | 2011-06-01 |
GB0802822D0 (en) | 2008-03-26 |
WO2009101452A8 (en) | 2009-10-22 |
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