Irradiation device

Abstract

An irradiation device for insertion into an orifice of the body to provide photodynamic therapy comprises: a housing moulded from a resilient material and adapted to be fully inserted and secured in the orifice, the housing enclosing an LED lamp system 22 and a power source 41 for powering the LED lamp system 22; wherein the device is independently operational while located in the orifice; characterised in that: the housing comprises a first housing part 2 for holding the power source 41 and a second housing part 4 for holding the LED lamp system 22, the first and second housing parts 2, 4 being separable and being preferably formed separately from the LED lamp system 22; and in that the first housing part 2 consists of a chamber 6 for holding the power source 41 and an opening 26 into the chamber 6 is provided through a resilient opening part 8, wherein the chamber 6 is closed when the first housing part 2 is joined to the second housing part 4.

Claims

1. An irradiation device for providing photodynamic therapy to the cervix, the device comprising: a housing comprising a separate first housing part for holding a power source for powering a LED lamp system, and a separate second housing part for holding the LED lamp system, which first and second housing parts are molded from a resilient material, wherein (a) the first housing part comprises: a chamber comprising the power source, a resilient opening part providing access to the chamber and which can be deformed to insert and/or remove the power source, and an electrical coupling passing from the power source to the LED lamp system in the second housing part, the resilient opening part comprising (i) a resilient neck part narrowing the entrance to the chamber to a size less than the width of the power source to thereby hold the power source within the chamber and (ii) a first coupling part; and (b) the second housing part comprises: a flexible outer portion which is frustoconical in shape that forms a continuous surface which tapers outwards towards a rear end of the device, a concave treatment surface, the LED lamp system, where the LED lamp system is arranged to emit light from the concave treatment surface onto the cervix, and a second coupling part; wherein the first coupling part on the first housing part is arranged to join to and form a seal with the second coupling part on the second housing part, thereby closing the chamber; and wherein the device, when in use, is fully inserted and secured in the vagina and is independently operational while located in the vagina.

2. The device as claimed in claim 1, wherein the first and second housing parts being formed separately from the LED lamp system.

3. The device as claimed in claim 1, wherein the resilient material of the first housing part is sized to fit the chamber tightly around the power source.

4. The device as claimed in claim 1, wherein the power source is sealed within the housing such that the housing is fluid tight in use.

5. The device as claimed in claim 1, wherein a sealing media is used at a joint between the first and second housing parts.

6. The device as claimed in claim 1, wherein one of the two coupling parts is arranged to be stretched to place it around the other of the two coupling parts, thereby using the elasticity of the resilient material to hold the two housing parts together.

7. The device as claimed in claim 1, wherein a part or all of the resilient material is at least partially transparent to light emitted from the LED lamp system, when the device is in use.

8. The device as claimed in claim 1, wherein the second housing part is molded of a resilient material that is at least partially transparent to light emitted from the LED lamp system.

9. The device as claimed in claim 1, wherein the second housing part has one or more molded cavity to fit the LED lamp system.

10. The device as claimed in claim 9, wherein the one or more molded cavity is enclosed by a fastening lip for securing the LED lamp system within the cavity.

11. The device as claimed in claim 1, wherein, in use, the device provides light with a mean irradiance below 50 mW/cm.sup.2.

12. The device as claimed in claim 1, further comprising a drug carrying area for carrying a composition comprising a photosensitizer or precursor of a photosensitizer.

13. The device as claimed in claim 12 wherein the drug carrying area is the treatment surface on the second housing part.

14. The device as claimed in claim 12 wherein the composition comprises a precursor which is 5-ALA, a derivative of 5-ALA or a pharmaceutically acceptable salt thereof.

15. The device as claimed in claim 14, wherein the composition comprises 5-ALA or a precursor of formula (I) or a pharmaceutically acceptable salts thereof:
R.sup.2.sub.2NCH.sub.2COCH.sub.2CH.sub.2COOR.sup.1(I) wherein R.sup.1 represents a substituted or unsubstituted alkyl group; and R.sup.2 each independently represents a hydrogen atom or a group R.sup.1.

16. The device as claimed in claim 15 wherein the composition comprises a precursor of formula (I) or a pharmaceutically acceptable salt thereof, wherein R.sup.1 is straight chain C.sub.1-C.sub.6 alkyl and both R.sup.2 represent hydrogen.

17. The device as claimed in claim 14 wherein the composition comprises 5-ALA hexyl ester or pharmaceutically acceptable salt thereof.

18. A kit comprising the device as claimed in claim 1 and at least one composition comprising a photosensitizer or precursor of a photosensitizer for use with the device.

19. The kit as claimed in claim 18 wherein the composition comprises 5-ALA or a derivative of 5-ALA or a pharmaceutically acceptable salt thereof.

20. The kit as claimed in claim 19, wherein the composition comprises 5-ALA or a precursor of formula (I) or a pharmaceutically acceptable salt thereof:
R.sup.2.sub.2NCH.sub.2COCH.sub.2CH.sub.2COOR.sup.1(I) wherein R.sup.1 represents a substituted or unsubstituted alkyl group; and R.sup.2 each independently represents a hydrogen atom or a group R.sup.1.

21. The kit as claimed in claim 20 wherein the composition comprises a precursor of formula (I) or a pharmaceutically acceptable salt thereof, wherein R.sup.1 is straight chain C.sub.1-C.sub.6 alkyl and both R.sup.2 represent hydrogen.

22. The kit as claimed in claim 18 wherein the composition comprises 5-ALA hexyl ester or pharmaceutically acceptable salt thereof.

23. The kit as claimed in claim 18 wherein said composition is provided separately from the device.

24. The kit as claimed in claim 18 wherein said device comprises a drug carrying area and said composition is contained in the drug carrying area.

25. A method of manufacturing the irradiation device of claim 1, the method comprising: molding the first housing part from a resilient material and molding the second housing part from a resilient material, the first and second housing parts being separate moldings, inserting the power source through the resilient opening part of the first housing part into the chamber, passing an electrical coupling from the power source to the LED lamp system in said second housing part and joining the first housing part to the second housing part in order to form the housing of the device.

26. The method according to claim 25, wherein the first and second housing part being formed separately from the LED lamp system.

27. A method of photodynamic therapy of the cervix, the method comprising: applying a composition comprising a photosensitizer or precursor to the cervix and using the device as claimed in claim 1 to provide illumination to the cervix.

28. The method as claimed in claim 27, wherein the composition comprises 5-ALA or a derivative of 5-ALA or a pharmaceutically acceptable salt thereof.

29. The method as claimed in claim 28, wherein the composition comprises 5-ALA or a precursor of formula (I) or a pharmaceutically acceptable salt thereof:
R.sup.2.sub.2NCH.sub.2COCH.sub.2CH.sub.2COOR.sup.1(I) wherein R.sup.1 represents a substituted or unsubstituted alkyl group; and R.sup.2 each independently represents a hydrogen atom or a group R.sup.1.

30. The method as claimed in claim 29 wherein the composition comprises a precursor of formula (I) or a pharmaceutically acceptable salt thereof, wherein R.sup.1 is straight chain C.sub.1-C.sub.6 alkyl and both R.sup.2 represent hydrogen.

31. The method as claimed in claim 27 wherein the composition comprises 5-ALA hexyl ester or pharmaceutically acceptable salt thereof.

32. The method as claimed in claim 27 wherein the device comprises a drug carrying area and the composition is applied to the cervix via said drug carrying area.

33. The method as claimed in claim 32, wherein the drug carrying area is the treatment surface.

34. The method as claimed in claim 27 comprising the photodynamic treatment of abnormalities, diseases, lesions or conditions of the cervix.

35. The method as claimed in claim 34 comprising the photodynamic treatment of HPV infections, intraepithelial neoplasia, dysplasia, precancerous lesions and cancer of the cervix.

Description

(1) Certain preferred embodiments of the present invention will now be described, by way of example only, with reference to the accompanying drawings in which:

(2) FIGS. 1 to 4 show a perspective view, side elevation, end elevation and cross-section view of a prior art irradiation device disclosed in WO 2010/078929;

(3) FIG. 5 shows an embodiment of a device with a two-part housing in perspective view

(4) FIG. 6 is a cross-section elevation through the device of FIG. 5

(5) FIGS. 7 and 8 show a first housing part of the device of FIG. 5 in cut-away perspective view;

(6) FIG. 9 shows a second housing part of the device of FIG. 5 in cut-away perspective view;

(7) FIG. 10 is a close up cut-away perspective view of the second housing part with an LED lamp system installed thereon;

(8) FIG. 11 is a perspective view of an alternative preferred embodiment for the second housing part;

(9) FIG. 12 shows the second housing part of FIG. 11 along with the LED lamp system and power source holder, i.e. battery holder; and

(10) FIG. 13 shows a schematic diagram of a control circuit for use in the irradiation device of the preferred embodiments.

(11) FIG. 14a shows the orientation of the LEDs of the LED lamp system of a device according to FIGS. 5-12 during irradiance measurement

(12) FIG. 14b shows the measured irradiance profile of a device according to FIGS. 6 and 12 across a concave treatment surface

(13) The prior art device of FIGS. 1 to 4 is an irradiation device 60 for photodynamic therapy of the cervix. FIGS. 1 to 3 show perspective, side and end views. FIG. 4 is a cross-section along line A-A on FIG. 3. The device 60 is arranged for use in photodynamic treatment of the cervix and has a single part housing 61 including an upper housing portion 61a and a lower cylindrical housing portion 61b extending beneath the upper housing portion. The upper housing portion 61a is flexible and includes an outer portion 67 that is approximately frustoconical in shape and tapers outwards from the front end of the device 60 to the rear. The outer portion 67 is resilient such that, in use, this presses against the walls of the vagina in order to securely hold the device 60 in place. The shape of the upper housing portion 61a and its outer portion 67 can most clearly be seen in FIG. 4.

(14) An LED lamp system 62 is sealed within the upper housing 61a. The power supply for the lamp system is a battery 68 enclosed within the cylindrical housing portion 61b. The battery is a AA size battery with the cylindrical housing portion 61b formed relatively tightly around it. The control circuit 69 is also enclosed with the battery, and advantageously this takes the form of a PCB with a diameter the same as the battery diameter, for efficient use of space.

(15) The front end of the upper housing 61a forms a treatment surface 63, which is a lens of transparent material covering the LEDs of the LED lamp system 62. This material is a transparent silicone which also forms the remainder of the flexible housing of the device 60. An opaque white silicone over-moulding is used to cover the sides of the upper housing portion 61a, both about the outer portion 67 and also on the sides within the outer portion 67, and to completely cover the cylindrical portion 61b. This white over-moulding acts as a reflector for the lens of the treatment surface, and hides internal parts in the cylindrical portion, which would include the battery 68 and control circuit 69.

(16) The treatment surface 63 is shaped so as to cover, in use, the opening of the cervix, thus ensuring that the illumination from the LEDs is directed on to the treatment area. Treatment surface 63 comprises a contact surface 63a, which typically has a diameter of 22 to 30 mm. The contact surface 63a acts as a drug delivery system, i.e. drug carrying area or reservoir, and hence carries a composition comprising a photosensitiser or a precursor.

(17) At the base of the cylindrical housing portion 61b a loop 64 is provided to facilitate insertion and removal of the device. A string can be attached to the loop 64, if required.

(18) A preferred embodiment of the invention is shown in FIGS. 5 to 11. This example is for photodynamic treatment of the cervix. FIG. 5 shows the outer features of the moulded housing, which is made up of a first housing part 2 and a second housing part 4. The two housing parts are moulded from a resilient material, for example a medical grade silicone material. The first housing part 2 consists of a chamber 6 for holding a power source and an opening part 8 enabling access to the chamber 6 and for joining to the second housing part 4. The chamber 6 is generally cylindrical in this embodiment, reflecting the shape of the power source that it encases. The opening part 8 has two main parts, being a neck part 10 at the end of the chamber 6 and a coupling part 12 extending away from the neck part 10.

(19) The second housing part 4 has a flexible outer portion 14 that, when moulded, forms a hollow frustoconical shape extending away from the first housing part 2 tapering outwardly away from the front of the device. When the device is in use the flexible outer portion 14 is folded back over the coupling part 12 of the first housing part 2 and hence forms a hollow frustoconical shape that tapers in the opposite direction, which would hence be tapering outwardly to the rear when the device is in use. In this context the rearward direction is the direction away from the cervix, out of the body, and the front of the device is the end of the device that faces toward the cervix with the forward direction in this embodiment hence being the direction in which light is emitted. It will be understood that the basic shape of the flexible outer portion 14 of the device of FIGS. 5 to 10, when in use, will be similar to the basic shape of the flexible outer portion 67 of the prior art device shown in FIGS. 1 to 4. Circumferential ribs 16 provide strength for the flexible outer portion 14 and also aid in the folding movement of the flexible outer portion 14 as it changes from the as-moulded shape (shown in FIG. 5) to the rearward tapering shape required for securing the device in the body.

(20) Further detail of the device can be seen in the cross-section of FIG. 6. The first housing part 2 encloses a power source 41 in the form of a AA sized lithium ion battery in the chamber 6. The battery 41 is held in an appropriate cradle 20, which also incorporates the required electrical connections for the battery 41. The chamber 6 is has a shape and size that is complementary to the shape and size of the battery 41 and cradle 20 and hence holds them tightly. In some embodiments the cradle may comprise a reed switch and an element such as a pin and the chamber 6 may comprise a notch (not shown). The notch will receive the pin and thus prevent a rotation of the cradle, i.e. rotation of the reed switch. This embodiment is preferred if the packaging of the device includes a magnet and where it needs to be ensured that the reed switch is held open while the device is inside the packaging. In some embodiments the chamber 6 may be moulded with a shape and size slightly smaller than the shape and size of the battery 41 and cradle 20 so that it is stretched around them via the resilience of the material of the first housing part 2. The battery 41 is electrically coupled to an LED lamp system 22 that is held on the second housing part 4. The LED lamp system 22 consists of LEDs 45 and a control circuit (described below with reference to FIG. 11) moulded on a circuit board 24.

(21) The electrical coupling for the LED lamp system 22 passes through the neck part 10, the details of which can be more clearly seen with reference to FIGS. 7 and 8. The neck part 10 has inner shoulders formed across the opening of the chamber 6 and outer shoulders across the width of the coupling part 12. The shoulders form a slot shaped hole 26, which is shown in transverse cross-section in FIG. 6. FIGS. 7 and 8 show one half of the slot shaped hole 26 with the first housing part 2 shown empty, omitting the battery 41 and cradle 20. The battery 41 and cradle 20 are inserted by deforming the resilient material of the first housing part 2 to stretch open the slot 26. When the battery 41 and cradle 20 are fully within the chamber 6 then the neck part 10 is allowed to return to its normal shape and the shoulders either side of the slot 26 hence hold the battery 41 and cradle 20 in place. It will be noted that the shape of the neck 10 also allows for the chamber 6 to bend along the line of the slot 26 so that it can move easily relative to the coupling part 12 and hence relative to the second housing part 4. This means that the device can deform whilst it is in use, making it more comfortable for the patient. FIGS. 7 and 8 also show the shape and form of the coupling part 12 effectively. In this example, since the device has a generally circular geometry for the second housing part 4, the coupling part 12 has a circular tube shaped section for joining to the second housing part 4. This circular tube section is attached to the outer shoulders of the neck part 10 by an asymmetric flange arrangement. The purpose of this is to make an angle between a central axis of the second housing part 4 and a central axis of the chamber 6 and battery 41 so that the device fits more comfortably within the body when in place for treatment of the cervix. Preferably, the first housing part 2 is moulded from a resilient material, preferably silicone. In a further preferred embodiment, the first housing part 2 is moulded from opaque silicone, i.e. the coupling part which will enclose the opening part 8 of the second housing part 4, once both housing parts 2 and 4 are joined together, is opaque to the light emitted by the LED lamp system 22, when the device is in use. In that way it is ensured that light emitted by the LED lamp system 22 only is emitted through the treatment surface 36 onto the cervix but not sideways onto the walls of the vagina.

(22) FIG. 9 shows the second housing part 4 which consists of the flexible outer portion 14 described above and a body and lens section 28. The first housing part 2 connects to the second housing part 4 via the coupling part 12 of the first housing part 2 and a corresponding coupling part 30 on the second housing part 4. In this example embodiment the coupling part 30 on the second housing part 4 is formed by the outer surface of the body and lens section 28, which has a cylindrical exterior. The two housing parts 2, 4 are joined by fitting the coupling part 12 of the first housing part 2 about the coupling part 30 on the second housing part 4. The resilient material of the coupling part 12 of the first housing part 2 can be stretched around the coupling part 30 on the second housing part 4 and will hence seal the device and securely hold the two housing parts 2, 4 together. The resilient fitting of the two coupling parts 12, 30 and the friction therebetween can be sufficient to keep the two housing parts 2, 4 together during use and form a fluid-tight seal. Optionally, however, a sealing and joining media such as an adhesive can be applied to ensure that the two housing parts 2, 4 cannot be separated during use of the device.

(23) When in use the chamber 6 can be gripped to hold and manoeuvre the device and in addition a hole 32 though the rearward end of the chamber 6 allows for a cord to be attached to make it easier to remove the device from the body. Since the device will be pulled by the cord it is important to ensure that the first and second housing parts 2, 4 are securely attached together. When the device is removed in this way the flexible outer portion 14 of the second housing part 4 may unfold from its rearward tapering position to resume its as-moulded position. This would mean that the taper now faces forward, into the body cavity, resulting in a more comfortable and easier removal of the device.

(24) FIGS. 9 and 10 illustrate the second housing part 4 and LED lamp system 22 in more detail in a perspective section view of the moulded housing part 4 alone and in a close up perspective section view of the body and lens section 28 with the LED lamp system 22 installed. The skirt-like flexible outer portion 14 has been described above. The body and lens section 28 has a cylindrical outer part forming the coupling part 30 and surrounding a solid lens 34, which is made of the resilient material. Since the resilient material used to mould the second housing part 4 is used to form the lens 34 then it should be at least partially transparent, as discussed above. The lens 34 has an outer treatment surface 36, which faces forward in use and is for placement against the cervix. Behind the lens 34 there are cavities 38 formed for holding elements of the LED lamp system 22. In this example the cavities 38 consist of six outer segments arranged symmetrically about an inner circular cavity. Each cavity can hold an LED 45 or LEDs 45 of the LED lamp system 22, which is mounted on a board 24 with a circular construction as seen in FIG. 10. The LEDs 45 hence direct light forward through the lens 34 and out via the treatment surface 36. Other components of the LED lamp system 22 are mounted on the rear face of the board 24. A lip 39 surrounds the rearward part of the lens and body section 28. This lip 39 is used to grip the outer circumference of the board 24 of the LED lamp system 22 and hence holds the LED lamp system 22 securely in position.

(25) An alternative preferred form for the second housing part 4 is illustrated in FIGS. 11 and 12. FIG. 11 shows the second housing part 4 in a perspective view and FIG. 12 shows a similar view with the LED lamp system 22 fitted to the second housing part 4 and the cradle 20 attached to the LED lamp system 22. The features of this second housing part 4 are generally similar to the features described above with reference to FIGS. 9 and 10. It will however been seen that there is a significant change in relation to the arrangement of the cavities 38 that receive and hold elements of the LED lamp system 22. In this alternative form the cavities 38 are arranged to fit more closely to the LEDs 45 of the LED lamp system 22. This has advantages in preventing movement of the LED lamp system 22 when it is fitted to the second housing part 4 and also the closer fit of the LEDs 45 to the material of the housing part 4 can improve transmission of light to the treatment area on a patient as well as more effectively dissipating heat from the LEDs 45.

(26) FIG. 12 shows the cradle 20 in the position that it would take when encased by the first housing part 2. The wires that connect the cradle 20 to the LED lamp system 22 would pass through the opening 26 in the first housing part 2 as described above.

(27) During manufacture, the two housing parts 2, 4 are moulded of a silicone material. The battery 41 and cradle 20 is inserted into the chamber 6 as described above. The LED lamp system 22 is manufactured separately and is snap-fit into the second housing part 4, secured by the lip 39. The cavities 38 ensure that the LEDs 45 are consistently placed during manufacture. The battery 41 can then be electrically connected to the LED lamp system 22 and the two housing parts 2, 4 joined via the coupling parts. Any excess length in the wire or other electrical couplings used for the electrical connection can be coiled in the cavity at the rear of the LED lamp system 22.

(28) A control circuit suitable for use in any of the preferred embodiments of the irradiation device is shown in FIG. 13. This control circuit 40 takes power from one or more lithium batteries 41 that are used to power the LEDs 45. The control circuit 40 comprises a microprocessor 42, which controls the operation of the LEDs 45.

(29) For example, the microprocessor 42 can comprise a timer and a memory into which can be programmed a dosage regime. The LEDs 45 can therefore be operated to illuminate the treatment area for a predetermined length of time and can be arranged to operate continuously or provide pulsed illumination. In addition the control circuit 40 comprises a light sensor 43. This forms a feedback circuit which enables the microprocessor 42 to adjust the operation of the LEDs 45 to ensure that any abnormalities or malfunction of the control circuit 40 do not affect the light dose received by the patient.

(30) Prior to the insertion of the device, a switch 46 is closed to begin operation of the control circuit 40. This may, for example, initiate timing of a delay period, after which the microprocessor 42 will begin operation of the LEDs 45 in accordance with the programmed treatment regime. After a predetermined time, or upon completion of delivery of a certain light dose (determined by light sensor 43) the microprocessor 42 will switch off the LEDs 45. The device can then be removed.

(31) In modified embodiments the control circuit also comprises two operation indicator lights (not shown). These may comprise two LEDs, one of which is illuminated if the device has operated correctly and a second LED which is illuminated if any malfunction has occurred; combinations of lights may indicate specific faults. Alternatively only a single operation indicator light may be provided, which is illuminated upon completion of correct operation of the device and which remains unlit if any malfunction has occurred. The control circuit may incorporate an alarm device for providing an audible signal, and/or a vibration device for providing a signal by vibration.

(32) This system alerts the patient and the medical practitioner if any malfunction has occurred which has prevented the patient from receiving the correct light dose. Signals from the control circuit can also indicate that the treatment has been completed successfully.

(33) As discussed above, with a device intended for treatment of the cervix it is advantageous to provide different sizes since it allows effective treatment for patients with different histories of pregnancy. These different sizes can be realised by adjusting the size of the second housing part 4 and in particular the treatment surface 36 and the flexible skirt 14, as these portions act to secure the device within the vagina with the treatment surface placed against the cervix. The first housing part 2, which houses the power source 41, can then be manufactured in a single size, enabling a standardised arrangement to be used for the power source 41 and cradle 20. The cavities 38 and lip 39 can also be standardised in size allowing a single LED lamp system 22 to be fitted to second housing parts 4 that vary in the size of the treatment surface 36 and flexible outer portion 14.

(34) However, it may be advantageous to vary the size of some elements of the first housing part 2, in particular the width of the slot 28 formed in the neck 10. The size of this part can be varied without changing the size of the chamber 6.

(35) The composition comprising a photosensitiser or precursor for the photodynamic therapy can be applied to the patient prior to insertion of the device, either directly to the treatment area, or systematically, e.g. by intravenously or orally administered compositions. Preferably, the composition is applied to the treatment surface 36 so that the composition is applied to the patient during insertion of the device. With embodiments using a concave treatment surface, the composition may be placed within the concave area providing a reservoir of the composition as discussed above. Alternatively, the material of the device may be selected so that the composition will adhere to the treatment surface sufficiently for transfer to the patient and the composition can then be simply applied on the treatment surface.

(36) Photodynamic Treatment of HPV Infections and Intraepithelial Neoplasia of the Cervix:

(37) A composition comprising 5% by weight of the hydrochloride salt of ALA n-hexyl ester (hexaminolevulinate hydrochloride), a precursor of a photosensitiser, was prepared according to example 1 of WO 2010/142457. A device according to FIGS. 5-12 was used as a light source for the photodynamic treatment and was provided in a sealed plastic wrapping. The device contained LEDs which emit, when the device is in use, light at a wavelength of about 629 nm at a mean irradiance of about 7-8 mW/cm.sup.2. A gynaecologist checked the operational status of the device followed by appropriate cleaning using disinfectant (e.g. alcohol). After cleaning the device, the gynaecologist applied 2 g of the composition onto the drug carrying area on the device. The composition was spread evenly over the surface of the drug carrying area using a spatula. Finally the gynaecologist inserted the device containing the composition into the vagina of a patient suffering from HPV infections and/or intraepithelial neoplasia of the cervix and positioned it correctly on the cervix. After insertion, the patients were allowed to leave the hospital at their convenience. The device delivered a total dose of about 125 J/cm.sup.2 continuously for 4.6 hours after an initial delay of 5 hours, i.e. a total treatment time of 9.6 hours. The patients were told to not removed the device earlier than 10 hours after cervical administration, but within 24 hours (a cord was attached to the device to ensure easy removal) and to discard the removed device.

(38) Determination of Irradiance

(39) Irradiances from 7 LEDs 45 comprised in a LED lamp system 22 in devices according to FIGS. 5-12 were measured across the surface of the concave treatment surface 36 using an optical probe that was moved across the full area of treatment surface (50). Irradiance was measured with the LED array in two orientations. The across profile corresponds to the measurement between the LEDs as shown in the schematic diagram on the left hand side of FIG. 14a while the in line profile is shown on the right hand side.

(40) The measured irradiance profiles for device 1 are shown in FIG. 14b: the y-axis shows the irradiance measured in mW/cm.sup.2 while the x-axis shows the angles in degrees. The diamond dotted line represents the measurements done with the across profile while the square dotted line represents the measurements done with the in line profile.

(41) A summary of the maximum and minimum measurements for both profiles and calculation of the mean irradiance for each of the seven devices which were measured is shown below in Table 1.

(42) TABLE-US-00001 TABLE 1 Max Min Max Min irradiance irradiance irradiance irradiance in line in line across across Mean Device profile profile profile profile irradiance no. (mW/cm.sup.2) (mW/cm.sup.2) (mW/cm.sup.2) (mW/cm.sup.2) (mW/cm.sup.2) 1 9.52 5.36 9.62 5.93 7.61 2 10.29 5.51 10.20 5.4 7.85 3 9.43 5.01 9.29 5.08 7.20 4 9.61 5.21 9.56 5.10 7.37 5 9.25 5.04 9.80 5.15 7.31 6 10.37 5.20 10.44 5.18 7.80 7 9.58 5.40 9.92 5.25 7.54

(43) As will be appreciated, the device of the present invention provides a convenient way for photodynamic therapy to be carried out in any orifice of the human or animal body over long time periods and at low mean irradiance. This increases the convenience to the patient and may also increase the efficacy of the treatment.

(44) The embodiments described above are for illustration only and should not be taken to limit the scope of protection. The skilled man will appreciate that adjustments could be made to these embodiments without deviating from the scope of the claims.

(45) For example, the housing may be any shape which allows full and secure insertion into the orifice and the exact shape of this housing will depend on whether the device is intended for use on a human or animal subject and on the orifice where the treatment is to occur. In addition other forms of control circuit and LED lamp systems with other arrays of LEDs can be used within the invention. Also, although the preferred embodiment relates to a device for vaginal use and in particular for photodynamic treatment of diseases, lesions and conditions of the cervix, e.g. HPV infections and/or intraepithelial neoplasia, it will be understood that the same principles can be applied in the structure and manufacture of devices for other conditions and for use in other orifices, for example anal or oral devices.

(46) Certain embodiments are as defined in the following numbered clauses:

(47) 1. An irradiation device for insertion into an orifice of the body to provide photodynamic therapy, the device comprising: a housing moulded from a resilient material and adapted to be fully inserted and secured in the orifice, the housing enclosing an LED lamp system and a power source for powering the LED lamp system; wherein the device is independently operational while located in the orifice;

(48) characterised in that: the housing comprises a first housing part for holding the power source and a second housing part for holding the LED lamp system, the first and second housing parts being separable and preferably being formed separately from the LED lamp system; and in that the first housing part consists of a chamber for holding the power source and an opening into the chamber is provided through a resilient opening part, wherein the chamber is closed when the first housing part is joined to the second housing part.

(49) 2. A device as defined in clause 1, wherein the resilient opening part allows for an electrical coupling to pass from the power source to the LED lamp system.

(50) 3. A device as defined in clause 1 or 2, wherein the resilient opening part can be deformed to insert and/or remove the power source into or from the first housing part.

(51) 4. A device as defined in clause 1 or 2, comprising a battery cap to provide an opening into the first housing part

(52) 5. A device as defined in clause 1, 2 or 3, wherein the resilient opening part comprises a neck part for holding the power source within the chamber.

(53) 6. A device as defined in clause 5, wherein the neck part is a resilient narrowing of the entrance to the chamber to a size less than the width of the power source to thereby hold the power source within the chamber.

(54) 7. A device as defined in any preceding clause, wherein the resilient material of the chamber is sized to fit tightly around the power source.

(55) 8. A device as defined in any preceding clause, wherein the power source and LED lamp system are arranged to permit the power source to be electrically connected to the LED lamp system whilst the first and second parts of the housing are separated from one another.

(56) 9. A device as defined in any preceding clause, wherein the power source is sealed within the housing such that the housing is fluid tight in use.

(57) 10. A device as defined in clause 9, wherein a sealing media is used at the joint between the first and second housing parts.

(58) 11. A device as defined in any preceding clause, wherein the resilient opening part has a coupling part arranged to join to and form a seal with a complementary shaped coupling part on the second housing part.

(59) 12. A device as defined in clause 11, wherein one of the two coupling parts is arranged to be stretched to place it around the other of the two coupling parts, thereby using the elasticity of the resilient material to hold the two housing parts together.

(60) 13. A device as defined in any preceding clause, wherein a part or all of the resilient material is at least partially transparent to light emitted from the LED lamp system, when the device is in use.

(61) 14. A device as defined in any preceding clause, wherein the second housing part to be moulded of a material that is at least partially transparent to light emitted from the LED lamp system when the device is in use, said light exits via a treatment surface on the second housing part and illuminates a treatment area on the patient and wherein the treatment surface has a size and/or shape adapted for complementary fit with said treatment area.

(62) 15. A device as defined in any preceding clause, wherein the second housing part has one or more moulded cavity to fit elements of the LED lamp system.

(63) 16. A device as defined in clause 15, wherein the one or more moulded cavity is enclosed by a fastening lip for securing elements of the LED lamp system within the cavity.

(64) 17. A device as defined in any preceding clause, wherein the device is adapted to be fully inserted and secured in the orifice and does not require connection to an external power supply or light source during operation.

(65) 18. A device as defined in any preceding clause, wherein, in use, the device provides light with a mean irradiance below 50 mW/cm.sup.2.

(66) 19. A device as defined in any preceding clause, wherein the housing comprises a flexible outer portion that can adjust its shape to form a secure fit with the orifice

(67) 20. A device as defined in any preceding clause, wherein the flexible outer portion forms a continuous surface which tapers outwards towards the rear end of the device.

(68) 21. A device as defined in any preceding clause, further comprising a drug carrying area for carrying a composition comprising a photosensitizer or precursor of a photosensitizer.

(69) 22. A device as defined in clause 21 wherein the drug carrying area is the treatment surface.

(70) 23. A device as defined in clause 21 or 22 wherein the composition comprises a precursor which is 5-ALA, a derivative of 5-ALA or a pharmaceutically acceptable salt thereof, preferably 5-ALA or a precursor of formula (I) and pharmaceutically acceptable salts thereof:
R.sup.2.sub.2NCH.sub.2COCH.sub.2CH.sub.2COOR.sup.1(I) wherein R.sup.1 represents a substituted or unsubstituted alkyl group; and R.sup.2 each independently represents a hydrogen atom or a group R.sup.1.

(71) 24. A device as defined in clause 24 wherein the composition comprises a precursor of formula (I) and pharmaceutically acceptable salts thereof, wherein R.sup.1 is straight chain C.sub.1-C.sub.6 alkyl and both R.sup.2 represent hydrogen.

(72) 25. A device as defined in clause 24 wherein the composition comprises 5-ALA hexyl ester or pharmaceutically acceptable salts thereof.

(73) 26. A kit comprising a device as defined in any of clauses 1 to 22 and at least one composition comprising a photosensitiser or precursor of a photosensitiser for use with the device.

(74) 27. A kit as defined in clause 26 wherein the composition comprises 5-ALA or a derivative of 5-ALA or a pharmaceutically acceptable salt thereof, preferably 5-ALA or a precursor of formula (I) and pharmaceutically acceptable salts thereof:
R.sup.2.sub.2NCH.sub.2COCH.sub.2CH.sub.2COOR.sup.1(I) wherein R.sup.1 represents a substituted or unsubstituted alkyl group; and R.sup.2 each independently represents a hydrogen atom or a group R.sup.1.

(75) 28. A kit as defined in clause 27 wherein the composition comprises a precursor of formula (I) and pharmaceutically acceptable salts thereof, wherein R.sup.1 is straight chain C.sub.1-C.sub.6 alkyl and both R.sup.2 represent hydrogen.

(76) 29. A kit as defined in clause 28 wherein the composition comprises 5-ALA hexyl ester or pharmaceutically acceptable salts thereof.

(77) 30. A kit as defined in any preceding clause wherein said composition is provided separately from the device.

(78) 31. A kit as defined in any of clauses 26 to 29 wherein said composition is contained in the drug carrying area of the device.

(79) 32. A device or kit as defined in any preceding clause for use in photodynamic therapy, preferably the photodynamic therapy of abnormalities, diseases, lesions or conditions of the female reproductive system, preferably the vagina or the cervix.

(80) 33. A device or kit as defined in clause 32 for use in the photodynamic therapy of HPV infections, intraepithelial neoplasia, dysplasia, precancerous lesions and cancer of the female reproductive system, preferably the vagina and cervix.

(81) 34. A method of manufacturing an irradiation device for insertion into an orifice of the body to provide photodynamic therapy, the device comprising: a housing adapted to be fully inserted and secured in the orifice, the housing enclosing an LED lamp system and a power source for powering the LED lamp system; wherein the device is independently operational while located in the orifice; the method comprising: moulding a first housing part from a resilient material and moulding a second housing part from a resilient material, wherein the first housing part consists of a chamber for holding the power source and an opening into the chamber is provided through a resilient opening part, and the second housing part is for holding the LED lamp system, the first and second housing parts being separate mouldings and preferably being formed separately from the LED lamp system; and the method further comprising: closing the chamber by joining the first housing part to the second housing part in order to form the housing of the device.

(82) 35. A method of manufacturing as defined in clause 34 comprising providing features of the device or kit as defined in any of clauses 1 to 33.

(83) 36. A method of photodynamic therapy of a treatment area within an orifice of the body, the method comprising: applying a composition comprising a photosensitiser or precursor to the treatment area and using the device as defined in any of clauses 1 to 25 to provide illumination to treat the treatment area.

(84) 37. A method as defined in clause 36, comprising the photodynamic treatment of abnormalities, diseases, lesions or conditions of the female reproductive system, preferably the vagina and cervix.

(85) 38. A method as defined in clause 36 or 37, comprising the photodynamic treatment of HPV infections, intraepithelial neoplasia, dysplasia, precancerous lesions and cancer of the female reproductive system, preferably the vagina and cervix.