IRRADIATION DEVICE

Abstract: The invention relates to an irradiation device for treating skin changes, especially skin tumours, said device comprising a radiation unit for radiation of a phototoxic substance accumulated in the skin changes, a cytotoxic effect arising in radiation of the phototoxic substance. The selected phototoxic substance forms new substances, so-called photoproducts, in radiation from the radiation unit, and the radiation unit is adapted to generate broad spectrum radiation in a selected wavelength range, in which a relatively high photoabsorption in the phototoxic substance and a relatively low photoabsorption in the photoproducts are obtained. The invention also relates to a method for radiation of a phototoxic substance and a method of determining a suitable wavelength range for treating a skin change.

Description: IRRADIATION DEVICE Field of the Invention The present invention relates to a device for treating skin changes, especially skin tumours, said device comprising a radiation unit for radiation of a phototoxic substance accumulated in the skin changes, a cytotoxic effect arising in radiation of the phototoxic substance. The invention also relates to a method for radiation of a phototoxic substance, and a method of determining a suitable wavelength range for treating skin changes. Background Art Applying a compound or composition containing delta- aminolevulinic acid (ALA) to a skin area in which skin changes are suspected is already known. After application, the ALA substance is allowed to act on the skin for e.g. 1-24 h, and in the meantime protoporphyrin IX is formed in the skin area. Protoporphyrin IX is formed or accumulated in a larger amount in the parts of the area which contain a skin change, compared with other skin portions. Protoporphyrin IX is a substance with several useful properties. First, the substance fluoresces, which can be used to detect skin changes (see Swedish patent application No. 9603095-2) . Second, protoporphyrin IX has a phototoxic effect in long-term radiation of the substance. This can be used to cause cell death in the skin area containing protoporphyrin IX and, thus, remove the skin change . The phototoxic effect is currently used for treating skin tumours. The skin area in question is then usually radiated with a broad spectrum lamp which covers the entire red band of the visible spectrum, with wavelengths of 570-680 nm, a phototoxic reaction occurring in the protoporphyrin IX which has accumulated in the tumour, thus killing the cancer cells. A disadvantage of this technique, however, is that the treatment causes pain in the patient. Especially in radiation of extensive skin areas, such as about 100 cm 2 , and skin areas with sensi- tive skin, this pain is difficult to endure, and therefore the treatment must in many cases be interrupted. Examples of diseases where this pain is a heavy problem is facial actinic keratosis and vulval dysplasia. Another prior art technique of using the phototoxic effect for treatment is to use a laser instead of a broad spectrum lamp. The wavelength of the light emitted by the laser is selected in the vicinity of a light absorption peak of protoporphyrin IX, usually about 630 nm. However, it is difficult to use a device containing a laser, espe- cially in the case of extensive skin areas. For treatment of a large skin area, the laser must be successively moved back and forth over the surface, which causes a risk that part of the area will not be radiated and, thus, a risk of insufficient treatment. Moreover, such a treatment takes a long time and requires great accuracy. A further disadvantage is the relatively high cost of a laser. The object of the present invention is to provide a device which does not have the above disadvantages, i.e. with which extensive skin areas can be quickly and easily treated while the patient's experience of pain is kept relatively low. Summary of the Invention This object is achieved by a device as described by way of introduction, in which the selected phototoxic substance forms new substances, so-called photoproducts, in radiation from the radiation unit, and the radiation unit is adapted to generate broad spectrum radiation in a selected wavelength range, in which a relatively high photoabsorption in the phototoxic substance and a rela- tively low photoabsorption in the photoproducts are obtained. By using a device according to the invention, it has been found that the patient's experience of pain decreases to a considerable extent compared with treatment using a broad spectrum lamp. This is due to the fact that the experience of pain largely depends on accumulation of heat in the patient's skin, which in turn is caused by high photoabsorption. In radiation of a photo- reactive substance, it frequently decomposes into photoproducts having an absorption spectrum which is different from the absorption spectrum of the photo-reactive substance. By avoiding those parts of the spectrum where the photoproducts have high absorption, the total photoabsorption and, consequently, the pain are reduced. At the same time a high absorption in the phototoxic substance is maintained, which yields a phototoxic cytotoxic effect, which can be compared with that obtained in the previously known radiations with broad spectrum lamps. The radiation spectrum that is generated by the inventive device is still to be considered a broadband spectrum and can therefore easily be used to treat a large skin area, in contrast to the previously mentioned laser method. The radiation unit in the device according to the invention can suitably be obtained with the aid of a broad spectrum radiation source, which is fitted with a suitable filtering device to obtain the desired wavelength range. The phototoxic substance can advantageously be a substance of the type which has the property that it is formed or accumulated selectively in skin changes. Advantageously the device can be adapted to a phototoxic substance of the type which is formed in skin when applying a substance which contains a compound or composition containing deltaaminolevulinic acid (ALA) . The phototoxic substance can preferably be protoporphyrin IX. Under these circumstances, the wavelength spectrum from the radiation unit suitably lacks essentially radiation with wavelengths outside the range 600-655 nm and in particular 610-645 nm. A wavelength spectrum is particularly preferred, which essentially lacks radiation with wavelengths outside the range 610-635 nm. The peaks in the absorption spectrum of protoporphyrin IX which are positioned in the short-wave part of the spectrum generally have too low penetration capacity in skin, and therefore cannot be used for the purpose of completely removing skin changes. The invention also relates to a method as mentioned by way of introduction, in which the phototoxic substance is radiated with a wavelength range in which a relatively high photoabsorption in the phototoxic substance and a relatively low photoabsorption in the photoproducts are obtained. Furthermore, the invention relates to a method of determining a suitable wavelength range for treating a skin change. The method comprises an examination of the photoabsorption for a selected phototoxic substance and its photoproducts. The range is selected, in which a relatively high photoabsorption in the phototoxic substance and a relatively low photoabsorption in the photoproducts are obtained. The range can advantageously be refined by excluding wavelengths whose penetration capac- ity in skin is insufficient for complete treatment of the skin tumour. The examination of the absorption capacities can advantageously occur in solution or suspension of the substances, which allows a simple examination method in laboratory environment . According to the invention, a device is thus provided, which makes it possible to treat a relatively extensive skin area, quickly and easily and without intolerable pain being experienced by the patient. According to a second aspect of the invention, a method is provided for radiation of a photoreactive substance, and according to a third aspect, a method of determining a suitable wavelength range for treating skin changes by means of phototoxic substances. Brief Description of the Accompanying Drawings Fig. 1 is a principle sketch of an embodiment of a device according to the invention. Fig. 2 shows the absorption spectrum of protoporphyrin IX and its photoproducts. Fig. 3 shows the integrated absorption of protopor- phyrin IX and its photoproducts between 600 and 700 nm, and the ratio of these two absorption curves. Description of Preferred Embodiments Fig. 1 is a principle sketch of the device according to the invention. A radiation unit 1 is shown, which radiates a skin area 2. A broad spectrum lamp 3 emitting light, preferably in the red band of the visible spectrum, is arranged in a casing 4 which is formed with an opening 5 for emitted light. The casing 4 is articulated to an arm 6, which in turn is articulated, for easy shifting and setting of the unit 1 relative to the skin area 2 of the patient. Behind the lamp 3, reflectors 7 are arranged in the casing 4 to catch and direct all light towards the opening 5. In the opening 5, a filter unit 8 is arranged, which filters the light emitted by the lamp 3. Fig. 2 shows the photoabsorption of protoporphyrin IX (full line) and its photoproducts (dashed line) . It can here be seen that the photoabsorption of the photo- products is low at wavelengths in the range 600-655 nm. In this range, there is also a photoabsorption peak of protoporphyrin IX in the range 610-645 nm. This justifies the choice of a broad spectrum lamp which together with a filter produces a radiation spectrum which essentially lacks radiation outside the wavelength range 600-655 nm and especially outside the wavelength range 610-645 nm. Fig. 3 shows the integrated absorption (arbitrary unit) of protoporphyrin IX and its photoproducts between 600 and 700 nm, and the ratio of these two absorption curves. The Figure shows that the absorption of protopor- phyrin IX does not increase very much for wavelengths above 635 nm. However, a considerable increase in the absorption for wavelengths above 635 nm occurs in the photoproducts. The ratio of these absorption curves clearly indicates that a maximum in relative integrated absorption is obtained at 635 nm. To prevent pain in treatment, the radiation spectrum should thus essentially lack radiation outside the wavelength range 610-635 nm. In experiments with treatment of some ten patients by means of the inventive device, it has been found that none of the patients interrupted the treatment in advance because of pain. In these experiments, the device was allowed to radiate a large skin area, and the treatment time was the same as for a broadband lamp according to prior art technique. A conceivable explanation of the pain when using prior art technique is that protoporphyrin IX decomposes into other substances, so-called photoproducts, under the action of light. The new substances have, in turn, absorption peaks which are positioned at other wave- lengths than that of protoporphyrin IX, but within the wavelength ranges that are used in prior art devices. As the treatment proceeds, more and more energy is thus absorbed, and the pain becomes more and more intense. Such a decomposition has also been observed in labo- ratory experiments where protoporphyrin IX is in suspension in a cuvette, which is radiated. The absorption spectrum of the sample in the cuvette has, after radiation corresponding to a normal treatment dose, changed radically (see Fig. 2) . A definite confirmation that the same reaction occurs in skin is difficult to obtain owing to the complex composition of skin. It may still be established by experiments that an irradiation device with an emission spectrum adapted to maximal radiation of the absorption peak in the photo-reactive substance and minimal radiation of the absorption peak in the photoproducts results in less pain being experienced, with maintained toxicity of the sick cells. A plurality of other embodiments of the invention are conceivable. Optionally, other phototoxic substances can be used, which require radiation spectra that are es- pecially adapted thereto. The radiation unit can be designed in a manner other than that described, with a broadband lamp and an adapted filter. For instance, a lamp can be constructed which, unfiltered, emits the desired spectrum. The method can be used, inter alia, for studies of phototoxic substances in laboratories or on tissue samples in vitro. The method of determining a suitable wavelength range for treatment of skin changes by means of a phototoxic substance can also be used for other photoreactive substances than those stated in the description.

Claims: CLAIMS 1. An irradiation device for treating skin changes, especially skin tumours, said device comprising a radiation unit (1) for radiation of a phototoxic substance accumulated in the skin changes, a cytotoxic effect arising in radiation of the phototoxic substance, c h a r a c - t e r i s e d in that the selected phototoxic substance forms new substances, so-called photoproducts, in radiation from the radiation unit (1) , and that the radiation unit (1) is adapted to generate broad spectrum radiation in essentially only a selected wavelength range, in which a relatively high photoabsorption in the phototoxic sub- stance and a relatively low photoabsorption in the photoproducts are obtained. 2. An irradiation device as claimed in claim 1, c h a r a c t e r i s e d in that the radiation unit (1) comprises a broad spectrum radiation source (3) which is fitted with a suitable filtering device (8) for producing the selected wavelength range. 3. An irradiation device as claimed in claim 1 or 2 , c h a r a c t e r i s e d in that the device (1) is adapted to interact with a phototoxic substance of the type which in turn has been formed selectively in skin changes from a substance applied to the skin. 4. An irradiation device as claimed in any one of claims 1-3, c h a r a c t e r i s e d in that the device is adapted to interact with the phototoxic substance pro- toporphyrin IX. 5. An irradiation device as claimed in claim 3 or 4 , c h a r a c t e r i s e d in that the device is adapted to interact with a phototoxic substance of the type which is formed in skin when applying a substance which con- tains a compound or composition containing deltaamino- levulinic acid (ALA) . 6. An irradiation device as claimed in any one of claims 1-5, c h a r a c t e r i s e d in that the selected wavelength spectrum from the radiation unit (1) essentially lacks radiation with wavelengths outside the range 600-655 nm, and especially outside the range 610- 645 nm. 7. An irradiation device as claimed in any one of claims 1-6, c h a r a c t e r i s e d in that the wavelength spectrum from the radiation unit (1) comprises an intensity peak in the wavelength range 610-645 nm. 8. An irradiation device as claimed in any one of claims 1-7, c h a r a c t e r i s e d in that the selected wavelength spectrum from the radiation unit (1) essentially lacks radiation with wavelengths outside the range 610-635 nm. 9. A method for radiation of a phototoxic substance, the radiation causing the substance to have a cytotoxic effect, c h a r a c t e r i s e d in that the phototoxic substance forms new substances, so-called photoproducts, in radiation, and that the radiation comprises essentially only a selected wavelength range, in which a relatively high photoabsorption in the phototoxic substance and a relatively low photoabsorption in the photoproducts are obtained. 10. A method for radiation of a phototoxic substance as claimed in claim 9, c h a r a c t e r i s e d in that the selected wavelength range is provided by a radiation unit comprising a broad spectrum radiation source fitted with suitable filtration. 11. A method as claimed in claim 9 or 10, c h a r a c t e r i s e d in that the phototoxic substance is formed selectively in skin changes of a patient. 12. A method as claimed in any one of claims 9-11, c h a r a c t e r i s e d in that the selected phototoxic substance is protoporphyrin IX. 13. A method as claimed in claim 11 or 12, c h a r a c t e r i s e d in that the substance applied to the skin and included in the forming of the phototoxic substance is a compound or composition containing deltaamino- levulinic acid (ALA) . 14. A method as claimed in any one of claims 9-13, c h a r a c t e r i s e d in that the selected wavelength spectrum essentially comprises radiation with wavelengths in the range 600-655 nm. 15. A method as claimed in any one of claims 9-14, c h a r a c t e r i s e d in that the selected wavelength spectrum comprises an intensity peak in the range 610- 645 nm. 16. A method as claimed in any one of claims 9-15, c h a r a c t e r i s e d in that the selected wavelength spectrum essentially comprises radiation with wavelengths in the range 610-635 nm. 17. A method of selecting a wavelength range for treating skin changes by radiation of a phototoxic sub- stance, c h a r a c t e r i s e d in that a phototoxic substance which in radiation forms new substances, so- called photoproducts, is selected, the photoabsorption in the phototoxic substance and its photoproducts being examined and the wavelength range being selected, in which a relatively high photoabsorption in the phototoxic substance and a relatively low photoabsorption in the photoproducts are obtained. 18. A method as claimed in claim 17, c h a r a c t e r i s e d in that the wavelength range is selected so that the wavelengths comprised therein have sufficient penetration capacity in skin for complete treatment of the skin change in question. 19. A method as claimed in claim 17 or 18, c h a r a c t e r i s e d in that the examination of the absorp- tion spectrum of the phototoxic substance and/or its photoproducts is performed in a solution of the substances. 20 A method as claimed in any one of claims 17-19, c h a r a c t e r i s e d in that the photoproducts are obtained by radiation of a solution of the phototoxic substance .

Inventors: GUDMUNDSON FREDRIK, GUDMUNDSON, FREDRIK
Applicants: GUDMUNDSON FREDRIK, MEDEIKONOS AB, GUDMUNDSON, FREDRIK
Application year: 2000
Main classification: A61N5
IPC codes: A61N5