Illumination for photodynamic therapy

Abstract

An illumination system (1) for photodynamic therapy is provided, the illumination system comprising an illumination source (2) configured to emit electromagnetic radiation (3) to illuminate a target surface (4) during operation, and an electronic control unit (5), wherein the illumination source is configured such that the intensity of the electromagnetic radiation emitted by the illumination source is variable, wherein the electronic control unit is operably connected to the illumination source and is configured to control the operation of the illumination source in accordance with an illumination protocol during an illumination session performed with the illumination system, and wherein the illumination protocol comprises instructions to operate the illumination source in a plurality of different modes during the illumination session, said modes comprising: a) a first mode, wherein in the first mode the electronic control unit controls the operation of the illumination source such that the intensity of the electromagnetic radiation emitted by the illumination source is continuously or quasi-continuously increased from a base intensity B to a target intensity T over a first mode time interval, b) a second mode, wherein in the second mode the electronic control unit controls the operation of the illumination source such that the intensity of the electromagnetic radiation emitted by the illumination source is constant or substantially constant over a second mode time interval, and c) a third mode, wherein in the third mode the electronic control unit controls the operation of the illumination source such that the illumination source is operated such that a dark phase and an illumination phase are alternated over a third mode time interval, wherein the intensity of the electromagnetic radiation emitted by the illumination source is lower in the dark phase than in the illumination phase, or wherein in the dark phase the illumination source does not emit electromagnetic radiation, while in the illumination phase the illumination source emits electromagnetic radiation. Furthermore, a computer program product and a kit for treating a disease and a method for operating an illumination source and a method for treating a skin disease are provided.

Description

[0001] The present disclosure relates to a lighting system for photodynamic therapy, the lighting system comprising a lighting source configured to emit electromagnetic radiation to illuminate a target surface during operation and an electronic control unit.

[0002] The present disclosure also relates to a method for operating a lighting source, a computer program product such as a data carrier, a kit for treating a disease and a method for treating a skin disease.

[0003] Photodynamic therapy (PDT) has been extensively studied and has been successfully used for treatment in a variety of ways. Generally, PDT has three requirements: a photosensitizer, molecular oxygen and light of a specific wavelength. For skin disease PDT, a prodrug (e.g. aminolevulinic acid (ALA)) is typically applied topically to the skin. Subsequently, the prodrug is converted by cells (e.g. tumor cells) into the actual photosensitizer. The molecular mechanism in PDT is based on cellular uptake of ALA, synthesis and accumulation of the photosensitizer, which is able to be excited by light of a specific wavelength to cause the formation of reactive oxygen species (ROS) in the presence of oxygen. ROS is able to induce forms of cell death such as apoptosis, necrosis and autophagy.

[0004] However, one of the main issues that hinders patients from widely accepting PDT is the relatively high amount of pain that patients experience during the illumination, ranging from mild inconvenience to severe pain to the extent that the treatment has to be aborted. Furthermore, although PDT is a very effective treatment, recurrence of some diseases such as actinic keratosis is common, so that patients, although successfully treated, often later develop different lesions in different skin areas and need medical intervention again. In addition, some patients are not fully cured after a single PDT session and need a second session. If the first PDT they received was very painful, the chances of starting or completing a second PDT are small, despite the fact that PDT offers the highest efficacy compared to other treatment options. As a result, the acceptance of treatment or retreatment by many patients decreases. This of course has a large negative impact on PDT alone and on the entire PDT.

[0005] Therefore, reducing pain is essential to improve the acceptance of PDT treatment as a whole, thereby increasing the use of this superior treatment.

[0006] However, the efficacy of PDT is also limited by any of the related factors, i.e. the photosensitizer, oxygen and light. Any reduction in the availability of these factors can hinder the formation of ROS. Optimized drug forms, pre-treatment and incubation patterns can ensure proper and sufficient deposition of the photosensitizer. Nonetheless, light has to reach a sufficient amount of molecules and oxygen needs to be present as an energy acceptor.

[0007] In particular, illumination light of a suitable wavelength is required to provide a sufficient dose for activating the respective photosensitizer. For topical applications, a commonly used photosensitizer is protoporphyrin IX (PpIX), which is mainly produced in skin cells by applying a precursor molecule such as ALA. PpIX can be activated by light of various different wavelengths, with red light (about 635 nm), blue light (about 420 nm), yellow light (about 542 nm) or green light (about 506 nm) being the most commonly used. Typically, the light dose received by the target (e.g. treated skin) depends on three main factors. The radiation provided by the light source, the distance between the target area and the light source and the duration of the illumination.

[0008] Current practice is to apply the full light dose in a short time interval (e.g. red light 7 to 12 minutes or blue light 15-20 minutes). Typically, this approach is limited by the occurrence of pain. Furthermore, photo-bleaching of the photosensitizer can occur to a greater extent at higher light intensities and can limit the treatment efficiency. Photo-bleaching describes the effect that the photosensitizer is deactivated by a permanent destruction of its chemical structure (e.g. by breaking of covalent bonds). This photo-bleaching effect can coincide with a temporal oxygen depletion in the target tissue due to the high amount of initial reactions. This leads to a rapid reduction of oxygen, which is necessary for the formation of ROS. All photo-bleaching that occurs in the phase of limited oxygen can be unproductive, as it produces less cytotoxic singlet oxygen.

[0009] It should be noted that the above statements are not to be interpreted as admitted prior art. They are only used to illustrate the background of the presently disclosed concepts and can not have been provided to the public yet.

[0010] It is an object of the present invention to provide an improved illumination system for photodynamic therapy, an improved method for operating an illumination source, an improved computer program product such as a data carrier, an improved kit for treating a disease, and / or an improved method for treating a skin disease, which preferably allows or is configured to limit the burden of pain, conveniently while maintaining an acceptable effectiveness of the treatment, and / or which allows or is configured to increase the effectiveness of the treatment.

[0011] The respective objects can be achieved, inter alia, by the subject matter of the independent claims. Advantageous embodiments and improvements are the subject matter of the dependent claims. However, in addition to the presently claimed concepts, further advantageous concepts can be disclosed herein.

[0012] One aspect of the present disclosure relates to an illumination system for use in photodynamic therapy, wherein the illumination system comprises an illumination source configured to emit electromagnetic radiation to illuminate a target surface during operation and an electronic control unit. The illumination source is configured such that the intensity of the electromagnetic radiation emitted by the illumination source can be varied. The electronic control unit is operably connected to the illumination source and configured to control the operation of the illumination source in accordance with an illumination protocol during an illumination session performed using the illumination system, and wherein the illumination protocol comprises instructions to operate the illumination source in a plurality of different modes during the illumination session, including:

[0013] a) a first mode, wherein in the first mode the electronic control unit controls the operation of the illumination source such that the intensity of the electromagnetic radiation emitted by the illumination source is continuously or quasi-continuously increased from a base intensity B to a target intensity or target intensity T over a first mode time interval,

[0014] b) a second mode, wherein in the second mode the electronic control unit controls the operation of the illumination source such that the intensity of the electromagnetic radiation emitted by the illumination source is constant or substantially constant over a second mode time interval, and / or

[0015] c) a third mode, wherein in the third mode the electronic control unit controls the operation of the illumination source such that the illumination source is operated such that a darker phase and an illuminated phase are alternated over a third mode time interval, wherein the intensity of the electromagnetic radiation emitted by the illumination source is lower during the darker phase than during the illuminated phase, or wherein the illumination source does not emit electromagnetic radiation during the darker phase and the illumination source emits electromagnetic radiation during the illuminated phase. The control unit can be configured to control the operating voltage and / or the operating current provided to the illumination source such that the illumination source operates as desired in the respective mode.

[0016] The proposed illumination system can limit or reduce the perceived pain burden. This is achieved, inter alia, by operating the illumination source in the different modes described above during an illumination session, which will be explained in more detail below. The proposed illumination system and in particular the illumination protocol can improve the effectiveness of PDT. Thus, the proposed system and / or protocol can provide a pain-optimized but still effective treatment.

[0017] In the first mode, the intensity of the electromagnetic radiation emitted by the illumination source is continuously or quasi-continuously increased from a base intensity B to a target intensity T. The term "quasi-continuously" can mean that the intensity of the emitted radiation is constant over a maximum duration less than or equal to one of the following values: 5 s, 4 s, 3 s, 2 s, 1 s or 500 ms. The term "continuously" can mean that the intensity of the emitted radiation is constant over a maximum duration less than the values associated with "quasi-continuously", preferably less than or equal to one of the following values: 400 ms, 300 ms, 200 ms, 100 ms, 50 ms, 25 ms, 20 ms, 15 ms, 10 ms, 5 ms, 4 ms, 3 ms, 2 ms, 1 ms. Since the emission intensity is characterized or determined by the electrical energy supplied to the illumination source, the corresponding values can be characterized as a continuously or quasi-continuously increased operating voltage and / or current.

[0018] The continuous or quasi-continuous increase in intensity can lead to the onset of a moderate reaction. The increase in intensity can reduce the initial photobleaching and / or promote the reoxidation of the treated skin. In addition to this, the continuous increase in radiation can trigger sufficient photodynamic effects, including an initial inflammatory reaction inducing vasodilation for better oxygen supply, where the photodynamic effects describe the processes leading to cell destruction during PDT. Thus, the efficiency of the treatment during the first mode can be ensured.

[0019] Another advantage of the first mode is that the continuous increase in radiation on the skin (radiation on the skin or radiation of the skin depending on the emission intensity and the distance between the illumination source and the skin) allows the sensory nerve endings of the skin to adapt to the stimulus, thus balancing the sensation of pain and ultimately reducing the pain burden on the patient. Slowly increasing the radiation over an interval of 4 to 10 minutes has been shown to be acceptable.

[0020] In the second mode, the intensity of the electromagnetic radiation emitted by the illumination source is constant or substantially constant. The term "substantially constant" can mean a maximum deviation from the intensity I less than or equal to one of the following values: 15%, 10%, 5%. I is the constant intensity during the second mode. I can be equal to T.

[0021] The constant or substantially constant intensity of the electromagnetic radiation in the second mode can provide a relatively high radiation, preferably over a short time span. It can help or be responsible for maintaining a sustained photodynamic effect, preferably without causing an unbearable pain burden, for example due to its limited duration.

[0022] In the third mode, the illumination source is operated such that dark phases and illumination phases alternate. The dark phases can allow the neuronal activation to fade to some extent, resulting in a less painful burden. The illumination phases can allow the target light dose of the illumination session to be achieved. In the illumination phases, the intensity is advantageously greater than in the dark phases. In the dark phases, the illumination source can be operated to emit lower intensity radiation or not to emit radiation at all.

[0023] Furthermore, another advantage of the third mode can be the balanced rate of oxygen consumption and oxygen resupply. Oxygen resupply in the dark phases can conveniently support the efficiency of the treatment by preventing late oxygen depletion.

[0024] Thus, the combination of the first, second and third mode can result in

[0025] - a moderate reaction onset to reduce the painful burden, reduce initial photobleaching and promote re-oxidation of the treated tissue,

[0026] - a sufficient photodynamic effect, including an initial inflammatory reaction inducing vasodilation for a better oxygen supply,

[0027] - re-oxidation, especially in later phases of illumination (e.g. when using high or higher flux rates), and thus additional photosensitizer activation to prevent late oxygen depletion, and

[0028] - a treatment duration that is only moderately increased or not increased at all to achieve a given light dose on the irradiated target without generating an unbearable painful burden, while maintaining an effective light dose.

[0029] In one embodiment, B can be less than or equal to one of the following values: 0.5T, 0.45T, 0.4T, 0.35T, 0.3T. Alternatively or additionally, B can be greater than or equal to one of the following values: 0.1T, 0.15T, 0.2T, 0.25T, 0.3T. Thus, B can be 0.1T to 0.5T or any other range formed by combining the values of the two lists.

[0030] Selecting B accordingly can allow the sensory nerve endings in the skin to sufficiently adapt to the stimulus, which can balance the pain sensation. This can result in a reduced painful burden. Furthermore, a sufficient photodynamic effect can be achieved or triggered. Higher values of B (e.g. greater than 0.6T) can cause excessive initial pain during the illumination session. Values below 0.1T can not be sufficient to trigger a substantial photodynamic effect and / or result in unstable illumination due to technical limitations.

[0031] In an embodiment, the constant or quasi-constant intensity during the second mode can be the target intensity T in the first mode. This can allow for a direct transition from the first mode to the second mode. Advantageously, once the target intensity is reached, the efficiency of the treatment is not jeopardized by changing the intensity. Moreover, a direct transition from the first mode to the second mode results in less stimulation of the patient’s nerve and thus can also result in a lower pain burden.

[0032] In an embodiment, the intensity during the illumination phase can be T. This can result in a reduced pain burden, as the nerve can have already adapted to T, e.g. according to the aforementioned pattern of the illumination protocol.

[0033] In an embodiment, the maximum intensity during the first, second and third mode can be T. Again, this can result in less stimulation of the patient’s nerve and thus also contributes to a lower pain burden.

[0034] In an embodiment, the intensity can linearly increase from B to T in the first mode. A linear increase can be comfortable for the patient, as he is able to easily adapt to the rate of the pain increase and the increase can be more predictable.

[0035] In an embodiment, the intensity can strictly monotonically increase in the first mode. A stepwise increase of the intensity is significantly more noticeable to the patient than a strictly monotonic increase of the intensity. Thus, a strictly monotonic increase of the intensity results in less pain.

[0036] In an embodiment, the intensity can non-linearly increase in the first mode. At the beginning or start of the first mode, the intensity can increase at a slower rate than later in the first mode. This can result in the beneficial effects of the photodynamic effect to occur earlier, with a reserved initial phase for the adaptation of the nerve and the intensity.

[0037] In an embodiment, the illumination protocol comprises a start-up mode. The start-up mode can be a mode of operation of the illumination source before the first mode. In the start-up mode of operation, the intensity of the electromagnetic radiation emitted by the illumination source can be constant or substantially constant for a start-up mode time interval. The intensity in the start-up mode can be P. P can be less than or equal to B, the base intensity in the first mode. During the initial operation of the illumination source in the start-up mode, the subject / patient using the protocol radiation is able to get used to the radiation. When the start-up mode is applied, the intensity in the first mode after the start-up mode can increase linearly and / or at a higher rate than without the start-up mode, preferably without significantly increasing the pain perceived by the user.

[0038] In an embodiment, during the illumination session, the illumination source can operate in the first mode before it operates in the second mode and / or before it operates in the third mode. The first mode can be to adapt the nerve to the radiation intensity or the pain burden during the illumination session. For this purpose, the first mode preferably initially uses a low intensity. To reduce the perception of pain, it can therefore be advantageous to perform the first mode before the other modes, for example a mode which can have a higher intensity than the initial light intensity (e.g. B) of the first mode.

[0039] In an embodiment, during the illumination session, the illumination source can operate in the second mode after the first mode and / or before the third mode. As the second mode can have a constant intensity, it is advantageous to reduce the pain when the first mode precedes the second mode, which can serve to adapt the nerve to the light intensity of the second mode. Furthermore, it is also advantageous to have a mode with constant intensity (second mode) between the increasing intensity (first mode) and the alternating illumination and darker phases (third mode), as the second mode can be the mode with the highest pain burden. The subsequent darker and illumination phases can make the higher pain in the middle part of the illumination session less noticeable to the user. The user can preferably remember the moderate pain during the third mode as well as the low initial pain.

[0040] In an embodiment, the start of the operation of the illumination source in the first mode can define the start of the illumination session, and the end of the operation of the illumination source in the third mode can define the end of the illumination session. If a start-up mode is applied, the start of the operation of the illumination source in the start-up mode can define the start of the illumination session.

[0041] In an embodiment, each of the modes selected from the first mode, the second mode and the third mode of the operation of the illumination source can occur once, preferably only once, during the illumination session. Thus, the total duration can be kept below 16 minutes, which is considered acceptable by most patients and physicians, for example in terms of pain burden and time consumption. This duration can or can not include the operation in the start-up mode.

[0042] In an embodiment, the illumination system can have or can define a target position in which a target surface will be arranged relative to the illumination source during the illumination session. The target position, i.e. the position of the target surface relative to the illumination source, can be defined by a support surface which is contacted by a part of the user's head, for example by the forehead or the chin. The part of the user's head can remain in contact with the support surface during the entire session. The target position can be arranged at a distance from the radiation exit surface of the illumination source. A gaseous medium can be present between the radiation exit surface of the illumination source, for example the surface of an optical element (e.g. a diffuser or a lens), and the target surface and / or the target position.

[0043] The term "target surface" as used herein can refer to a surface that is to be illuminated by electromagnetic radiation emitted by the illumination source.

[0044] The term "target position" as used herein can refer to a position of the target surface relative to the illumination source. In other words, the target position can be a position that is determined by the design of the illumination device. The target position can be a position at which the surface to be illuminated should be arranged relative to the illumination device during operation of the device, i.e. during an illumination session. For example, at the target position, the radiation generated by the illumination device can have a desired radiation profile, e.g. along the target surface. If the target surface is arranged at a different position relative to the illumination source, the radiation profile can be different and / or can not be suitable for the desired purpose.

[0045] The term "support surface" as used herein can refer to a surface that is suitable for supporting a body part of a user, such as a head, preferably at the target position during operation. The body part can comprise the target surface that should be illuminated using the illumination device. The support surface can be formed by a mechanical support.

[0046] In one embodiment, the distance between the radiation exit surface of the illumination source and the target position can be less than or equal to one of the following values: 20 cm, 15 cm, 10 cm, 8 cm, 7 cm, 6 cm, 5 cm. Alternatively or additionally, the distance between the radiation exit surface of the illumination source and the target position can be greater than or equal to one of the following values: 1 cm, 2 cm, 3 cm, 4 cm, 5 cm. The distance between the radiation exit surface of the illumination source and the target position can be in the range of 1 cm to 20 cm, preferably 5 cm to 8 cm.

[0047] PDT efficiency is potentially limited by any of the relevant factors, i.e. photosensitizer, oxygen and light dose. Generally, the light dose received by the target, e.g. the skin to be treated, depends on three main factors. One of them is the distance between the target surface and the light source. This distance has a direct influence on the light dose received by the target, since the intensity at a particular position depends on the distance of this position to the illumination source. A distance of 1 cm to 20 cm, preferably 5 cm to 8 cm, is advantageous, since it enables the effects of PDT to be optimally deployed. Furthermore, within the above specified distance, the pain perceived by the patient can be acceptable, in particular for the radiation that is usually applied.

[0048] In one embodiment, the illumination source can comprise at least one optoelectronic semiconductor chip, e.g. a light emitting diode chip, for generating electromagnetic radiation. This allows the illumination source to be reliably, cost-effectively and accurately implemented. The optoelectronic chip allows the emission wavelength to be easily tuned to the required (peak) wavelength, e.g. by appropriately designing the active region of the chip, e.g. by bandgap engineering. Thus, electrical energy can be efficiently converted into radiant energy in the relevant wavelength range.

[0049] In an embodiment, the radiation emitted by the illumination source can be non-coherent radiation. Non-coherent radiation is easier to handle compared to coherent radiation.

[0050] In an embodiment, the radiation emitted by the illumination source can be monochromatic, e.g. a specific color of light.

[0051] In an embodiment, the electromagnetic radiation can have a peak wavelength in the visible light spectrum range, e.g. in the red, blue, green or yellow light spectrum range.

[0052] In an embodiment, the electromagnetic radiation has a peak wavelength in the red light spectrum range (hereinafter also referred to as “red light”). The peak wavelength of the illumination source can be larger than 500 nm, larger than 600 nm or larger than 630 nm. The peak wavelength can be smaller than 700 nm. The peak wavelength can be 635 nm. Red light has the advantage that it can more easily reach body regions further away from the skin at high intensities than shorter wavelengths of light which are more easily absorbed in body tissue than red light. Hence, the present disclosure is exemplified with red light.

[0053] In an embodiment, the illumination system can be configured to irradiate the target surface with a predetermined light dose during the illumination session. When the target surface is arranged in the target position relative to the illumination source during the illumination session, the light dose can be larger than or equal to one of the following values: 30 J / cm 2 , 35 J / cm 2 , 37 J / cm 2 . Alternatively or additionally, when the target surface is arranged in the target position relative to the illumination source during the illumination session, the light dose can be smaller than or equal to one of the following values: 45 J / cm 2 , 40 J / cm 2 , 37 J / cm 2 . The above values are particularly suitable for red light at least.

[0054] A sufficient light dose is one of the key requirements for a successful PDT. However, when selecting the light dose, also the maximum tolerable pain level of the patient has to be taken into account. A light dose of 30 to 45 J / cm 2 , in particular a light dose of 37 J / cm 2 , can be considered as the best trade-off between sufficient treatment efficiency and pain burden, e.g. when using red light.

[0055] In another embodiment, the electromagnetic radiation has a peak wavelength in the blue light spectrum range (hereinafter also referred to as “blue light”). The peak wavelength of the illumination source can be 400 nm to 490 nm, e.g. 420 nm.

[0056] In an embodiment, during the illumination session, the illumination system can be configured to irradiate the target surface with a predetermined light dose. When, during the illumination session, the target surface is arranged in the target position relative to the illumination source, the light dose can be greater than or equal to one of the following values: 8 J / cm 2 , 9 J / cm 2 , 10 J / cm 2 . Alternatively or additionally, when, during the illumination session, the target surface is arranged in the target position relative to the illumination source, the light dose can be less than or equal to one of the following values: 12 J / cm 2 , 11 J / cm 2 , 10 J / cm 2 . The above values apply at least particularly for blue light.

[0057] A light dose of 8 to 12 J / cm 2 , particularly a light dose of 10 J / cm 2 , can be considered a good trade-off between sufficient therapeutic efficacy and pain burden, for example when using blue light.

[0058] It should be noted that yellow or green light can also be used. This is particularly true if ALA is used as a prodrug, because the photosensitizer PpIX not only absorbs red and / or blue light, but also green and / or yellow light.

[0059] In an embodiment, the first mode time interval, the second mode time interval, and / or the third mode time interval can be greater than or equal to one of the following values: 1 min, 1.5 min, 2 min, 2.5 min, 3 min, 3.5 min, 4 min, 4.5 min, 5 min. Alternatively or additionally, the first mode time interval, the second mode time interval, and / or the third mode time interval can be less than or equal to one of the following values: 10 min, 9.5 min, 9 min, 8.5 min, 8 min, 7.5 min, 7 min, 6.5 min, 6 min, 5.5 min, 5 min.

[0060] In an embodiment, the first mode time interval and / or the second mode time interval can be shorter than the third mode time interval. Thus, the third mode can provide the largest contribution to the total light dose delivered to the target surface during the illumination session.

[0061] In an embodiment, the start-up mode time interval can be shorter than the first mode time interval, the second mode time interval, and / or the third mode time interval.

[0062] In one embodiment, the start-up mode time interval can be less than or equal to one of the following values: 4 min, 3 min, 2 min, 1 min. Alternatively or additionally, the start-up mode time interval can be greater than or equal to one of the following values: 10 s, 20 s, 30 s, 1 min.

[0063] In one embodiment, the first mode time interval can be shorter than the second mode time interval. In this way, the illumination duration at intensities less than T can be kept relatively small. Thus, the treatment duration is not unnecessarily prolonged.

[0064] In one embodiment, the first mode time interval and / or the second mode time interval can be longer than the duration of a single dim phase and / or a single illumination phase, preferably at least 5 d, 6 d, 7 d, 8 d, 9 d, 10 d, 11 d, 12 d, 13 d, 14 d, 15 d, wherein d is the duration of a single dim phase and / or a single illumination phase.

[0065] In one embodiment, the duration of a dim phase and / or an illumination phase can be less than or equal to one of the following values: 60 s, 50 s, 45 s, 40 s, 35 s, 30 s, 25 s, 20 s. Alternatively or additionally, the duration of a dim phase and / or an illumination phase can be greater than or equal to one of the following values: 15 s, 20 s, 25 s, 30 s. A phase duration of 15 to 60 seconds can be advantageous to exploit the benefits of the positive effect without unnecessarily increasing the treatment duration.

[0066] In one embodiment, the duration of different dim phases in the third mode can be equal. In one embodiment, the duration of different illumination phases in the third mode can be equal. In one embodiment, the duration of a dim phase can be constant and can be equal to or different from the duration of an illumination phase.

[0067] In one embodiment, the duration of a dim phase can be less than the duration of an illumination phase. This results in a shorter illumination interruption during the third mode, which can help to keep the treatment duration at a desired time.

[0068] In an embodiment, the duration of the second mode time interval and / or the duration of the first mode time interval and the second mode time interval together is less than or equal to one of the following values: 12 min, 11 min, 10 min, 9 min, 8 min. Thus, for example, the first pain relief brought by the darker phase in the third mode after the second mode can occur at or before the time at which the patient experiences the maximum pain. For example, it is reported that patients feel the most severe pain or unbearable pain after about 10 min during a PDT session. Thus, keeping the second mode or the combination of the first and second mode together below 10 min can be beneficial for pain management.

[0069] In an embodiment, the duration of the entire illumination session can be greater than or equal to one of the following values: 10 min, 11 min, 12 min, 13 min. For example, the duration of the session can be between 10 min and 20 min.

[0070] In an embodiment, the duration of the entire illumination session can be greater than or equal to one of the following values: 10 min, 11 min, 12 min, 13 min. For example, the duration of the session can be between 10 min and 20 min.

[0071] In an embodiment, the intensity during each illumination phase in the third mode can be the same.

[0072] In an embodiment, the intensity during the darker phase can be less than or equal to B or equal to 0. Thus, the re-supply of oxygen can be facilitated in the dark phase.

[0073] In an embodiment, the intensity in a single illumination phase can be constant or substantially constant. A constant or substantially constant intensity in a single illumination phase facilitates a more predictable photodynamic effect.

[0074] In an embodiment, the intensity can vary between different illumination phases. The variation of different intensities can help to adjust the pain burden or load of the patient during the treatment. For example, the intensity of the illumination phase can be higher at the beginning of the third mode than at the end of the third mode.

[0075] In an embodiment, the illumination protocol can govern the entire illumination session.

[0076] Another aspect of the present disclosure relates to a method for operating an illumination source, wherein the illumination source is operated according to an illumination protocol, for example during an illumination session performed with the above-described illumination system, and wherein the illumination protocol comprises instructions to operate the illumination source in the above-described different modes during the illumination session.

[0077] Further, the disclosure also relates to a computer program product, such as a data carrier, e.g. a non-transitory data carrier, containing machine readable instructions, in particular causing a lighting source to operate according to the above described protocol, when loaded into and / or executed by a computer system, e.g. by its electronic control unit.

[0078] Further, another aspect relates to a kit for treating a disease, e.g. a skin disease, such as a neoplastic skin disease. The kit can comprise a medicinal substance suitable for topical application into a region of the skin to be treated and a lighting system as described above, wherein the lighting system is configured to irradiate the region of the skin to which the substance has been applied.

[0079] In an embodiment, the medicinal substance can be a photosensitive drug or a precursor of such a drug, which drug is excitable by light in the emission spectrum.

[0080] In an embodiment, the medicinal substance can comprise 5-aminolevulinic acid. 5- Aminolevulinic acid has been well studied and is considered a reliable prodrug to produce photosensitizers.

[0081] Yet another aspect relates to a method of treating a skin disease, comprising the steps of: applying a medicinal substance to the surface of a region of the skin to be treated; and irradiating the region with a lighting source according to the method and / or using the lighting system as specified above.

[0082] In an embodiment, the lighting system, the kit and / or the method can be used for treating a skin disease or disorder. The skin disease or disorder can be or can comprise a neoplastic skin disease, such as actinic keratosis, basal cell carcinoma, squamous cell carcinoma in situ, warts, acne, impaired wound healing / chronic wounds, bacterial and / or fungal infections or inflammatory skin diseases.

[0083] It should be noted that the disclosure encompasses non-therapeutic methods.

[0084] Due to the small pain burden, the lighting system can be universally used for treating various diseases.

[0085] Of course, the features described above in connection with the different aspects and embodiments can be combined with each other and with the features described below. Thus, features relating to the system also apply to the method and the kit, and vice versa.

[0086] Other features and improvements will become apparent from the following description of exemplary embodiments, given in connection with the accompanying drawings.

[0087] Figure 1 A perspective view of the lighting system and the target surface is schematically shown.

[0088] Figure 2A graph illustrating a lighting protocol is shown.

[0089] Figure 3 A graph illustrating a variant of the lighting protocol is shown. Figure 2

[0090] Figure 4 A graph illustrating another variant of the lighting protocol is shown. Figure 2

[0091] Figure 1 A lighting system 1 is shown, for example for use in photodynamic therapy (PDT). The lighting system 1 comprises a lighting source 2 configured to emit electromagnetic radiation 3 to illuminate a target surface 4 during operation. The target surface 4 can be human skin, for example skin on the head or other area to be treated. Furthermore, PDT requires a photosensitizer and molecular oxygen (not explicitly shown). The photosensitizer is typically obtained by a prodrug (not explicitly shown) which is applied topically to the skin, conveniently into the target area, and then converted to the actual photosensitizer by cells, preferably by tumor cells. The prodrug can be 5-aminolevulinic acid (5-ALA), which is an endogenous precursor of heme biosynthesis.

[0092] The molecular mechanism of action in PDT is based on cellular uptake, synthesis and accumulation of the photosensitizer aminolevulinic acid, which is excited by light of a specific wavelength to cause the formation of reactive oxygen species (ROS) in the presence of oxygen. These ROS species are able to induce cell death in the form of apoptosis, necrosis and / or autophagy.

[0093] The lighting source 2 is configured such that the intensity of the electromagnetic radiation 3 emitted by the lighting source 2 and / or reaching the target surface 4 can be varied. Furthermore, the distance between the target surface 4 and the lighting source 2 of the lighting system 1 is adjustable and thus variable. Preferably, however, the target surface 4 has a fixed position relative to the lighting source.

[0094] The lighting source 2 can comprise one light emitting diode (LED) or a plurality of light emitting diodes. In particular, a lighting source such as the one distributed by the company Biofrontera AG under the trade name Lightstar® is suitable. The light emitted by the light emitting diode promotes the formation of reactive oxygen species (ROS). The wavelength of the light emitted by the lighting source can be greater than 400 nm, greater than 500 nm or greater than 600 nm. For example, the wavelength can be 635 nm, i.e. radiation in the red spectral range. As another example, the wavelength can be 420 nm, i.e. radiation in the blue spectral range. Alternatively, yellow or green light radiation can also be applied to suitably activate the photosensitizer.

[0095] ​​The lighting system 1 can have or can define a target position in which the target surface 2 will be arranged relative to the lighting source 2 during a lighting session. The target position can be defined by a support surface that is contacted by a portion of the user’s head, for example by the forehead or chin. This portion can remain in contact with the support surface throughout the session. The target position can be arranged at a distance from a radiation exit surface of the lighting source 2. A gaseous medium can be present between the radiation exit surface of the lighting source 2, for example the surface of an optical element such as a diffuser or a lens, and the target surface 4 and / or the target position.

[0096] The distance between the radiation exit surface of the lighting source 2 and the target position can be less than or equal to one of the following values: 20 cm, 15 cm, 10 cm, 8 cm, 7 cm, 6 cm, 5 cm. Alternatively or additionally, the distance between the radiation exit surface of the lighting source 2 and the target position can be greater than or equal to one of the following values: 1 cm, 2 cm, 3 cm, 4 cm, 5 cm. The distance between the radiation exit surface of the lighting source 2 and the target position can be comprised between 1 cm and 20 cm, preferably between 5 cm and 8 cm.

[0097] The lighting source 2 can comprise at least one optoelectronic semiconductor chip, for example a light emitting diode chip, for generating electromagnetic radiation. The radiation emitted by the lighting source 2 can be incoherent radiation. It can be monochromatic, for example light of one particular color. The electromagnetic spectrum emitted by the lighting source 2 can have a peak wavelength in the visible light spectrum range, for example in the red or blue light spectrum range. The emission spectrum can be narrow. For example, the full width at half maximum (FWHM: Full Width at Half Maximum) of the spectrum can be less than 100 nm, for example less than or equal to 50 nm.

[0098] The electronic control unit 5 is operatively connected to the lighting source 2 and is configured to control the operation of the lighting source 2 according to a lighting protocol during a lighting session performed with the lighting system 1. The electronic control unit can be part of a computer. The electronic control unit can be a CPU (Central Processing Unit) or a microcontroller. The lighting protocol comprises instructions to operate the lighting source 2 in a plurality of different modes during a lighting session, which is disclosed in detail in Figure 2 .

[0099] Figure 2 A graph showing a lighting protocol with two axes is shown, the first axis representing the duration of the radiotherapy in s and the second axis representing the degree of light intensity in percent. The lighting protocol can govern the entire lighting session.

[0100] During a first mode a, which is performed first in use of the illumination system 1, the electronic control unit 5 controls the operation of the illumination source 2 such that the intensity of the electromagnetic radiation 3 emitted by the illumination source 2 is continuously or quasi-continuously increased from a base intensity B (30%) to a target intensity T (100%) over a first mode time interval.

[0101] As shown in Figure 2 , a linear ramp of light intensity from 30% to 100% is applied over the course of 5 or 5.5 min. Of course, other durations are possible as well. The intensity of 100% is not necessarily the maximum intensity that can be emitted by the illumination source 2, but designates the maximum intensity during the illumination session. Alternatively, the intensity can be increased non-linearly under the first mode a (see, e.g., Figure 3 ). It is preferred here that the initial slope is smaller than the later slope, which can be beneficial to sensitize the nerve endings.

[0102] The first mode a can provide a moderate reaction onset to reduce initial photobleaching and promote re-oxygenation of the treated tissue, and a slow but continuous increase of the irradiation to trigger sufficient photo-dynamic effects, including an initial inflammatory response inducing vasodilatation, to reach a better oxygen supply. Photo-dynamic effects describe processes leading to cell destruction during PDT, wherein photobleaching describes the effect of deactivation of the photosensitizer by a permanent destruction of its chemical structure, e.g. by breaking of covalent bonds. Due to the large initial reaction, this photobleaching effect can coincide with a temporal oxygen depletion in the target tissue. This leads to a rapid decrease of oxygen and thus limits the formation of ROS. Furthermore, the more gentle start phase allows the sensory nerve endings in the skin to adapt to the stimulus, thereby reducing the perceived pain by the patient.

[0103] After reaching the 100% light intensity, a second mode b follows, wherein the electronic control unit 5 controls the operation of the illumination source 2 such that the intensity of the electromagnetic radiation 3 emitted by the illumination source is constant or substantially constant over a second mode time interval. As shown in Figure 2 , under the second mode b, the maximum light intensity of the first mode a is maintained. The light intensity can be kept constant for about 4.5 min. Of course, other durations are possible as well.

[0104] This second mode b is important to provide high energy to the target over a relatively short time span and thus keep the overall session duration below 16 min, which is an acceptable pain burden for most patients and physicians. In addition to this, the electronic control unit 5 controls the operation of the illumination source 2 such that the illumination source 2 is operated to stop the irradiation or to reduce the intensity after 10 min, e.g. by a first darker phase in a subsequent mode (mode c discussed below), thereby counteracting an excessive increase of pain.

[0105] In the second mode b, the intensity of the electromagnetic radiation emitted by the illumination source is constant or substantially constant. The intensity during the second mode b can be equal to the target intensity T in the first mode.

[0106] The second mode b is then followed by a third mode c. The third mode c is the last mode of the protocol. In the third mode c, the electronic control unit 5 controls the operation of the illumination source 2 such that the illumination source 2 is operated such that dark phases and illumination phases are alternating within a third mode time interval, for example 6 min. The duration of the third mode can be adjusted such that a desired light dose is received at the target surface, for example at least particularly suitable for red light is 37 J / cm 2 , or particularly suitable for blue light is 10 J / cm 2 .

[0107] The intensity of the electromagnetic radiation 3 emitted by the illumination source 2 is lower in the dark phases than in the illumination phases. In the shown example, the illumination source 2 does not emit electromagnetic radiation in the dark phases, while the illumination source 2 emits electromagnetic radiation 3 in the illumination phases, wherein the light intensity of the illumination phases is in line with the light intensity of mode 2 and the maximum light intensity of mode 1. Of course, the relative intensities can be adjusted as desired.

[0108] In the third mode c, this alternating intensity can be maintained for about 4 min or longer. In Figure 3 the shown example, the protocol contains seven illumination phases and seven dark phases, which particularly allow the neuronal activation to be attenuated to some extent to reduce the pain. The duration of one of the dark phases in the third mode c is constant and equal to the duration of one of the illumination phases. The duration of the phases is 20 s, respectively. During the illumination phases, the light intensity is maintained at 100%. After about 14 min, the illumination is stopped completely and the third mode c ends. Of course, the number of illumination phases and dark phases can be varied, as well as the absolute or relative duration. Furthermore, during the dark phases, it can still be tolerable to use a low intensity, for example at most 30% of the maximum intensity, instead of not operating the light source to emit no radiation at all. The intensity in a single illumination phase can be constant or substantially constant.

[0109] Due to the alternating phases, the target tissue can be provided with sufficient dark phases to reduce the photo-bleaching and / or to promote the re-oxidation of the treated tissue, which can lead to an increase in efficiency. Furthermore, the pause of illumination of the last mode c allows the neuronal activation to be attenuated to some extent. As a result, the perceived pain is significantly reduced.

[0110] This third mode c is continued until a total light dose of about 37 J / cm 2 can be reached. In order to maintain a total light dose of about 37 J / cm 2Increasing the duration of the protocol while simultaneously increasing the light dose is beneficial, as it may ensure the most balanced rate of oxygen consumption and resupply. 37 J / cm 2 The value is particularly suitable for red light. It remains at approximately 37 J / cm. 2 Increasing the duration of the protocol while increasing the light dose is beneficial, as it may ensure the most balanced rate of oxygen consumption and resupply.

[0111] Alternatively, this third mode c extends until it can reach approximately 10 J / cm². 2 Total light dose. 10 J / cm 2 The value is particularly suitable for blue light. Maintaining approximately 10 J / cm 2 Increasing the duration of the protocol while increasing the light dose is beneficial, as it may ensure the most balanced rate of oxygen consumption and resupply.

[0112] If yellow or green light is used, the total target light dose can be adjusted accordingly.

[0113] The duration of the entire lighting treatment should be advantageously kept below 20 minutes or even 16 minutes.

[0114] By grading the illumination with dark intervals alternating with higher-intensity light, re-oxidation and thus additional photosensitizer activation are allowed, especially in the later stages of high-flux illumination, to prevent later oxygen depletion. Therefore, limited treatment time due to pain can be utilized in a time-saving manner.

[0115] As depicted, the durations of the different darker phases under third mode c can be equal and / or constant, as can the durations of the different illumination phases under third mode c. Alternatively, the durations can vary between different darker phases and / or different illumination phases. The same applies to the intensity of the illumination phases, which can be varied, for example, reduced towards the end of the illumination session. In one embodiment, the duration of the darker phases can be less than the duration of the illumination phases. This results in shorter illumination interruptions during the third mode, which may help maintain the session duration for the desired time.

[0116] The start of operation of light source 2 in the first mode a can define the start of the lighting treatment, and the end of operation of light source 2 in the third mode c can define the end of the lighting treatment.

[0117] Figure 3 Explanation Figure 2This is a variant of the lighting protocol shown. Here, in the first operating mode (mode a), initially, the intensity increases non-linearly at a slower rate than later. In interval a1, the increase may be non-linear, while in subsequent intervals a2, it may be linear. The (constant) slope in the linear portion can be greater than or equal to each slope in the non-linear portion. For example, starting with mode b, the protocol could be as follows: Figure 2 Continue as shown.

[0118] Figure 4 Explanation Figure 2 Another variation of the lighting protocol shown. Here, a startup mode p is included before mode a begins. The duration of the startup mode can be 3 minutes or less. The intensity P during the startup mode can be equal to... Figure 2 The intensity B discussed in [the text]. Figure 3 and Figure 4 In one embodiment, the start of the second mode (mode b) is shown as approximately 340 seconds, only as an example.

[0119] The duration of the entire lighting treatment can be less than or equal to one of the following values: 20 min, 19 min, 18 min, 17 min, 16 min, 15 min, 14 min, or 13 min.

[0120] The time interval for the first mode and / or the time interval for the second mode can be shorter than the time interval for the third mode. The time interval for the first mode can be shorter or longer than the time interval for the second mode.

[0121] The durations for the modes have already been specified above. However, the corresponding modes (Mode 1, Mode 2, and / or Mode 3) can be applied with time intervals greater than or equal to one of the following values: 1 min, 1.5 min, 2 min, 2.5 min, 3 min, 3.5 min, 4 min, 4.5 min, 5 min. Alternatively or additionally, the corresponding modes can be applied with time intervals greater than or equal to one of the following values: 10 min, 9.5 min, 9 min, 8.5 min, 8 min, 7.5 min, 7 min, 6.5 min, 6 min, 5.5 min, 5 min. This allows the lighting protocol to be adjusted for different situations, for example.

[0122] This disclosure also provides a computer program product such as a data carrier or data stream, the data carrier being, for example, a non-transitory data carrier, which may contain machine-readable instructions, particularly when loaded into and / or executed by the computer system, for example, through its electronic control unit 5, to cause the lighting source 2 to operate in accordance with the aforementioned protocol.

[0123] The illumination system 1 can be used for treating a skin disease or disorder. The skin disease or disorder can be or can include a neoplastic skin disease, such as actinic keratosis, basal cell carcinoma, squamous cell carcinoma in situ or warts, acne, wound healing disorders / chronic wounds, bacterial and / or fungal infections or inflammatory skin diseases. It should be noted, however, that it can also be used for non-therapeutic methods.

[0124] A kit for treating a disease, for example a skin disease, such as a neoplastic skin disease, can comprise a medicinal substance suitable for topical application into the area of the skin to be treated and an illumination system 1 as specified above, wherein the illumination system 1 is configured to irradiate the area of the skin to which the substance has been applied. The medicinal substance can be a photosensitizing drug or a precursor of such a drug, which can be excited by light in the emission spectrum.

[0125] A method for treating a skin disease, for example one of the methods further mentioned above, can comprise the steps of applying a medicinal substance, for example a precursor as specified above, to the surface of the area of the skin to be treated; irradiating the area, for example with an illumination source 2 according to the method as specified above and / or using an illumination system 1 as specified above.

[0126] Not only is an increase in efficiency expected when applying the illumination protocol as specified above, but also a reduction in the perceived pain or the overall perceived pain intensity of the patient / user. A high amount of perceived pain is one of the main issues that hinders patients from widely accepting PDT. Often patients report experiencing a relatively high amount of pain during illumination, ranging from a slight inconvenience to severe pain up to a degree that the treatment has to be aborted. This has a large negative impact on the individual PDT session and the overall PDT treatment, of course.

[0127] The proposed application of an illumination system for photodynamic therapy reduces the pain during PDT to a tolerable level. In addition to this, the acceptance of the treatment itself and the willingness to undergo PDT again is greatly improved when using such an illumination system.

[0128] Although PDT is a very effective treatment method, the recurrence of the treated disease, for example actinic keratosis or another disease as mentioned in the foregoing of the present disclosure, is common, so that patients, although successfully treated, often develop different lesions in different areas of the skin later on and need medical intervention again. Furthermore, some patients do not clear completely after a single PDT session and need a second session. If the first PDT they underwent was very painful, the likelihood of completing a second PDT is small, despite the higher efficacy it offers compared to other treatment options.

[0129] The proposed illumination system and protocol therefore improve the acceptance level of photodynamic therapy.

[0130] A specific lighting system and / or its associated protocol have been described above. However, it will be appreciated that different systems and protocols can also be applied, especially using the features already discussed in the introductory part of the present disclosure, even if these features are not explicitly described above in connection with the figures. Therefore, by explicit reference to these features, the features discussed in the introductory part are subject to the exemplary embodiments of the present disclosure.

[0131] Reference signs

[0132] 1 lighting system

[0133] 2 lighting source

[0134] 3 electromagnetic radiation

[0135] 4 target surface

[0136] 5 electronic control unit

[0137] p start-up mode

[0138] a first mode

[0139] b second mode

[0140] c third mode

Claims

1. An illumination system for use in photodynamic therapy, the illumination system comprising an illumination source and an electronic control unit, the illumination source being configured to emit electromagnetic radiation to illuminate a target surface during operation, wherein the illumination source being configured such that the intensity of the electromagnetic radiation emitted by the illumination source can be varied, wherein the electronic control unit is operatively connected to the illumination source and is configured to control the operation of the illumination source in accordance with an illumination protocol during an illumination session performed with the illumination system, and wherein the illumination protocol comprises instructions to operate the illumination source in a plurality of different modes during the illumination session, the modes comprising: a) a first mode, wherein in the first mode the electronic control unit controls the operation of the illumination source such that the intensity of the electromagnetic radiation emitted by the illumination source is continuously or quasi-continuously increased from a base intensity B to a target intensity T over a first mode time interval, b) a second mode, wherein in the second mode the electronic control unit controls the operation of the illumination source such that the intensity of the electromagnetic radiation emitted by the illumination source is constant or substantially constant over a second mode time interval, and c) a third mode, wherein in the third mode the electronic control unit controls the operation of the illumination source such that the illumination source is operated such that a dark phase and an illumination phase are alternated over a third mode time interval, wherein the intensity of the electromagnetic radiation emitted by the illumination source is lower in the dark phase than in the illumination phase, or wherein in the dark phase the illumination source does not emit electromagnetic radiation, while in the illumination phase the illumination source emits electromagnetic radiation, and wherein the duration of one dark phase is less than or equal to 60 s and greater than or equal to 15 s.

2. The illumination system according to claim 1, wherein, B is less than or equal to 0.5T.

3. The illumination system according to claim 1, wherein B is less than or equal to 0.45T.

4. The illumination system according to claim 1, wherein B is less than or equal to 0.4T.

5. The illumination system according to claim 1, wherein B is less than or equal to 0.35T.

6. The illumination system according to claim 1, wherein B is less than or equal to 0.3T.

7. The illumination system according to any one of claims 1 to 6, wherein B is greater than or equal to 0.1T.

8. The illumination system according to any one of claims 1 to 6, wherein, B is greater than or equal to 0.15T.

9. The illumination system according to any one of claims 1 to 6, wherein B is greater than or equal to 0.2T.

10. The illumination system according to any one of claims 1 to 6, wherein, B is greater than or equal to 0.25T.

11. The illumination system according to any one of claims 1 to 6, wherein B is greater than or equal to 0.3T.

12. The illumination system according to any one of claims 1 to 6, wherein, during the illumination session the illumination source is operated in the second mode after the first mode and / or before the third mode.

13. The illumination system according to any one of claims 1 to 6, wherein The start of operation of the illumination source in the first mode defines the start of the illumination session, and the end of operation of the illumination source in the third mode defines the end of the illumination session.

14. The illumination system according to any one of claims 1 to 6, wherein Each of the modes selected from the first mode, the second mode and the third mode of operation of the illumination source occurs once during the illumination session.

15. The illumination system according to any one of claims 1 to 6, wherein, The electromagnetic radiation has a peak wavelength in the visible spectral range.

16. The illumination system according to any one of claims 1 to 6, wherein During the illumination session, the target surface is arranged at a target position relative to the illumination source, and wherein the illumination system is configured to irradiate the target surface with a predetermined radiation dose during the illumination session.

17. The lighting system of claim 16, wherein, The radiation dose is greater than or equal to 30 J / cm2when the target surface is arranged at a target position relative to the illumination source during the illumination session.

18. The lighting system of claim 16, wherein, The radiation dose is greater than or equal to 35 J / cm2when the target surface is arranged at a target position relative to the illumination source during the illumination session.

19. The lighting system of claim 16, wherein, The radiation dose is greater than or equal to 37 J / cm2when the target surface is arranged at a target position relative to the illumination source during the illumination session.

20. The illumination system according to claim 16, wherein The radiation dose is less than or equal to 45 J / cm2when the target surface is arranged at a target position relative to the illumination source during the illumination session.

21. The illumination system according to claim 16, wherein The radiation dose is less than or equal to 40 J / cm2when the target surface is arranged at a target position relative to the illumination source during the illumination session.

22. The illumination system according to claim 16, wherein The radiation dose is less than or equal to 37 J / cm2when the target surface is arranged at a target position relative to the illumination source during the illumination session.

23. The illumination system of claim 16, wherein The radiation dose is greater than or equal to 8 J / cm2when the target surface is arranged at a target position relative to the illumination source during the illumination session.

24. The illumination system of claim 16, wherein, The radiation dose is greater than or equal to 9 J / cm2when the target surface is arranged at a target position relative to the illumination source during the illumination session.

25. The illumination system of claim 16, wherein, The radiation dose is greater than or equal to 10 J / cm2when the target surface is arranged at a target position relative to the illumination source during the illumination session.

26. The illumination system of claim 16, wherein, The radiation dose is less than or equal to 12 J / cm2when the target surface is arranged at a target position relative to the illumination source during the illumination session.

27. The illumination system of claim 16, wherein, The radiation dose is less than or equal to 11 J / cm2when the target surface is arranged at a target position relative to the illumination source during the illumination session.

28. The illumination system of claim 16, wherein, The radiation dose is less than or equal to 10 J / cm2when the target surface is arranged at a target position relative to the illumination source during the illumination session.

29. The illumination system according to claim 16, wherein The distance between the radiation exit surface of the illumination source and the target position is 1 cm to 20 cm.

30. The illumination system of claim 29, wherein The distance between the radiating exit surface of the illumination source and the target position is comprised between 5 cm and 8 cm.

31. The illumination system of claim 29, wherein The distance between the radiating exit surface of the illumination source and the target position is comprised between 10 cm and 15 cm.

32. Illumination system according to any one of claims 1 to 6, wherein The duration of the entire illumination session is less than or equal to 20 min.

33. Illumination system according to any one of claims 1 to 6, wherein, The duration of the entire illumination session is less than or equal to 19 min.

34. Illumination system according to any one of claims 1 to 6, wherein The duration of the entire illumination session is less than or equal to 18 min.

35. Illumination system according to any one of claims 1 to 6, wherein The duration of the entire illumination session is less than or equal to 17 min.

36. Illumination system according to any one of claims 1 to 6, wherein The duration of the entire illumination session is less than or equal to 16 min.

37. Illumination system according to any one of claims 1 to 6, wherein The duration of the entire illumination session is less than or equal to 15 min.

38. Illumination system according to any one of claims 1 to 6, wherein, The duration of the entire illumination session is less than or equal to 14 min.

39. Illumination system according to any one of claims 1 to 6, wherein The duration of the entire illumination session is less than or equal to 13 min.

40. The illumination system of any one of Claims 1-6, wherein, The first, second and / or third mode time interval is greater than or equal to 1 min.

41. The illumination system of any one of claims 1 to 6, wherein, The first, second and / or third mode time interval is greater than or equal to 1.5 min.

42. The illumination system of any one of claims 1 to 6, wherein, The first, second and / or third mode time interval is greater than or equal to 2 min.

43. The illumination system of any one of claims 1 to 6, wherein, The first, second and / or third mode time interval is greater than or equal to 2.5 min.

44. The illumination system of any one of Claims 1-6, wherein, The first, second and / or third mode time interval is greater than or equal to 3 min.

45. The illumination system of any one of Claims 1-6, wherein, The first, second and / or third mode time interval is greater than or equal to 3.5 min.

46. The illumination system of any one of Claims 1-6, wherein, The first, second and / or third mode time interval is greater than or equal to 4 min.

47. The illumination system of any one of claims 1 to 6, wherein, The first, second and / or third mode time interval is greater than or equal to 4.5 min.

48. The illumination system of any of claims 1 to 6, wherein, The first, second and / or third mode time interval is greater than or equal to 5 min.

49. The illumination system of any one of Claims 1-6, wherein, The duration of one dimmer phase is greater than or equal to 20 s.

50. The illumination system of any one of Claims 1-6, wherein, The duration of one dimmer phase is greater than or equal to 25 s.

51. The illumination system of any one of claims 1 to 6, wherein, The duration of one dimmer phase is greater than or equal to 30 s.

52. The illumination system of any one of claims 1 to 6, wherein, The duration of one illumination phase is greater than or equal to 15 s.

53. The illumination system of any one of claims 1 to 6, wherein, The duration of one illumination phase is greater than or equal to 20 s.

54. The illumination system of any one of Claims 1 to 6, wherein, The duration of one illumination phase is greater than or equal to 25 s.

55. The illumination system of any one of Claims 1-6, wherein, The duration of one illumination phase is greater than or equal to 30 s.

56. The illumination system of any one of claims 1 to 6, wherein, the duration of a dark phase and a light phase is greater than or equal to 15 s.

57. The illumination system of any one of claims 1 to 6, wherein, the duration of a dark phase and a light phase is greater than or equal to 20 s.

58. The illumination system of any one of Claims 1-6, wherein, the duration of a dark phase and a light phase is greater than or equal to 25 s.

59. The illumination system of any one of claims 1 to 6, wherein, the duration of a dark phase and a light phase is greater than or equal to 30 s.

60. The illumination system of any one of Claims 1-6, wherein, the duration of the dark phase is constant and different from the duration of the light phase.

61. A computer program product comprising machine readable instructions which cause a lighting source to operate according to the lighting protocol of claim 1.

62. The computer program product of claim 61, which is a data carrier or a data stream.

63. The computer program product of claim 61, wherein, the machine readable instructions, when loaded into a computer system and / or executed by the computer system, cause a lighting source to operate according to the lighting protocol of claim 1.

64. A kit for treating a disease, the kit comprising: a medicinal substance adapted to be topically applied to an area of skin to be treated, and a lighting system according to any one of claims 1 to 60, wherein the lighting system is configured to irradiate the area of the skin to which the medicinal substance has been applied.

65. The kit of claim 64, wherein, the disease is a skin disease.

66. The kit of claim 64, wherein, the medicinal substance is a photosensitive drug or a precursor of such a drug, the drug being capable of being excited by radiation in the emission spectrum.

67. The kit of claim 65, wherein, the skin disease is selected from the group comprising neoplastic skin diseases, warts, acne, impaired wound healing / chronic wounds, bacterial infections, fungal infections, inflammatory skin diseases.

68. The kit of claim 67, wherein, the neoplastic skin disease is selected from the group comprising actinic keratosis, basal cell carcinoma, squamous cell carcinoma in situ. the neoplastic skin disease is selected from the group comprising actinic keratosis, basal cell carcinoma, squamous cell carcinoma in situ.

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