DEVICE AND METHOD FOR THE TREATMENT OF DYSPLASIA

Abstract

Devices, fiber optic systems, and procedures and methods are provided that are capable of delivering low-intensity radiation to specific parts of the human or animal body. These include, in particular, laser devices and procedures used in the medical field that emit radiation in the red and infrared range, as well as optical fibers that transmit this radiation to a treatment site, such as areas of abnormal cell growth or development (e.g., dysplasia) or areas with viral or bacterial infections.

Description

Short description

[0001] The invention relates to radiation-emitting devices and optical fibers for transmitting this radiation to a specific location. In particular, these devices are laser devices used in the medical field that emit radiation in the red and IR range, as well as optical fibers that transmit this radiation to a treatment site, e.g., to sites where abnormal cell growth or development occurs, such as dysplasia. State of the art

[0002] Dysplasia is the general term for the abnormal growth or development of cells, which can occur at the microscopic (cells) or macroscopic (organs) level. Dysplasias at the cellular level include epithelial dysplasias and fibrous dysplasias of bone tissue. Some of these histopathological changes are usually precancerous and can develop into cancerous tissue. These precancerous dysplasias can be treated in several ways. The most modern treatments consist either of lift-off techniques with subsequent excision of the diseased mucosal sections or of thermal techniques in which the mucosa is irradiated with lasers (e.g., CO2 lasers) [1]. Laser treatment is used in numerous medical fields for various diseases and is a well-known tool, especially in surgery [2], [3].Photodynamic therapy (PDT) has also been used in some cases, e.g., for dysplasia of the oral cavity, dysplasia of the esophagus (Barrett's esophagus), or dysplasia of the vulva. PDT usually requires the systemic or local ingestion or administration of a drug (a photosensitizer, e.g., Photofrin) followed by appropriate light irradiation. The combination of photosensitizer, light, and the oxygen present in all cells generates reactive oxygen species that damage the irradiated abnormal cells. However, PDT is associated with prolonged photosensitivity in the treated patient, as some of the photosensitizer accumulates in the skin [4]. Current methods, e.g.,Surgery, thermal laser ablation, or PDT, achieves the goal of removing the mucous membrane and thus the precancerous lesion that might otherwise have developed into cancer. However, the associated discomfort is often disproportionate to the comparatively low risk of cancer transformation, and only a small proportion of patients opt for diagnosis and treatment. These treatments typically also involve the removal of relatively large portions of tissue in the affected area.

[0003] Dysplasias in the female genital area, such as cervical dysplasia, are a particularly serious problem. As already mentioned in the general considerations, treatment options include medication, electrocautery, cryosurgery, laser vaporization, and surgery. Cryotherapy involves cooling the cervix to subzero temperatures, damaging the cells through freezing. The main advantage of this method is that it is simple and inexpensive. A major disadvantage is that it cannot freeze the abnormal cells located deep down, leaving them untreated. Therefore, it is not suitable for treating advanced dysplasias. Loop excision is another conventional method in which the tissue is removed using a wire loop.Loop excision, also known as LEEP (Loop Electrosurgical Excision Procedure), uses a fine wire loop through which electrical energy is passed to remove the abnormal area of ​​the cervix. Cramping is common during the procedure, and some bleeding is to be expected. Cone biopsy involves removing a cone of tissue in and around the cervix, either surgically or with the aid of a laser. This procedure requires anesthesia and is performed in a surgical setting. Minor bleeding and discomfort are common after the procedure. For advanced stages of the disease, hysterectomy is another option, but it can only be performed on women who do not plan to have children in the future. Hysterectomy has the lowest recurrence rate of all treatments but is a major surgical procedure.Even after a hysterectomy, dysplasia in the vagina can recur, so regular Pap smears are essential even after a hysterectomy. It is especially not suitable for women of childbearing age. Laser therapy, for example, uses a carbon dioxide laser to vaporize the abnormal cells. Using a colposcope, the laser is aimed precisely at the affected area. However, due to the vaporization process, it is an invasive procedure. Healing after laser treatment is much faster than after freezing, as no dead tissue remains. Studies on laser treatment show that failure rates are lower with laser than with freezing. Another important advantage is that as the cervix heals, the squamocolumnar junction usually remains visible, making later evaluation easy.Another option for treating cervical dysplasia is PDT, although, as mentioned above, it is usually associated with a prolonged period of photosensitivity of the skin. All of these methods are very effective in treating invasive cancers. Although most of these methods are effective to some extent in treating dysplasia, they can unfortunately have a detrimental effect on fertility and the ability to conceive normally. In attempting to enclose all the abnormal tissue and the cervical remodeling zone, the cervix may lose the ability to withstand the weight of a normal pregnancy to term. One solution for an incompetent cervix is ​​surgical cerclage, which carries a high risk of failure, infection, and compromised future fertility.Furthermore, ablative techniques can leave behind microscopic remnants of abnormal tissue. This problem is typically addressed with additional ablative treatments, which further increase damage to the cervix. These existing treatments for dysplasia, and dysplasia of the female genital region in particular, demonstrate the need to find less invasive methods that are still capable of combating the abnormal cells and that also allow for faster healing of the affected area after treatment. Furthermore, it is becoming clear that it is necessary to find treatments for the early stages of the disease to avoid the need for highly invasive treatments in advanced stages.

[0004] For example, WO 94 / 15666A1, WO 93 / 21842A1, and US 8292935B2 present light irradiation devices for the treatment of cancer and dysplasia. However, these devices were designed for use in combination with photosensitizers during PDT treatment and are particularly unsuitable or oversized for early-stage dysplasia. US20150375194 describes and discloses a quantum dot laser diode for the treatment of tumors and non-tumorous diseases such as inflammation in bacterial infections. However, this document does not address dysplasia or the specific conditions of early-stage dysplasia. Dysplasia is not cancer, but a potential precancerous condition. Task of the invention and solution

[0005] It is the object of the invention to propose a gentle treatment of dysplasias and / or the treatment of associated tissue changes or tissue damage caused by inflammations, such as those caused by bacteria and / or epithelizing diseases or wound treatment or the regeneration phase of wounds and inflammations.

[0006] The problem is solved by overcoming these shortcomings of existing treatments for dysplasia and similar diseases through a light-mediated treatment with a power density suitable for the respective individually tailored case (application) in combination with irradiation in the red and NIR range of the electromagnetic spectrum (600 nm - 3000 nm). More specifically, the light-mediated treatment disclosed here refers to light irradiation at wavelengths between 600 - 1300 nm, and in particular to irradiations at 627±10 nm, 690±10 nm, 760±10 nm, 810±10 nm, 920±10 nm, 1065±30 nm, or 1270±30 nm, in particular 1270±6 nm, and particularly suitably at a central wavelength of 1267±3 nm.According to the invention, the low and suitable power density for the respective application lies in a preferred range of 2 watts to 4 watts, for example 20-50 J / cm2, a power intensity so as not to excessively heat the tissue and thus avoid unnecessary damage to the collagen tissue. By controlling the irradiation duration. For a first laser, for example, 6-7 diodes with a power of 300 milliwatts (mW) to 400 mW each can be used. Light-mediated treatment with such wavelengths is able to directly excite the oxygen present in the cells to singlet oxygen and thereby generate singlet oxygen and other reactive oxygen species through additional biochemical mechanisms. Furthermore, such irradiation, e.g. at 1240-1300 nm, has an immunogenic effect and stimulates the release of cytokines and chemokines, thereby modulating the body's immune response.By combining such irradiation with a low power density, the dysplasia cells are eliminated—in contrast to existing methods—while preserving the collagen matrix, promoting and facilitating the healing process. The treatment promotes the migration of new cells into the affected area and prevents scarring. In general, a low dose of laser radiation promotes cell growth and promotes cell division. This contributes to accelerated healing and a better cosmetic and functional outcome. The desired homogenous, low power density is achieved by the design of the entire irradiation device, including the fiber optic and applicator components, and by limiting the light irradiance, thus ensuring a specific temperature range.In some embodiments of the present invention, this is achieved by continuous wave (CW) irradiation, which may also be interrupted; in others, the effect is achieved by pulsed red and NIR irradiation. In further embodiments of the present invention, this is achieved by temperature monitoring, for example by means of sensors, which ensure, via a control loop or an alarm system, that the temperature or power density remains below a critical value. According to one embodiment of the invention, two (or more) wavelengths are mixed (e.g., 1265±2 nm and 1272±2 nm). The narrowband excitation according to the device and method of the present invention makes it possible to increase the proportion of radiation absorption that specifically leads to the excitation of oxygen and the formation of reactive oxygen species, compared to the proportion of radiation absorption that simply leads to tissue heating.As explained above, this lower thermal stress on the tissue preserves the collagen matrix and allows the migration of new cells into the existing matrix, thereby promoting and facilitating the healing process.

[0007] The inventive treatment of dysplasia is based on the light-induced generation of reactive oxygen species at the treatment site and on the immunostimulatory and immunomodulatory effects of this light. These effects can be enhanced—in another embodiment of the invention—by combining PDT (photodynamic therapy) with light and a suitable photosensitizer.

[0008] Dysplasias are frequently associated with viral infections, such as HPV (human papillomavirus). The combination of light-induced reactive oxygen species and immune stimulation, as induced by the device and method of the present invention, is also effective in eliminating viruses and reducing viral load [5]. Elimination of viruses through treatment also contributes to the prevention of dysplasia, since dysplasias are partly caused by viruses. The present method and procedure are thus also suitable as a preventative treatment for the treatment of pre-dysplasia lesions (PAP II, see below).

[0009] A very high power density is often used for the elimination of tumor cells, whereas the power density according to the invention for the effective treatment of dysplasias while preserving the collagen matrix tissue, as disclosed here, is considerably lower.

[0010] Embodiments of the present invention include devices and / or fiber optic equipment / instruments of various shapes and sizes that enable homogeneous irradiation of dysplasia areas in the red and near-infrared range, primarily at 600–1300 nm, with a low power density. The invention utilizes laser irradiation at 600–1300 nm, specifically at 1240–1300 nm, to directly stimulate oxygen in the tissue, thereby eliminating mucosal cells. This occurs without overheating the intercellular matrix, allowing it to be preserved and new cells to colonize the matrix and the surface. Deeper in the tissue, the low intensity and dose of radiation can stimulate cell proliferation and activity to support the healing process and shorten the recovery time of the treated area.

[0011] Typically, fiber optic devices such as diffusers, frontally steered illumination probes, balloon catheters, etc., are connected to a laser source and used for irradiation. Pulsed radiofrequency sources (MHz range or higher) can also be used. Temperature monitoring and additional cooling can be employed to prevent overheating of the treatment area. Raman spectroscopy can also be used to characterize the tissue and delineate the area, or the device can be combined with optical coherence tomography (OCT) for diagnosis and treatment monitoring. The device and procedure described here were developed for the treatment of dysplasia tissue in various body areas, such as dysplasia in the mouth, pharynx, esophagus, genital, or anal region. However, the device and procedure, which uses low power density in the red and near-infrared range, can also be applied to other tissues.Although the device and method are particularly effective for precancerous lesions such as dysplasia, they can also be used for cancerous lesions as well as inflamed and other diseased tissue. Furthermore, this device and method can also be used to treat or alleviate diseases or local or systemic viral or bacterial infections. The device and method described here can also be combined with suitable substances, such as pro-oxidative substances [6], to enhance their effectiveness. Furthermore, the device and method described here can also be combined with other light-based treatment methods, such as PDT (see below). Fig. The particular advantage of the device and method described here is that the generation of reactive oxygen species at the treatment site occurs both indirectly – through excitation of the photosensitizer – and directly through the excitation of oxygen in the treatment area. Such photosensitizers can be approved PDT dyes such as temoporfin, talaporfin, talaporfin sodium, padeliporfin, verteporfin, HpD, porfimer sodium, chlorin e6, fimaporfin, redaporfin, photochlor, protoporphyin IX, ALA (as a photosensitizer prodrug), IRDye700DX, methylene blue, or safranin. In addition, such photosensitizers can also be endogenous protoporphyrin IX or other endogenous photosensitizers. Added to this is the immunostimulating and immunomodulatory effect of light. This allows the amount of photosensitizer used to be significantly reduced, which is associated with reduced side effects of the treatment.The combination with another light-based treatment method, such as PDT, also has the advantage that different tissue areas can be treated differently. For example, the tumor area can be treated using a photosensitizer and a suitable wavelength—corresponding to the photosensitizer's absorption spectrum—and the peripheral areas can be treated with laser irradiation at 600–1300 nm, specifically 1240–1300 nm, to treat these areas in a tissue-sparing manner and to utilize the immune-stimulating effect of light at this wavelength. Furthermore, the combination of two wavelengths in the device and method described here can also be used to stimulate two oxygen absorption transitions, thus increasing the efficiency of the treatment.

[0012] Furthermore, the device and method described here can also be used to specifically irradiate and stimulate various tissues (e.g., skin tissue layers, white and brown fat tissue) by utilizing the specific absorption of these tissues, or to reach underlying tissue layers through them. For example, due to the relatively low light absorption of fat at 1270±30 nm, light irradiation at these wavelengths in particular can be particularly well-reached and treated with these laser systems and methods, even in tissue areas covered (or surrounded) by fat cells, including areas with dysplasia.

[0013] In dysplasias of the female genital area (vulva, cervix and vagina), the observed tissue changes are classified according to Papanicolaou as follows: PAP I: normal findings PAP II: Inflammatory / degenerative changes (still normal) PAP III: Severely inflammatory and / or dysplastic changes, unclear findings, neoplasia (precancerous stage) cannot be ruled out PAP IIID: Mild to moderate dysplasia PAP IVA: Severe dysplasia PAP V: Suspected invasive carcinoma (cancer)

[0014] The device and method of the present invention can be used for all stages of PAP II and above, but are particularly suitable for the treatment of stages PAP II and III.

[0015] The basic structure of the device or the general scheme according to the present invention is shown in the Fig. shown.

[0016] The device consists of a light source with a wavelength of 600–3000 nm and an optical delivery system for irradiating the treated area. In a preferred embodiment, the device consists of a light source with a wavelength of 1240–1300 nm and an optical delivery system for irradiating the treated area.

[0017] The optical unit for delivering light to the treated area can be a fiber bundle or a solid optical fiber. The optical fiber can be a single-mode or multimode fiber (quartz-quartz or quartz-polymer), a hollow-core quartz fiber, or a balloon fiber.

[0018] When combining the device and procedure described here with other light-based treatment methods, such as PDT, radiation of a second wavelength is required.

[0019] This combination of two light sources as an embodiment of the present invention is described in Fig. shown.

[0020] Fig. shows the basic structure of an inventive device for red and NIR irradiation with low power density with the option for combining two irradiation wavelengths.

[0021] The general scheme is Fig. The device contains two light sources at 600–3000 nm. In a preferred embodiment, one of these is a light source at 1240–1300 nm. The device contains a wavelength combiner for the two wavelengths and an optical delivery system for directing the combined radiation to the treated area.

[0022] A bundle of optical fibers or a free-space multiplexer containing a dichroic mirror and collimating lenses or a fused fiber wavelength division multiplexer (WDM) can be used as a wavelength combiner.

[0023] The optical unit for the combined light delivery to the treated area can be a fiber bundle or a solid optical fiber. The optical fiber can be a single-mode (SM) or multimode (MM) fiber (quartz-quartz or quartz-polymer), a hollow-core quartz fiber, or a balloon fiber. To irradiate the affected area with the most uniform intensity possible, it can be advantageous to design the transmission fiber with a square core cross-section, which results in top-hat radiation intensity distributions. Split sections can also be helpful in this regard in the transmission path.

[0024] In brief, the embodiments include light-emitting and light-guiding devices for delivering low-power density red and NIR radiation. The embodiments include devices for delivering low-power density red and NIR radiation in combination with cooling and temperature control.

[0025] The above and other objects, features and advantages of the present invention will become apparent from the following description taken in conjunction with the accompanying drawings. Detailed description of the embodiments

[0026] Embodiments include devices that provide red and NIR irradiation with low power density (see Fig. ). These versions can be combined with a cooling unit and temperature control to prevent overheating of the treated area (see Fig. A few watts of laser power, 1-10 watts, preferably 2 to 4 watts, depending on the size of the irradiated area, may be sufficient. Another option to prevent overheating is cooling at the exit surface or the irradiated surface. Cooling devices, such as those used in other laser treatments, can also be used.

[0027] Out of Fig. is an illustration of an example of a device according to the present invention that enables red and NIR irradiation with low power density and cooling and temperature control.

[0028] Fig. shows an illustrative example of a device according to the present invention enabling red and NIR irradiation with low power density and cooling and temperature control, with the option for combining two irradiation wavelengths.

[0029] In addition, such devices can be equipped with a balloon fiber to enable even illumination of the area to be treated. This is described in the Fig. illustrated.

[0030] Fig. : Visualization of a low power density red or NIR irradiator equipped with a balloon fiber.

[0031] Fig. : Visualization of a low power density red and NIR irradiator equipped with a balloon fiber, with the option to combine two irradiation wavelengths.

[0032] In a preferred embodiment of the present invention, the device for low-power irradiation in the red and NIR range is a laser emitting radiation between 600 and 1300 nm. In a particularly preferred embodiment, the low-power density irradiation device is a laser operating at wavelengths of 627±10 nm, 690±10 nm, 760±10 nm, 810±10 nm, 920±10 nm, 1065±30 nm, or 1270±30 nm.

[0033] In a preferred embodiment, the laser, which delivers NIR radiation between 1240 and 1300 nm, is combined with a cooling device and a temperature control device. In another particularly preferred embodiment, the laser, which operates at a wavelength between 1240 and 1300 nm, is equipped with a balloon fiber to enable uniform illumination of the area to be treated. In another particularly preferred embodiment, the laser that emits NIR radiation is a pulsed laser or is used in pulsed laser mode. Embodiments also include the combination of such low-power-density red and NIR radiation lasers with a Raman or OCT device for diagnosis or therapy monitoring. The laser systems can operate in both CW and pulsed laser mode.

[0034] In further embodiments of the present invention, the device and method for treating dysplasias can also be used or in conjunction with the treatment of proliferative diseases and / or local and / or systemic viral and / or bacterial infections and / or epithelial dysplasias and / or wound healing.

[0035] In another particular embodiment, the device and method of the present invention are combined with a PDT treatment in the manner illustrated above, using a photosensitizer and light irradiation with a suitable wavelength corresponding to the absorption spectrum of the photosensitizer. Such photosensitizers can be, for example, tetrapyrrole systems such as porphyrins, chlorins, bacteriochlorins, or phthalocyanines, or their metal complexes. In a preferred embodiment, the device and method of the present invention are combined with a PDT treatment, wherein the photosensitizer is selected from the group of temoporfin, talaporfin, talaporfin sodium, padeliporfin, verteporfin, HpD, porfimer sodium, chlorin e6, fimaporfin, redaporfin, photochlor, protoporphyin IX, ALA (as photosensitizer prodrug), IRDye700DX, methylene blue or safranin.Such photosensitizers can also be endogenous protoporphyrin IX or other endogenous photosensitizers. In this case, the device and the method of the present invention are used, among other things, to irradiate peripheral regions of the PDT-treated area in order to counteract tumor recurrences.

[0036] The following example is intended to provide those skilled in the art with a full and illustrative disclosure and description of how to make a device according to the present invention and to illustrate its operation, but is not intended to limit the scope of what the inventor considers to be the invention. Examples

[0037] Examples of a laser system according to the device and the method of the present invention Examples of a laser system according to the device and the method of the present invention are shown in the Fig. See the details and descriptions in the illustrations.

[0038] Explanation: The laser consists of a light source with a wavelength of e.g. 1267 nm ±3 nm (or as in the Fig. specified 1265 nm) and a second light source with a wavelength in the range of 600 - 3000 nm, a beam combiner and an optical delivery cable, which ensure the delivery of the combined beams (of e.g. 1267 nm and 600 - 3000 nm) to the treatment area.

[0039] The laser, with a wavelength of, for example, 1267 nm, can have a fiber-coupled or free-space output. The second laser, with a wavelength of 600–3000 nm, for example, 690±10 nm, can also have a fiber-coupled or free-space output.

[0040] In special applications, the second laser may also be a laser emitting radiation at 627±10 nm, 690±10 nm, 760±10 nm, 810±10 nm, 920±10 nm, 1065±30 nm or 1270±30 nm.

[0041] The laser beam of the first laser with a wavelength of e.g. 1267 nm and the laser beam of the second laser are combined by a beam combiner.

[0042] The beam combiner can be manufactured in several ways. It can be a free-space optical system containing collimating and focusing lenses as well as dichroic and reflecting mirrors ( Fig. , or a fused single-mode wavelength division multiplexer (WDM) that connects single-mode fibers ( Fig. or multimode fibers ( Fig. ). This can also be done on the basis of a coupler, which is an arrangement of single-mode or multimode fibers drawn in a polymer layer and having an optical contact (GTWave technology, Fig. 7d).

[0043] It is also possible to combine the light beams simply by using a fiber bundle ( Fig. 7e).

[0044] The combined light beam (e.g., 1265 nm or 1267 nm plus 600-3000 nm) is delivered to the surgical site via a special delivery cable. This can be a quartz-quartz fiber, a quartz-polymer fiber, a hollow-core fiber, or a balloon fiber.

[0045] Having described preferred embodiments of the invention with reference to the present examples, it is to be understood that the invention is not limited to the precise embodiments and that various changes and modifications may be made therein by those skilled in the art without departing from the scope of the invention as defined in the appended claims.

[0046] The device and the method with the various embodiments of the invention can also be equipped with a control and computing unit, with or without a combination of photodynamic therapy (PDT), whereby a control program can make the treatment stages variable depending on the measurement data of the previous treatment stage(s). References [1] D. Condor, C. Culcitchi, R. Blum, O. Baru, S. Buduru, A. Kui, I. Tig, A Review of CO2 Laser-Mediated Therapy for Oral Mucosal Lesions, Appl. Sci., 11, 7744 (2021) [2] E. Khalkhal, M. Rezaei-Tavirani, MR Zali, Z. Akbari, The Evaluation of Laser Application in Surgery: A Review Article, J. Lasers Med. Sci., 10 (Suppl 1), pp. S104-S111 (2019). [3] DJ Jordan, P. Mafi, R. Mafi, M. Malahias, A. El Gawad, The Use of LASER and its Further Development in Varying Aspects of Surgery, Open Med. J., 3 (Suppl-3, M2), pp. 288-299 (2016). [4] JH Correia, JA Rodrigues, S Pimenta, T Dong, Z Yang, Photodynamic Therapy Review: Principles, Photosensitizers, Applications, and Future Directions, Pharmaceutics, 13, 1332 (2021). [5] A. Wiehe, JM O'Brien, MO Senge, Trends and targets in antiviral phototherapy, Photochem. Photobiol. Sci., 18, 2565-2612 (2019). [6] DG Choi, J. Venkatesan, MS Shim, Selective Anticancer Therapy Using Pro-Oxidant Drug-Loaded Chitosan-Fucoidan Nanoparticles, Int. J. Mol. Sci., 20, 3220 (2019). QUOTES CONTAINED IN THE DESCRIPTION

[0000] This list of documents submitted by the applicant was generated automatically and is included solely for the convenience of the reader. This list is not part of the German patent or utility model application. The DPMA assumes no liability for any errors or omissions. Cited patent literature

[0000] WO 94 / 15666A1

[0004] WO 93 / 21842A1

[0004] US 8292935B2

[0004] US 20150375194

[0004] Zitierte Nicht-Patentliteratur

[0000] D. Condor, C. Culcitchi, R. Blum, O. Baru, S. Buduru, A. Kui, I. Tig, A Review of CO2 Laser-Mediated Therapy for Oral Mucosal Lesions, Appl. Sci., 11, 7744 (2021

[0046] E. Khalkhal, M. Rezaei-Tavirani, M. R. Zali, Z. Akbari, The Evaluation of Laser Application in Surgery: A Review Article, J. Lasers Med. Sci., 10 (Suppl 1), pp. S104-S111 (2019

[0046] D. J. Jordan, P. Mafi, R. Mafi, M. Malahias, A. El Gawad, The Use of LASER and its Further Development in Varying Aspects of Surgery, Open Med. J., 3 (Suppl-3, M2), S. 288-299 (2016

[0046] J. H. Correia, J. A. Rodrigues, S. Pimenta, T. Dong, Z. Yang, Photodynamic Therapy Review: Principles, Photosensitizers, Applications, and Future Directions, Pharmaceutics, 13, 1332 (2021

[0046] A. Wiehe, J. M. O'Brien, M. O. Senge, Trends and targets in antiviral phototherapy, Photochem. Photobiol. Sci., 18, 2565-2612 (2019

[0046] D. G. Choi, J. Venkatesan, M. S. Shim, Selective Anticancer Therapy Using Pro-Oxidant Drug-Loaded Chitosan-Fucoidan Nanoparticles, Int. J. Mol. Sci., 20, 3220 (2019

[0046]

Claims

[1] Device for the treatment of dysplasia, consisting of at least one laser emitting radiation at 627±10 nm, 690±10 nm, 760±10 nm, 810±10 nm, 920±10 nm, 1065±30 nm or 1270±30 nm, and a fiber optic device transmitting this radiation to the treatment site. [2] Device for treating dysplasia according to claim 1, consisting of a laser emitting radiation at 1267±3 nm and a fiber optic device transmitting this radiation to the treatment site. [3] Device for the treatment of dysplasia according to claim 1, consisting of two separately controllable lasers, - wherein one laser emits radiation at 627±10 nm, 690±10 nm, 760±10 nm, 810±10 nm, 920±10 nm, 1065±30 nm or 1270±30 nm and - the second laser emits radiation at 1240 - 1300 nm, in particular at 1267±3 nm - and a fiber optic device that transmits this radiation to the treatment site. [4] Device for the treatment of dysplasia according to at least one of claims 1 to 3, wherein the optical unit for supplying light to the treated area is a fiber bundle or an optical fiber, wherein the optical fiber can be a single-mode or multi-mode fiber (quartz-quartz or quartz-polymer) or a hollow-core quartz fiber or balloon fiber. [5] Device according to at least one of claims 1 to 4, which is used in the treatment of dysplasias and / or proliferative diseases and / or local and / or systemic viral and / or bacterial infections and / or epithelial dysplasias and / or wound healing. [6] Device according to any one of claims 1 to 4 for use in the treatment of oral, pharyngeal, nasopharyngeal, esophageal, gastrointestinal, genital or anal dysplasias. [7] Device according to at least one of claims 1 to 4, which is used for light-mediated immunomodulation of dysplasias and proliferative diseases. [8] Device according to at least one of claims 1 to 4, which is used for light-mediated immunomodulation or treatment of cancerous and precancerous lesions. [9] Device according to at least one of claims 1 to 4 for the treatment of dysplasias and proliferative diseases, which operates in continuous (CW) or pulsed mode. [10] Method for treating dysplasia with at least one laser, - wherein the laser emits radiation at 627±10 nm, 690±10 nm, 760±10 nm, 810±10 nm, 920±10 nm, 1065±30 nm or 1270±30 nm and - and a fiber optic device through which this radiation is transmitted to the treatment site. [11] Method for the treatment of dysplasia with two separately controllable lasers, - wherein one laser emits radiation at 627±10 nm, 690±10 nm, 760±10 nm, 810±10 nm, 920±10 nm, 1065±30 nm or 1270±30 nm and - the second laser emits radiation at 1240 - 1300 nm, in particular at 1267±3 nm, - and a fiber optic device that transmits these radiations to the treatment site. [12] A method according to at least one of claims 10 and 11 for emitting light capable of converting oxygen from the ground state to singlet oxygen or of exciting oxygen in the ground state to singlet oxygen, for the treatment of dysplasias and proliferative tissue and / or for the treatment or alleviation of local or systemic viral or bacterial infections. [13] Method according to at least one of claims 10 to 12 for the treatment of dysplasias and proliferative diseases or local or systemic viral or bacterial infections, in which at least one temperature control and / or at least one cooling option is used. [14] Method according to at least one of claims 10 to 13 for the treatment of dysplasias and proliferative diseases or local or systemic viral or bacterial infections, in which the treatment is combined with photodynamic therapy with a photosensitizer. [15] A method according to any one of claims 10 to 14 for the treatment of dysplasias and proliferative diseases or local or systemic viral or bacterial infections, in which a unit for diagnosing dysplasia tissue areas is used. [16] Method according to at least one of the preceding claims 10 to 15 for the treatment of dysplasias and / or proliferative diseases and / or local and / or systemic viral and / or bacterial infections and / or epithelial dysplasias and / or wound healing in combination with photodynamic therapy (PDT) with a photosensitizer from the group of temoporfin, talaporfin, talaporfin sodium, padeliporfin, verteporfin, HpD, porfimer sodium, chlorin e6, fimaporfin, redaporfin, photochlor, protoporphyrin IX, ALA (as photosensitizer prodrug), IRDye700DX, methylene blue or safranin. [17] Method according to at least one of the preceding claims 10 to 16 for the treatment of dysplasias and / or proliferative diseases and / or local and / or systemic viral and / or bacterial infections and / or epithelial dysplasias and / or wound healing, wherein a control and computing unit is used and wherein a control program is designed to modifiable the treatment stage(s) and the course of therapy.

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