PHOTOTHERAPEUTICAL APPARATUS

Abstract: The subject matter of this invention is a phototherapeutical apparatus, which is suited for the treatment and prevention of diseases of the body, favourable for diseases of the nose, paranasal sinuses, mouth cavity, throat, oesophagus, stomach, small and large intestines, rectum, ear, trachea, urogenital tract, portio, uterus and conjuctiva.The characteristic features of the apparatus are, that is provided with an ultaviolet source (1), an optical coupling unit (3) which focuses the ultraviolet beam (2) going out from the light source, a light delivery system (4) connected to the coupling unit (3) and an ultraviolet light irradiating unit (5).The subject matter of the invention is furthermore a light source and optical coupling units.

Description: PHOTOTHERAPEUTICA APPARATUS The subject matter of this invention is a phototherapeutical apparatus, a light source and optical coupling for this, and the application of this apparatus. This invention relates to an apparatus, which is applicable for the treatment and prevention of common inflammatory diseases of the body cavities, for example for the treatment of the diseases of the nasal mucous membrane and paranasal sinuses such as allergic rhinitis (hay fever), vasomotor rhinitis, non-allergic eosinophilic rhinitis, chronic sinusitis (inflammation in the paranasal sinuses), or nasal polyps with ultraviolet light. Rhinitis is an inflammatory disorder of the nasal mucous membrane, which is characterised by nasal itch, sneeze, nose running, nasal blockage, and rarely by loss of smelling. The inflammation of the nasal mucous membrane is frequently associated with the inflammation of the paranasal sinuses (rhinosinusitis, chronic sinusitis). As a consequence of the frequent and persistent inflammation of the mucous membrane hyperproliferative lesions, the so-called polyps develop on the mucous membrane. One characteristic disease is the allergic rhinitis (hay fever). The allergic rhinitis or hay fever is the most frequent allergic disease affecting 10-20% of the population. The number of patients with allergic rhinitis especially in the well developed industrial countries increase veiy rapidly in the last few years. Because of the high number of patients the direct and indirect costs of the treatment are huge. Although the hay fever is not a very severe disease, its, unpleasant symptoms largely worsen the quality of life. Hay fever is frequently associated with allergic conjunctivitis, and sometimes by general symptoms. The symptoms last only for a few months in some patients (seasonal rhinitis), while in others it last in the whole year (perennial rhinitis). For the development of the symptoms the allergen-induced specific IgE binding to the surface of mast cells, then after repeated exposure with the antigen the activation of cells possessing IgE receptors are responsible. As a result of this activation stamin and other preformed mediators will be released from the mast cells, and in these cells new inflammatory mediators will be produced attracting further mflammatory cells into the mucous membrane (Howarth PH, Salagean M, Dokic D: Allergic rhinitis: not purely a histamine- related disease. Allergy 55: 7-16, 2000). The treatment of the disease is not solved. To block the released mediators from the increased number of inflammatory cells in the nasal mucous membrane, which are responsible for the clinical symptoms, antihistamines are used locally or systemically; to inhibit the mediator release sodium cromoglycate is available and to block new mediator synthesis corticosteroids are used locally or systemically. In special circumstances desensitizing therapy might be introduced. Although the pathogenesis of the development of the clinical symptoms is already well known in general, with the available drugs for the treatment of this disease complete symptom-free state might not be reached frequently, therefore, every new method for the treatment of this disease has a great medical significance. Another characteristic disease is vasomotor rhinitis. Nasomotor rhinitis is an inflammatory disorder of the nasal mucous membrane with unknown origin, which might be induced by different unspecific factors. The clinical symptoms are largely similar to that of allergic rhintitis; permanent nasal blockage, nasal itch, sneeze, nose running, and rarely loss of smelling can be found. For the symptoms mastocyte-activating mediators are responsible, which are released from the nerve endings of the nasal mucous membrane upon irritative effects. Another characteristic disease is the nonallergic eosinophilic rhinitis. This disease is characterised by the high number of eosinophils in the nasal secretions and by the lack of allergic origin. The disease is frequently associated with the development of nasal polyps, the hyperproliferative condition of the nasal mucous membrane. The clinical symptoms are the same as in allergic rhinitis. Another diseases are rhinosinusitis and sinusitis. The inflammation of the paranasal sinuses is frequently associated with the inflammatory condition of the nasal mucous membrane (nasosinusitis), but isolated inflammatory condition of the paranasal sinuses is also a frequent disease (sinusitis). This disease has oft an allergic origin, although its exact cause remains frequently unknown. The treatment is not solved, but usually the same therapy is used as for rhintitis. Ultraviolet light is used for more than 20 years for the treatment of allergic and auto-immune skin diseases. Ultraviolet light inhibits the antigen-induced cellular immune response, and is able to induce tolerance (Streilein JW, Bergstresser PR: Genetic basis of ultraviolet-B on contact hypersensitivity. Immunogenetics 27: 252-258, 1988). The immune reaction suppressive effect of ultraviolet light is based on its inhibitory effect on the antigen presentation, and on the induction of T-cell apoptosis. Irradiation of the skin with ultraviolet-B light (280 nm - 320 nm), or with ultraviolet-A light (320 nm - 400 nm) on a previously psoralen- photosensitized skin, inhibits the iπimunological processes in the skin. For the treatment of skin diseases there are a number of phototherapeutical devices available. At present there are many different ultraviolet light sources available. These light sources might be grouped based on different aspects, (operational principle, output energy or power, operating in impulse mode or in continuous mode, emitting monochromatic or polychromatic light, etc). Broadband ultraviolet light sources were used earlier for the treatments with ultraviolet light (broadband UVB, BB-UVB), in the last years more efficacious narrow-band ultraviolet light sources (narrow-band, NB-UVB) came into general use (Degitz K, Messer G, Plewig G, Rocken M: Schmalspekrrum-UVB 311 nm versus Breitspektrum-UVB. Neue Entwicklungen in der Phototherapie. Hautarzt 49: 795-806, 1998). Based on our previous investigations on psoriatic patients, the 308 nm xenon chloride excimer laser is more effective in the treatment than the NB-UVB one (Bόnis B, Kemeny L, Dobozy A, Bor Zs, Szabό G, Ignacz F: 308 nm UVB excimer laser for psoriasis. Lancet 35: 1522, 1997; Kemeny L, Bόnis B, Dobozy A, Bor Z, Szabo G, Ignacz F: 308-nm excimer laser therapy for psoriasis. Arch Dermatol. 137: 95-96, 2001). In the phototherapy a significant progress was achieved by the appearance of the ultraviolet light delivering optical systems. Such an ultraviolet light delivering phototherapeutical system with fibre optic is used in the Saalmann Cup instrument, in which the concentrated ultraviolet light is conducted into a fibre optic cable. Therefore, it is suitable for the treatment of smaller lesions of the skin or mucous membrane (Taube KM, Fiedler H: Hochkonzentrierte UN Bestrahlung kleiher Hautbezirke m ' it. einem neuen Punktstrahler. Grundlagen und klinische Ergebnisse. Deutsche Dermatologe, 10: 1453, 1992). This system is, however, unsuitable to be introduced into smaller cavernous organs because of the large diameter of the area, which is in contact with the skin or mucous membrane. It cannot be introduced into smaller cavernous organs, such as the nasal cavity, because of the thickness of the fibre optic cable. Only the cavernous organs might be treated with it, in which the distal end of the fibre optic cable and the area to be treated can be controlled by eye (i.g. oral cavity). It is also unsuitable for the treatment of body areas, which cannot be controlled by eye (nasal and paranasal mucous membrane, gastrointestinal or urogenital mucous membrane). There are a number of light delivery systems to conduct and to emit ultraviolet light of ultraviolet light entitting laser light sources. The 308 nm xenon chloride excimer laser light delivered by fibre optic cable is suitable for the treatment of smaller cavities, like for the cleaning of root canal by ablation (Folwaczny M, Mehl A, Haffner C, Hickel R: Substance removal on teeth with and without calculus using 308 nm XeCl excimer laser radiation. An in vitro investigation. J Clin Periodontol 26: 306-12, 1999). It is suitable to treat atherosclerosis by treating the blood vessel walls (U.S. Patent 4,686,979), or to enhance the cardiac oxygenisation with tiansmyocardial laser revascularisation (U.S. Patent 5,976, 124), or ώ biting neovascularisation during angioplasty by destroying myocardial cells (U.S. Patent 5,053,033). It is an important common feature of these systems, that the high-energy ultraviolet light at the end of the light delivering system reaches small areas of only a few hundred microns, where the mechanism of action is to induce breakage in the chemical bondage, thereby a tissue damaging ablative effect. Using a multitude of small fibre optic cables the treatment of larger skin lesion has become possible (U.S. 6,071,302; WO9607451, Asawanonda P, Anderson RR, Chang Y, Taylor CR: 308-nm excimer laser for the treatment of psoriasis: a dose-response study. Arch Dermatol 136: 619-24, 2000). Phototherapeutical systems attached to endoscope are used for the photodynamic treatment of tumours (bladder carcinoma or bronchial cancer), however, in these instruments no ultraviolet light is used, and they have special distal ends for tumour treatment (U.S. Patents of Nos. 4,313,431; 4,612,938; 4,676,231; 4,998,930; 5,146,917). At present, the phototherapeutical systems delivering ultraviolet light consist of a hand piece specifically shaped to a special problem, and they are either unsuitable or little suitable for the treatment of small body cavities such as the nasal cavity with visual control. We aimed to develop an ultraviolet light emitting phototherapeutical apparatus for the treatment of small cavities, and to construct a special ultraviolet light source, furthermore the subject-matter of the present invention is the application of this phototherapeutical apparatus. Only the light of ultraviolet light delivering lasers can be lead with good efficiency into thin optical fibre cables having diameter of a few tenth of millimeti'e in the most of cases, because of the properties of the laser light, but the laser apparatuses are expensive. It is necessary an ultraviolet light enύtting apparatus by this reason, which emits light from a small volume, enabling to lead light energy necessary for the actual phototherapeutic treatment even into an optical fibre cable of small diameter (of a few tenth of millimeti'e). It is desirable that this light source should be relatively cheap to manufacture in comparison with the laser ones. One of the potential light sources is a high- pressure gas filled lamp with short arch. Although ultraviolet light has been used for the treatment of hyperproliferative and inflammatory skin diseases since many years, ultraviolet light has not been used for the treatment of common, immunologically mediated disorders of the nasal mucous membrane. Neuman and Finkelstein used narrow-band, low energy, red-light phototherapy for the treatment of the nasal mucous membrane, and they found it effective for perennial allergic rhinitis and for nasal polyposis (Neuman I, Finkelstein Y Narrow-band red light phototherapy in perennial allergic rhinitis and nasal polyposis. Ann Allergy Asthma Immunol 78: 399-406, 1997). The experimental data underlying the present invention show that single and/or repeated irradiation of the nasal mucous membrane and paranasal sinuses with ultraviolet light of different wavelengths (UVB, UVA, UVB plus UVA, and photochemotherapy with psoralen plus UVA) inhibit the clinical symptoms of rhinitis, sinusitis and rhinosinusitis of different origins, and result the regression of nasal polyps. The constructed apparatus proved to be effective also for the prevention of these diseases, when ultraviolet phototherapy was applied before the appearance of the clinical syττφtoms. The subject-matter of this invention is a phototherapeutical apparatus, which is used for the treatment and for the prevention of the diseases of the body, preferably for disorders of the nasal mucous membrane and paranasal sinuses, mucous membrane of the cavities of mouth, throat, oesophagus, stomach, small and large intestines, gastrointestinal tract, rectum, ear, trachea, urogenital tract, portio, uterus and the conjunctiva. The characteristic featui'e of the apparatus is that it is provided with a source of ultraviolet light, an optical coupling unit focusing the light, a light delivery system and a contact unit of ultraviolet irradiation. The subject matters of the invention are furthermore a light source and optical coupling apparatuses for the said apparatus characterised by that the power supply unit is connected to electrodes built into a quaitz bulb. The bulb is filled with a gas or a mixture of gases, e. g. a mixture of xenon, argon and mercury vapour. The gas or mixture of gases is able to emit light also in the ultraviolet spectrum under influence of electric discharge. The bulb is furthermore provided with a concave mirror reflecting a part of ultraviolet light beam and a condensing lens focusing the ultraviolet light. The quartz bulb, the concave mirror, the condensing lens and an outlet opening are mounted into housing, and an optical filter and a light forwarding system are mounted behind the outlet. The apparatus described in the present invention can be used effectively for the treatment and for the prevention of inflam atory disorders of the body cavities, such as in hay fever, vasomotor rfώiitis, nonallergic eosinophilic rhinitis, chronic sinusitis and in nasal polyposis. The phototherapeutical apparatus according to invention, its structural elements, as well as the results of application of the apparatus are shown in the Figures 1 to 11. The Figure 1 shows the main elements of the phototherapeutical apparatus and their arrangement. The Figure 2 shows an advantageous embodiment of the ultraviolet light source and the optical coupling unit. The Figure 3 shows an embodiment of the optical coupling unit, wherein the light of the targeting light source is simultaneously lead into the unit, which enables to monitor the treated surface at the same time. The Figure 4 shows an embodiment of the contact unit for irradiation with ultraviolet light, wherein the light forwarding unit is inserted into the body of the ultraviolet light irradiating contact unit. The Figure 5 shows an embodiment of the ultraviolet light irradiating contact unit, wherein the body of ultraviolet light irradiating contact unit does not contain any light delivery system. The ultraviolet light is directed by a dichroic mirror, while the scanning light is directed with a concave mirror having a hole in the middle onto the surface to be treated. The Figure 6 shows an embodiment of the ultraviolet light irradiating contact unit, which ends with a light reflecting surface, and which is applicable for treatment of a flat surface. The Figure 7 shows an embodiment of the ultraviolet light irradiating contact unit, which ends with a reflecting surface, applicable for cylindrical!/ symmetric treatment. The Figure 8 shows an embodiment of the ultraviolet light irradiating contact unit, which is applicable for a dot-like treatment. The Figure 9 shows a phototherapeutical apparatus, which is applicable for a treatment using a flexible endoscop. In fig. 10. we show that the 308 nm xenon chloride laser decreases the clinical scores of the nasal blockage, nasal itch, nose running, sneeze and itching of the palate in patients with allergic rhinitis. In Figure 11 we show that ultraviolet photochemotherapy decreases the clinical scores of the nasal blockage, nasal itch, nose running, sneeze and itching of the palate in patients with allergic rhinitis. The phototherapeutical apparatus described in the present invention is suited for the treatment and prevention of common inflammatory diseases of the body, among these specifically for the treatment of the diseases of the nasal mucous membrane and paranasal sinuses such as allergic rhinitis (hay fever), vasomotor rhinitis, nonallergic eosinophilic rhinitis, chronic sinusitis (inflammation in the paranasal sinuses), or nasal polyps with ultraviolet light. The Figure 1 shows the connection arrangement of the phototherapeutical apparatus applicable to the treatment of nasal mucous membrane. The Figure 1 shows the ultraviolet light source 1 the outgoing ultraviolet light beam 2, the optical coupling unit 3, wherein the ultraviolet light beam is focused, while it goes through. The light beam enters the light delivery system 4, then goes into the ultraviolet light irradiating contact unit 5. The contact unit is inserted into nostril 6 of the patient. The light is directed from the contact unit onto nasal mucous membrane. A variety of monochromatic light sources (lasers) can be used as ultraviolet light source, among others xenon chloride laser, nitrogen laser, frequency multiplied Nd laser or any other solid state laser, xenon fluoride excimer laser, any type of UV diode lasers or other lasers emitting light in the UV spectrum. In addition to the monochromatic light sources, any other light source emitting ultraviolet light in several wavelength ranges is applicable for the treatment. Such sources are: arc lamps filled with xenon, mercury vapour, xenon and mercury vapour, fluorescent lamp and UV-LED. Any known ultraviolet light source is applicable as UV light source 1 of the apparatus according to invention, nevertheless we apply the ultraviolet light source designed according to invention and shown in the Figure 2. The Figure 2 shows the electric power supply unit 7 and the wires 8 connecting it to the electrodes 11. The electrodes 11 enter the internal space of quartz bulb 12 filled with gas. The ultraviolet light beam 2 generated in the internal space goes partially reflected by the concave mirror 9, partly immediately to the condensing lens 15. The focused ultraviolet light beam 2 goes from the housing 10 through the output opening 14 to the optical filter 13 then to the light delivery system 4. The Figure 2 shows that electric current flowing from power supply unit 7 through the wires 8 and the electrodes 11 generates the discharge in the quartz bulb 12 filled with gas or gas mixture, consisting of e. g. xenon, argon and mercury vapour, which emits light partially in the ultraviolet spectrum. The volume of the discharge varies in the range from some mm 3 to some tenth of mm 3 . This discharge volume emitting light beam, consisting partially of ultraviolet light is placed in the focus of a concave mirror 9, so a part of the light beam emitted by the discharge goes to the mirror 9, then the reflected parallel beam goes into the condensing lens 15. Another part of the light beam 2 containing ultraviolet light goes immediately to the condensing lens 15. The condensing lens 15 focuses the light rays reaching it. The focused light rays go out of the housing 10 through the output opening 14 onto optical filter 13. The optical filter 13 performs the spectral filtering, of the emitted light. According to choice of the optical filter 13 ultraviolet A and/or ultraviolet B rays go through and enter the light forwarding system. The monochromatic or polychromatic ultraviolet light is lead by the optical coupling unit 3 to the light forwarding system 4 connected to the ultraviolet light irradiating contact unit 5 which serves for the treatment. An advantageous embodiment of the optical coupling unit is shown in the Figure 3. The ultiaviolet light beam 2 entering the optical coupling unit 3 is directed by the dichroic mirror 16 into the light forwarding system through the lens system 17. The dichroic mirror 16 makes also a spectral filtering at the same time. The light of the targeting light source 18, e. g. a HeNe laser or. a light diode emitting red light or that of any other colour. The light of the targeting light source 18 passes the dichroic mirror 16, so the targeting light enters the light delivery system 4 through the lens system 17, too. The light delivery system 4 is also applicable to lead back the reflected light if necessary and the reflected light passing the dichroic mirror can be seen through the observing optical device 19. The light delivery system 4 can be any optical cable or arm suited to lead ultraviolet light. The optical cable can be built up of a multitude of known materials like quartz glass or capillary tubes filled with a liquid conducting ultraviolet light and the internal surface of the tubes are covered with ultraviolet reflecting material. The diameter of cable can vary between 1 micron and 10 mm. The light forwarding system 4 can make also a spectral filtering if necessary. The treatment of the nasal mucous membrane and paranasal sinuses can be performed using differently shaped ultiaviolet light irradiating contact units 5. The unit is placed and positioned in the nostril. The most suited ultraviolet light iπadiating contact unit 5 for the treatment can be chosen from the multitude of contact units carried out according to invention. One advantageous embodiment of the ultraviolet light irradiating contact unit 5 is shown in the Figure 4. In this embodiment the light delivery system 4 enters the handgrip 20 goes through the optical tube 22 and ends slightly overhanging in a tapered end piece 24. The head 25 of the UV irradiating contact unit 5 is connected to the optical tube 22 by fastening 23. A light source of scanning light 27 is built into handgrip 20, which can be powered by either an internal or an external power supply unit. Mirror 28 projects the scanning light onto the surface to be illuminated. The ultraviolet light, the scanning light and, if necessary, the targeting light go through the output opening 26 onto surface to be tieated. A magnifying glass 21 mounted onto UV irradiating contact unit serves to visual control of the surface being treated with ultraviolet light. The Figure 5 shows an embodiment of the UV mediating contact unit, wherein the ultraviolet light beam 2 goes from the light delivery system 4 to the lens 29 of the handgrip 20, then reflected on the dichroic mirror 16 of optical tube 22 it aπives onto surface to be treated through output opening 26 of the head 25. The scanning light source 27 is mounted into handgrip 20. The scanning light passes the dichroic mirror 16 and reflected by concave mirror with hole 30 illuminates the surface to be treated. One can apply also UV irradiating contact units 5, wherein the surface treated by ultraviolet light can be controlled using external scanning light. The Figure 6 shows an embodiment of the UV iιτadiating contact unit wherein the light forwarding system 4 is inserted into a pen-shaped handgrip 31. The ultraviolet light beam 2 is projected by the optical coupling unit 3 into the light delivery system 4, and it arrives into the flat surface treating head 32. The flat surface treating head 32 is coupled to the pen-shaped handle 3.1 with the fastener 23. The ultraviolet light beam 2 arrives onto surface to be treated after reflection on the surface of a quartz prism or a flat mirror. The Figure 7 shows an UV irradiating contact unit 5 suited for the cylindrical symmetric treatment of the nasal cavity. The light delivery system 4 is inserted into the pen-shaped handle 31 in this embodiment. The ultiaviolet light beam 2 is lead into the head for cylindrical symmetric treatment 33 of the UV irradiating contact unit 5, and reflected on the conical or spherical reflecting surface it arrives radially onto surface to be treated. The head for cylindrical symmetrical treatment 33 is coupled to the pen-shaped handle 31 with the fastener 23. The nasal cavity can be cylindrically symmetrically treated with this apparatus. The embodiment shown in the Figure 8 is suited for dot type treatment of nasal mucous membrane. The light delivery system 4 is inserted into the pen-shaped handle 31. The ultraviolet light beam 2 arrives onto surface to be treated through an end piece 35 for dot type treatment, shaped either as piano-parallel disk or lens 36 made of quartz or plastic transparent to ultraviolet light. Another embodiment suited for dot type treatment of the mucous membrane is shown in the Figure 9. The ultiaviolet light beam 2 outgoing from the light source 1 is focused in the optical coupling unit 3, forwarded by the light delivery system 4 built into flexible endoscope 37 and aπives to the UV irradiating contact unit 5. The optical cable of the scanner light 42 and the image processing optical cable 38 are mounted into endoscope, as well. A light source 27 of the scanning light supplies the visible light. The lens 41 of scanning light directs the light into the cable of scanning light 42. A piano-parallel disk or a lens 36 covers the end of the endoscope contacting with mucous membrane. The surface treated by ultraviolet light can be visually controlled by the image processing unit 39 of the flexible endoscope 37. The light forwarding system 4 built into flexible endoscsope 37 can be twisted around its axis by means of the position setting unit 40, so the direction of light beam 2 outgoing from the sloped distal end of light delivery system 4 can be changed. This solution enables also the treatment of other hollow organs, like larynx, digestive canal, urogenital apparatus. An embodiment of PAL (Panoramic Annular Lens) optical system transparent to the ultraviolet light can be advantageously used instead of the cylindrically symmetric treating head 33 and piano-parallel disk or lens 36 of dot type treatment of the UV irradiating contact unit 5. As the PAL optical apparatus is also suited for optical image processing, it enables the observation of the surface to be treated and the cylindrically symmetric and dot-type treatment at the same time. The application of the phototherapeutical apparatus described in the present invention is as follows. The phototherapeutical apparatus described in the present invention is used for the treatment and prevention of diseases of the body, among these preferably for the treatment of common inflammatory diseases of the nasal mucous membrane and paranasal sinuses such as allergic rhinitis (hay fever), vasomotor rhinitis, nonallergic eosinophilic rhinitis, chronic sinusitis (inflammation in the paranasal sinuses), or for the treatment of nasal polyps (a frequent hyperproliferative lesion in chronic inflammatory conditions of the nasal mucous membrane) with ultraviolet light. These applications are based on our research results, which show that ultraviolet light decreases the number and the activity of inflammatory cells (mast cells, eosinophils, lymphocytes) responsible for the mediator release and synthesis in the mucous membrane, and thereby it reduces the clinical symptoms of allergic and hyperproliferative diseases. This effect of the ultiaviolet light is partly due to apoptosis induction. The 308 nm xenon chloride excimer laser is one of the most suited light sources for ultraviolet irradiation. Our results showed that 308 nm xenon chloride laser induces dose and time-dependent T-cell apoptosis. The comparison of the T-cell apoptosis inducing capacity of xenon chloride laser and narrow-band UVB light (NB-UVB) revealed that xenon chloride laser induced significantly higher T-cell apoptosis rate than NB-UVB light. Other monochromatic light sources can also be used as ultraviolet light sources for the treatment besides the xenon chloride laser, e. g. nitrogen laser, frequency multiplied Nd laser or other solid-state one, xenon fluoride excimer laser, UV diode lasers or other lasers, emitting light in the ultiaviolet spectrum. In addition, ultiaviolet light sources emitting in multiple wavelengths, e. g. arc discharge lamps filled with xenon, mercury vapour, xenon and mercury vapour, fluorescent lamp, NB-UVB, UV-LED, paint laser can be used in the treatment. Before starting the ultraviolet phototherapy of the nose and paranasal sinuses, the light threshold is measured on the skin of the patient previously not exposed to sunlight with the light source applied later for the phototherapy. The most suited phototherapeutical hand piece for the treatment of mucous membrane of the nose and paranasal sinuses is then chosen, its distal end which contacts to the mucous membrane to be treated is introduced into the nose. The choice of the most suited hand piece depends on the location of the area to be treated, and on the anatomy of the nose and paranasal sinuses of the patient. The first effective dose for the treatment of nasal mucous membrane with ultraviolet light is between 20 mJ/cm and 1000 mJ/cm , depending on the applied light source. The treatment with ultraviolet light is repeated once or more times per week using the same dose, or increasing doses, depending on the patient's tolerance and on the improvement of the clinical symptoms. These treatments based on ultraviolet light inhibit rapidly and significantly the clinical symptoms such as the nasal blockage, nasal itch, nose rurining, sneeze and itching of the palate in patients with allergic rhinitis. In the Figure 10 the severity scores of hay fever (0= no symptoms, 3= very severe symptoms) are shown before treatment with xenon chloride laser and after a 3-week long treatment when always the same irradiation dose was given twice a week. The clinical symptoms and complaints of the patients decreased greatly after the treatment. Similar improvement is observed after ultiaviolet phototherapy in the clinical symptoms of vasomotor rhinitis, nonallergic eosinophilic rhinitis, chronic sinusitis, and the sizes of nasal polyps considerably decreased. For the prevention of seasonal allergic rhinitis the ultraviolet phototherapy is started before the appearance of the clinical symptoms. In this case, the treatment is also based on the minimal erythema dose (MED) of the patient, and is given once or several times per week. To increase the efficacy of the ultraviolet phototherapy, photosensitising substances (for example psoralens) are given before the ultraviolet phototherapy, this is the so-called photochemotherapy. Photosensitising psoralens (5- methoxypsoralen, 8-methoxypsoralen or tiimethoxypsoralen) are used in concentrations between 0.0005% and 0.5% in creams or in solutions. When a photosensitising substance (e. g. psoralen) and ultiaviolet light is used together for the treatment, the minimal phototoxicitiy dosis (MPD) is measured first on the patient's skin not exposed to sunlight before starting the therapy, this is the smallest ultraviolet dose, which induces erythema on skin after 72 hours. The treatment of the nasal mucous membrane is started depending on the severity of the symptoms of the patient with 0.1 x MPD to 5.0 x MPD, which dose is further increased depending on the patient's tolerance, and repeated once or many times per week. The photochemotherapy inhibits rapidly and effectively the clinical symptoms, such as the nasal blockage, nasal itch, nose running, sneeze and itching of the palate in patients with hay fever. The Figure 11 shows the severity scores of patients with hay fever before photochemotherapy and after a 3 -week of ultraviolet photochemotherapy given twice per week with the same doses. All the clinical symptoms and complaints of the patients decreased greatly after the photochemotherapy. Similar improvement is observed after ultiaviolet photochemotherapy in the clinical symptoms of vasomotor rhinitis, nonallergic eosinophilic rhinitis, chronic sinusitis, and sizes of nasal polyps considerably decreased. Similarly to ultraviolet phototherapy, photochemotherapy is also suitable for the prevention of the clinical symptoms of patients with seasonal allergic rhinitis, when the treatment is started before the appearance of the symptoms. For prevention, photochemotherapy is started depending on the severity of the allergy with doses between 0.1 x MPD and 2 x MPD, which are given then once or several times per week depending on the tolerance of the patient. The phototherapeutical apparatus described in the invention is suitable for the treatment and for the prevention of allergic or autoimmune inflammatory diseases of other organs (gastrointestinal and urogenital tract, conjunctiva). Potential side effects Similarly to that of topical corticosteroides used for the treatment of the disease, ultraviolet light - related to its immunosuppressive effect - might facilitate the appearance of viral and bacterial infections on the treated areas. However, the likelihood for this is lower to that of the presently used local immunity- suppressive preparations, because ultraviolet light has also a direct microbicidal effect (Folwaczny M, Liesenhoff T, Lehn N, Horch HH: Bactericidal action of 308 nm excimer-laser radiation: an in vitro investigation. J Endodontics, 24: 781-785, 1998), and ultraviolet light increases the direct microbicidal activity of epithelial cells (Csatό M, Kenderessy SzA, Dobozy A: Enhancement of Candida albicans killing activity of separated human epidermal cells by ultiaviolet radiation. Br J Dermatol 116: 469-475, 1987). It is well known that repeated ultraviolet light irradiation in high doses has carcinogenic potency. The ultraviolet light-induced carcinogen effect is connected with the cumulative dose of the ultraviolet light given in years. As the' carcinogenic effect of ultraviolet light depends on its cumulative dose, and the irradiation doses for the phototherapy or photochemotheapy of the nasal mucous membrane are much lower compai'ed to the dosages that increases the risk of cancer; the increased risk for carcinogenesis in the present therapeutical schemes is very low. The advantages of the phototherapeutical apparatus and of its application are as follows: For the drug-treatment of common diseases of the nasal mucous membrane and paranasal sinuses such as allergic rhinitis (hay fever), vasomotor rhinitis, nonallergic eosinophilic rhinitis, chronic sinusistis or nasal polyps billions of dollars are expended worldwide. Despite of the available therapeutical opportunities the work-ability of the patients frequently highly decreases. The phototherapeutical apparatus and its application decreases rapidly and effectively the clinical symptoms of the patients, therefore the direct and indirect costs related to the treatment of the diseases decrease in a great extent. Additionally, the ultraviolet light source described in the present invention might be used for the treatment of every known ultraviolet light responsive disease. The application of the phototherapeutical apparatus according to the invention is shown in the following examples. Example 1 The symptoms of a patient suffering from raqweed-induced hay fever 10 years ago did not respond satisfactorily to the used ant stamine and topical corticosteroid nasal drops. At examination the patient complained of severe nasal blockage, nasal itching, nose running, frequent sneezing and itching of the nasal palate. On the back of the patient not exposed to sunlight the minimal erythema dosis (MED) was determined using 308 nm xenon chloride laser light source, which proved to be 200 mJ/cm 2 . One day later the phototherapy of the nasal mucous membrane was stalled. For this purpose the ultraviolet light beam 2 of wavelength of 308 nm outgoing from he ultraviolet light source (xenon chloride laser) was directed by optical focusing into an optical cable 4 made of quartz and having diameter of 1.6 mm. The cable was connected to an UV irradiating contact unit 5 shown in the Figure 4. The output window 26 of this unit covered by a piano-parallel transparent plastic disk of diameter of 4 mm was connected to the nasal mucous membrane and the surface was irradiated with a dose of 100 mJ/cm 2 . The irradiation was performed with a frequency of 1 Hz, the lengths of the impulses were 15 ns, and the energy of one impulse at the output window 26 of the irradiating contact unit 5 was 1.79 mJ. Reckoning with the diameter of the output window 26 of 4 mm, its surface is 0,1256 cm 2 , so the energy density of irradiation is 14,25 mJ/cm 2 . Altogether 7 impulses were done to issue the dose of 100 mJ/cm 2 . In each nostril 16 such areas Were irradiated. The treatment was controlled visually under protection of UV protecting glasses using the visible light beam of the scanning light source 27 mounted into handgrip 20 of the UV irradiating contact unit 5. The complete time of a treatment was 5 minutes, including the time necessary to change the position of the unit. The treatment did not cause any complaint to the patient. This treatment was repeated in the patient two times per week using the same phototherapeutical apparatus, but the irradiation dose was increased by 50 mJ/cm weekly. After the second treatment the symptoms and complaints of the patient have already decreased greatly, and in the third week after the 6 th treatment the patient was completely free of symptoms. The tieatment was stopped and no recurrence was observed. The treatment was quick and caused no complaint for the patient. The patient did not receive any drugs during the tieatment. In comparison to the therapies used earlier, phototherapy was found to be more efficacious by the patient. Example 2 Patients with perennial allergic rhinitis induced with house dust mite, whose treatment with antihistamine and local steroids proved to be ineffective, phototherapy was started with xenon chloride excimer laser of wavelength of 308 nm. The MED was measured for each patient, and phototherapy was started with 0.5 x MED doses. The head 33 for cylindrically symmetric treatment of the UV irradiating contact unit 5 was inserted into meatus nasi inferior area of the nasal cavity for the treatment, then a cylindrically symmetric irradiation was given onto surface with the xenon chloride laser. The length of impulses was 15ns, the frequency of irradiation was 10 Hz. The energy density of each impulse was 2 mJ/cm 2 . The administering of the dose of 100mJ/cm2 took up 5 sec. The head 33 for cylindrically symmetric tieatment was then inserted into middle and thereafter into upper part of the nasal cavity and the treatment was repeated in these positions in the same way. The treatment of the right and left nasal cavities took up approximately 2 minutes. The treatment was repeated with the same doses two times per week. After the 8 th treatment the clinical symptoms of the hay fever improved considerably at each patient, whereas no side effects were observed. Example 3 The severe symptoms of a patient suffering from raqweed-induced hay fever did not improved satisfactory after using antihistamines and topical corticosteroid nasal drops. At examination the symptoms (nasal blockage, nasal itching, nose running, frequent sneezing and itching of the nasal palate) of the patient were severe, therefore we decided to start photochemotherapy. The minimal phototoxicity dose was measured on the forearm of the patient not exposed to sunlight. The ultraviolet light source 1 shown in the Figure 2 was used for the irradiation in the way that 2 ultiaviolet light beams of wavelengths between 310 and 350 nm were lead into light delivery system (optical cable) 4 after usage of optical filters. The MPD was 500 mJ/cm 2 and the treatment of the nasal mucous membrane was started with a dose of 2.0 x MPD (=1000 mJ/cm 2 ) using the UV irradiating contact unit 5 shown in the Figure 4. Photochemotherapy was performed after using 8-methoxypsoralen nasal spray. The head 25 of the UV irradiating contact unit 5 shown in the Figure 4 was inserted into nasal cavity and the mucous membrane was irradiated with the dose of 1000 mJ/cm . The power density of the ultraviolet light was 43.2 mW/cm at the output window 26 of the UV irradiating contact unit. The treatment was visually controlled under protection of UV protecting eyeglasses using the visible light beam of the scanning light source 27. The UV irradiating contact unit 5 was put onto mucous membrane altogether in eight positions in each nostril. The treatment of the nostrils took up approximately 3 minutes and caused no complaints to the patient. This photochemotherapy was repeated once per week. The symptoms of the patient improved considerably already after the second treatment, and after the 3 rd tieatment the patient was completely free of symptoms. The treatment was stopped after the 4 th photochemotherapy, and the symptoms of the patient did not come back. Example 4 A patient was examined because of a large polyp in the left nostril, which did not improve after dosage local corticosteroids and which caused chronic sinusitis, therefore phototherapy with xenon chloride laser was started. The minimal erythema dose (MED) was determined on the back of the patient, which proved to be 250 mJ/cm . For the purpose of phototherapy the ultraviolet light beam 2 of wavelength of 308 nm going out from the laser was lead after optical focusing into a quartz ultraviolet light conducting cable 4 of diameter 0.5 mm, which was coupled to the UV iπ'adiating contact unit 5 shown in the Figure 8. The piano-parallel disk 36 of thickness of 2 mm made of transparent plastic of the said irradiating unit 5 was brought into contact with the surface of the polyp, than a round area of diameter 2 mm was irradiated with the dose of 750 mJ/cm 2 . The irradiation was conduced at the frequency of 5 Hz, the length of impulses was 15 ns, the energy of impulse was 1.96 mJ, so altogether 12 impulses were issued to give irradiation of 750 mJ/cm . Five days after one single treatment the nasal polyp disappeared without any scar formation and also the complaints of the patient disappeared. Example 5 In a patient with chronic rhinosinusitis with unknown origin the different drugs (antihistamines, corticosteroids, antibiotics) used earlier for the treatment of the symptoms were ineffective, therefore phototherapy was indicated. The ultiaviolet light source 1 shown in the Figure 2 was used for the treatment. The minimal erythema dosage (MED) was first determined on the forearm of the patient not exposed to sunlight, then treatment of the nasal mucous membrane was started with a dose of 140 mJ/cm2. The piano-parallel disk 36 of diameter of 4 mm of the UV irradiating contact unit 5 shown in the Figure 4 was brought into contact with the affected mucous membrane and this surface was irradiated for the treatment. The treatment was controlled visually under protection of UV protecting eyeglasses using the visible light of the scanning light source 27. The hand-held apparatus was applied in altogether 8 positions per nostril to irradiate the whole affected mucous membrane. This phototherapy was repeated several times per week. After the 6 th treatment the symptoms of the patient decreased considerably, and after the 10 th treatment the patient became free of symptoms. One month after stopping the therapy the patient is still free of symptoms. List of references 1 Ultraviolet light source 2 Ultraviolet light beam 3. Optical coupling unit 4 Light delivery system 5 Ultiaviolet light irradiating contact unit 6 Nostril 7 Electric power supply unit 8 Electric wire 9 Concave mirror 10 Housing 11 Electrode 12 Quartz bulb 13 Optical filter 14 Output opening 15 Condensing lens 16 Dichroic mirror 17 System of lenses 18 Targeting light source 19 Optical system for observation 0 Handgrip Magnifying lens Optical tube Fastener Tapered end piece Head Output window Light source of scanning light Mirror Lens Concave mirror with a hole in the middle Pen-shaped handle Head for treatment of flat surfaces Head for cylindrically symmeti'ic treatment Lateral wall transparent for ultiaviolet light Head for dot-shaped treatment Piano-parallel disk or lens Flexible endoscope Optical cable for image processing Image processing unit Position setting device Lens of scanning light Optical cable for scanning light

Claims: CLAIMS 1. A phototherapeutical apparatus for the treatment and for the prevention of inflammatory diseases of the body, favourable for diseases of the nose, paranasal sinuses, mouth cavitiy, throat, oesophagus, stomach, small and large intestines, rectum, ear, trachea, urogenital tract, portio, uterus and conjuctiva, char acteri se d by that it comprises an ultraviolet light source (1) issuing an ultraviolet light beam (2), an optical coupling unit (3), a connected light delivery system (4) and an UV irradiating contact unit (5) connected to it. 2. An apparatus according to Claim 1 characteris ed by that the light source (1) is an electric discharge lamp wherein an electric power supply unit (7) is connected to electrodes (11) in a quartz bulb (12) filled with a gas or gas mixture emitting light partially in the ultraviolet spectrum, e. g. xenon or mixture of xenon, argon and mercury vapour, it is provided with a concave mirror (9) reflecting a part of the produced ulti'aviolet light beam (2) and a condensing lens (15) focusing the whole ulti'aviolet light beam (2), the quartz bulb (12), the concave mirror (9), the condensing lens (15) and an output opening (14) are mounted in a housing (10) and an optical filter (13) and a light forwarding system are arranged behind the said light source. 3. The apparatus according to Claim 1 characteris e d by that the ultraviolet light source (1) is a laser. 4. The apparatus according to Claim 1 characteri s e d by that the optical coupling unit (3) comprises a dichroic mirror (16) and a system of lenses (17) which leads in addition to the ultraviolet light beam (2) the light of the targeting light source (18) into light delivery system (4), and it is applicable to observe also the reflected light if necessary using an observing optical system (19). 5. The apparatus according to Claims 1 to 4 characteri s ed by that the light delivery system (4) consists of an optical cable or an optical arm having diameter from 1 micron to 10.0 mm containing quartz glass fibre or capillary tubes filled up with ultraviolet light conducting fluid and the internal surfaces of tubes are covered with a coating reflecting ultraviolet light. 6. The apparatus according to Claims 1 to 5 characteri s ed by that it is provided with an UV irradiating contact unit (5), the light delivery system (4) connects to the handgrip (20) thereof, it is provided with an optical tube (22), a tapered end piece (24) and a light source (27) of the scanning light, a magnifying lens (21) and a miπ'or (28) or a dichroic mirror (16) is mounted on one end of the tube (22) while a head (25) .is mounted onto its other end, which has an output window (26) to lead out the ultraviolet light beam, the targeting light and the scanning light together. 7. The apparatus according to Claims 1 to 5 characteri s ed by that it is provided with an UV irradiating contact unit (5) with a pen-shaped handle (31), and the said unit is provided with a flat surface treating head (32), a head for cylindrically symmetric treatment (33) or a head for dot-shaped treatment (35). 8. The apparatus according to Claims 1 to 5 characterised by that it is provided with an UV irradiating contact unit (5) wherein the light delivery system (4) is connected to a flexible endoscope (37) containing an optical cable of the scanning light (42) and an optical cable for image processing (38) and the flexible endoscope (37) ends with a piano-parallel disk or lens (36), its other end is connected to an image processing unit (39) through the said optical cable for image processing (38). 9. The apparatus according to Claims 1 to 8 characterised by that it is applicable to iπ'adiate the body one or more times with unchanged or increasing doses of ultraviolet light in the wavelength range of 300 to 400 nm. 10. The apparatus according to Claims ltoδcharacterised by that it is applicable for the treatment or prevention of inflammatory or hype roliferative diseases of the body. 11. The apparatus according to Claims 1 to 8 characterised by that it is applicable for the treatment or prevention of inflammatory diseases among them allergic rhinitis (hay fever) or rhinusitis. 12. The apparatus according to Claims 1 to 8 characterised by that it is applicable for the treatment or prevention of inflammatory diseases among them vasomotor rhinitis, non-allergic eosinophilic rhinitis and chronic sinusitis. 13. The apparatus according to Claims 1 to 8 characterised by that it is applicable for the treatment of inflammatory diseases among them for the tieatment of mucous membranes of the gastrointestinal and urogenital systems. 14. The apparatus according to Claims 1 to 8 characterised by that it is applicable for the treatment of hyperproliferative diseases among them nasal polyposis. 15. The apparatus according to Claims 1 to 8 characterised by that it is applicable for the tieatment of mucous membranes previously treated by light sensitising substances.

Inventors: BOR ZSOLT, DOBOZY ATTILA, IGNACZ FERENC, KEMENY LAJOS, RACZ BELA, SZABO GABOR, BOR, ZSOLT, DOBOZY, ATTILA, IGNACZ, FERENC, KEMENY, LAJOS, RACZ, BELA, SZABO, GABOR
Applicants: BOR ZSOLT, DOBOZY ATTILA, IGNACZ FERENC, KEMENY LAJOS, RACZ BELA, SZABO GABOR, BOR, ZSOLT, DOBOZY, ATTILA, IGNACZ, FERENC, KEMENY, LAJOS, RACZ, BELA, SZABO, GABOR
Application year: 2001
Main classification: A61N5
IPC codes: A61B18, A61N5