Apparatus for use in irradiation therapy comprising ionization module and UV-light source

Abstract

The present invention relates to an apparatus (1) for use in irradiation therapy, comprising an ionization module (2) adapted to emit ionization irradiation, and a power source (4) and a control unit (5) to provide a user interface. The apparatus is characterized in that the apparatus comprises an UV module (3) adapted to emit UVA, UVB and/or UVC irradiation (9), whereby the ionization module and the UV module emit irradiation simultaneously or alternately, and the ionization module emits irradiation (8) at a wave length at least below 100 nm. The invention also relates to a use of the apparatus for radiating an object (7) and use of the apparatus and method for treatment of a mammal (7). A detector may measure and/or create an image of the irradiation (6).

Claims

1. An apparatus (1) for use in irradiation therapy, comprising a first light source configured for emitting X-ray or gamma-irradiation at a wavelength below 100 nm, and a second light source configured for emitting ultraviolet (UV) light at a wave length between 100 and 450 nm; wherein the first and second light sources are non-laser light sources wherein the first and second light sources are positioned in a circular, as semi-circular or juxtaposed with respect to each other and are aligned to cooperate for administrating even irradiation over a human body part simultaneously or alternately, such that irradiation from the first light source over the body part overlaps with irradiation from the second light source over the same body part; and a power source (4) and a control unit (5) configured to provide a user interface for controlling irradiations of said first and second light sources.

2. The apparatus according to claim 1, wherein the irradiation is emitted from the first and second light sources simultaneously and sequentially.

3. The apparatus according to claim 1, wherein an ionization irradiation (8) is photo irradiation or particle irradiation.

4. The apparatus according to claim 1, wherein the ionization irradiation (8) is at a wave length between 0.001 and 10 nm.

5. The apparatus according to claim 1, whereby the UV irradiation (9) is UVA irradiation at a wave length between 315 and 400 nm.

6. The apparatus according to claim 1, whereby the UV irradiation (9) is UVB irradiation at a wave length between 280 and 315 nm.

7. The apparatus according to claim 1, whereby the UV irradiation (9) is UVC irradiation at a wave length between 100 and 280 nm.

8. The apparatus according to claim 1, wherein the irradiation from the first light source is at a maximum power of 1.00 mGy/s and the irradiation from said second light source is at a minimum power of 0.2 mW/cm{circumflex over ( )}2.

9. The apparatus according to claim 1, wherein the irradiation from the first light source is at a maximum power of 0.333 mGy/s and the irradiation from said second light source is at a minimum power of 3.8 mW/cm{circumflex over ( )}2.

10. A method for radiating an object (7), comprising: providing an apparatus (1) comprising: a first light source configured for emitting X-Ray or gamma-irradiation at a wave length below 100 nm, a second light source configured for emitting UV light at a wave length between 100 and 450 nm, a power source (4) and a control unit (5) configured to provide a user interface for controlling irradiations of said first and second light sources, wherein the first and second light sources are non-laser light sources, wherein the first and second light sources are positioned in a circular, a semi-circular with respect to each other and are aligned to cooperate for administrating even irradiation over a human body part; emitting irradiation (8,9) from the first and second light sources simultaneously or alternately, for a period of time, such that irradiation from the first light source over the body part overlaps with irradiation from the second light source over the same body part.

11. A method for use of the apparatus (1) according to claim 1, comprising providing the apparatus (1) according to claim 1, positioning an object (7) to be irradiated on a surface, emitting irradiation from the first and second light sources simultaneously or alternately for a period of time between 1 minute and 48 hours, optionally repeat the emitting irradiation (8,9), optionally administering one or more photochemically active compound to the object (7) before or between irradiations.

12. The method according to claim 11, whereby the irradiation from the first and second light sources is simultaneous and sequential.

13. The method according to claim 11, whereby period of time for simultaneous irradiation is between 1 and 10 minutes and a non-irradiation period between sequential irradiations is between 5 minutes and 48 hours.

14. The method according to claim 11, whereby period of time for alternate irradiation is between 1 and 5 minutes for ionization irradiation and between 1 and 10 minutes for UV irradiation with a non-radiating period of between 5 minutes and 48 hours.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) The invention will now be explained more closely by the description of different embodiments of the invention and with reference to the appended figures.

(2) FIG. 1 shows one embodiment of an apparatus of the invention, whereby both irradiation modules in positioned next to each other.

(3) FIG. 2 shows another embodiment of an apparatus of the invention whereby the two irradiation modules are positioned parallel to each other.

(4) FIGS. 3 to 8 shows different embodiments of the apparatus of the invention in different sizes and shapes.

(5) FIG. 9 illustrates how the apparatus can be used for irradiation treatment of a body of a human.

(6) FIG. 10 illustrates how the apparatus can be used for irradiation treatment of part of a body of a human

(7) FIGS. 11 to 13 illustrate different embodiments of the apparatus of the invention in different sizes and shapes for treatment of a horizontal positioned object.

(8) FIGS. 14 to 18 illustrate different embodiments of an apparatus of the invention in different sizes and shapes for treatment of a vertically positioned object.

(9) FIG. 19a-e show how the apparatus can be used for irradiation treatment.

(10) FIG. 20 shows a flow diagram for a method of treating an object using the apparatus.

(11) FIG. 21 shows a ratio (%) of necrotic versus living cells when exposed to the apparatus comprising UVA irradiation 2.76 J/cm2 and ionization irradiation concomitant with 0.5 Gy X-ray (II) in increased amounts of Bergamot enteric oil. The combination irradiation of UV and ionization with the apparatus of the invention (UVII) is denoted by a line of alternating lines and dots (highest line), UVA irradiation is denoted by a dotted line and ionization irradiation (II) is denoted by dotted line (middle line) with smaller dots (lowest line).

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS OF THE INVENTION

(12) Following detailed description of the invention, and the examples are provided to describe and illustrate certain embodiments of the invention and do not limit the scope of the invention in any way.

(13) FIG. 1 shows an example of an apparatus 1 for use in irradiation therapy according to the invention.

(14) The apparatus comprises an ionization module 2, an UV module 3, a power source 4 and a control unit 5. The control unit may provide a user interface with input means, such as a keyboard, and a screen. In one embodiment, more than one power source and/or more than one control unit 5 is used in the apparatus 1. In FIG. 1, both modules are positioned next to each other. FIG. 1a shows a bottom view of the apparatus. FIG. 2 shows another embodiment, whereby the two modules are positioned next to each other, with a computer tomograph (CT) as ionization module and a UV module, held in place by an adjustable member 11, such as an drop arm as shown in FIG. 2. The invention is not limited to these examples and many variations are possible, whereby the two modules are aligned to cooperate for administrating irradiation to an object. In one embodiment, the irradiation may come from the table were the patient is conveyed in supine- or prone position into the CT. Further examples are outlined below.

(15) The ionization module is adapted to emit ionization irradiation 8. This ionization irradiation may be selected from the group comprising or consisting photo irradiation, particle irradiation, X-ray irradiation or gamma irradiation. The wavelength of the ionization irradiation is between 0.0001 and 100 nm, or between 0.001 and 100 nm. The wavelength of X-ray or gamma irradiation may be between 0.0001 and 15 nm, or between 0.001 and 10 nm.

(16) There is a range of different sources of ionization irradiation, both from different sources of ionization irradiation, gamma irradiation and particle irradiation. The ionization module may be an X-ray device or a computed tomograph (CT).

(17) Any X-ray device can be used in the apparatus of the invention. Usually these devices include an anode, a cathode opposite the anode and a detector 6. The object 7 to be radiated is position such that both modules can radiate the object.

(18) The UV module is adapted to emit ultraviolet light (UV) 9 and comprises a light source that can emit light at a wavelength between 90 and 450 nm, or between 100 and 400 nm. The light source may emit light in the UVA range between 315 and 400 nm, or in the UVB range between 280 and 315 nm or in the UVC range between 100 and 280 nm, or any combinations thereof. The light source may be a source having a narrow bandwidth within the UV range (A, B or C) of about 50, or 25 or 10 or 5 or 3 nm.

(19) There is a range of different sources of ultraviolet light type A or type B on the market which are used within medical technique.

(20) The invention concerns an apparatus emits UV and ionization irradiation simultaneously, alternately and/or sequentially in order to administer ultraviolet light and ionization irradiation to an object, in one or several combined or alternately pulsations.

(21) The control unit 5 may include a regulatory system configured to emit the ionization irradiation in one or several pulses before, during or after emitting the UV irradiation. The apparatus may also be configured such that UV irradiation is emitted in one or several periods before under or after the emitting pulses from the ionization irradiation.

(22) One example may be to assemble an UV-lamp together with a X-ray-tube, whereby the emission of UV and ionization irradiation is regulated by the control unit, which “turn on” and “turn off” the UV lamp and the irradiation of the X-ray-tube.

(23) Another example can be a UVB source assembled together with a projector for gamma irradiation, whereby the emission of irradiation is controlled as exemplified above.

(24) A third example can be a UVA and a UVB source assembled together with a source for X-ray irradiation. A fourth example can be a source for UVA assembled together with a projector for gamma irradiation. In the same manner, UVA and/or UVB sources may be assembled together with projectors for particle irradiation.

(25) Alternatively, the UVA and/or the UVB modules may be moved in a lumen of a vessel or an intestine or another cavity of a body and the module/source for ionization irradiation may be outside the body. The position of UVA and/or the UVB module may need to be verified with optics or by radiography. This allows for very precise targeting of an object inside a body, thereby minimizing side effects of irradiation.

(26) The sources for ultraviolet irradiation and ionization irradiation may be placed mixed in a grid, the sources of light or the sources of ionization irradiation may be square sized or circular or of any other polygonal shape or form. The number of sources of UV-light or ionization irradiation may depend on the size of the apparatus.

(27) The sources of ultraviolet light and ionization irradiation may be positioned in a way so that the modules envelope each another mixed linearly, the sources of light or the sources of ionization irradiation may be square or circular or of any polygonal shape. The number of sources of UV-light or ionization irradiation may vary dependent on the size of the apparatus.

(28) FIGS. 3 to 8 show the apparatus in different sizes and forms. The UV module and the ionization module may be positioned differently with regards to each other. These are only illustrative and the number of areas within each apparatus may be more or less than what is shown in these figures. The different examples on positioning and the different size and shapes of the modules need to be coordinated with each other.

(29) FIGS. 9 and 10 show how the object can be placed in relation to the apparatus. As shown in FIG. 6, the UV module and the ionization module may be positioned in alternating rows.

(30) Alternatively, as shown in FIGS. 5 and 7 one module may fill the circumference of the other module. FIG. 8 shows the apparatus in the form of a circle that can circumvent the object.

(31) FIG. 9 shows how the apparatus can be used for irradiation of a body of an object, such as a human. 10. The apparatus can cover the total area of the object and even enable to allow an even irradiation of the total object area. The apparatus may be assembled to circulate around the object, or the object may circulate inside the apparatus.

(32) FIG. 10 shows how the apparatus can be used for irradiation of part of a body of the object.

(33) A smaller size of the apparatus can be used when the object is in standing position. The modules may be positioned in turn or with one module circumventing the module or any other variation thereof. These smaller forms of UVII may be developed to cover a part of a human, and may be able to move back and forth, up and down or around a patient. The smaller apparatus may also be shaped in a size that is suitable for irradiation of a film or fluid, or a bag with fluid, a surface or an item that passes on a transporter.

(34) The modules may be removably mounted on a grid. The modules may also be removably mounted on a tripod or stand or frame. Such stands may be of different types dependent on the object to be radiated and the environment where the apparatus is to be used. The design of the stand is also dependent on what type of ionization irradiation that is to be combined with ultraviolet irradiation, where different forms of ionization irradiation may suit better than others to be emitted from a certain kind of source. If the module is small in relation to the object the object instead has to be moved back and forth under the module, or the module has to be moved back and forth over their object until the intended treatment effect has been reached.

(35) The stand that the apparatus is assembled on may be portable. The apparatus may be conformed in a way that it is placed within a shield that is easy to disinfect by e.g. 5% chlorhexidine or 70% alcohol or another suitable solution for disinfection such that apparatus easily may be moved between different objects or patients without the risk for contamination within or between places on sites, such as hospitals. One part of or the entire shield may be transparent to allow passage of irradiation.

(36) The apparatus may be assembled on a vehicle or on a drone or on a remote vehicle or a robot, including a vehicle with a pre-programmed movement pattern.

(37) The apparatus may be part of a line of production where the apparatus is radiating towards a conveyor.

(38) The apparatus may fastened on a therapeutic instrument that is introduced endoscopically into a vessel, into the peritoneal cavity, gastro- or colposcopy- or through the urinary tract retroscopically or antegradely likewise through the choledoccus.

(39) In FIG. 11 the apparatus has a semi-circular form, and in FIG. 13 the apparatus has a circular form. FIG. 12 shows a cross section of the apparatus in FIG. 13 showing the object inside the circular apparatus. The apparatus may have an elliptic form. The apparatus that radiates only one part of the object. In these cases, the apparatus may move over the part of the object to reach a larger part of the object, or the object may move below the apparatus.

(40) FIG. 14 shows the apparatus having a circular form and FIG. 15 shows a cross section of the apparatus in FIG. 14 from a top side. FIG. 16 shows a combination of a semi-circular unit and a straight unit.

(41) FIGS. 16 and 17 show other alternatives for positioning the units around the object. The units may comprise one module each or the units may comprise a combination of the UV module and ionization module. In one embodiment, one unit comprises the ionization module and the other unit comprises the UV module. In another embodiment, each unit comprises both modules, whereby the modules are positioned alternately in parallel or one module may be positioned around the other module. The modules are positioned on the inside, which enables the whole object to be radiated concomitantly.

(42) The shape or form of the apparatus can actually be any at all. When the apparatus has an oval-, semi-circular-, three-quarter- or a round shape, it may move back and forth, or up and down or around the object. Likewise the object may move in relation to the apparatus.

(43) The apparatus may also be used to emit irradiation onto everything around, as a circular or a semi-circular apparatus that radiates outward in all directions on the whole or half the room, respectively. In the case where the human may be totally enveloped by the apparatus, the apparatus may be fitted with a door, with the apparatus mounted on the inside, which allows for the whole object or human to be radiated at the same time.

(44) Even if the figures show an adult human body, the apparatus may be fitted in a size and shape for children of different ages as well as for other objects in different sizes and shapes.

(45) It is an advantage if the UV modules and the ionization modules are positioned in a way so that they give an even exposure on the intended object. The spread of the UV irradiation or ionization irradiation ionization determine how the modules may be positioned, both in relation to each other, but also in relation to the distance to the object and the size of the object in width, height and dependent on whether the object itself shifts in depth in relation to the modules.

(46) The maximal effect of the apparatus is accomplished when the irradiation hit different parts of the object. Another alternative is that the object is moved in relation to the apparatus in a way so that different parts of the object are hit with the maximal effect of the apparatus during different parts of the irradiation session.

(47) Another variant may be that the UV-light is given from several directions from a semi-circular or from a polygonal shaped apparatus or UV module, while the ionization irradiation is given from an opposite direction. In the same way, the ionization irradiation is given from several directions, i.e. from a semi-circular or from a polygonal form of the ionization module and the UV-light is given from an opposite direction from the UV module. ionization

(48) FIG. 19 illustrates how the apparatus of the invention can be used in a method for radiating an object. The method comprises providing the apparatus as defined above and any variation thereof. A power source 4 and a control unit 5 may be present to provide a user interface. In FIG. 19a, the UV module 3 is positioned above the object or human and the ionization module 2 is positioned behind the object 7. After placing the object or human on the apparatus 1 as shown in FIG. 19b irradiation may be emitted from the UV module. In this embodiment, the object is first moved or placed into the ionization module before emitting ionization irradiation (FIG. 19c). The ionization module may be a computed tomograph (CT), which is a device with an imaging procedure that uses special X-ray equipment to create detailed pictures, or scans, of areas inside the body. Once the object is inside the CT irradiation can be emitted from the ionization module and the UV module simultaneously or alternately, for a period of time (FIG. 19d), whereby the ionization module emits irradiation at a wave length at least below 100 nm. FIG. 19e shows a cross section of the apparatus in FIG. 19d through a vertical axis. The irradiation from the two modules may be emitted simultaneously and sequentially as well.

(49) The period of time for simultaneous irradiation may be between 0.1 and 30 minutes, or between 1 and 10 minutes and a non-irradiation period between sequential irradiations may be between 1 and 7 days, or between 5 minutes and 48 hours.

(50) The period of time for alternately irradiation is between 0.1 and 30 minutes, or between 1 and 5 minutes for ionization irradiation and between 1 and 10 minutes for UV irradiation with a non-radiating period of between 1 and 7 days, or between 5 minutes and 48 hours.

(51) The apparatus may be comprise a UV module that emits only one peak (a small bandwidth of wavelength) of UVA or UVB. Likewise, the ionization module may be adapted to emit one peak of ionization irradiation. For example, there may be only one peak of emission in the UVB area and one in the gamma-area. The strength of the emitted irradiation may be such that the DNA-damage is larger than the background irradiation within 30, or more preferable 10 minutes, or most preferable within less than five minutes of irradiation time.

(52) The invention relates to a method for use of the apparatus as defined above and any variation thereof, for treating an object. FIG. 20 schematically illustrates the method in a flow diagram. The method comprises providing the apparatus as outlined above and positioning an object to be radiated on a surface, which may be a surface of a detector 6. Consequently, irradiation is emitted from both modules simultaneously or alternately for a period of time between 0.1 minute and 7 days, or between 1 minute and 48 hours,

(53) Optionally, the step is repeated after a non-irradiation period.

(54) The irradiation from the two modules may be emitted simultaneously and sequentially as well.

(55) The period of time for simultaneous irradiation may be between 0.1 and 30 minutes, or between 1 and 10 minutes and a non-irradiation period between sequential irradiations may be between 1 and 7 days, or between 5 minutes and 48 hours.

(56) The period of time for alternately irradiation is between 0.1 and 30 minutes, or between 1 and 5 minutes for ionization irradiation and between 1 and 10 minutes for UV irradiation with a non-radiating period of between 1 and 7 days, or between 5 minutes and 48 hours.

(57) Photochemically active compounds i.e. psoralens may be used in combination with irradiation therapy. The apparatus can thus be used to provide a photochemical reaction between DNA and one or more psoralen and/or to evoke phytodermatitis, or photosenzibilization in an object to be radiated. One or more photochemically active compound may be administered to the object before or between irradiations.

(58) These photochemically active compounds or psoralens may be selected from the group comprising Ficus earica, Pastinaca sativa, Heracleum sphondylium, Heracleum gigantum, Pastinaea sativa, Heraeleum mantegazzianum, Foeniculum vulgare, Anethum graveolens, Peucedanum oreoselium, Daucus earota, Daueus sativa, Peucedanum ostruthium, Apium graveolens, Ammi majus, Angelica species, Ruta graveolens, Dictamus albus, Citrus bergamia, Dictamnus fraxinella, Citrus aurantiom, Citrus aurantifolia, Citrus aurantifolia, var. Swingle, Renuneulus species, Brassiea species, Sinapsis arevensis, Convolvulus arevensis, Agrimony eupatoria, Achilleae millefolium, Chenopodium species, Psoralea coryiloli, Hypericum perforatum or Hypericum concinnum, psoralen, xanthotoxin, bergapten, isoimperatorin and bergamotin, or66-97-7, 7H-Furo[3,2-g]chromen-7-one, Ficusin, Furocoumarin, Psoralene, 7H-Furo[3,2-g][1]benzopyran-7-one, Psorline-P, furo[3,2-g]chromen-7-one, Furo[3,2-g]coumarin, 6,7-Furanocoumarin, 7H-Furo[3,2-g]benzopyran-7-one, NSC 404562, Furo(2′,3′,7,6)coumarin, Furo(4′,5′,6,7)coumarin, Furo[2′,3′:7,6]coumarin, Furo[4′,5′:6,7]coumarin, UNII-KTZ7ZCN2EX, Furo(3,2-g)-coumarin, 7H-Furo(3,2-g)(1)benzopyran-7-one, CCRIS 4343, CHEMBL164660, Furo[2′.3′:7.6]coumarin, CHEBI:27616, HSDB 3528, ZCCUUQDIBDJBTK-UHFFFAOYSA-N, TNP00293, EINECS 200-639-7, BRN 0152784, 6-Hydroxy-5-benzofuranacrylic acid beta-lactone, 5-Benzofuranacrylic acid, 6-hydroxy-, delta-lactone, 2-Propenoic acid, 3-(6-hydroxy-5-benzofuranyl)-, delta-lactone, Manaderm, Psoralene (DCF), Manaderm (TN), Furo[4′,7]coumarin, KTZ7ZCN2EX, Oprea1_841692, SCHEMBL17835, MLS001304059, Bio-0831, P8399_SIGMA, furano[3,2-g]chromen-2-one, AC1L1M09, MEGxp0_001172, ACon1_001579, CTK2F4103, pyrano[5,6-f]benzofuran-7-one, 2H-furo[3,2-g]chromen-2-one, MoIPort-001-741-377, 7-furo[3,2-g][1]benzopyranone, HMS2267L05, ZINC120283, HY-N0053, 7H-Furo[3,2-g]chromen-7-one #, ANW-73223, BDBM50331544, DNC000841, DNC001160, KT6528, MFCD00010520, NSC404562, ZINC00120283, AKOS004110987, AN-8451, CS-3756, MCULE-2236160968, NSC-404562, RTX-010528, NCGC00017351-01, NCGC00017351-02, NCGC00017351-03, NCGC00142529-01, 4CN-1081, AC-20293, AJ-11687, AK105376, BT000248, DR000253, LS-70690, PL066320, SC-18328, SMR000112587, ST057250, ZB004095, KB-249864, FT-0603268, N1332, P2077, ST24045730, W1301, C09305, D08450, P-7850, 6-hydroxy-5-benzofuranacrylic acid delta-lactone, 6-hydroxy-5-benzofuranacrylic acid gamma-lactone, 5-19-04-00445 (Beilstein Handbook Reference), A835599, 3B2-4155, I06-0551, BRD-K47264279-001-01-4, 5-Benzofuranacrylic acid, 6-hydroxy-, .delta.-lactone, 7H-Furo[3,2-g]benzopyran-7-one; Furo[3,2-g]coumarin, 3-(6-Hydroxy-5-benzofuranyl)-2-propenoic Acid|A-Lactone, 3-(6-hydroxy-5-benzofuranyl)-2-propenoic acid delta-lactone, 2-Propenoic acid, 3-(6-hydroxy-5-benzofuranyl)-, .delta.-lactone, and InChI=1/C11H603/c12-11-2-1-7-5-8-3-4-13-9(8)6-10(7)14-11/h1-6.

(59) Most commonly used photochemically active compounds or psoralen are 8-Methoxypsoralen (8-MOP) and 5-Methoxypsoralen (5-MOP).

(60) Irradiation by the apparatus is believes to create synergy between the effect of UV irradiation and ionization irradiation in the DNA of the object. The invention also can be used for disinfection of surfaces, blood products, cell therapies and biotechnical products and may be used in therapeutic purposes in humans and animals. The apparatus may be used together with pharmaceuticals or substances that increases the effect of the UV irradiation or ionization irradiation as mentioned above. One example of such a use is the use of the apparatus together with photosensitizing substances, e.g. furanocoumarins, in a manner that is made in photochemotherapy or in extracorporeal photophoresis or when platelets are treated before transfusion of blood. The invention also may be used together with radio nucleoid therapy.

(61) When it comes to the DNA-damage, induced by UVA combined with photochemotherapy and ionization therapy, such as particle irradiation, within the mentioned periods of time, it is enough if the DNA-damage or the change in DNA, which may be photo chemically induced bindings from furanocoumarins and DNA, only is measurable when it is combined with photosensitizing substances as administration of 8-MOP topically or per orally or with a solution of DNA or living cells or blood before exposures of UVA.

(62) The synergistic biological effects is especially useful for patients that has received total-body-irradiation in combination with bone-marrow-transplantation. Within hundred days after bone-marrow-transplantation the patient may develop an acute graft-versus-host reaction in the skin as well as in one or more visceral organs, such as liver- or gastrointestinal channel. These patients may successfully be treated with photochemotherapy for their graft-versus-host disease of the skin.

(63) In a clinical cohort study of the patients that received total body irradiation before transplantation compared to patients that did not receive total-body-irradiation, it shows that the patients that received total-body-irradiation responded best to photo chemotherapy. Further, patients that received fractionated total-body-irradiation may achieve an increased effect on visceral graft-versus-host disease after photochemotherapy (UVA and 8-methoxypsoralen). The effects of photo chemotherapy is caused by double stranded DNA-damages.

(64) The apparatus used for ionization irradiation and UV irradiation combined with photo chemotherapy concomitantly maximizes the biological effect and minimizes the dose of ionization and UV irradiation.

(65) TABLE-US-00001 Table of The conformation of the apparatus in relation to the target of the irradiation of the apparatus (UVII) Semi circularly Apparatus formed formed apparatus as a polygon where Apparatus where or an apparatus the irradiation the irradiation Round or eleptiform with the form of inwards towards comes from two Apparatus where apparatus with an ellipse, with the target comes opposite directions, the irradiation irradiation inwards irradiation inwards from different e.g. from the comes from one Target: towards the middle towards the middle directions front and from behind direction Standing human The target is a Standing Standing in front Standing in front Standing in front standing human UVII semicircle and at the sides and behind is administered in form of a from an apparatus polygon that stretches around Laying human Laying Around Laying Laying In front Laying In front Laying In front Semicircle and on the sides or behind (e.g.) in form of a on a net or in a polygon hammock of net to let through the light. Part of the body Part of the body Part of the body Part of the body Part of the body Part of Around Around In front and on In front or behind the body the sides in (In combination with In front form of a a net, or the part polygon of the body lays of own weight Item Item Item Item In front Item in front Item In front Around Semicircle and on the sides and behind in form of a polygon Tube that Blood tubing Blood tubing Blood tubing In Blood tubing In Blood tubing in lets through Semicircular front and on the front and at the front UVA sides in form of sides a polygon Fluid film, e.g. Fluid film or thin Fluid film, Blood Blood or blood layer with blood film In front product in a semicircle

(66) The therapeutic effect of the apparatus is dependent on where the apparatus is positioned in relation to the object and the medium (air or liquid) between the object that may absorb the light or ionization irradiation from the apparatus. If the skin is the first area that is hit by UVB irradiation, the epidermis is effecting foremost, while UVA irradiation gives effect in both the epidermis and dermis of the skin. Ionization irradiation may give effect on different depth in the objects' body dependent on the type of ionization irradiation and the setting/protocol of the therapy.

(67) The apparatus may also be used to effect blood, plasma, cells or tissue that may be transplanted allogenically, exogenically or be given back in an autologous manner.

(68) Be used to have an effect on blood or plasma in a circuit that is coupled extra corporeally to a patient. Be used therapeutically, including the used for dermatological diseases as and systemic autoimmune disease as.

(69) One primary effect of irradiation by the apparatus is inducing changes in DNA by an additive or possibly synergistic effect of UV and ionization irradiation. This effect on DNA is even more apparent when irradiation is combined with photosensitizing psoralen. One measure that the effect has been achieved is by measuring the number of single-stranded or double stranded DNA-damages in the living cells that are radiated by the apparatus. Also, the number of regulatory T-cells is expected to be increased in the patient that is treated by the apparatus.

(70) The apparatus may be used in irradiation treatment of a mammal, such as a human. The apparatus may be used on the outer surface or skin of an object, e.g. for the treatment of skin diseases, such as psoriasis, skin cancer.

(71) The apparatus may also be used to treat diseases in the inner organs to treat disease, which affects one or more of the following organs: vessels such as arteries & veins, sinuses, adrenals, parathyroid glands, appendix, thymus, chest, mammae, nipples, pancreas, diaphragm, gall-bladder, brain, hypophysis, joints, liver, uterus, trachea, lip, lungs, stomach, esophagus, spleen, oral cavity, muscles, different sphincter muscles, nerves, kidneys, prostate, skeletal bones, vertebras and cranium, rectum, anus, thyroid, larynx, throat, intestines, testicles, large bowel, duodenum, bladder, veins, ovaries or eyes.

(72) The disease may related to transplantation of organs and may be a rejection after stem cell transplantation, e.g. a graft-versus-host reaction. While the graft-versus-host reaction has similarities to a type-IV-reaction, where activated T-cells attacks antigens, which they are sensitized against, the apparatus could be used against a range of diseases or states following the transplantation.

(73) The disease may selected from the group comprising cancer, including metastasis from the cancer, which involves one or several organs, an autoimmune disease within one or several organs, such as Crohns disease, which may spread to different parts of the bowel or ulcerous colitis, which may engage different parts of the bowel, and also engage liver and gallbladder, an auto-immune disease, which attacks the central nerve system, such as multiple sclerosis, Guillaume Barres Syndrome and Amyotrophic lateral sclerosis, a reaction after a pharmaceutical treatment with a drug that affects the immune-defense, such as the so-called protein therapeutics, which may be recombined cytokine analogues, such as aldesleukin, interking or fusion therapeutics, such as denileukin diftitox, a reaction after a vaccination, an acute-state in the lung, such as acute-respiratory-distress syndrome (ARDS) and chronical inflammation in organs including the lung, such as pneumonitis and fibrosis, acute or chronic inflammations in any organs, e.g. the heart or the kidney.

(74) The apparatus and method can thus be used for the treatment of a mammal, whereby the disease (disorder or illness) may be selected from the group cancer Acute-Respiratory-Distress-Syndrome, pancreatitis, multiple sclerosis and graft-versus-host disease (GVHD).

(75) Because the apparatus administers ionization irradiation, it is necessary that the advantages of the irradiation must be weight against the risks thereof.

(76) The following examples illustrate certain details in the invention and are not intend to limit the scope of the invention in anyway.

(77) An apparatus that administers ultraviolet light or ionization irradiation, in one or several combined or alternately irradiation periods/pulsations.

(78) The ultraviolet light is preferably from the spectra for ultraviolet light of type A and/or type B, i.e. within the spectra from 400 nm to 280 nm, which may include a mix of different emission spectra within this spectra.

(79) It is preferable if the ionisation irradiation which is photon irradiation with wavelengths within the spectra for X-rays and/or gamma irradiation, i.e. within the spectra from 10 nm down to 0.001 nm, which may include a mixture of different emission spectra within this spectra.

(80) It is an advantage if the ionisation irradiation is X-rays. One method where the apparatus is used is to treat material or fluid that has living cells on the surface or within themselves or a combination thereof. One method where the apparatus is used to treat animals or mammals. One method where the apparatus is used to treat humans that has diseases in inner organs. One method is where the apparatus is used to treat humans that has graft-versus-host disease (GVHD). One method where the apparatus is used after administration of psoralen has been provided to the human, the blood product or the surface that the apparatus is illuminating/radiating. It may be preferred if the ultraviolet light is UVA. It may be preferable if the emission-peak in the ultraviolet light in is between 300-400 nanometers. The apparatus may for example be provided with UV module for UVB irradiation and X-rays irradiation, or UVA irradiation and gamma rays irradiation or UVB irradiation and gamma rays irradiation and UVA irradiation and gamma rays irradiation, respectively.

(81) It is a preferable if the UVA is used to induce the photochemical reaction between psoralen and DNA.

(82) The UV irradiation, which is combined with ionisation irradiation may be long-wave UVA and/or narrowband UVB.

(83) Especially, an apparatus that administer UVA and/or UVB and ionisation irradiation of shorter wavelength than UVC is described.

(84) UV irradiation and ionisation irradiation of an intensity that lies above the normal room light, such as ceiling light, point light, indicator lights and lights that are to mark different areas, to administer irradiation in the apparatus for therapy. It is understood that the ionisation irradiation described lies above the background irradiation.

(85) Treatment of an object with the apparatus of the invention is believed to have an effect on systematic disease in human due to the combined effect of ionisation irradiation and photo chemotherapy.

Example 1

(86) Patients with acute graft-versus-host disease in the skin, and in one or both of the visceral organs; (liver or the gastrointestinal channel), that were treated with photochemotherapy for their graft-versus-host disease in the skin were evaluated on whether the visceral graft-versus-host disease was healed or not. 28 patients had been treated with fractionated total-body-irradiation and cyclophosphamide together with the bone-marrow transplantation 35 (13-77) median (min-max) days before start of photochemotherapy. Five patients were not conditioned with total-body-irradiation but instead had received busulfan and cyclophosphamide before the bone-marrow-transplantation. These started photo chemotherapy 26 (13-68) days after bone-marrow-transplantation.

(87) The total healing (complete response) of the visceral graft-versus-host disease was significantly better among the patients who had received total-body-irradiation before photo chemotherapy compared to the patients that had not received total-body-irradiation, (p=0.045).

Example 2

Proof-of-Concept Study on the Effect on Lethal Acute-Respiratory-Distress Syndrome (ARDS) by Tailored DNA-Damage

(88) Background

(89) ARDS is a common lethal complication secondary to abdominal surgery and pancreatitis.

(90) ARDS has been coupled to an activation of Th17, which also has been identified as a key factor in pancreatitis and pancreatic cancer (Chepalla 2016, Oiva 2010). Apoptosis is an established inducer of tolerance and DNA-damaging pathways are explored to find new drug-targets to induce tolerance (Neves-Costa A and Luis F Moita 2016) Specially, photochemotherapy attenuates Th17 and induces vitamin-D, both which may attenuate ARDS (Furuhashi 2013, Sage 2010, Li Q 2016, Li J T 2005). The combination of low-dose irradiation and photochemotherapy has a synergistic effect in vitro. Separate reports suggest that Low-dose irradiation and photochemotherapy both may affect the CD 4 compartment (Gridley 2009, Singh 2010). The patients with ARDS related secondary to abdominal complications are frequently (every 3-4 day) undergoing computer-tomography (CT)ach a clinical effect by the addition of photochemotherapy within the half-time of repair of double-stranded DNA-lesions from imaging radiology (e.g. CT)<10-30 minutes.

(91) Method

(92) After granting an ethical application, to use an animal model of mouse (balb/c) or guinea pig or pig or sheep with intra peritoneal injection of lipopolysaccharide (LPS) with a an LD 50 of 24 h up to one week is used to perform a proof of concept study of a prototype of the combined DNA-damaging method (Gugliemotti 1997, Shi-Ping 2003). Imaging radiology and topical photochemotherapy will be used to induce combined DNA damage.

(93) Outcome

(94) Survival of the animal model is evaluated. ARDS is quantified by radiology and NET (Liu S. 2016). DNA-fibre and DNA-comets can quantify the DNA damage. Flow cytometry is used to evaluate the effects on apoptosis (annexin), necrosis (propidium Iodide (PI)), DNA-repair; p53 and p21, and on the lymphocytic cell populations. Liu S et al. Neutrophil extracellular traps are indirectly triggered by lipopolysaccharide and contribute to lung injury, 2016 Scientific Report November 16. 1-8. Shi-Ping D. A mouse model of severe pancreatitis induced with caerulein and lipopolysaccharide World J Gastroenterology 2003; 9(3):584-589 Gugliemotti A., Benzydamine protection in a mouse model of endotoxemia, Inflammation res. 46 (1997) 332-335. Zhou M T., Acute Lund Injury and ARDS in acute Pancreatitis: Mechanisms and potential intervention 2010 May 7; 16(17): 2094-2099 Iclozan C., T helper 17 are sufficient but not necessary to induce Acute Graft-versus-host disease Kappel W. IL-17 contributes to CD4-mediated graft-versus-host disease, 2009 Blood, January 22; 113(4): 945-954 Mauermann N., et al. Interferon-gamma regulates idiopathic pneumonia syndrome, a Th17+CD4+ T-cell mediated Graft-versus-host disease. 2008 Pp 379-388, 2008 Chellappa S. et al. Regulatory T cells that co-express ROR-gamma-t and FOXP3 are pro-inflammatory and immunosuppressive and expand in pancreatic cancer 2016, VOL. 5, NO. 4. Oiva et al. Acute pancreatitis with organ dysfunction associates with abnormal blood lymphocyte signalling: controlled laboratory study 2010, Critical Care 14:R207 Li Q., et al. Resolution of acute respiratory distress syndrome through reversing the imbalance of Treg/Th17 by targeting the cAMP pathway Mol Med Rep. 2016 July; 14(1): 343-8. Li J T et al. Unexpected Role for Adaptive alpha-beta Th17 Cells in Acute respiratory distress syndrome J Immunol 205 jul 1; 195(1):87-95 Sage R J and Lim H W. UV-based therapy and vitamin D Dermatoll Ther. 2010 January-February 23(1):72-81.

(95) Association between prehospital vitamin D status and incident acute respiratory failure in critically ill patients: a retrospective cohort study BMJ Open respir res. 2015 Jun. 13; 2(1) 1-9 Gridley D. S., et al. International Journal of Radiation Biology 2009, v85:3, pp250-261.

Example 3

(96) Measurements were made with RTI Piranha med dose probe (an external detector) as electrometer. The program used was Ocean, 2014, ver. 2016-12-07. 242.

(97) The source of irradiation was GE C-arm Stenoscop. Soma Technology Inc., the UVA and the X-ray modules tube were mounted in a ninety degree angle in relation to each other (FIG. 1).

(98) Ten seconds measurements of ionization irradiation were done.

(99) TABLE-US-00002 Distance UVA irradiation Ionization irradiation (cm) (mW/cm{circumflex over ( )}2) (mGy/s) [min-max] 4  1.8 [1.7-1.8]  3.4 [3.4-4.02] 19/32 0.9 0.92 32/33 0.30 [0.2-0.4] 0.94 [0.94-1.00]

(100) The [0.2-0.4] was the difference between the central and the peripheral position of mW/cm.sup.2 in the combined target area.

(101) TABLE-US-00003 Vertical position on the tubes Distance UVA irradiation Ionization irradiation (cm) (mW/cm.sup.2) (mGy/s) [min-max] 5/10.5 cm 1.6 [1.6-1.6] 3.99 [4.00-4.03]

Example 4

(102) The source for the ionization module is a C-arm Ziehm-Solo and for the UV module a UVA-source.

(103) Measurement of UVA is made on the effect through one-layer of 5mLBD Falcon™ FACS tube on a distance from an object, e.g. a tube to a shield.

(104) Maximum outside shield lateral 0.1, above 0.0 of mW/cm.sup.2 in the combined target area.

(105) Measurements were made with pulses of ionization irradiation during one minute.

(106) The detection was made with an electrometer from Solidose and an ionizing chamber from Victoreen m.55-4-5.

(107) TABLE-US-00004 Distance UVA irradiation Ionization irradiation (cm) (mW/cm{circumflex over ( )}2) (mGy/s) [min-max] 4 1.8 [1.8-1.9] 1.03 [0.67-1.23] 8 1.3 [1.0-1.4] 1.01 [0.89-1.20] 32 0.30 0.41

Example 5

(108) An X-ray tube, Opti 150/30/50HC-100 was assembled together with a Verifix UVA-star 500, 230 V/18 W, length 500 mm. The UV-light was measured with a digital ultraviolet radiometer with a spectral response of 280-400 nm and a peak response of 370 nm, accuracy +−5%, (Bohle, art no BO 55 003 00).

(109) The Verifix UVA star was assembled at a distance where 3.6-3.8 mW/cm.sup.2 were administered to the area of the object. The effect drop over the FACS tube plastic was measured to be 50%.

(110) 1 mL of fresh buffy-coat blood from human blood donors was aliquoted into 5 ml BD dual snap cap (BD Falcon round-bottom tubes) and a concentration of 1%, 0.1%, 0.05% and 0% of 100% pure Bergamot Eteric Oil from Citrus Bergamia peel was added. Then, the tubes were radiated to 0.5 gray with iterated pulses over a 25 minutes period during which the tubes where illuminated with UVA, which was emitted at a dose of 2.76 J/cm.sup.2 (2.69-2.84).

(111) The ionization irradiation was followed with a run of UVA of 2.76 J/cm.sup.2 and a run of X-ray 0.5 gray (II).

(112) The cells were held in the dark in a styrofoam box until radiated by the modules, and the non-radiated control cells stayed in the rack in the dark in the styrofoam box during the exposure. After irradiation, all batches were subsequently put into a water bath at 38 degree Celsius for 30 minutes.

(113) The cells where shaken, coloured with trypan-blue and put onto a C-chip of a disposable hemocytometer with Bürker chamber (DHC-B01) for counting the Erythrocytes, Leukocytes, Mammalian Cells, i.e.

(114) The ratio of necrotic versus living cells were counted with a microscope. Apoptotic cells or cell bodies were excluded from counting. The results are shown in Table 1 and FIG. 21.

(115) TABLE-US-00005 TABLE 1 The ratio of necrotic versus living cells when exposed to UVII, UVA 2.76 J/cm.sup.2 concomitant with 0.5 Gy X-ray from an apparatus comprising Verifix UVA-star 500 and Opti 150/30/50HC-100. The control ratio is subtracted from the analysis. n mean minimum maximum St-Dev UVII 2 0.317 0.213 0.421 0.147 UVA or II 4 0.038 0.069 0.122 0.098 T-test showed that T-value was 2.86 n = 4 P = 0.046
Abbreviations CT=computed tomograph UV=Ultraviolet light/irradiation type NBUVB=Narrow-band UVB PUVA=UVA administered after that the patient or the animal has been given psoralen administered orally or topically where the UV-light thereafter hits the skin. PUVA-sol=PUVA with the sun as a light source GVHD=Graft-versus-host-disease or Transplantation versus host reaction
Definition

(116) The terms “irradiation” and “radiation” are both used describe processes of transferring energy to and from an object including the transfer of energy via electromagnetic waves or the emission of particles during nuclear decay, and further including a process by which an object may be exposed to radiation.

(117) The term “object” is understood to mean a mammal body, such as a human or animal body, as well as a part of a body, or a non-mammal body, such as a surface or a fluid.

REFERENCES

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