DE19852524A1 - Irradiation facility for therapeutic and cosmetic purposes - Google Patents

Abstract

The invention relates to a radiation device for therapeutic and cosmetic purposes, for treating primarily T-cell- transmitted skin diseases, especially atopic dermatitis (neurodermititis), cutaneous T-cell lymphomas, lichen ruber, alopecia areata, systematic lupus erythematodes and psoriasis and for cosmetic tanning. The device comprises at least one optical radiation source that produces a radiation intensity of at least 2 mW/cm<2> in the wavelength range of 400-440 nm and a radiation intensity of less than 21 % of the radiation intensity in the wavelength range of 400-440 nm in the wavelength range 300-400 nm on a surface to be irradiated.

Description

The invention relates to an irradiation device for therapeutic and cosmetic purposes.

Primarily T cell-mediated skin diseases such as atopic Dermatitis (neurodermatitis), cutane T-cell lymphoma, lichen planus and Psoriasis is based on a skin infiltrate of activated T lymphocytes own body. Neurodermatitis in particular is on the rise Newborns and children affected. Because of the inflamed areas of the skin, as well as the associated itching, this disease is both a heavy burden physiologically as well as psychologically.

The previously known therapies for the treatment of neurodermatitis can be essentially divided into two classes, namely chemotherapy and UVA 1 light therapy.

Chemotherapy is the current gold standard in the treatment of atopic dermatitis the glucocorticoid therapy. With this therapy comes partly after systemic as well as after topical application serious side effects. Alternative procedures for the treatment of Atopic dermatitis include therapy with strongly immunomodulating Pharmaceuticals, such as FK 506 or Cyclosporin A, via their Long-term consequences have no experience yet.

UVA 1 light therapy has proven to be effective for the treatment of acute Episodes of neurodermatitis, urticaria pigmentosa and localized scleroderma proven. Currently, UVA 1 therapy according to Meffert and the UVA 1 therapy according to Krutmann offered two device types. UVA 1 therapy according to Meffert, the fire band is between 340 and 500 nm UVA therapy according to Krutmann at 340-400 nm.  

A very good overview of the state of the art in UVA 1 therapy offers "position on quality assurance in UVA 1 phototherapy, version the subcommittee on Photo (Chemo) Therapy and Diagnostics physical procedures in dermatology, May 1998 ", as well as the" guidelines for quality assurance in photo (chemo) therapy and diagnostics ", which in "Krutmann, S., Hönigsmann, H .: Handbook of Dermatological Phototherapy and Diagnostics, Springer-Verlag, Heidelberg, pp. 392-395 " is published. As long-term risks there is premature aging and Carcinogenicity listed. Because of this situation, it is explicitly stated there that an application of medium and high doses of UVA 1 in childhood are not recommended. However, this is the largest group affected exempted from neurodermatitis.

It is also known to cause acne, unlike neurodermatitis of bacterial growth in clogged follicles rich in sebaceous glands Skin areas with cornification disorders caused by skin disease blue light in the range of 400-440 nm without significant UVA components treat, with limited success. For this, please refer to the Article "V. Sigurdsson et al., Phototherapy of Acne Vulgaris with visble Light, Dermatology 1997; 194; Vol. 3, 256-260 "with further references referred. This form of therapy was initiated that acne follicles in the As part of the dermatological examination with a so-called "woodlamp" fluoresce red. The source of fluorescence was the Storage of large amounts of porphyrins in the acne propion bacteria detected (Mc Ginley et al., Facial follicular porphyrin fluorescence. Correlation with age and density of propionibacterium acnes, Br. J. Dermatol Vol. 102, Vol. 3, 437-441, 1980). Since porphyrins have their main absorption (Soret- Band) around 400 nm, it was for Meffert et al. obvious, bacterial Treat acne follicles with visible light or blue light. Since the Hair follicles are several mm deep in the skin, these are of violet or blue light barely reached, which is why the observed effect only has been described as moderate. The longest wave absorption band of the Porphyrine is at 630 nm with a penetration depth of 4 mm, which for a  photodynamic follicle treatment appears more favorable.

The invention is therefore based on the technical problem, a Irradiation device for the treatment of primarily T-cell-mediated To create skin diseases that have fewer side effects and is particularly suitable for the treatment of children.

The solution to the technical problem results from the characteristics of Claim 1. Due to the surprising effectiveness of the radiation in Range of 400-440 nm on the T cells it is thus possible to use a Irradiation device for the treatment of primarily T-cell mediated To create skin diseases that, on the one hand, are barely treatable Allows to treat skin diseases such as lichen planus and on the other hand due to the carcinogenicity compared to UVA, which is ten orders of magnitude lower also enables treatment of children. The effectiveness is clinical Attempts have already been impressively confirmed. Here are the Subjects with radiation doses between 20 and 200 joules been treated. In addition, the test subjects surprisingly set a sustainable tan, so that the Irradiation device can also be used for cosmetic purposes and also there the known UV devices with the problems with regard to the risk of Can replace skin cancer. Further advantageous embodiments of the invention result from the subclaims.

In a preferred embodiment, the optical radiation source of the irradiation device is designed as at least one low-pressure mercury discharge lamp with preferably Sr ₂ P ₂ O ₇ : Eu or (SrMg) ₂ P ₂ O ₇ : Eu phosphor as the phosphor. With these, irradiance levels greater than 50 mW / cm ² can already be achieved at a distance of 50 cm. The effective irradiance can be increased even further by appropriately focusing the radiation emitted by the optical radiation sources onto the radiation surface, which in principle also applies to the subsequent optical radiation sources.

In a further preferred embodiment, the optical Radiation source as a high-pressure mercury discharge lamp with Metal halide additives gallium indium iodide and / or gallium iodide formed, the weight ratio between the mercury and the Metal halide additives is 10-100. To increase efficiency the quartz bulb partially mirrored with zirconium oxide in the area of the electrodes.

To suppress the radiation components emitted due to the mercury in the UVA range, the radiation device is assigned a UVA filter which in the simplest case from a glass pane or a UVA-impermeable one transparent plastic. The UVA filter is preferably a cladding tube formed, which is arranged around the optical radiation source and the Area between cladding tube and quartz bulb to a gas pressure of 10-500 Torr is evacuated.

In a further preferred embodiment there is an optical radiation source designed as an electrodeless high pressure mercury discharge lamp, which then preferred due to their higher vapor pressure Metal halides gallium chloride and / or bromide primarily used can come, as well as the pure metal gallium itself with its low Number of branch lines. The electromagnetic energy for the discharge is then by means of a magnetron with an associated antenna into one by one Coupled metal shield formed resonator.

Furthermore, an IR filter is preferably provided to avoid the unwanted Suppress heat radiation.

On the one hand, the optical radiation sources with sufficiently high power to operate and on the other hand the distance between the optical Choose radiation source and the radiation area as small as possible can, in order to achieve a correspondingly high irradiance a cooling unit assigned to optical radiation sources. The cooling unit is preferably designed as a liquid cooling. Preferably there is  the cooling unit consists of two radiation cooler sockets with integrated inlet and outlet Processes between which a transparent cladding tube is arranged. The advantage this arrangement is that the radiation cooler detachable with the optical radiation source are connected, resulting in their reuse defective optical radiation sources allowed. This transparent cladding tube Cooling unit also acts as a UVA filter, so that the electrodeless High-pressure mercury discharge lamp on the additional evacuated cladding tube can be dispensed with. In particular, water and for come as coolants the electrodeless high pressure lamp silicone oil. The silicone oil has a number of other advantages. In addition to a large stable Temperature range, cooling down to 4 ° C is possible. Silicone oil has one low absorption of microwave energy and at the same time acts as an IR Filters, so that separate IR filters can largely be dispensed with.

The invention is based on a preferred Embodiment explained in more detail. The figure shows:

Fig. 1 shows a cross section through a high-pressure mercury discharge lamp,

Fig. 2 shows a cross section through a high-pressure mercury discharge lamp with integrated water cooling,

Fig. 3 vapor pressure curves of gallium and gallium halides,

Fig. 4 shows a cross section through an electrodeless high-pressure discharge lamp with a cooling unit and a magnetron,

Fig. 5 is a cross-sectional view of an electrodeless high-pressure discharge lamp with a cooling unit and two magnetrons,

Fig. 6 is a spectrum of a high pressure discharge lamp with a weight ratio between mercury and gallium iodide of 44,

Fig. 7 is a spectrum of a high pressure discharge lamp with a weight ratio between mercury and gallium iodide of 22,

Fig. 8 is a spectrum of a high pressure discharge lamp having a weight ratio of mercury and gallium iodide of 8.8,

Fig. 9 shows a spectrum of a known gallium indium effect lamp and

Fig. 10 is a schematic cross-sectional representation of a whole body irradiation device.

The optical radiation source of the radiation device for the treatment of primarily T-cell-mediated skin diseases can be designed as a low-pressure as well as a high-pressure discharge lamp. However, as explained in more detail later, a high-pressure mercury discharge lamp 1 has some advantages in the spectrum over the known low-pressure discharge lamps for the spectral region of interest.

The high-pressure mercury discharge lamp 1 comprises a quartz bulb 2 , in which two electrodes 3 are arranged. Electrical connecting lines 4 for the voltage supply are connected to the electrodes 3 , which lead to a screw socket 5 . Arranged around the quartz bulb 2 is a cladding tube 6 which is closed at one end and is hermetically sealed to the screw socket 5 at its other end. The space between cladding tube 6 and quartz bulb 2 is evacuated to a gas pressure of 10-500 torr. The quartz bulb 2 contains mercury, argon and a metal halide additive such as gallium iodide and / or gallium indium iodide, which preferably emits in the wavelength range from 400-440 nm. The irradiance and the spectra will be discussed in more detail later. The amount and mixing ratios of the dopants 7 within the quartz bulb 2 are also performance-dependent. The weight ratio of mercury to the metal halide additives is 10-100. In the power range of 400 W, a mixing ratio of 1-5 mg metal halide additive to 44 mg mercury is preferably used. The quartz bulb 2 is also partially mirrored in the area 8 of the electrodes 3 by means of zirconium oxide in order to increase the temperature in the area of the quartz bulb 2 near the electrodes. The cladding tube 6 essentially has two functions. On the one hand, it serves as a UVA filter to reduce this unwanted spectral component as much as possible. On the other hand, the cladding tube 6 is used for thermal insulation, since the surface of the quartz bulb 2 becomes very hot during operation. Another advantage of the cladding tube 6 is the protection of the actual high-pressure discharge lamp against external temperature changes.

FIG. 2 shows a cross section through the high-pressure mercury discharge lamp 1 according to FIG. 1 with an integrated coolant unit. The coolant unit comprises a first and a second radiation cooler socket 9 , 10 and a transparent cladding tube 11 . An inlet or outlet 12 , 13 is integrated into each of the two radiation cooler sockets 9 , 10 , to which a hose can then be connected. The first radiation cooler 9 is simply pushed onto the screw 5 . The transparent cladding tube 11 is then inserted into the radiation cooler holder 9 and is closed on the opposite side by the screw connection 5 by the second radiation cooler holder 10 . A hermetically sealed circuit for the coolant 17 is formed between the inlet 12 and the outlet 13 by means of O-shaped sealing rings 14 , 15 , 16 . In the simplest case, the coolant 17 can be water. In this case, the coolant 17 mainly serves to dissipate the heat generated on the evacuated cladding tube 6 in order to keep it at a temperature of 40-60 ° C.

Since the depth of penetration of the blue light is limited, nevertheless in the case of diseases of the underlying skin layers or skin appendages, such as the hair roots, or in the case of inflammation-related thickening of the skin, such as in psoriasis and scleroderma, the radiation must penetrate very deeply, an irradiation device is advantageous for the circulating coolant 17 is significantly cooler than the skin temperature. Then the cooled cladding tube 11 can be placed directly on the affected skin, in which case irradiations of the order of magnitude of approximately 1-2 W / cm ² can be applied with an electrical connected load of 1000 W, since higher irradiations lead to a shorter treatment time . As a result of the high tissue absorption of the blue light, there is very strong heat development in the upper tissue layers, which would otherwise lead to burns without this cooling to, for example, 4 ° C. This cooling allows the depth effect limited by a threshold dose to be extended to several millimeters and thus into the follicle area. The preferred coolant 17 for electrode lamps is water.

In addition, the cladding tube 6 can be coated on the inside with the phosphors known from the low-pressure discharge lamps in order to transform additional portions of the UVC radiation emitted by the mercury into the wavelength range of 400-440 nm of interest. Since the phosphor itself has only a low absorption in the 400-440 nm range, an effective increase in the emission in this wavelength range is thus possible. Cooling of the phosphor is a prerequisite for the use of blue phosphors in the evacuated cladding tube, which may be filled with noble gas. Under normal operating conditions without cooling, the cladding tube reaches up to 600 ° C. However, the efficiency of the blue phosphors drops sharply at temperatures above 100 ° C., so that their use only makes sense when the thermostat is used below 100 ° C., as can be achieved with the coolant unit described above. The efficiency of the optical radiation source can be increased further by using phosphors in connection with other doping in the quartz burner, which preferably emit in the UV range. Halide compounds of the metals selenium, antimony, zinc and cadmium are suitable for this.

In FIG. 3, the vapor pressure curves in Torr over the absolute temperature of the pure metal and its gallium halide salts gallium iodide, gallium chloride and gallium bromide are shown. At the permissible wall temperatures without liquid cooling, the pure gallium is inferior to the halides by several orders of magnitude, so that efficient discharge with gallium can only be achieved at extremely high plasma temperatures, which in turn requires more cooling with, for example, silicone oil. The advantage of pure gallium compared to the halides is the smaller number of secondary lines in the spectral range outside the range of 400-440 nm that is not of interest. Of the gallium halides shown, gallium iodide has the lowest vapor pressure. Gallium bromide is an order of magnitude better from this point of view. However, these bromides or chlorides are so aggressive that they would quickly destroy the electrodes 3 in the exemplary embodiments according to FIGS. 1 and 2.

Therefore, when using gallium bromides or chlorides, an irradiation device without electrodes 3 as shown in FIG. 4 is preferred. The irradiation device 1 comprises a quartz bulb 2 in which the gallium or gallium halides are distributed. The cooling unit already described is arranged around the quartz piston 2 . A magnetron 18 with an associated antenna 19 is arranged on at least one end face of a radiation cooler detection 9 . Furthermore, a metallic shield 20 is arranged around the cooling unit, which forms a resonator for the electromagnetic waves emitted by the antenna 19 . The use of water as a coolant 17 is ruled out in this arrangement, since water would absorb the electromagnetic waves of the magnetron 18 too strongly, so that silicone oil is preferably used as the coolant here.

Electrode-free lamps have a useful life of 10,000-20,000 hours and a better efficiency than conventional light sources with electrodes 3 . However, the emission of these lamps is affected by temperature differences within the lamp. If parts of the quartz bulb 2 (plasma ampoule) are not heated uniformly, dark bands result which are caused by self-absorption of the plasma. The temperature differences within the plasma source are often the result of an uneven field distribution of the microwave energy in the resonator. This leads to an uneven discharge and a deterioration in the lamp output. In a preferred embodiment, control over the electromagnetic field distribution is achieved by a resonance cylinder which supports the E ₀₁ mode. In this case the field distribution is such that the electric field in the resonator axis has its highest value and the electric field vector points in the radial direction. The field strength drops to the conductive walls of the resonator to disappear on the conductive surface of the cylindrical shield 20 . The required power depends on the achievable plasma density. The plasma is concentrated in the middle of the discharge vessel. In the case of coaxial alignment, the entire cylinder jacket of the quartz piston 2 is in the region of the same field strength, so that irregularities in this regard are excluded. The resonant waveguide has a diameter of 9.37 cm in the E ₀₁ mode and the preferred excitation frequency of 2450 MHz. Under these conditions, any length is permissible for the resonator without the E ₀₁ resonance condition being changed, as a result of which the resonator can be easily adapted to different powers by changing the length.

Another advantage of the E ₀₁ mode is that, due to the symmetry, electromagnetic energy can be injected from two sides, as shown in FIG. 5, which is particularly important in the case of longer lengths of the quartz bulb 2 . Because of the standing wave, only the diameter of the waveguide must be strictly observed. The distance between the two magnetrons 18 is comparatively uncritical. It is only necessary to ensure that the energy absorption in the plasma is sufficiently high that no undamped waves hit the other magnetron 18 , as this could lead to destruction.

As already stated, water is eliminated as a coolant. Silicone oils such as dimethyl polysiloxane are therefore preferably used, which have only a low microwave absorption of less than 0.2 W / cm per kilowatt of power. Silicone oil is transparent in the visible range and absorbs a significant IR component in the wavelength range greater than 1 µm. This means that separate IR filters can either be dispensed with altogether or can be dimensioned in a less critical manner. Furthermore, dimethyl polysiloxane can be used over a wide temperature range from -70 ° C to 250 ° C. With this arrangement it is possible to couple up to 300 W / cm ^{3 of} plasma without melting the quartz bulb 2 . Compared to the usual air cooling of a plasma source, the noises that otherwise occur with a high air flow are eliminated, which is psychologically more pleasant for the patient.

If you want to do without silicone oil cooling in the electrodeless system, a rotating plasma quartz ball can be used, which is arranged on a shaft, for example, and when rotating in an E ₁₁₁ or E ₁₁₂ mode resonator, an average field distribution results on average. It also increases the effective surface area for convection cooling. The ball rotation preferably takes place in two planes, so that on average there is complete field mixing. A so-called wobble rotation is alternatively and technically simpler to implement, ie the rod itself rotates around a cone shell during a rotation about the z-axis.

In FIGS. 6-9 different spectra are shown at different dopings, wherein on the Y-axis, the irradiance in mW / cm ² per 0.5 nm at 50 cm distance is applied. The spectra shown show that with a weight ratio of mercury to gallium iodide of 8.8, the emission in the spectral range between 400-440 nm decreases considerably. With the weight ratios 22 and 44, the yield in the spectral region of interest is much better. A further increase in the emission in the range between 400-440 nm is possible by adding indium iodide in the mercury / indium iodide ratio of 20-200. With the addition of small amounts of indium iodide, an increase in indium emission in the 405 nm range is possible without the blue emission in the 500 nm range worsening the energy yield in the spectral range of interest between 400-440 nm.

In Fig. 10 is a schematic illustration of a whole-body irradiation device for a patient 21 is shown. For this purpose, a large number of the optical radiation sources are arranged in an array with respect to one another, a parabolic reflector 22 being associated with each optical radiation source. When using the cooling units described, they can be connected to each other in a meandering shape. Alternatively, however, only individual cooling units of the radiation sources can be combined, so that several cooling circuits with pumps are then used.

Claims (14)

1. Irradiation device for therapeutic and cosmetic purposes, comprising at least one optical radiation source which generates an irradiance of at least 20 mW / cm ² on a surface to be irradiated in the wavelength interval of 400-440 nm and an irradiance of less in the wavelength interval of 340-400 nm than 2 mW / cm ² , characterized in that the radiation device for the treatment of primarily T-cell-mediated skin diseases, in particular atopic dermatitis (neurodermatitis), cutaneous T-cell lymphoma, lichen planus, alopecia areata, systemic lupus erythematosus and psoriasis and is used for cosmetic tanning. 2. Irradiation device according to claim 1, characterized in that the optical radiation source as a mercury low-pressure discharge lamp with one of the following phosphors Sr ₂ P ₂ O ₇ : Eu, (SrMg) ₂ P ₂ O ₇ : Eu, Sr ₅ Cl (PO ₄ ) ₃ : Eu, BaMg ₂ Al ₁₆ O ₂₇ : Eu, SrMgAl ₁₈ O ₃₉ : Eu, BaMg ₂ Al ₁₆ O ₂₇ : Eu: Mn, Sr ₃ (PO ₄ ) ₂ : Eu, Ba ₃ (PO ₄ ) ₂ : Eu, CaWO ₄ : Pb or CaWO _{4 is} formed. 3. Irradiation device according to claim 1, characterized in that the optical radiation source as a metal halide lamp with a Ignition gas and mercury as well as with metal halide additives gallium Indium iodide, gallium iodide, selenium, antimony, zinc and / or cadmium is trained. 4. Irradiation device according to claim 3, characterized in that the weight ratio between the mercury and the Metal halide additive is 10-100. 5. Irradiation device according to one of the preceding claims, characterized in that the discharge tube is partially mirrored in an electrode region ( 8 ) by means of zirconium oxide. 6. Irradiation device according to one of the preceding claims, characterized in that between the optical radiation source and the surface to be irradiated is a sheet of glass or a transparent, UVA-impermeable plastic, especially Acryl GS or polycarbonate is arranged as a UVA filter. 7. Irradiation device according to claim 6, characterized in that the UVA filter is designed as an evacuated cladding tube ( 6 ) around the optical radiation source. 8. Irradiation device according to claim 7, characterized in that the inside of the cladding tube ( 6 ) is coated with one of the phosphors according to claim 2. 9. Irradiation device according to claim 1, characterized in that the optical radiation source is designed as an electrodeless mercury-metal halide lamp which is filled with gallium, gallium iodide, gallium bromide and / or chloride and the at least one magnetron ( 18 ) with antenna ( 19 ), via which electromagnetic energy can be coupled into a resonator formed by a metallic shield ( 20 ) and in which a quartz bulb ( 2 ) containing the dopants is arranged. 10. Irradiation device according to claim 9, characterized in that the resonator is designed as an E ₀₁ -mode resonator for the electromagnetic radiation coupled in by the magnetron ( 18 ). 11. Irradiation device according to one of the preceding claims, characterized in that the irradiation device with a  IR filter is formed. 12. Irradiation device according to one of the preceding claims, characterized in that the irradiation device Cooling unit is assigned. 13. Irradiation device according to claim 12, characterized in that the cooling unit is designed as a transparent cladding tube ( 11 ) with an inlet and an outlet ( 12 , 13 ) which is arranged around the optical radiation source, with the inlet and outlet ( 12 , 13 ) a coolant ( 17 ) circulates. 14. Irradiation device according to claim 13, characterized in that the coolant ( 17 ) is water or silicone oil.