WO2011001342A1

WO2011001342A1 - Body illumination system for controlling the biological clock of a mammal by radiation exposure of the skin

Info

Publication number: WO2011001342A1
Application number: PCT/IB2010/052892
Authority: WO
Inventors: Victoria Caroline Patrizia Kolb-Bachofen; Jörg LIEBMANN; Matthias Born; Ulrich Niemann
Original assignee: Koninklijke Philips Electronics N.V.; Philips Intellectual Property & Standards Gmbh
Priority date: 2009-06-30
Filing date: 2010-06-24
Publication date: 2011-01-06

Abstract

The invention relates to a method and body illumination system configured for controlling a biological rhythm of a mammal. The illumination system comprises one or more light sources configured for emitting light in a wavelength range of 400-480 nm. The body illumination system is configured for exposing a surface area greater than 0.5 m2 of the body to the emitted light. The body illumination system is configured such that the power density of the emitted light on the surface area of the body is greater than 125 mW/cm2. The method and system provide an illumination system capable of exposing a larger part of a body to radiation in a non-toxic dominant wavelength regime with a much greater power density in order to obtain effective control of a human biological rhythm within a reasonable period of time. The exposure of the skin of the mammal allows for the administering of the radiation without exposing the eyes of the person to the radiation, e.g. during sleep.

Description

Body illumination system for controlling the biological clock of a mammal by radiation exposure of the skin

FIELD OF THE INVENTION

The invention relates to a body illumination system for controlling the biological rhythm of a mammal, such as a human. More specifically, the invention relates to a body illumination system for controlling the biological rhythm of a mammal using extra- ocular radiation.

BACKGROUND OF THE INVENTION

In the last decade the knowledge of human photobiology has increased tremendously in the sense that it is clear that light radiation that is administered to the human subject through the eye -in addition to vision- is of major importance in controlling a variety of biological rhythms. Consequently, light radiation has influence not only on many physical body functions but also on mental performance and mood.

In a 24-hour society many people have to work and drive at night and be alert to perform well and safe, and to sleep well at abnormal hours. Under these conditions many people run an enhanced risk of making mistakes, for example causing car accidents, and/or are likely to suffer from a distorted sleeping behavior. As another example, airplane passengers passing several time zones during a flight often experience jetlag. Control of the biological rhythm, such as the circadian rhythm, is therefore desirable.

A disadvantage of the administering of radiation through the eye of a person in order to affect the biological rhythm is that it requires the person to be awake. Furthermore, visual exposure of persons to blue light that, as typically applied, may cause so-called "blue light hazard".

GB 2 378 656 discloses a means for modulating circadian rhythm where the output wavelength of the applied light source is concentrated around a wavelength of 440- 480 nm. The light is directed extra-ocularly, especially to blood vessels in or subjacent to the skin. The light energy in the selected wavebands is in the range of 2OxIO¹² - 100x10¹² photons per square centimeter per second. SUMMARY OF THE INVENTION

A body illumination system configured for controlling a biological rhythm of a mammal is disclosed. The illumination system comprises one or more light sources configured for emitting light in a wavelength range of 400-480 nm. The body illumination system is configured for exposing a surface area greater than 0.5 m² of the body to the emitted light. The body illumination system is configured such that the power density of the emitted light on the surface area of the body is greater than 125 mW/cm².

Furthermore, a method for controlling the biological rhythm of a mammal is disclosed. The method involves exposing a part of a body greater than 0,5 m² to a body illumination system emitting light in a wavelength range of 400-480 nm such that the power density of the emitted light on the surface area of the body is greater than 10 mW/cm².

Investigations reported by Kawara et al, J. Invest. Dermatol. 119, 1220-1223, 2002) have confirmed that UVB irradiation targeting superficial layers of skin, namely keratinocytes, represent a pathway for circadian rhythm modulation via changes in the expression of epidermal clock genes using keratinocyte cultures. The UVB irradiation used comprises a wavelength range of 280-320 nm and the power density of the emitted light was 0.35 mW per cm².

The experimental system of Kawara et al is not practically applicable for controlling biological rhythms, since the applied wavelength of the radiation is toxic for mammals and the power density is too small to obtain a noticeable effect within a reasonable time period. While the wavelength range of the radiation as disclosed in GB 2 378 656 substantially avoids toxic radiation effects, the document prescribes that very low power densities, i.e. smaller than 40 microwatts per square centimeter, should be used. The light sources of GB 2 378 656 may be mounted on a human body, e.g. using a head- worn device.

The applicant of the present invention has found that it is possible to use an illumination system capable of exposing a larger part of a body to radiation in a non-toxic dominant wavelength regime with a much greater power density in order to obtain effective control of a human biological rhythm within a reasonable period of time. The exposure of the skin of the mammal allows for the administering of the radiation without exposing the eyes of the person to the radiation, e.g. during sleep.

The embodiments as defined in claims 2 and 11 provide for a further reduction of the toxicity of the applied radiation to which the mammal is exposed.

The embodiment as defined in claim 3 provides for a highly effective type of light source to accomplish a body illumination system with the required parameters defined in claim 1. Although other light sources, such as high intensity discharge lamps, may be applied, more heat is generated by such light sources towards the body. Furthermore, such light sources generate light at other visible wavelengths which is experienced as annoying by users. The high power blue light sources may e.g. be Luxeon^® Rebel LED's. The LED's may have an optical power in the range of 175-740 mW and an operating current between

350-700 niA.

The embodiment as defined in claim 4 has the advantage of efficient placement and control of the light sources.

The embodiments of claims 5 and 12 define a relatively short exposure time of the mammal to the specified radiation to control the biological rhythm. This short exposure time is possible as a result of the high power density and large surface area that is radiated by the body illumination system.

The embodiments of claims 6-8, 13 and 14 define suitable means for incorporating at least a part of the body illumination system. Both resting means and clothing can be used as a result of the illumination of the skin of the mammal as opposed to the eye, i.e. extra-ocular application of the radiation. These can be conveniently applied during sleep.

Hereinafter, embodiments of the invention will be described in further detail. It should be appreciated, however, that these embodiments may not be construed as limiting the scope of protection for the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings:

FIGS. IA- 1C show schematic illustrations of a body illumination system according to various embodiments of the invention;

FIG. 2 shows a further illustration of a body illumination system incorporated in clothing of a human being;

FIGS. 3A-3F provide results of in vitro experiments using 453 nm radiation on human skin cell cultures; DETAILED DESCRIPTION OF THE DRAWINGS

FIGS. IA- 1C provide schematic illustrations of a body illumination system 1 for controlling a biological rhythm of a person 2. In FIG. IA, a person 2 lies on a bed 3 to be illuminated by the body illumination system 1. The body illumination system 1 comprises a plurality of light sources 4 configured for emitting light L to the person 2 in a sun-bed like arrangement.

In FIG. IB, two panels, oriented at an angle of 45° with respect to the bed 3, are provided that comprise light sources 4.

It should be appreciated that the light sources 4 are not necessarily provided over the entire body of the person 2.

It should also be appreciated that the person 2 is not necessarily on a bed. The body illumination system 1 may e.g. be comprised in a room R, the light sources 4 being accommodated in the walls of the room R, or being integrated in a standing system, as shown in FIG. 1C.

The body illumination system 1 is arranged for exposing a surface area greater than 0.5 m² of the person 2 to the emitted light, or greater than 0.75 or 1 m² of the skin of the person 2.

The light sources 4 are preferably high power light-emitting diodes (LED's).

These LED's 4 may be Luxeon^® Rebel^® LED's of Lumileds. The LED's have an optical power in the range of 175-740 mW and an operating current between 350-700 mA. The number of LED's may vary between 10 and 1000, dependent on the application. The LED's 4 may be provided in modules 5 (see e.g. FIG. IA).

The body illumination system 1 comprises a control unit 6 containing a controller 7 and a timer 8. It is noted that the control unit 6 may also be provided for the body illumination systems 1 of FIGS. IB and 1C.

The light sources 4 of the body illumination system 1 are specifically configured for emitting light in a wavelength range of 400-480 nm. The controller 5 is programmed such that the power density is greater than 10 mW/cm², particularly greater than 50, 75, 100, 120, 125 or even 200 mW/cm² of the body of the person 2. These settings effectively expose the person 2 to the radiation in order to control a biological rhythm, such as the circadian clock, of the person 2 within a reasonable period of time. The control unit 6 may comprise further modules, including e.g. a memory module for data storage, including storage of the settings of the power density.

The control unit 6 is configured for controlling the light sources 4 by means of the controller 7 and the timer 8. The controller 7 may be triggered to activate the light sources 4 (and, possibly, to set operating parameters of the light sources) by the timer 8. The timer 8 may be programmed to allow exposure to the radiation of the light sources 4 for only a limited period of time, e.g. 1 hour or 40 minutes, during a particular time period, e.g. a day.

FIG. 2 schematically depicts a plurality of light sources 4 of a body

illumination system 1 incorporated in a shirt 10. Of course, other types of clothing, such as trousers, jackets or other garment, may be used as well.

Cell culture experiments have been performed using primary human skin- derived keratinocytes, fibroblasts and endothelial cells. FIGS. 3A-3F provide results of in vitro experiments using 453 nm radiation on human skin cell cultures using different energy densities of 33, 66 and 100 J/cm² delivered three times during three consecutive days. The radiation was applied to the human skin cell cultures at a power density of about 125 mW/cm².

FIGS. 3 A and 3B illustrate the relative proliferation of endothelial cells and keratinocytes, respectively, for various energy densities. Clearly, cell proliferation is inhibited with increasing energy density. For the keratinocytes, the decrease of the cell proliferation results from an increased cell differentiation, as shown in FIG. 3C. The differentiation measurement was performed using Involucrin as a differentiation marker.

FIG. 3D shows the analysis of cleavage of poly(ADP-ribose) polymerase (PARP), which is a marker for programmed cell death (apoptosis). The more cleaved PARP is found, the more toxic the radiation is. From FIG. 3D it can be observed that that toxicity at 453 nm is substantially the same as for non-exposed control samples C. Thus, the results of FIG. 3D show that the 453 nm radiation is non-toxic.

It is known that particular proteins within cells are blue light acceptors and that these proteins control the human circadian clock, wherein the cyclic induction and suppression of these proteins is partly responsible for the 24-hour biorhythm of human beings. Two of these biorhythm controlling proteins, Cry-1 and Cry-2, are photoreceptors for 453 nm radiation and are present in the human skin. FIG. 3E shows a real-time polymerase chain reaction (PCR) analysis of the expression of circadian clock cycle genes Cry-1 and Cry-2 in human keratinocytes after exposure to 453 nm radiation at a energy density of 100 J/cm². Clearly, the 453 nm radiation affects the expression of both Cry-1 and Cry-2, while similar test samples that were not radiated (see FIG. 3F) did not show the variation. This indicates that there is a time-dependent change in the gene expression resembling the circadian rhythm.

As opposed to UV radiation, light at the wavelength range of 430-475 nm does not induce an inflammatory response. Evidence comes from measuring cellular secretion of cytokines into the cell culture. Secretion of interleukin-6 and interleukin-8 by keratinocytes and endothelial cells remains unchanged. Experimental data demonstrate that no

inflammation, i.e. no increase of cytokine production, occurs in response to the radiation and that also the normal state of homeostasis is not affected, i.e. the cytokine production does not decrease below base level.

It is noted that while the above experimental data relate to a 453 nm radiation, generally wavelength ranges of 400-480 nm may be used. While in the lower part of this range toxic effects have been observed for the in vitro cell cultures, it is believed that practical in vivo application on humans may not show these toxic effects as a result of absorption and scattering of part of the radiation.

Other variations to the disclosed embodiments can be understood and effected by those skilled in the art in practicing the claimed invention, from a study of the drawings, the disclosure, and the appended claims. In the claims, the word "comprising" does not exclude other elements or steps, and the indefinite article "a" or "an" does not exclude a plurality. The mere fact that certain measures are recited in mutually different dependent claims does not indicate that a combination of these measured cannot be used to advantage. Any reference signs in the claims should not be construed as limiting the scope.

Claims

CLAIMS:

1. A body illumination system comprising one or more light sources, the light sources being configured for emitting light in a wavelength range of 400-480 nm, wherein the system is configured for exposing to the emitted light a surface area greater than 0.5 m² of the body such that the power density of the emitted light on the surface area of the body is greater than 125 mW/cm².

2. The body illumination system according to claim 1, wherein the light sources are configured for emitting light in a wavelength range of 430-475 nm.

3. The body illumination system according to claim 1, wherein the light sources are high power light-emitting diodes (LED's).

4. The body illumination system according to claim 3, wherein the LED's are arranged in modules, each module comprising a plurality of the LED's.

5. The body illumination system according to claim 1, further comprising timing means configured for setting a time limit of less than 1 hour, preferably less than 40 minutes, for exposing the surface area to the emitted light.

6. The body illumination system according to claim 1, wherein the one or more light sources are contained in a wearable means for the body.

7. The body illumination system according to claim 6, wherein the wearable means comprises a clothing.

8. The body illumination system according to claim 1, wherein the one or more light sources are contained in a resting means, such as a bed or a chair.

9. A method for controlling the biological clock of a mammal comprising the step of exposing a part of a body greater than 0,5 m² to a body illumination system emitting light in a wavelength range of 400-480 nm such that the power density of the emitted light on the surface area of the body is greater than 10 mW/cm².

10. The method according to claim 9, wherein the power density of the emitted light is greater than 125 mW/cm².

11. The method according to claim 9, wherein the emitted light is in a wavelength range of 430-475 nm.

12. The method according to claim 9, wherein the part of the body is exposed for a period of time less than 1 hour, preferably less than 40 minutes.

13. The method according to claim 9, wherein the body is exposed using a wearable means containing the one or more light sources.

14. The method according to claim 9, wherein the body is exposed using a resting means, such as a bed or a chair.