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    • 专利摘要:
    The present invention relates to a method for controlling the degree of tension of a human body and a light source used in the method and the use of a light source in the method. The present invention includes the step of exposing the human body to appropriate light radiation for a period of time without substantially affecting the phase of the melatonin cycle. Melatonin is a sleeping hormone that can be used to control the tension of the body. Appropriate optical radiation is specified as the output fraction (melatonin watts / watt) and light output (lumens / watt) of the melatonin suppression radiation, and this output fraction and optical power are adjusted to have the desired effect on the phase of the period.
    公开号:KR20020062942A
    申请号:KR1020027005891
    申请日:2001-09-07
    公开日:2002-07-31
    发明作者:스켄데보라제이；아렌트죠세핀；태판카비타；반덴벨드게리트제이；반더버그트페트루스제이엠
    申请人:코닌클리즈케 필립스 일렉트로닉스 엔.브이.；유니버시티 오브 서레이；
    IPC主号:
    专利说明:

    BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method of controlling a strain of a human body and a light source used in the method. 2. Description of the Related Art < RTI ID = 0.0 >
    [3] Over the past decade, knowledge of human photobiology has increased significantly, indicating that light emission to the human body through the eyes is crucial to controlling a variety of physiological rhythms. Thus, light radiation affects not only a number of physical functions but also mental states and functions. Most of all the scientific evidence is based on eyeing a "white light radiation" of varying intensity, which is generally known and is disclosed, for example, in US-5,545,192. These reports show the sensitivity of melatonin suppression due to the light emission applied through the eye, where the melatonin inhibition depends on the dose of the light emission and on the spectral composition (Annals New York Academy of Sciences 453 (1985) ), p. 376-378). Melatonin is a hormone that is seen as a measure of the phase of the physiological rhythm with a 24-hour cycle. Melatonin is commonly known as a sleeping hormone that affects the tension of the human body. Therefore, when the melatonin cycle is controlled, the risk of mistakes due to relaxation of the tension is reduced. Relatively low melatonin levels cause tension, while relatively high melatonin levels cause more drowsiness. Annals New York Academy of Sciences 453 (1985), p. 376-378, the inhibition of melatonin is said to exhibit the highest sensitivity at a wavelength of about 509 nm. Suppression of melatonin is possible in "dark" times in a natural 24 hour cycle, where only available artificial lighting exists. During the day, the level of melatonin is relatively low, and the level of melatonin increases in the evening, reaching its maximum during the night, gradually decreasing by about the time of the weather. 24 hours a day In an active community, many people have to work at night, drive, nervously to work safely and well, and sleep well at non-regular times. Under such circumstances, many people are at greater risk of making mistakes, such as motor vehicle accidents, and are more likely to experience abnormal sleep behavior.
    [1] The present invention relates to a method of controlling alertness of a human body through appropriate light emission.
    [2] The present invention relates to a method of conditioning a circadian pacemaker and a light source used in such a method.
    [4] It is an object of the present invention to provide a method for reducing the risk that a person who has to work at a non-regular time of a day can make a mistake.
    [5] According to the present invention, this object is achieved by a method of controlling the degree of tension of a human body through appropriate light emission, wherein the human body has a cycle of melatonin change comprising at least a phase of melatonin accumulation and melatonin depression, The method comprising exposing the human body to suitable light radiation for an exposure period according to a desired effect on the phase of the cycle by inhibiting or allowing accumulation or by causing the melatonin degradation Wherein said desired effect is to inhibit said melatonin accumulation or to cause said melatonin degradation, or optionally to block the emission of ambient light or, optionally, between said two exposure periods, By making the non-display period, Wherein the appropriate light emission is specified by the output fraction of the melatonin suppression radiation (melatonin watts / watt) and the light output (lumens / watt), the output fraction and the light The output is adjusted to have a desired effect on the phase of the period.
    [6] Recent reports are inconsistent with previous statements that the sensitivity of melatonin suppression would be similar to that of dark-adapted visual sensitivity, since the maximum sensitivity to scotopic vision is at a wavelength of about 509 nm. Surprisingly, the melatonin inhibition sensitivity is shifted to shorter wavelength regions as compared to the dark-sighted visual sensitivity. Particularly surprising is that the majority of the perceived photoreceptors within the retina have an active wavelength of 500 nm or greater, so short wavelengths have a substantial effect on melatonin inhibition. At wavelengths below 500 nm, only the recognized receptors are blue cones, which have a λ max of 420 nm, which corresponds to less than 1% of any other family of photoreceptors in the retina Lt; / RTI >
    [7] Because of the increased efficiency, it is particularly advantageous that such short wavelength light can suppress melatonin formation, because very little light is required. In addition, the amount of light required to inhibit melatonin can be substantially reduced if the optimal wavelength or wavelength band is selected, thereby avoiding any problems in the field of vision caused by excessive flashing or intense illumination.
    [8] Melatonin is produced by the pineal gland, and it is believed that the appropriate afferent optic nerve affects the production of melatonin by the pineal gland. In particular, subjects looking directly at short wavelength light sources suffer a sharp decrease in melatonin production. However, the addition of light to other parts of the body in the body also affects the melatonin inhibition of the subject. Therefore, it is preferable that the light of the present invention is applied to the visual field, but it is also considered to apply to other parts of the body. Also, the dose for inhibiting melatonin as a function of wavelength is known for fully enlarged pupils.
    [9] Experiments show that the maximum sensitivity to short wavelength light exists in the region just above the ultraviolet light. Ultraviolet radiation is generally regarded as light emission of about 380 nm or less. In particular, a high sensitivity to light appears in the 420 to 460 nm region, and this sensitivity tail off as the wavelength increases and becomes almost zero at 560 nm. As described above, the wavelength of light is greater than ultraviolet , The present invention considers a wider wavelength range including ultraviolet rays. Generally, however, ultraviolet light should be avoided when considering the hazards of the subject. Applying the melatonin suppression radiation may be accomplished using a light source for vision, or another additional light source, such as a monitor, TV, reading or dining table, goggle, visors, May be integrated within the device. Numerous optical radiation applications for effective melatonin suppression or melatonin maintenance are found in home, workplace and traffic environments. Based on the current data, the following basic options for the spectral distribution of optical radiation are presented: 1. sufficient visible light for melatonin suppression radiation and adequate performance (for example, the allowed standard light level is at least 200 lux (lux means lumens / m 2 )). This application is found, for example, in indoor and outdoor shift work, including morning, evening, and night shifts. 2. Melatonin suppression radiation and hazy visible light levels below about 10 lux. In comparison, the full-moon light means a visible light level of 1 lux or less. Specifications for this, for example, are present at night and at night to drivers, security guards, nurses, and monitors. 3. Melatonin retaining radiation and sufficient visible light for moderate performance. Most applications are expected from evening activities, for example, and provide conditions for good quality sleep for the elderly in the home.
    [10] The evaluation of the efficiency of the spectral power distribution of the emission for melatonin suppression and luminous flux is done through calculations. In the calculation, only spectral power is considered to be in the wavelength range of 380-740 nm. All spectra are normalized such that the sum of the spectral power at 380-740 nm is 1 watt. Watt, where [lambda] is from 380 to 740 nm.
    [11] To calculate the luminous flux and melatonin effective wattage (melatonin watts), the following formula is used. Beam , Melatonin wat , Where V (λ) is the eye sensitivity flux, M (λ) is the melatonin sensitivity, and the constant value of 683 is the flux obtained by the 1 watt light with a wavelength of 555 nm, It is the maximum.
    [12] Figure 4 shows a typical melatonin sensitivity curve for people aged 20 to 40 years, obtained from an experiment. Since the sensitivity of melatonin is au, which is dependent on the transmittance of the lens of the eye, depending on the age of the subject, the efficiency of melatonin suppression through light emission generally decreases with increasing age of the subject. Melatonin Effective Watts Formula: Melatonin Watts , Where T ( ) Is the fraction of lens penetration.
    [13] Figure 4 shows a typical example of a melatonin sensitivity curve for an older age (60 years old or older) with corrected lens penetration.
    [14] The method of an embodiment is characterized in that the output fraction of the melatonin suppression radiation is greater than or equal to 0.45 melatonin watts / watt and the light output is less than or equal to 60 lumens / watt. Through this method, the melatonin is sufficiently suppressed, and the output of visible light emission is relatively low. This method is particularly suitable for nursing activities. However, since the visual sensitivity to light depends on the age of the human, it is preferred that the output fraction of the melatonin suppression radiation is greater than or equal to 0.45 melatonin watts / watt and the light output is less than or equal to 20 lumens / Do. This method is particularly suitable for use in relatively young layers with high sensitivity to light, the melatonin is sufficiently inhibited and the output of visible light emission is very low. When melatonin suppression is achieved by a very low amount of visible light / lumen, i.e. deep blue emitting light emission, the melatonin suppression radiation has little effect on the visual conditions produced by light for vision purposes. Applications of this method are found in activities that require blurred visible light levels, such as airfield control towers, but need to be awake and tense. However, for truck drivers driving at night, more is required for light levels, which the driver must keep awake during driving and have good visibility to the road. Therefore, the output fraction of the melatonin suppression radiation is greater than or equal to 0.45 melatonin watts / watt, and the light output is preferably less than or equal to 10 lumens / watt. A low light output of less than or equal to 10 lumens / watt can easily acquire light levels inside the cab of a truck that is low enough not to disturb the truck driver. As a result, the truck driver can stay awake and have a good view of the road.
    [15] In an environment where it is necessary to keep awake and the visual condition is only determined by a relatively simple task, a melatonin suppression radiation with a sufficient amount of visible light may be applied. An example of this environment is the shipyard's outdoor container work activity, where objects must be distinguishable by their shape and / or text. The method for such an environment is that the output fraction of the melatonin suppression radiation is greater than or equal to 0.45 melatonin watts / watt and the light output is greater than or equal to 60 lumens / watt.
    [16] Melatonin-suppressing radiation with a relatively high amount of visible light can be applied in an environment that must always be awake and requires good color vision conditions to perform the task. An example of such an environment is shift work, a hospital emergency medical center. An embodiment of the method for such an environment is characterized in that the output fraction of the melatonin suppression radiation is greater than or equal to 0.45 melatonin watts per watt and the light output is greater than or equal to 100 lumens per watt and the light source is greater than or equal to 65, It is preferable to have an index (CRI). Another example of a melatonin suppression luminescent method is in schools, colleges, in-class libraries, classrooms, and meeting rooms. Preferably, the embodiment of this method is characterized in that the output fraction of the melatonin suppression radiation is greater than or equal to 0.6 melatonin watts / watt, the light output is greater than or equal to 100 lumens / watt, and the light source is greater than or equal to 65 A rendering index (CRI) and a color temperature of 6500 K or more. This method is suitable, for example, for people who can not receive enough sunlight during the winter, older people with unstable rhythms, and people with hangover on Monday morning. The color temperature is relatively high, which has the effect of increasing the degree of tension due to melatonin inhibition and then psychologically stabilizing the degree of tension. Light having a melatonin watts / watt greater than or equal to 0.45 and lumens / watt greater than or equal to 100 may be obtained by a single light source, but otherwise may be obtained by a combination of light sources. In such a combination, a first light source having a relatively high lumen output, such as a / 80 low pressure mercury discharge fluorescent lamp with a lumen / watt greater than or equal to 200 and a color rendering index (CRI) greater than or equal to 80, Is coupled with a second light source having a relatively high melatonin suppression radiation output, such as a / 03 low pressure mercury discharge fluorescent lamp, watt / watt greater than or equal to 0.7. This combination makes it possible to add a second light source to an existing light emitting system with only a first light source in order to obtain an appropriate light emissivity. As a result, the obtained light emitting system has the advantage that it has a light source emitting moderate light radiation and is relatively inexpensive.
    [17] If the visual condition requires a few hours of work in the evening, for example, and the quality of sleep is not reduced so that the risk of making mistakes during the day needs to be reduced, light should be provided that affects the melatonin cycle to a relatively small extent. For such an application, the method of the present invention is characterized in that the output fraction of the melatonin suppression radiation is less than or equal to 0.2 melatonin watts / watt, the light output is greater than or equal to 100 lumens / Rendering Index (Ra), and preferably the output fraction of the melatonin suppression radiation is less than or equal to 0.1 melatonin watts / watt. These applications can be found in people who need to wake up at night or need to be checked during the night, such as old age homes, home raising children, hospitals, and nurseries. In this case, the melatonin suppression light for " sleepers " can be combined with an alerting light for " watchers " of the working / viewing room. This type of light can be a special night light and can optionally be embedded in the bed head, in the hall, in the entrance, in the direction of the stairs, and so on.
    [18] The method of one embodiment is such that the output fraction of the melatonin suppression radiation is shifted to > 0.2 melatonin watts / watt at ≥ 0.45 melatonin watts / watt and vice versa, the output light is greater than or equal to 100 lumens / Has a color rendering index (Ra) equal to or greater than 65. Through this method, a controlled gradual change from the melatonin suppression radiation to the non-suppression radiation can be achieved, thereby providing sufficient light in succession, allowing people to work correctly. This method starts with the suppression light for a short period of time and ends with the non-suppression light for a certain period of time because it performs a rapid rotary shift work, so that it can easily sleep after the nightclub work and any state shift of the biological clock Lt; RTI ID = 0.0 > light < / RTI > Depending on the time of day, methods involving movement from melatonin non-inhibiting to inhibitory radiation may be used in applications that resynchronize physiological clocks when traveling over various time zones, i.e., in the case of a zet-lag It is possible.
    [19] Having a color rendering index (CRI) of greater than or equal to 65 and having a light output greater than or equal to 100 lumens / watt and having a color rendering index (CRI) greater than or equal to ≥0.45 melatonin watts / A light emitting system having the potential may comprise a single light source, but may alternatively comprise a first and a second light source. In an embodiment of a light emitting system comprising a single light source, the output of a single light source is adjustable, for example by adjusting the lamp voltage. An example of such a light source is an electrodeless low pressure mercury discharge fluorescent lamp (QL). In an embodiment of the light emitting system including the first and second light sources, the light emitting system moves from use of the first light source to use of the second light source, or vice versa. In such a light emitting system, the first light source has a relatively high melatonin suppression radiation output, such as, for example, a high-pressure mercury discharge lamp with ≥0.45 melatonin watts / watt and the second light source has a white light with a melatonin wattage / It has a relatively low melatonin suppression radiation output, such as a high pressure sodium discharge lamp. Both of these light sources have an optical output power greater than or equal to 200 lumens / Watt and a color rendering index (CRI) greater than or equal to 65 during nominal operation.
    [20] Alternatively, in the method of an embodiment of the present invention, the filtering means is used to adjust the degree of light emission suitable for the human body. Through this method, the melatonin suppression radiation can be applied to the human body, while the acceptance of such radiation to the eye can be selected as desired. Thus, in the same environment, it is possible to control so that one keeps awake by blocking his melatonin accumulation, and the other does not block his melatonin accumulation.
    [21] The present invention also relates to a method of adjusting a 24-hour period pacemaker by applying light to a subject.
    [22] All vertebrates show time organisms in their activities. The vertebrates to which such methods are preferably used are mammals and are generally preferred, especially to humans. For example, humans are generally night-sleeping and daytime running. However, this pattern of activity is not fixed and it is possible to control this 24-hour period rhythm. This adjustment of the 24-hour period rhythm is not without problems, and may take several days to adjust depending on the size of the 24-hour period axis displacement and the individual involved. During this adjustment, an individual typically exhibits a state of awakening when he or she is sleeping, and a state of drowsiness when it is awake. Even when in a fully awake state, it is common for an individual to be under control if the ability and efficiency to deal with it is low.
    [23] For humans, adjustment or reordering of a 24-hour period pacemaker, which determines the rhythm of each individual's 24-hour cycle, is common. For example, shift workers, trans-meridian travelers, people suffering from emotional disturbances, or older people can benefit from 24-hour cycle pacemaker reordering. Studies conducted on animals have indicated that the emission of broad spectrum synthesis was needed to affect the 24-hour periodic system, but only a few studies were done on humans. Using a single emission of monochromatic light, Brainard and colleagues concluded that light at 509 nm was more effective than light at 448, 474, 542, 576 and 604 nm (Ann. NY Acad. Sci., 453 (1985) 376- 378).
    [24] WO 98/51372 (Campbell) discloses a method for resetting a human ' s 24 hour clock, optionally including applying sunlight to a portion of the body other than the eye, during sleeping time.
    [25] Both US-A-5176133 and US-A-5167288 and US-A-5163426 (Czeisler) are endogenous 24 hour cycle pacemakers over at least 36 hours, discloses a method for accurately evaluating and rapidly correcting the phase and amplitude of a circadian pacemaker. It is believed that the reason why the prior art has said that a wavelength of about 509 nm is the most effective wavelength for inhibiting melatonin generation is due to the problem of experimenting with the human body. Typically, a single dose of light can be applied without having to obtain a baseline reading, and the effect on the reduction of melatonin production is measured.
    [26] The light applied to the object need not be limited to the desired wavelength. However, in order to suppress melatonin, it is necessary that the wavelength required for the light applied to the object is sufficient.
    [27] In general, the lux level of the light source, in which monochromatic light is substantially used, must be present in an area greater than or equal to 40 lux for wavelengths below 480 nm. A typical lux level of 100,000 (equivalent to bright sunlight) is feasible, but higher lux levels are not only inconvenient to the human body, they are expensive to produce and have high power consumption. Therefore, a lux level of about 60 to 500 lux is preferable, and 70 to 300 lux is more preferable. Suitable levels may be between 80 and 150 lux.
    [28] The duration of the light application will be determined by a number of factors including the condition of the individual, the degree of control over the 24-h periodic pacemaker and the desired outcome. In general, the application of light should occur when the subject is not exposed to bright sunlight, and occasionally when melatonin production is in progress, or when the membrane is about to be formed or is about to be terminated. Peak generation generally occurs between 01.00 and 05.00 hours. Applying light in this amount of time and in this pit period can move the 24 hour period rhythm substantially forward, i.e. delay it. Similarly, applying light after such a peak can move the rhythm backwards, either of which can be selected to assist adaptation after the parallax travel and shift work.
    [29] In addition to the above, other conditions may better compensate for the 24-hour cycle rhythm of time-lapse travelers or shift workers. Other conditions may be treated as being considered appropriate by the subject or responsible therapist. For example, many people experience seasonal affective disorder (SAD) during the winter. The present invention is not limited to theory, and people can not receive sufficient direct sunlight during this period or are not sufficiently sensitive to the large amount of sunlight present during that period, and their 24 hour rhythm is not sufficiently robust, During this winter, the rhythm may be unclear or abnormally lengthened or delayed. Whatever the reason, during the day, especially in the morning and evening, the supplemental light of the present invention alleviates the disorder by reordering the 24-hour cycle rhythm of the human body.
    [30] Surprisingly, the present invention is particularly advantageous for the elderly. Usually, the 24-hour rhythm of older people is less robust, becoming awake at night and sleepy during the day.
    [31] The receptiveness to short wavelengths is greatly reduced in old age due to aging of the cornea and lens. Thus, treating an enhanced level of short wavelength radiation according to the present invention allows for a more normal lifestyle by re-adjusting and enhancing the 24-hour period rhythm of the elderly. Treatments for older patients are similar to those suffering from SAD, but the intensity is typically higher, with lux levels ranging from 200 to 1000 lux, more typically 200 to 600 lux, and advantageously about 400 lux Can be used. A lux level at the lower end of the preferred range can be used, where this shortwave light is used by older people during much of the normal daylight hours. A suitable level can be easily determined by the caregiver, for example.
    [32] By directing light to the eyes or other parts of the body, a person who has lost sight can also benefit from the present invention. Treatment is highly dependent on the state of loss of vision of the parties.
    [33] As described above, although the wavelength of light is larger than ultraviolet light, the present invention considers a wider wavelength range including ultraviolet light. In general, ultraviolet radiation should be avoided to minimize the risk to human health.
    [34] The invention will be illustrated by the following non-limiting examples.
    [35] Example
    [36] A fluence response curve for each individual, monochromatic wavelength of each object is established. This is achieved by first measuring the baseline for each photodetection and then applying different amounts of light of a given wavelength to the object at a particular time so as to be able to establish a dose response curve for each wavelength under study. This makes it possible for the ED 50 read to be obtained from each dose fluence response curve. From this, it was established that the effective wavelength for inhibiting melatonin production was in the range of 400 to 460 nm which was considerably lower than expected.
    [37] A) Method
    [38] The wavelength is performed in study legs consisting of three consecutive nights. The first night is the baseline nighttime, followed by two light exposure nights. A total of 20 study legs were performed and each subject was completed between 1 to 16 legs. When three or four study legs are performed consecutively, they become a study session.
    [39]
    [40] Twenty-two subjects (4F; 18M) were selected over the age range 18-45 years (mean ± SD = 27 ± 7 years). The subjects were healthy adults who did not take any medication except for weak analgesics or pill.
    [41] Three days before testing, the subject was asked to maintain a regular sleeping cycle and was asked to wake up at 23:00 and wake up at 7:00.
    [42] Study nights
    [43] The test protocol started at 19:00. An indwelling cannula was placed in the arm of the subject. From 21 to 23 o'clock, the subject was placed in a dim light (less than 10 lux). 90 minutes before phototherapy, one drop of the pupil dilator, Mimins Tropicamide 0.5% (Chauvin Pharma, Romford, UK), is dropped on each eye. Immediately after insertion of the dilated pupil, the subject was asked to lie down in a half-lying position using an eye mask. At 23 o'clock, the light of the laboratory is turned off and all subjects are lying in a half-lying posture in a completely dark state wearing a mask.
    [44] Subjects were photographed for 30 minutes at a fixed time between 23:30 and 02:30. The time of phototherapy was tailored to the individual to occur on a rising slope of endogenous (natural) melatonin rhythm prior to melatonin peak generation. Blood samples were taken just before 90 min of pupil dilation and then at 15 min intervals, from 15 min before light exposure to one hour after the light was turned off, and the last samples were taken at 30 min intervals. Blood samples were collected in a lithium heparin tube and centrifuged at 3000 rpm for 10 minutes. The plasma was separated and stored at -20 ° C until analysis.
    [45] Each different phototherapy was performed in 3 to 7 subjects between 23:30 and 02:30 for 30 minutes at various time points. Subjects were asked to place their heads in the light sphere (infra), place their jaws on the chin rest, and put their heads in the headband to correct posture. They kept their eyes open and stared at the point marked in the rear center of the block.
    [46] A summary of optical treatments is given in Table 1 below.
    [47] For these optical treatments, subjects placed their heads in a 45 cm diameter aperture (Apollo Lighting, Leeds, UK). This sphere has an opening cut for receiving the subject's head. The interior of the sphere was coated by 8 coatings of a white reflective coating (Kodak White Reflective Coating, Integra Bioscience Ltd., Letchworth, Hertfordshire, UK) providing 96% reflectance surface (Macam Photometrics Ltd., Livingstone, Scotland, UK) . The adjustable chin rest is constructed in house and painted with a reflective coating. This chin rest is placed with the headband to fit the sphere.
    [48]
    [49] This block uniformly illuminates the entire retina of the enlarged individual. The sphere was illuminated through a twenty-angled fiber optic cable on top of the dome. This cable was connected to a light source provided by a metal halide arc lamp (Enlightened Technologies Associates Inc., Fairfax, Va. USA).
    [50] Four different light boxes are used in the experiment. Light Boxes A and B use a 21 Watt (W) small metal halide arc lamp developed by Welch-Allyn. Light Box C and D are 50 Watt small metal halide arc lamps developed by Welch-Allyn use. Each light box includes a heat mirror between the light source and the fiber optic cable to allow ultraviolet (UV) and infrared (IR) radiation to be filtered (Enlightened Technologies Associates Inc., Fairfax. VA, USA).
    [51] In the later experiments (Study Period 17-20), which required higher light emission, the two fiber optic cables from the two light boxes were fed into one compartment by aligning the input ports.
    [52] All light sources did not show any UV emission when tested with a UV radiometer (UVP Inc., San Gabriel, Calif., USA). The light source was also tested for electromagnetic field (EMF) generation. All photoprocessing conditions showed no EMF greater than the background level of 0.1 μT.
    [53] 430, 460, 480, 500, of 560 nm 6 different maximum transmission wavelength (λ max) a solid filter (half λ 0.5 of the maximum band width 10nm Im) (monochromatic filters) (Coherent Ealing, Watford, Herts. UK) Were placed in the input port of the sphere. The intensity of the monochromatic light was adjusted using a combination of Kodak Wratten neutral density filters (Richard Frankfurt, Croydon, Surrey, UK) placed in the input port of the sphere between the light probe and the sphere.
    [54] The set up of the light source slightly changed the spectral quality of the monochromatic light and the measurement with a spectrophotometer (Spectrascan 650 portable, Photoresearch, Chadsworth, CA, USA) Proving the actual wavelength. Their λ max was 424, 456, 472, 496, 520, 548 nm (λ 0.5 is 5-13 nm).
    [55] Light was measured at the visual level of the subject using a portable radio meter (Macam Photometrics Ltd., Livingstone, Scotland, UK). When the detector was rotated at right angles, the emissivity did not change. The emissivity measured in [mu] W / cm < 2 > was converted to the number of photons by the calculation described below.
    [56] The spectral characteristics of the monochromatic light were measured at the visual level of the subject to determine the percent transmittance of light at each wavelength through the filter. This has been done so that if a spherical or fiber optic cable changes the spectral characteristics of the filter, it can be taken into account in photon calculations.
    [57] To calculate the number of photons at a given irradiance of monochromatic light, the measured emissivity and the energy / photon for each nanometer light are used. Photon / cm 2 / s = Emissivity (μW / cm 2 ) / Energy of one photon at wavelength. For example, the energy of one photon of 500 nm light can be calculated by the following equation. E = hV (where, h is the Planck constant (6625 * 10-34 watts / s 2), V is a frequency C / λ (speed (C) of the light wave is 3.00 * 10 17 nm / s) . Thus, When 3 μW / cm 2 of light of 500 nm is measured, the number of photons is calculated as follows: First, the energy of one photon of this light is calculated: E = hV (V = C / λ), E = * 10-34 watts / s 2) * (3.00 * 10 17 nm / s) / 500nm, E = 3.975 * 10 -13 μW / photon / s. Thus, the three-in μW / cm 2, the number of photons / cm 2 / s = (3 μW / cm 2 ) / (3.975 * 10 -13 μW / photon / s) = 7.5 * 10 12 photons / cm 2 / s Calculating the total number of photons for a light exposure of 30 minutes The total number of photons is (7.5 * 10 12 photons / cm 2 / s) * (1800) = 1.35 * 10 16 photons / cm 2 .
    [58] The manufacturer provided% transmittance for each monochromatic filter. The total number of photons was calculated by adding the transmitted photons / cm 2 / s at each 10 nm wavelength. For example, if a 500 nm filter transmits 50% at 500 nm, 1% at 490 nm and 1% at 510 nm, the number of photons of measured light consisting of 500 nm of 96% and 490 nm and 510 nm of 2% The photon / cm 2 / s was calculated as described above and the actual percent transmittance was multiplied. Next, photons / cm 2 / s at each 10 nm wavelength were summed and the total number of photons / cm 2 / s was calculated for the measured emissivity. This value was corrected for the duration of light exposure. In the overall calculation, the actual measured photons were used.
    [59] Plasma melatonin levels were determined by direct RIA (Radioimmunoassay). All plasma samples for each subject during each period were measured with the same component analysis. Samples were analyzed at night sequence (ie, at 23 o'clock n1, n2, n3 and the next time point for all the sernite) to minimize the effect of assay drift on the measurement. The RIAcalc program determines the percent of total counts bound or free and shows them as a function of the known concentration of the melatonin standard. A gentle curve is fitted through the standard point, and the concentration of the unknown sample is determined from this curve.
    [60] Data Analysis
    [61] For each optical treatment for each individual, each time point was expressed as a percentage of the corresponding baseline time point. At each emissivity studied, the personal data were averaged over each time point. Pair of students' tests checked for significant differences between the baseline night and the light treatment night at each time point. This data indicated that maximal melatonin inhibition occurred at about 30 to 45 minutes when light was turned on. Therefore, these two time points were used in the calculation of the melatonin inhibition rate.
    [62] The light-induced suppression of plasma melatonin is the average of the baseline line (N1) at 30 and 45 minutes after light on the photocoagulation night (N2) is illuminated for each individual It is calculated by comparing as follows.
    [63] % Melatonin inhibition = (N1 (mean 30 + 45 min) -N2 (mean 30 + 45 min) ) / N1 (mean 30 + 45 min)
    [64] Data from all subjects receiving the same phototherapy were averaged (arithmetic mean). Each individual data was log transformed and then averaged. Geometric mean ± deviation was generated by re-modifying these values.
    [65] Emissivity response curve control. The emissivity response curves for each wavelength are shown (photon / cm 2 for percent melatonin inhibition). The best-fit curves were generated using the following four-parameter logistic equation. y = (ac) / (1+ (x / b) d) + c, where y is% inhibition of melatonin, a is the emissivity (I) is at zero response, c is the response when the emissivity is maximum, x is the photon B is the half saturation response, and d is the slope of the line.
    [66] B) Results
    [67] The method of the present invention will be better understood with reference to the accompanying drawings.
    [68] 1 is a diagram of an emissivity response curve using a four-variable logistic equation,
    [69] Figure 2 is a plot of the activity spectrum, plotted for 456 nm with a maximum sensitivity (sigma) of 50% calculated for each wavelength,
    [70] Figure 3 is a drawing of the best fitting of the activity spectrum of Figure 2,
    [71] Figure 4a shows the wavelength dependence of the relative scale of the curve for the melatonin suppression and dark time (chart C) and phothpic time (curve D) for lens correction for the youth layer (graph A) I,
    [72] Figure 4b shows the relative scale of the degree of melatonin depression S depending on the wavelength of 500 * 10 -6 m (= 500 nm) and the radiant density of watts per m 2 ,
    [73] 5 shows three regions A, B, C of suitable radiation to control the degree of awakening of the human body (where the x axis represents the fraction F of melatonin watts per watt, the Y axis represents the light flux per watt, / 03 low pressure mercury discharge fluorescent lamp).
    [74] 6 is a view of the emission spectrum of a low pressure mercury discharge lamp suitable for melatonin suppression at low emission levels (where the x axis represents the wavelength lambda and the y axis represents the relative emission intensity E)
    [75] 7 is a view of the emission spectrum of a white high-pressure sodium discharge lamp with no filter (Graph A) and with a filter (Graph B), where x axis represents wavelength λ and y axis represents relative emission intensity E.
    [76] The emissivity response curve from the four-variable logistic equation was constructed for each wavelength using zero as response (a) to zero emissivity (FIG. 1). The range of values was used for the maximum response (c), and the slope (d) was fixed and free in these calculations. Optimal control over the data is achieved when the maximum response is fixed at 70 (r ≥ 0.99). The slope was fixed at 1.5. Therefore, the equation at this maximum is: The measured and calculated inhibition rate = (0 - 70) / (1 + (I / σ) 1.5 ) + 70, where I is the total number of photons and σ is half the value of the saturated constant.
    [77] For each wavelength, the 50% maximum sensitivity (sigma) calculated from the regulated line was 1.86 * 10 16 photons / cm 2 at 424 nm, 1.79 * 10 16 photons / cm 2 at 456 nm, 2.29 * 10 16 where photons / cm 2, 496 nm in a 3.60 * 10 16 photons / cm 2 and, in the 520nm - 4.23 10 16 where photons / cm 2, the 548nm 1.49 * 10 17 photons / cm 2. These data were then shown for 456 nm (Figure 2).
    [78] The activity spectrum of FIG. 2 was adjusted using monograms generated using Dartnall's monogram for four known photoreceptors. Individual monograms for rod (500 nm) receptor, blue (420 nm) blue cone, green (535 nm) corn, red (560 nm) corn were generated and different ratios of combinations were observed for the observed melatonin inhibition activity spectrum Lt; / RTI > Optimal control was obtained using 65% blue crown and 35% load receptor (Figure 3).
    [79] Experimental results show that blue crowns (λ max 420 nm) among known photoreceptors are most related to melatonin inhibition. About two times the number of photons of 496 nm light (load photo receptor Max ) compared to 424 nm light is required to produce an equivalent inhibition rate. The number of photons over 2.2 times is required at 520 nm to achieve the same effect. 548 light requires about eight times more light to achieve the same effect, which means that the red crown has minimal effect on this system.
    [80] FIG. 4A is a graphical representation of a typical corrected corrected for lens attenuation at nighttime (graph C), normal color timing (graph D), young adult (20-40 years, graph A) It is a sensitivity graph of the rate of melatonin inhibition, shown as the relative scale (i.e., the maximum value for each independent sensitivity graph is set to 1). Figure 4a shows that the melatonin suppression sensitivity is shifted to the shorter wavelength region compared to the nominal sensitivity, even compared to the dark sensitivity. The sensitivity of melatonin shows a peak at 400 to 460 nm, a decrease of about zero at 560 nm, and a wavelength of 560 nm is close to the maximum sensitivity to the reference time at 555 nm. The visual response time (visual sensitivity flux) has a 683 lumen value obtained by 1 watt of light with a wavelength of 555 nm. FIG. 4A shows that the sensitivity of melatonin suppression through the eyes of the elderly is greatly reduced, and its maximum sensitivity is shifted to a longer wavelength, i.e., a wavelength of about 475 nm.
    [81] Figure 4b shows the relationship between the degree of melatonin inhibition and the radiant density of watts per m < 2 > for an exposure time of 30 minutes. Given a curve for a wavelength of 500 nm, the dependence on other wavelengths is similar, for 420 to 490 nm, the curve is shifted to a lower radial density, and for 510 to 560 nm, the curve has a higher radiation density . About 50% Melatonin inhibition occurs at about 0.08 W / m 2 for fully enlarged pupils.
    [82] Figure 5 is a plot of the area of suitable radiation that produces various desired effects on the melatonin cycle. The three areas, A, B and C, are distinguished. In region A, the light has a high melatonin inhibition rate of low light emission level, greater than 0.45 melatonin watts / watt, less than 60, even less than 20 lumens / watt. In Region B, the light has a high melatonin inhibition rate at an acceptable high light emission level. The main characteristics of this zone B are melatonin watts / watt greater than 0.45 and greater than 60 lumens / watt. In region C, light has a low melatonin inhibition rate and a high light emission level. The main characteristic of this region C is that the melatonin watts / watt is less than 0.2 (and / or 0.1 melatonin watts / watt each) lumens / watt is greater than 100. In this area, distinctions can be made between a white source, a slightly white source and a colored source.
    [83] In the case of treating the human body by the method according to the present invention, the present invention is characterized in that it comprises a step of determining the phase of the human body cycle, a step of evaluating a desired effect on the human body cycle, an ambient light radiation effect on the human periodic melatonin change Determining the desired light emission (spectrum, intensity, exposure period, interval period) for inhibiting or allowing melatonin accumulation or causing melatonin degradation, respectively, and determining regions A, B, C Selecting a light source having a light emission output in accordance with one of the plurality of light emission modes; and selectively exposing the human body to appropriate light radiation during the exposure period, The appropriate light emission is indicated by the output fraction (melatonin watts / watt) and the light output (lumens / watt) of the melatonin suppression radiation, Group output fraction and light output comprises the regulated ━ crazy the desired effect on the phase of the cycle.
    [84] Figure 6 is part of a low-pressure mercury discharge lamp of the system with a nominal power of 15 watts is approximately 20% is converted into radiation (the lamp is activated by SPE (Eu 2+, strontium pyrophosphate (strontium pyrophosphate activated with Eu 2+) Lt; RTI ID = 0.0 > inner < / RTI > coating). Usually, this lamp is used for photocopying. However, it is suitable for use in the method according to the invention, since the emission spectrum of the lamp is at about 420 nm or at or near the maximum of the melatonin suppression sensitivity. This lamp can be effectively used in the method according to the invention because it is very suitable for suppressing melatonin at low light emission levels. The present invention is effectively used when an exposure period of 30 minutes is applied to the human body, with a (dark) unexposed period, i.e., a period of about 30 minutes when the lamp is turned off. This method can be applied to his application in activities where a low light level is required, such as a control tower of a night aerodrome, a truck cab, but must be awake and tense. When this system of 15 watts containing the lamp is provided in the cab of the truck, a luminous level of about 3 lux and a melatonin suppression radiation intensity of about 0.08 W / m < 2 > are obtained in this cab. The light emission level of 3 lux corresponds to the faint light emission level. The melatonin suppression radiation intensity of about 0.08 W / m 2 is a value suitable for melatonin inhibition of about 50%. The emission spectrum of the lamp has some unwanted radiation (Figure 6). In some parts, it has undesired radiation in the ultraviolet region, i.e. at a wavelength shorter than 380 nm, and beyond the blue-green region, i.e. at a wavelength longer than 540 nm. This undesired radiation can be removed relatively simply by using a suitable filter. For example, the emission level produced by emission in the region beyond the blue-green region can be reduced very simply by an absorption filter having a band edge at, for example, about 510 nm. By using this filter, the emission level is reduced down to about 1 lux, which is the appropriate emission level for the truck cab. This filter causes a relatively small reduction in melatonin watts / watt.
    [85] 7 is a diagram of the emission spectrum of a white high-pressure sodium discharge lamp (A) without a filter (Graph A) and a white high-pressure sodium discharge lamp (B) with a filter (Graph B). This filter is a generally available absorption filter having an absorption edge at 460 nm. Lamp (B) with this filter has a suitable light emission having a power fraction of melatonin suppression radiation of about 0.09 melatonin watts / watt. The lamp A without a filter has a very high output fraction of the melatonin suppression radiation, as evident from its very high emission, especially in the wavelength region of 400 to 475 nm, i.e. in the maximum region of approximately melatonin suppression sensitivity. Both lamp A and lamp B have an excellent color rendering index, CRI > = 80, and an efficiency of about 220 or more lumens / watt. In particular, lamp B is suitable for situations where a visual good condition is required and sleep quality should not be reduced. These applications can be applied to people who get up at night or need to be checked at night, such as homes with the elderly, parents with the young children, elderly homes, hospitals, nurseries, and so on.
    权利要求:
    Claims (15)
    [1" claim-type="Currently amended] A method for controlling the degree of tension of a human body through appropriate light emission,
    The human body has a cycle of melatonin changes comprising at least a phase of melatonin build-up and melatonin depression, and by inhibiting or allowing the melatonin accumulation, or by causing the melatonin depression to occur within a predetermined phase of the cycle And,
    Exposing the human body to suitable light radiation for an exposure period, according to a desired effect on the phase of the period,
    The desired effect is to inhibit the melatonin accumulation, or to cause the melatonin degradation, or optionally to block ambient light emission or, optionally, between the two exposure periods, By the unexposed period, the human body is illuminated with little influence on the phase of the period,
    The appropriate light emission is specified by the output fraction of the melatonin suppression radiation (melatonin watts / watt) and the light output (lumen / watt), the output fraction and the light output being adjusted to have the desired effect on the phase of the period
    A method for controlling the tension of a human body.
    [2" claim-type="Currently amended] The method according to claim 1,
    The output fraction of the melatonin suppression radiation is 0.45 melatonin watts /
    The light output is < = 60 lumens / watt
    A method for controlling the tension of a human body.
    [3" claim-type="Currently amended] The method according to claim 1,
    The output fraction of the melatonin suppression radiation is 0.45 melatonin watts /
    The light output is 20 lumens / watt
    A method for controlling the tension of a human body.
    [4" claim-type="Currently amended] The method according to claim 1,
    The output fraction of the melatonin suppression radiation is 0.45 melatonin watts /
    The light output is < = 10 lumens / watt
    A method for controlling the tension of a human body.
    [5" claim-type="Currently amended] The method according to claim 1,
    The output fraction of the melatonin suppression radiation is 0.45 melatonin watts /
    The light output is ≥60 lumens / watt
    A method for controlling the tension of a human body.
    [6" claim-type="Currently amended] The method according to claim 1,
    The output fraction of the melatonin suppression radiation is 0.45 melatonin watts /
    The light output is ≥100 lumens / Watt,
    When the color rendering index (CRI) of the light source is ≥65
    A method for controlling the tension of a human body.
    [7" claim-type="Currently amended] The method according to claim 1,
    The output fraction of the melatonin suppression radiation is > = 0.6 melatonin watts /
    The light output is ≥100 lumens / Watt,
    When the color rendering index (CRI) of the light source is ≥65 and the color temperature is ≥6500K
    A method for controlling the tension of a human body.
    [8" claim-type="Currently amended] The method according to claim 1,
    The output fraction of the melatonin suppression radiation is 0.2 melatonin watts /
    The light output is ≥100 lumens / Watt,
    When the color rendering index (Ra) of the light source is ≥65
    A method for controlling the tension of a human body.
    [9" claim-type="Currently amended] The method according to claim 1,
    The output fraction of said melatonin suppression radiation is < = 0.1 melatonin watt /
    The light output is ≥100 lumens / Watt,
    When the color rendering index (Ra) of the light source is ≥65
    A method for controlling the tension of a human body.
    [10" claim-type="Currently amended] The method according to claim 1,
    The output fraction of the melatonin suppression radiation is shifted to 0.2 melatonin watts / watt at 0.45 melatonin watts / watt, or vice versa,
    The light output is ≥100 lumens / Watt,
    When the color rendering index (Ra) of the light source is ≥65
    A method for controlling the tension of a human body.
    [11" claim-type="Currently amended] The method according to one of claims 1 to 10,
    Wherein the means for adjusting the appropriate light emission received by the body is selected from the group consisting of filtering means, a movable light source, and a light emitting system comprising adjustable first and second light sources
    A method for controlling the tension of a human body.
    [12" claim-type="Currently amended] A method for inhibiting melatonin production in a vertebrate organism,
    Applying a large amount of non-UV light having a wavelength less than 480 nm effective to inhibit melatonin production of said organism
    A method for inhibiting melatonin formation.
    [13" claim-type="Currently amended] In a method for regulating a 24-hour cycle in a spinal cord organism,
    And applying a large amount of non-ultraviolet light having a wavelength less than 480 nm effective for inhibiting melatonin production of said organism
    Adjusting the 24 hour period.
    [14" claim-type="Currently amended] The method according to claim 12 or 13,
    Wherein the light has a wavelength in the range of 452 to 454 nm
    Way.
    [15" claim-type="Currently amended] A light source or a combination of light sources used in the method claimed in any one of claims 1 to 14.
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    同族专利:
    公开号 | 公开日
    KR100935313B1|2010-01-06|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    法律状态:
    2000-09-08|Priority to GB0022089.7
    2000-09-08|Priority to GB0022089A
    2000-09-13|Priority to EP00203180.5
    2000-09-13|Priority to EP00203180
    2000-10-13|Priority to GB0025207A
    2000-10-13|Priority to GB0025207.2
    2001-09-07|Application filed by 코닌클리즈케 필립스 일렉트로닉스 엔.브이., 유니버시티 오브 서레이
    2002-07-31|Publication of KR20020062942A
    2010-01-06|Application granted
    2010-01-06|Publication of KR100935313B1
    优先权:
    申请号 | 申请日 | 专利标题
    GB0022089.7|2000-09-08|
    GB0022089A|GB0022089D0|2000-09-08|2000-09-08|Methods of circadian adjustment|
    EP00203180.5|2000-09-13|
    EP00203180|2000-09-13|
    GB0025207A|GB0025207D0|2000-10-13|2000-10-13|Method of circadian adjustment|
    GB0025207.2|2000-10-13|
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