WO2012010996A2

WO2012010996A2 - Improvements in phototherapy

Info

Publication number: WO2012010996A2
Application number: PCT/IB2011/052783
Authority: WO
Inventors: Gerrit Oversluizen; Liesbeth Van Pieterson; Luc Schlangen
Original assignee: Koninklijke Philips Electronics N.V.
Priority date: 2010-07-22
Filing date: 2011-06-24
Publication date: 2012-01-26
Also published as: WO2012010996A3

Abstract

A method of bio-stimulating phototherapy of a subject's body portion (3) is herewith provided. The method comprises non-invasively determining the optical absorption of a subjects skin portion (1), providing a first phototherapeutic dose to the subjects body portion with light having a bio-stimulating wavelength by illuminating the body portion as a function of the determined optical absorption, wherein the determination of the optical absorption comprises measuring least one of the of the melanin index and the lightness of the subjects skin portion. A phototherapy apparatus (27) is also provided.

Description

Improvements in phototherapy

TECHNICAL FIELD OF THE INVENTION

The present disclosure relates to phototherapy, in particular to apparatus and methods for dermatological phototherapy. The apparatus and methods may be used both in professional and domestic use, and for curative, cosmetic and wellness purposes.

BACKGROUND OF THE INVENTION

In the field of phototherapy, treating a patient with light, it is known that skin parameters need to be taken into account when ultraviolet (UV) and/or infrared (IR) treatment is used. Both treatments can cause damage to the skin when the radiation absorbed by the skin exceeds a threshold. This threshold may depend on skin type.

UV treatment is often used in treatment of various dermatological diseases such as e.g. psoriasis. A major problem of UV treatment is that the absorbed UV radiation can cause DNA damage and skin cancer when the irradiation dose is too high. Often a MED value (minimum erythemal dose) is used as a guide to determine a safe UV dose. The MED is the smallest dose to produce visible reddening of the skin, which is indicative of a skin irritation. The MED is known to vary with skin type. For characterizing skin type, the Fitzpatrick scale is commonly used. However, large differences in MED are found between different individuals of the same Fitzpatrick type, requiring determination of the MED by applying different amounts of light to the skin and observing at what dose erythema has occurred. This method inherently imposes irritation and potential damage to the tested skin portion. A method of optimizing the use of a tanning-related apparatus and an apparatus for performing such a method based on the MED are disclosed in US 6, 736, 832.

IR phototherapy is often used in the context of hair removal (depilation), where a sufficient amount of heat energy is needed near the hair shaft and hair bulb to 'burn' the hair, without damaging the skin through energy absorption. To prevent undesired hurting and skin damage, short high energy light pulses are used that inject, locally and focused to the depth of the hair shaft or bulb, an energy dose in the skin to efficiently attack the hair. After the high intensity light pulse, a thermal relaxation period is provided to allow the skin some time to dissipate the energy absorbed at or near the hot spot. The thermal relaxation time is chosen so short that the hair and/or hair follicle remain at an elevated temperature at the time of the next light pulse to ensure burning the hair.

In the field of photodepilation, for determining the dose to be administered without hurting the patient and/or visibly damaging the patients' skin again the Fitzpatrick scale and the MED are used. However, IR radiation may not produce erythema, reducing usefulness of the MED, and also here, large person-to-person fluctuations and unpredictable responses to the used doses are reported for people of the same Fitzpatrick type. Hair depilation using (near) infrared laser radiation is disclosed in GB 2 381 752, which states that only hair and skin of particular melanin values may be successfully treated and which discloses a treatment apparatus comprising a pigment sensor.

A presently increasingly relevant field - and being the field of the present disclosure - is that of bio-stimulation of living tissue. Bio-stimulating skin phototherapy may be applied for treating jaundice and psoriasis and may comprise curative phototherapy like wound healing or cosmetic phototherapy like rejuvenation. A particular branch of bio- stimulating phototherapy is known as Low Level Light Therapy (or: LLLT). In the field of bio-stimulation of living tissue, any damage to the tissue must be prevented. This poses significantly stricter requirements on the applied dose, since doses that are considered acceptable for the earlier-referenced fields of phototherapy may in fact already exceed stimulatory effective thresholds. On the other hand, reducing the applied illumination doses for safety reasons can easily lead to administration of a dose that is therapeutically ineffective. Successful treatment may thus require individual adjustment of dose and protocol. The MED indicates an upper dose limit but provides no useful information for doses below the MED. Indeed, for bio-stimulatory treatments clinical test results based on MED or the Fitzpatrick scale have proven inconclusive.

Consequently, there is a desire for equipment and methods for providing both safe and effective bio-stimulation phototherapy, in particular for domestic use.

SUMMARY OF THE INVENTION

A method of bio-stimulating phototherapy of a subject's body portion is herewith provided. The method comprises non-invasively determining an optical absorption property of a subjects skin portion, providing a first phototherapeutic dose to the subjects body portion with light having a bio-stimulating wavelength by illuminating the body portion as a function of the determined optical absorption, wherein the determination of the optical absorption property comprises measuring at least one of the of the melanin index and the lightness of the subjects skin portion.

Melanin absorbs radiation, hindering attaining an intended treatment dose in the body portion. The melanin index M indicates the melanin content in the skin considered and the lightness L* is defined in 1976 by the Commission International d'Eclairage (CIE) and is a measure of how the human eye perceives the lightness of the skin, see M.D. Shriver and E.J. Parra, "Comparison of Narrow-band reflectance spectroscopy and tristimulus colorimetry for measurements of skin and hair color in persons of different biological ancestry", Amer. J Phys Anthropology 112: 17-27 (2000). In humans, melanin is almost exclusively located in the epidermis. It has now been found that by determination of the melanin index or the lightness the irradiation losses in the epidermis may be assessed, and that for deeper-lying tissue (e.g. dermis, hypodermic tissue) absorption losses due to melanin are of little to no influence. Hence, the actually administered phototherapeutic dose into these deeper-lying tissues can be reliably assessed. Determining the melanin index or the lightness of the skin portion provides quantitative information on, and determination of, the effective filtering function of the skin due to the melanin. The melanin index M may be measured by apparatus commonly used in cosmetic industry, e.g. the Skin Pigmentation Analyzer © SPA 99 of CK electronic GmbH, or the DSM II ColorMeter by Cortex Technology, which latter apparatus can measure both the melanin index M and the lightness L*.

Measurement of the melanin index is preferred over measuring the lightness since it has been found that the melanin index is a more reliable parameter for quantifying the melanin content of the skin, see Shriver and Parra cited above.

Bio-stimulating phototherapy may comprise inter alia pain reduction, growth promotion, tissue restoration, treatment of (infantile) jaundice, for curative and/or

substantially cosmetic treatments.

The method may comprise the steps of selecting a bio-stimulating wavelength range to be used; determining a first phototherapeutic dose to be administered to the subjects body portion; measuring the melanin index and/or the lightness at least at or near a skin portion of the body portion; calculating a second phototherapeutic dose based on the first dose, the selected wavelength range and the determined melanin index and/or lightness, respectively of the skin portion; and providing the second phototherapeutic dose to the body portion by illuminating at least the skin portion with light in the selected wavelength range.

The first and second phototherapy doses may comprise a full treatment dose or a predetermined portion thereof. The melanin concentration and thus the melanin index and the lightness may, and generally will be, dependent on the body portion, the skin portion and the tanning of the skin portion. Further, the absorption and thus the filtering function of melanin are dependent on the wavelength of the phototherapy light. Considering such features allows providing an accurate prediction of the attenuation of an applied dose so that a second dose of phototherapeutic radiation may reliably be determined for achieving a desired first dose phototherapeutic radiation.

The function may comprise a wavelength and melanin-index dependent irradiance correction factor Icf = Icf(M, λ) = exp(Cm μ(λ) d), wherein Cm is a measure of the concentration of melanosomes in the epidermis of the skin portion which may be stated in terms of the melanin index M as Cm = (M-20)/150 and may be approximated in terms of the lightness L* as Cm = 1.925 - 0.44 ln(L*), μ(λ) describes the wavelength dependent absorption of the melanin and may be approximated as μ(λ) = μο λ^" 3 ^' 33 = 6.6 x 101 1 λ^" 3 ^' 33 in units of cm^"1 with λ in units of nm and wherein μο is the average absorption coefficient of a single melanosome, and wherein d accounts for the optical path in the epidermis. The thickness of the epidermis generally varies between about 0.4 mm to about 1.2 mm, taking scattering into account d may be in a range from about 0.004 to about 0.024 cm, averaging over thickness variations and scattering provides a generally applicable range of about 0.008- 0.016 cm, and a practical approximation is d = 0.012 cm. The function Icf corresponds to the inverse of the attenuation of the radiation by melanin absorption and it provides an approximation of the filtering function of the skin under consideration. The function is applicable to usefully provide correction factors over a large wavelength range, from UV to near IR wavelengths, and for substantially all skin types, ranging from light Caucasian type skin to dark Negroid type skin.

Advantageously, the melanin index or the lightness, respectively, is determined in a wavelength range between approx. 400 nm and approx. 2000 nm, in particular between approx. 500 nm and approx. 1500 nm, more in particular between approx. 600 nm and approx. 900 nm, and the body portion is illuminated with a phototherapy wavelength in that wavelength range.

It has been found than in the wavelength range between ca. 400-2000 nm several phototherapeutic treatments may be provided. From ca 450 nm, absorption of light by haemoglobin and oxyhaemoglobin generally decays with increasing wavelength. A local maximum is located between ca 550-600nm with a steep decrease for longer wavelengths. On the other hand, absorption by water generally increases from ca 450 nm to 2000nm with a number of absorption peaks near particular wavelengths, in particular around ca 1600nm. Melanin has a generally decreasing absorption over the wavelength range 400-2000nm. Between ca 500-1500 nm absorption of (oxy-) haemoglobin and water is reduced and in the wavelength range of ca 600-900 nm the main absorber is melanin. However, since the wavelength dependent absorption profile of melanin is known and rather smooth, correction may also be effectively employed in wavelength ranges where (oxy)haemoglobin and water have a significant absorption influence.

In accordance with the above, a phototherapy apparatus is provided herewith for use in the method and/or its various embodiments.

At least a portion of the apparatus may be formed to conform to at least part of the subject's body portion, e.g. by comprising a flexible, pliable or generally deformable portion such as a patch or bandage. The apparatus being formed for conforming to at least part of the body portion to be treated improves user comfort and allows prolonged treatment. Such apparatus, in particular in the form of a patch or bandage, may be worn inconspicuously under clothing. Such apparatus allows improved and predictable illumination of the body portion since shifted illumination portions and/or shadows caused by relative movement of the apparatus and the body portion are prevented. Further, illumination at an oblique angle may be prevented which may otherwise cause undesired reflection of the light and inaccurate dosing.

The light source may comprise one or more light emitting diodes (LEDs). LEDs may provide light in various well-defined wavelengths (colors) at high efficiency and produce little heat compared to other light sources. The LEDs may therefore be placed close to the body portion. LEDs are generally well controllable with respect to output power and may be rapidly switched, enabling fine control over the operation of the apparatus. Moderate and high-power LEDs that do not exhibit superluminous or laser operation are particularly suited for use in bio stimulation since such LEDS do not exhibit a threshold-behavior in the emitted power and continuous power control is facilitated. A light source comprising plural LEDs facilitates a large effective surface area.

These and other aspects will hereafter be elucidated with reference to the figures of the drawings, which indicate examples for explanatory purposes only. Various other embodiments may be conceived within the scope of the appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

In the drawings:

Fig. 1 is a schematic representation of a skin portion; Fig. 2 indicates typical irradiance correction factors for different skin types; Fig. 3 is a block scheme of an embodiment of a method of bio-stimulating phototherapy of a subject's body portion;

Fig. 4 is a schematic side view of a phototherapy apparatus;

Fig. 5 is a schematic side view of another phototherapy apparatus.

DETAILED DESCRIPTION OF EMBODIMENTS

It is noted that in the drawings, like features may be identified with like reference signs. It is further noted that the drawings are schematic, not necessarily to scale and that details that are not required for understanding the present invention may have been omitted. The terms "upward", "downward", "below", "above", and the like relate to the embodiments as oriented in the drawings. Further, elements that are at least substantially identical or that perform an at least substantially identical function are denoted by the same numeral.

Fig. 1 illustrates illumination of a human body portion 1, showing a skin portion 3, and illumination light 5. The skin 3 comprises an epidermis layer 7 of ca 0.1 mm thickness, a ca 1-4 mm thick dermis layer 9 covering hypodermic tissue 11. A fraction of the illumination light 5 penetrates into the dermis 9, and another fraction may penetrated into the hypodermic tissue 11 indicated with the arrows 13 and 15, respectively.

In the epidermis 7, the main optical absorbers are melanin and water. In the dermis 9, the main optical absorbers are water and blood. Hence, the absorbing or filtering effect of melanin is concentrated in the epidermis 7. It has now been found that once the reduction in optical energy by the epidermis 7 is known, the fraction of the energy available for deposition in the dermis 9 and hypodermic tissue 11 can be calculated. It has further been found that determining the melanin index of the skin portion 3 in fact substantially returns the melanin index of the epidermis 7 and thus provides a reliable quantification of the filtering effect of the epidermis 7 and determination of the dose available for deeper-lying tissue. Similarly, the absorption of the illumination light 5 by the melanin can be readily determined and heating of the epidermis 5 can be predicted to prevent overheating or hurting.

The filtering effect of the melanin in the epidermis can be substantial. The resulting correction factor Icf for different skin types are indicated in Fig. 2: light Caucasian skin with M = 26 (full lines), Asian skin with M = 42.5 (dotted lines) and dark Negroid skin with M = 80 (dashed lines). From Fig. 2 it becomes clear that the irradiance dose to be applied onto the skin may be a large multiple of the dose to be deposited in the dermis or hypodermic tissue, in particular for phototherapy with blue light for Asian or Negroid skin types.

The dose is a combination of illumination irradiance and illumination time. Adapting the irradiance and the dose to the local melanin index of the subject's skin will significantly affect and improve the effectiveness of the phototherapy. Also, safety of phototherapy is improved since irritation, damage and/or pain are substantially prevented. Phototherapy may therefore be made available for domestic use with little to no risk of damage or maltreatment.

An operating scheme of an embodiment of the method is provided in Fig. 3. A phototherapeutic wavelength (range) λ is selected and a suitable dose Dl to be administered to the body portion 1 are determined in step 17, e.g. by a practitioner. As an example, D. Barolet, "Light-emitting diodes (LEDs) in dermatology", Semin Cutan Med Surg 27:227-238 (2008), elucidates the existence of suitable wavelengths and optimal doses or fluences for different phototherapies, dependent on the tissue and condition to be treated. An overview of conditions which may be treated with bio-stimulating phototherapy, the mechanism believed to underlie the treatment effect and the associated wavelengths is provided in the following table:

Table 1. Phototherapy condition, mechanism (proposed) & action spectrum

Condition Mechanism Wavelength [nm]

Neonatal jaundice Bilirubin- Lumirubin conversion 460

Acne Reactive Oxygen + Anti-inflammatory 415 + 630, 660

Psoriasis Inhibit DNA synthesis 311

NO-mediated decreased proliferation¹ 450

(in vitro test)

Wound healing ATP-up-regulation and tissue 660

repair(inconclusive clinical evidence) (620, 670, 760, 830)

Rejuvenation ATP-up-regulation 660

(limited clinical evidence) (620, 670, 760, 830)

Pain of muscles and Heat induced vasodilatation IR-A

joints ATP-up-regulation and tissue repair 660

(limited clinical evidence) (620, 670, 760, 830) NO-mediated vasodilatation and/or UV-A or 450

pain signalling¹'² 1. J. Liebmann, M. Born, and V. Kolb-Bachofen, "Blue-light irradiation regulates proliferation and differentiation in human skin cells", J. of Investigative Dermatology 130(2010) 259-269

2. C.V. Suschek, C. Oplander, E.E. van Faassen, "Non-enzymatic NO production in human skin; effect of UVA on cutaneous NO stores", Nitric Oxide 22(2010)120-135.

The melanin index M of the skin portion 3 of the body portion 1 is determined in step 19. This may be performed by measuring light reflectance of the skin portion 3 at one or more wavelengths and deducing the skins absorbance at the used wavelength(s). Using plural wavelengths facilitates removing contribution to the absorption by (oxy)haemoglobin and/or water.

In step 21 the absorption of light at the phototherapeutic wavelength (range) λ to be used is determined and the factor Icf is calculated according to the above-reference formula.

In step 23 a phototherapy dose D2 to be applied onto the skin portion 3 is calculated based on the dose Dl to be administered. This may comprise straightforward multiplication with the correction factor Icf, or: D2(D1, Icf) = D2(D1, M, λ) = Icf(M, λ) * ϋΐ(λ). More complicated calculation is also conceivable. The phototherapy dose D2 may be applied by suitable selection of illumination intensity and duration, which may comprise illumination in one or more pulses of which the pulse intensity, duration and interval may be selected.

In step 25 the thus calculated phototherapy dose D2 is applied to the body portion 1 by illuminating the skin portion 3, resulting in administering the suitable dose Dl .

In calculating the phototherapy dose D2 to be applied, the effect of heating of the epidermis by the absorbed radiation may be included, to determine a maximum applied irradiance in order not to overheat the skin. A skin temperature of below 42°C is considered suitable, higher temperatures, in particular during prolonged periods, are undesired and temperatures of ca 45°C and higher are painful.

The method may be employed in separate stages, wherein the melanin index is determined at one moment and later on used for determining the function for operation of the light source, but since the melanin index may, and generally will, depend inter alia on the particular location of the skin portion and on its tanning, it is preferred to (re-)determine the melanin index shortly before applying a phototreatment. A phototherapy apparatus 27 for use in the above described method may comprise a light source 29 for providing light at a bio-stimulating phototherapeutic wavelength, here comprising a plurality of sub-light sources 31 mounted to a carrier 33, a sensor 35 for determining the melanin index of a subjects skin portion 3, the apparatus being arranged for illuminating the subjects skin portion 3 with light emitted by the light source 29, the apparatus further comprising a controller 37 for controlling operation of the light source 29 as a function of the determined melanin index. The apparatus 27 may be powered from any suitable power source 39, for portability powering from a battery is preferred. The controller 37 may comprise user operable knob with selectable settings. Also or alternatively, the controller may be configured to take additional input, e.g. for determining parameters of a therapy, user settings, timing, driving schemes for different skin colors etc. Advantageously, the controller is arranged, programmable or programmed for controlling operation of the light source 29 based on the Icf function discussed above. Such program may be stored on or in a memory comprised in the apparatus.

The controller 37 may be configured for controlling operation of the light source 29 during use, possibly automated, e.g. for adaptation to skin heating, tanning, inadvertent erythema etc.

The phototherapy apparatus 27 may be a human wearable patch, such as an apparatus conforming to human physique, preferably being deformable or even pliable, indicated in Fig. 5. The patch may be maintained in position with any suitable means such as one or more adhesive portions, hook-and- loop-type fastener and/or a strap 41 closable around the body portion.

Alternatively (not shown) a phototherapy apparatus may be an assembly comprising the light source, the sensor and/or the controller as separate objects, which may be interconnected for communicating with each other, e.g. with cables or via wireless communication.

A phototherapy apparatus 27 may comprise plural sensors 35 for determining the melanin index of the subject's skin portion 3 to detect local variations of the skin portion. As shown, the light source 29 may comprise plural sub-light sources 31. Advantageously, the light source 29 comprises one or more Light Emitting Diodes or LEDs, which are available for numerous suitable wavelengths, provide significant optical output power per watt input power and generate little heat. Incoherent LEDs are considered particularly advantageous, since lasers require additional control, increasing complexity and cost of the apparatus 27 and relatively narrowband radiation poses a high risk of overheating skin. Laser radiation may also present a danger to eyes of a user.

The sensor may comprise at least one light source and at least one detector for detecting light, the sensor being configured to illuminate a subject's skin portion and detect light reflected off the subject's skin portion, wherein the sensor is configured for determining a reflectivity of the subject's skin portion at a plurality of wavelengths. This allows accurate determination of the reflectance of the skin portion and thus of determining the melanin index.

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. Features from different embodiments may be suitably combined within the scope of the appended claims, unless explicitly mentioned otherwise. "Light emitting diode" or LED includes "organic light emitting diode" or OLED. 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. A single processor or other unit may fulfill the functions of several items recited in the claims. 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. A computer program may be stored/distributed on a suitable medium, such as an optical storage medium or a solid-state medium supplied together with or as part of other hardware, but may also be distributed in other forms, such as via the Internet or other wired or wireless telecommunication systems. Any reference signs in the claims should not be construed as limiting the scope.

Claims

CLAIMS:

1. A method of bio-stimulating phototherapy of a subjects body portion (1) comprising:

non-invasively determining an optical absorption property of a subjects skin portion (3); and

providing a first phototherapeutic dose to the subjects body portion with light having a bio-stimulating wavelength by illuminating the body portion as a function of the determined optical absorption;

wherein determination of the optical absorption property comprises measuring at least one of the melanin index (M) and the lightness (L*) of the subjects skin portion.

2. The method of claim 1, comprising the steps of:

selecting a bio-stimulating wavelength range to be used;

determining a first phototherapeutic dose (Dl) to be administered to the subjects body portion (1);

measuring at least one of the melanin index (M) and the lightness (L*) at least at or near a skin portion (3) of the body portion;

calculating a second phototherapeutic dose (D2) based on the first dose, the selected wavelength range and the determined melanin index or lightness, respectively, of the skin portion;

providing the second phototherapeutic dose to the body portion by illuminating at least the skin portion with light in the selected wavelength range.

3. The method of claim 1,

wherein the function comprises an irradiance correction factor Icf = exp(Cm μ(λ) d), with: Cm = (M-20)/150 or Cm = 1.925 - 0.44 ln(L*), μ(λ) = μ₀ λ^"333 = 6.6 x 10¹¹ λ^"333 cm^"1, and d is selected from a range of 0.004-0.024 cm,

wherein Cm is a measure of the concentration of melanonosomes in the epidermis of the skin portion, M is the melanin index, and L* is the lightness of the skin portion (3), respectively, μ(λ) is the wavelength dependent absorption coefficient of the melanin (in units of cm^"1 with λ in units of nm), and d accounts for the optical path in the epidermis (in cm).

4. The method of claim 1,

wherein the melanin index or the lightness, respectively, is determined in a wavelength range between approx. 400 nm and approx. 2000 nm, in particular between approx. 500 nm and approx. 1500 nm, more in particular between approx. 600 nm and approx. 900 nm, and wherein the skin portion (3) body portion (1) is illuminated with a phototherapy wavelength in that wavelength range.

5. A phototherapy apparatus (27) for use in the method of any preceding claim, comprising a light source (29) for providing light at a bio-stimulating phototherapeutic wavelength, and a sensor (35) configured to determine non-invasively at least one of the melanin index (M) and the lightness (L*) of a subjects skin portion (3),

wherein the apparatus is arranged for illuminating the subjects skin portion with light emitted by the light source, and

wherein the apparatus further comprises a controller (37) for controlling operation of the apparatus as a function of the determined melanin index or lightness, respectively. 6. The phototherapy apparatus (27) of claim 5,

wherein the function comprises an irradiance correction factor Icf = exp(Cm μ(λ) d), with: Cm = (M-20)/150, or Cm = 1.925 - 0.44 ln(L*), μ(λ) = μ₀ λ^"333 = 6.

6 x 10¹¹ λ^"333 cm^"1, and d is selected from a range of 0.004-0.024 cm,

wherein Cm is a measure of the concentration of melanonosomes in the epidermis of the skin portion (3), M is the melanin index, and L* is the lightness of the skin portion (3), respectively, μ(λ) is the wavelength dependent absorption coefficient of the melanin (in units of cm^"1 with λ in units of nm), and d accounts for the optical path in the epidermis (in units of cm).

7. The phototherapy apparatus (27) of claim 5, wherein the light source (29) comprises at least one light emitting diode (31).

8. The phototherapy apparatus (27) of claim 5, wherein the apparatus is formed for conforming to at least part of the body portion.