Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N5/00—Radiation therapy
  • A61N5/06—Radiation therapy using light
  • A61N5/0613—Apparatus adapted for a specific treatment
  • A61N5/0616—Skin treatment other than tanning
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N5/00—Radiation therapy
  • A61N5/06—Radiation therapy using light
  • A61N5/0613—Apparatus adapted for a specific treatment
  • A61N5/0621—Hyperbilirubinemia, jaundice treatment
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P17/00—Drugs for dermatological disorders
  • A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/20—Hypnotics; Sedatives
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P27/00—Drugs for disorders of the senses
  • A61P27/02—Ophthalmic agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P35/00—Antineoplastic agents
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N5/00—Radiation therapy
  • A61N5/06—Radiation therapy using light
  • A61N2005/0635—Radiation therapy using light characterised by the body area to be irradiated
  • A61N2005/0643—Applicators, probes irradiating specific body areas in close proximity
  • A61N2005/0645—Applicators worn by the patient
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N5/00—Radiation therapy
  • A61N5/06—Radiation therapy using light
  • A61N2005/065—Light sources therefor
  • A61N2005/0651—Diodes
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N5/00—Radiation therapy
  • A61N5/06—Radiation therapy using light
  • A61N2005/065—Light sources therefor
  • A61N2005/0656—Chemical light sources
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N5/00—Radiation therapy
  • A61N5/06—Radiation therapy using light
  • A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
  • A61N2005/0659—Radiation therapy using light characterised by the wavelength of light used infrared
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N5/00—Radiation therapy
  • A61N5/06—Radiation therapy using light
  • A61N2005/0658—Radiation therapy using light characterised by the wavelength of light used
  • A61N2005/0662—Visible light
  • A61N2005/0663—Coloured light
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N5/00—Radiation therapy
  • A61N5/06—Radiation therapy using light
  • A61N5/0613—Apparatus adapted for a specific treatment
  • A61N5/0618—Psychological treatment
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
  • A61N5/00—Radiation therapy
  • A61N5/06—Radiation therapy using light
  • A61N5/0613—Apparatus adapted for a specific treatment
  • A61N5/062—Photodynamic therapy, i.e. excitation of an agent

Definitions

• Phototherapy also known as heliotherapy, is the use of light to treat medical disorders. Modern-day phototherapy was pioneered by Niels Finsen, who was awarded the 1903 Nobel Prize for Physiology and Medicine for his work on the treatment of disease with concentrated light radiation. Finsen' s initial work involved the separation of ultraviolet (UV) rays using quartz crystals, which was successful in the treatment of lupus vulgaris. Finsen also found that red light could be used to reduce scar formation in smallpox.
• UV ultraviolet
• phototherapy has been used to treat a wide range of conditions, including skin disorders, circadian rhythm and seasonal affective disorders, neonatal jaundice, and tumours.
• Treatment of skin conditions using phototherapy e.g. psoriasis, eczema, dermatitis, acne vulgaris, is largely reliant on radiation in the UV region, however red to infrared (IR) light can be used to promote wound healing.
• phototherapy e.g. psoriasis, eczema, dermatitis, acne vulgaris
• red to infrared (IR) light can be used to promote wound healing.
• Hyperbilirubinaemia better known as neonatal jaundice is a common condition, typically affecting over 50 % of newborn babies. Jaundice results from the inability of the liver to break down bilirubin, allowing it to accumulate in the blood. Phototherapy can be used to photo-oxidise trans- bilirubin to the water-soluble czs-isomer, which can then be more easily broken down by the liver and removed from the blood. According to the 2010 guidance set out by the National Institute of Health and Clinical Excellence (NICE) in the UK, treatment for neonatal jaundice depends on level of serum bilirubin.
• NICE National Institute of Health and Clinical Excellence
• Second-line treatment for babies born at or after 37 gestational weeks should be conventional "blue light" phototherapy, while for premature babies a fibre optic or "biliblanket” may be used in the first instance.
• Blue light is chosen to match the breakdown of bilirubin (which is optimal at 458 nm), though studies suggest that green light may be just as effective, thus providing a slightly less harmful alternative [H.Ayyash et ah, Archives of Disease in Childhood, 1987, 62, 843]. It is suggested that since green light is more penetrating than blue light, this compensates for its poorer match to the absorption spectrum of bilirubin, [H.J. Vreman et al., Pediatric Research, 1998, 44, 804] which peaks at around 458 nm.
• cancerous tissue is more responsive to the uptake of photosensitisers than healthy tissue, the approach can be used to selectively target cancerous cells.
• Selective photosensitiser uptake relies on the differences in chemical composition between healthy and tumorous tissues, which include the number of low-density lipoprotein receptors, the tissue pH, and water content.
• Suitable photoactive drugs can include porphyrin-based molecules, absorbing red light below 640 nm for treatment or tumours just beneath the surface of the skin or organ lining. For deeper penetration, IR-photoabsorbers are required. Chromophores within tissue, i.e. haemoglobin, melanin and water, will also absorb any incoming light.
• One first generation photosensitiser used for tumour phototherapy is haematoporphyrin derivative (HpD), which has five absorption bands at 400- 410 nm, 500-505 nm, 535-540 nm, 565-575 nm and 620-635 nm. Since penetration depth decreases with decreasing wavelength, photoactivation is typically implemented with a 630 nm-emitting dye laser. Studies suggest that green light may be more efficient for treatment of tumours just below the surface of the skin or tissue [J.C. van Gemert et ah, Br. J. Cancer, 1985, 52, 43]. Second and third generation photosensitisers absorb more strongly in the 650-850 nm range.
• Light sources for PDT include lasers, discharge and fluorescent lamps, and light-emitting diodes (LEDs).
• the choice of light source depends on the depth of the legion, the absorption spectrum of the photosensitiser, and the attributes of the light source itself (reliability, ease of maintenance, cost, and size). At illumination rates in excess of 150 mW cm “2 , hyperthermia usually results, which can lead to oxygen depletion. Therefore, lower rates are often preferable. Hyperthermia should be especially avoided in the skin, since it causes increased pain. Thus high power laser outputs are not always favourable.
• broad spectrum light sources such as halogen and metal halide lamps, may also be disadvantageous due to thermal effects and difficulty in controlling the light dosage.
• White light phototherapy is commonly used in the treatment of circadian rhythm disorders and seasonal affective disorder (SAD). It is believed that white light therapy early in the morning, during the winter months where there are fewer hours of daylight, can help to regulate the circadian rhythm and treat seasonal depressive symptoms.
• SAD seasonal affective disorder
• fluorescent light boxes are most commonly used, incorporating filters to block out harmful UV rays.
• red and IR light have been used for cosmetic phototherapy to improve the appearance of fine lines, wrinkles and skin tone.
• red to IR light is believed to stimulate collagen production and remodelling, resulting in smoother skin with a more even skin tone.
• QDs quantum dots
• One embodiment is a medical dressing having an occlusive layer and translucent layer.
• Quantum dot light-emitting diode chips are configured within the occlusive layer to provide light of a specific wavelength for use in phototherapy.
• Another embodiment is a medical dressing having an occlusive layer and translucent layer, wherein quantum dot material is embedded or impregnated within one or both layers.
• Figure 3 is a diagram of a multi-layer dressing comprising an array of QD LED chips (and circuitry) embedded in an occlusive dressing, covered with a translucent dressing layer, for the administration of phototherapy to wounds.
• FIG 4 is a diagram of a white phototherapy lamp for the treatment of circadian rhythm disorders, comprising a primary light source and a transparent or translucent lampshade comprising QDs.
• Figure 5 shows the colour coordinates of a white light produced from a white LED and red and green QDs, in the Commission Internationale de I'Eclairage 1931 colour space.
• the correlated colour temperature (CCT) is 5,536 K and the white point lies close to the Planckian locus.
• Figure 6 shows the emission spectrum of an LED chip comprising a blue solid-state LED backlight and a red QD phosphor emitting at 625 nm.
• the relative peak intensities can be tuned by altering the QD concentration.
• Figure 7 shows the emission spectrum of an LED chip comprising a blue solid-state LED backlight and a red QD phosphor emitting at 653 nm.
• the relative peak intensities can be tuned by altering the QD concentration.
• QDs quantum dots
• QDs and methods to prepare QD materials are provided in the Applicant's U.S. Patent Nos. 7,803,423, 7,985,466, 8,062,703, 7,588,828 and 7,867,556, which are incorporated herein by reference.
• the emission of QDs can be tuned across the entire visible spectrum and into the near- IR simply by changing the particle size.
• the high quantum yields and narrow band emission from QDs results in high colour purity with low energy loss from the solid-state backlight. Both the tunability and the colour quality and intensity of light available using QDs make QD materials promising materials for use in phototherapy.
• QDs to tune or "down convert" light from an LED light source to provide wavelengths of light needed for specific phototherapies.
• UV or blue emitting solid-state LEDs may be suitable, however, due to the harmful effects of UV radiation on the skin it may be preferable to use blue LEDs.
• QDs are incorporated into an LED chip package with a blue solid-state LED backlight.
• the preparation of LED chip packages incorporating QDs is described in the Applicant's commonly owned U.S. Patent Application Pub. Nos. 2010/1023155 (published 20 th May, 2010) and 2013/0140600 (published 6 th June, 2013), which are hereby incorporated by reference in their entireties.
• Such LED chip packages may be incorporated into articles for use in specific modalities of phototherapy, as described below.
• remote QD phosphors can be fabricated for use with a solid-state LED backlight.
• the preparation of remote QD phosphors is described in the applicant's co-pending GB Patent Application No. 1116517.2 (23 rd September, 2011), which is hereby incorporated by reference in its entirety.
• the QD phosphor may take the form of an article that is in close proximity to, or in direct contact with, the human tissue such as the skin.
• Remote phosphor-based systems have the advantage that one remote phosphor can be substituted for another having a different colour of emission, thus a single LED backlight system can be used for treatment of a number of different conditions by simply swapping out remote phosphors.
• an article described herein is a medical dressing incorporating QDs.
• dressing can refer to any article applied to the body to aid in phototherapy, but generally refers to a fabric or textile article, such as a bandage, blanket, article of clothing, sponge, compress, wrap, or the like.
• the dressing may incorporate LEDs, as described above, a remote phosphor, or may be impregnated, coated, or treated with a QD material.
• the articles herein described can encompass QDs emitting at one or more wavelengths depending on the application.
• the QDs can optionally be incorporated into beads prior to use, to enhance their stability.
• the devices may utilise heavy metal-containing (Cd, As or Pb) or heavy metal-free QDs such as III- V and I-III-VI 2 semiconductor QDs, and including doped species and alloys thereof.
• the photoluminescence quantum yield (QY) of the nanoparticles can be improved by coating the QD "cores" with one or more shell layers of a wider bandgap material to form a core/(multi)shell QD.
• Beading and/or encapsulation techniques used in the device fabrication process significantly reduce the risk of exposure to toxic heavy metals from QDs, yet legislative restrictions on their use may make heavy metal-free QDs preferable, particularly for embodiments where the QDs are incorporated into an article that is in contact with human tissue.
• green QDs are incorporated into a dye to stain a translucent or loose-weave textile material, which is used to produce bedding or a canopy that emits blue-green light when illuminated by a blue solid- state LED lamp.
• the QD dye is prepared by combining QDs with an appropriate solvent and, optionally, additives to modify, for example, the coating properties of the dye and/or its adherence to the textile.
• the QD dye is applied to the textile material by any suitable deposition method including, but not restricted to, immersing the material in the dye solution, drop casting, or inkjet printing. After applying the dye to the material, the material is allowed to dry, optionally with the application of gentle heat, to evaporate the solvent.
• QD phosphors Unlike with colour filters, for which unwanted wavelengths are absorbed, QD phosphors absorb high energy radiation and emit at a longer wavelength with relatively little loss of energy, determined by the photoluminescence QY of the nanoparticles. QYs greater than 80 % are well-documented in the prior art for core/(multi)shell QDs.
• green QDs are incorporated into an incubator component, which is illuminated remotely using a blue solid-state LED lamp.
• the incubator component can be fabricated by incorporating QDs into the plastic from which it is constructed.
• the Applicant's U.S. Patent No. 8,168,457 which is incorporated herein by reference, describes the preparation of a moulded QD-containing plastic material.
• the QDs can be applied as a coating to the outer and/or inner surface of a pre-fabricated incubator.
• CdSe- and InP-based QDs can be synthesised to provide blue to green emission.
• Examples of methods to prepare such QD materials are provided in the Applicant's U.S. Patent Nos. 7,803,423, 7,985,466, 8,062,703, 7,588,828 and 7,867,556.
• the embodiments described herein are not limited to QDs prepared by any specific method.
• QDs it is possible to tune emission of a solid-state LED to match the peak wavelengths and relative intensities (by altering the relative concentrations of each colour of QDs) in the absorption spectrum of photosensitising molecules for the treatment of tumours and benign conditions such as wet age-related macular degeneration. Emission in the 600-850 nm "optical window" for PDT is possible using QDs.
• QDs it is also possible to achieve polychromatic emission from a single light source; by including the more activating but less penetrating wavelengths, i.e. blue-green emission, this may enhance tumour necrosis near the surface of the tissue, while the more penetrating wavelengths, i.e. red-IR, can still be emitted to target cells deeper in the tissue.
• PDT systems may employ a fibre optic catheter to direct a specific wavelength of light towards a target tissue in the body.
• An optical fibre filled with QDs dispersed in a liquid support medium is taught in the European patent application EP 0 783 784.
• a solid-state light source such as LEDs or laser light
• QDs emitting at a specific wavelength within the optical window for PDT such a fibre optic device can be employed for PDT applications.
• Red and/or IR-emitting QDs may be incorporated into devices that can be applied to the skin for use in wound healing and cosmetic phototherapy. Using blue solid-state LEDs as the primary light source, red and/or IR QD phosphors may be used to down-convert the emission to stimulate collagen production and remodelling.
• QDs may be incorporated into a dye that is subsequently used to stain sterile gauze or loose-weave surgical dressings, allowing light from a primary light source (located near to or in the dressing, depending on the thickness) to excite the QDs in the dressing, which is in contact with the skin.
• a multi-layer dressing may be assembled comprising an array of QD LED chips (and circuitry) embedded in an occlusive dressing layer, covered with a translucent dressing layer, as illustrated in Figure 3. Light emitted by the QD LED chips passes through the translucent dressing layer to the wound.
• the device By embedding the QD LED chips into an occlusive dressing, the device enables the administration of phototherapy to wounds that must not be exposed to the air, for example to prevent infection.
• the QDs may be incorporated into a transparent or translucent shaped article, as described in the Applicant's U.S. Patent No. 8,168,457.
• the shaped article may be moulded in a cast of the body part of the patient to whom it is to be applied.
• a shaped article in the form of a QD mask can be fabricated and applied to the face.
• the QD mask is then illuminated by a primary light source, such as a blue LED lamp.
• a primary light source such as a blue LED lamp.
• the QDs in the mask down-convert a proportion of the light to emit at wavelengths promoting skin rejuvenation.
• QDs can be used to fabricate LEDs emitting white light with a tunable correlated colour temperature (CCT), which can be used in the treatment of circadian rhythm and seasonal affective disorders.
• CCT correlated colour temperature
• the CCT quantifies the "shade" of white light emitted, which can be tuned for therapeutic purposes.
• a CCT close to that of natural daylight round 5,500 - 6,500 K
• can be beneficial for the treatment of circadian rhythm disorders such as seasonal affective disorder.
• a white-emitting phototherapy lamp comprising a primary light source and a lampshade comprising QDs, as shown in Figure 4.
• the lampshade may be prepared by incorporating the QDs into a transparent or translucent shaped article, as described in the U.S. Patent No. 8,168,457.
• the QDs absorb a proportion of the primary light to produce white light with a desired colour temperature.
• a phototherapy lamp comprises a blue LED primary light source in combination with a lampshade comprising red and green QDs to produce cool white light with a CCT in the range 5,500 - 6,500 K, to mimic natural daylight for the treatment of seasonal affective disorder.
• FIG. 5 An example of a white lighting device comprising a blue LED backlight and red and green QDs, with a CCT of 5,536 K, is shown in Figure 5.
• the white point lies close to the Planckian locus (the path that a black body radiation source would take in chromaticity space as the colour temperature changes), indicating that the emitted light is close to that which would be emitted by the Sun at the same colour temperature.
• the CCT can be tuned by varying the emission wavelength of the QDs and/or the ratio of blue ligh green QDs:red QDs.
• Suitable examples of red- and green-emitting nanoparticles include, but are not restricted to, CdSe and InP, and including doped species and alloys thereof.
• Example 1 QD LED Emitting within the Photodynamic
• a QD LED chip comprising a blue solid-state LED as the primary light source and a red quantum dot silicone resin, with red emission in the optical window for PDT, was fabricated using CdSe/CdS/CdZnS/ZnS core-multishell QDs illuminated by a blue solid-state LED backlight emitting at 446 nm.
• the QD photoluminescence maximum (PL max ) of 625 nm is within the red absorption band of HpD (620-635 nm), with a narrow FWHM of 35 nm. Therefore, it could be suitable for PDT with a porphyrin-derived photosensitiser as an alternative to a diode laser lamp.
• the relative blue and red peak intensities can be adjusted by altering the QD concentration.
• a QD LED chip comprising a blue solid-state LED as the primary light source and a red quantum dot silicone resin was fabricated according to the following procedure:
• Silicone resin was mixed with a small amount of a Pt catalyst, then red InP/ZnS QD beads (20 ODs per 10 mmol solution in toluene) were added and the mixture was transferred to an LED case. The LED was cured under a nitrogen atmosphere.
• the QD LED was illuminated by a 22 mW blue solid-state LED.

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