Patent Application
20080269849
1. Technical Field
The present relates to the field of phototherapy (PT), which is the use of electromagnetic radiation (EMR) in the near UV, visible and near IR ranges for therapeutic effect.
2. Discussion of Related Art
Light is a form of energy which has obvious effects on plants and animals. Light energy is converted to chemical energy in plants by chlorophyll. Light too has effects on animal physiology, beyond its role in vision. Some of these effects are detrimental, such as damage to the skin and eyes from UV light, while other effects are beneficial, such as the production of Vitamin D in the skin.
Phototherapy (PT) has been shown to increase microcirculation, decrease inflammation, promote angiogenesis, and decrease pain. Phototherapy has also been shown to decrease time for wound healing, and improve diabetic neuropathy.
The therapeutic use of light dates back over several thousand years. In India use of black seeds containing psoralen compounds were used with sunlight to treat non-pigmented lesions around 1500 B.C., and Hippocrates is said to have prescribed heliotherapy (sunlight therapy) around 400 BC. More recently, Niels Finsen was awarded the Nobel Prize in medicine for his 1893 discovery that ultraviolet radiation was beneficial in treatment of cutaneous tuberculosis. Throughout much of the 20th century UV light was used in an updated version of the ancient treatment for psoriasis, using artificial light. In 1981 Parrish published an action spectrum for UV light for treatment of psoriasis, and found that wavelengths around 310 nm was most effective for treatment with less tissue injury. UV light is often used in photodynamic therapy, where a chemical agent is used along with light.
Treatment of infants with neonatal jaundice was discovered serendipitously by an observant nursing sister in a clinic in the U.K. in 1957. The nun reported that the infants with jaundice in the sunlight areas of the nursery had their jaundice fade, while those in other areas did not.
About 50% of full term newborns, and a higher percentage of preterm infants have sufficient hyperbilirubinemia to cause mild jaundice. Neonatal hyperbilirubinemia is mostly unconjugated (unbound to albumin), and thus is free to pass the blood brain barrier. This may cause a form of brain damage called kernicterus, where there is deposition of bilirubin in the basal ganglia and brain stem nuclei. Newborns with health difficulties are at higher risks for multiple reasons, not feeding, lower serum albumin, and use of medications which compete for albumin binding.
Phototherapy is an established treatment for hyperbilirubinemia in neonates, and has greatly reduced the need for exchange transfusions. Phototherapy produces configurational photoisomerization and photo-oxidation of bilirubin in the skin and subcutaneous tissues which makes the bilirubin more water soluble. This prevents the bilirubin from crossing the blood brain barrier and causes it to be excreted more rapidly.
Phototherapy is also used in other areas of medicine. Lasers designed for use to cut and destroy tissue were later found to improve healing when used as dispersed light applied to the tissue. Phototherapy with light in the red and near infrared (R/NIR) portion of the spectrum (about 600 to 1400 nanometers (nm)) regions has gained much interest for therapeutic use. (Light from about 590 to 610 nm is amber/orange in color, but for simplicity herein visible light longer than 590 nm will be referred to as red light.)
A wide range of disorders of biological tissue, or their symptoms, have been treated with R/NIR phototherapy, including but not limited to acute and chronic musculoskeletal conditions such as arthritis, back and joint pain, tendonitis, muscle pain, stiffness and myofascial pain. R/NIR Phototherapy is also used to treat such conditions as post surgical complications such as swelling, inflammation, scarring and stiffness; acute trauma, chronic post-traumatic conditions in the soft tissues, bones including sprains, strains, wounds, neurological and neuromuscular conditions, ulcers including infected or non-infected chronic ulcers of different etiology such as venous ulcers, diabetic ulcers, decubitus ulcers, and pressure sores. Red/IR phototherapy is reported to reduce wrinkles, and other signs of aging of the skin. It has been shown to increase microcirculation, decrease inflammation, help diabetic neuropathy, promote angiogenesis, and decrease time for wound healing. It has recently been used for treatment of memory loss.
R/NIR phototherapy is able to affect deeper tissue levels than the UV therapy which is used for superficial skin disorders. The skin is made up of several distinct layers. Light must traverse these layers to reach the target molecules. UV light does not penetrate deeply enough to be effective in treating deep tissue, and carries risks. UV light is mostly absorbed by the outer layers of the epidermis and therefore has limited effect on deep tissue. UV light is also known to cause DNA damage, skin aging, burn injuries and to impair immune function.
The epidermis is made up of 5 layers. The Stratum Basale contains stem cells which can continuously multiply and produce kerotinocytes, as well as containing melanocytes. The next layer is the stratum spinosa which contains 8 to 10 layers of kerotinocytes which phagocytize melanin granules from projections from the melanocytes in the stratum basale. Next are three to five layers of stratum granulosum cells which are aging kerotinocytes, the stratum lucidum which is a thinner layer of dead cells with droplets of eledin which is eventually transformed to keratin, and the outer layers is the stratum corneum which is made up of 20-30 layers of flat dead cells filled with keratin. Melanin, a UV absorbing molecule, is taken up by the kerotinocytes and functions to protect the underlying tissue from UV light, thus preventing most of the UV, as well as short wave visible light (blue and green light) from crossing the epidermis.
Below the epidermis is the dermis which is composed of connective tissue containing collagen and elastic fibers. There are sparse cells in the dermis, which include fibroblasts, macrophages and fat cells. Blood vessels, nerve endings, sweat glands and hair follicles are embedded in the dermis.
R/NIR can penetrate into the dermis, and thus can have an effect on this tissue. It is theorized that R/NIR therapy stimulates fibroblast in the dermis to produce substances involved with healing and growth. Specifically it is thought that much of the action of the light is caused by its effects on the electron carriers of the electron transport chain in the inner membrane of the mitochondria of these cells.
Wound healing may be described as having four component processes.
1. Inflammation increases blood flow to the area, increased delivery of white blood cells which phagocytize microbes and mesenchymal cells which develop into fibroblasts. Blood clotting helps unite the wound.
2. In the Migration component epithelial cells migrate below a scab and cover the wound area. Fibroblasts migrate along fibrin threads and begin the synthesis of collagen and glycoproteins. During this phase damaged blood vessels begin to regenerate.
3. During the Proliferative component there is further growth of the epithelial cells and deposition of collagen fibers and continued growth of blood vessels.
4. In the final Maturation phase the scab disconnects and the collagen fibers become more organized, fibroblasts decrease in number and the blood vessels return to normal.
The specific wavelengths commonly used in R/NIR phototherapy are those for which commercial medical lasers were already available, for example He—Ne laser (lambda=632.8 nm), rather than finding the wavelengths corresponding to the target molecules. In recent years, Karu has tested the stimulation of DNA and RNA synthesis rate and cell adhesion when exposed to monochromatic light sources. She found several active regions for phototherapy in the R/NIR range. These active regions have peaks around 620, 680, 760, and 820 nm. Currently phototherapy is used in short sessions typically lasting only several minutes, and repeated in later days. This results in inconvenience and increased therapy costs.
Blue or white light is typically used for treatment of hyperbilirubinemia. Fluorescent lights, halogen lams, and sun light have been used. It was originally thought that UV light was necessary for treating neonatal jaundice. This is incorrect and dangerous for infants. The infant lens is very transparent to blue and UV light, and the retina is susceptible to damage from light especially below 450 nm. The risk of retinal injury is even greater when the infant is given oxygen therapy. There is even concern that the UV light from the mercury bands in normal fluorescent lights poses risk to neonates receiving oxygen therapy.
In view of the foregoing description of the current status of the field of phototherapy, the present disclosure advances the state of the art of phototherapy by temporal control in phototherapy. In particular, the present disclosure relates to an apparatus for delivering phototherapy that includes at least one substrate configured to enable mounting at least one light emitter; at least one emitter mounted on the at least one substrate, and that is capable of emitting at least two peak wavelengths of light; and an electronic circuit configured to control the timing of emission of the at least one emitter. The electronic circuit is in electronic communication with the at least one emitter and the apparatus is configured as a dressing for optical communication enabling irradiation of a target tissue.
In one embodiment, the one, or more than one, light emitter is a laser emitter and/or a light emitting diode. The electronic circuit may include at least one processor and the one, or more than one, processor is configured to control temporal sequencing of emission of light by the one, or more than one, emitter at least two different peak wavelengths.
In one embodiment of the phototherapy apparatus, the one, or more than one, emitter is configured with at least one of the following: (1) a blue emitter and one of a phosphor and a scintillator, the phosphor and the scintillator emitting light at least one peak wavelength longer than 500 nanometers (nm); (2) a light emitting diode emitting white light; and (3) at least one light emitter that is configured to deliver a pulse of irradiation to the tissue with a duration of less than a second.
In another embodiment of the phototherapy apparatus, the one, or more than one, substrate includes at least a first and a second substrate; and the one, or more than one, emitter includes at least a first emitter mounted on the first substrate and at least a second emitter mounted on the second substrate, wherein the first substrate and the at least first emitter define a first modular phototherapy apparatus and the second substrate and the at least second emitter define a second modular phototherapy apparatus, and wherein the first and second modular phototherapy apparatuses are at least one of the following: (1) physically connected to at least one another; (2) mounted at least one of on and within a common structure; and (3) in electric communication with each other.
In another embodiment of the phototherapy apparatus, the phototherapy apparatus further includes at least one power source, wherein the one, or more than one, power source is configured to provide power to the apparatus to effect the emission of the light, and wherein the one, or more than one, power source is at least one of the following: (1) a power source having sufficient capacity to power the emitters for at least one hour; (2) a battery; and (3) a power source configured for ambulatory use. In one embodiment, the phototherapy apparatus further includes a reflective surface that is configured to reflect light from the one, or more than one, emitter towards the target tissue.
In still another embodiment, at least a portion of the phototherapy apparatus is configured to be wearable by a subject, and the at least a portion that is wearable is configured as a piece of apparel and/or a bandage. In one embodiment, phototherapy apparatus further includes a translucent dressing that is configured wherein the light of the one, or more than one, emitter is directed through the translucent dressing.
In yet another embodiment, the phototherapy apparatus further includes at least one of the following: at least one light sensor configured to detect data samples of light passing through the target tissue and of changes in the light passing through the target tissue; and at least one processor wherein the processor is: (1) capable of determining from the data samples, and with respect to a subject, at least one of the timing of the pulse, the pulse pressure, and the respiratory cycle, and with respect to at least one of a subject and a target tissue, determining from the data samples at least one of the oxygen saturation of the blood and the hemoglobin content of the blood; and (2) capable of timing the delivery of phototherapy according to a predetermined phase of the pulse cycle.
In another embodiment of the phototherapy apparatus, with respect to the one, or more than one, the one, or more than one, processor at least one of:
(1) is configured to control the one, or more than one, emitter to deliver at least a first pulse and at least a second pulse of light for irradiation to the target tissue;
(2) is configured to control the one, or more than one, emitter to repeat the at least first pulse of light and at least second pulse of light as pulse sets; and
(3) is configured to create a delay between pulse sets; and/or with respect to the one, or more than one, emitter at least one of:
(1) is a blue emitter with a wavelength ranging between about 450 and about 500 nanometers (nm) and wherein light emitted from the blue emitter is delivered with a first pulse, and includes at least one second emitter with a wavelength ranging between about 500 and about 700 nanometers (nm) and wherein light emitted from the at least one second emitter is delivered with a second pulse in the pulse set; and
(2) is an emitter with a wavelength ranging between about 800 and about 900 nanometers (nm) and wherein light emitted from the at least one emitter is delivered with a first pulse, and includes at least one second emitter with a wavelength ranging between about 600 and about 700 nanometers (nm) and wherein light emitted from the at least one second emitter is delivered with a second pulse in the pulse set.
In another embodiment, the phototherapy apparatus includes at least one light source configured to deliver phototherapy with a peak wavelength between 580 and 1350 nm; at least one light sensor configured to detect light passing through the target tissue and changes in the light passing through the target tissue and at least one processor configured to at least one of: (1) measure changes in at least one of blood volume and light absorption of the blood passing through the target tissue; (2) enable correlation with respect to the subject of the changes in the light passing through the target tissue with at least one of the timing of the pulse, the pulse pressure, the oxygen saturation of the blood, the hemoglobin content of the blood, and the respiratory cycle; and (3) control timing of delivery of phototherapy according a portion of the pulse cycle.
The present disclosure relates also to a method of applying phototherapy to a subject, and includes the steps of: providing at least one light emitter; delivering a first pulse of light to the target tissue of a subject from the one, or more than one, emitter with a peak wavelength of light; and delivering at least a second pulse of light to the target tissue of the subject from the one, or more than one, emitter wherein the one, or more than one, emitter provides at least one peak wavelength of light that is different from the peak wavelength of the first pulse of light, wherein the steps of delivering a first pulse of light and of delivering a second pulse of light define a method of delivering a series of pulse sets of light, and wherein the first pulse of light and the second pulse of light define a pulse set of light. The method may be implemented wherein the one, or more than one, emitter is at least one of a light emitting diode and a laser.
In one embodiment, the method may further include wherein at least one of: (1) the step of delivering of the at least second pulse of light occurs at a time period of less than about one second after the step of delivering the first pulse of light; (2) the step of delivering of the at least a second pulse set of light occurs at a time period of less than about one minute after the step of delivering the first set of pulses; (3) the step of delivering the at least a second pulse set occurs at a time period of less than about one second after the step of delivering the first set of pulses; and (4) wherein the method of delivering a series of pulse sets of light includes the step of delivering at least three pulse sets over a time period greater than about one hour.
In another embodiment, the method may include wherein at least one of: (1) the first pulse of light in the pulse set has a peak wavelength between about 450 nanometers and about 500 nanometers; (2) the at least a second pulse of light has a peak wavelength between about 500 to about 700 nanometers (nm); (3) the at least a second pulse of light has a peak wavelength between about 565 to about 700 nm; and (4) the phototherapy is applied for treatment of at least one of hyperbilirubinemia, jaundice, hematoma and bruising.
In still another embodiment, the method is implemented wherein at least one of:
(1) wherein the pulse set includes at least: a first pulse of light having a peak wavelength between about 800 nanometers and about 900 nanometers, and wherein the at least second pulse of light has at least one peak wavelength between about 600 nanometers and about 700 nanometers; and (2) wherein the method of applying phototherapy is applied for treatment of at least one of injury, tissue degeneration, tissue discoloration, and hair loss.
The present disclosure relates also to a method for phototherapy for a subject that includes the steps of: providing at least one light source emitting light with a peak wavelength less than about 500 nanometers; providing at least a second light source emitting light with at least one peak wavelength ranging between about 565 nanometers and about 700 nanometers (nm); delivering the light with a peak wavelength of less than about 500 nanometers to tissue of the subject for a time period of greater than about one hour; and at least partially concurrently delivering the light with a peak wavelength ranging between about 565 and about 700 nanometers for a time period of greater than about one hour. In one embodiment, the method for phototherapy for a subject may be implemented wherein the phototherapy is for a subject with at least one of hyperbilirubinemia, jaundice, hematoma and bruising.
The present disclosure relates also to a method of timing delivery of phototherapy to a subject that includes the steps of: measuring at least one phase of the circulatory cycle of the subject; identifying a desired phase of the at least one phase of the circulatory cycle of the subject wherein the desired phase is beneficial for delivery of phototherapy to the subject; and delivering phototherapy to the subject during at least a portion of the desired phase of the circulatory cycle of the subject. The method may be implemented wherein the desired phase of the circulatory cycle is determined by detecting a variance in transmission of light through tissue of the subject.
Additionally, the present disclosure relates also to a method of phototherapy treatment that includes the steps of: providing at least one light emitter, and irradiating target tissue of a subject with light from the one, or more than one, emitter for sufficient time to give therapeutic effect, wherein the one, or more than one, emitter is at least one of:
(1) a blue emitter emitting light with a peak wavelength less than 500 nanometers (nm), the light emitted from the blue emitter including at least a portion of the light irradiating the tissue from the one, or more than one, emitter, the blue emitter coupled with one of a phosphor and a scintillator, the phosphor and the scintillator emitting light at least one peak wavelength longer than 500 nanometers (nm), the light from the one of a phosphor and a scintillator being at least a portion of the light irradiating the tissue from the one, or more than one, emitter; (2) a light emitting diode emitting white light, the white light emitted from the light emitting diode being at least a portion of the light irradiating the tissue from the at least one emitter; (3) configured to emit light cycling in intensity at a rate of at least one cycle per second, the light from the one, or more than one, emitter cycling in intensity being at least a portion of the light irradiating the tissue from the one, or more than one, emitter; and (4) configured to emit light delivering a pulse of irradiation with a duration of less than one second, the light from the one, or more than one, emitter delivering a pulse of irradiation with a duration of less than one second being at least a portion of the light irradiating the tissue from the at least one emitter. The method may be implemented wherein the subject has at least one of hyperbilirubinemia and jaundice.
It is understood that light energy can cause changes in the chemical activity or structural conformation of certain molecules. The present disclosure teaches that sequential application of light at specific wavelengths can drive the conformational changes or the energetic changes in the desired direction making phototherapy more efficient in certain applications. The present disclosure also teaches that in certain applications sustained phototherapy has advantages over the current practice of short term phototherapy which is usually applied by a physician or therapist in a medical setting and lasting only a few minutes per session. The present disclosure also teaches the use of sustained pulsed phototherapy which may be applied for hours or days, and may be worn as apparel or applied to an area of the body as a fixture, bandage or appliance.
The present disclosure teaches the use of timed and sequenced narrow spectrum EMR for improving the beneficial effects of phototherapy, as well as to improve efficiency and reduce risk. It also teaches the use of timing the delivery of phototherapy to the certain parts of the circulatory pulse cycle, and a method of integrating plethysmography and/or pulse oximetry into the phototherapy apparatus. Several embodiments of the present disclosure include single use and wearable PT apparatuses. Also disclosed is the uses of sustained red/NIR phototherapy lasting several hours or longer that is made possible with wearable phototherapy apparatuses.
The present disclosure further teaches that long wave visible light may be used in the photo-conversion of bilirubin to lumirubin.
For purposes of this disclosure and claims, the term light is not limited to visible light but rather includes electromagnetic radiation including the visible, ultra violet and infrared spectrum.
Reference will now be made to the accompanying drawing figures, which are not necessarily drawn to scale:
Phototherapy requires that light be transmitted to the target molecules in the body, but non-target substances in the skin and underlying tissue (which absorb light) prevent it from reaching the target molecules.
The vertical axis on the right shows the relative penetration depth for light for different wavelengths. For phototherapy to have biological affect, light must penetrate to the target tissue.
In
The sum of hemoglobin (saturated or unsaturated), melanin and water absorbance gives an estimate of the penetration of light. Bracket 110 indicates an area between about 580 nm and 1125 nm where light most easily gives sufficient penetration for therapeutic exposure of the tissue. The areas between 460 and 580 and between 1125 and 1320 allow lesser transmission of light, but still may also be used for phototherapy The optical window, between about 580 nm to about 1320 nm herein referred to as the red/near infrared (R/NIR) window, is used in phototherapy for healing.
Hemoglobin's absorbance depends on its oxygenation state, as well as the amount of hemoglobin present. Thus, a person with anemia would have less interference for light passage. An area of poor perfusion would tend to have a higher percentage of reduced hemoglobin (Hb), and light transmission would be affected by this. Tissues such as cartilage have little blood supply and may transmit light better.
Melanin absorbs heavily in the UV and blue area of the spectrum, and plays an important role in protecting the underlying dermis from UV radiation. The layer of melanin is very thin. There is as much as a 10 fold difference in melanin content between individuals, with Caucasians having a lower content than most other racial groups. There is also a wide variance within individuals depending on sun exposure which promotes production of melanin. Disrupted skin, wounds and depigmented lesions may not have melanin deposits that block light, as well the palms and soles are less pigmented.
Use of alternating or sequential targeted wavelength light to induce or impede molecular reactions in a desired direction can be thought of as “optical pumping”. The present disclosure teaches the concept of optical pumping for phototherapy. One example of optical pumping with clinical utility is its use in the photo-conversion of bilirubin.
The conversions of Bilirubin to Lumirubin is a two step process. The present disclosure teaches the method of inducing this process by sequential irradiation of bilirubin with two or more targeted narrow spectrum light emitters in order get a more efficient conversion of bilirubin to lumirubin.
Bilirubin is hydrophobic and lipophylic, allowing it to cross the blood brain barrier where it can damage the brain. Photo-oxidation of bilirubin changes it into a more hydrophilic form. Light exposure causes bilirubin to undergo structural isomerization and photo-oxidation. Hyperbilirubinemia is treated with light in infants because light changes the bilirubin from a water-insoluble form to a water soluble form which prevents it from crossing the blood brain barrier and makes it filterable by the kidneys and thus allows it to be eliminated, principally into the urine.
When photo-isomerized bilirubin becomes Lumirubin (EZ-cyclobilirubin), the water soluble form. The photoconversion reaction bilirubin is as follows:
4Z, 15E Bilirubin4Z, 15Z Bilirubin
4E, 15Z Bilirubin→15Z Lumirubin,
and where simplified nomenclature is used:
ZE BilirubinZZ Bilirubin
EZ Bilirubin→Lumirubin.
ZZ Bilirubin refers to native bilirubin, ZE bilirubin is also referred to as photobilirubin, and lumirubin is also known as cyclobilirubin. The first step occurs when ZZ bilirubin is photoisomerized to either the ZE or the EZ form. This isomerization is reversible, and the reaction generally greatly favors the formation of the ZE form. The photo-oxidation of EZ bilirubin is irreversible, and forms lumirubin which is water soluble and can be eliminated through the kidneys.
This stepped conversion of bilirubin is an example of optical pumping, where a first reaction (irradiation of ZZ bilirubin at its absorption spectrum) primes a second reaction (the conversion of ZE bilirubin to lumirubin) Thus, the present disclosure teaches the method of sequential phototherapy also referred to herein as optical pumping. In the present example sequential exposure of two or more narrow spectrum wavelength light sources can be used for the efficient photoisomerization of bilirubin to lumirubin. The first narrow spectrum emitter in the blue range, followed by longer wavelength light, for the second irreversible step from photoisomerized bilirubin to lumirubin.
The present disclosure further teaches cycling of narrow wavelength emitters for phototherapy.
In one embodiment of the present disclosure, a narrow spectrum light source with a peak output at or near the absorption maxima for ZZ bilirubin may be used for the first narrow spectrum emitter of electromagnetic radiation (EMR), followed by a second emitter selected for stimulating the conversion of EZ bilirubin to lumirubin.
In the case of phototherapy for hyperbilirubinemia, the first light source 205 thus causes the first conformational change in bilirubin, and the second light source 210 causes an irreversible second change to lumirubin. This sequential pulse set may be repeated immediately, or there may be a delay as before the cycle is repeated.
Zietz et al (2004) found that the decay of bilirubin fluorescence is very rapid, peaking after about 250 to 1000 femtoseconds. During this stimulated emission, there is an excited state absorption at a peak wavelength of about 515 nm.
The second photo-induced transformation of EZ bilirubin occurs about 150 to 2000 femtoseconds after the first transformation. Femtosecond lasers may be quick enough to time this reaction, but it is simpler to overlap the timing with more easily accessible L.E.D. emitters. Thus overlapping L.E.D. output of various wavelengths will give the desired sequential illumination. Some commonly used divisions of time are: Femtosecond=10−15 seconds, Picosecond=10−12 seconds, Nanosecond=10−9 seconds, Microsecond (μs)=10−6 seconds, and Millisecond=10−3 seconds.
Since it may be costly or impractical at present to use high speed narrow spectrum light sources, such as femtosecond lasers which can switch this quickly, narrow spectrum light sources which overlap sequentially may be used.
L.E.D. emitters may be used for phototherapy. However the time it takes for an L.E.D. to turn on and off may not be a quick as the time it takes for sequential photo-induced biological reaction to occur. A typical L.E.D. may have for example, a rise time of 40 ns, a pulse of 10 μs, and a fall time of 60 ns. This rise and fall time are indicated in
As illustrated in
In the embodiment illustrated by
In this illustration the plateau phases of the two emitters overlap, however this present disclosure is not limited to use of overlapping pulse phases for sequential pulse phototherapy. The illustration also shows an off time 215 following the two emitter pulses. The pair or set of pulses by the emitters forms a pulse set. This pulse set is shown to repeatedly cycle with an off time after each set. In other embodiments of this present disclosure one or more emitters of a certain peak wavelength may remain illuminated while one or more emitters of a different peak wavelength cycle. In one embodiment the pulse time for emitters in this present disclosure may be as slow as one minute. In another embodiment very rapid cycling well under a second is utilized, and many cycles of the pulse sets may be delivered per second.
Thus, in view of
providing at least one light emitter; delivering a first pulse 205 of light to the target tissue of a subject from the one or more emitters with a peak wavelength of light; and
delivering at least a second pulse 210 of light to the target tissue of the subject from the one or more emitter wherein the one or more emitters provides at least one peak wavelength of light 210 that is different from the peak wavelength 205 of the first pulse of light 205. The steps of delivering a first pulse of light 205 and of delivering a second pulse of light 210 define a method of delivering a series of pulse sets 220 of light, and
the first pulse of light 205 and the second pulse of light 210 define a pulse set of light 220. The one or more emitters may be a light emitting diode and/or a laser.
Furthermore, the present disclosure teaches a method of phototherapy wherein at least one of the following occurs:
(1) the step of delivering of the at least second pulse of light 210 occurs at a time period of less than about one second after the step of delivering the first pulse of light 205;
(2) the step of delivering of the at least a second pulse set 220′ of light occurs at a time period of less than about one minute after the step of delivering the first set of pulses 220;
(3) the step of delivering the at least a second pulse set 220′ occurs at a time period of less than about one second after the step of delivering the first set of pulses 220; and
(4) wherein the method of delivering a series of pulse sets of light 220, 220′, 220″, 220″′ etc. includes the step of delivering at least three pulse sets 220, 220′ and 220″ over a time period greater than about one hour.
Continuing to refer to
(1) the first pulse of light 205 in the pulse set 220 has a peak wavelength between about 450 nanometers and about 500 nanometers;
(2) the one or more second pulses of light 210′, 210″, 210″ etc. has a peak wavelength between about 500 to about 700 nanometers (nm);
(3) the one or more second pulses of light 210′, 210″, 210″ etc. has a peak wavelength between about 565 to about 700 nm; and
(4) the phototherapy is applied for treatment of at least one of hyperbilirubinemia, jaundice, hematoma and bruising.
The emitters may cycle without any off time, however there is typically advantage to having an off time. These advantages include more efficient use of power saving and less heat build up in the tissue. There may also be therapeutic benefits. This method may be used with the various embodiments of this disclosure.
Cycling the L.E.D.s allows delivery of more EMR energy with less risk of tissue damage, lowers risk of heat injury to the patient, and saves energy, which may be important for battery operated and wearable apparatuses. Using specific wavelengths of light which target the absorption maxima for the target molecules also greatly increases the efficiency of the phototherapy and lowers the EMR required.
Since the molecular reactions in phototherapy occur in response to specific wavelengths of light, it is desirable to use emitters specifically targeted to these reactions. For example, broad spectrum white light is often used in phototherapy for hyperbilirubinemia. However, much of the light does not specifically target the bilirubin molecule, and thus much higher light intensities are required for this use. The subject of this therapy is often a premature infant, who is thus exposed to light and heat which may have undesirable effects including increased body temperature, dehydration and photo-damage to the skin and eyes. Further this non-specific light uses large amounts of electrical energy and creates waste heat. Heat and the energy consumption of such lights make them impractical for use as portable devices or for use in close proximity to the skin.
The use of narrow spectral output emitters, such as lasers and light emitting diodes (L.E.D.s), can allow for the specific targeting of the molecular reactions which respond to phototherapy by selecting emitters with peak spectral outputs at the target wavelengths for the photo-reaction. By selecting narrow band emitters with a peak wavelength output which matches the wavelengths for the maximum photoreaction, phototherapy can be much more efficient than with use of broad spectrum emitters.
In one embodiment of the present disclosure small diode lasers may be used for phototherapy. An example of such diode laser is the Sanyo DL-8142-201 830 nm, infrared wavelength laser diode which is supplied in a 5.6 mm housing. Even smaller package sizes are expected to be commercially available in the near future. Lasers emit light narrowly around a single wavelength, with a full width half maximum (FWHM) of a few nm to well under one nm. This is illustrated in
Sequential R/NIR Phototherapy
The R/NIR window 110 between 580 nm and 1125 nm, and less so the area up to about 1325 nm, is important in the application of phototherapy for healing and other therapeutic effects as it allows EMR in the red and near infrared range to reach the target molecules. Red/Near Infrared light passing through this optical window is thought by many scientists in the field to exert action by its effect on electron transport in the mitochondrial proton pump. The inner mitochondrial membrane contains five (5) complexes of integral membrane proteins which are involved in the electron transport chain; NADH dehydrogenase, succinate dehydrogenase, cytochrome c reductase, cytochrome c oxidase, ATP synthase as well as two freely diffusible molecules; ubiquinone and cytochrome c that shuttle electrons. These contain metallic atoms; iron copper, zinc, magnesium, and it is thought that these metallic complexes may be the targets for phototherapy. In particular it is the copper atoms in cytochrome c oxidase that are thought to participate in the beneficial effects of phototherapy.
Time resolved spectroscopy of cytochrome C oxidase reveals that in its resting state it absorbs light at about 830 nm. It is thought that light stimulates electron transfer in cytochrome C oxidase. After this it then absorbs light at 606 nm and at 430 nm for a few nanoseconds. Light at about 430 nm or at 605 nm may cause photolysis of the bonding between cytochrome c, and cytochrome c oxidase. Removal of this oxidized cytochrome c, a soluble heme protein, allows it to disassociate with the cytochrome c oxide complex more quickly, thus leaving the bonding site available to a reduced cytochrome c molecule. Here, the present disclosure teaches another example where the sequential irradiation of tissue by different wavelengths of light act as an optical pump advantageous for phototherapy. Thus, in order to more efficiently photoactivate cytochrome c oxidase the tissue is first exposed to light at about 830 nm as a first step and then by light at about 606 and or 430 nm as a second step. In one embodiment red light at about 606 nm is used for the second step because of the increased transmission of red light through the tissue as compared to blue light at 430 nm.
Karu demonstrated that simultaneous irradiation of cell cultures with two (2) monochromatic sources could decrease DNA synthesis compared to one source, and that depending on the order which the light source were applied would either promote or decrease DNA synthesis. When several minutes of irradiation with light at 760 nm was followed a few minutes later with several minutes of EMR at 633 nm the amount of DNA synthesis was greater, and if first exposing the cells with 633 nm light followed a few minutes later by 760 nm light DNA synthesis over the next several days was decreased.
Karu has identified four active areas for phototherapy for red to near infrared light. These are about 613-624 nm, and 667-684 nm in the visible spectra, and two near infrared maxima with peak positions in the ranges of 750-773 nm and 812-846 nm. These correlate well to the four cytochrome c oxidase redox active metal centers; two heme A prosthetic groups (cytochrome a and cytochrome a3) and two copper centers (CuA and CuB). These redox centers absorb light according to their redox state. These four areas are referred to as 620, 680, 760 and 830 herein for simplicity, and are shown in
The present disclosure teaches the use of rapid sequential cycling of short pulses of light for the therapeutic phototherapy such as low level laser phototherapy. In one configuration of the invention the tissue is irradiated with a short burst of infrared light at around 830 nm, followed by irradiation with red light at around 620 nm.
While traditional low level laser phototherapy uses lasers, the present disclosure teaches the use of L.E.D. light sources in place of lasers for therapeutic phototherapy. In one embodiment of the present disclosure a pulse of narrow spectrum light such as may be produced with an EMR emitter such as an L.E.D. or laser at about 830 nm is followed by a narrow light spectrum emitter at about 680 nm, as illustrated in
This method of photoactivation is implemented by sequential irradiation from at least two different emitters, as illustrated in
In the method of phototherapy illustrated in
(1) the pulse set includes at least:
a first pulse of light 305 having a peak wavelength between about 800 nanometers and about 900 nanometers, and
the at least second pulse 310 of light has at least one peak wavelength between about 600 nanometers and about 700 nanometers; and
(2) the method of applying phototherapy is applied for treatment of at least one of injury, tissue degeneration, tissue discoloration, and hair loss.
An electronic controller or processor (e.g., a microprocessor) such as 430 as shown in
The present disclosure thus teaches the method of rapid sequential irradiation using narrow wavelength emitters for phototherapy.
Referring specifically to
(2) an emitter with a wavelength ranging between about 800 and about 900 nanometers (nm) and wherein light emitted from the one or more emitters is delivered with a first pulse, and includes at least one second emitter with a wavelength ranging between about 600 and about 700 nanometers (nm) and wherein light emitted from the one or more second emitters is delivered with a second pulse in the pulse set.
Specific Spectrum for treatment of Hyperbilirubinemia
When bilirubin absorbs light, some of this energy is released in the form of fluorescence. This occurs most efficiently with light at the peak absorption area for bilirubin. Irradiated bilirubin emits light with a peak emissive wave length of about 515 nm as shown by the dashed line in
The skin acts as a filter for external light passing though it.
A shift in the absorption and emission spectra for ZZ bilirubin can be seen. The most effective wavelengths for photoisomerization for ZZ bilirubin centers at about 470 nm, and this may be slightly greater in persons with high melanin content in their skin. The photo conversion of EZ bilirubin to lumirubin however has a broad range which results from the relative ease which red light transmits through the skin. The dashed line in
Filtering by the absorbing substances in the tissue also affect light used for R/NIR phototherapy. Since hemoglobin, water and melanin absorb light, the acts as skin slightly skews the effective peak wavelengths for phototherapy, to a slightly longer wavelengths. Thus in one embodiment of Red/NIR phototherapy a first emitter at about 840 nm may be used. Similarly in one embodiment of Red/NIR phototherapy a second emitter at about 620 nm my be used.
It is generally understood that shorter wavelengths of light (ultraviolet, blue and even green light) are more damaging to the tissues, and more likely to cause retinal injury, aptosis and cell death. Light at around 435 nm is near the peak for “blue hazard” light which can damage the retinal pigmented epithelial cells in adults, but because of the increased transmittance of blue light by the lenses of infants, shorter wavelength blue light can be even more damaging to infants than adults. Longer wavelength light is less hazardous.
The present disclosure teaches that light sources for phototherapy should minimize light exposure which is harmful to the eye. There is also less potential for photo-damage to the skin within the longer wavelength range. Standard neonatal phototherapy has been found to be a strong risk factor for pigmented nevus development in childhood, and may be associated with a lifetime increase in risk for malignant melanoma. Phototherapy for hyperbilirubinemia may increase the incidence of retinopathy of prematurity if an eye shield is not used correctly. Use of narrow wavelength phototherapy for treatment of hyperbilirubinemia as described in the present disclosure avoids or reduces this risk.
For photo conversion of bilirubin blue light may be used in constant emission as the first emitter and with the second emitter turning off and on within the present disclosure. However, there is an advantages to embodiments which cycle the blue light, thus limiting exposure to the shorter and more potentially damaging wave lengths. Further it can be seen in
Referring to
providing at least one light source 405a emitting light with a peak wavelength less than about 500 nanometers;
providing at least a second light source 405b emitting light with at least one peak wavelength ranging between about 565 nanometers and about 700 nanometers (nm);
delivering the light from light source 405a with a peak wavelength of less than about 500 nanometers to tissue 10 of the subject for a time period of greater than about one hour; and
at least partially concurrently delivering the light from light source 405b with a peak wavelength ranging between about 565 and about 700 nanometers for a time period of greater than about one hour.
Referring to FIGS. 4C and 11A-11B, it can be appreciated that the present disclosure describes a method of phototherapy that, while being a general method of phototherapy, is particularly suitable as a method of phototherapy for subjects having hyperbilirubinemia or jaundice. (
In still another embodiment, the one or more emitters 405 may be configured to emit light 470 cycling in intensity at a rate of at least one cycle per second. The light 470 from the one or more emitters 405 that cycles in intensity may form or be included as at least a portion of the light irradiating the tissue 10 from the one or more emitters 405. In yet another embodiment, the one or more emitters 405 may be configured to emit light 470 delivering a pulse of irradiation with a duration of less than one second. The light 470 from the one or more emitters delivering a pulse of irradiation with a duration of less than one second may form or be included as at least a portion of the light irradiating the tissue 10 from the one or more emitters 405.
Thus it can also be appreciated that in view of the foregoing method of phototherapy treatment of a subject, with reference to
Referring now to
In another embodiment at least one RGB L.E.D. may be used for treatment of hyperbilirubinemia where the blue emitter emission is pulsed followed by the at least one of the green and red emitters.
The present disclosure teaches that phototherapy apparatuses may be timed so that the delivery of light occurs when there is less absorption of light by interfering absorbers which vary temporally, such as occurs during the circulatory pulse with hemoglobin. For example, phototherapy pulses for one condition may be delivered during the nadir of perfusion when the arterial capillaries are less distended, when blood movement is slower and when the ratio of arterial to venous blood in the tissue is lower. Thus, phototherapy may be used in concert with a plethysmograph or pulse oximeter to time the delivery of phototherapy during the portion of the pulse most favorable to transmission of the therapeutic wavelengths. Alternatively the phototherapy apparatus according to the present disclosure, for example as illustrated in
As shown in
A pulse oximeter typically uses two or more narrow spectrum light source such as L.E.D.s to determine the difference in hemoglobin saturation levels.
Pulse oximeters also detect the pulse through photoplethysmography. With each pulse of the heart there is enough pressure to distend the arteries and arterioles in the skin and subcutaneous tissues. The increased amount of blood is sufficient to decrease light transmission. A small venous plexus pulse may be detected, as well as other physiologic changes including the respiratory cycle. Photoplethysmography may be used to monitor circulation in the area being treated with phototherapy, such as might be important in the treatment of diabetic ulcers of pressure sores.
A photoplethysmograph requires only a single light source, the transmission of which is attenuated by the increase in blood flow, while the pulse oximeter requires two different narrow spectrum light sources.
Plethysmographic data for timing of phototherapy pulses can be done even if pulse oximetry is not. Only a single emitter and detector are required. Any of the emitters used for phototherapy between about 580 nm and 1150 nm are adapted to be used to obtain plethysmographic data. The housing for the microprocessor 905 may also house the power supply for the microprocessor and the phototherapy modules. As with other configuration of this disclosure, batteries may be used with this apparatus which allow mobility during phototherapy.
Since the wavelengths used for pulse oximetry are similar to those which may be used in phototherapy, the light from phototherapy may be used for pulse oximetry measures in some applications, or supply at least some of the required wavelengths. An embodiment of this is illustrated as phototherapy apparatus 701 in
For treatment of hyperbilirubinemia, photoplethysmographic data would also allow timing of the phototherapy to deliver phototherapy during the nadir of perfusion. It can be seen in
Referring to
measuring at least one phase of the circulatory cycle of the subject;
identifying a desired phase of the one or more phases of the circulatory cycle of the subject wherein the desired phase is beneficial for delivery of phototherapy to the subject; and
delivering phototherapy to the subject during at least a portion of the desired phase of the circulatory cycle of the subject.
In
If a perfusion timing detector or pulse oximeter is used with one or more miniature phototherapy apparatuses, it or several of the miniature modules may be triggered by a single perfusion detector. Because of cost this perfusion timing detector may not be disposable or for single patient use.
Timing phototherapy so that it is not on continuously has the additional advantages of creating less heat buildup, and better utilizes battery power. These apparatuses could be made for single patient use, and this makes it easier to allow the infant to be treated at home. Battery power makes this easier. Use of single patient use hyperbilirubinemia apparatuses may allow earlier hospital discharge and may save on cost, especially in infants with mild hyperbilirubinemia.
The present disclosure thus teaches the method of timing the delivery of phototherapy to correlate to certain phases of the pulse cycle. Further the present disclosure teaches the method of incorporating a photoplethysmograph or pulse oximeter into a phototherapy apparatus, wherein at least some of the light required is provided by phototherapy emitters.
Thus, phototherapy apparatus 701 illustrated in
at least one light sensor 785 that is configured to detect light passing through the target tissue and changes in the light passing through the target tissue and
at least one processor, e.g., a microprocessor housed in pulse oximeter 740, that is configured to do at least one of the following:
a. (1) measure changes in at least blood volume and/or light absorption of the blood passing through the target tissue; (2) enable correlation with respect to the subject, of the changes in the light passing through the target tissue with at least the timing of the pulse, and/or the pulse pressure, and/or the oxygen saturation of the blood, and/or the hemoglobin content of the blood, and/or the respiratory cycle; and (3) control the timing of delivery of phototherapy according a portion of the pulse cycle.
Referring specifically to
Several embodiments of phototherapy apparatuses are now disclosed or disclosed in further detail which are capable of timing and delivering phototherapy according to the methods discussed in the present disclosure.
One embodiment of the present disclosure is as a miniature phototherapy (PT) apparatus which is illustrated in
Illustration
Thus, the phototherapy apparatus 400 may include reflective surface 450 that is configured to reflect light from the one or more emitters 405 towards the target tissue 10. The Phototherapy unit 400 is illustrated with an oval shape as per one embodiment of this disclosure. The small oval shape is illustrated as it has the advantages of lacking pointed edges and being adaptable to multiple areas where it may be used as a dressing for a wound. The phototherapy units may be used individually or multiple units may be used. When multiple units are used together they may have a single power source. It can be appreciated that, with reference to
As defined herein, a dressing is an adjunct used for application to a wound in order to promote healing and/or prevent further harm, or applied to the body as a treatment for a condition, which is usually intended to remain in place for at least for several hours. As also defined herein, a dressing is designed to be in direct communication with the wound or tissue to be treated, which makes it different from a bandage, which is primarily used to hold a dressing in place, but does not itself have a medicinal property. Thus, various embodiments of this disclosure use phototherapy units and modules as dressings for treatment.
Returning to
Phototherapy may be applied, for example, to the leg 950 at the area of the lateral ankle, a site which may be affected by arterial insufficiency for example.
Thus it can be appreciated that phototherapy apparatus 1001 includes a translucent wound dressing 1000 that is configured wherein the light 1030 of the one or more emitters 405 is directed through the translucent dressing 1000.
If a bandage is applied with excessive pressure it can potentially be damaging to the tissue. A hydrogel or other wound dressing which is transparent to the light frequencies used by the PT unit or module can be flexible, and thus conform to the shape of the area being treated. The adhesive allows a bandage which does not require pressure in order to hold the phototherapy units in place. This is intended to help decrease the use of pressure on the treatment area.
Miniature phototherapy units and modules may be configured for use within a bandage, or as apparel which may be worn. In one embodiment the phototherapy apparatus 1100 may be configured as a bootie as shown in
In one embodiment of this apparatus the phototherapy units and/or modules may be structured into booties that may be worn, as illustrated in
In
Thus, referring to
Along the inside of the bootie are shown PT modules 400 or 700. In
The phototherapy technology as described in the above booty may be incorporated into bandages or clothing including mittens, leg wraps, arm wraps, body wraps, head bonnet, skin dressing, diaper or other clothing. In particular, with reference to
The phototherapy units and modules may be of various shapes and sizes.
Multiple single units or modules may be used to tiled and provide phototherapy over a broader area, as illustrated in
In one embodiment the apparatus may take the form of a mask so that it can be easily worn for treatment around the eyes as illustrated in
The present disclosure teaches that phototherapy may be used to treat hair loss. Transcranial phototherapy may also be done to treat intracranial lesions. For example, it has been demonstrated that animals with induced stroke like lesions recover better if they receive transcranial phototherapy. Various embodiments according to the present disclosure may be used to treat superficial conditions such as skin lesions and hair loss, to improve healing of the tissues, and to treat intracranial conditions including memory loss and other conditions of the brain amenable to phototherapy.
The present disclosure shows miniature phototherapy units and modules used modularly for delivery of phototherapy to various areas. Other configurations for miniature phototherapy modules are illustrated in
In view of the previous discussion of phototherapy apparatus 400 with respect to
A roughly triangular embodiment 1515 is shown in
The illustrations in
The present disclosure also teaches the use of long duration (hours) cycling sequential wavelength, and timed (to phase of pulse) phototherapy. It may be designed to be used for extended periods of hours or even days rather than minutes. Phototherapy is typically used with a constant light source for a short session, for example, a 15 minute session of high intensity light. The present disclosure teaches the use of multiple pulses of light, delivered over an extended period. Thus in place of a 15 minute session once a day or even less frequently, the present disclosure teaches the use of pulses of light over several hours or delivered continuously, for example overnight or may be worn for days.
The present disclosure teaches the use of ambulatory phototherapy, where the user may wear a phototherapy apparatus with a self contained power supply.
In particular,
at least one power source 905 and
One method for the delivery of phototherapy as taught here is the use of a wearable apparatus which can be applied to or worn by the patient. Although U.S. Pat. No. 6,866,687 describes a light bandage, it is not intended for continuous or ambulatory use, and does not have a self contained power supply. It would not fit under typical clothing. The current invention is intended to be produced at low cost, so that it would be inexpensive enough for single patient use, or disposable.
The present disclosure illustrates multiple embodiments for phototherapy which use a miniature and modular apparatuses. These incorporate L.E.D. emitters, which may be of multiple narrow wavelength emitters. These apparatuses may include photosensors, or use L.E.D.s as photo-sensors for photoplethysmography. These apparatuses may include or be controlled by microprocessors which allow for rapid sequential timing of the emitters. These apparatuses may include or be controlled by microprocessors which allow for timing according to a portion of the circulatory pulse cycle. These apparatuses may be integrated into wearable embodiments such as booties, gloves, masks, bandages, caps or other wearable configurations. These apparatuses may be integrated to a transparent dressing configured to hold the phototherapy units and modules in place, and direct the phototherapy to the target tissue. This dressing may be a hydrogel or similar material, and may have healing or anti-infective properties of its own, and may allow the placement of this dressing directly to a wound area.
As described herein, the phototherapy apparatuses are applied to emit light to a subject, or target tissue thereof, wherein the subject, or target tissue thereof, is a human being, an animal, an insect or a plant or a biological substance such as blood, saliva or other similar fluid. The target tissue may be either internal to a subject or external to a subject. In particular, the biological substance may be either internal to a subject or external to a subject, e.g., outside of the body. Those skilled in the art will recognize that the phototherapy apparatus described herein may also be applied to emit light to influence or affect or effect the outcome or direction of a chemical reaction or a physical process.
Many modifications and other embodiments of the present disclosures set forth herein will come to mind to one skilled in the art to which these disclosures pertain having the benefit of the teachings presented in the foregoing descriptions and the associated drawings. Therefore, it is to be understood that these disclosures are not to be limited to the specific embodiments disclosed and that modifications and other embodiments are intended to be included within the scope of the appended claims. For example, although the embodiment shown in
Although phototherapy for the conversion of bilirubin is principally used for infants, it may also be used in older patients, and may be used to treat jaundice, and be used locally to treat hematoma, thus this disclosure does not limit phototherapy for conversion of bilirubin to neonatal hyperbilirubinemia.
This list of embodiments enumerated above is not intended to limit the scope of the present disclosure described herein, but rather to highlight the scope of the disclosure. It is intended that the broadest interpretation of this disclosure is claimed by this disclosure.
This application claims benefit and priority of U.S. Provisional Patent Application Serial U.S. 60/925,240 filed Apr. 19, 2007, the entire contents of which is hereby incorporated by reference herein.
| Number | Date | Country | |
|---|---|---|---|
| 60925240 | Apr 2007 | US |
