WO2018177182A1 - Portable therapeutic device for use in treating alzheimer's disease by using light stimulation of optic nerve - Google Patents

Abstract

The present invention sets forth a portable therapeutic device which uses light to stimulate the optic nerve. By means of stimulating the eye(s) of a subject by using light-emitting diode (LED) light, the effects of Alzheimer's disease treatment, improvement, and prevention are attained. The portable therapeutic device comprises: an eye mask which may be fixed to the face and which covers the eyes; a light source which is fixed to the eye mask; and a power source which provides energy to the light emitting light source. The portable therapeutic device has the characteristics of simple operation, convenient application and being highly cost effective. The portable therapeutic device is suitable not only for various levels of medical treatment institutions, but also for various rehabilitation institutions, elderly health management institutions, and various uses within the home. The portable therapeutic device may not only be used in a fixed place and the like, but may also be carried as a wearable device, and thus use is not limited by location or time.

Description

Portable therapeutic device for treating Alzheimer's disease by using light stimulation optic nerve Technical field

The invention relates to the fields of neurobiology, biochemistry, physiology, therapeutic instruments for degenerative diseases of the elderly and the like.

Background technique

Alzheimer disease (AD), also known as Alzheimer's disease, is a central nervous system degenerative disease, insidious onset, slow course, continuous, difficult to find early, is the most common one for senile dementia Types. The clinical manifestations of AD are progressive mental state decay, including progressive mental memory disorders, cognitive dysfunction, personality changes, language disorders and other neuropsychiatric symptoms, behavioral disorders and even confusion. AD seriously affects people's social, professional and life functions [1].

The initial onset age of AD patients is more than 50 years old, and the incidence of AD increases with age. The prevalence rate of 65 years and older is about 5%, 20% is over 85 years old, and the prevalence rate of women is 3 times that of men. . Patients with AD usually die of secondary infection and systemic failure within 5 to 6 years after onset. Harvard School of Public Health, 2011 According to a survey released by the Public Health, AD is the second-largest concern after cancer in major European and American cities [2]. By 2050, the number of AD patients worldwide is expected to increase from today's 44 million to 135.5 million. Increasing AD will lead to significant economic and social costs [3]. In the United States alone, the treatment of Alzheimer's disease costs nearly $226 billion. Therefore, new methods of prevention, diagnosis and treatment are urgently needed.

The etiology and pathogenesis of AD have not been elucidated. The currently widely accepted doctrine has deposited plaques formed by the accumulation of Aβ-amyloid on the outer surface of brain nerve cells [4], neuronal fibrillation in neuronal cells formed by hyperphosphorylation of tau [5], and Neuronal loss with gliosis and so on. The neurofibrils are entangled in the cytoplasm of the neurons. This neurofibrillary tangles develop to a certain extent, which can degenerate and destroy the neurons, leaving the spiral plaques of silver stains in the middle, and the middle is the amyloid core, ie the senile plaques. The mechanism of Aβ-amyloid aggregation in the cerebral cortex and hippocampus is most prevalent, and Aβ deposits are also found in the striatum, amygdala and thalamus. Locally, A[beta]-amyloid deposits are a product of the development of neurofibrillary tangles to advanced stages. In addition, AD patients also have neuronal loss, cortical purple pigmentation and astrocytic hyperplasia.

Because the etiology and pathogenesis of AD are unknown, there is currently no specific treatment. Common methods include medication to improve cognitive function and memory impairment; symptomatic treatment improves mental symptoms; good care delays disease progression. Drugs and rehabilitation to improve cognitive and memory functions, to maintain the patient's independent living ability, and to improve the quality of life [6]. However, these treatments have had little effect, especially since there are no effective drugs and methods for dissolving and reducing Aβ-amyloid deposit plaques. Studies have shown that if the Aβ-amyloid deposit plaque is formed, the therapeutic effect on AD is very limited [6]. To date, Alzheimer's disease is in a predicament that cannot be prevented, cannot be detected early, and cannot be treated.

The brain's response to light stimulation has long been known [7], but the role of light stimulation in the brains of Alzheimer's patients has only received attention in recent years [8].

Icaccarino et al. reported a study [9]. AD model mice (5XFAD) were placed in a black test chamber, and the mice were stimulated with LED light for one hour: then Aβ-soluble protein and Aβ-amyloid deposit plaques in the visual cortex of AD mice were examined. Six different stimulation methods were used in the experiment: 20 Hz regulated scintillation light, 40 Hz regulated scintillation light, 80 Hz regulated scintillation light, disordered scintillation light, continuous light, and no light. The results of the assay showed that AD mice stimulated with 40 Hz-regulated LED scintillation light were significantly different. The expression levels of soluble A _1-40 and soluble A _1-42 in the visual cortex of AD mice were reduced by 57.96% and 57.97%, respectively. The same experiment was also validated in another AD model mouse (APP/PS1) experiment. Immunohistochemistry results also showed that there was no change in the number of microglia in the visual cortex of 5XFAD mice, but the diameter of microglia increased by 65.8%. The other five stimulation methods did not change the soluble A _1-40 and soluble A _1-42 expression levels of the mice.

In a further long-term stimulation experiment, 40 Hz scintillation light-stimulated mice were stimulated for one hour per day for 7 days, and the results also showed that A on the visual cortex of 5XFAD mice compared with the control group (no light stimulation). The number of deposited plates was reduced by 67.2%, and the area of A-deposited plates was reduced by 63.7%. This suggests that LED light stimulation of the eye can improve the disease state of AD mice. Based on the same principle, light irritating the human eye can also achieve the same disease state in treating AD patients. To this end, the present invention provides a portable therapeutic device that uses LED light to stimulate the eye to treat, ameliorate and prevent Alzheimer's disease.

references

[1] Siarkosa, K. T. et al. A Review of Pharmacological Treatments for Depression in Alzheimer’s Disease. J. Alzheimer’s Disease 48, 15–34 (2015)

[2] Beydoun, M. A. et al. Nationwide Inpatient Prevalence, Predictors, and Outcomes of Alzheimer's Disease among Older Adults in the United States, 2002-2012. J Alzheimers Dis. 48(2): 361-375 (2015)

[3] Gauthier, S. Et al. Current and future management of Alzheimer's disease. Alzheimers Dement. 4(1): S48-50 (2008)

[4a] Oakley, H. Et al. Intraneuronal β-amyloid Aggregates, neurodegeneration, and neuron loss in transgenic mice with five Familial Alzheimer’s disease Mutations: potential factors in amyloid plaque formation. J. Neurosci. 26, 10129–10140 (2006)

[4b] Bero, A. W. Et al. Neuronal activity regulates the regional vulnerability to amyloid-β deposition. Nature Neurosci. 14, 750–756 (2011)

[4c] Butterfield, D. A. et al. Evidence of oxidative damage in Alzheimer’s disease brain: central role for amyloid β β-peptide. Trends in Mol. Med. 7(12): 549-554, 2001.

[5a] Mattsson, N. et al. Plasma tau in Alzheimer disease. Neurology. 87(17): 1827-1835 (2016)

[5b] Gratuze, M. Et al. Tau hyperphosphorylation in the brain of ob/ob mice is due to Hypothermia: Importance of thermoregulation in linking diabetes and Alzheimer's Disease. Neurobiol Dis. 98:1-8 (2017)

[5c] Gratuze, M. Et al. High-fat, high-sugar, and high-cholesterol consumption does not impact Tau pathogenesis in a mouse model of Alzheimer's disease-like tau pathology.Neurobiol Aging. 47:71-73 (2016)

[6a] Klimova, B. Et al. Alzheimer's Disease and Chinese Medicine as a Useful Alternative Intervention Tool: A Mini-ReviewAlzheimer's Disease and Chinese Medicine. Curr Alzheimer Res. (2017) Jan 16.

[6b] Liao, X. et Al. Repetitive Transcranial Magnetic Stimulation as an Alternative Therapy for Cognitive Impairment in Alzheimer's Disease: A Meta-Analysis. J Alzheimers Dis. 48(2): 463-472 (2015)

[6c] Gauthier, S. et al. Effects of the Acetylcholine Release Agent ST101 with Donepezil in Alzheimer's Disease: A Randomized Phase 2 Study. J Alzheimers Dis. 48(2): 473-481 (2015)

[6d] Siarkos, K. T. et al. A Review of Pharmacological Treatments for Depression in Alzheimer's Disease. J Alzheimers Dis. 48(1): 15-34 (2015)

[6e] Ashford, J. W. et al. A Role for Complementary and Integrative Medicine in Alzheimer's Disease Prevention. J Alzheimers Dis. 48(1):13-14 (2015)

[7a] Gray, C. M., König, P., Engel, A. K. & Singer, W. Oscillatory responses in cat Visual cortex exhibit inter-columnar synchronization which Stimulus properties. Nature 338, 334–337 (1989).

[7b] Eckhorn, R. Et al. Coherent oscillations: a mechanism of feature linking in the visual Cortex Multiple electrode and correlation analyses in the cat. Biol. Cybern. 60, 121–130 (1988).

[8a] Cardin, J. A. et al. Driving fast-spiking cells induces gamma rhythm and controls sensory Responses. Nature 459, 663–667 (2009)

[8b] Sekiguchi, H. et al. Bright light therapy for sleep disturbance in dementia is most Effective for mild to moderate Alzheimer's type dementia: a case series. Psychogeriatrics. (2017)

[9] Hannah F. Iaccarino, Annabelle C. Singer, Anthony J. Martorell1, et al, Gamma frequency Entrainment attenuates amyloid load and modifies microglia. Nature. 540, 230-235 (2016).

technical problem

Provided is a portable therapeutic device that uses an LED light source to stimulate the eye to treat, improve, and prevent Alzheimer's disease.

Technical solution

A portable therapeutic apparatus for treating Alzheimer's disease using light-stimulated optic nerve, characterized in that:

The treatment device includes:

An eye mask that can be attached to a person's face and cover the eye;

a light source fixed to the eyecup;

a power source that supplies energy to the light source;

A control element that regulates changes in the light source.

The portable therapeutic apparatus for treating Alzheimer's disease by using light stimulating optic nerve is characterized in that the eye mask is an eye mask made of an opaque material.

The portable therapeutic apparatus for treating Alzheimer's disease by using light stimulation optic nerve is characterized in that the light source is fixed on one side of the eyecup contacting the face.

Further, the light source is an annular light source array composed of a plurality of point light sources, and two annular light source arrays are arranged on the eye mask. When the eye cover covers both eyes, the two annular light source arrays cover the eyes.

Further, the point light source is a light emitting diode, and the light emitting diode is circular or square.

Further, the circular light-emitting diode has a diameter of 2 - 5 mm.

The portable therapeutic apparatus for treating Alzheimer's disease by using light stimulation optic nerve is characterized in that: the annular array consisting of the point light sources is filled with other point light sources, and the arrangement is one at the center of the circle, at the center of the circle 6 between the ring and the ring.

The portable therapeutic apparatus for treating Alzheimer's disease by using light stimulating optic nerve is characterized in that the light source has a wavelength of 400-800 nm and a brightness modulation frequency of 40 Hz, wherein the illumination time is 1 - 20 ms. Tune, illuminance is 20 – 2000 lux.

The portable therapeutic apparatus for treating Alzheimer's disease by using light stimulation optic nerve is characterized in that the power source is a power supply device connected to a light source through a power line.

The portable therapeutic apparatus for treating Alzheimer's disease by using light stimulating optic nerve is characterized in that the power source is a battery fixed to an eye mask.

The portable therapeutic device for treating Alzheimer's disease by using light stimulating optic nerve is characterized in that the control element is a controller for adjusting the brightness frequency of the light fixed on the power supply device.

The portable therapeutic apparatus for treating Alzheimer's disease by using light stimulating optic nerve is characterized in that the control element is a controller fixed on the eye mask and regulating the frequency of the light brightness by receiving an instruction sent by the mobile communication device.

The portable therapeutic apparatus for treating Alzheimer's disease by using light stimulation optic nerve is characterized in that the annular light source array is composed of 12 point light sources.

Beneficial effect

The portable therapeutic device has the characteristics of simple operation, convenient application and high cost performance. The portable therapeutic device is not only suitable for medical institutions at all levels (high-end top three hospitals, community hospitals, township hospitals), but also for various types of rehabilitation institutions, elderly health management institutions, and families. The portable therapeutic device can be used not only in a fixed place, but also as a wearable therapeutic device, and the use is not limited by location and time. This portable therapeutic device will be mainly used for the treatment and improvement of patients with Alzheimer's disease, and for the prevention of Alzheimer's disease in the middle-aged and elderly population.

DRAWINGS

1 and 2 are schematic views showing the distribution of the eye mask and the LED light source inside the eye mask;

3 is a schematic diagram of light intensity modulation of an LED light source on an eye mask. T2 is the LED light source lighting time.

In the picture:

1 eye mask for covering the eye;

2 LED light sources arranged in a ring pattern mounted on the eye mask.

BEST MODE FOR CARRYING OUT THE INVENTION

This embodiment includes the following technical features:

The treatment device includes:

An eye mask that can be attached to a person's face and cover the eye;

a light source fixed to the eyecup;

a power source that supplies energy to the light source;

A control element that regulates changes in the light source.

Wherein: the eye mask is an eye mask made of an opaque material. The light source is fixed on one side of the eye contact contacting the face; the light source is an annular light source array composed of a plurality of point light sources, and two annular light source arrays are arranged on the eye cover, and when the eye cover covers both eyes, the two annular light source arrays cover the eyes on. The light source adopts a circular light-emitting diode with a diameter of 2 mm; the annular array composed of the point light source is filled with other point light sources, and the arrangement is one at the center of the circle and six at the center of the circle and the ring. The light source has a wavelength of 600 nm and a brightness modulation frequency of 40 Hz, with a bright time of 1 – 20 ms and an illumination of 1500 lux.

Embodiments of the invention

The invention relates to a portable therapeutic apparatus for treating Alzheimer's disease by using light stimulating optic nerve, and the technical idea thereof is to stimulate the eye of a patient by LED light to achieve the effect of treating, improving and preventing Alzheimer's disease.

The specific structure and features of the present invention include:

A portable therapeutic apparatus for treating Alzheimer's disease using light-stimulated optic nerve, characterized in that:

The treatment device includes:

An eye mask that can be attached to a person's face and cover the eye;

a light source fixed to the eyecup;

a power source that supplies energy to the light source;

A control element that adjusts the change in brightness of the source.

The eye shield is an eye mask made of an opaque material, preferably black.

The light source is fixed to the side of the eyecup that contacts the face.

The light source is an array of annular light sources composed of a plurality of point light sources, and two annular light source arrays are arranged on the eye mask. When the eye cover covers both eyes, the two annular light source arrays cover the eyes. The light source is preferably arranged in a laterally elliptical ring shape.

The point source is a light-emitting diode, the light-emitting diode is circular or square, and for a circle, preferably has a diameter of 2 - 5 mm.

Another form of light source arrangement is that the annular array of point sources is filled with other point sources, preferably one at the center of the circle and six between the center of the circle and the ring.

The focus of the invention to achieve therapeutic effects lies in the parameters of the light source, as shown in FIG. 3, specifically: the light source has a wavelength of 400-800 nm, the brightness modulation frequency is 40 Hz, and the illumination time is adjustable from 1 to 20 milliseconds. The illuminance is 20 – 2000 lux. After extensive experiments and research by the inventors, the above parameters of the light source can effectively treat and improve the patient's disease state.

The power source is a power supply device connected to the light source through a power line. Or a battery that is attached to the eye shield.

The control element is a controller that adjusts the brightness of the light on the power supply unit. Or a controller that is fixed to the eyecup to regulate the brightness frequency by receiving an instruction sent by the mobile communication device.

The annular light source array is composed of 12 point light sources, and the effect is better.

The mobile communication device includes a mobile phone, a wristwatch or a wearable device.

The method of use of the present invention is as follows:

Use an elastic strap to secure the eye shield to the face and cover the eye, adjusting the elastic strap to comfort. Connect the eyecup power cable to the power source and activate the light scintillation therapy program. The brightness can be adjusted by setting the T2 time according to personal comfort. The setting range of T2 time is 1 - 20 ms (T1 time has been fixed to 25 ms). Click "Start" to start the light flashing stimulus. Depending on the individual's specific condition, one of the treatment options for light scintillation stimulation can be selected: (1) 15 minutes/time, 4 times/day; (2) 30 minutes/time, 2 times/day; (3) 60 minutes / time, 1 time / day. Every seven days is a course of treatment.

Example 1:

This embodiment includes the following technical features:

The treatment device includes:

An eye mask that can be attached to a person's face and cover the eye;

a light source fixed to the eyecup;

a power source that supplies energy to the light source;

A control element that regulates changes in the light source.

Wherein: the eye mask is an eye mask made of an opaque material. The light source is fixed on one side of the eye contact contacting the face; the light source is an annular light source array composed of a plurality of point light sources, and two annular light source arrays are arranged on the eye cover, and when the eye cover covers both eyes, the two annular light source arrays cover the eyes on. The light source adopts a circular light-emitting diode with a diameter of 2 mm; the annular array composed of the point light source is filled with other point light sources, and the arrangement is one at the center of the circle and six at the center of the circle and the ring. The light source has a wavelength of 600 nm and a brightness modulation frequency of 40 Hz, with a bright time of 1 – 20 ms and an illumination of 1500 lux.

Example 2:

This embodiment includes the following technical features:

The treatment device includes:

An eye mask that can be attached to a person's face and cover the eye;

a light source fixed to the eyecup;

a power source that supplies energy to the light source;

A control element that regulates changes in the light source.

Wherein: the eye mask is an eye mask made of an opaque material. The light source is fixed on one side of the eye contact contacting the face; the light source is an annular light source array composed of a plurality of point light sources, and two annular light source arrays are arranged on the eye cover, and when the eye cover covers both eyes, the two annular light source arrays cover the eyes on. The light source uses a circular light-emitting diode with a diameter of 5 mm; the light source has a wavelength of 600 nm and a brightness modulation frequency of 40 Hz, wherein the light-on time is adjustable from 1 to 20 milliseconds and the illumination is 20 lux.

Example 3:

This embodiment includes the following technical features:

The treatment device includes:

An eye mask that can be attached to a person's face and cover the eye;

a light source fixed to the eyecup;

a power source that supplies energy to the light source;

A control element that regulates changes in the light source.

Wherein: the eye mask is an eye mask made of an opaque material. The light source is fixed on one side of the eye contact contacting the face; the light source is an annular light source array composed of a plurality of point light sources, and two annular light source arrays are arranged on the eye cover, and when the eye cover covers both eyes, the two annular light source arrays cover the eyes on. The light source uses a circular light-emitting diode with a diameter of 5 mm; the light source has a wavelength of 600 nm and a brightness modulation frequency of 40 Hz, wherein the light-on time is adjustable from 1 to 20 milliseconds and the illumination is 2000 lux.

The foregoing provides a preliminary description of the invention provided. The above description of the embodiments is merely for helping to understand the core idea of the present invention. It should be noted that those skilled in the art can make several improvements and modifications to the present invention without departing from the patent principle of the present invention. These improvements and modifications are also within the scope of protection of the patent claims of the present invention. .

Claims (13)

A portable therapeutic apparatus for treating Alzheimer's disease using light-stimulated optic nerve, characterized in that: The treatment device includes: An eye mask that can be attached to a person's face and cover the eye; a light source fixed to the eyecup; a power source that supplies energy to the light source; A control element that regulates changes in the light source. The portable therapeutic apparatus for treating Alzheimer's disease using light-stimulated optic nerve according to claim 1, wherein the eye shield is an eye mask made of an opaque material. A portable therapeutic apparatus for treating Alzheimer's disease using light-stimulated optic nerve according to claim 1, wherein the light source is fixed to a side of the eyecup contacting the face. The portable therapeutic apparatus for treating Alzheimer's disease by using light stimulating optic nerve according to claim 3, wherein the light source is an annular light source array composed of a plurality of point light sources, and two annular light source arrays are arranged in On the eye shield, when the eye mask covers both eyes, two annular light source arrays are covered on both eyes. The portable therapeutic apparatus for treating Alzheimer's disease by using light-stimulated optic nerve according to claim 4, wherein the point light source is a light-emitting diode, and the light-emitting diode is circular or square. A portable therapeutic apparatus for treating Alzheimer's disease using light-stimulated optic nerve according to claim 5, wherein said circular light-emitting diode has a diameter of 2 - 5 mm. The portable therapeutic apparatus for treating Alzheimer's disease by using light stimulating optic nerve according to claim 4, wherein the annular array of the point light sources is filled with other point light sources, and the arrangement is at the center of the circle. There are 6 between the center of the circle and the ring. The portable therapeutic apparatus for treating Alzheimer's disease by using light stimulating optic nerve according to claim 1, wherein the light source has a wavelength of 400 - 800 nm and a brightness modulation frequency of 40 Hz, wherein the light-emitting time is 1 – Adjustable for 20 milliseconds with an illumination of 20 – 2000 lux. A portable therapeutic apparatus for treating Alzheimer's disease using light-stimulated optic nerve according to claim 1, wherein said power source is a power source device connected to a light source through a power line. A portable therapeutic apparatus for treating Alzheimer's disease using light-stimulated optic nerve according to claim 1, wherein said power source is a battery fixed to an eye shield. A portable therapeutic apparatus for treating Alzheimer's disease using light-stimulated optic nerve according to claim 9, wherein said control element is a controller for adjusting a luminance frequency fixed to a power supply unit. The portable therapeutic apparatus for treating Alzheimer's disease by using light stimulating optic nerve according to claim 9 or 10, wherein the control element is an optical lens fixed to the eyecup to regulate light by receiving an instruction transmitted by the mobile communication device. Controller for brightness frequency. The portable therapeutic apparatus for treating Alzheimer's disease by using light stimulating optic nerve according to claim 4, wherein the annular light source array is composed of 12 point light sources.