CN115192922A - Phototherapy instrument - Google Patents

Abstract

The invention discloses a phototherapy instrument, relating to the technical field of rehabilitation physiotherapy instruments, comprising: the irradiation device, the temperature control overload protector and the base; the irradiation device comprises a plurality of laser modules with different optical powers, is arranged on the upper surface of the base and is used for emitting lasers with different optical powers; the temperature control overload protector is arranged on the irradiation device and used for powering off the irradiation device when the temperature of an object to be irradiated, which is placed on the irradiation device, exceeds a set temperature. The laser generated by the irradiation device penetrates through the cerebral cranium of rats and mice to depolymerize fibrous bodies formed by amyloid protein, reduce the number and area of senile plaques, reduce Abeta oligomers and enhance the generation of adenosine triphosphate, thereby improving the activity of neurons and achieving the purpose of improving the memory of APP/PS1 mice.

Description

Phototherapy instrument

Technical Field

The invention relates to the technical field of rehabilitation physiotherapy instruments, in particular to a phototherapy instrument.

Background

The pathogenesis of senile dementia (Alzheimer's disease) is unclear, and no clinical medicine capable of reversing AD exists. And clinical imaging finds that: brain tissues of dementia patients including hippocampus, temporal lobe, frontal lobe, occipital lobe and the like are aggregated with spatiotemporal amyloid-beta (Α β) to form a large number of Senile Plaques (SP), and accompanied with dysfunction of cognition, memory, emotion and the like of the patients. Similarly, the pathological features and behavior disorders of APP/PS1 transgenic dementia mice are similar to those of AD patients. Endogenous formaldehyde in mouse, rat, human brain accumulates rapidly with age; the accumulated formaldehyde can induce the cross-linking of A beta monomer to form A beta oligomer and fiber body, and tau protein over-phosphorylation, which leads to the occurrence of neuron death and dementia.

Currently, there is no drug that can reverse dementia clinically, and therefore, there is a strong need for a physical therapy for dementia that can reduce neurotoxicity of a β oligomers.

Disclosure of Invention

The invention aims to provide a phototherapy instrument which can reduce the neurotoxicity of the Abeta oligomer.

In order to achieve the purpose, the invention provides the following scheme:

a phototherapy instrument comprising: the irradiation device, the temperature control overload protector and the base;

the irradiation device comprises a plurality of Diode (DL) laser modules with different optical powers, and is arranged on the upper surface of the base and used for emitting lasers with different optical powers;

the temperature control overload protector is arranged on the irradiation device and used for powering off the irradiation device when the temperature of an object to be irradiated, placed on the irradiation device, exceeds a set temperature.

Optionally, the phototherapy apparatus further comprises: a power adjustment knob and a controller;

the power adjusting knob is arranged on the side surface of the base, is connected with the controller, and is used for selecting the optical power and sending a gear signal corresponding to the optical power to the controller;

and the controller is arranged in the base, is connected with the irradiation device and is used for controlling the switch of the power supply of the corresponding laser module according to the gear signal.

Optionally, the phototherapy instrument further comprises a light power display screen; the optical power display screen is arranged on the side face of the base, connected with the controller and used for displaying the optical power.

Optionally, the phototherapy apparatus further comprises a time adjustment knob; the time adjusting knob is arranged on the side surface of the base, is connected with the controller and is used for selecting the time length of the object to be irradiated for receiving laser irradiation and sending a signal of the time length to the controller; and the controller controls the working time of the irradiation device according to the time length.

Optionally, the phototherapy instrument further comprises a time display screen; the time display screen is arranged on the side face of the base, connected with the controller and used for displaying the duration.

Optionally, the laser module comprises a plurality of diode lasers and a plurality of resistors; one end of the diode laser is connected with one end of the power supply; the other end of the diode laser is connected with one end of the resistor; the other end of the resistor is connected with the other end of the power supply.

Optionally, the diode laser emits laser light with a wavelength of 630-680 nanometers.

Optionally, the irradiation device comprises a first laser module, a second laser module and a third laser module;

the optical power of the laser emitted by the first laser module is 5mW/cm ² ；

The optical power of the laser emitted by the second laser module is 20mW/cm ² ；

The optical power of the laser emitted by the third laser module is 50mW/cm ² 。

Optionally, when the power adjusting knob is rotated to a first gear, the first laser module works;

when the power adjusting knob is turned to a second gear, the second laser module works;

when the power adjusting knob is turned to a third gear, the third laser module works;

when the power adjusting knob is turned to a fourth gear, the first laser module, the second laser module and the third laser module work simultaneously.

Optionally, the phototherapy instrument further comprises a three-grid glass cover; the three-grid glass cover covers the irradiation device; three lattices of the three-lattice glass cover correspond to the first laser module, the second laser module and the third laser module one to one respectively.

According to the specific embodiment provided by the invention, the invention discloses the following technical effects:

the invention provides a phototherapy apparatus, comprising: the irradiation device, the temperature control overload protector and the base; the irradiation device comprises a plurality of laser modules with different optical powers, is arranged on the upper surface of the base and is used for emitting the lasers with different optical powers; the temperature control overload protector is arranged on the irradiation device and used for powering off the irradiation device when the temperature of an object to be irradiated placed on the irradiation device exceeds a set temperature. The laser generated by the irradiation device penetrates through the cerebral cranium of rats and mice to depolymerize the fibrous bodies formed by amyloid protein, reduce the number and area of senile plaques, reduce Abeta oligomers, and enhance the generation of Adenosine Triphosphate (ATP), so that the neuron activity is improved, and the aim of improving the memory of APP/PS1 mice is fulfilled.

Drawings

In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required in the embodiments will be briefly described below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art that other drawings can be obtained according to these drawings without creative efforts.

FIG. 1 is a schematic view of the structure of a phototherapy apparatus according to the present invention;

FIG. 2 is a circuit diagram of a diode laser driver according to the present invention;

FIG. 3 is a test chart of the present invention for a DL diode laser source;

FIG. 4 is a graph of the control time and optical power inside the pulsed laser treatment device according to the present invention;

FIG. 5 is a schematic diagram of a phototherapy apparatus of the present invention employing a FLA4000+ spectrometer to detect laser irradiation;

FIG. 6 is a schematic diagram of the phototherapy apparatus of the present invention employing a mouse ATP kit to detect neurons;

FIG. 7 is a schematic view of the phototherapy apparatus of the present invention using a transmission electron microscope to detect Abeta corpus fibrosum;

FIG. 8 is a schematic view of the phototherapy apparatus of the present invention employing an FS5 fluorescence spectrophotometer to detect the structure of A β;

FIG. 9 is a schematic diagram of a laser confocal detection of A11 antibody in a phototherapy apparatus according to the present invention;

FIG. 10 is a schematic diagram of the 4G8 antibody detection using confocal laser scanning of the phototherapy apparatus of the present invention;

FIG. 11 is a schematic diagram of the laser confocal detection of p-tau181 antibody in the phototherapy apparatus of the present invention;

FIG. 12 is a schematic diagram of the use of the Morris water maze to detect memory in the phototherapy apparatus of the present invention.

Detailed Description

The technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

The invention aims to provide a phototherapy instrument which can reduce the neurotoxicity of the Abeta oligomer, is simple to operate, is economical and applicable, is a low-intensity laser therapeutic instrument and can be used for researching, using and popularizing an Alzheimer disease animal model.

In order to make the aforementioned objects, features and advantages of the present invention more comprehensible, the present invention is described in detail with reference to the accompanying drawings and the detailed description thereof.

As shown in fig. 1 and 2, the present invention provides a phototherapy apparatus including: irradiation device, control by temperature change overload protection ware and base.

The irradiation device comprises a plurality of laser modules with different optical powers, is arranged on the upper surface of the base and is used for emitting lasers with different optical powers.

The temperature control overload protector is arranged on the irradiation device and used for powering off the irradiation device when the temperature of an object to be irradiated placed on the irradiation device exceeds a set temperature. The temperature control overload protector is a 38-DEG C temperature control overload protector. When the temperature detected by the temperature sensor is 38 ℃, the irradiation device is automatically powered off, and the skin of the mouse is prevented from being burnt by laser heating. Specifically, a 38-DEG C temperature-sensitive electronic element in the temperature control overload protector is connected with a power supply, is arranged on the back of the laser module and is used for detecting temperature change, and when the temperature of an irradiated object exceeds 38℃, the power supply of the irradiation device is automatically cut off, so that the continuous temperature rise caused by laser irradiation is avoided.

As a specific embodiment, the phototherapy apparatus further comprises: a power adjustment knob and a controller.

The power adjusting knob is arranged on the side face of the base, is connected with the controller, and is used for selecting the optical power and sending the gear signal corresponding to the optical power to the controller.

And the controller is arranged in the base, is connected with the irradiation device and is used for controlling the switch of the power supply of the corresponding laser module according to the gear signal.

Furthermore, the phototherapy apparatus further comprises a light power display screen; the optical power display screen is arranged on the side face of the base, connected with the controller and used for displaying the optical power.

As a specific embodiment, the phototherapy apparatus further comprises a time adjustment knob; the time adjusting knob is arranged on the side surface of the base, is connected with the controller, and is used for selecting the duration of laser irradiation of the object to be irradiated and sending a signal of the duration to the controller; and the controller controls the working time of the irradiation device according to the time length. Specifically, the continuous time can be adjusted to 0-60 minutes by rotating the time adjustment knob.

Furthermore, the phototherapy apparatus also comprises a time display screen; the time display screen is arranged on the side face of the base, connected with the controller and used for displaying the duration.

Wherein the laser module comprises a plurality of diode lasers and a plurality of resistors; one end of the diode laser is connected with one end of the power supply; the other end of the diode laser is connected with one end of the resistor; the other end of the resistor is connected with the other end of the power supply. Specifically, as shown in fig. 3, the diode laser emits laser light having a wavelength of 630 to 680 nanometers.

The irradiation device comprises a first laser module, a second laser module and a third laser module; power of diode laser of different laser modules (5-50 mW/cm) ² Error of + -1 mW/cm ² ) The combination of (2) provides measurement of regulation parameters, and the regulation parameters can be regulated into three different optical powers by regulating the resistance: the three different optical powers are: 5. 20, 50mW/cm ² . The optical power of the laser emitted by the first laser module is 5mW/cm ² (ii) a The optical power of the laser emitted by the second laser module is 20mW/cm ² (ii) a The optical power of the laser emitted by the third laser module is 50mW/cm ² . Specifically, the first laser module, the second laser module and the third laser module are independent of each other. The laser module can generate diode laser-630-680 nanometer low-intensity laser which can penetrate through skull of rat and mouse. In vitro experiments show that the laser with the wavelength can obviously depolymerize the fibrous body formed by amyloid; in vivo experiments show that the number and the area of senile plaques are reduced, and the A beta oligomer is reduced. At the same time, can enhance the generation of energy substance Adenosine Triphosphate (ATP) and improve the vitality of neuronsAnd the damaged spatial memory of the APP/PS1 mice is saved.

Specifically, the parameters of the diode laser for the optical power of the three laser modules provided by the present invention are shown in table 1:

TABLE 1 parameters of diode lasers of three laser modules

Model number

Voltage of

Electric current

Power of

Luminous flux

Light efficiency

Optical radiation power

Single particle (Bright)

1.89V

0.0099A

0.018W

775mlm

43072mlm/W

5.8mW

Single particle (Bright)

1.95V

0.0150A

0.029W

1137mlm

39194mlm/W

8.6mW

Single particle (Bright)

1.99V

0.0200A

0.039W

1480mlm

37947mlm/W

11.4mW

Single particle (Bright)

2.03V

0.0250A

0.050W

1794mlm

35883mlm/W

14.0mW

Single particle (Bright)

2.06V

0.0300A

0.061W

2075mlm

34022mlm/W

16.6mW

Single particle (super bright)

1.88V

0.0099A

0.018W

1013mlm

56253mlm/W

5.5mW

Single particle (super bright)

1.92V

0.0149A

0.028W

1498mlm

53503mlm/W

8.2mW

Single particle (super bright)

1.96V

0.0200A

0.039W

1950mlm

49993mlm/W

10.7mW

Single particle (super bright)

2.00V

0.0250A

0.050W

2391mlm

47824mlm/W

13.1mW

Single particle (super bright)

2.06V

0.0300A

0.061W

2099mlm

34408mlm/W

16.7mW

Type number

Voltage of

Electric current

Power of

Luminous flux

Light effect

Radiant flux

Head lamp

4.999V

1.564A

7.820W

88.608lm

11.33lm/W

690.28mW

Big head

4.000V

1.107A

4.429W

68.298lm

15.42lm/W

496.47mW

Big head

3.000V

0.6112A

1.833W

37.305lm

20.35lm/W

265.58mW

Big head

2.000V

0.1383A

0.2765W

7.1463lm

25.84lm/W

50.226mW

Small head

4.999V

0.5582A

2.791W

23.719lm

8.50lm/W

187.95mW

Small head

4.000V

0.3866A

1.546W

15.336lm

9.92lm/W

119.99mW

Small head

3.000V

0.2153A

0.6458W

7.5027lm

11.62lm/W

57.317mW

According to the parameters of the diode laser, the maximum light radiation power of a single lamp bead is 16.7mW. Three lamp beads with power of 16.7mW are evenly distributed in each square centimeter of PCB circuit, so that the total light radiation power is 16.7 multiplied by 3=50.1mW, namely 50.1mW/cm ² The current is 30mA, and the energy loss in propagation is subtracted, so that the requirements of 40mW/cm are met ² The requirements of (1).

Three lamp beads with the power of 16.7mW are used per square centimeter, the current of each light bead is 20mA, and the energy loss in propagation is subtracted, so that the power of 20mW/cm is satisfied ² To beAnd (5) obtaining.

Three lamp beads with the power of 16.7mW are used per square centimeter, the current of 10mA flows through each light bead, and the energy loss in propagation is subtracted, so that the power of 5mW/cm is satisfied ² The requirements of (1).

Therefore, the PCB size and the layout of the laser module are the same.

The method for calculating the current-limiting resistor takes the current flowing through a lamp bead as an example, the resistor and the light bead are connected in series, the total voltage is 5V, the resistor is x, x is multiplied by 0.03A, then 2 is added to be equal to 5, therefore, x =100 omega, and 40mW/cm ² The current limiting resistor is 100 omega, and the power is 0.09W,20mW/em ² The current limiting resistance is 150 omega, the power is 0.06W,5mW/cm ² The current limiting resistance is 300 omega, and the power is 0.03W.

As a specific embodiment, when the power adjusting knob is rotated to a first gear, the first laser module works; when the power adjusting knob is turned to a second gear, the second laser module works; when the power adjusting knob is turned to a third gear, the third laser module works; when the power adjusting knob is turned to a fourth gear, the first laser module, the second laser module and the third laser module work simultaneously.

Specifically, the power adjusting screw consists of four-gear adjustment, wherein the first gear, the second gear and the third gear respectively correspond to 5mW/cm, 20mW/cm and 50mW/cm ² Respectively irradiating the light power; and 4, simultaneously irradiating by three laser modules.

In addition, the phototherapy instrument also comprises a three-grid glass cover; the three-grid glass cover covers the irradiation device; three lattices of the three-lattice glass cover correspond to the first laser module, the second laser module and the third laser module one to one respectively.

Specifically, three glass covers in the three-grid glass cover for the mouse correspond to three laser irradiation modules with different light powers respectively; that is, no. 1 corresponds to 5mW/cm ² (ii) a No. 2 corresponds to 20mW/cm ² (ii) a No. 3 corresponds to 50mW/cm ² 。

As a specific embodiment, the adjustment of the optical power adjusting knob to 1 gear corresponds to 5mW/cm in the No. 1 glass cover ² A laser module; the optical power adjusting knob is adjusted to 2 grades corresponding to 20mW/cm in the No. 2 glass cover ² A laser module; the optical power adjusting knob is adjusted to 3 grades corresponding to 50mW/cm in the No. 3 glass cover ² A laser module; the optical power adjusting knob is adjusted to 4 grades corresponding to 5, 20 and 50mW/cm in No. 1, no. 2 and No. 3 glass covers ² The laser modules illuminate simultaneously.

The phototherapy apparatus provided by the invention has the following effects:

as shown in fig. 4 and 5, the internal control time and optical power of the pulsed laser therapeutic apparatus are tested, a diode laser with 630-680nm is used to irradiate the whole body of the mouse, the laser with the wavelength can penetrate through the whole head of the mouse, and the detection apparatus: FLA4000 and spectrometer (Hangzhou crystal fly), DL diode laser penetrated the skull of mice by 47.5%.

As shown in FIG. 6, the phototherapy apparatus provided by the present invention employs 630-680nm low-intensity laser to activate hippocampal neurons, improve mitochondrial metabolism in neurons, and synthesize cell energy substance Adenosine Triphosphate (ATP), which is beneficial to improving neuron functions. The detection kit comprises: the results of the mouse ATP kit (Isogen Life Science, netherlands) showed that the ATP content in hippocampal neurons was significantly increased after laser treatment.

As shown in fig. 7, in vitro experiments show that the therapeutic apparatus adopts 630-680 nanometer low-intensity diode laser to prevent the aggregation of A beta and reduce the formation of A beta fibrous bodies. A detection instrument: transmission electron microscopy (JEOL JEM-100CX electronic microscope); in the figure, a represents a Diode Laser (DL) pulse pattern; in the figure, B represents the formaldehyde induced cross-linking of amyloid (A β) by diode laser irradiation; in the figure, C represents the diode laser pulse to depolymerize formaldehyde induced amyloid (A β) cross-linking; d is Transmission Electron Microscope (TEM) detection of amyloid (Abeta 42) aggregation; e is formaldehyde aggravated (Abeta 42) aggregation; f is the laser pulse depolymerization effect.

As shown in fig. 8, the phototherapy apparatus provided by the present invention employs 630-680nm laser to irradiate a β, which induces rapid quenching of a β fluorescence, indicating that a β structure is destroyed, and diode laser pulses have different degrees of influence on different amyloid structures. A detection instrument: the model is as follows: FS5 spectrofluorometer, manufacturer: edinburgh instruments, UK.

As shown in fig. 9, fig. 10 and fig. 11, in vivo experiments show that the treatment device adopts a low-intensity diode laser with 630-680 nanometers to reduce A beta oligomer, phosphorylate the formation of tau and reduce the number and the area of senile plaques. And (3) detecting the medicine: a11 antibody (# AHB0052, thermo Fisher Scientific), 4G8 antibody (# MAB1561, chemicon and Upstate ore Millipore), p-tau181 antibody (# KHO0631, thermo Fisher Scientific). A detection instrument: laser confocal (A1R + N-SIM + N-STORM Nikon, japan); as can be obtained from fig. 9, the results of the histochemical structure of the amyloid oligomer (a β O) antibody showed a significant reduction of the expression of a β -pair in hippocampal neurons after laser treatment; as can be obtained from fig. 10, the results of the formation of senile plaque (4G 8) antibody showed that the number of hippocampal senile plaques was significantly reduced after laser treatment; as can be seen in FIG. 11, the results of the organization of antibodies to phosphorylated tau protein (p-tau) show that hyperphosphorylation of tau within hippocampal neurons is significantly reduced following laser treatment.

As shown in figure 12, in vivo experiments show that the APP/PS1 mice irradiated by the therapeutic apparatus with 630-680nm low-intensity diode laser can save the damaged spatial memory of the mice. A detection instrument: the Morris water maze (hardware: hikvision camera; software: ANY-maze; grobel, suzhou, china). As can be seen from fig. 12, the diode laser pulses significantly reduced the escape latency of the demented mice and increased the time in the target platform quadrant, changing the target platform search pattern from edge-to-trend.

In conclusion, the laser generated by the irradiation device penetrates through the cerebral cranium of rats and mice to depolymerize the fibrous bodies formed by amyloid, reduce the number and the area of senile plaques, reduce A beta oligomers, and enhance the generation of Adenosine Triphosphate (ATP), so that the neuron activity is improved, and the aim of improving the memory of APP/PS1 mice is fulfilled.

The embodiments in the present description are described in a progressive manner, each embodiment focuses on differences from other embodiments, and the same and similar parts among the embodiments are referred to each other.

The principles and embodiments of the present invention have been described herein using specific examples, which are provided only to help understand the method and the core concept of the present invention; meanwhile, for a person skilled in the art, according to the idea of the present invention, the specific embodiments and the application range may be changed. In view of the above, the present disclosure should not be construed as limiting the invention.

Claims (10)

1. A phototherapy instrument, comprising: the irradiation device, the temperature control overload protector and the base;

the irradiation device comprises a plurality of laser modules with different optical powers, is arranged on the upper surface of the base and is used for emitting lasers with different optical powers;

the temperature control overload protector is arranged on the irradiation device and used for powering off the irradiation device when the temperature of an object to be irradiated placed on the irradiation device exceeds a set temperature.

2. The phototherapy instrument according to claim 1, further comprising: a power adjustment knob and a controller;

the power adjusting knob is arranged on the side surface of the base, is connected with the controller, and is used for selecting the optical power and sending a gear signal corresponding to the optical power to the controller;

and the controller is arranged in the base, is connected with the irradiation device and is used for controlling the switch of the power supply of the corresponding laser module according to the gear signal.

3. The phototherapy instrument of claim 2 further comprising an optical power display screen; the optical power display screen is arranged on the side face of the base, connected with the controller and used for displaying the optical power.

4. The phototherapy apparatus of claim 2 further comprising a time adjustment knob; the time adjusting knob is arranged on the side surface of the base, is connected with the controller and is used for selecting the time length of the object to be irradiated for receiving laser irradiation and sending a signal of the time length to the controller; and the controller controls the working time of the irradiation device according to the time length.

5. The phototherapy instrument of claim 4 further comprising a time display screen; the time display screen is arranged on the side face of the base, connected with the controller and used for displaying the duration.

6. The phototherapy apparatus of claim 1, wherein the laser module comprises a plurality of diode lasers and a plurality of resistors; one end of the diode laser is connected with one end of the power supply; the other end of the diode laser is connected with one end of the resistor; the other end of the resistor is connected with the other end of the power supply.

7. A phototherapy instrument according to claim 6, characterized in that the diode laser emits laser light at a wavelength of 630-680 nm.

8. The phototherapy instrument of claim 1 wherein the irradiation device comprises a first laser module, a second laser module, and a third laser module;

the optical power of the laser emitted by the first laser module is 5mW/cm ² ；

The optical power of the laser emitted by the second laser module is 20mW/cm ² ；

The optical power of the laser emitted by the third laser module is 50mW/cm ² 。

9. The phototherapy instrument of claim 8 wherein the first laser module operates when the power adjustment knob is rotated to a first gear;

when the power adjusting knob is turned to a second gear, the second laser module works;

when the power adjusting knob is turned to a third gear, the third laser module works;

when the power adjusting knob is turned to a fourth gear, the first laser module, the second laser module and the third laser module work simultaneously.

10. The phototherapy instrument of claim 8 further comprising a three-pane glass cover; the three-grid glass cover covers the irradiation device; and three lattices of the three-lattice glass cover correspond to the first laser module, the second laser module and the third laser module one to one respectively.

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