Method and device for irradiating ultrasonic waves to a living body

Abstract

To provide a simple method for improving eliminating activity of active oxygen in a living body.SOLUTION: A method for irradiating a living body with an ultrasonic wave executes an ultrasonic irradiation step for bringing at least part of the living body into contact with liquid, and irradiating a part of a living body with an ultrasonic wave in a frequency range of 1-10 MHz whose strength ISPTA is 720 mW / cm2 or less through the liquid over a time of 10 seconds or more and 10 minutes or less a plurality of times at time intervals.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention relates to a method and an apparatus for irradiating a living body with ultrasound. [Background technology]

[0002] Numerous diseases are considered to be oxidative stress-related, including neurological diseases such as dementia, arteriosclerosis, carcinogenesis, eye diseases such as age-related macular degeneration, ischemic heart disease, diabetes, chronic respiratory diseases, aging, etc. It is said that increasing the antioxidant capacity (ability to scavenge active oxygen) of the body is essential to prevent these diseases, but the only means currently recommended for this purpose are the intake of antioxidant foods and the improvement of lifestyle habits, centered on moderate exercise.

[0003] Reactive oxygen species (ROS), including active oxygen, are produced in the body not only through normal breathing, but also through the environment (ultraviolet rays, electromagnetic waves, air pollution) and lifestyle habits (stress, smoking, etc.), and excess reactive oxygen species have various adverse effects on the body. For example, reactive oxygen causes lipids to become overoxidized, proteins to denature, and enzymes to become inactive, and this deterioration makes it more likely to cause heart disease, cerebrovascular disease, arteriosclerosis, etc. Reactive oxygen also causes DNA damage and misreplication, making it more likely to cause malignant neoplasms. [Prior art documents] [Non-patent literature]

[0004] [Non-Patent Document 1] Noriko Noguchi, "Oxidative Stress and Antioxidant Effects Associated with Exercise," Japanese Journal of Exercise Physiology, 2003, Vol. 10, No. 1, pp. 1-8 Summary of the Invention [Problem to be solved by the invention]

[0005] Therefore, an object of the present invention is to provide a simple method for improving the activity of scavenging active oxygen in a living body. [Means for solving the problem]

[0006] The method of irradiating a living body with ultrasound according to the present invention comprises contacting at least a part of the living body with a liquid, and irradiating the living body with ultrasound having a frequency in the range of 1 MHz to 10 MHz and an intensity of I through the liquid. SPTA is 720mW / cm 2 An ultrasonic irradiation step of irradiating the part of the living body with the following ultrasonic waves for a period of 10 seconds to 10 minutes is performed multiple times at time intervals.

[0007] The ultrasonic irradiation device for a living body according to the present invention includes a living body support part that brings at least a part of the living body into contact with a liquid, Through the liquid in the biosupport part, a frequency in the range of 1 MHz to 10 MHz, and an intensity I SPTA is 720mW / cm 2 An ultrasonic oscillator for irradiating the part of the living body with the following ultrasonic waves: A control unit that controls irradiation conditions of the ultrasonic oscillator; Equipped with. Effect of the Invention

[0008] According to the ultrasonic irradiation method and ultrasonic irradiation device of the present invention, ultrasonic waves can be irradiated to at least a part of a living body multiple times at appropriate time intervals. · It is possible to improve the antioxidant ability against active oxygen including OH radicals. [Brief description of the drawings]

[0009] [Figure 1] 1 is a schematic diagram showing a configuration of an example of an ultrasonic irradiation device according to a first embodiment. [Diagram 2] FIG. 2 is a schematic diagram showing a schedule of Example 1 of the ultrasonic irradiation method according to the first embodiment. [Diagram 3] 2 is a table showing ultrasonic irradiation conditions in an ultrasonic irradiation method according to Example 1, which shows an example of an ultrasonic irradiation method according to the first embodiment. [Figure 4]FIG. 2 is a schematic diagram showing the scavenging activity of six types of radicals in Example 1. [Diagram 5] This table compares the radical scavenging activity in blood samples taken from a living subject simply exposed to degassed water (CTL) and from a subject exposed to ultrasound every other day for one week (1week US) for the six types of radicals shown in Figure 4. [Figure 6] 6 is a table showing p values ​​of the six radicals in FIG. 5. [Figure 7] Regarding the scavenging activity of the six types of radicals in Figure 5, the table shows the percentage of radical scavenging activity when the living body is simply exposed to deaerated water (CTL), assuming that the radical scavenging activity is 100, and when the living body is exposed to ultrasound every other day for one week (1 week US). [Figure 8] This is a bar graph showing the OH radical scavenging activity when a living body is simply exposed to deaerated water (CTL) and when it is exposed to ultrasound every other day for one week (1week US). [Figure 9] This is a bar graph showing the 1O2 radical scavenging activity when a living body is simply brought into contact with degassed water (CTL) and when it is exposed to ultrasound every other day for one week (1 week US). [Figure 10] This is a bar graph showing the O2 ·-radical scavenging activity when a living organism is simply placed in contact with deaerated water (CTL) and when it is exposed to ultrasound every other day for a week (1week US). [Figure 11] This is a bar graph showing the RO radical scavenging activity when the living body is simply exposed to deaerated water (CTL) and when it is exposed to ultrasound every other day for one week (1week US). [Figure 12] This is a bar graph showing the ROO radical scavenging activity when the living body is simply exposed to deaerated water (CTL) and when it is exposed to ultrasound every other day for one week (1week US). [Figure 13] This is a bar graph showing the CH3 radical scavenging activity when the living body is simply exposed to deaerated water (CTL) and when it is exposed to ultrasound every other day for one week (1week US). DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0010] (Progress leading to the present invention) It is known that the body produces active oxygen through stimulation from repeated exercise such as training, which induces the induction of antioxidant enzymes (see, for example, Non-Patent Document 1). In other words, it is speculated that when exposed to moderate oxidative stress, the body's own antioxidant capacity is enhanced as an adaptive response.

[0011] Therefore, the inventors hypothesized that ultrasound exposure might change the antioxidant ability of the living body, and conducted ultrasound exposure experiments using rats as living bodies to examine changes in the activity of scavenging active oxygen in the blood, which led to the present invention.

[0012] Each aspect of the present invention will be described below.

[0013] The method for irradiating a living body with ultrasound according to the first aspect includes contacting at least a part of the living body with a liquid, and irradiating the living body with ultrasound having a frequency in the range of 1 MHz to 10 MHz and an intensity I SPTA is 720mW / cm 2 An ultrasonic irradiation step of irradiating the part of the living body with the following ultrasonic waves for a period of 10 seconds to 10 minutes is performed multiple times at time intervals.

[0014] The method of irradiating a living body with ultrasound according to a second aspect may be such that, in the above-mentioned first aspect, the ultrasound irradiation step is carried out four times at intervals of two days.

[0015] The ultrasonic irradiation device for a living body according to a third aspect includes a living body support part that brings at least a part of the living body into contact with a liquid; Through the liquid in the biosupport part, the frequency is in the range of 1MHz to 10MHz, and the intensity is I SPTA is 720mW / cm 2 An ultrasonic oscillator for irradiating a part of a living body with the following ultrasonic waves; A control unit that controls the irradiation conditions of the ultrasonic oscillator; Equipped with.

[0016] In the device for irradiating an ultrasonic wave to a living body according to the fourth aspect, the control unit may irradiate ultrasonic waves to at least a part of the living body at time intervals.

[0017] Hereinafter, an ultrasonic irradiation method and an ultrasonic irradiation device according to embodiments will be described with reference to the accompanying drawings. Note that in the drawings, substantially the same components are given the same reference numerals.

[0018] (Embodiment 1) <Ultrasonic irradiation device> 1 is a schematic perspective view showing an example of the configuration of an ultrasound irradiation device 20 according to embodiment 1. This ultrasound irradiation device 20 includes living body supports (containers) 4a and 4b for bringing at least a part of a living body (rat) 1 into contact with a liquid (water) 2, an ultrasound oscillator (transducer) 6 for irradiating ultrasound, and a control unit 10 for controlling irradiation conditions of the ultrasound oscillator 6. According to the ultrasonic irradiation device 20, ultrasonic waves can be irradiated to at least a part of a living body multiple times at appropriate time intervals. · It is possible to improve the antioxidant ability against active oxygen including OH radicals.

[0019] Each of the members constituting this ultrasonic irradiation device 20 will be described below.

[0020] <Living organism> Although the drawing shows a rat as the living body 1 to which the ultrasound is irradiated, the living body is not limited to rats and may be any animal including humans. The part to which the ultrasound is irradiated may be at least a part of the living body, for example, the abdomen, back, legs, or any part thereof.

[0021] <Reactive oxygen species> The reactive oxygen species that are the targets of antioxidant activity include, for example, six types of radicals ( · OH, 1 O 2 , O 2 ·- , R.O. · , R.O.O. · , · CH 3 In the ultrasonic irradiation method according to the first embodiment shown in Figs. 4 to 13 described later, · OH and 1 O 2 However, the present invention is not limited to this, and depending on the irradiation conditions, it is possible that the scavenging activity of other radicals than active oxygen species can be improved.

[0022] <Ultrasonic oscillator, control unit> The frequency of the ultrasound emitted by the ultrasound oscillator (transducer) 6 is between 1 MHz and 10 MHz. Generally, the lower limit of ultrasound that cannot be sensed by the ear is sometimes said to be 2 MHz, but it is believed that sounds of 1 MHz or higher can improve antioxidant capacity. Sounds exceeding 10 MHz tend to attenuate before reaching the living body, making them less efficient. Furthermore, the ultrasound irradiation time is between 10 seconds and 10 minutes per session. If the duration is less than 10 seconds per session, sufficient effect cannot be obtained. Furthermore, irradiation for more than 10 minutes increases the total amount of energy, which may cause damage to the living body.

[0023] The intensity of the ultrasound is the average intensity I SPTA at 720mW / cm 2 The upper limit is below 1.9. The mechanical index MI is an index used to evaluate the safety of non-thermal effects caused by cavitation and other phenomena caused by ultrasound. These upper limits are based on the Ministry of Health, Labor and Welfare, Appendix 3-20 Standards for Mobile Ultrasound Diagnostic Imaging Devices, Notification No. 267: July 10, 2018. The intensity of the ultrasonic wave is I SPTA at 8mW / cm 2Above this limit. If it is less than this, sufficient effect will not be obtained.

[0024] The control unit may irradiate ultrasonic waves at time intervals. The time intervals are not limited to every other day as shown in the schedule of the ultrasonic irradiation method of the first embodiment shown in FIG. 2, but may be appropriately set intervals such as every day or every 12 hours.

[0025] <Body support part> The living body support members 4a and 4b may be any member capable of bringing at least a part of a living body into contact with a liquid. The living body support members 4a and 4b may be, for example, a container such as a glass container, a plastic container, a metal container, a wooden container, or a ceramic container capable of housing a part of a living body, or a mesh member such as a plastic net, a metal net, a wooden lattice, or a ceramic lattice on which a part of a living body can be placed. The liquid to be brought into contact with the living body is, for example, water. The water may be any water that can be brought into contact with a part of the living body, such as degassed water, distilled water, or ultrapure water. If the living body is a fish, an amphibian, or the like, a liquid similar to the habitat of the living body may be used. The liquid may be, for example, physiological saline solution.

[0026] <Ultrasonic irradiation method> The ultrasound irradiation method according to the first embodiment performs an ultrasound irradiation step of bringing at least a part of a living body into contact with a liquid and irradiating the part of the living body with ultrasound through the liquid a plurality of times at time intervals. As a result, in the living body, · It is possible to improve the antioxidant ability against active oxygen including OH radicals.

[0027] (Effect of ultrasonic irradiation) The ultrasound irradiation device and the ultrasound irradiation method according to the first embodiment can irradiate the living body with ultrasound multiple times at time intervals. ·The effect of improving antioxidant capacity against active oxygen, including OH radicals, is still unclear. For example, it is speculated as follows. In other words, as in the case of moderate exercise that is not too intense, ultrasonic irradiation produces active oxygen in the body, which activates IKK, phosphorylates I-κB, and decomposes it by proteases. As a result, it is possible that NF-κB is activated and its migration to the nucleus is promoted, inducing genes under its control, and improving antioxidant capacity. Alternatively, it is possible that under non-oxidative stress, it is due to an antioxidant response under the control of Nrf2-Keap1, a complex of Nrf2, a gene expression activator, and Keap1, an oxidative stress sensor.

[0028] Example 1 The ultrasonic irradiation method according to the first embodiment will be described below using a first specific example. Fig. 2 is a schematic diagram showing a schedule of Example 1 of the ultrasonic irradiation method according to the embodiment 1. Fig. 3 is a table showing ultrasonic irradiation conditions in the ultrasonic irradiation method according to Example 1, which shows an example of the ultrasonic irradiation method according to the embodiment 1. In the ultrasonic irradiation method according to Example 1,

[0029] The rat 1 is placed in degassed water 2 in the double box-shaped container 4a consisting of an outer box 4a and an inner box 4b, with the inner box 4b being made up of two boxes, with the lower half of the rat 1 submerged in the degassed water 2. The outer box 4a also contains degassed water 2, and a transducer 6 is placed at the bottom of the water, and ultrasonic waves are irradiated from the transducer 6 to the rat 1 in the inner box 4b through the degassed water 2 in the outer box 4a and the degassed water 2 in the inner box 4b. The transducer 6 is connected to a control unit 10 having a power amplifier 8 and a waveform generator 9, and ultrasonic irradiation conditions are set.

[0030] The ultrasound irradiation conditions in the ultrasound irradiation method according to Example 1 were as follows: ultrasound was irradiated onto the abdomen of a rat 1 in warm water 2 at 35°C for one minute each time, a total of four times on alternate days (1st, 3rd, 5th, and 7th days). The frequency of the ultrasound emitted from the transducer 6 was 2 MHz. The intensity of ultrasound irradiation per time was I SPTA is 0.34W / cm 2 The mechanical index MI was 0.23, and the total energy was 2.0 J. After that, one week later (on the eighth day), the activity of scavenging active oxygen (hydroxyl radicals, singlet oxygen) in the blood was measured using the ESR spin trapping method.

[0031] <Evaluation method> The radical scavenging activity (antioxidation level) was evaluated as follows. First, six types of radicals ( · OH, 1 O 2 , O 2 ·- , R.O. · , R.O.O. · , · CH 3 ) is generated in a certain amount. The degree to which each radical has been reduced by the blood sample is then quantified using ESR (Electron Spin Resonance) to evaluate the scavenging activity (antioxidation level). ESR is a method of observing the resonance of electron spin and electromagnetic waves using a spectrophotometer that detects molecules with unpaired electrons. The scavenging activity of each radical is shown as an equivalent amount of antioxidants (reduced GSH, SOD, trolox, α-lipoic acid, BSA). The statistical significance of the effect of ultrasonic irradiation in the examples is shown by the p-value, which is a statistical indicator shown in Figure 5.

[0032] (result) FIG. 4 is a schematic diagram showing the scavenging activity of six kinds of radicals in Example 1. FIG. 5 is a table comparing the radical scavenging activity in blood collected from a rat (living body) 1 that was only brought into contact with deaerated water 2 and not irradiated with ultrasound (CTL) with that in blood that was irradiated with ultrasound every other day for one week (1 week US) for the six kinds of radicals in FIG. 4. FIG. 6 is a table showing the p-values ​​of the six kinds of radicals in FIG. 5. FIG. 7 is a table showing the ratio (in %) of the radical scavenging activity in the case where a rat (living body) 1 was only brought into contact with deaerated water 2 and not irradiated with ultrasound (CTL) as 100 for the six kinds of radical scavenging activity in the case where a rat was irradiated with ultrasound every other day for one week (1 week US) for the six kinds of radicals in FIG. 5. Figures 8 to 13 are bar graphs showing the radical scavenging activity of six types of radicals when the living body was only exposed to degassed water and not irradiated with ultrasound (CTL), and when it was irradiated with ultrasound every other day for one week (1 week US). The values ​​shown are the mean ± standard deviation (SD), and the number of samples n is 3. Figures 8 and 9 also show that there was a significant difference at the 1% significance level (p<0.01) compared to the group not irradiated with ultrasound (CTL).

[0033] As shown in Figures 4 to 13, the rat 1 irradiated with ultrasound according to Example 1 has improved scavenging activity for all six types of radicals compared to the case (CTL) where the rat (living body) 1 was simply brought into contact with degassed water 2 and not irradiated with ultrasound. In particular, referring to the p-value in Figure 6, the following statistically significant difference was observed: · OH radical and 1 O 2 As shown in Figures 7, 8, and 9, the scavenging activity of · The OH radical scavenging activity is approximately 8.34 times higher. 1 O 2 The scavenging activity of was improved by approximately 2.18 times.

[0034] (Effect of ultrasonic irradiation)

[0035] As mentioned above, the blood's active oxygen scavenging activity increased significantly due to ultrasound exposure. This finding suggests that frequent ultrasound exposure may increase the body's antioxidant capacity, and it is speculated that its application to humans may be useful in preventing oxidative stress-related diseases, including aging. The antioxidant activity of the body enhanced by ultrasound irradiation is highly likely to be effective in preventing many oxidative stress-related diseases, and from the perspective of antioxidants, we believe that this could contribute to maintaining the health of the nation in place of antioxidant foods. In addition, considering that the ultrasound irradiation conditions used in this study comply with the already established output safety standards for ultrasound diagnostic equipment, we are convinced that the method and device for irradiating humans with ultrasound multiple times at time intervals will directly lead to the creation of a new health industry.

[0036] In addition, the present disclosure includes appropriate combinations of any of the various embodiments and / or examples described above, and can achieve the effects of each embodiment and / or example. [Industrial Applicability]

[0037] According to the ultrasonic irradiation method and ultrasonic irradiation device of the present invention, ultrasonic waves can be irradiated to at least a part of a living body multiple times at appropriate time intervals. · It is possible to improve the antioxidant ability against active oxygen including OH radicals. [Explanation of symbols]

[0038] 1. Rat (live) 2 Degassed water 4a, 4b container 6 Transducers 8. Power Amplifier 9 Waveform Generator 10 Control section 20 Ultrasonic irradiation device

Claims

1. A frequency in the range of 1 MHz to 10 MHz and an intensity I ＳＰＴＡ is 720 mW / cm ２ An ultrasonic irradiation method for a living body, comprising: performing an ultrasonic irradiation step of irradiating the part of the living body with the following ultrasonic waves for a period of 10 seconds to 10 minutes, multiple times at time intervals: The ultrasonic irradiation method is an ultrasonic irradiation method for producing active oxygen in a living body by ultrasonic irradiation and improving the antioxidant ability against the active oxygen in the living body, The active oxygen is a radical of six types: ・ O.H. １ O ２ , O ２ ・－ , R.O. ・ , R.O.O. ・ , ・ CH ３ ) is at least one of the above.

2. 2. The method for irradiating a living body with ultrasound according to claim 1, wherein the ultrasound irradiation step is performed four times at intervals of two days.

3. The active oxygen is a radical that is a mixture of two types of radicals: ・ O.H. １ O ２ 3. The method for irradiating a living body with ultrasound according to claim 1 or 2, wherein the ultrasonic irradiation is performed in a manner similar to that described in claim 1.

4. The method for irradiating a living body with ultrasound according to claim 1 , further comprising contacting at least a part of the living body with a liquid and irradiating the living body with ultrasound via the liquid.

5. The frequency is in the range of 1 MHz to 10 MHz, and the intensity is I ＳＰＴＡ is 720 mW / cm ２ An ultrasonic oscillator for irradiating at least a part of a living body with the following ultrasonic waves; A control unit that controls irradiation conditions of the ultrasonic oscillator; An ultrasonic irradiation device for a living body, comprising: The ultrasonic irradiation device is an ultrasonic irradiation device for producing active oxygen in a living body by ultrasonic irradiation and improving the antioxidant ability against the active oxygen in the living body, The active oxygen is a radical of six types: ・ O.H. １ O ２ , O ２ ・－ , R.O. ・ , R.O.O. ・ , ・ CH ３ ) is at least one of the above.

6. The ultrasonic irradiation device for a living body according to claim 5 , wherein the control unit irradiates at least a part of the living body with ultrasonic waves at time intervals.

7. The active oxygen is a radical that is a mixture of two types of radicals: ・ O.H. １ O ２ 7. The ultrasonic irradiation device for a living body according to claim 5 or 6,

8. The ultrasonic irradiation device for a living body according to claim 5 , further comprising a living body support part that supports at least a part of the living body.

9. The apparatus for irradiating an ultrasonic wave to a living body according to claim 8 , wherein the living body support unit brings at least a part of the living body into contact with a liquid.

Images