WO2020091464A1 - Procédé pour augmenter la viabilité d'une cellule par exposition de la cellule à un rayonnement d'ondes ultrasonores et appareil d'exposition à un rayonnement ultrasonore faisant appel à celui-ci - Google Patents

Procédé pour augmenter la viabilité d'une cellule par exposition de la cellule à un rayonnement d'ondes ultrasonores et appareil d'exposition à un rayonnement ultrasonore faisant appel à celui-ci Download PDF

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Publication number
WO2020091464A1
WO2020091464A1 PCT/KR2019/014611 KR2019014611W WO2020091464A1 WO 2020091464 A1 WO2020091464 A1 WO 2020091464A1 KR 2019014611 W KR2019014611 W KR 2019014611W WO 2020091464 A1 WO2020091464 A1 WO 2020091464A1
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ultrasound
wst
xtt
ultrasonic
cells
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Korean (ko)
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김철우
박동희
원종호
오해리
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Bioinfra Life Science Inc
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Bioinfra Life Science Inc
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Publication of WO2020091464A1 publication Critical patent/WO2020091464A1/fr
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
    • A61N7/00—Ultrasound therapy

Definitions

  • the present invention relates to a method for increasing the survival rate of cells by irradiating ultrasound and an ultrasound irradiation apparatus using the same.
  • Minoxidil is a formulation applied to the scalp and was developed as a treatment for hypertension due to the effect of expanding blood vessels at Pfizer in the past, but was sold as a treatment for hair loss after studying side effects of hair on the forehead and hands.
  • the mechanism of action of minoxidil has not been clarified, it is known that it theoretically expands the blood vessels of the scalp, opens the potassium channel of the cell membrane, supplies oxygen and nutrients to the hair follicle, suppresses hair loss, promotes hair growth, and thickens hair.
  • side effects such as erythema, scalp dryness, chest palpitations, tachycardia, and arrhythmia may occur.
  • the ingredient of Propecia sold by Merck is finasteride, which was originally developed to treat prostatic hyperplasia, but has been used as a hair loss treatment agent because it promotes hair growth.
  • 5 ⁇ -reductase converts the male hormone testosterone to dihydrotestosterone (DHT), which is a major component of hair loss.
  • Finasteride inhibits this 5 ⁇ -reductase enzyme and lowers the concentration of DHT that causes hair loss.
  • Typical side effects include erectile dysfunction, decreased libido, sexual dysfunction, and sexual dysfunction, dizziness, headache, edema, and skin rash. Men with low infertility or sperm count should be cautious about taking medication. In addition, there is a fear of birth defects, so women of childbearing age should not take or contact with medications, and there are restrictions on prescribing.
  • avodot is a component of the dutasteride family, and was developed as a treatment for prostate hyperplasia, like finasteride, but has been found to be used as a treatment for hair loss because of its anti-hair loss effect.
  • dutasteride has a slightly stronger hair loss suppression effect than finasteride.
  • it is known to have strong side effects such as decreased libido and decreased kidney function, so it is used in a limited way compared to finasteride, and has not been approved by the FDA as a treatment for hair loss in the United States.
  • reddensyl Although there are various raw materials included in the functional cosmetics for preventing hair loss, such as reddensyl, these are mostly peptides and growth factors, and most of them have high molecular weight (e.g., 0.5 to 10 kDa), so skin absorption rate when used directly It is difficult to transfer raw materials through the skin, which is difficult.
  • Iontophoresis is a technique that promotes the absorption of drugs by using a potential difference by generating a micro-current through a device such as a patch on an application site. It has the advantage of being available for a wide range of applications, non-invasive and painless, but if the polarity of the drug is not sufficient, the application may be limited, and the size or depth of application may be limited. In addition, erythema may occur when an excessively strong current is applied, and there may be side effects such as itching.
  • the microneedle creates a hole hundreds of micrometers deep in the skin and delivers it.
  • the laser system laser system
  • the stomach system may cause pain, It can irritate the skin and cause erythema.
  • the present invention aims to solve all of the above-mentioned problems.
  • Another object of the present invention is to increase the survival rate of cells without pain, non-invasively by irradiating ultrasound.
  • Another object of the present invention is to increase the survival rate of cells by irradiating only ultrasonic waves without using expensive drugs.
  • the ultrasound generating unit is a critical range from the epidermis of the subject.
  • the ultrasound parameters are irradiated to the epidermis of the object by positioning within, but the ultrasound parameters include at least the pressure of the ultrasound and the duty percentage of the ultrasound, the pressure of the ultrasound is 0.5 MPa to 1 MPa, and the duty percentage of the ultrasound is 1%.
  • a method characterized by being between 5% and 5% is disclosed.
  • the ultrasonic parameters further include an intensity of ultrasonic waves, and the intensity of the ultrasonic waves is 166.7 mW / cm 2 to 416.7 mW / cm 2 .
  • the ultrasound parameters further include a frequency of ultrasound, and the frequency of the ultrasound is 0.5 MHz to 4.6 MHz.
  • the ultrasonic parameters further include a total irradiation time of ultrasonic waves, and a method characterized in that the total irradiation time of ultrasonic waves is within 10 minutes.
  • a method characterized by a method characterized in that the cell is an outer root sheath cell is disclosed.
  • an ultrasonic irradiation apparatus for increasing the survival rate of cells by irradiating ultrasound, comprising: an ultrasonic generator; And a controller configured to position the ultrasound generating unit within a critical range from the epidermis of an object to cause the ultrasound generating unit to irradiate ultrasound to the epidermis of the object, while each of the ultrasound parameters is preset to a predetermined range.
  • the ultrasonic parameters include at least the pressure of the ultrasonic wave and the duty percentage of the ultrasonic wave, the pressure of the ultrasonic wave is 0.5 MPa to 1 MPa, and the ultrasonic irradiation device is characterized in that the duty percentage of the ultrasonic wave is 1% to 5%. .
  • the ultrasonic parameters further include the intensity of ultrasonic waves, and the ultrasonic intensity of the ultrasonic waves is 166.7 mW / cm 2 to 416.7 mW / cm 2 .
  • the ultrasonic parameters further include a frequency of ultrasonic waves, and the ultrasonic wave frequency is 0.5 MHz to 4.6 MHz.
  • the ultrasonic parameters further include a total irradiation time of the ultrasound, and the total irradiation time of the ultrasound is disclosed within 10 minutes.
  • the ultrasonic irradiation device is characterized in that the cells are outer root sheath (outer root sheath) cells.
  • the present invention has an effect of increasing the survival rate of cells without pain non-invasively by irradiating ultrasound.
  • the present invention has an effect of increasing the survival rate of cells by irradiating only ultrasound without using expensive drugs.
  • FIGS. 1A and 1B are schematic views for explaining the concept of parameters of ultrasound in a method of increasing the survival rate of cells by irradiating ultrasound according to an embodiment of the present invention
  • Figure 2 schematically shows the skin stability test results for a method of increasing the survival rate of cells by irradiating ultrasound according to an embodiment of the present invention
  • 3A and 3B schematically illustrate the survival rate of human lateral myocardial cell according to the concentration of the existing drug when only the existing drug is applied
  • FIG. 4 schematically shows the experimental results of the survival rate of human lateral root sheath cells by the method of increasing the survival rate of cells by irradiating ultrasound according to an embodiment of the present invention together with the experimental results by other drugs,
  • Figure 5 schematically shows the experimental results of human outer root cell viability for the control group
  • Figure 6 schematically shows the results of the experiment immediately after irradiation with ultrasound (pressure: 0.5 MPa, duty percentage: 1%) to human lateral root sheath cells;
  • Figure 7 schematically shows the results of the experiment 12 hours after the ultrasound (pressure: 0.5 MPa, duty percentage: 1%) was irradiated to human lateral root sheath cells
  • Figure 9 schematically shows the results of the experiment 12 hours after the irradiation of ultrasound (pressure: 0.5 MPa, duty percentage: 2%) to human lateral root sheath cells
  • FIG. 11 schematically shows the results of the experiment 12 hours after irradiation of ultrasound (pressure: 0.5 MPa, duty percentage: 3%) to human lateral root sheath cells;
  • FIG. 12 schematically shows the experimental results immediately after irradiating ultrasound (pressure: 1 MPa, duty percentage: 1%) to human lateral root sheath cells;
  • Figure 13 schematically shows the results of the experiment 12 hours after the ultrasound (pressure: 1 MPa, duty percentage: 1%) was irradiated to human lateral root hair cells.
  • FIG. 14 schematically shows the experimental results immediately after irradiation with ultrasound (pressure: 1 MPa, duty percentage: 2%) to human lateral root sheath cells;
  • FIG. 15 schematically shows the results of the experiment 12 hours after the irradiation of ultrasound (pressure: 1 MPa, duty percentage: 2%) to human lateral root sheath cells;
  • FIG. 16 schematically shows the experimental results immediately after irradiation of ultrasound (pressure: 1 MPa, duty percentage: 3%) to human lateral root sheath cells;
  • Figure 17 schematically shows the results of the experiment 12 hours after irradiation of ultrasound (pressure: 1 MPa, duty percentage: 3%) to human lateral root sheath cells
  • Figure 18 schematically shows the experimental results immediately after irradiation with ultrasound (pressure: 1.5 MPa, duty percentage: 5%) to human lateral root sheath cells;
  • Figure 19 schematically shows the results of the experiment 12 hours after irradiation of ultrasound (pressure: 1.5 MPa, duty percentage: 5%) to human lateral root sheath cells
  • Figure 20 schematically shows the experimental results immediately after irradiation with ultrasound (pressure: 1.5 MPa, duty percentage: 10%) to human lateral root sheath cells
  • Figure 21 schematically shows the results of the experiment 12 hours after irradiation of ultrasound (pressure: 1.5 MPa, duty percentage: 10%) to human lateral root sheath cells,
  • 22 is a diagram schematically showing the results of experiments on the survival rate of human outer root sheath cells by the method of increasing the survival rate of cells by irradiating ultrasound according to an embodiment of the present invention with the pressure and duty percentage of ultrasound as variables;
  • 23 and 24 schematically show the results of experiments on the survival rate of human lateral root sheath cells by the method of increasing the survival rate of cells by irradiating ultrasound according to an embodiment of the present invention with the intensity of ultrasound as a variable Did,
  • FIG. 25 is an ultrasound (pressure: 0.5 MPa, duty percentage: 2%, intensity: 166.7 mW / cm 2 ) irradiated to human lateral root sheath cells, schematically showing experimental results according to various frequencies of ultrasound,
  • FIG. 26 schematically shows experimental results according to various frequencies of ultrasound while irradiating ultrasound (pressure: 1 MPa, duty percentage: 1%, intensity: 333.3 mW / cm 2 ) to human lateral root sheath cells,
  • FIG. 27 is an ultrasound (pressure: 0.5 MPa, duty percentage: 5%, intensity: 416.7 mW / cm 2 ) irradiated to human lateral root sheath cells, schematically showing experimental results according to various frequencies of ultrasound,
  • FIGS. 1A and 1B are diagrams for explaining the concept of parameters of ultrasound in a method of increasing the viability of cells by irradiating ultrasound according to an embodiment of the present invention.
  • the ultrasonic parameters are as follows.
  • Duty percentage The percentage value divided by one cycle of the actual irradiation time at which the ultrasound is irradiated
  • PRF pulse repetition frequency
  • the duty percentage in FIG. 1B has a value of Ton / (Ton + Toff) * 100 as a value for a time (Ton) at which ultrasonic waves are actually irradiated among one cycle (Ton + Toff) in which ultrasonic waves are irradiated.
  • Table 1 shows intensity values according to pressure and duty percentage of each ultrasonic wave.
  • Figure 2 schematically shows the results of a skin stability test for a method of increasing the survival rate of cells by irradiating ultrasound according to an embodiment of the present invention.
  • the skin temperature increased by about 1.2 degrees Celsius for 30 minutes, and only an average temperature change of 0.05 degrees Celsius per minute was observed. . That is, it can be confirmed that the degree of temperature change due to irradiation with ultrasonic waves does not reach the extent to damage the skin.
  • Table 2 below shows cell seeding density.
  • Table 3 shows the required amount of cells according to the number of conditions.
  • cell culture is human hair outer root sheath cells (HHORSC), mesenchymal stem cell medium (MSCM), FBS 0.25% trypsin / EDTA solution, trypsin neutralization solution, dulbecco's phosphate-buffered saline (DPBS), It consists of poly-L-lysine, T75 flask.
  • HHORSC human hair outer root sheath cells
  • MSCM mesenchymal stem cell medium
  • FBS 0.25% trypsin / EDTA solution trypsin neutralization solution
  • DPBS dulbecco's phosphate-buffered saline
  • WST-1 cell proliferation assay system is used for WST-1 assay, and Trizol, sensiFAST probe Hi-ROX one step kit, PrimeTime qPCR assay is used for PCR.
  • MSCM 500ml basal medium, 25ml FBS, 5ml Mesenchymal stem cells are used to make whole medium.
  • the frozen cell vial is dissolved in a 37 degree water bath, the dissolved cell is placed in 3 ml of a medium, and centrifuged at 3000 rpm for 3 minutes to cell down. Then, after washing with DPBS, centrifugation is performed at 3000 rpm for 3 minutes, and the cell is down. This process is repeated twice. Then, 8 ml of the medium is added to a T75 flask coated with Poly-L-lysine, the cell pellet is released, seeded, and cultured in a 37 ° C 5% CO2 incubator.
  • poly-L-lysine coating is added according to Table 4 for each plate, and then the culture dish coating method is performed.
  • the cells seeded in a 6 well plate are cultured for 12 to 18 hours and then checked under a microscope. Then, after removing the media, wash it twice with DPBS, switch to growth factor free media, and irradiate the cells for 10 minutes. Then, incubated for 24 hours in a 37% 5% CO2 incubator, the medium was removed, washed with DPBS, treated with 0.2 ml of WST-1 drug, and incubated for 3 hours, and then, in a 6 well plate, 3 wells of 96 well plates per well The solution is transferred and the 96 well plate is measured at 450 nm with an absorbance meter.
  • the cells seeded in a 96 well plate are cultured for 12 to 18 hours, and then confirmed whether they are well seeded. And after removing the media, wash it twice with DPBS, change it to growth factor free media, and apply the drug to the cells. Then, incubated for 24 hours in a 37% 5% CO2 incubator, the medium was removed, washed with DPBS, treated with 0.2 ml of WST-1 drug, incubated for 3 hours, and measured at 450 nm with a 96 well plate absorbance meter.
  • FIGS. 3A and 3B schematically illustrate the survival rate of human lateral myocardial cell according to the concentration of the existing drug when only the existing drug is applied.
  • FIG. 3a shows the cell survival rate according to the concentration of lidensil when the hair loss treatment drug lidensil is applied
  • FIG. 3b shows the cell survival rate according to the concentration of minoxidil when the hair loss treatment drug minoxidil is applied.
  • Table 5 shows the experimental conditions for the case where only the drug is applied. At this time, the solubility of minoxidil is 0.2% dissolved in PBS, and the condition is measured 24 hours after application of the drug.
  • Figure 4 shows the results of experiments with the survival rate of human lateral root sheath cells by the method of increasing the survival rate of cells by irradiating ultrasound according to an embodiment of the present invention together with the results of experiments with other drugs.
  • a media comparison experiment was performed.
  • complete media was treated with Redensyl and observed for 24 hours.
  • the time is not limited to 24 hours, and the time may be changed depending on the cell state.
  • redensyl treatment was performed on media that did not contain growth factors and observed for 24 hours. As in the first experiment, the second experiment may be able to change the time according to the cell state.
  • Tables 6 to 9 show the conditions of ultrasonic irradiation experiments to evaluate the physical effects of ultrasound on cells.
  • Tables 6 and 7 show the conditions observed by redensyl treatment on serum free media, overnight, and complete media during the stabilization process after seeding.
  • Table 8 and Table 9 show the conditions observed by stabilization by seeding and then treated with Redensyl in serum free media.
  • Table 10 shows experimental conditions for irradiating ultrasonic waves while varying the pressure and duty percentage of ultrasonic waves.
  • ultrasonic waves were irradiated with a pressure of 0.5 MPa or 1 MPa and a duty percentage of ultrasonic waves of 1% to 3%.
  • FIG. 5 schematically shows the survival rate at a specific time point and the survival rate after 12 hours from a specific time point for human lateral root sheath cells that have not been irradiated with ultrasound, and a control group for comparison with the group irradiated with ultrasound is shown. it means.
  • FIG. 6 schematically shows the results of the experiment immediately after irradiation with ultrasound (pressure: 0.5 MPa, duty percentage: 1%) to human lateral hair root sheath cells.
  • FIG. 7 schematically shows the results of the experiment 12 hours after irradiation of ultrasound (pressure: 0.5 MPa, duty percentage: 1%) to human lateral root sheath cells.
  • FIG. 8 schematically shows the experimental results immediately after irradiating ultrasound (pressure: 0.5 MPa, duty percentage: 2%) to human lateral capillary cells.
  • Figure 9 schematically shows the results of the experiment 12 hours after the irradiation of ultrasound (pressure: 0.5MPa, duty percentage: 2%) to human lateral root root cells.
  • FIG. 10 schematically shows the experimental results immediately after irradiation with ultrasound (pressure: 0.5 MPa, duty percentage: 3%) to human lateral hairy root cells.
  • FIG. 11 schematically shows the results of an experiment 12 hours after irradiation of ultrasound (pressure: 0.5 MPa, duty percentage: 3%) to human lateral root sheath cells.
  • FIG. 12 schematically shows the experimental results immediately after irradiation with ultrasonic waves (pressure: 1 MPa, duty percentage: 1%) to human lateral capillary cells.
  • FIG. 13 schematically shows the results of the experiment 12 hours after irradiation of ultrasound (pressure: 1 MPa, duty percentage: 1%) to human lateral hair root cells.
  • FIG. 14 schematically shows the experimental results immediately after irradiation with ultrasound (pressure: 1 MPa, duty percentage: 2%) to human lateral hair root cells.
  • FIG. 15 schematically shows the results of the experiment 12 hours after the irradiation of ultrasound (pressure: 1 MPa, duty percentage: 2%) to human lateral root sheath cells.
  • FIG. 16 schematically shows the experimental results immediately after irradiation with ultrasound (pressure: 1 MPa, duty percentage: 3%) to human lateral hairy root cells.
  • FIG. 17 schematically shows the results of an experiment 12 hours after irradiation of ultrasound (pressure: 1 MPa, duty percentage: 3%) to human lateral hairy root cells.
  • cell viability such as cells bursting or deforming when 12 hours elapsed immediately after irradiation with ultrasound (pressure: 1 MPa, duty: 3%) and after irradiation You can see that it has decreased.
  • FIG. 18 schematically shows the experimental results immediately after irradiation with ultrasound (pressure: 1.5 MPa, duty percentage: 5%) to human lateral hairy root cells.
  • Figure 19 schematically shows the results of the experiment 12 hours after irradiation of human lateral root root cells with ultrasound (pressure: 1.5 MPa, duty percentage: 5%).
  • FIG. 20 schematically shows the experimental results immediately after irradiation with ultrasonic waves (pressure: 1.5 MPa, duty percentage: 10%) to human lateral capillary cells.
  • FIG. 21 schematically shows the results of an experiment 12 hours after irradiation of ultrasound (pressure: 1.5 MPa, duty percentage: 10%) to human lateral root sheath cells.
  • the ultrasound irradiation apparatus positions the ultrasound generator within a critical range from the epidermis of the subject, Irradiating ultrasound to the epidermis, the ultrasound parameters include at least the pressure of the ultrasound and the duty percentage of the ultrasound, the pressure of the ultrasound is 0.5 MPa to 1 MPa, and the duty percentage of the ultrasound may be 1% to 5%.
  • the parameters of the ultrasound may further include the intensity of the ultrasound, and the intensity of the ultrasound may be 166.7 mW / cm 2 to 416.7 mW / cm 2 .
  • the parameters of the ultrasound may further include the total irradiation time of the ultrasound, and the total irradiation time of the ultrasound may be 10 minutes, but is not limited thereto, and may be an irradiation time within 10 minutes or more than 10 minutes. have.
  • the ultrasound generating unit may irradiate ultrasound to the epidermis of the subject in a state in contact with the epidermis of the subject or spaced apart from the epidermis of the subject.
  • the ultrasonic generator may have a shape surrounding the epidermis of the object in the form of a helmet or head gear.
  • the cells may be outer root sheath cells.
  • FIG. 22 schematically shows the survival rate test results of human lateral myocardial cell derived by irradiating ultrasound according to pressure and duty percentage of various ultrasounds
  • FIGS. 23 and 24 show ultrasounds according to the intensity of various ultrasounds. It is a schematic illustration of the survival rate test results of human lateral root sheath cells derived by examining.
  • the pressure of the ultrasonic wave is 0.5MPa to 1MPa
  • the duty percentage of the ultrasonic wave is 1% to 5%
  • the intensity of the ultrasonic wave is 166.7 mW / cm
  • Table 11 shows the cell viability measured for each pressure and duty percentage of ultrasonic waves irradiated to the cells.
  • the parameters of the ultrasound may further include the frequency of the ultrasound, the frequency of the ultrasound may be 0.5MHz to 4.6MHz.
  • 25 to 27 are diagrams schematically showing experimental results obtained by varying the frequency of ultrasonic waves while irradiating ultrasonic waves to human lateral root sheath cells while maintaining the pressure and the duty percentage of ultrasonic waves.
  • FIG. 25 shows ultrasonic waves (pressure: 0.5 MPa, duty percentage: 2%, intensity: 166.7 mW / cm 2 ) to human lateral root sheath cells, but the frequencies of ultrasonic waves are 0.2 MHz, 0.5 MHz, 1 MHz, and 4.6. The experimental results obtained by changing to MHz and 10 MHz are shown.
  • the cell survival rate in the section where the frequency of the ultrasound is 0.5 MHz to 4.6 MHz is significantly higher than the cell survival rate in the other section.
  • FIG. 26 irradiates ultrasonic waves (pressure: 1 MPa, duty percentage: 1%, intensity: 333.3 mW / cm 2 ) to human outer root sheath cells, but the frequencies of ultrasonic waves are 0.2 MHz, 0.5 MHz, 1 MHz, The experimental results obtained by changing to 4.6 MHz and 10 MHz are shown.
  • the cell survival rate in the section where the frequency of the ultrasound is 0.5 MHz to 4.6 MHz is significantly higher than the cell survival rate in the other section.
  • FIG. 27 irradiates ultrasonic waves (pressure: 0.5 MPa, duty percentage: 5%, intensity: 416.7 mW / cm 2 ) to human outer root sheath cells, but the frequencies of ultrasonic waves are 0.2 MHz, 0.5 MHz, 1 MHz, The experimental results obtained by changing to 4.6 MHz and 10 MHz are shown.
  • the cell survival rate in the section where the frequency of the ultrasound is 0.5 MHz to 4.6 MHz is significantly higher than the cell survival rate in the other section.
  • FIG. 28 schematically shows the results of WNT10B and Beta Catenin-related gene expression when ultrasonic waves having a frequency of 1 MHz were irradiated to human lateral root sheath cells while changing pressure and duty percentage.
  • the intensity of the ultrasound was set to 166.7 mW / cm 2 (0.5 MPa, 2%), 333.3 mW / cm 2 (1MPa, 1%) and 416.7 mW / cm 2 (0.5MPa, 5%) to human lateral root sheath cells.
  • the ultrasound was examined, it was confirmed that the observed WNT10B and Beta Catenin-related gene expression levels were significantly higher than those in the Control group.
  • FIG. 29 schematically shows the results of Keratin 15 and VDR-related gene expression when ultrasonic waves having a frequency of 1 MHz are irradiated to human lateral root sheath cells while changing pressure and duty percentage.
  • the intensity of ultrasonic waves was set to 166.7 mW / cm 2 (0.5 MPa, 2%), 333.3 mW / cm 2 (1 MPa, 1%) and 416.7 mW / cm 2 (0.5 MPa, 5%).
  • FIG. 30 schematically shows the results of gene expression related to PCNA and Ki67 when irradiated to human lateral root sheath cells while changing the pressure and duty percentage of ultrasonic waves having a frequency of 1 MHz.
  • the intensity of ultrasonic waves was set to 166.7 mW / cm 2 (0.5 MPa, 2%), 333.3 mW / cm 2 (1 MPa, 1%) and 416.7 mW / cm 2 (0.5 MPa, 5%).
  • FIG. 31 schematically shows the results of BCL2-related gene expression when ultrasonic waves having a frequency of 1 MHz are irradiated to human lateral root sheath cells while changing pressure and duty percentage.
  • the intensity of ultrasonic waves was set to 166.7 mW / cm 2 (0.5 MPa, 2%), 333.3 mW / cm 2 (1 MPa, 1%) and 416.7 mW / cm 2 (0.5 MPa, 5%).
  • the ultrasonic parameters may further include PRF or PRP, PRF may be 1 Hz to 100 Hz, and PRP may be 0.01 to 1 second.

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Abstract

L'invention concerne un procédé destiné à augmenter la viabilité d'une cellule en exposant la cellule à un rayonnement d'ondes ultrasonores et un appareil d'exposition à un rayonnement ultrasonore faisant appel à celui-ci. Dans un état dans lequel chacun des paramètres ultrasonores est préconfiguré dans une plage prédéfinie, l'appareil d'exposition à un rayonnement ultrasonore place une unité de génération d'ultrasons dans une zone à portée de l'épiderme d'un objet pour exposer l'épiderme de l'objet à un rayonnement d'ondes ultrasonores. Les paramètres ultrasonores comprennent au moins une pression d'ondes ultrasonores et un pourcentage cyclique des ondes ultrasonores, la pression des ondes ultrasonores étant comprise entre 0,5 MPa et 1 MPa, et le pourcentage cyclique des ondes ultrasonores étant compris entre 1 % et 5 %.
PCT/KR2019/014611 2018-10-31 2019-10-31 Procédé pour augmenter la viabilité d'une cellule par exposition de la cellule à un rayonnement d'ondes ultrasonores et appareil d'exposition à un rayonnement ultrasonore faisant appel à celui-ci Ceased WO2020091464A1 (fr)

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Citations (3)

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WO1999034858A1 (fr) * 1998-01-12 1999-07-15 Georgia Tech Research Corporation Estimation et regulation des effet de l'energie acoustique sur des tissus
US20140257146A1 (en) * 2013-03-06 2014-09-11 B.G. Negev Technologies And Applications Ltd. Low intensity ultrasound therapy
WO2017080891A1 (fr) * 2015-11-13 2017-05-18 Koninklijke Philips N.V. Dispositif de soin capillaire, et procédé pour améliorer l'absorption d'un médicament topique dans les cheveux

Patent Citations (3)

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Publication number Priority date Publication date Assignee Title
WO1999034858A1 (fr) * 1998-01-12 1999-07-15 Georgia Tech Research Corporation Estimation et regulation des effet de l'energie acoustique sur des tissus
US20140257146A1 (en) * 2013-03-06 2014-09-11 B.G. Negev Technologies And Applications Ltd. Low intensity ultrasound therapy
WO2017080891A1 (fr) * 2015-11-13 2017-05-18 Koninklijke Philips N.V. Dispositif de soin capillaire, et procédé pour améliorer l'absorption d'un médicament topique dans les cheveux

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Title
FAN, Z. ET AL.: "Characterization of the dynamic activities of a population of microbubbles driven by pulsed ultrasound exposure in sonoporation", ULTRASOUND MEDICINE BIOLOGY, vol. 40, no. 6, June 2014 (2014-06-01), pages 1260 - 1272, XP055705460 *
SASAKI, N. ET AL.: "Low intensity pulsed ultrasound stimulates hair follicle cells in 3D culture", ABSTRACTS OF INTERNATIONAL SOCIETY FOR THERAPEUTIC ULTRASOUND CONFERENCE 2017. JOURNAL OF THERAPEUTIC ULTRASOUND 2018, vol. 6, no. 2, pages 1 - 122, Retrieved from the Internet <URL:https://doi.org/10.1186/s40349-018-0110-x> *

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