WO2022138347A1 - Method for improving vascular function by applying high-frequency electrical stimulation - Google Patents
Method for improving vascular function by applying high-frequency electrical stimulation Download PDFInfo
- Publication number
- WO2022138347A1 WO2022138347A1 PCT/JP2021/046146 JP2021046146W WO2022138347A1 WO 2022138347 A1 WO2022138347 A1 WO 2022138347A1 JP 2021046146 W JP2021046146 W JP 2021046146W WO 2022138347 A1 WO2022138347 A1 WO 2022138347A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- high frequency
- skin
- electrode
- voltage
- beauty
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 27
- 230000004218 vascular function Effects 0.000 title abstract description 8
- 230000000638 stimulation Effects 0.000 title description 2
- 230000014509 gene expression Effects 0.000 claims abstract description 20
- 230000003796 beauty Effects 0.000 claims abstract description 16
- 230000001965 increasing effect Effects 0.000 claims abstract description 7
- 230000002792 vascular Effects 0.000 claims description 26
- 230000000087 stabilizing effect Effects 0.000 claims description 14
- 210000004204 blood vessel Anatomy 0.000 claims description 12
- 102100032817 Integrin alpha-5 Human genes 0.000 claims description 6
- 108010041014 Integrin alpha5 Proteins 0.000 claims description 6
- 102000008790 VE-cadherin Human genes 0.000 claims description 6
- 108010018828 cadherin 5 Proteins 0.000 claims description 6
- 230000002708 enhancing effect Effects 0.000 claims description 3
- 238000011017 operating method Methods 0.000 claims 1
- 230000006872 improvement Effects 0.000 abstract description 6
- 210000003491 skin Anatomy 0.000 description 40
- 239000000284 extract Substances 0.000 description 27
- 238000002474 experimental method Methods 0.000 description 21
- 210000003556 vascular endothelial cell Anatomy 0.000 description 11
- 238000005259 measurement Methods 0.000 description 6
- 102000008186 Collagen Human genes 0.000 description 5
- 108010035532 Collagen Proteins 0.000 description 5
- 229920001436 collagen Polymers 0.000 description 5
- 210000004207 dermis Anatomy 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 230000008859 change Effects 0.000 description 3
- 230000007423 decrease Effects 0.000 description 3
- 230000006641 stabilisation Effects 0.000 description 3
- 238000011105 stabilization Methods 0.000 description 3
- 238000001356 surgical procedure Methods 0.000 description 3
- 235000016623 Fragaria vesca Nutrition 0.000 description 2
- 235000011363 Fragaria x ananassa Nutrition 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000017455 cell-cell adhesion Effects 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 206010033675 panniculitis Diseases 0.000 description 2
- 230000008929 regeneration Effects 0.000 description 2
- 238000011069 regeneration method Methods 0.000 description 2
- 210000004304 subcutaneous tissue Anatomy 0.000 description 2
- KIUKXJAPPMFGSW-DNGZLQJQSA-N (2S,3S,4S,5R,6R)-6-[(2S,3R,4R,5S,6R)-3-Acetamido-2-[(2S,3S,4R,5R,6R)-6-[(2R,3R,4R,5S,6R)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2-carboxylic acid Chemical compound CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 KIUKXJAPPMFGSW-DNGZLQJQSA-N 0.000 description 1
- 244000298715 Actinidia chinensis Species 0.000 description 1
- 235000009434 Actinidia chinensis Nutrition 0.000 description 1
- 235000009436 Actinidia deliciosa Nutrition 0.000 description 1
- 240000006063 Averrhoa carambola Species 0.000 description 1
- 235000010082 Averrhoa carambola Nutrition 0.000 description 1
- 241000167854 Bourreria succulenta Species 0.000 description 1
- 244000160089 Crataegus cuneata Species 0.000 description 1
- 235000008440 Crataegus cuneata Nutrition 0.000 description 1
- 241000975394 Evechinus chloroticus Species 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 244000307700 Fragaria vesca Species 0.000 description 1
- 240000009088 Fragaria x ananassa Species 0.000 description 1
- 241001071795 Gentiana Species 0.000 description 1
- 239000009429 Ginkgo biloba extract Substances 0.000 description 1
- 239000004378 Glycyrrhizin Substances 0.000 description 1
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 description 1
- 244000237986 Melia azadirachta Species 0.000 description 1
- 235000013500 Melia azadirachta Nutrition 0.000 description 1
- 244000245214 Mentha canadensis Species 0.000 description 1
- 235000016278 Mentha canadensis Nutrition 0.000 description 1
- 244000132436 Myrica rubra Species 0.000 description 1
- 235000014631 Myrica rubra Nutrition 0.000 description 1
- 240000007594 Oryza sativa Species 0.000 description 1
- 235000007164 Oryza sativa Nutrition 0.000 description 1
- 244000185701 Pasania edulis Species 0.000 description 1
- 235000006579 Pasania edulis Nutrition 0.000 description 1
- 235000008331 Pinus X rigitaeda Nutrition 0.000 description 1
- 235000011613 Pinus brutia Nutrition 0.000 description 1
- 241000018646 Pinus brutia Species 0.000 description 1
- 238000011529 RT qPCR Methods 0.000 description 1
- 240000001490 Stauntonia hexaphylla Species 0.000 description 1
- 235000014570 Stauntonia hexaphylla Nutrition 0.000 description 1
- 240000002657 Thymus vulgaris Species 0.000 description 1
- 235000007303 Thymus vulgaris Nutrition 0.000 description 1
- 238000010162 Tukey test Methods 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 150000004347 all-trans-retinol derivatives Chemical class 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 229940041514 candida albicans extract Drugs 0.000 description 1
- 229940008396 carrot extract Drugs 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 230000021164 cell adhesion Effects 0.000 description 1
- 235000019693 cherries Nutrition 0.000 description 1
- 238000012790 confirmation Methods 0.000 description 1
- 239000001599 crocus sativus l. flower extract Substances 0.000 description 1
- 238000012258 culturing Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- KCIDZIIHRGYJAE-YGFYJFDDSA-L dipotassium;[(2r,3r,4s,5r,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl] phosphate Chemical compound [K+].[K+].OC[C@H]1O[C@H](OP([O-])([O-])=O)[C@H](O)[C@@H](O)[C@H]1O KCIDZIIHRGYJAE-YGFYJFDDSA-L 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 229940068052 ginkgo biloba extract Drugs 0.000 description 1
- 235000020686 ginkgo biloba extract Nutrition 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 229960005150 glycerol Drugs 0.000 description 1
- LPLVUJXQOOQHMX-UHFFFAOYSA-N glycyrrhetinic acid glycoside Natural products C1CC(C2C(C3(CCC4(C)CCC(C)(CC4C3=CC2=O)C(O)=O)C)(C)CC2)(C)C2C(C)(C)C1OC1OC(C(O)=O)C(O)C(O)C1OC1OC(C(O)=O)C(O)C(O)C1O LPLVUJXQOOQHMX-UHFFFAOYSA-N 0.000 description 1
- 229960004949 glycyrrhizic acid Drugs 0.000 description 1
- UYRUBYNTXSDKQT-UHFFFAOYSA-N glycyrrhizic acid Natural products CC1(C)C(CCC2(C)C1CCC3(C)C2C(=O)C=C4C5CC(C)(CCC5(C)CCC34C)C(=O)O)OC6OC(C(O)C(O)C6OC7OC(O)C(O)C(O)C7C(=O)O)C(=O)O UYRUBYNTXSDKQT-UHFFFAOYSA-N 0.000 description 1
- 235000019410 glycyrrhizin Nutrition 0.000 description 1
- LPLVUJXQOOQHMX-QWBHMCJMSA-N glycyrrhizinic acid Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@H](O[C@@H]1O[C@@H]1C([C@H]2[C@]([C@@H]3[C@@]([C@@]4(CC[C@@]5(C)CC[C@@](C)(C[C@H]5C4=CC3=O)C(O)=O)C)(C)CC2)(C)CC1)(C)C)C(O)=O)[C@@H]1O[C@H](C(O)=O)[C@@H](O)[C@H](O)[C@H]1O LPLVUJXQOOQHMX-QWBHMCJMSA-N 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229920002674 hyaluronan Polymers 0.000 description 1
- 229960003160 hyaluronic acid Drugs 0.000 description 1
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 description 1
- 229960000367 inositol Drugs 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 238000012423 maintenance Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 229940069825 okra extract Drugs 0.000 description 1
- 230000010355 oscillation Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 108090000623 proteins and genes Proteins 0.000 description 1
- 235000009566 rice Nutrition 0.000 description 1
- 239000008132 rose water Substances 0.000 description 1
- 229940092258 rosemary extract Drugs 0.000 description 1
- 235000020748 rosemary extract Nutrition 0.000 description 1
- 239000001233 rosmarinus officinalis l. extract Substances 0.000 description 1
- 229940076591 saffron extract Drugs 0.000 description 1
- 238000007665 sagging Methods 0.000 description 1
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 239000001585 thymus vulgaris Substances 0.000 description 1
- 230000037303 wrinkles Effects 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
- 239000012138 yeast extract Substances 0.000 description 1
- 239000009538 yokuinin Substances 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B18/00—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body
- A61B18/04—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating
- A61B18/12—Surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body by heating by passing a current through the tissue to be heated, e.g. high-frequency current
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61N—ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY
- A61N1/00—Electrotherapy; Circuits therefor
- A61N1/18—Applying electric currents by contact electrodes
- A61N1/32—Applying electric currents by contact electrodes alternating or intermittent currents
Definitions
- the present invention relates to a technique for improving vascular function by applying high-frequency electrical stimulation, for example, a beauty method.
- a high frequency beauty method is known that can improve wrinkles and sagging of the skin by passing a high frequency (RF) current to the skin such as the face and limbs.
- RF high frequency
- a high-frequency current is applied to the skin, the temperature of the dermis layer and subcutaneous tissue rises. It is expected that the heating action promotes the flow of blood and promotes the regeneration of collagen in the dermis layer by causing heat damage to the collagen in the dermis layer.
- various beauty treatment devices using such high frequencies have been proposed (for example, Patent Document 1).
- Patent Document 1 Japanese Unexamined Patent Publication No. 2018-489
- the conventional high-frequency cosmetology method promotes blood circulation and collagen regeneration based on the heating action of the dermis layer and subcutaneous tissue by high frequency, and is a temporary treatment. With increasing awareness of health in recent years, more fundamental improvement of function at the constitutional level is desired.
- One of the objects of the present invention is to provide a cosmetic method based on the improvement of vascular function obtained by applying high frequency to the skin.
- a cosmetological method comprising applying high frequency to the skin to enhance gene expression of a vascular structure stabilizing factor.
- a method for enhancing gene expression of a vascular structure stabilizing factor which comprises a step of applying high frequency to the skin.
- Yet another aspect of the invention provides a method of increasing the thickness of a blood vessel, comprising the step of providing high frequency to the skin.
- a method of operating a high frequency beauty treatment apparatus having a pair of electrodes and a control circuit for applying a high frequency voltage to the pair of electrodes.
- a high frequency voltage that enhances the gene expression of the vascular structure stabilizing factor is applied to the pair of electrodes.
- the high frequency voltage is applied with the pair of electrodes in contact with the skin.
- applying high frequency and “applying high frequency” mean applying a high frequency voltage to an object by applying a high frequency voltage between a pair of electrodes arranged in contact with the object at intervals. It means that a high frequency current is passed.
- the word "about” used to indicate a numerical value means that it includes a numerical value of 5% before and after the numerical value modified by this word.
- a cosmetological effect can be brought about by improving the vascular function.
- a cosmetic method comprises applying a high frequency to the skin to enhance gene expression of a vascular structure stabilizing factor.
- a vascular structure stabilizing factor By enhancing the gene expression of the vascular structure stabilizing factor, the vascular structure is stabilized (for example, the thickness of the blood vessel becomes thicker), and a strong blood vessel can be created. Since strong blood vessels contribute to the tension of the skin, it can be said that the application of RF current to the skin contributes to the tension of the skin.
- the frequency of the high frequency applied to the skin is in the range of 0.5 MHz to 4 MHz, for example, 0.5 MHZ, 1 MHz, 2 MHZ, 3 MHz or 4 MHz, or the range defined by any of the above frequencies (eg, for example. Any frequency included in the range of 1 to 4 MHz) may be used. In some embodiments of the invention, the frequency is about 1 MHz.
- VE-Cadherin and Integrin ⁇ 5 are known as vascular structure stabilizing factors.
- VE-cadherin is a factor responsible for the adhesion between vascular endothelial cells.
- Integrin ⁇ 5 is an important factor in the interaction between vascular endothelial cells and collagen. Therefore, the vascular structure stabilizing factor is preferably at least one factor selected from VE-cadherin and integrin ⁇ 5.
- the application of high frequency to the skin may be combined with the application of drugs to the skin and various extracts.
- applicable drugs and various extracts include inositol, retinol derivative, xylitol, hyaluronic acid, glycerin, yeast extract, cherry leaf extract, keihi extract, pine extract, bulgarian rose water, okra extract, ibukijakou extract, waremokou extract, and glycyrrhizin.
- Dipotassium acid Dipotassium acid, Ginkgo biloba extract, Tencha extract, Yokuinin extract, Kanzo extract, Otaneninjin extract, Clara extract, Star fruit leaf extract, Carrot extract, Juyaku extract, Neem leaf extract, Saffron extract, Kina extract, Confree extract, Thyme extract, Fuyu strawberry , Yomena, Mube, Ryukyu Strawberry, Indian Yomena, Matebashii, Ogon Extract, Rosemary Extract, Anzu Nucleus Granules, Gentiana Extract, Hakka Powder, Taisou Extract, Hop Extract, Kiwi Extract, Roman Camille Extract, Apple Extract, Sanzashi Extract, Examples include Ukon extract, Yamamomo, Futomomo, and Konara. These can be used alone or in combination.
- a high frequency beauty treatment device (hereinafter, also referred to as “high frequency device” or “beauty device”) can be used for applying high frequency to the skin.
- high frequency device also referred to as “high frequency device” or “beauty device”
- a form of the high frequency device will be described with reference to FIG.
- the high frequency device 1 has an electrode unit 10 and a control circuit 20.
- the electrode unit 10 has a first electrode 10a and a second electrode 10b connected to the control circuit 20.
- a contact surface that comes into contact with the user's skin is provided on the electrode portion 10, and the first electrode 10a and the second electrode 10b are arranged at intervals from each other on the contact surface, whereby the first electrode 10a and the second electrode 10b are provided. They can be easily brought into contact with the skin at intervals.
- the first electrode 10a and the second electrode 10b may be connected to the control circuit 20 via a wiring cable instead of the contact surface, whereby the first electrode 10a and the second electrode 10b can be freely arranged. can do.
- the control circuit 20 can have a power supply unit, a voltage control unit, and a resistance measurement unit.
- the power supply unit applies a high frequency voltage (voltage indicating a high frequency) between the first electrode 10a and the second electrode 10b.
- the power supply unit has an oscillation circuit that generates a high frequency voltage, a booster circuit that boosts the oscillated voltage, and the like.
- a high frequency voltage of about 0.5 MHz to 4 MHz is applied to the first electrode 10a and the second electrode 10b. It is configured to apply between.
- the voltage control unit controls the high frequency voltage applied by the power supply unit by controlling the power supply unit. Further, the voltage control unit uses the measurement result by the resistance measurement unit for voltage control.
- the resistance measuring unit measures the resistance value (electrical resistance value) between the first electrode 10a and the second electrode 10b when the first electrode 10a and the second electrode 10b are in contact with the user's skin.
- This resistance value changes depending on the condition of the user's skin and the type of external skin preparation such as lotion applied to the skin. For example, it is known that when a high-frequency current is applied to the skin of a human body, the skin generates heat and the impedance inside the skin decreases as the temperature of the skin rises. Therefore, as the temperature of the skin rises, the current flowing between the first electrode 10a and the second electrode 10b increases, and the measured resistance value decreases.
- the resistance measuring unit measures the resistance value at a predetermined time interval (for example, every 0.5 seconds), and supplies the measured resistance value to the voltage control unit each time.
- the voltage control unit controls the high-frequency voltage according to the resistance value measured by the resistance measurement unit, for example, so that the larger the measured resistance value, the higher the high-frequency voltage (increasing the amplitude of the high-frequency voltage).
- the lower limit of the high frequency voltage applied between the first electrode 10a and the second electrode 10b is preferably 50 Vpp or more, more preferably 70 Vpp or more in the peak voltage.
- the upper limit of the high frequency voltage applied between the first electrode 10a and the second electrode 10b is preferably 100 V or less, more preferably 90 Vpp or less in the peak voltage.
- the applied high frequency voltage can be, for example, 88 Vpp.
- the application of the high frequency voltage may be continuous application or pulse application.
- application (ON) and non-application (OFF) of high frequency voltage are periodically repeated.
- the cycle of repeating the pulse application may be 0.1 seconds to 2 seconds, for example, 0.1 seconds, 0.2 seconds, 0.3 seconds, 0.5 seconds, 0.8 seconds, 1 second or 1 second. It can be .2 seconds.
- the duty ratio which is the ON time ratio of the high frequency voltage in pulse application, is preferably in the range of 10% to 99%, and more preferably in the range of 20% to 80%.
- the duty ratio can be, for example, 40%.
- the application conditions of high frequency such as high frequency voltage and duty ratio may be set by the user.
- the high frequency device may have an input device operated by the user.
- any device such as a switch can be used.
- the control circuit 20 accepts the input operation through the input device, and according to the received input operation, the high frequency voltage, continuous application or pulse application, and pulse application are performed.
- Control parameters such as cycle and duty ratio.
- each parameter may be set independently, or a plurality of combinations of high frequency voltage, period and duty ratio in pulse application are preset in the control circuit 20. The user may be able to select a preset combination.
- the high frequency device By using the high frequency device as described above, the high frequency can be easily applied to the user's skin.
- the high frequency device can be operated as follows. First, the first electrode 10a and the second electrode 10b are placed in contact with the user's skin at intervals from each other. Next, the control circuit 20 applies a high-frequency voltage between the first electrode 10a and the second electrode 10b arranged in contact with the user's skin so as to enhance the gene expression of the vascular structure stabilizing factor.
- Intravascular cell adhesion includes adhesion between vascular endothelial cells and adhesion between vascular endothelial cells and extracellular matrix (collagen group, etc.), and the strength of these adhesions is the strength of the blood vessel itself. Is known to keep. In addition, it has been investigated in previous studies that this cell-cell adhesion decreases with aging and the capillaries become thinner.
- vascular endothelial cells (HUVEC) as follows. First, vascular endothelial cells were seeded in a culture vessel (Petri dish) in which the first electrode was placed at the bottom. Next, the first electrode and the second electrode were placed in contact with the culture solution of the vascular endothelial cells in the culture vessel and at intervals from each other.
- HAVEC vascular endothelial cells
- a high frequency having a frequency of 1 MHz and a peak voltage of 88 Vpp was applied to the culture solution via the first electrode and the second electrode for 1 minute.
- the high frequency was applied by applying a pulse with a repetition period of 1 second and a duty ratio of 40%.
- the vascular endothelial cells were cultured for 24 hours in an incubator. After culturing, vascular endothelial cells were collected, RNA was extracted, and gene expression was confirmed by qPCR.
- Experiment 1-1 and Experiment 1-2 are shown in FIG.
- gene expression was confirmed under the same conditions as in Experiment 1-1 except that high frequency was not applied, and the result is also "control" in FIG. Also shown as.
- the gene expression levels in Experiment 1-1 and Experiment 1-2 are shown as relative values when the gene expression level in the control is 1.
- VE-cadherin the expression level was significantly increased by applying high frequency and as the application time was longer (Tukey's test showed a significant difference at the significance level of 5%).
- integrin ⁇ 5 it cannot be said that it has increased significantly, but it can be said that it tends to increase due to the application of high frequency. From the above, it was shown that the application of high frequency enhances the adhesion factor of vascular endothelial cells and, as a result, contributes to the stabilization of vascular structure.
- Experiment 2 Changes in vascular structure due to application of high frequency to surplus skin after surgery
- the surplus skin for surgery was used as the subject, and the change in the vascular structure was confirmed by applying a high frequency with a frequency of 1 MHz and an inter-peak voltage of 88 Vpp as in Experiment 1.
- the high frequency was applied for 3 minutes.
- the high frequency was applied by applying a pulse with a repetition period of 1 second and a duty ratio of 40%.
- high frequency was applied once a day, and changes in vascular structure were confirmed on the 1st, 3rd, and 5th days. Changes in the vascular structure were confirmed by visualizing the vascular structure.
- FIG. 3A The images of the first day and the fifth day obtained by the experiment 2 are shown in FIG. 3A.
- the vascular structure was visualized under the same conditions as above except that high frequency was not applied, and the result is also shown as "control" in FIG. 3A. From FIG. 3A, comparing the 1st day and the 5th day, it can be seen that the vascular structure of the skin to which the high frequency is applied is thin and thin, while the vascular structure is maintained in the skin to which the high frequency is applied. confirmed.
- the thickness of blood vessels was measured on the 1st, 3rd, and 5th days of the skin to which high frequency was applied and the skin to which high frequency was not applied, respectively.
- the number of blood vessels measured was 90 each.
- the measurement results are shown in FIG. 3A. From the results shown in FIG. 3A, it was confirmed that the blood vessels tended to thicken by applying high frequency, and in particular, it was found that the effect was remarkable when the application of high frequency was continued regularly (according to Welch's test). On the 3rd day, a significant difference was observed at the significance level of 5%, and on the 5th day, a significant difference was observed at the significance level of 1%).
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biomedical Technology (AREA)
- Animal Behavior & Ethology (AREA)
- Veterinary Medicine (AREA)
- Surgery (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Plasma & Fusion (AREA)
- Molecular Biology (AREA)
- Medical Informatics (AREA)
- Heart & Thoracic Surgery (AREA)
- Physics & Mathematics (AREA)
- Otolaryngology (AREA)
- Radiology & Medical Imaging (AREA)
- Electrotherapy Devices (AREA)
Abstract
The present invention provides a beauty method based on an improvement in vascular function obtained by applying high-frequency waves to the skin. This beauty method includes applying high-frequency waves to the skin and increasing the gene expression for a vascular-structure-stabilizing factor.
Description
本発明は、高周波電気刺激の適用による血管機能の改善技術、例えば美容方法に関する。
The present invention relates to a technique for improving vascular function by applying high-frequency electrical stimulation, for example, a beauty method.
顔や手足などの皮膚に対して高周波（ＲＦ）電流を流すことにより、皮膚のしわやたるみなどの改善を図ることが可能な高周波美容方法が知られている。皮膚に高周波電流を流すと、真皮層や皮下組織の温度が上昇する。その加熱作用によって、血液の流れを促進させること、および、真皮層のコラーゲンに熱ダメージを与えることで真皮層のコラーゲンの再生を促進させること等の効果が期待されている。近年は、そのような高周波を利用した様々な美容処理装置が提案されている（例えば、特許文献１）。
A high frequency beauty method is known that can improve wrinkles and sagging of the skin by passing a high frequency (RF) current to the skin such as the face and limbs. When a high-frequency current is applied to the skin, the temperature of the dermis layer and subcutaneous tissue rises. It is expected that the heating action promotes the flow of blood and promotes the regeneration of collagen in the dermis layer by causing heat damage to the collagen in the dermis layer. In recent years, various beauty treatment devices using such high frequencies have been proposed (for example, Patent Document 1).
特許文献１：特開２０１８－４８９号公報
Patent Document 1: Japanese Unexamined Patent Publication No. 2018-489
しかし、従来の高周波美容方法は、高周波による真皮層および皮下組織の加熱作用に基づく血行およびコラーゲン再生を促進するものであり、いわば一時的な処置であった。近年の健康に対する意識が高まる中、より根本的な、体質レベルでの機能の改善が望まれている。
However, the conventional high-frequency cosmetology method promotes blood circulation and collagen regeneration based on the heating action of the dermis layer and subcutaneous tissue by high frequency, and is a temporary treatment. With increasing awareness of health in recent years, more fundamental improvement of function at the constitutional level is desired.
本発明は、皮膚に高周波を適用することによって得られる血管機能の改善に基づく美容方法を提供することを目的の一つとする。
One of the objects of the present invention is to provide a cosmetic method based on the improvement of vascular function obtained by applying high frequency to the skin.
本発明の一つの側面によれば、皮膚に高周波を適用して血管構造安定化因子の遺伝子発現を増強させることを含む美容方法が提供される。
また、本発明の別の側面によれば、皮膚に高周波を適用する工程を含む、血管構造安定化因子の遺伝子発現の増強方法が提供され、
本発明のさらに別の側面によれば、皮膚に高周波を提供する工程を含む、血管の太さの増大方法が提供され、
本発明のさらに別の側面によれば、一対の電極と、前記一対の電極に高周波電圧を印加する制御回路と、を有する高周波美容処理装置の作動方法であって、
前記制御回路により、一対の電極に、血管構造安定化因子の遺伝子発現を増強させる高周波電圧を印加すること、
を含み、
前記高周波電圧は、前記一対の電極を皮膚に接触させた状態で印加される、
高周波美容処理装置の作動方法が提供される。 According to one aspect of the invention, there is provided a cosmetological method comprising applying high frequency to the skin to enhance gene expression of a vascular structure stabilizing factor.
Further, according to another aspect of the present invention, there is provided a method for enhancing gene expression of a vascular structure stabilizing factor, which comprises a step of applying high frequency to the skin.
Yet another aspect of the invention provides a method of increasing the thickness of a blood vessel, comprising the step of providing high frequency to the skin.
According to still another aspect of the present invention, there is a method of operating a high frequency beauty treatment apparatus having a pair of electrodes and a control circuit for applying a high frequency voltage to the pair of electrodes.
By the control circuit, a high frequency voltage that enhances the gene expression of the vascular structure stabilizing factor is applied to the pair of electrodes.
Including
The high frequency voltage is applied with the pair of electrodes in contact with the skin.
A method of operating a high frequency cosmetological treatment device is provided.
また、本発明の別の側面によれば、皮膚に高周波を適用する工程を含む、血管構造安定化因子の遺伝子発現の増強方法が提供され、
本発明のさらに別の側面によれば、皮膚に高周波を提供する工程を含む、血管の太さの増大方法が提供され、
本発明のさらに別の側面によれば、一対の電極と、前記一対の電極に高周波電圧を印加する制御回路と、を有する高周波美容処理装置の作動方法であって、
前記制御回路により、一対の電極に、血管構造安定化因子の遺伝子発現を増強させる高周波電圧を印加すること、
を含み、
前記高周波電圧は、前記一対の電極を皮膚に接触させた状態で印加される、
高周波美容処理装置の作動方法が提供される。 According to one aspect of the invention, there is provided a cosmetological method comprising applying high frequency to the skin to enhance gene expression of a vascular structure stabilizing factor.
Further, according to another aspect of the present invention, there is provided a method for enhancing gene expression of a vascular structure stabilizing factor, which comprises a step of applying high frequency to the skin.
Yet another aspect of the invention provides a method of increasing the thickness of a blood vessel, comprising the step of providing high frequency to the skin.
According to still another aspect of the present invention, there is a method of operating a high frequency beauty treatment apparatus having a pair of electrodes and a control circuit for applying a high frequency voltage to the pair of electrodes.
By the control circuit, a high frequency voltage that enhances the gene expression of the vascular structure stabilizing factor is applied to the pair of electrodes.
Including
The high frequency voltage is applied with the pair of electrodes in contact with the skin.
A method of operating a high frequency cosmetological treatment device is provided.
（定義）
本明細書において、「高周波の適用」および「高周波を適用する」とは、互いに間隔をあけて対象物に接触して配置された一対の電極間に高周波電圧を印加することによって、対象物に高周波電流を流すことを意味する。 (Definition)
As used herein, "applying high frequency" and "applying high frequency" mean applying a high frequency voltage to an object by applying a high frequency voltage between a pair of electrodes arranged in contact with the object at intervals. It means that a high frequency current is passed.
本明細書において、「高周波の適用」および「高周波を適用する」とは、互いに間隔をあけて対象物に接触して配置された一対の電極間に高周波電圧を印加することによって、対象物に高周波電流を流すことを意味する。 (Definition)
As used herein, "applying high frequency" and "applying high frequency" mean applying a high frequency voltage to an object by applying a high frequency voltage between a pair of electrodes arranged in contact with the object at intervals. It means that a high frequency current is passed.
また、数値を示す際に用いる「約」の語は、この語が修飾する数値の前後５％の数値を含むことを表す。
Also, the word "about" used to indicate a numerical value means that it includes a numerical value of 5% before and after the numerical value modified by this word.
本発明によれば、血管機能の改善による美容効果をもたらすことができる。
According to the present invention, a cosmetological effect can be brought about by improving the vascular function.
本発明は、皮膚への高周波（ＲＦ）の適用が、血管機能の改善、例えば血管構造の安定化、に大きく寄与するという、本発明者らの新たな知見に基づくものであり、本発明の一態様として、皮膚に高周波を適用して血管構造安定化因子の遺伝子発現を増強させることを含む、美容方法が提供される。血管構造安定化因子の遺伝子発現が増強することにより、血管構造が安定化し（例えば、血管の太さが太くなる）、丈夫な血管を作ることができる。丈夫な血管は皮膚の張りに寄与することから、皮膚へのＲＦ電流の適用は、皮膚に張りを与えることに寄与するといえる。
The present invention is based on the new findings of the present inventors that the application of high frequency (RF) to the skin greatly contributes to the improvement of vascular function, for example, the stabilization of vascular structure. As one embodiment, a cosmetic method is provided that comprises applying a high frequency to the skin to enhance gene expression of a vascular structure stabilizing factor. By enhancing the gene expression of the vascular structure stabilizing factor, the vascular structure is stabilized (for example, the thickness of the blood vessel becomes thicker), and a strong blood vessel can be created. Since strong blood vessels contribute to the tension of the skin, it can be said that the application of RF current to the skin contributes to the tension of the skin.
皮膚に適用する高周波の周波数は、０．５ＭＨｚ～４ＭＨｚの範囲、例えば、０．５ＭＨＺ、１ＭＨｚ、２ＭＨＺ、３ＭＨｚまたは４ＭＨｚのいずれかの周波数、または上記の任意の周波数により規定される範囲（例えば、１～４ＭＨｚの範囲）に含まれる任意の周波数が使用されてもよい。本発明の一部の形態においては、周波数は約１ＭＨｚである。
The frequency of the high frequency applied to the skin is in the range of 0.5 MHz to 4 MHz, for example, 0.5 MHZ, 1 MHz, 2 MHZ, 3 MHz or 4 MHz, or the range defined by any of the above frequencies (eg, for example. Any frequency included in the range of 1 to 4 MHz) may be used. In some embodiments of the invention, the frequency is about 1 MHz.
血管構造安定化因子としては、ＶＥ－カドヘリン（VE-Cadherin）およびインテグリンα５（Integrinα5）が知られている。ＶＥ－カドヘリンは、血管内皮細胞同士の接着を担う因子である。インテグリンα５は、血管内皮細胞とコラーゲンの相互作用に重要な因子である。したがって、血管構造安定化因子は、ＶＥ－カドヘリンおよびインテグリンα５から選択される少なくとも１つの因子であることが好ましい。
VE-Cadherin and Integrin α5 are known as vascular structure stabilizing factors. VE-cadherin is a factor responsible for the adhesion between vascular endothelial cells. Integrin α5 is an important factor in the interaction between vascular endothelial cells and collagen. Therefore, the vascular structure stabilizing factor is preferably at least one factor selected from VE-cadherin and integrin α5.
皮膚への高周波の適用は皮膚への薬剤や各種抽出液等の適用を組み合わせてもよい。例えば、適用できる薬剤や各種抽出液として、イノシトール、レチノール誘導体、キシリトール、ヒアルロン酸、グリセリン、酵母エキス、サクラリーフエキス、ケイヒエキス、マツエキス、ブルガリアローズウォーター、オクラエキス、イブキジャコウエキス、ワレモコウエキス、グリチルリチン酸ジカリウム、イチョウ葉エキス、テンチャエキス、ヨクイニンエキス、カンゾウエキス、オタネニンジンエキス、クララエキス、スターフルーツ葉エキス、ニンジンエキス、ジュウヤクエキス、ニームリーフエキス、サフランエキス、キナエキス、コンフリーエキス、タイムエキス、フユイチゴ、ヨメナ、ムベ、リュウキュウイチゴ、インドヨメナ、マテバシイ、オウゴンエキス、ローズマリーエキス、アンズ核粒、ゲンチアナエキス、ハッカ末、タイソウエキス、ホップエキス、キウイエキス、ローマカミツレエキス、リンゴエキス、サンザシエキス、ウコンエキス、ヤマモモ、フトモモ、コナラなどが例示される。これらは単独で又は複数組み合わせて使用することができる。
The application of high frequency to the skin may be combined with the application of drugs to the skin and various extracts. For example, applicable drugs and various extracts include inositol, retinol derivative, xylitol, hyaluronic acid, glycerin, yeast extract, cherry leaf extract, keihi extract, pine extract, bulgarian rose water, okra extract, ibukijakou extract, waremokou extract, and glycyrrhizin. Dipotassium acid, Ginkgo biloba extract, Tencha extract, Yokuinin extract, Kanzo extract, Otaneninjin extract, Clara extract, Star fruit leaf extract, Carrot extract, Juyaku extract, Neem leaf extract, Saffron extract, Kina extract, Confree extract, Thyme extract, Fuyu strawberry , Yomena, Mube, Ryukyu Strawberry, Indian Yomena, Matebashii, Ogon Extract, Rosemary Extract, Anzu Nucleus Granules, Gentiana Extract, Hakka Powder, Taisou Extract, Hop Extract, Kiwi Extract, Roman Camille Extract, Apple Extract, Sanzashi Extract, Examples include Ukon extract, Yamamomo, Futomomo, and Konara. These can be used alone or in combination.
皮膚への高周波の適用には、高周波美容処理装置（以下、「高周波装置」または「美容装置」ともいう）を用いることができる。高周波装置の一形態について、図１を参照して説明する。
A high frequency beauty treatment device (hereinafter, also referred to as "high frequency device" or "beauty device") can be used for applying high frequency to the skin. A form of the high frequency device will be described with reference to FIG.
高周波装置１は、電極部１０と制御回路２０とを有する。電極部１０は、制御回路２０に接続された第１電極１０ａおよび第２電極１０ｂを有する。ユーザの皮膚に接触する接触面を電極部１０に設け、この接触面に、第１電極１０ａおよび第２電極１０ｂを互いに間隔をあけて配置することにより、第１電極１０ａおよび第２電極１０ｂを容易に皮膚に互いに間隔をあけて接触させることができる。第１電極１０ａおよび第２電極１０ｂを、接触面にではなく、配線ケーブルを介して制御回路２０と接続してもよく、こうすることによって、第１電極１０ａおよび第２電極１０ｂを自由に配置することができる。
The high frequency device 1 has an electrode unit 10 and a control circuit 20. The electrode unit 10 has a first electrode 10a and a second electrode 10b connected to the control circuit 20. A contact surface that comes into contact with the user's skin is provided on the electrode portion 10, and the first electrode 10a and the second electrode 10b are arranged at intervals from each other on the contact surface, whereby the first electrode 10a and the second electrode 10b are provided. They can be easily brought into contact with the skin at intervals. The first electrode 10a and the second electrode 10b may be connected to the control circuit 20 via a wiring cable instead of the contact surface, whereby the first electrode 10a and the second electrode 10b can be freely arranged. can do.
制御回路２０は、電源部、電圧制御部および抵抗測定部を有することができる。電源部は、第１電極１０ａと第２電極１０ｂとの間に高周波電圧（高周波を示す電圧）を印加する。電源部は、高周波の電圧を生成する発振回路、および発振された電圧を昇圧する昇圧回路等を有し、例えば、０．５ＭＨｚ～４ＭＨｚ程度の高周波電圧を第１電極１０ａと第２電極１０ｂとの間に印加するように構成される。ユーザの皮膚に第１電極１０ａおよび第２電極１０ｂを接触させた状態で第１電極１０ａと第２電極１０ｂとの間に高周波の電圧を印加することで、皮膚に高周波の電流を流すことができる。
The control circuit 20 can have a power supply unit, a voltage control unit, and a resistance measurement unit. The power supply unit applies a high frequency voltage (voltage indicating a high frequency) between the first electrode 10a and the second electrode 10b. The power supply unit has an oscillation circuit that generates a high frequency voltage, a booster circuit that boosts the oscillated voltage, and the like. For example, a high frequency voltage of about 0.5 MHz to 4 MHz is applied to the first electrode 10a and the second electrode 10b. It is configured to apply between. By applying a high-frequency voltage between the first electrode 10a and the second electrode 10b with the first electrode 10a and the second electrode 10b in contact with the user's skin, a high-frequency current can be passed through the skin. can.
電圧制御部は、電源部を制御することで電源部が印加する高周波電圧を制御する。また、電圧制御部は、電圧の制御に抵抗測定部による測定結果を用いる。抵抗測定部は、第１電極１０ａと第２電極１０ｂとがユーザの皮膚に接触した状態での第１電極１０ａと第２電極１０ｂとの間の抵抗値（電気抵抗値）を測定する。
The voltage control unit controls the high frequency voltage applied by the power supply unit by controlling the power supply unit. Further, the voltage control unit uses the measurement result by the resistance measurement unit for voltage control. The resistance measuring unit measures the resistance value (electrical resistance value) between the first electrode 10a and the second electrode 10b when the first electrode 10a and the second electrode 10b are in contact with the user's skin.
この抵抗値は、ユーザの皮膚の状態、および皮膚に塗布される化粧水といった皮膚外用剤の種類等によって変化する。例えば、人体の皮膚に高周波電流を流した場合、皮膚が発熱し、皮膚の温度上昇に伴って皮膚内部のインピーダンスが減少することが知られている。従って、皮膚の温度上昇に伴って、第１電極１０ａおよび第２電極１０ｂの間に流れる電流が増加し、測定される抵抗値が小さくなる。抵抗測定部は、抵抗値の測定を決められた時間間隔（例えば０．５秒毎など）で行い、その度に測定した抵抗値を電圧制御部に供給する。
This resistance value changes depending on the condition of the user's skin and the type of external skin preparation such as lotion applied to the skin. For example, it is known that when a high-frequency current is applied to the skin of a human body, the skin generates heat and the impedance inside the skin decreases as the temperature of the skin rises. Therefore, as the temperature of the skin rises, the current flowing between the first electrode 10a and the second electrode 10b increases, and the measured resistance value decreases. The resistance measuring unit measures the resistance value at a predetermined time interval (for example, every 0.5 seconds), and supplies the measured resistance value to the voltage control unit each time.
電圧制御部は、抵抗測定部で測定された抵抗値に応じて、例えば、測定された抵抗値が大きいほど高周波電圧を高くする（高周波電圧の振幅を大きくする）ように高周波電圧を制御する。
The voltage control unit controls the high-frequency voltage according to the resistance value measured by the resistance measurement unit, for example, so that the larger the measured resistance value, the higher the high-frequency voltage (increasing the amplitude of the high-frequency voltage).
第１電極１０ａと第２電極１０ｂとの間に印加される高周波電圧の下限値は、ピーク間電圧で５０Ｖｐｐ以上であることが好ましく、より好ましくは７０Ｖｐｐ以上である。また、第１電極１０ａと第２電極１０ｂとの間に印加される高周波電圧の上限値は、ピーク間電圧で１００Ｖ以下であることが好ましく、より好ましくは９０Ｖｐｐ以下である。印加される高周波電圧は、例えば８８Ｖｐｐとすることができる。
The lower limit of the high frequency voltage applied between the first electrode 10a and the second electrode 10b is preferably 50 Vpp or more, more preferably 70 Vpp or more in the peak voltage. The upper limit of the high frequency voltage applied between the first electrode 10a and the second electrode 10b is preferably 100 V or less, more preferably 90 Vpp or less in the peak voltage. The applied high frequency voltage can be, for example, 88 Vpp.
高周波電圧の印加は、連続印加であってもよいしパルス印加であってもよい。パルス印加の場合、高周波電圧の印加（ＯＮ）と不印加（ＯＦＦ）とが周期的に繰り返される。パルス印加の繰り返しの周期は、０．１秒～２秒であってよく、例えば０．１秒、０．２秒、０．３秒、０．５秒、０．８秒、１秒または１．２秒とすることができる。パルス印加における高周波電圧のＯＮ時間比であるデューティー比は、１０％～９９％の範囲であることが好ましく、より好ましくは２０％～８０％の範囲である。デューティー比は、例えば４０％とすることができる。
The application of the high frequency voltage may be continuous application or pulse application. In the case of pulse application, application (ON) and non-application (OFF) of high frequency voltage are periodically repeated. The cycle of repeating the pulse application may be 0.1 seconds to 2 seconds, for example, 0.1 seconds, 0.2 seconds, 0.3 seconds, 0.5 seconds, 0.8 seconds, 1 second or 1 second. It can be .2 seconds. The duty ratio, which is the ON time ratio of the high frequency voltage in pulse application, is preferably in the range of 10% to 99%, and more preferably in the range of 20% to 80%. The duty ratio can be, for example, 40%.
高周波電圧およびデューティー比といった高周波の適用条件はユーザが設定可能であってもよい。高周波の適用条件をユーザが設定できるようにするため、高周波装置は、ユーザにより操作される入力デバイスを有することができる。入力デバイスとしては、例えばスイッチなど任意のデバイスを用いることができる。高周波の適用条件をユーザが設定可能である場合、制御回路２０は、入力デバイスを通じた入力操作を受け付け、その受け付けた入力操作に従って、高周波電圧、連続印加かパルス印加か、並びにパルス印加の場合の周期およびデューティー比などのパラメータを制御する。高周波の適用条件の設定に際し、各パラメータは、それぞれ独立して設定可能であってもよいし、パルス印加における高周波電圧、周期およびデューティー比について複数の組み合わせが制御回路２０にプリセットされており、そのプリセットされた組み合わせをユーザが選択するようになっていてもよい。
The application conditions of high frequency such as high frequency voltage and duty ratio may be set by the user. In order to allow the user to set the application conditions of the high frequency, the high frequency device may have an input device operated by the user. As the input device, any device such as a switch can be used. When the application condition of the high frequency can be set by the user, the control circuit 20 accepts the input operation through the input device, and according to the received input operation, the high frequency voltage, continuous application or pulse application, and pulse application are performed. Control parameters such as cycle and duty ratio. When setting the high frequency application conditions, each parameter may be set independently, or a plurality of combinations of high frequency voltage, period and duty ratio in pulse application are preset in the control circuit 20. The user may be able to select a preset combination.
以上説明したような高周波装置を用いることで、ユーザの皮膚に容易に高周波を適用することができる。高周波装置は、次のように作動させることができる。まず、第１電極１０ａと第２電極１０ｂとを、互いに間隔をあけてユーザの皮膚に接触させて配置する。次に、制御回路２０により、血管構造安定化因子の遺伝子発現を増強させるように、ユーザの皮膚に接触させて配置した第１電極１０ａと第２電極１０ｂとの間に高周波電圧を印加する。
By using the high frequency device as described above, the high frequency can be easily applied to the user's skin. The high frequency device can be operated as follows. First, the first electrode 10a and the second electrode 10b are placed in contact with the user's skin at intervals from each other. Next, the control circuit 20 applies a high-frequency voltage between the first electrode 10a and the second electrode 10b arranged in contact with the user's skin so as to enhance the gene expression of the vascular structure stabilizing factor.
［高周波の適用による血管機能改善の確認］
以下、発明者らが行った高周波の適用による血管機能改善の確認実験について説明する。 [Confirmation of improvement of vascular function by applying high frequency]
Hereinafter, the experiments for confirming the improvement of vascular function by applying high frequency waves conducted by the inventors will be described.
以下、発明者らが行った高周波の適用による血管機能改善の確認実験について説明する。 [Confirmation of improvement of vascular function by applying high frequency]
Hereinafter, the experiments for confirming the improvement of vascular function by applying high frequency waves conducted by the inventors will be described.
［実験１：血管内細胞への高周波の適用による血管構造安定化因子の発現］
血管内細胞の接着には、血管内皮細胞同士の接着、および血管内皮細胞と細胞外マトリックス（コラーゲン群など）との接着が存在し、これらの接着が丈夫であることが、血管自体の丈夫さを保つことが知られている。また、この細胞間接着は、老化により減少し、毛細血管が細くなることが、これまでの研究で調べられてきている。 [Experiment 1: Expression of vascular structure stabilizing factor by application of high frequency to intravascular cells]
Intravascular cell adhesion includes adhesion between vascular endothelial cells and adhesion between vascular endothelial cells and extracellular matrix (collagen group, etc.), and the strength of these adhesions is the strength of the blood vessel itself. Is known to keep. In addition, it has been investigated in previous studies that this cell-cell adhesion decreases with aging and the capillaries become thinner.
血管内細胞の接着には、血管内皮細胞同士の接着、および血管内皮細胞と細胞外マトリックス（コラーゲン群など）との接着が存在し、これらの接着が丈夫であることが、血管自体の丈夫さを保つことが知られている。また、この細胞間接着は、老化により減少し、毛細血管が細くなることが、これまでの研究で調べられてきている。 [Experiment 1: Expression of vascular structure stabilizing factor by application of high frequency to intravascular cells]
Intravascular cell adhesion includes adhesion between vascular endothelial cells and adhesion between vascular endothelial cells and extracellular matrix (collagen group, etc.), and the strength of these adhesions is the strength of the blood vessel itself. Is known to keep. In addition, it has been investigated in previous studies that this cell-cell adhesion decreases with aging and the capillaries become thinner.
そこで、このような接着に関わる因子として、細胞同士の接着に関わるＶＥ－カドヘリン、および細胞と細胞外マトリックスとの接着に関わるインテグリンα５の、２つの遺伝子の発現量の変化を確認した。
Therefore, we confirmed changes in the expression levels of two genes, VE-cadherin, which is involved in cell-cell adhesion, and integrin α5, which is involved in cell-extracellular matrix adhesion, as factors involved in such adhesion.
［実験１－１］
実験１では、図１に示した構成において、第１電極および第２電極をそれぞれリード線によって制御回路に接続し、第１電極および第２電極を任意の位置に配置できるようにした高周波装置を用い、以下のようにして、血管内皮細胞（ＨＵＶＥＣ）に対して高周波を適用した。まず、第１電極を底部に配置した培養容器（シャーレ）に血管内皮細胞を播種した。次いで、第１電極および第２電極を、培養容器内の血管内皮細胞の培養液と接し、かつ、互いに間隔をあけて配置した。その後、第１電極および第２電極を介して培養液に、周波数１ＭＨｚ、ピーク間電圧８８Ｖｐｐの高周波を１分間適用した。高周波の適用は、繰り返し周期が１秒、デューティー比が４０％のパルス印加とした。その後、培養器にて血管内皮細胞を２４時間培養した。培養後の血管内皮細胞を回収してＲＮＡを抽出し、ｑＰＣＲにより遺伝子発現を確認した。 [Experiment 1-1]
In Experiment 1, in the configuration shown in FIG. 1, a high-frequency device is provided in which the first electrode and the second electrode are connected to the control circuit by lead wires, respectively, so that the first electrode and the second electrode can be arranged at arbitrary positions. High frequency was applied to the vascular endothelial cells (HUVEC) as follows. First, vascular endothelial cells were seeded in a culture vessel (Petri dish) in which the first electrode was placed at the bottom. Next, the first electrode and the second electrode were placed in contact with the culture solution of the vascular endothelial cells in the culture vessel and at intervals from each other. Then, a high frequency having a frequency of 1 MHz and a peak voltage of 88 Vpp was applied to the culture solution via the first electrode and the second electrode for 1 minute. The high frequency was applied by applying a pulse with a repetition period of 1 second and a duty ratio of 40%. Then, the vascular endothelial cells were cultured for 24 hours in an incubator. After culturing, vascular endothelial cells were collected, RNA was extracted, and gene expression was confirmed by qPCR.
実験１では、図１に示した構成において、第１電極および第２電極をそれぞれリード線によって制御回路に接続し、第１電極および第２電極を任意の位置に配置できるようにした高周波装置を用い、以下のようにして、血管内皮細胞（ＨＵＶＥＣ）に対して高周波を適用した。まず、第１電極を底部に配置した培養容器（シャーレ）に血管内皮細胞を播種した。次いで、第１電極および第２電極を、培養容器内の血管内皮細胞の培養液と接し、かつ、互いに間隔をあけて配置した。その後、第１電極および第２電極を介して培養液に、周波数１ＭＨｚ、ピーク間電圧８８Ｖｐｐの高周波を１分間適用した。高周波の適用は、繰り返し周期が１秒、デューティー比が４０％のパルス印加とした。その後、培養器にて血管内皮細胞を２４時間培養した。培養後の血管内皮細胞を回収してＲＮＡを抽出し、ｑＰＣＲにより遺伝子発現を確認した。 [Experiment 1-1]
In Experiment 1, in the configuration shown in FIG. 1, a high-frequency device is provided in which the first electrode and the second electrode are connected to the control circuit by lead wires, respectively, so that the first electrode and the second electrode can be arranged at arbitrary positions. High frequency was applied to the vascular endothelial cells (HUVEC) as follows. First, vascular endothelial cells were seeded in a culture vessel (Petri dish) in which the first electrode was placed at the bottom. Next, the first electrode and the second electrode were placed in contact with the culture solution of the vascular endothelial cells in the culture vessel and at intervals from each other. Then, a high frequency having a frequency of 1 MHz and a peak voltage of 88 Vpp was applied to the culture solution via the first electrode and the second electrode for 1 minute. The high frequency was applied by applying a pulse with a repetition period of 1 second and a duty ratio of 40%. Then, the vascular endothelial cells were cultured for 24 hours in an incubator. After culturing, vascular endothelial cells were collected, RNA was extracted, and gene expression was confirmed by qPCR.
［実験１－２］
高周波の適用時間を３分間とした以外は実験１－１と同じ条件で遺伝子発現を確認した。 [Experiment 1-2]
Gene expression was confirmed under the same conditions as in Experiment 1-1 except that the application time of high frequency was set to 3 minutes.
高周波の適用時間を３分間とした以外は実験１－１と同じ条件で遺伝子発現を確認した。 [Experiment 1-2]
Gene expression was confirmed under the same conditions as in Experiment 1-1 except that the application time of high frequency was set to 3 minutes.
実験１－１および実験１－２の結果を図２に示す。なお、高周波の適用による遺伝子発現の変化の効果を確認するため、高周波を適用しなかった以外は実験１－１と同じ条件で遺伝子発現を確認し、図２には、その結果も「コントロール」として併せて示した。実験１－１および実験１－２の遺伝子発現量は、コントロールでの遺伝子発現量を１としたときの相対値で示した。
The results of Experiment 1-1 and Experiment 1-2 are shown in FIG. In order to confirm the effect of the change in gene expression by applying high frequency, gene expression was confirmed under the same conditions as in Experiment 1-1 except that high frequency was not applied, and the result is also "control" in FIG. Also shown as. The gene expression levels in Experiment 1-1 and Experiment 1-2 are shown as relative values when the gene expression level in the control is 1.
図２より、次のことがいえる。ＶＥ－カドヘリンについては、高周波を適用することによって、また、適用時間が長いほど、発現量が有意に増加している（テューキーの検定によると、有意水準５％で有意差が認められた）。インテグリンα５については、有意に増加しているとまではいえないが、高周波を適用することによる上昇傾向があるといえる。以上より、高周波の適用は、血管内皮細胞の接着因子を増強させ、結果的に、血管構造の安定化に寄与することが示された。
From Fig. 2, the following can be said. For VE-cadherin, the expression level was significantly increased by applying high frequency and as the application time was longer (Tukey's test showed a significant difference at the significance level of 5%). Regarding integrin α5, it cannot be said that it has increased significantly, but it can be said that it tends to increase due to the application of high frequency. From the above, it was shown that the application of high frequency enhances the adhesion factor of vascular endothelial cells and, as a result, contributes to the stabilization of vascular structure.
［実験２：手術余剰皮膚への高周波の適用による血管構造変化］
実験２では、対象として手術余剰皮膚を用い、実験１と同様に、周波数１ＭＨｚ、ピーク間電圧８８Ｖｐｐの高周波を適用して血管構造の変化を確認した。高周波は、３分間適用した。高周波の適用は、繰り返し周期が１秒、デューティー比が４０％のパルス印加とした。また、高周波の適用は、１日１回行い、１日目、３日目および５日目の血管構造の変化を確認した。血管構造の変化の確認は、血管構造を可視化することによって行った。 [Experiment 2: Changes in vascular structure due to application of high frequency to surplus skin after surgery]
In Experiment 2, the surplus skin for surgery was used as the subject, and the change in the vascular structure was confirmed by applying a high frequency with a frequency of 1 MHz and an inter-peak voltage of 88 Vpp as in Experiment 1. The high frequency was applied for 3 minutes. The high frequency was applied by applying a pulse with a repetition period of 1 second and a duty ratio of 40%. In addition, high frequency was applied once a day, and changes in vascular structure were confirmed on the 1st, 3rd, and 5th days. Changes in the vascular structure were confirmed by visualizing the vascular structure.
実験２では、対象として手術余剰皮膚を用い、実験１と同様に、周波数１ＭＨｚ、ピーク間電圧８８Ｖｐｐの高周波を適用して血管構造の変化を確認した。高周波は、３分間適用した。高周波の適用は、繰り返し周期が１秒、デューティー比が４０％のパルス印加とした。また、高周波の適用は、１日１回行い、１日目、３日目および５日目の血管構造の変化を確認した。血管構造の変化の確認は、血管構造を可視化することによって行った。 [Experiment 2: Changes in vascular structure due to application of high frequency to surplus skin after surgery]
In Experiment 2, the surplus skin for surgery was used as the subject, and the change in the vascular structure was confirmed by applying a high frequency with a frequency of 1 MHz and an inter-peak voltage of 88 Vpp as in Experiment 1. The high frequency was applied for 3 minutes. The high frequency was applied by applying a pulse with a repetition period of 1 second and a duty ratio of 40%. In addition, high frequency was applied once a day, and changes in vascular structure were confirmed on the 1st, 3rd, and 5th days. Changes in the vascular structure were confirmed by visualizing the vascular structure.
実験２によって得られた、１日目と５日目の画像を図３Ａに示す。なお、高周波の適用による効果を確認するため、高周波を適用しなかった以外は上記と同じ条件で血管構造を可視化し、図３Ａには、その結果も「コントロール」として併せて示した。図３Ａより、１日目と５日目を比較すると、高周波を適用しなかった皮膚は、血管構造が痩せ細り、その一方で、高周波を適用した皮膚は、血管構造が維持されていることが確認された。
The images of the first day and the fifth day obtained by the experiment 2 are shown in FIG. 3A. In order to confirm the effect of applying high frequency, the vascular structure was visualized under the same conditions as above except that high frequency was not applied, and the result is also shown as "control" in FIG. 3A. From FIG. 3A, comparing the 1st day and the 5th day, it can be seen that the vascular structure of the skin to which the high frequency is applied is thin and thin, while the vascular structure is maintained in the skin to which the high frequency is applied. confirmed.
また、高周波を適用した皮膚および高周波を適用しない皮膚のそれぞれについて、１日目、３日目および５日目における血管の太さを測定した。測定した血管の数は、それぞれ９０本であった。測定結果を図３Ａに示す。図３Ａに示す結果より、高周波を適用することにより、血管が太くなる傾向が確認され、特に、高周波の適用を定期的に継続すると、その効果は顕著に現れることが分かった（ウェルチの検定によると、３日目は有意水準５％で有意差が認められ、５日目は有意水準１％で有意差が認められた）。
In addition, the thickness of blood vessels was measured on the 1st, 3rd, and 5th days of the skin to which high frequency was applied and the skin to which high frequency was not applied, respectively. The number of blood vessels measured was 90 each. The measurement results are shown in FIG. 3A. From the results shown in FIG. 3A, it was confirmed that the blood vessels tended to thicken by applying high frequency, and in particular, it was found that the effect was remarkable when the application of high frequency was continued regularly (according to Welch's test). On the 3rd day, a significant difference was observed at the significance level of 5%, and on the 5th day, a significant difference was observed at the significance level of 1%).
［実験１、２のまとめ］
上述したとり、血管内皮細胞を使った実験１と、手術余剰皮膚を使った実験２のそれぞれの結果より、高周波の適用が血管の安定化や血管構造の維持に関わっていることが明らかになった。 [Summary of Experiments 1 and 2]
From the results of Experiment 1 using vascular endothelial cells and Experiment 2 using surplus skin for surgery, it is clear that the application of high frequency is involved in the stabilization of blood vessels and the maintenance of vascular structure. rice field.
上述したとり、血管内皮細胞を使った実験１と、手術余剰皮膚を使った実験２のそれぞれの結果より、高周波の適用が血管の安定化や血管構造の維持に関わっていることが明らかになった。 [Summary of Experiments 1 and 2]
From the results of Experiment 1 using vascular endothelial cells and Experiment 2 using surplus skin for surgery, it is clear that the application of high frequency is involved in the stabilization of blood vessels and the maintenance of vascular structure. rice field.
１ 高周波装置
１０ 電極部
１０ａ 第１電極
１０ｂ 第２電極
２０ 制御回路 1High frequency device 10 Electrode part 10a 1st electrode 10b 2nd electrode 20 Control circuit
１０ 電極部
１０ａ 第１電極
１０ｂ 第２電極
２０ 制御回路 1
Claims (13)
- 皮膚に高周波を適用して血管構造安定化因子の遺伝子発現を増強させることを含む、美容方法。 A cosmetological method that involves applying high frequency waves to the skin to enhance gene expression of vascular structure stabilizing factors.
- 高周波の周波数が約１ＭＨｚである、請求項１記載の美容方法。 The beauty method according to claim 1, wherein the high frequency frequency is about 1 MHz.
- 高周波のピーク間電圧が５０～１００Ｖｐｐである、請求項１または２に記載の美容方法。 The beauty method according to claim 1 or 2, wherein the high frequency peak voltage is 50 to 100 Vpp.
- 高周波の適用が、デューティー比１０％～９９％のパルス印加である、請求項１～３のいずれか一項に記載の美容方法。 The beauty method according to any one of claims 1 to 3, wherein the application of high frequency is pulse application with a duty ratio of 10% to 99%.
- 前記パルス印加の周期は０．１秒～２秒である、請求項４に記載の美容方法。 The beauty method according to claim 4, wherein the pulse application cycle is 0.1 to 2 seconds.
- 前記パルス印加の周期は１秒である、請求項５に記載の美容方法。 The beauty method according to claim 5, wherein the pulse application cycle is 1 second.
- 血管構造安定化因子が、ＶＥ－カドヘリン、及びインテグリンα５から選択される少なくとも１つの因子である、請求項１～６のいずれか一項に記載の美容方法。 The cosmetological method according to any one of claims 1 to 6, wherein the vascular structure stabilizing factor is at least one factor selected from VE-cadherin and integrin α5.
- 皮膚の張りを向上させる、請求項１～７のいずれか一項に記載の美容方法。 The beauty method according to any one of claims 1 to 7, which improves the tension of the skin.
- 皮膚に高周波を適用する工程を含む、血管構造安定化因子の遺伝子発現の増強方法 。 A method for enhancing gene expression of vascular structure stabilizing factor, including the step of applying high frequency to the skin.
- 皮膚に高周波を適用する工程を含む、血管の太さの増大方法 。 A method for increasing the thickness of blood vessels, including the process of applying high frequency to the skin.
- 一対の電極と、前記一対の電極に高周波電圧を印加する制御回路と、を有する高周波美容処理装置の作動方法であって、
前記制御回路により、前記一対の電極に、血管構造安定化因子の遺伝子発現を増強させる高周波電圧を印加すること、
を含み、
前記高周波電圧は、前記一対の電極を皮膚に接触させた状態で印加される、
高周波美容処理装置の作動方法。 A method of operating a high-frequency beauty treatment apparatus having a pair of electrodes and a control circuit for applying a high-frequency voltage to the pair of electrodes.
By the control circuit, a high frequency voltage that enhances the gene expression of the vascular structure stabilizing factor is applied to the pair of electrodes.
Including
The high frequency voltage is applied with the pair of electrodes in contact with the skin.
How to operate the high frequency beauty treatment device. - 高周波のピーク間電圧が５０～１００Ｖｐｐである、請求項１１に記載の作動方法。 The operating method according to claim 11, wherein the high frequency peak voltage is 50 to 100 Vpp.
- 高周波電圧の印加が、１秒周期、デューティー比１０～９９％のパルス印加である、請求項１１または１２に記載の作動方法。 The operation method according to claim 11 or 12, wherein the application of a high frequency voltage is a pulse application having a cycle of 1 second and a duty ratio of 10 to 99%.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202180078656.3A CN116546934A (en) | 2020-12-23 | 2021-12-14 | Vascular function improving method using high-frequency electrical stimulation |
| JP2022572208A JPWO2022138347A1 (en) | 2020-12-23 | 2021-12-14 |
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2020214353 | 2020-12-23 | ||
| JP2020-214353 | 2020-12-23 | ||
| JP2021152025 | 2021-09-17 | ||
| JP2021-152025 | 2021-09-17 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2022138347A1 true WO2022138347A1 (en) | 2022-06-30 |
Family
ID=82159126
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/JP2021/046146 WO2022138347A1 (en) | 2020-12-23 | 2021-12-14 | Method for improving vascular function by applying high-frequency electrical stimulation |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JPWO2022138347A1 (en) |
| WO (1) | WO2022138347A1 (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013524946A (en) * | 2010-04-19 | 2013-06-20 | ザ プロクター アンド ギャンブル カンパニー | Combination of energy and topical composition for regulating mammalian skin condition |
| JP2018000489A (en) * | 2016-06-30 | 2018-01-11 | 株式会社メディカ ボーテ | Cosmetic device |
| JP2018504976A (en) * | 2015-02-03 | 2018-02-22 | ジョンジュ ナ | Treatment device for blood vessels in the skin |
| JP2018188365A (en) * | 2017-04-28 | 2018-11-29 | ハザー株式会社 | Cosmetic composition, cosmetic treatment device and cosmetic treatment method |
| WO2019098302A1 (en) * | 2017-11-17 | 2019-05-23 | 株式会社資生堂 | VE-CADHERIN EXPRESSION PROMOTING AGENT AND/OR INTEGRIN α5 EXPRESSION PROMOTING AGENT |
-
2021
- 2021-12-14 JP JP2022572208A patent/JPWO2022138347A1/ja active Pending
- 2021-12-14 WO PCT/JP2021/046146 patent/WO2022138347A1/en active Application Filing
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2013524946A (en) * | 2010-04-19 | 2013-06-20 | ザ プロクター アンド ギャンブル カンパニー | Combination of energy and topical composition for regulating mammalian skin condition |
| JP2018504976A (en) * | 2015-02-03 | 2018-02-22 | ジョンジュ ナ | Treatment device for blood vessels in the skin |
| JP2018000489A (en) * | 2016-06-30 | 2018-01-11 | 株式会社メディカ ボーテ | Cosmetic device |
| JP2018188365A (en) * | 2017-04-28 | 2018-11-29 | ハザー株式会社 | Cosmetic composition, cosmetic treatment device and cosmetic treatment method |
| WO2019098302A1 (en) * | 2017-11-17 | 2019-05-23 | 株式会社資生堂 | VE-CADHERIN EXPRESSION PROMOTING AGENT AND/OR INTEGRIN α5 EXPRESSION PROMOTING AGENT |
Also Published As
| Publication number | Publication date |
|---|---|
| JPWO2022138347A1 (en) | 2022-06-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Sano et al. | In-vitro bipolar nano-and microsecond electro-pulse bursts for irreversible electroporation therapies | |
| JP7402889B2 (en) | Spatial multiplexed waveforms for selective cell ablation | |
| Meng et al. | Electrical stimulation in tissue regeneration | |
| Mahnič-Kalamiza et al. | Scratching the electrode surface: Insights into a high-voltage pulsed-field application from in vitro & in silico studies in indifferent fluid | |
| US20190255321A1 (en) | Skin treatment device comprising a pulse modulator | |
| CN108472071A (en) | Method, system and equipment for the ablation of tissue for using pulse shape design | |
| CN105744984B (en) | Electrial medical apparatus | |
| US11911611B2 (en) | Method for electroporation controlled by electrical impedence measurements | |
| Lorenzo et al. | Rapid impedance spectroscopy for monitoring tissue impedance, temperature, and treatment outcome during electroporation-based therapies | |
| Pakhomov et al. | Interference targeting of bipolar nanosecond electric pulses for spatially focused electroporation, electrostimulation, and tissue ablation | |
| Chiapperino et al. | Experimental and numerical study of electroporation induced by long monopolar and short bipolar pulses on realistic 3D irregularly shaped cells | |
| WO2022138347A1 (en) | Method for improving vascular function by applying high-frequency electrical stimulation | |
| KR102556144B1 (en) | Megahertz compression of nanosecond pulse bursts | |
| Hess et al. | A novel approach for in vitro studies applying electrical fields to cell cultures by transformer-like coupling | |
| EP3841999B1 (en) | Combined cardiac pacing and irreversible electroporation (ire) treatment | |
| CN116546934A (en) | Vascular function improving method using high-frequency electrical stimulation | |
| WO2022138350A1 (en) | Method for promoting regeneration of dermis by applying high-frequency electric stimulus | |
| Polo-Corrales et al. | Recent advances in biophysical stimulation of MSC for bone regeneration | |
| Vrabec et al. | A novel waveform for no-onset nerve block combining direct current and kilohertz frequency alternating current | |
| CN114146311A (en) | Tumor electric field treatment system and electric field application method | |
| CN114177528A (en) | Tumor electric field treatment system and electric field application method thereof | |
| US20230011197A1 (en) | Device and method for stimulating skin cells using a microcurrent | |
| US20230310848A1 (en) | Using Interleaved Cooling Periods to Increase the Peak Intensity of Tumor Treating Fields | |
| CN116669645A (en) | Method for promoting dermis regeneration by application of high frequency electric stimulation | |
| KR102548891B1 (en) | Device of accelerating apoptosis by using combination of electroporation and electrolysis |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application |
Ref document number: 21910496 Country of ref document: EP Kind code of ref document: A1 |
|
| ENP | Entry into the national phase |
Ref document number: 2022572208 Country of ref document: JP Kind code of ref document: A |
|
| WWE | Wipo information: entry into national phase |
Ref document number: 202180078656.3 Country of ref document: CN |
|
| NENP | Non-entry into the national phase |
Ref country code: DE |
|
| 122 | Ep: pct application non-entry in european phase |
Ref document number: 21910496 Country of ref document: EP Kind code of ref document: A1 |