Confidential

Study Report

Preclinical Study to Evaluate the Safety and Efficacy of the High-Frequency

Study Title
Stimulator on the Skin and Subcutaneous Tissue

Receipt Date November 19, 2018

Study No. 20180142 Study
Completion December 30, 2018
Date

Study Period November 19, 2018 – December 30, 2018

Executing Institution Department of Dermatology, Chung-Ang University Hospital

Address 102 Heukseok-ro, Dongjak-gu, Seoul, South Korea

Study
Principal Investigator Beom Joon Kim
Institutions
Tae-Rin Kwon, Jong Hwan Kim, Sung Eun Lee, and Byung
Researchers
Chul Lee

Phone Tel: 02-6299-3081

Company Name K1 Med Co., Ltd.

CEO Sang Sik Kim

Room 205, Woolim E-Biz Center II

Address
12 Digital-ro, 33-gil, Guro-gu, Seoul, South Korea
Sponsor
Name Senior Manager Chang Ho Park

Person in
Phone 02-871-0657
Charge

E-mail 90895383@hanmail.net
 Principal Investigator CV

 Beom Joon Kim (Head, Professor, Department of Dermatology Chung Ang

University Hospital, MD, PhD, Dermatologist)

[Work Experience]

Duration Contents

• Obtained M.D. degree (License no. 71628, Ministry of Health and

2000~
Welfare)
• Board-certified Dermatologist (License no. 1486, Ministry of Health and
2005~
Welfare)

2005-2006 • Clinical fellowship, Dermatology, Seoul National University Hospital

• Invited reviewer, British Journal of Dermatology (BJD)
2005-2015 • Reviewer, Journal of the American Academy of Dermatology
• Reviewer, International Journal of Dermatology (IJD)

2006-2007 • Assistant professor, Dong-Kuk University Ilsan Hospital

• Assistant professor, Department of Dermatology, Chung-Ang
2007-2010
University College of Medicine
• Invited reviewer, Clinical and Experimental Dermatology (CED)
2007-2015 • Invited reviewer, Dermatologic Surgery
• Member, Editorial Board, Chung-Ang Journal of Medicine

2010~ • Member, Editorial Board, Asian Aesthetic Guide

• Medical Device Clinical Specialist, Advisory Committee, Ministry of
2011-2014
Food and Drug Safety
• Associate Professor, Department of Dermatology, Chung-Ang
University College of Medicine
2011~
• Committee member, Medical Equipment Board, Ministry of Health and
Welfare

2012 • Member, International Advisory Board, Aesthetics Asia 2012

• Member, Editorial Board, Journal of Cosmetics, Dermatological
2012~ Sciences, and Applications
• Member, Editorial Board, Annals of Dermatology
• Professor, Department of Dermatology, Chung-Ang University Hospital
2013~ • Member, Editorial Board, Journal, Dermatology Aspects
 • Member, Evaluation Board, Institute of Planning and Evaluation for
Technology in Food, Agriculture, and Forestry

• Member, Self-regulating Review Committee, Ministry of Food and Drug

Safety
2013-2015
• Member, Steering Committee, PM system, Korea Health Industry
Development Institute, Ministry of Health and Welfare
• Member, Organization Committee, 3rd Eastern Asia Dermatology
2014
Congress
• Head, Department of Dermatology, Chung-Ang University Hospital
• Member, Education Committee, Korean Academy of Asthma, Allergy,
and Clinical Immunology
• Member, Editorial Board, Plastic and Aesthetic Research
• Member, Editorial Board, Allergy Asthma & Respiratory Disease
2014~ • Member, Editorial Board, International Journal of Dermatology
Research and Therapy
• Specialist, Central Pharmaceutical Affairs Council, Ministry of Food
and Drug Safety
• External specialist, National Institute of Food and Drug Safety
Evaluation
• Member, Editorial Board, Investigative Dermatology and Venereology
Research
2015~ • Member, Editorial Board, Journal of Cosmetology & Trichology
• Member, Editorial Board, Journal of Procedural Dermatology
• Expert commissioner, National Court Administration
• Member, Editorial Board, World Journal of Methodology
• Dean, Biomedical Research Institute, Chung-Ang University Hospital
• Expert member, Korean Standards (KS) of Medical Product, Ministry of
Food and Drug Safety
• Member, Editorial Board, Journal of Dermatology and Plastic Surgery
2016~ • Member, Editorial Board, Source Journal of Investigative Dermatology
• Member, Medical Device Adverse Events Review Committee, Medical
Device Information & Technology Assistance Center
• Member, Editorial Board, The Society of Cosmetic Scientists of Korea
• Member, Editorial Board, Current Updates in Dermatology Research
• Member, Editorial Board, Journal of Case Reports & Imaging
 • Member, Policy Advisory Committee, Ministry of Food and Drug Safety
• Member, Communication Advisory Committee, Ministry of Food and
Drug Safety
• Committee member, Plastic and Aesthetic Research

• Committee member, 38th annual meeting of the International Society

for Dermatologic Surgery
2017
• Member, International Science Committee, 8th annual meeting of the
International Congress of Aesthetic Dermatology
• Member, Specialists Council, Medical Device Re-Evaluation, Ministry
of Food and Drug Safety
• Member, Editorial Board, Journal of Dermatology & Cosmetology
• Member, Editorial Board, Clinical Dermatology Open Access Journal
• Member, Editorial Board, Allergy Asthma & Respiratory Disease
2017~ • Member, Editorial Board, The Scientific Pages of Surgical Dermatology
• Member, Editorial Board, MDfaculty
• Member, Medicine Review Advisory Board, Ministry of Food and Drug
Safety
• Member, Medical Device Adverse Events Review Board, Medical
Device Information & Technology Assistance Center
• Member, Organizing Committee, 2018 Asia International Master
2018
Course on Aging Science
• Member, Medical Advisory Committee, Health Insurance Dispute
Mediation Committee
2018~
• Member, Editorial Board, Journal of Dermatology Forecast
• Review member, Medical Device Adverse Event Review Committee
[Awards]

Duration Contents
• Scholarship, The Korean Society for Investigative Dermatology
2003
• Novartis Award, Korean Society for Medical Mycology
• Best Paper Award, Symposium of Korean Information Processing
2006
Society
• Dr. Paul Janssen Award, Korean Dermatological Association
2007 • Medical Scientist of the Year (2007). International Biographical Centre
• Best Poster Award, Symposium of Korean Dermatological Association

2008 • Scholarship, The American Academy of Dermatology

2009 • Academic Research Award, Chung-Ang University

• “Aesthetic Dermatology,” selected as an outstanding academic book
by the Ministry of Culture, Sports, and Tourism
• Vision 2010 Grand Prize, Seoul Newspaper
2010
• Outstanding Paper, Korean Society of Medical Mycology
• Scholarship, Korean Hair Research Society and World Congress for
Hair Research
• Excellent Assessor, Basic Research Projects, National Research
Foundation of Korea, Ministry of Educational Science and Technology
2011
• Chungsan Outstanding Paper Award, Korean Academy of Asthma,
Allergy, and Clinical Immunology
• Dong-ah Academic Award, Korean Dermatological Association
2012 • Excellent Professor, Chung-Ang University Industrial-Academic
Cooperation Foundation
• Textbook Compilation Committee Recognition, Dermatology (6th
2013 edition)
• Academic Contribution Award, Chung-Ang University Hospital

2014 • Presidential Citation, Man of Merit, Science and Technology Promotion

• 25th Science Technology Outstanding Paper Award, Korean
2015
Federation of Science and Technology Societies
• Academic Contribution Award, Chung-Ang University
2016
• PR Special Award, Chung-Ang University
• Academic Contribution Award, Chung-Ang University
2017
• Outstanding Paper (Internal medicine part), Chung-Ang University

2018 • Ming-Chien Kao Award, Japanese Laser Therapy Journal

[Academic Activities]

Duration Contents
2000~ • Member, Public Relations Committee, Korea Medical Association
• Member, Korean Dermatological Association
2001~
• Member, Korean Society for Investigative Dermatology

2006~ • Member, American Academy of Dermatology

2007-2011 • Member, Educational Committee, Korean Dermatological Association

• Member, Korean Society for Medical Mycology
2009~ • Journal reviewer, Korean Dermatological Association
• Journal reviewer, Korean Journal of Dermatology

2011-2013 • Member, Publication Committee, Korean Dermatological Association

• Member, Textbook Compilation Committee, Korean Dermatological
2011~ Association
• Board member, Korean Society for Pigment Cell Research
• Member, Advisory Committee, Korean Society of Hair Restoration
2012~
Treatment
• Board member, Korean Society for Aesthetic and Dermatologic
2013-2014
Surgery

2013~ • Member, Korean Atopic Dermatitis Association

• Director at Large, Korean Hair Research Society
• Member, Expert Committee, National Research Foundation of Korea
Basic Science Research Program, Medical Research Center
• Member, Corporate Relations Committee, Korean Dermatological
2014~ Association
• Assistant administrator, Finance Committee, Korean Dermatological
Association
• Member, Computer Information Communication Committee, Korean
Dermatological Association
• Program director, Korea Association of Anti-Aging Medicine
2015~ • Member, Legislation Committee, Korean Academy of Asthma, Allergy,
and Clinical Immunology

2016~ • Public relations director, Korean Hair Research Society

• International relations director, Korea Association of Anti-Aging
2017~ Medicine
• Member, Dermatologist Board Exam Question Preparation Committee
 for 2018, Korean Dermatological Association
• Member, Corporate Relations Committee, Korean Society for
Investigative Dermatology
• Member, Information Committee, Korean Society for Investigative
Dermatology
• Public relations director, Korean Hair Research Society
2018~ • Member, Board of Directors, Korean Society for Skin Barrier Research
 Table of Contents

#Summary

1. Overview and Background.......................................................................................... 14

2. Test Device ................................................................................................................. 15

3. Materials and Methods............................................................................................... 16

4. Results

4-1. Efficiency evaluation.............................................................................................. 23

4-2. Safety evaluation................................................................................................... 24

4-3. Efficacy evaluation................................................................................................. 33

5. Conclusion.............................................................................................................. 36

6. References.............................................................................................................. 37
 Overview
Preclinical Study to Evaluate the Safety and Efficacy of the High-Frequency Stimulator on
Study title
the Skin and Subcutaneous Tissue

Study
Study no. 20180142 November 19, 2018 – December 30, 2018
period

K1 Med Co., Ltd. / Sang Sik Kim

Sponsor Room 205, Woolim E-Biz Center II
12 Digital-ro, 33-gil, Guro-gu, Seoul, South Korea

Study Principal
Department of Dermatology, Chung- Beom Joon Kim
institution investigator
Ang University Hospital

Test devices SNE-7100, MD-308 (one of each)

1. Efficiency evaluation
- Skin surface temperature measurement
2. Safety evaluation
- Macroscopic evaluation: Macroscopic evaluation of burn and inflammation
Test items
- Equipment evaluation: Folliscope (LeedM, Seoul, South Korea), dermascope
(DermLite Pro, California, USA)
- Histological evaluation: H&E (hematoxylin and eosin), Masson’s trichrome, NBTC
(nitroblue tetrazolium chloride) stain

- Preclinical evaluation was conducted to obtain data on the safety and efficiency of
SNE-7100 (RF stimulator).

- The formation of a 38-45℃ skin surface temperature with high-frequency radiation

under each study condition was confirmed.

- The macroscopic and device evaluation showed that there was no damage or

Study contents laceration on the skin surface in the high-frequency radiation region.

and results - H&E stain showed that there was no inflammation or adverse events in the skin tissue
in the high-frequency radiation group. The evaluation of the cell viability rate through
NBTC stain showed that there was no difference between the high-frequency
radiation group and the non-radiation group.
Based on the above results, the safety and efficiency of the three types of probes (RET,
CET, and bipolar types) of SNE-7100 (RF stimulator) sponsored by K1 Med Co., Ltd.
were confirmed.
1. Overview and Background

The high-frequency stimulator converts radio frequency (RF) to thermal energy by

applying RF to the living tissues in the human body, and obtains clinical and aesthetic effects

by increasing the body’s internal temperature from the thermal energy. In addition, it has

been reported that the high-frequency stimulator can increase the temperature, dilate the

vessels, increase the blood flow, and alleviate pain. The mechanism of action of this

equipment is adding a high-frequency current to the tissue and generating thermal energy

converted from high-frequency energy, which will increase the tissue temperature, dilate the

vessels, increase the blood flow in the tissue, and alleviate the pain in the affected area.

The treatment methods of physical therapy using a helium or infrared lamp, thermal

therapy, and high-frequency stimulator radiation have been developed and have become

widely used of late.

High frequency is defined as radio transmission frequency (300-1,200 kHz). A high

frequency in therapeutic equipment, however, means a high-frequency current. Although the

general common alternating current (AC) uses a 60 Hz frequency, therapeutic equipment

uses 300 kHz to hundreds of kHz AC. In other words, a treatment method using a high

frequency adds a high-frequency current to the biological tissue in the human body and

obtains clinical and cosmetic effects using frictional heat from the oscillating intracellular ions

between the cathode and the anode.

When thermal energy from a high frequency delivers heat with an average temperature of

38-45℃ into the deep part repetitively and continuously, the vessels are dilated. This

promotes healthy metabolism and multiplies the self-healing ability of the human body.

Furthermore, it helps in blood and lymph circulation, sterilizes due to the high temperature,

and induces collagen generation in the dermal layer of the skin tissue. Also, heat loosens

tight muscle tissues and is known to produce excellent effects for obesity treatment, pore

tightening, wrinkle removal, hair growth, and pain alleviation.

 The traditional high-frequency stimulator operates the generator to generate a high

frequency, and fixes the large electrode pad part, which is several times bigger than the

electrode (usually 10 times bigger), by attaching to a wide area (e.g., the back or abdomen)

of the human body. It then attaches electrodes releasing high-frequency energy to the area

that needs treatment or aesthetic procedures. At this time, the practitioner fixes the electrode

pad part or attaches an electrode to the human body, and electrodes are attached to several

parts of the body for about 10-30 minutes, for the procedure.

Heat is transferred largely in two parts. Resistive electrode transfer (RET) uses the

principles of generating body heat by accelerating the electronic activity from the center of

the tissue between the electrode and the opposite electrode. This is a deep-heating

electrode transfer method that can be applied to subcutaneous and visceral fat. Capacitive

electric transfer (CET) uses the principle of generating body heat through active ionic activity

around the electrode attached to the skin, and acts on specific fat cells and helps detoxify

the tissue by activating venous circulation.

The high-frequency stimulator secures skin adverse-reaction results and ensures the

safety of the biological tissue due to the characteristics of heat generation, by conducting

procedures directly on the human body. Therefore, efficiency and safety evaluations are

essential (Ministry of Food and Drug Safety No. 2013-183 (’13.5.8) “Regulations for

Approval, Notification, and Review of Medical Devices,” the Article 24, paragraph 1,

subparagraph 4 regulation, data on efficiency).

Efficiency data is among the required data for the review of technical documents, and

specifically, it is applicable to data proving the efficacy of medical devices used for

diagnostic or therapeutic purposes. If the efficiency of the product cannot be confirmed

based on an in-vitro study, it should be confirmed based on animal study data. In this case,

for the criteria of animal study data and study methods, papers should be referred to.

This study was conducted to secure safety and efficiency data, and conducted

comparative evaluation of the SNE-7100 high-frequency stimulator (RET, CET, and bipolar
types) and the already-approved INDIBA MD-308 provided by K1 Med, Co., Ltd.

2. Test Devices

This section was written based on the data provided by the sponsor.

2-1. SNE-7100

[1] Regulations on the medical device item and the grades of the item

① Item name: High-frequency stimulator

② Classification no. and grade: A16085.01 [3]

[2] Product specifications

① Product name: SINESON

② Model name: SNE-7100

③ Item license no.: Will be written after the approval

④ Weight of packaging unit: 18 kg, 1 set

⑤ Rating: 220 V, 60 Hz

⑥ Power consumption: 350 VA

⑦ Protection type and/or degree of protection from electric shock: Grade 1 equipment,

BF-type equipment
2-2. Storage and Handling

The study device had been stored indoors at room temperature, avoiding exposure to direct

light and humidity (temperature: 5-60℃; humidity: 0-90%). The device was returned to the

sponsor after the study completion.

3. Materials and Methods

3-1. Study Animals

The study was conducted after obtaining the approval of the Institutional Animal Care and

Use Committee operated by CRONEX, Co., Ltd. White Yorkshire pigs with 40-50 kg weights

were purchased from CRONEX Co., Ltd. (Gyeonggi, South Korea) and were used in this

study (individual no. CU-74, 75). They were raised in SPF under the optimal environmental

condition (temperature: 22±3℃; humidity: 50±10%; cleanliness: 1,500; ventilation: 15T/HR;

internal pressure: 3 mmHg; air velocity: 5 cm/sec; noise level: 10 dB) and were evaluated in

GLP facilities.

3-2. Reason for Selecting the Study Animals

The skin of the white Yorkshire pig has a similar skin absorption power, allergic response,
and epithelial structure as the human skin; thus, it is appropriate for dermal-administration

skin test evaluation. Furthermore, it is convenient to be utilized for skin test evaluation as it

has less hair than other types.

3-3. Study Group and Equipment Radiation

Before radiating the high-frequency stimulator, the study device, anesthesia was conducted

by administering general anesthetics, mixing 50 Zoletil and 2 Narcoxyl at a certain ratio, and

administering the inhalation anesthetics isofluorane:O2 (2.5:2.5) as an in-depth anesthetic

agent. After shaving the hair on the Yorkshire pigs’ back areas, each Yorkshire pig back

area was subdivided and irradiated on using the SNE-7100 high-frequency stimulator (RET,

CET, and bipolar types) and the already-approved INDIBA MD-308, under the equipment

conditions. Equipment radiation was conducted after installing grounding connection to the

lower part of the pig’s abdomen, and radiation was conducted after sufficient and even

application of RF-exclusive lotion for 10 minutes, like massaging the target areas.

<Study device (K1 Med SNE-7100) group>

Table 1. High-frequency radiation group

G1 RF non-radiation group

0.5 MHz
G2 A
MONOPOLAR Representative value: 350 VA + 10%

RET

handpiece

0.5 MHz
G3 B
70% of the representative value, “A”
G4 C 0.5 MHz

85% of the representative value, “A”

G5 Normal 0.5 MHz

MONOPOLAR

CET

G6 handpiece Deep 0.3 MHz

BIPOLAR
G7 0.5MHz bipolar handpiece (probe)
handpiece

Figure 1. High-frequency radiation section diagram (SNE-7100).

 <Control device (INDIBA MD-308) group>

Table 2. High-frequency radiation group

G1 RF non-radiation group

G2 A Stage 1

MONOPOLAR

RET
G3 B Stage 5
handpiece

G4 C Stage 9

G5 A Stage 1

MONOPOLAR

G6 CET B Stage 5
handpiece

G7 C 9 단계
 Figure 2. High-frequency radiation section diagram (INDIBA MD-308).

3-4. Study Schedule

Table 3. Study schedule

Day 0

(immediately
Day 1 Day 7 Day 15 Day 30
after

treatment)

Clinical evaluation √ √ √ √ √

Folliscope

(LeedM, Seoul, √ √ √ √ √

South Korea)

Dermascope

(DermLite Pro, √ √ √ √ √

California, USA)
 H&E, M&T staining √ √ √ √ √

NBTC staining √ √ √ √

Figure 3. Study schedule diagram.

3-5. Efficiency Evaluation

After anesthetizing the Yorkshire pigs, the target areas for high-frequency radiation were

shaved. After shaving, 3-cm-wide and 3-cm-high areas were drawn in the study area, and

they were irradiated on according to the contents of section 3.3 and their conditions. After

the use of each probe, a heat camera was used to evaluate the temperature formatted in the

skin surface from the high-frequency stimulator radiation.

3-6. Safety Evaluation

3-6-1. Macroscopic evaluation

To evaluate the skin irritation due to high-frequency stimulator radiation using the study

device, the skin conditions of the radiated and non-radiated areas were observed.

Macroscopic evaluation was conducted by dermatology specialists right after radiation (day

0) and 1 day (day 1), 7 days (day 7), 15 days (day 15), and 30 days (day 30) after radiation.

Abnormal findings like inflammation, burn, rash, and urticaria were obtained from the clinical

evaluation.

3-6-2. Device evaluation

To observe the changes in the skin surface condition due to high-frequency radiation using

the study device, a polarized photograph was taken using a dermascope, and a

magnification photograph was taken using a folliscope. These were done together with

macroscopic evaluation.

3-6-3. Histological evaluation

H&E, M&T, and NBTC staining were conducted for histopathological evaluation and to

evaluate the cell viability rates of the skin irradiated with a high-frequency stimulator using

the study device. The skin tissues from 8mm punch biopsy right after radiation (day 0) and 1

(day 1), 7 (day 7), 15 (day 15), and 30 days (day 30) after radiation were stored in a freezer

at -20℃. Using a surgical blade, the high-frequency radiation areas were vertically incised 8

mm deep. Some of them were fixed using a 10% neutral buffered formalin (NBF) solution

and then embedded in paraffin. 5μm sections were prepared and stained using hematoxylin

and eosin, and Masson’s trichrome was used for optical-microscope observation. Other

tissues were stained using nitroblue tetrazolium chloride (NBTC, Sigma, USA), for

photographing using a dermascope to identify any necrosis area in the tissue.

4. Study Results
4-1. Efficiency Evaluation

For skin care improvement using a high-frequency stimulator, the increased temperature of

the heat formed on the skin surface should be identified. Therefore, in this study, the skin

surface temperature was measured using a thermal camera, in accordance with the

condition of the SNE-7100 high-frequency stimulator (RET, CET, and bipolar types) and of

the already-approved equipment, INDIBA MD-308. For the control equipment, the maximum

temperature was identified as 40.5℃, and it was confirmed to be safe, without any

macroscopic problem, even with heat sensation on the skin right after use. Furthermore, it

was confirmed that all the three probes of the study device are safe (Figure 4-1, 4-2).
 Figure 4-1. Study progress pictures.

Figure 4-2. Identifying the temperature on the skin surface using a thermal camera

before (0) and after the application of the CET, RET, and bipolar-type high-frequency

stimulators.

4-2. Safety Evaluation

4-2-1. Macroscopic evaluation

To evaluate the macroscopic skin irritation due to high-frequency stimulator radiation, the
skin conditions on the radiated and non-radiated areas were evaluated. All the evaluations

were conducted as a macroscopic evaluation by dermatology specialists right after radiation

(day 0) and 1 day (day 1), 7 days (day 7), 15 days (day 15), and 30 days (day 30) after

radiation. From the radiation with the SNE-7100 high-frequency stimulators (RET, CET, and

bipolar types) and the already-approved equipment, INDIBA MD-308, based on the

conditions of each equipment, there was no skin adverse reaction including epidermis

damage, erythema such as blister, and heat damage in the macroscopic evaluation (Figure

5-1, 5-2).
 Figure 5-1. Radiation from each probe of the high-frequency stimulator on pig skin.

Figure 5-2. DSLR camera photograph and macroscopic evaluation before (0) and after

the application of the CET, RET, and bipolar-type high-frequency stimulators.

4-2-2. Device evaluation

To observe the changes in the skin surface condition due to high-frequency stimulator
radiation, polarized photographs were taken using a dermascope, and a magnification

photograph was taken using a folliscope. Radiation under each condition was conducted

using the SNE-7100 high-frequency stimulator (RET, CET, and bipolar types) and the

already-approved equipment, INDIBA MD-308. When the high-frequency stimulator radiation

group was compared to the non-radiated group, no skin surface damage or erythema was

found right after radiation (day 0) and 1 day (day 1), 7 days (day 7), 15 days (day 15), and

30 days (day 30) after radiation (Figure 6).

<Study device (K1 Med SNE-7100) group result>

\
 <Control device (INDIBA MD-308) group result>

Figure 6. Magnification and polarized photographs of the skin surface right after high-

frequency stimulator radiation (day 0) and 1 day (day 1), 7 days (day 7), 15 days (day

15), and 30 days (day 30) after radiation - dermascope, folliscope (original

magnification: x15).

4-2-3. Histological evaluation

4-2-3-1. H&E staining

H&E staining was conducted for the histopathological evaluation of the skin that had been

irradiated with the high-frequency stimulator using the study device. 8mm punch biopsy was

conducted right after radiation (day 0) and 1 day (day 1), 7 days (day 7), 15 days (day 15),

and 30 days (day 30) after radiation, and the skin tissues were stored in a -20℃ freezer.

Using a surgical blade, the high-frequency stimulator radiation areas were vertically incised 8
mm deep. Some of them were fixed using a 10% NBF solution and then embedded in

paraffin, and 5μm sections were prepared and stained using hematoxylin and eosin for

observation using an optical microscope. There was no abnormal infiltration of the

inflammation cells or dermis necrosis in all the skin tissues irradiated with both the study and

control devices, and there was no epidermis damage or dermis adverse event (Figure 7).

<Study device (K1 Med SNE-7100) group result>

 <Control device (INDIBA MD-308) group result>

Figure 7. H&E staining - microscope (OLYMPUSIX71, Japan, x100).

4-2-3-2. NBTC staining

NBTC staining was conducted to evaluate the cell viability rate of the skin tissues that had

been irradiated with the high-frequency stimulator using the study device. 8mm punch biopsy
was conducted right after radiation (day 0) and 1 day (day 1), 7 days (day 7), 15 days (day

15), and 30 days (day 30) after radiation, and the biopsy skin tissues were stored in a -20℃

freezer. Using a surgical blade, the high-frequency-radiated areas were vertically incised 8

mm deep, and some of them were put in a 500µM NBTC solution for 24 hours. Then the skin

tissues in the NBTC solution were transferred to a petri dish for polarized photography.

When there was a smudge in the frozen tissue after NBTC staining, a dark-blue cytoplasmic

pigment was formed due to the NBTC decrease by nicotinamide adenine dinucleotide

(NADH). NADH promptly decreases the cell apoptosis; thus, the cells with a blue smudge

from the NBTC staining showed viability, and the regions without a blue smudge presented

coagulation necrosis. The period and group comparison showed a dark-blue cytoplasmic

pigment in all the surrounding tissues, including the epidermis. Normal cell viability was

identified in the skin tissue that had been irradiated with both the study and control devices,

under their own conditions (Figure 8).

<Study device (K1 Med SNE-7100) group result>
 <Control device (INDIBA MD-308) group result>

Figure 8. NBTC staining - dermascope close-up pictures.

4-3. Efficacy Evaluation

Collagen is a major ingredient of the skin dermis and can cause skin wrinkle formation as it

decreases by age. As identified in clinical studies, the efficacy of the high-frequency

stimulator was investigated using pig skin tissue to identify the patterns of collagen formation

within the tissue. The high-frequency stimulator system transfers heat to the inside of the

skin through comprehensive actions, including heat and immune responses, and the

temperature of the deep part further down from the skin surface reaches 38-45℃. This

induces the regeneration of collagen and elastic fiber by transferring the heat to the inside of

the skin, and complex processes, including the synthesis and restructuring of the collagen

fiber, are carried out to restore the cell and tissue.

4-3-1. Masson’s trichrome staining

In this study, the effects of collagen synthesis in the dermis of the skin were investigated

using each probe, and the morphological changes of the collagen fiber during the tissue

restoration process after high-frequency stimulator application were observed. The optical-

microscope observation of the loss and degenerative changes of the elastic fibers in the skin

tissues that had been irradiated with the SNE-7100 high-frequency stimulator (RET, CET,

and bipolar types) and the already-approved equipment, INDIBA MD-308, under each

condition revealed that on day 15, the tissues showed that although the collagen fiber had a

low density, it was relatively more dense and had regular arrangements in all the high-

frequency-radiation-treated groups than in the non-treated group (Figure 9).

<Study device (K1 Med SNE-7100) group result>
 <Control device (INDIBA MD-308) group result>

Figure 9. Masson’s trichrome staining - microscope (OLYMPUS IX71, Japan, x100).

5. Conclusion

In this study, the skin temperature increases due to the heat generation from high-frequency

stimulator radiation were investigated and compared using the SNE-7100 high-frequency

stimulator (RET, CET, and bipolar types) and the already-approved INDIBA MD-308 of K1
Med Co., Ltd. There was no skin surface damage, adverse inflammation reaction, laceration

reaction, or tissue necrosis due to high-frequency stimulator radiation from each device.

Furthermore, the observation of the changes, loss, amount, and shape of the elastic fibers in

the skin dermis showed that the generated heat infiltrated the inside and induced the

regeneration of collagen and elastic fibers.

This study secured safety and efficacy data on the efficiency of the high-frequency

stimulator equipment SNE-7100 (RET, CET, and bipolar types).

6. References

1) Radiofrequency in cosmetic dermatology, KL Beasley, RA Weiss - Dermatologic clinics,

2014

2) Radiofrequency-based treatment in therapy-related clinical practice – a narrative review.

Part I: acute conditions, B Kumaran, T Watson - Physical Therapy Reviews, 2015

3) Effect of capacitive and resistive electric transfer on haemoglobin saturation and tissue

temperature, Y Tashiro, S Hasegawa, Y Yokota - International Journal of Hyperthermia,

2017

4) Effect of Capacitive and Resistive electric transfer on changes in muscle flexibility and

lumbopelvic alignment after fatiguing exercise, Y Yokota, T Sonoda, Y Tashiro, Y Suzuki-

Journal of Physical Therapy Science, 2018

5) Capacitive Radiofrequency Skin Rejuvenation, MT Abraham, JJ Rousso - Cosmetic

Surgery, 2013
 - Notice -

1. This study was conducted with the devices provided by the study sponsor, and it does not guarantee the quality of all the

products.

2. This report may not be used for promotion, propagation, advertisement, and lawsuit purposes without the approval of this
institution, and should not be used for any purpose other than the approved ones.