TargetCool_Boosting

Revolutionizing Targeted Solution Delivery with Supersonic CO2 Jet TargetCool Boosting Mode

TargetCool is a breakthrough FDA/CE Class II medical device that provides precise, controlled CO2 cooling for the reduction of pain, inflammation, swelling, and bruising across an array of procedures.

Skin aging is a natural process that leads to visual and structural changes

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Visible signs : Wrinkles, fine lines, age spots, uneven pigmentation, loss of elasticity, and a dull, rough texture.

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Structural changes : Decline in collagen and elastin, decreased cell turnover, and reduced moisture

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Factors for changes : Intrinsic factors : genetics, hormonal changes, metabolic processes Extrinsic factors : UV radiation, environmental factors, lifestyle choices.

Normal

Aging

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Skin aging process involves changes in multiple layers of the skin §

Epidermis: • Reduce thickness and delay keratinocyte turnover cycle • Reduce replacement rate for new cells • Decrease in Melanocytes and Langerhans cells

§

Old Skin Epidermis

Dermal-Epidermal Junction: • Dermal-Epidermal Junction flattens and this leads to a decrease in the strength of the tissue bonding in the skin.

§

Young Skin

Dermis

Dermis : • Reduces collagen, elastin, and hyaluronic acid • Decrease in capillary and lymphatic function

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Conventional approach on Anti-aging treatment : Focusing on the dermis ▪

New approach on Anti-aging treatment : Targeting on the DEJ

Dermal treatments primarily focus on stimulating collagen production and improve skin elasticity.

▪

DEJ-targeted treatments focus not only on stimulating collagen production and improving skin elasticity, like dermal treatments but also on optimizing the

vs.

interface between the dermis and epidermis.

▪

DEJ treatments can provide long-

lasting effects by addressing the underlying factors contributing to ** Both approaches have their merits and can be complementary in addressing different aspects of skin aging.

skin aging.

A comprehensive anti-aging plan may involve a combination of DEJ-targeted and dermal treatments, tailored to individual needs and desired outcomes.

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What is the DEJ (Dermal-Epidermal Junction)?

▪

The DEJ is the utmost upper part of the dermal layer that provides strong

cohesion between the epidermis and the dermis, ultimately enhancing the skin's resilience.

▪

Distinct protein components in the DEJ include collagen, integrin, and

laminin playing a vital role in maintaining integrity and functionality of the DEJ.

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Age-related changes in protein distribution and structural integrity of the DEJ §

In intrinsically aged skin, there is a significant changes occur in in structure, quantity, and distribution of collagen IV, collagen VII, and collagen XVII, integrin 4, and laminin332.

§ These changes ultimately leads to a loss of structural integrity and increased fragility of aged skin.

In skin from young volunteers, abundant staining for each DEJ component was observed. However, analysis of skin samples from intrinsically aged volunteers identified a significant diminution of signal for each of the markers examined, except perlecan.

Scale bar = 50 m, ** P < 0.01 & *** P < 0.001.

Reference: The impact of intrinsic aging on the protein composition of the dermalepidermal junction Abigail K. Langtona,b, Poonam Halaia,b, Christopher E.M. Griffithsa,b, Michael J. Sherrattc, Rachel E.B. Watsona,b,∗ (2016)

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Benefits of DEJ-targeted treatments 1

DEJ integrity

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Help strengthen the barrier, improving moisture retention and reducing transepidermal water loss (TEWL).

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Protect protein components

Can be beneficial for maintaining and restoring critical components of the basement membrane components

Activate cellular communication Facilitates the exchange of nutrients, growth factors, and signaling molecules

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Enhance growth factors and extracellular matrix Improve the synthesis and organization of collagen and elastin fibers in the dermis, ultimately benefiting the overall skin structure and appearance.

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Revolutionizing Targeted Solution Delivery with Supersonic CO2 Jet

Conventional Transdermal Drug Delivery System (TDDS) and its limitations 1

Liquid jet: Contamination of affected area and risk of bleeding and bruising due to bulky jet.

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Powder injection: limitation of versatility due to the high manufacturing cost for freeze drying solutions into mcro-powders.

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Lontophoresis: Limited to ionized drugs only.

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Sonophoresis: No proven effects of drug delivery and risk of burns

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Micro-needle: Risk of pain and side effect due to the invasive procedures. hydrophobic pores are difficult for drugs to penetrate

Methods in TDDS(Transdermal Drug Delivery System)

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A new paradigm in TDDS : the power of SUPERSONIC Solution delivery jet 1

Cryogenic drug delivery: Cryo-freeze

Game Changer

Supersonic Drug Delivery Jet

Liquid Jet

Powder Injection

Lontophoresis

Sonophoresis Micro-needleis

solution to solid microparticles and deliver at supersonic speeds at the high pressure without any other energy such as electric field, ultrasound, or heat, etc.

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Minimal invasive delivery: Minimize infection and tissue damage by delivering solutions in the form of microparticles

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Cooling aesthetic effect: Reduced pain during the procedures and post-procedural freshness through cooling

“Enhanced drug delivery efficacy” “Safe and faster therapeutic effects” Methods in TDDS(Transdermal Drug Delivery System)

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TargetCool’s Targeted solution delivery to DEJ and dermal layer 1

The solution is instantly cryo-frozen into

micro-particles and accelerated close to the speed of sound by a supersonic CO2 jet 2

Ultra high-speed cryo-frozen micro-particles penetrate through the stratum corneum and accumulate in

extremely high concentrations below the DEJ layer and penetrate extends up to the upper dermis(approx. 0.3mm).

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Facilitate the diffusion of the solution into the deep dermis layer and surrounding tissues.

*The thickness of the skin can vary in different areas. Here is a general overview of the approximate 11 thickness of the facial skin layers

Benefit using TargetCool boosting mode associated with micro-needling (Ultrasound or RF) STEP 1.

Conventional Protocol

Ultrasound or RF

1

solution delivery

STEP 2.

STEP 3.

STEP 4.

Apply solution

Rolling w/finger

LDM

▪ TargetCool’s supersonic CO2 jet enhances the delivery of solution, deep into the dermal layer with high speed and pressure.

Complete of Procedure 2

STEP 1.

New Protocol with TargetCool

Ultrasound or RF

A simple and effective method for

STEP 2.

TargetCool Supersonic CO2 jet

Complete of Procedure

CO2 cooling effect for post-procedure § Reduce pain and skin discomfort § Minizine swelling and inflammation § Induces the Bohr effect supplying oxygen to cell

tissues. § Relieve the burning sensation § Help control irritation and allergic reactions

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Higher efficacy associated with micro-needling (Ultrasound or RF) MTS Only

MTS + TargetCool

▪ A higher penetration effect when

in using MTS combination with TargetCool compared to manual hand rolling after MTS only use.

VS.

▪ With TargetCool, the solution rapidly freezes and penetrates the skin surface with high speed and pressure extended to reaching the dermis.

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Proven effect of TargetCool’s solution delivery Solution Detection Imaging Results from In Vivo Animal Skin Tissue

▪ The absorption level was

significantly high when using TargetCool boosting mode paired with MTS. ▪ With single treatment of TargetCool boosting mode shows a relatively high enough absorption level, compared to the ‘Single MTS rolling condition’.

CTL

MTS

TargetCool

MTS+TargretCool (STEMON, 2022)

◆ ◆ ◆ ◆

Controlled: Topical application MTS treatment: Topical application after MTS rolling TargetCool treatment: Application only with TC Boosting mode TargetCool treatment: Paired with MTS treatment

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Proven effect of TargetCool’s solution delivery Fluorescence Transillumination Imaging Results from Ex Vivo Human-Derived Skin Tissue HA

TargetCool

MTS+TargetCool

MTS

Approx. 0.3mm

Depth of skin penetration

Skin Absorption

[Fluorescence penetration depth] μm

[Fluorescence intensity] Approx. 0.3mm

800

TargetCool helps increase skin penetration and absorption of the solution ▪ TargetCool showed a 252% increase in fluorescent intensity and a 37% increase in penetration depth compared to the negative control group.

632 400 300

357

376

322

600

60%▲↑

235

37%▲↑

404

493%▲

375

400

200

252%▲

200

100 0

HA

MTS

MTS TargetCool +TargetCool

107

0 HA

MTS

MTS +TargetCool

TargetCool

▪ MTS+TargetCool showed the highest level of fluorescence intensity and penetration depth.

Additional benefits of CO2 skin permeation 1

Reduce inflammation: CO

2

regulates NF-kappa B, which induces the expression of genes that cause inflammation.

2

Improvement of blood circulation: CO induces vasodilation, 2

providing nutrients and oxygen to the skin tissue.

3

Oxygen supply: CO lowers blood 2

pH and induces the Bohr effect to supply oxygen to cell tissues.

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Formation of blood vessels: Increase vascular endothelial growth factor to form new blood vessels and promote blood circulation.

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Synergistic effects of **Exosome when paired with TargetCool’s CO2 treatment Applying exosomes using TargetCool Boosting Mode after micro-needling enhances the synthesis of collagen and elastic fibers at the DEJ, leading to improved epidermal-dermal adherence, mechanical support, and increased surface area.

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induces vasodilation, leading to increased blood flow and microcirculation in the DEJ region.

** Exosome optimizes skin rejuvenation and regeneration Exosomes, small extracellular vesicles, have emerged as potential therapeutic agents due to their ability to synthesize collagen and elastic fibers and counteract age-related changes in the DEJ, and restore the integrity and functionality of aged skin.

Skin Microcirculation : The application of CO2 to the skin

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Uptake and penetration of the solution: CO2-induced vasodilation promotes cellular metabolism, supports waste removal, and enhances the uptake and penetration of Exosome, ultimately contributing to skin rejuvenation.

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The 20 MHz sonogram image provides a detailed view of the DEJ and its components, the epidermal entrance echo (E), and the Subepidermal low echogenic band (SLEB).

Exosome treatments targeted on the DEJ E

E

S L E B

D

S L E B

D

▪

The subepidermal low echogenic band (SLEB) is a crucial parameter for assessing skin aging and evaluating the efficacy of solution ingredients and other procedures for skin regeneration.

▪

The integrity and continuity of the SLEB indicate a healthy and intact DEJ, which is essential for proper skin structure and function.

The 20 MHz sonogram Image 2 indicates that SLEB is continuous and well-defined, and the SLEB is marked as it extends along the DEJ. Image 1: Before Treatment

Image 2 : After Treatment

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A new paradigm for skin rejuvenation with TargeCool

STEP 1.

STEP 2.

Microscopic skin puncture with MTS

Delivery exosome into the Skin

by TargetCool

Procedure Complete

▪

Micro-needling Treatment System (MTS) creates microchannels in the skin, triggering a controlled wound healing response.

▪

This process stimulates collagen production, enhances cell turnover, and promotes the absorption of solution.

A new paradigm for skin rejuvenation with TargeCool

STEP 1.

STEP 2.

Microscopic skin puncture with MTS

Delivery exosome into the Skin

by TargetCool

Procedure Complete

▪ TargetCool boosting mode maximizes absorption of the solution, such as exosomes, deep into the dermal layer with simple and effective procedures.

B/A : MTS + Exosome(E-50) + TargetCool (only one-time treatment)

Enhancement in PIH from Acne

Enhancement in Jawline Lifting

Before

After

Before

After Provided by Dr. Youngseob Lee

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B/A: LDM(Local Dynamic Micro wave) + Exosome(E-50) + TargetCool (only one-time treatment)

Enhancement in Infraorbital dark circles

Enhancement in Nasolabial folds

Before

After

Before

After Provided by Dr. Youngseob Lee

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B/A: Laser treatment + Solution + TargetCool (without MTS)

Enhancement in Rosacea w/ Blue LED light therapy

Before

After

Enhancement in skin elasticity and brightness w/ Revs RMT

Before

After Provided by Dr. Tony Seo

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A new paradigm for skin rejuvenation with ’TargeCool’ Boosting Mode

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Three.

Interchangeable modes.

One. revolutionary device.

TargetCool is compatible with three nozzle types configured to spray cryogen at a controlled temperature to the target area.

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Notice: This document contains information intended solely for INTERNAL TRAINING NOT for EXTERNAL DISTIRIBUTION. It is strictly prohibited to distribute, share, or disclose any part of this document to external entities.

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