SE-tripeptide.com under website construction SupadElixir INCI named tripeptides Distributed by Equipforskin Co Ltd. www.equipforskin.com AA. About us Company Overview SupadElixir Co Ltd was founded by Prof. Dr. JH Hahn, PhD. in December of 2009 as a bioventure company for the research, development, manufacturing and marketing of biomimetic Tri-Peptides for bio-drugs, OTC drugs and cosmetic / cosmeceutical products. SupadElixir has developed lots of the excellent tri-peptides with less than 500 Dalton molecular weight that are to be percutaneously penetrated without any delivery agents or additives. Such ultra-light 500 Dalton molecular weight tripeptides are quite innovative and effective not only for the development of the new bio-drugs, but also for their cosmetic and OTC drug applications as subcutaneously penetrating ingredients. SupadElixir has many INCI named and PCPC (Personal Care Products Council, formerly CTFA) registered tripeptides as cosmetic ingredients and plenty of additional new tri-peptides are able to be applied for PCPC cosmetic ingredients. Major Businesses 1. Research and development of new and efficient tri-peptides 2. Research and development of new bio-drugs using tri-peptides 3. Manufacturing and sales/marketing of cosmetic/ cosmeceutical products using tripeptides 4. Manufacturing and sales/marketing of OTC new drugs using tripeptides Company History - Established in 2009 as a bio-venture company. - In 2012, While focusing on the research and development of bio new drugs using tri-peptides, in 2012, a new business of cosmetic, cosmeceutical and OTC drug products using SupadElixir s own exclusively patented tri-peptides was launched. - In 2013, - 4 SE-tripeptides like Synepin, Syndermin, Binterin and Tenefrin were INCI-named and PCPC registered as cosmetic ingredients in 2013. - Some of our major tri-peptides were registered for PCT and patents in the US, Japan, EU and China. 1
- In 2013, The development project of anti-inflammation and soothing cosmetic product using our Binterin anti-inflammation tri-peptide was selected as a promising subject by the Korean SMBA (Korean Small and Medium Business Administration). - In 2014, - Tryprime (3P) serum and cream product for wrinkle enhancement was commercially produced. - Bamboo Beauty, a whitening combo of aqua skin and lotion, was also successfully launched for the market. - Dr Hahn soothing serum, cream and masks were also launched and started to be commercialized by our US distributor successfully. - Some more tri-peptides were applied for PCT patents and Enfibin, Adiponin and Winhibin were INCI- named and PCPC- registered. -In 2015, - Binterin, Winhibin and Enfibin tripeptides were applied for the US, Japan and PCT patents. - Ilonerin tri-peptide was also INCI named and PCPC registered. - Mitefin whitening tripeptide was selected as one of the promising development projects by SMBA. - 4 x AquaPeel products, a post laser soothing product and a diet body-managing cosmetic product were also launched. - In addition to Binterin soothing mask and serum, 3P serum was also launched for the US market. - In 2016, - 3P serum and cream, Dr Hahn soothing and several OEM/ODM products started to expand the markets to the US, South Asia and other countries. - In addition to cosmetic markets, the market is extended to OTC drug markets in the US with a new development of analgesic, skin protectant and post-sunscreen soothing OTC products. 2
BB. Features of our exclusively patented Tripeptides, all INCI names registered. 1. Unlike most of the existing high molecular weight (MW) polypeptides in the skin care markets, all of our SE-tripeptides consist of 3 amino acid (AA) sequence with a low MW. 2. Our SE-tripeptides less than 500 Dalton (Da) can be transdermally penetrated into either epidermis or dermis layers without any delivery agents. * 500 Da rule The general rule is that almost nothing larger than 500 Daltons can pass through the skin barrier (Experimental Dermatology). This is based off of a few things: 1. Nearly all of the contact allergens that we know of are smaller than 500 Daltons. 2. The most common pharmaceutical ingredients applied topically are under 500 Daltons. 3. Effective drugs that contain a transdermal delivery system are under 500 Daltons. Binterin (SE209), CD99-derived tripeptide, can easily penetrate mouse dorsal skin without delivery agents. 3
3. Our SE-tripeptides properly interact with specific target proteins. For example, they bind to receptors on the cell surface as ligands and subsequently control intracellular signaling events.as agonist, antagonist or inverse agonist as following. -Agonists SE-Tripeptide that occupy receptors and activate them. -Antagonists SE-Tripeptide block receptor activation by agonists. -Inverse agonist SE-Tripeptide induces a pharmacological response opposite to that agonist. 4
4. SE-tripeptides are safe and stable at room temperature or even at 50 for 4 weeks. HPLC data shows that SE-tripeptide preserves the structural integrity in the harsh environmental conditions. Control. After 4 weeks at 50 5) SE-tripeptides are able to be sterilized without decomposition in an autoclave at 121 for 15 minutes. This fact that our tripeptides can be sterilized at steamed-autoclave proves that tripeptides are so stable and may be able to be clinically applied after selfsterilization in future. Control. After autoclave 5
CC. List of SE-tripeptides with INCI name registration & applications 1. List of INCI named SE-tripetides INCI name (peptide No.) Palmitoyl Tripeptide- 52 Amide (SE201) Palmitoyl sh- Tetrapeptide- 2 Amide (SE203) Palmitoyl sh- Tripeptide-1 Amide (SE204) Palmitoyl sh Tripeptide-2 Amide (SE205) Palmitoy shl Tripeptide-3 Amide (SE208) Palmitoyl sh Tripeptide-4 Amide (SE209) Palmitoyl Tripeptide- 54 Amide (SE214) Palmitoyl Tripeptide- 53 Amide (SE215) Trade Name Enfibin Ilonerin Syndermin Tenefrin Synepin Binterin Adiponin Winhibin Target Molecules NF-kB IL1R FGFR TNFR EGFR CD99 Adiponectin Receptor Sfrp-5 Cosmeceutical Functions & Applications -Inhibiting a gene expression of NF-kBp65, an inflammatory signaling protein causing the skin aging and inflammation - Skin soothing/anti-inflammation/anti-aging -Inhibiting Interleukin-1, an inflammatory adipokine, soothing skin with its anti-inflammation process -Skin soothing/anti-inflammation -Activating the function of FGF-receptor, leading to proliferation of skin cells and inducing a collagen synthesis -Skin rejuvenation and regeneration -Inhibiting TNF-α ( tumor-necrosis factor-α), another inflammatory factor, leading to skin soothing with anti- inflammation reaction - Skin soothing/anti-inflammation -As an EGF receptor agonistic protein, facilitating the growth of keratinocytes and dermal fibroblasts and also facilitating the collagenous fibers (collagenesis ) -Skin rejuvenation and regeneration -Not only modulating leukocyte extravasation (diapedesis: the movement of leucocytes out of the blood circulatory system towards the site of tissue damage or infection), but also inhibiting the systemic inflammatory reaction, soothing the inflammatory tissues - Skin soothing,/anti-aging -Facilitating the proliferation of the epidermal cells and the generation of the ceramides existing in cell membrane, - Working for the fibroblasts in dermis and inducing the generation of collagens and H/A, - Inhibiting the inflammatory reactions with prevention of fibrosis and cellulite formation - Formation of skin protection barrier/skin regeneration/soothing/anti-agong -Preventing the activation of Wnt-signaling pathway, leading to inhibition of melanogenesis and related cytokines. In addition, inhibiting the inflammatory reaction related with metabolic diseases like diabetes and obesity. - Whitening/Soothing 6
2. Our SE-tri-Peptide and the applications. Our transdermal SE-tripeptides are variously applicable for cosmetic, cosmeceutical and OTC drug products. Below table briefly summarizes the various applications of our percutaneous tripeptides. One, two or three of our SE-tripeptide can be used in a single or with combination as in below table. INCI number of SE-Tripeptide Trade Name Applications Remarks SE201 SE205 SE209 Enfibin Tenefrin Binterin Anti-photo-aging Soothing Anti inflammation Singe, two or all 3 can be combined for use. SE204 SE208 SE214 Syndermin Synepin Adiponin Skin Rejuvenation Skin/ Hair regeneration Singe, two or all 3 can be combined for use. SE214 SE215 Adiponin Winhibin Whitening Both can be combined. SE204 SE208 SE214 SE215 Syndermin Synepin Adiponin Winhibin Repairing Whitening All 4 or each 2 can be combined for use. SE201 SE205 SE209 SE215 Enfibin Tenfrin Binterin Winhibin Anti-photoagaing Whitening All 4 or each 2 can be combined for use. SE208 SE214 Synepin Adiponin Moisturizing Skin Barrier Both can be combined. SE209 Binterin Soothing Post sunscreen soothing Anti-Photoaging SE209 then SE215 Binterin, then, Adiponin Bodycare/ Lipolysis Binterin first, then (15 minutes) Adiponin 7
DD. Available for our high-performance Tri-Peptide base materials in bulk Tri-Peptide Formulated Base materials in bulk We are available to supply our clients with the formulated base materials in bulk containing our high performance tri-peptides as active ingredients. Our tri-peptide cosmetic bases are specially formulated so that the manufacturers can purchase our tri-peptide base materials in bulk and make easy their own brand products with the addition of their preferred ingredients like essential oils, carrier oils, floral waters, botanical and fruit extracts, exfoliants or whatever they like. 1. Bulk Base Items for Anti-photo-aging /Soothing / Anti-inflammation Hi-Perfomance Tri-peptide Base for Anti-photo-aging /Soothing / Anti-inflammation Bulk Items Enfinbin Base, Tenefrin Base, Binterin Base Active Ingredients Inactive ingredient Good & recommended for Single, two or all 3 among below tri-peptides : - Enfibin : NF-kBp65, an inflammatory signaling protein, inhibitor tripeptide - Tenefrin : TNF-alpha ( tumor-necrosis factor) pro-inflammation signaling protein inhibitor tripeptide - Binterin ( CD-99 derived anti inflammation/ soothing tri-peptide) N/A post laser, post Co2 Fx laser, microdermabrasion, skin exfoliation, fx microneedle or fx RF microneedle, post-sunscreen, post tattoo recovery etc..otc analgesic 2. Bulk Base Items for Skin Rejuvenation, Skin/ Hair regeneration Hi-Perfomance Tri-peptide Base for Skin Rejuvenation, Skin/ Hair regeneration Bulk Items Active Ingredients Syndermin Base, Synepin Base, Adiponin Base Single, two or all 3 among below tri-peptides : - Syndermin: FGF receptor agonistic tri-peptide - Synepin : EGF receptor agonistic tri-peptide - Adiponin : Adiponectin tri-peptide 8
Inactive ingredient Good & recommended for N/A Skin protectant, skin moisturizing, skin rejuvenation, facial regeneration, collagen-regeneration, personal care, recovery kit 3. SE-triPeptide Base for Repairing and Whitening Hi-Perfomance Tri-peptide Base for Repairing and Whitening Bulk Items Active Ingredients Inactive ingredient Good & recommended for Syndermin Base, Synepin Base, Adiponin Base, Winhibin Base Any two or all 4 among below tri-peptides : - Syndermin: FGF receptor agonistic tri-peptide - Synepin : EGF receptor agonistic tri-peptide - Adiponin : Adiponectin tri-peptide - Winhibin : Wnt signaling inhibitor, whitening tri-peptide N/A Skin repairing, whitening, moisturizing, hyperpigmentation 4. SE-tripeptude for Anti-photoagaing /Whitening Hi-Perfomance Tri-peptide Base for Anti-photo-aging /Soothing /whitening Bulk Items Active Ingredients Inactive ingredient Good & recommended for Enfinbin Base, Tenefrin Base, Binterin Base, Winhibin base Any two or all 4 among below tri-peptides : - Enfibin : NF-kBp65, an inflammatory signaling protein, inhibitor tripeptide - Tenefrin : TNF-alpha ( tumor-necrosis factor) pro-inflammation signaling protein inhibitor tripeptide - Binterin ( CD-99 derived anti inflammation/ soothing tri-peptide) - Winhibin : Wnt signaling inhibitor, whitening tri-peptide N/A Sun burn, sun damaged skin, post Co2 Fx laser, skin exfoliation, fx microneedle or fx RF microneedle, post-sunscreen, post tattoo recovery, whitening 9
5. SE-tripeptude for Moisturizing /Skin Barrier Hi-Perfomance Tri-peptide Base for Moisturizing /Skin Barrier Bulk Items Active Ingredients Inactive ingredient Good & recommended for Synepin plus Adiponin Base Both can be combined. - Synepin : EGF receptor agonistic tri-peptide - Adiponin : Adiponectin tri-peptide N/A skin moisturizing, skin protectant 6. SE-tripeptude for Soothing /Post sunscreen soothing /Anti-Photoaging Hi-Perfomance Tri-peptide Base for Soothing /Post sunscreen soothing /Anti- Photoaging Bulk Items Binterin Base Active Ingredients Only Binterin as active ingredient : - Binterin ( CD-99 derived anti inflammation/ soothing tri-peptide) Inactive ingredient Good & recommended for N/A Skin protectant, post sunburn or sun damaged skin, anti-photo aging, soothing or anti inflammation for troubled skin. 7. SE-tripeptude for Bodycare/ Lipolysis Hi-Perfomance Tri-peptide Base for bodycare/ lipolysis Bulk Items Active Ingredients Binterin base, Adiponin Base Apply Binterin base first, then apply Adipnin base : - Binterin ( CD-99 derived anti inflammation/ soothing tri-peptide) - Adiponin : Adiponectin tri-peptide 10
Inactive ingredient Good & recommended for * lipolysis by Binterin, Glucose uptake by Adiponin N/A Body care, lipolysis, Abdormin / Cellulite management EE. Our brands and available products 1. US OTC products - Topical Analgesic - skin protectants - post-sunscreen skin protectant - oral care - Opthalmic care - Diabetic/ Metabolic 2. Our brands - Dr Hahn soothing/ cream - 3P serum/ cream - Reverse aging Miracle Serum and Cream - Bamboo Beauty 3. OEM / OEM - Cellpid - Yeah-erl - Body N Skin 11
FF. Our Tri-Peptide Science I. SE201 (Enfibin, NF-kB inhibiting Tripeptide) NF-kB is a transcription factor involved in the proinflammatory responses causing the skin aging and inflammation. Enfibin tripeptide inhibits NF-kB activity, thereby functions as cosmetic ingredients for skin soothing, anti-inflammation, and anti-photo-aging. 1. Inhibition of the activation of NF-κB in the mouse macrophage RAW264.7. - Enfibin treatment suppressed the LPS-induced activation of the nuclear factor NF-κB. 2. The expression of type I procollagen and MMP-1 in human dermal fibroblast - Enfibin treatment does-dependently restored the UV-induced degradation of type I procollagen and reduced MMP-1 expression which was upregulated by UV stimulation. 12
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II. SE203 (Ilonerin, Interleukin-1 inhibiting tetrapeptide) Ilonerin tetrapeptide inhibits Interleukin-1R, an inflammatory cytokine receptor, and can be used as a cosmeceutical ingredient for soothing skin. 1. In vitro transendothelial migration assay of mouse monocytes - Ilonerin treatment decreased the extravasation of monocytes (WEHI274.1) through a monolayer of the brain vascular endothelia cell (bend.3) which was increased by IL-1 stimulation. 14
2. In vivo inhibition assay of IgE-mediated immune hypersensitivity - After injection of IgE antibody into the vessel of a mouse (Balb/c) tail and inducing a hypersensitivity to the ear of the mouse with 2,4-dinitrofluorobenzene (DNFB), the hypersensitivity was inhibited by treatment with Ilonerin. 15
III. SE204 (Syndermin, FGFR activating tripeptide) Syndermin is a low molecular-weight tripeptide derived from FGF-1 (fibroblast growth factor -1) that is involved in various cellular processes, including angiogenesis, keratinocyte organization, and wound healing. 1. The proliferation of cultured human keratinocyte cell line, HaCaT. Syndermin treatment promoted the proliferation of HaCaT in a dose-dependent manner. 16
2. The activation of ERK and Akt in Fibroblasts. Treatment of fibroblasts with Syndermin dose-dependently induced the activation of ERK1/2 and Akt, intracellular signaling molecules. 3. Promotion of neo-angiogenesis in vitro Syndermin treatment significantly increased tubular formation of human umbilical vein endothelial cells in vitro. 17
IV. SE205 (Tenefrin, TNF-α inhibiting anti-inflammatory tripeptide) Tenefrin tripeptide inhibits TNF-α (tumor-necrosis factor- α), another inflammatory factor, leading to skin soothing or anti-photo aging with its anti- inflammation reaction. 1. In vivo transendothelial migration assay of mouse monocytes. - PMA-induced ear inflammation in mice stimulates the extravasation of monocytes from blood vessels into the inflamed tissues. Tenefrin significantly reduced the monocyte extravasation. 2. Expression of MMP-1 in human fibroblasts. - Tenefrin treatment dose-dependently suppressed the expression of MMP-1 which was induced by inflammatory cytokine. 18
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V. SE208 (Synepin, EGFR activating tripeptide) Synepin, an INCI named cosmeceutical / cosmetic ingredient (SE208), is a low molecular-weight tripeptide derived from epidermal growth factor(egf) that stimulates cell growth, proliferation and differentiation by binding to its receptor EGFR. 1. The activation of EGFR (Epidermal Growth Factor Receptor) Synepin treatment induced the interaction between Gab1 and Shp2 that was induced by the activation of EGFR. 20
2. The promotion of the proliferation of the Cultured Human Keratinocyte cell line, HaCaT. Synepin tripeptide significantly promoted the proliferation of human keratinocyte HaCaT cell line. 3. The activation of ERK and Akt Synepin treatment induced the activation of ERK1/2 and Akt in a dose-dependent manner. 4. The promotion of neo-angiogenesis in vitro Syndermin treatment significantly increased the tubular formation of the human umbilical vein endothelial cells in vitro. 21
VI. SE209 (Binterin, CD99-activating tripeptide) Binterin, an INCI named cosmeceutical / cosmetic ingredient (SE209), is a low molecular-weight tripeptide (316.3 Da) derived from CD99, an anti-inflammatory molecule that is expressed in all human cells. Binterin suppresses inflammatory processes and can soothe the inflammation areas excellently and quickly. Good for post laser treatment like CO 2 fractional laser or fractional RF micorneedling or tattoo removal. 1. Binterin also suppresses inflammatory responses by inhibiting the pro-inflammatory cytokines such as TNF-α and IL-1 - Binterin suppresses inflammatory cytokine-induced receptor clustering and NF-kB activation. 22
2. CD99 tripeptide suppresses TNF-α-induced adhesions of the leucotyes to endothelial cells. 3. CD99 tripeptide suppresses collagen-induced arthritis in mice. 4. CD99 tripeptide suppresses the tumor growth and metastasis in nude mouse xenograft 23
model. 5. CD99 tripeptide proves safe at repeated dose toxicity tests. 24
VII. SE214 (Adiponin, Adiponectin-receptor activating tripeptide) Adiponin, an INCI named cosmeceutical / cosmetic ingredient (SE214), is a low molecular-weight tripeptide derived from Adiponectin, an adipose-tissue specific releasing adipokine. This protein circulates through the human body and suppresses not only inflammatory reaction and carcinogenic metastasis, but also works for skin regeneration, moisturization and wrinkle enhancement. - Adiponectin facilitates the proliferation of keratinocytes and fibroblasts, induces the generation of extracellular matrix (ECM) like collagen and facilitates the expression of fillaggrin while adiponectin heals the damaged skin, suppresses fibrosis, enhances the wrinkles and forms the skin barrier, moisturizing the skin. - In addition, adiponectin enhances insulin sensitivity and improves insulin resistance, which leads to amelioration of the cardiovascular diseases like hyperglycemia, hyperinsulinemia, obesity and atherosclerosis. Adiponectin also suppresses the metastasis of cancer cells and inflammatory reactions. 1. The proliferation of Cultured mouse fibroblast ( NIH3T3) - The proliferation of the fibroblasts was observed to be significantly enhanced by Adiponin. 25
2. The activated expression of Procollagen Type-1 in fibroblasts - Adiponin dose-dependently induced the expression of type 1 procollagen in human dermal fibroblasts. 3. The expression of skin-barrier related protein in cultured human keratinocyte HaCaT cell line. - Adiponin treatment upregulated the expression of the skin-barrier forming Profillagrin, Involucrin and Ioricrin dose-dependently. 4. Suppression of the activation of the inflammatory transcription factor, NF-κB 26
- Dose-dependent treatment with adiponin significantly inhibited the activation of proinflammatory transcription factor NF-κB, which was induced by TNFα. 5. In vitro suppression of the extravasation of monocytes 27
- Adipoinin treatment prominently suppressed the extravasation of monocytes U937 through the Human Umbilical Vein Endothelial Cell layer. 28
VIII. SE215 (Winhibin, Wnt-inhibiting tripeptide) Winhibin, an INCI named cosmeceutical / cosmetic ingredient (SE215) is a low molecular-weight tripeptide derived from Sfrp5 (Secreted frizzled protein5) and known as a modulator adipokine of wntsignaling. SE215 Winhibin peptide inhibits skin pigmentation and works for skin whitening. 1. The effect of Winhibin tripeptide on the interaction of MITF with β-catenin in B16F1 mouse melanoma cell line. - Treatment of mouse melanocytes with winhibin significantly reduced the interaction between MITF and β-catenin. * α-melanocyte-stimulating hormone (α-msh) 29
2. The effect of winhibin tripeptides on the expression of β-catenin and the phosphorylation of GSK-3 in human dermal melanocytes. - Winhibin tripeptide inhibits the β-catenin expression and the GSK-3 phosphorylation by preventing Wnt activation. 3. The effect of Winhibin tripeptide on malanogenesis in B16F1 mouse melanoma cell line. - Winhibin treatment significantly suppressed the synthesis of melanin in melanoma cell line in a dosedependent manner. 30