Concept. To fulfill the unmet need - to protect or shield the skin from the harmful effects of HEV light, Liposhield HEV Melanin was invented.

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2 Concept Scientific articles published in 2007 by Research Universities and by the R&D Groups of Consumer Products Manufacturers detailed the harmful effects of HEV light. To fulfill the unmet need - to protect or shield the skin from the harmful effects of HEV light, Liposhield HEV Melanin was invented. Liposhield HEV Melanin provides the benefit to offer skin care formulations that shield or protect from HEV light.

3 What is High Energy Visible Light? High frequency light in the violet/blue band from 400 to 500 nm in the visible spectrum

4 Skin Penetration of the Different Wavelengths Visible light penetrates deeper into the skin than UVC, UVB and UVA, reaching beyond the dermis

5 Facts about the Harmful Effects of HEV Light Shown to be responsible for the generation of about 50% of the Reactive Oxygen Species (ROS) generated in the skin as a result of sun exposure Equal to the amount generated by UVA (46%) and UVB (4%) combined O - (superoxide radical) NO 2 (nitrous oxide) and HO 2 (hydroxy radical) are among the 2 radicals generated UVA-like: promotes indirect DNA damage that is mediated by ROS Activates matrix metalloproteinases (MMP s) that lead to wrinkle formation and premature aging May promote uneven pigmentation May cause photo-sensitivity disorder and solar urticaria

6 What are Melanins? Melanin and its intermediates are heteropolymeric pigments produced naturally by melanocytes in the skin The precursors for melanin are the amino acids tyrosine or tryptophan Melanin and its derivatives are distributed in melanosomes among keratinocytes to provide skin protection from irradiation During the natural biochemical cascade of melanin production, it is possible that intermediates are formed. These may be of a lower MW then the finished polymer and partially responsible for the unique skin tone of each individual

7 Liposhield HEV Melanin Chemical Structure Unfractionated Conglomerate Molecule of Melanin de-stacking, fractionation Fractionated Melanin (FM)

8 Liposhield HEV Melanin Absorption Spectra Liposhield HEV Melanin Liposhield HEV Melanin Optical Absorption of standard (full size) and Liposhield HEV Melanin at the different wavelengths of the visible spectrum normalized at 500 nm Between nm, where HEV light is dominant, Liposhield HEV Melanin absorbs significantly more when compared to standard melanin Between nm (red spectrum) both melanins have relatively low absorption Jim Gallas

9 What is Liposhield HEV Melanin? It is a synthetic, fractionated melanin, tailored to absorb in the violet/blue range of nm with minimal absorption in the beneficial red range It is synthesized in a special manner from vegetable derived tyrosine It is designed to have a MW that is estimated between 5,000 to 10,000 Daltons and therefore will not penetrate healthy intact skin

10 How does Liposhield HEV Melanin Work? When applied to skin, Liposhield HEV Melanin remains on the surface of the skin and absorbs specifically in the HEV range. Thus providing a barrier preventing radiation from penetrating the skin Designed to minimally absorb the red light wavelengths (~ nm), Liposhield HEV Melanin allows passage of these therapeutic wavelengths

11 Cytotoxicity: non-cytotoxic Safety Testing Phototoxicity: non-phototoxic Genotoxicity: non-genotoxic Photogenotoxicity: non-photogenotoxic Skin irritation and sensitization (RIPT): not a skin irritant or sensitizer Eye irritation: not an eye irritant

12 Safety Testing Micronuclei Some of the safety studies suggest that Liposhield HEV Melanin induces a protective effect on cells when exposed to UVA/VIS light The figure on the left represents the positive control of nuclei of cells exposed to UVA/VIS light in the presence of a mutagenic compound This resulted in the formation of micronuclei that can be seen in the uneven structure of the nucleus The cells on the right were exposed to UVA/VIS light in the presence of Liposhield HEV Melanin. There the nuclei remain intact

13 Gene Expression Study Results Demonstrate This in vitro gene expression study on artificial skin demonstrated a change in key genes when exposed to HEV light. Based on this analysis Liposhield HEV Melanin shielded the following effects: Inflammatory response Barrier disruption Aging at the cellular level affecting normal cell cycle and death patterns Melanogenesis leading to uneven pigmentation This change was shielded when the skin was protected by Liposhield HEV Melanin

14 Bio-information Map Effect of HEV Light

15 Hypothesized Pathways Based on Affected Genes

16 Product Information and Typical Properties INCI name: Melanin CAS No: EINECS No: Solubility: Soluble in water Appearance: Dark brown liquid Odor: Characteristic Solid Content: %

17 Formulation Guidelines Solubility and ph: Liposhield HEV Melanin is a 10% aqueous solution The ph should be adjusted to and held between At higher ph levels the formulation might darken Recommended use level: % of Liposhield HEV Melanin Incorporation: In emulsions, should be added after emulsification at a temperature of 45ºC or below with medium propeller mixing Will impart a yellowing effect to o/w emulsions, which can be mitigated with the addition of dyes, resulting in pale pastel formulations Incorporation of Liposhield HEV Melanin into water-in-oil (w/o) or water-insilicone (w/si) emulsions may partially mask the yellowing effect Incorporation of Liposhield HEV Melanin to liquid makeup foundation should not affect the foundation color

18 Approaches to Mitigate Color The color of Liposhield HEV Melanin can be mitigated somewhat by formulating into W/O emulsions and W/Si makeups, or by the addition of titanium dioxide or pigments.

19 Approaches to Mitigate Color For O/W emulsions, the addition of dyes will mitigate the color.

20 Stability in Formulations Liposhield HEV Melanin is stable in formulations, under UV exposures at ambient temperature and during long term high temperature stability testing

21 Suggested Applications Daily wear moisturizing creams and lotions Anti-aging treatment products Foundation make-ups Hand creams

22 Liposhield HEV Melanin Facial Cream #1578 SEQUENCE PERCENT INGREDIENT INCI NAME Deionized Water Water Disodium EDTA (119) Disodium EDTA Pemulen TM TR-1 (9) Acrylates/C10-30 Alkyl Acrylate Crosspolymer Liponic EG-1 (1) Glycereth Lipomulse Luxe (1) Cetearyl Alcohol (and) Glyceryl Stearate (and) PEG-40 Stearate (and) Ceteareth Lipocol SC (1) Cetearyl Alcohol Lipocol S-2 (1) Steareth Lipocol S-20 (1) Steareth Liponate NPGC-2 (1) Neopentyl Glycol Dicaprylate/Dicaprate Liponate TDS (1) Tridecyl Stearate Liponate NEB (1) C12-15 Alkyl Benzoate Liponate DPC-6 (1) Dipentaerythrityl Hexacaprylate/Hexacaprate Sodium Hydroxide 18% Solution (119) Sodium Hydroxide Hylasome EG-10 (1) Sodium Hyaluronate Crosspolymer Liposhield TM HEV Melanin (1) Melanin Fragrance Fragrance 5 qs Preservative (Preservative) %

23 Black Pearl Treatment Serum #1584 SEQUENCE PERCENT RAW MATERIAL INCI NAME Deionized Water Water Disodium EDTA (119) Disodium EDTA Carbopol 980 (9) Carbomer NaOH 18% Sol. (119) Sodium Hydroxide Glycerin 99% (119) Glycerin Liponic EG-1 (1) Glycereth Liposhield HEV Melanin (1) Melanin SD Alcohol 40B Ethanol Microna Matte Black (38) Mica (and) Black Iron Oxide Timiron MP-111 Ultra Luster (38) Pearl Powder Mica (and) Titanium Dioxide Pearl Powder 5 qs Preservative (Preservative) % 23

24 Regulatory Status- INCI: Melanin To the best of our knowledge, the use of Liposhield HEV Melanin in Cosmetic and Personal Care products does not carry any regulatory restrictions. For country specific regulatory requirements, consult your local regulations. Liposhield HEV Melanin is not a sun screen active!

25 Summary Studies published since 2007 suggest that HEV light is harmful to skin, promoting pre-mature aging and possibly disease. To date, there is no cosmetic product in the market that can effectively shield the skin from exposure to HEV light. Liposhield HEV Melanin is a patent-pending compound that was shown to effectively shield from this HEV violet/blue wavelengths.

26 References 1. Zastrow L., Groth N., Klein F., Kockott D., Lademann J., Ferrero L. Detection and identification of free radicals generated by UV and visible light in Ex Vivo human skin. IFSCC Magazine 11(3) (2008) Besaratinia A., Kim S.I., Pfeifer G.P. Rapid repair of UVA induced oxidized purines and persistence of UVB induced dipyrimide lesions determine the mutagenicity of sun light in mouse cells. The FASEB Journal 22(2008) Denda M. and Fuziwara S. Visible radiation affects epidermal permeability barrier recovery: selective effects of red and blue light. J. Invest. Dermatol. 128 (2008) Lee J.H., Roh M.R., Lee K.H. Effects of infrared radiation on skin photo-aging and pigmentation. Yonsei Medical Journal 47(4) (2006)

27 All data, including the formulations and procedures discussed herein, to the knowledge of Lipo Chemicals, Inc. (Lipo), are believed to be correct, reliable and accurate. Please note, however, that Lipo does not warrant or guarantee any accuracy, reliability or completeness of the information contained herein. It is the user s responsibility to determine the suitability and completeness of such information for the user s particular use (including performing any necessary confirmatory tests). Lipo is not responsible or liable for any loss or damage that may occur from the use of this information, nor do we warrant against any patent infringement. Nothing contained herein shall be construed as providing any permission, recommendation, or inducement to practice any patented invention without permission of the patent owner. Sales of all products are pursuant to terms and conditions included in Lipo s sales documents. Nothing contained herein shall constitute a guarantee or warranty of any kind with respect to the products described or their use. Safety information regarding these products is contained in their Material Safety Data Sheets (MSDS). The user is directed to review the applicable MSDS prior to using the product.

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