COSMOPERINE : Q & A. Authors: Muhammed Majeed, Ph.D., Lakshmi Prakash, Ph.D Sabinsa Corporation. 1 of 7

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1 COSMOPERINE : Q & A Authors: Muhammed Majeed, Ph.D., Lakshmi Prakash, Ph.D. 1 of 7 Our Innovation Is Your Answer from published scientific literature info@sabinsa.com compiled therein.

2 COSMOPERINE * Lakshmi Prakash, Ph.D. and Muhammed Majeed, Ph.D. What is Cosmoperine? Cosmoperine is Tetrahydropiperine, prepared from piperine (found in black pepper and long pepper) by a patented proprietary process. Its use in improving the skin penetration of active compounds is also covered by the patent. Uses of Cosmoperine : 1. To increase the absorption of drugs and nutrients through the skin. Laboratory studies 1 with betamethasone dipropionate (BMDP), a steroidal anti-inflammatory agent that is commonly used in topical anti-inflammatory formulations, revealed faster absorption of the drug when combined with Cosmoperine. The experiments tested the transdermal diffusion of BMDP through hydrated skin mounted on a Franz diffusion cell. Figure 1 shows the effect of Cosmoperine on the transdermal diffusion of BMDP. The drug diffused completely in about 5 minutes in the presence of Cosmoperine. 120 Percent diffused Test (with Cosmoperine) Control (No Cosmoperine) Time (min) Figure 1: Beneficial effect of Cosmoperine on the transdermal penetration of BMDP * Patents pending 2 of 7

3 2. Increase the penetration of substances through surfaces. Cosmoperine was found to increase the effectiveness of the insecticide Fenvalerate 20E against the tobacco cut worm Spodoptera litura. This synergestic action is probably linked to the increased cuticular penetration of the insecticidal compound in the presence of Cosmoperine. In this study, Cosmoperine at 0.5% and 0.25% when applied with 250 ppm a.i. of Fenvalerate 20EC was found to significantly increase insect mortality as compared to the insecticide alone (Figure 2) Percent Mortality Fenvalerate 20EC 250 ppm Cosmoperine 0.25%+250 ppm Fenvalerate 20EC Cosmoperine 0.5%+250 ppm Fenvalerate 20EC Figure 2: Synergistic effect of Cosmoperine on Fenvalerate 20EC action 3. Bioavailability testing. Three sample botanical extracts used as cosmeceutical ingredients were tested for bioavailability enhancement by Cosmoperine : Green Tea extract (polyphenols rich, a well known antioxidant), Coleus forskohlii extract (forskolin, a skin conditionaing agent) and Tetrahydrocurcumin (derived from Curcuminoids extracted from Tumeric root, a potent antioxidant). 3 The permeation of green tea extract and forskolin in the presence and absence of Cosmoperine was studied in a Franz diffusion cell system, across hydrated skin substitute. Cosmoperine enhanced the permeation of green tea polyphenols across the egg membrane by about 30% on average (Figure 3). 3 Cosmoperine enhanced the permeation of forskolin by about 40% in the first thirty minutes, when used at a level of 5% of the forskolin concentration 3 of 7

4 (Figure 4). The antioxidant action of Tetrahydrocurcumin was enhanced by adding Cosmoperine (Figure 5). Figure 3: Effect of THP on penetration of green tea polyphenols across egg membrane. 4 of 7

5 Figure 4: Effect of THP on the dermal penetration of forskolin The free radical scavenging efficacy of Tetrahydrocurcumin in the presence and absence of Cosmoperine was studied. The Antioxidant activity of Tetrahydrocurcuminoids was found to be enhanced by Tetrahydropiperine (Figure 5). Percent inhibition refers to inhibition of free radicals in a standard DPPH (1,1 diphenyl 2-picrylhydrazyl) radical scavenging in vitro assay. 3 Figure 5: Tetrahydropiperine enhances the antioxidant action of Tetrahydrocurcumin. 5 of 7

6 Safety Aspects: The 48 hour Repeat Insult Patch Test was used to evaluate skin irritation potential of Cosmoperine. Cosmoperine at a level of 0.01% and 0.1%, (an effective dose range for the compound), was used in the skin patch test in a petrolatum vehicle. The test was conducted on 50 healthy volunteers for 48 hr with reading of the results after 48 hr and 72 hr. Neither dose caused skin irritation at the time of clinical evaluation of the study subjects. The supervising physician, a practicing dermatologist, reported the irritation score as 0. This study was conducted by the US FDA accredited BioScreen Testing Inc. laboratory. These results indicate that Cosmoperine does not act as a skin irritant in a dose range considered effective for topical nutrient delivery. References: 1. Studies on Transdermal Penetration Enhancement Activity of RD/TP/09 Research Report, Sami Labs Ltd. April Determination Of Synergistic Activity Of Tetrahydropiperine With Fenvalerate 20 EC Against Tobacco Cut Worm, Spodoptera litura, F. Research Report, Sami Labs Ltd. May Research Reports, Sami Labs Ltd of 7

7 USA: GLOBAL CONTACT & PROFILE Sabinsa Corporation NJ Sabinsa Corporation UT 70 Ethel Rd West, #6 750 S. Innovation Circle Piscataway, NJ Payson, UT O: O: F: F: E: E: Australia: Sabinsa Australia Pty Ltd O: +61 (02) F: +61 (02) E: China: Sabinsa China Office O: +86 (25) /33 F: +86 (25) E: Europe: Sabinsa Europe GmbH O: F: E: Japan: Sabinsa Japan Corporation O: +81 (42) F: +81 (42) E : info@sabinsa.co.jp South Africa: Sabinsa S.A. (Pty) Limited O: F: E: sa@sabinsa.com ʺThe vision of a research scientist takes on social and commercial expressions.ʺ This in short explains the genesis and growth of the Sabinsa Sami Labs Group of Companies. Company Profile: Sabinsa Corporation, founded in 1988, is a manufacturer and supplier of herbal extracts, cosmeceuticals, minerals and specialty fine chemicals. Sabinsa s mission is to provide alternative and complementary natural products for human nutrition and well being. Over the past ten years, Sabinsa has brought to market more than 50 standardized botanical extracts and privately funded several clinical studies in conjunction with prestigious institutions in support of these products. Its present operations have grown to employ 1000 people worldwide in ten manufacturing, R&D and/or distribution facilities. Additionally, botanical cultivation efforts undertaken by the organization now total nearly 40,000 acres to ensure sustainable supplies on its key products. All products intended for human consumption are certified Kosher. Visit us: 7 of 7