A technology of the new natural vitamin E metabolite industrial synthesis and application for protecting organism against oxidative stress

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1 A technology of the new natural vitamin E metabolite industrial synthesis and application for protecting organism against oxidative stress Palladin Institute of Biochemistry of the National Academy of Sciences of Ukraine 1 The Ukrainian Biochemical Institute was founded in 1925 and guided by current director Prof. Serhiy Komisarenko. The Institute s staff is about 367 persons of which 137 scientific researchers, 23 Dr. Sci. and 82 Ph.D. Nowadays, the Institute is an owner of about 45 National patents and trademarks as well as 2 International patents.

2 Licensed patents and trademarks Medikhronal Calmivid Corektin Mebiphon Alcohol and Degenerative hangover abuse Osteoporosis Antitumor Antitumor Darnitsa Kiev vitamin factory Darnitsa (in progress) Farmak 2

3 3 Department of Coenzyme Biochemistry

4 Investigation of the biological activity of vitamin E analogue Vitamin E 4 Vitamin E analogue with side chain modification This analogue is an active natural metabolite of the vitamin E both in the human and animals organisms. We proposed technology of the vitamin E analogue which has same vitamin activity compare to the α-tocopherol, but gives a great economic effect. Due to the technology simplification the production of this vitamin E analogue is cheaper compare to the vitamin E production by 30% and poses antioxidant, membrane stabilizing, hepatoprotector, antihypoxic activity.

5 Investigation of the anticancer activity of vitamin E derivative 5 Normal Cancer Cancer treated by vitamin E analogue

6 6 Antitumor and antimetastatic effect of vitamin E analogue on Lewis lung carcinoma * * * 10 5 * * * * Metastases, number * * * * * * *, # Tumor diameter, mm 0 0 Cancer Cicplatin Different conc. of vitamin E analogue Different conc. of vitamin E analogue With Cicplatin Olive oil Cancer Cicplatin Different conc. of vitamin E analogue Different conc. of vitamin E analogue With Cicplatin Olive oil

7 Comparison of product characteristics Important product Cisplatin Our vitamin E derivative characteristics as a standard anticancer drug proposed as an anticancer drug Anticancer effectiveness Administration Decreases tumor size and number of metastases. Intravenously (Patient should be accompanied by nurse). Decreases tumor size and number of metastases. Orally (Patient can take medication by oneself without nurse assistance). Toxicity, LD50 8 mg/kg for rats intravenously mg/kg for rats orally (600 times less toxic compare to Cisplatin, 5000/8= 625 times). Alopecia (hair loss), Alopecia (hair loss) is not occurs. Side effects Nephrotoxicity (kidney damage), Neurotoxicity (nerve damage), Ototoxicity (hearing loss) and Vomiting. Nephrotoxicity (kidney damage) is not occurs. Other not determined. Combinatory use Used in combination with other medications to decrease Cisplatin toxicity Successfully decreases Cisplatin toxicity in jointly administration. Obstacles Use of expensive metals such as Pt. Does not Contains metals such as Pt. Ingredients and technology for this vitamin E derivative production are quite similar to the vitamin E. Thus, an existing apparatus, trained and available personal can be used. 38 to 58 US$ per 1 gram 90 to 290 US$ per kilogram 7 Substances cost (approximately US$ per 1 kilogram). (200 times cheaper compare to Cisplatin, /290= 165 times).

8 Advantages of investing into the vitamin E analogue The side chain modified vitamin E analogue is capable to serve as an initial substance for attaining the new generation of vitamin preparations being more active metabolites of vitamin E for their application in the clinics at different pathological states including cancer. Introduction of the vitamin E generation technology is capable to simplify the problem of supplying the population and the agriculture by vitamin E as well as to come out with new vitamin E medications to the International Market. 8

9 Perspective Partners and Collaborators in China Implementation of this technology is mostly suitable for the factories as well as plants which are already synthesizing vitamin Е or SME specializing in organic synthesis in China. We would like to order synthesis of this vitamin E derivative in China. How to avoid unrestricted use of our technology after fulfillment of the contract? 9 What we should pay attention collaborating with Chinese market as to the commercial contracts, technology transfers, etc.?

10 10 Problematic legal issues 1) Taking to the account that Institute is a state budget organization the question is who is the owner of the intellectual property rights of the technologies created in the Institute, Institute itself or State? 2) Taking to the account that the procedure of assignment of nonmaterial objects of the state entities is not defined according to the Ukrainian laws, the only way of transfer technology is legal for Institute today - to enter into license agreement. What other alternative ways of transfer technologies are possible for the Institute?

11 Contact Information Oleksandr Kuzmenko, PhD -Group Head Cell Phone: Fax: Palladin Institute of Biochemistry web site 11

12 Thank you for your attention!

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