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Vitamin From

E

Eisai Food & Chemical

Vitamin E from

Eisai Food & Chemical

Eisai Food & Chemical, as a 100% subsidiary company of Eisai, commits to the well-being of customers using the products or products containing ingredients supplied by Eisai Food & Chemical based on the hhc (human health care) principle. We are trying to achieve this by improving the quality of our products through innovative research and by giving true and accurate information, on the benefits of Vitamin E, to the customers. Eisai has its own laboratories, researching on product improvements and health benefits of Vitamin E, in addition to supporting similar research at other institutions. This enables us to produce both natural and synthetic Vitamin E products, with a quality and purity of the highest level, and to recommend the best use of Vitamin E in cosmetics to achieve maximum benefits for the customers.

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Vitamin Back to Basics −The Structure of Vitamin E "Vitamin E" is a collective name for a group of related compounds and their derivatives that qualitatively exhibit the same type of biological activity, but their functions vary. For this reason, it is worthwhile to review what Vitamin E is and how it functions. Vitamin E compounds can be divided into two groups, one called the Tocopherols and the other the Tocotrienols. The Tocopherols are the most important type of Vitamin E compounds. As shown below, all of the Tocopherols have a chromane head unit to which is attached a hydroxyl group, at carbon number 6, and a phytyl side chain at carbon number 2. What distinguishes the various Tocopherols is the different numbers and positions of methyl groups in the chromane head. Alpha Tocopherol has three methyl groups, one each on carbon numbers 5,7 and 8. Gamma Tocopherol has two methyl groups in the ortho positions at carbon numbers 7 and 8. Beta Tocopherol also has two methyl groups, but they are in the para positions at carbon numbers 5 and 8. Delta Tocopherol has only one methyl group at carbon number 8.

CH3

CH3 8

7 HO 6

CH3 CH3 H

O 2

5 CH3

3

4'

CH3 H

CH3

CH3

H

CH3 CH3 H

CH3 H

CH3

CH3

8'

CH3 HO

4

CH3

Fig 1. d-(or RRR-) Alpha Tocopherol

CH3 CH3

O

O

CH3 CH3 H

CH3 H

Fig 2. d-(or RRR-) Beta Tocopherol

CH3

CH3 H

O

CH3 CH3 H

CH3 H

CH3

CH3

CH3

HO

HO H

H

Fig 3. d-(or RRR-) Gamma Tocopherol

Fig 4. d-(or RRR-) Delta Tocopherol

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These differences give rise to quantitative differences in the biological activity as well as in the in vitro antioxidant activity of these compounds. Further examination of the structure of the Tocopherols shows that they all contain 3 asymmetrical centres at the 2', 4' and 8' positions and therefore display optical activity. In practice natural Vitamin E is only a single optical isomer commonly given the D prefix (e.g., d -Alpha tocopherol) whereas synthetic Vitamin E is a racemic mixture of 8 isomers and is given the DL prefix (e.g., dl -Alpha tocopherol). The natural D form has a higher biological activity compared to the synthetic DL form. Due to the presence of the hydroxyl group at the 6 position of the chromane head, it is possible to produce, by chemical synthesis, ester derivatives of the Tocopherols, of which the most common ester is the acetate but also Succinate, Nicotinate and Linoleate esters have been produced.

CH3 CH3

O

CH3 CH3 H

CH3 H

CH3 CH3

CH3COO

dl-Alpha Tocopheryl Acetate

CH3

CH3 CH3

O

CH3 CH3 H

CH3 H

CH3 CH3

COO

dl-Alpha Tocopheryl Nicotinate

CH3 N

These esters also exhibit biological activity since once ingested they are hydrolysed back to the free tocopherol form, however, they do not exhibit any in vitro antioxidant activity since it is the hydroxyl group which is responsible for this activity. The esterification can improve the stability of the Tocopherols, but also can impart extra properties relating to the parent acid. This is particularly so for the nicotinate, linoleate and succinate derivatives.

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Vitamin Many Functions, Lots of Benefits Vitamin E in cosmetics has many benefits and properties including,

4. Anti-inflammatory Properties 5. Superb Moisturization Effects, Quick Absorption 6. Promoting Smoother Skin 7. Inhibiting Skin and Tissue Aging 8. Assisting Microcirculation and Hair Growth 9. Safe Substance, Enhancing Cosmetic Shelf Life

1. Antioxidant Properties 2. Cell Membrance/Active Ingredient Stabilization 3. UV Ray Protection

Antioxidant Properties smoke and UV light. Polyunsaturated phospholipids in biological membranes are particularly prone to attack by peroxyl free radicals. Vitamin E protects these membranes from peroxyl radicals, by "neutralising" the radical through donation of the hydrogen atom of the hydroxyl group to the radical.

Vitamin E is one of the most powerful oil soluble antioxidants and free radical scavengers available today. Its antioxidant activity is well known and well proven. The antioxidant activity of Vitamin E is the result of the presence of the hydroxyl group on the chromane ring. Free radicals are molecules which contain an unpaired electron and are as such generally very reactive. They are produced in our bodies as a result of natural processes but we are also exposed to free radicals from the outside, such as generated from atmospheric pollutants,

As a powerful antioxidant Vitamin E can protect cell membranes as well as active ingredients in cosmetics. It also may help to maintain the younger look, by prevention of the accumulation of lipofuscin or age pigments.

Cell Membrane Stabilization membrane stabilisation effect, believed to be due to the location of an antioxidant at the potential site of oxidation and/or by some kind of physical effect.

The phytyl side chain of the Vitamin E molecule is lipophilic and can be associated with the fatty acid portion of phospholipids in cellular membranes. This action creates a

Protection from UV Radiation The ultra violet radiation of sunlight can cause carcinogenic effects and photoaging of the skin. This is mainly due to the free radicals formed by UV light but, as a powerful free radical scavenger, Vitamin E can reduce this damage. Interestingly, Vitamin E has been effective in this regard whether it is applied before or after the irradiation. The

ester forms of Vitamin E may take a longer time to act as there need to be first converted into free form (active antioxidant form) to show an antioxidant effect. The antioxidant activity of Vitamin E has also been effective in inhibiting inflammatory reactions caused by sun light or by other means.

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Superb Moisturization Effects, Quick Absorption loss through the skin have been reported in research upon topical applications of Vitamin E. This will not only ameliorate dry skin conditions but will also help conceal wrinkles and blemishes. In addition to the improvements in outward appearance, absorbed Vitamin E, from topical applications, can be beneficial against oxidative damage inside the body.

Unlike occlusive moisturisers, Vitamin E can be readily absorbed through the skin to provide a better moisturising effect from within. A few hours after a topical application of Vitamin E, a significant portion can be found in the dermis. The absorbed Vitamin E can inhibit lipid peroxidation providing a better water binding ability to the skin. Significant reductions (up to 33%) in water

Promoting Smoother Skin in lipid peroxidation, malondialdehyde (MDA) is known to cross-link collagen, resulting is a decreased elasticity of the skin. The free radical scavenging and antioxidant effects of Vitamin E can protect connective tissues and thereby help to maintain the smoothness of the skin.

The smoothness of a skin depends on factors such as firmness, texture and tone, which are maintained by the integrity of elastic fibers in the dermis and in the collagen in connective tissues. Free radicals can cause fragmentation in elastic fibers and degeneration of connective tissue collagen fibers. One of the breakdown products

Enhancing Hair Growth Vitamin E absorbed through the skin has a strong affinity for small blood vessels and therefore can improve microcirculation. In this respect, the Nicotinate derivative was found to be the most effective due to a direct vasodilatory action. Improvements in microcirculation and in the general nutritive condition of the scalp are believed

to be the main reasons why Vitamin E in the form of Alpha Tocopherol and its Acetate derivative have been shown to enhance the growth of hair. The microcirculatory effects of the nicotinate derivative also make it useful for anti-cellulite creams, since cellulitis is believed to result partially from a failure in microcirculation.

Safe Subtances, Enhancing Shelf Life of Cosmetics When it comes to safety, Vitamin E creates a win-win situation. For the customer, it is a very safe vitamin to use and for cosmetics products it provides safety from environmental oxidation. Vitamin E has not shown any significant adverse effects when taken topically, orally or injected. It is generally considered to be free of allergic skin

reactions. In addition, the antioxidant properties of Vitamin E can protect other cosmetic ingredients from oxidation. However, only the free form of Vitamin E is effective in protecting cosmetic ingredients from oxidation, whereas both the free and ester forms are effective in biological oxidation systems.

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Vitamin Information for Formulations Eisai Food & Chemical Products Currently used in Cosmetics: A) dl- Alpha Tocopheryl Acetate B) dl -Alpha Tocopheryl Nicotinate C) Vitamin E Linoleate Mixture D) d -Delta-Rich Tocopherols Concentrate

Suggested amounts to achieve benefits in topical applications: 1) Moisturising effect 2) Improvement of microcirculation 3) Anti-inflammatory properties 4) Ingredient antioxidant

A, B and/or C A and/or B A and/or B D

6

0.2 − 0.2 − 0.2 − 0.02 −

5.0% 5.0% 5.0% 0.1%.

2-13-10 Nihonbashi, Chuo-ku, Tokyo, 103-0027 Japan TEL：81-3-3548-3560 FAX：81-3-3273-2084

The information contained in this publication is believed to be accurate and presented in good faith. However, because of conditions which are beyond our control, we do not offer a guarantee or warranty. Each customer is advised to conduct evaluations to determine the suitability of our products for their specific applications. Nothing contained herein should be construed as a recommendation to use our products in a way that might otherwise cause infringement on a patent held by other concerns.

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