MXPA00012049A - Novel polyoxypropylenepolyoxyethylene vitamin e and preparation thereof - Google Patents

Abstract

Disclosed is polyoxypropylenepolyoxyethylene vitamin E, represented by formula (I). It is prepared by subjecting vitamin E to polyethoxylation and then, to polypropoxylation to a proper extent. The vitamin E is of superior anti-oxidation activity with water solubility. The bent chain of the polyoxypropylenepolyoxyethylene vitamin E increases the cross-sectional area of the whole molecule, making it difficult for the molecule to penetrate into the skin. It is very safe to apply to the skin. The polyoxypropylenepolyoxyethylene vitamin E has superb surface activity by forming close bilayer vesicle structures, like phospholipids or dialkyl surfactants, so it can be advantageously used in the cosmetic industry, the food industry and the medical industry. In said formula, R1 is -(OCH2CH2)m- wherein m is an integer of 0 to 150;R2 is (a)wherein n is an integer of 1 to 200;A is (b) or (c);B is -CH3 at the 5-, 7- or 8- position of vitamin E;and p is an integer of 1 or 3.

Description

NEW POLIOXIPROPILENPOLIOXIETILEN VITAMINA E AND PREPARATION OF THE SAME TECHNICAL FIELD The present invention relates to a novel polyoxypropylene polyoxyethylene vitamin E and a method for preparing it. More particularly, the present invention relates to an amphipathic polyoxypropylene polyoxyethylene vitamin E having high surface activity with excellent skin safety properties. Also, the present invention relates to the uses of said novel polyoxypropylene polyoxyethylene vitamin E.

BACKGROUND OF THE INVENTION In general, the surfactants are adsorbed on the interfaces or surfaces of the aqueous solutions in order to significantly reduce the interfacial tension or surface tension of the same. Depending on their concentration in a solution, the surfactants form several types of micelles, which are an assembly of molecules or ions, which can be used for several purposes. Lipids, which have surface activity in vivo (biotensives), play a role in regulating the physiological activities of organs and tissues. The biotensoactivos, which can be manufactured at industrial level, have useful applications in a wide range of industries including medicines, food, cosmetics, etc., are classified as dispersants, emulsifiers, solubilizers, foaming agents, antifoaming agents, agents of polishing, sliding agents, agents for surface treatment, wetting agents, etc. In addition to these functions and purposes, the ionic property also gives rise to a standard classification for the surfactants, which comprises ionic and nonionic surfactants and the latter can also be classified into hydrophilic and lipophilic surfactants. While the water solubility of ionic surfactants is attributed to the presence of ions in hydrophilic groups, the water solubility of nonionic surfactants is due to their hydrogen bond with water. It is known that the abundance of ionic materials in organisms makes nonionic materials more bioavailable than ionic materials. In fact, surfactants are generally used in products that are applied to living organisms. Non-ionic hydrophilic surfactants do not contain hydrophilic atomic groups that are ionized and those that have a hydroxy group are representative (-0H). Also, the hydrophilic nonionic surfactants may contain ester linkages (-C00-), amide bonds (- CONH-) and / or intramolecular ether linkages (-0-), although they are weaker in hydrophilicity than a hydroxy group. Of the nonionic hydrophilic surfactants, which are used most widely and the most important are the polyethylene glycol condensates that are exemplified by the condensates of fatty acids and polyethylene glycol (Niosol, Myrj), condensates of fatty acid amides and polyethylene glycol, condensates of aliphatic alcohols and polyethylene glycol (Leonil, Peregal C), condensates of aliphatic amines and polyethylene glycol, condensates of aliphatic mercaptans and polyethylene glycol (Nyon 218), condensates of alkylphenyls and polyethylene glycol (Igepal) and condensates of polypropylene glycol and polyethylene glycol (Pluronics). In addition, several non-ionic surfactants with complicated structures have been developed in recent years and have been used for various purposes that demonstrate their importance. In general, as mentioned above, it is known that both ionic and nonionic surfactants form micelles, which are an assembly of ions or molecules. As for the reason why they form micelles, there are several differences between ionic and non-ionic surfactants. The formation of micelles is one of the most important properties of surfactants and is greatly affected by the structure of the surfactants. Taking advantage of these properties, a large number of surfactants have been developed for specific purposes. The mechanism by which nonionic surfactants form micelles in aqueous solutions, can be determined by studies of surface tension, light diffusion and interaction with pigmentps in micelles and other studies. The reason why nonionic surfactants form micelles is the property by which the alkyl chains of the surfactant molecules are released from an aqueous phase by the adhesion force of the water when they reach a critical concentration. In other words, the structure of a honeycomb is inherent to the structure of the molecules of nonionic surfactant, specifically to its amphipathic character. These properties and structural characteristics of the nonionic surfactants are determined primarily by the hydrophobic alkyl structure of the surfactant molecules. In fact, hydrophobic interactions are the main driving force for the formation of micelles or lipid bilayers. Intensive and in-depth research on new surfactants for skin care, repeated by the present inventors, led to discover that because vitamin E was very well inserted into the ordered and dense lipid bilayers of cell membranes for To protect them from oxidation, vitamin E played an important role as a hydrophobic group if applied to surfactants. As a result of the investigation, polyoxyethylene vitamin E was invented by subjecting vitamin E to an addition reaction with ethylene oxide and was patented including its high surface activity, its moisturizing and renewing action for the skin and the protection of the cell from the harmful active oxygen. (Korean Patent No. 083024, U.S. Patent No. 5,235,073 and Japanese Patent Application No. Hei 4-10362). Due to its structural characteristics, polyoxyethylene vitamin E is well absorbed at the interface, showing excellent surface activity. However, improvement is required with respect to skin safety. Because the inflexible, flat and hydrophobic chroman ring unit is carefully stacked one at a time while the terminal phyllil group has a relatively small cross-sectional area and also has fluidity, polyoxyethylene vitamin E is very well inserted into the lipid bilayers. of cell membranes, which causes a security problem. This safety problem can be solved by controlling the length of the ethylene oxide chain of the surfactant, that is, by prolonging the ethylene oxide chain. In this case, however, polyoxyethylene vitamin E is too hydrophilic to exhibit a suitable surfactant function.

DESCRIPTION OF THE INVENTION In general, a surfactant consists of a hydrophobic atomic group and a hydrophilic atomic group with a chemical bond balanced between them. Through intensive study, the inventor of the present recognized that most of the surfactants are structured in such a way that they have hydrophobic atomic groups at one end and hydrophilic atomic groups at the other, but not all. For example, the nonionic surfactant marketed under the tradename "Pluronics" has polypropylene oxide as a hydrophobic atomic group, which on both sides has repeatedly added ethylene oxide (TH Vaughan, J. Am. Oil Chemists' Soc. 2p, 240 (1950)), as represented by the following formula: HO (C2H40) a (C3H60) b (C2H40) CH where each a, b and c are an integer from 20 to 80. It is necessary to consider special examples similar to this one (Synthesis of surfactants and applications thereof). p.4 'mj-i ** 3ft-1Z, 9! S 1956 Tokyo, Japan). Hydrophilicity prevails over hydrophobicity in ethylene oxide while propylene oxide is a little more hydrophobic than hydrophilic, so its polymers, polyethylene oxide and polypropylene oxide play a role as a hydrophilic atomic group and a hydrophilic atomic group, respectively, within a certain degree of polymerization (Daves, JT, Proc. 2nd Int. Congr. Surface Activity, London 1, 426 (1953)). As a consequence of the active research that the present inventors have carried out on the constituents of the cell membranes, with the aim of developing surfactants that have great improvements in safety for the skin, it was observed that the phospholipids have a diacyl group. hydrophobic and are present in a significant amount in all living microorganisms as well as being important constituents of all cell membranes. Natural or synthetic phospholipids are used commercially to form liposomes or vesicles. Another important aspect discovered by the inventors is that the lysophospholipids, each of which contains an acyl group, are used commercially as emulsifiers because of their surface activity superior to that of the phospholipids themselves (JL Harwood and NL Russel, Lipids in Plants an Microbes, George Allen and Unwin, London, 1984). The formation of closed liposomes or bilayer vesicles can be easily achieved by means of phospholipids, but with difficulty by lysophospholipids. Fatty acids, which are components of phospholipids, are safe materials and are widely used in cosmetics, skin ointments, etc. However, fatty acids have a strong toxic influence on cell membranes, so their use is allowed in a very low concentration range; Either way, they can occasionally break cells. In the phospholipids, the fatty acids are linked through ester bonds, while in the free state traces of extracellular fatty acids are found. Thus, fatty acids must be esterified in some proportion if they are found in intercellular regions including envelopes (Surfactant Science Series p27, Vol. 48, 1993, New York, Marcel Dekker Inc.). Based on the above, it is considered that the surfactants that are diacil phospholipid structure are lower in general surface activity such as emulsification, but higher in capacity to form liposomes or cell membrane type vesicles and especially also in biosecurity, with respect to the lysophospholipids that are acyl type.

Considering the background of the invention, the inventors of the present have made additional research to improve the safety of polyoxyethylene vitamin E while maintaining its high surface activity and finally found that if a hydrophobic fraction is added to the end of the hydrophilic fraction of polyoxyethylene vitamin E, the resulting compound has a controlled ratio of the hydrophilic group to the hydrophobic group and a different orientation characteristic. In this respect, the hydrophilic polyoxyethylene chain is present between two hydrophobic fractions, so that the extended alkyl chain is converted from an almost linear state to a curved state, which results in an increase in the cross-sectional area of the surfactant molecule . Accordingly, prepared vitamin E is a non-ionic amphipathic material that has excellent surface activity with a significant improvement in skin safety. This material can be prepared by subjecting vitamin E to the addition of a hydrophilic polyethylene oxide chain and a hydrophobic polypropylene oxide chain, in sequence, to such an extent that the ratio of the hydrophilic group to the hydrophobic group is adequate to form the vesicles . Therefore, it is an object of the present invention to provide a novel modified vitamin E that exhibits high surface activity with reliable safety for the skin. It is another object of the present invention to provide a novel modified vitamin E that is useful in cosmetics, foods, medicines. It is another object of the present invention to provide a method for preparing that novel modified vitamin E. It is still another object of the present invention to provide uses of the novel modified vitamin E. According to one aspect of the present invention, a novel polyoxypropylene polyoxyethylene vitamin E, represented by the following general formula I, is provided: [I] where, Ri is - (OCH2CH2) m- where m is an integer from 0 to 150; CH3 I R2 is H (0-CHCH2) n- where n is an integer from 1 to 200; CH3 CH3 I I A is -CH2 CH- or -CH = C-; B is -CH3 in the 5-, 7- or 8- position of vitamin E; and p is an integer of 1 or 3. According to another aspect of the present invention, there is provided a method for preparing the novel polyoxypropylene polyoxyethylene vitamin E, wherein the vitamin E represented by the following general formula II, is subjected to a reaction of addition with ethylene oxide, represented by the following formula III, in the presence of a catalyst and then with propylene oxide, represented by the following formula IV, in the presence of a catalyst: According to another aspect of the present invention, a skin care agent containing the novel polyoxypropylene polyoxyethylene vitamin E is provided. In the present invention, the polyoxypropylene polyoxyethylene vitamin E can be prepared from natural or synthetic vitamin E. In this regard, vitamin E is subjected to polyethoxylation and then to polypropoxylation in the presence of a catalyst. It can be a Lewis acid catalyst or an alkaline catalyst. The prepared polyoxypropylene polyoxyethylene vitamin E is tested to assess whether it works well as a surfactant, an antioxidant and a skin care agent, without harmful effects on the body. In this regard, the antioxidant activity is evaluated by determining the peroxide index, the foaming capacity and foam stability by means of the dynamic foam test, its surface tension by the Nuoy method and the surface activity by the formation of vesicles. The safety in the human body is confirmed through tests of irritation of the eyes and patch tests.

BRIEF DESCRIPTION OF THE DRAWINGS The foregoing and other objects, features and other advantages of the present invention will be understood more clearly from the following detailed description considering the accompanying drawings, in which: Figure 1 is a spectrum of 1H -NMR of synthetic vitamin E (di a -tocopherol); Figure 2 is a 1H-NMR spectrum of the polyoxypropylene polyoxyethylene vitamin E (1) prepared in Example I; Figure 3 is a spectrum of ""? -NMR of the polyoxypropylene polyoxyethylene vitamin E (2) prepared in Example II; Figure 4 is a spectrum of ^ "H-NMR of the polyoxypropylene polyoxyethylene vitamin E (3) prepared in Example III, Figure 5 is a spectrum of 1H-NMR of the polyoxypropylene polyoxyethylene vitamin E (4) prepared in Example IV: Figure 6 is a 1H-NR spectrum of the polyoxypropylene polyoxyethylene vitamin E (5) prepared in Example V. Figure 7a is an electron microphotograph showing a vesicle formed by the polyoxypropylene polyoxyethylene vitamin E (3). ) prepared in Example III; Figure 7b is an electron microphotograph showing a vesicle formed by the polyoxypropylene polyoxyethylene vitamin E (4) prepared in Example IV.

PREFERRED MODALITIES FOR CARRYING OUT THE INVENTION The present invention relates to a novel polyoxypropylene-polyoxyethylene vitamin E. This modified vitamin E is prepared by the sequential addition of vitamin E reaction with ethylene oxide and propylene oxide in the presence of a catalyst. of Lewis acid or alkaline. In the preparation of polyoxypropylene polyoxyethylene vitamin E, it should be considered that vitamin E is a secondary alcohol with antioxidant properties. Another pertinent consideration is that the reactive hydroxy group of vitamin E reacts slowly in the first stage of the reaction due to steric hindrance of the surrounding CH3 groups. Accordingly, a suitable selection of the amount of acid or alkaline catalyst and of the temperature and pressure to be used in the reaction is required. As a raw material, vitamin E can be synthetic, like di a-tocopherol or natural as that extracted from vegetable seeds. Useful examples of alkaline catalysts include CH3ONa, NaOH and KOH, while Lewis acid catalysts can be selected from BF3, SnCl4 and SbCl5. Based on the weight of the raw material or polyoxyethylene vitamin E, each of the catalysts is used in an amount between 0.02 and 0.8% by weight, but the amount may vary depending on the reaction conditions.

In general, the addition reaction is carried out at a temperature of 120 to 180 ° and preferably of 145 to 160 ° at a pressure of 1.0 to 8.0 kg / cm3 and preferably between 3.5 and 5.5 kg / cm2. A better understanding of the present invention may be obtained by considering the following examples which are set forth for purposes of illustration and are not considered to be limiting of the present invention.

EXAMPLE I Preparation of polyoxypropylene polyoxyethylene vitamin E (1) In a double stainless steel autoclave of 1L, 112 g (0.26 mol) of synthetic vitamin E (di a-tocopherol) and then 0.15 g of high purity sodium methoxide were introduced. (CH3ONa). The interior humidity of the reactor was removed by heating at 70 ° in vacuo at about 720 mmHg for about 20 min. Then, 132 g (3.0 mol) ethylene oxide was added to the reactor under pressure and they were allowed to react at 150-160 EC for about 6 hours with stirring, to give 244 g of a liquid phase of polyoxyethylene vitamin E, which was a little dispersed in water. This was subjected to an addition reaction with 35 g (0.6 mol) of propylene oxide for 8 hours at 145-155 ° in the presence of 0.1 g of sodium methoxide to give a yellow liquid phase. At the end of the reaction, the reactor was purged three times with nitrogen gas to remove unreacted ethylene oxide and propylene oxide and 1,4-dioxane, a by-product. The reaction mixture was cooled to about 30 ° and then a small amount of citric acid was added to neutralize the alkaline catalyst. It was purified by Sephadex LH-50 column chromatography eluting with a mixture of chloroform-methanol (1: 1, v / v) to obtain 265.5 g of polyoxypropylene-polyoxyethylene vitamin E (l) in a liquid phase. (1) Appearance: pale yellow liquid at room temperature (2) Elemental Analysis: as relative molecular weight of C55H? OO4 Calculated (%): C 66.94; H 10.34; N: 0.00 Found (%): C 67.16; H 10.82; N: 0.04 (3) Yield: 95.0% (4) Ethylene oxide moles added: 10 moles on average (5) Added propylene oxide moles: 2 moles on average (6) NMR spectrum The ^? - NMR spectra for synthetic vitamin E and polyoxypropylene polyoxyethylene vitamin E (l) are shown in Figures 1 and 2, respectively. As seen, the NMR spectrum of Figure 1 has a peak for -CH2CH2- or -CH3 registered at 1.17-1.3 d, three peaks for the -CH3 of the phenyl group at 4.1 d and a peak for the -OH group of the trimethyl phenol to 4.1 d. In Figure 2, the peak at 4.1 d disappears while peaks appear for the H of the polyethylene oxide - (CHCH20) m- and for the H, of the - (CH-CH2-0) n- of polypropylene oxide - ( CH (CH3) -CH2-0) nH at 3.5-3.8 d. Also, a peak of the -OH end of the propylene oxide appears at 3.97 d and in addition a peak is detected for the -CH3 of the polypropylene oxide - (CH (CH3) -CH2-0) n- a 1. 3 d.

EXAMPLE II Preparation of polyoxypropylene polyoxyethylene vitamin E (2) 220 g (0.51 mol) of synthetic vitamin E (di a-tocopherol) and then 0.2 g of high purity sodium methoxide were introduced in a 1 L double stainless steel autoclave. (CH3ONa). The internal humidity of the reactor was removed by heating at 75 ° under vacuum at about 750 mmHg for about 20 min. Then, 130 g (3.0 mol) ethylene oxide was added to the reactor under pressure and they were allowed to react at 145-155 ° for about 6 hours with stirring, to give 348 g of a liquid phase of polyoxyethylene vitamin E, which was a little scattered in the water. This was subjected to an addition reaction with 70 g (0.6 mol) of propylene oxide for 8 hours at 145-155 ° in the presence of 0.1 g sodium methoxide to give a yellow liquid phase. At the end of the reaction, the reactor was purged twice with nitrogen gas to remove unreacted ethylene oxide and propylene oxide and 1,4-dioxane, a by-product. The reaction mixture was cooled to about 30 ° and then a small amount of citric acid was added to neutralize the alkaline catalyst. It was purified by Sephadex LH-50 column chromatography eluting with a mixture of chloroform-methanol (1: 1, v / v) to obtain 405.4 g of polyoxypropylene-polyoxyethylene vitamin E (2) in liquid phase. (1) Appearance: pale yellow liquid at room temperature (2) Elemental analysis: as relative molecular weight of C45H8209 Calculated (%): C 70.5; H 10.7; N: 0.00 Found (%): C 71.3; H 11.4; N: 0.03 (3) Yield: 96.5% (4) Moles of ethylene oxide added: 5 moles on average (5) Added propylene oxide mole: 2 moles on average (6) NMR spectrum A spectrum of 1H is shown -NMR for polyoxypropylene-polyoxyethylene vitamin E (2) in Figure 3. In this NMR spectrum, when compared to the NMR spectrum of the Figure, the peak for -OH at 4.1 d disappears while peaks appear for H of polyethylene oxide - (CH2CH20) m- and for the H of - (CH-CH2-0) n- of the polypropylene oxide - (CH (CH3) -CH2-0) n H at 3.5-3.8 d. Also, an H peak of the -OH end of the propylene oxide appears at 3.97 d and in addition a peak is detected for the -CH3 of the polypropylene oxide - (CH (CH3) -CH2-0) n- at 1.3 d. The spectrum of Figure 3 is similar in its pattern to that of Figure 2 but more reduced, because fewer moles of polyoxyethylene and polyoxypropylene are used than those of polyoxyethylene and polyoxypropylene used in Example I.

EXAMPLE III Preparation of polyoxypropylene polyoxyethylene vitamin E (3) 125 g (0.29 mol) of synthetic vitamin E (di a-tocopherol) and then 0.2 g of high purity KOH were introduced into a 2L double stainless steel autoclave (99.9) %). The internal humidity of the reactor was removed by heating at 77 ° under vacuum of about 740 m Hg for about 30 min. Then, 300 g (6.8 mol) of ethylene oxide under pressure were added to the reactor and they were allowed to react at 160-165 ° for about 6 hours with stirring, to give a liquid phase of polyoxyethylene vitamin E, which was well dispersed in water . This was subjected to an addition reaction with 95 g (1.69 mol) of propylene oxide for 8 hours at 155-160 ° in the presence of 0.15 g of KOH (99.9%) to give a yellow liquid phase. At the end of the reaction, the reactor was purged three times with nitrogen gas to remove unreacted ethylene oxide and propylene oxide and 1,4-dioxane, a by-product. The reaction mixture was cooled to approximately 40 ° and then added a small amount of citric acid to neutralize the alkaline catalyst. After the unreacted vitamin E was removed with toluene, the reaction was purified by Sephadex LH-50 column chromatography eluting with a mixture of chloroform-methanol (1: 1, v / v) to obtain 505.7 g of polyoxypropylene-polyoxyethylene. Vitamin E (3) in liquid phase. (1) Appearance: pale yellow semisolid phase at room temperature (2) Elemental analysis: as relative molecular weight of C85H? 60O27 Calculated (%): C 63.28; H 9.93; N: 0.00 Found (%): C 64.21; H 10.7; N: 0.03 (3) Yield: 97.3% (4) Moles of ethylene oxide added: 20 moles on average (5) Added propylene oxide mole: 5 moles on average (6) NMR spectrum A spectrum of " "? -NMR for polyoxypropylene-polyoxyethylene vitamin E (3) in Figure 4. In this NMR spectrum, when compared to the NMR spectrum of Figure 1, the peak for -OH at 4.1 d disappears while the peaks for the H of the polyethylene oxide - (CH2CH20) m- and for the H of the - (CH-CH2-0) n- of the polypropylene oxide - (CH (CH3) -CH2-0) nH appear at 3.5-3.8 d .

Also, an H peak of the -OH end of the propylene oxide appears at 3.97 d and in addition a peak is detected for the -CH3 of the polypropylene oxide - (CH (CH3) -CH2-0) n- at 1.3 d. The spectrum of Figure 4 is similar in its pattern to that of Figure 2 but larger, because the moles of polyoxyethylene and polyoxypropylene used in this Example were more than those of polyoxyethylene and polyoxypropylene used in Example I.

EXAMPLE IV Preparation of polyoxypropylene polyoxyethylene vitamin E (4) In a 2L double stainless steel autoclave, 234 g (0.56 mol) of natural vitamin E (mixture of a, β, β, d-tocopherol), extracted from seeds, were introduced. vegetable, then 0.15 g of high purity sodium methoxide (CH3ONa) was added. The interior humidity of the reactor was removed by heating at 75 ° in vacuum at about 750 mmHg for about 25 min. Then, 80 g (1.83 mol) of ethylene oxide was added to the reactor under pressure and they were allowed to react at 150-160 ° for approximately 8 hours with stirring, to give a liquid phase of polyoxyethylene vitamin E, which was poorly dispersed in water. . This was subjected to an addition reaction with 36 g (0.62 mol) of propylene oxide for 8 hours at 145-155 ° in the presence of 0.1 g sodium methoxide (CH3ONa) to give a yellow liquid phase. At the end of the reaction, the reactor was purged three times with nitrogen gas to remove unreacted ethylene oxide and propylene oxide and 1,4-dioxane, a by-product. The reaction mixture was cooled to about 30 ° and then a small amount of citric acid was added to neutralize the alkaline catalyst. After the unreacted vitamin E was removed with toluene, the reaction was purified by Sephadex LH-50 column chromatography eluting with a mixture of chloroform-methanol (1: 1, v / v) to obtain 328.5 g of polyoxypropylene-polyoxyethylene vitamin. E (4) in liquid phase. (1) Appearance: a yellow liquid phase at room temperature (2) Elemental analysis: as relative molecular weight of C38H6806 Calculated (%): C 73.55; H 10.97; N: 0.00 Found (%): C 72.53; H 11.4; N: 0.03 (3) Yield: 93.9% (4) Ethylene oxide moles added: 3 moles on average (5) Added propylene oxide mole: 1 mole on average (6) NMR spectrum A spectrum of 1H is shown -NMR for polyoxypropylene-polyoxyethylene vitamin E (4) in Figure 5. In this NMR spectrum, when compared to the NMR spectrum of Figure 1, the peak for -OH at 4.1 d disappears while peaks appear for the H of polyethylene oxide - (CH2CH20) m- and for the H of - (CH-CH2-0) n- of the polypropylene oxide - (CH (CH3) -CH2-0) nH at 3.5-3.8 d. Also, an H peak of the -OH end of the propylene oxide appears at 3.97 d and in addition a peak is detected for the polypropylene oxide -CH3 - (CH (CH3) -CH2-0) n- at 1.3 d. The spectrum of Figure 4 is similar in its pattern to that of Figure 2, but smaller, because the moles of polyoxyethylene and polyoxypropylene used in this Example were less than those of polyoxyethylene and polyoxypropylene used in Example I.

EXAMPLE V Preparation of polyoxypropylene polyoxyethylene vitamin E (5) 125 g (0.30 mol) synthetic vitamin E (di a-tocopherol) and then 0.2 g high purity KOH (99.9%) were introd into a 2L double stainless steel autoclave. ). The internal humidity of the reactor was removed by heating at 77 ° under vacuum of about 740 mmHg for about 30 min. Then, 600 g (13.64 mol) of ethylene oxide under pressure were added to the reactor and they were allowed to react at 160-165 ° for about 6 hours with stirring, to give a liquid phase of polyoxyethylene vitamin E, which was well dispersed in water . This was subjected to an addition reaction with 175 g (1.64 moles) of propylene oxide for 8 hours at 155-160 ° in the presence of 0.15 g of KOH (99.9%) to give a yellow liquid phase. At the end of the reaction, the reactor was purged three times with nitrogen gas to remove unreacted ethylene oxide and propylene oxide and 1,4-dioxane, as a by-product. The reaction mixture was cooled to approximately 40 ° and then added a small amount of citric acid to neutralize the alkaline catalyst. Then, the unreacted vitamin E was removed with toluene, the reaction was purified by column chromatography on Sephadex LH-50 eluting with a mixture of chloroform-methanol (1: 1, v / v) to obtain 893.3 g of polyoxypropylene-polyoxyethylene. Vitamin E (5) in liquid phase. (1) Appearance: a pale yellow solid phase at room temperature (2) Elemental analysis: as relative molecular weight of C? 5oH248058 Calculated (%): C 58.5; H 8.1; N: 0.00 Found (%): C 59.2; H 8.0; N: 0.03 (3) Yield: 96.3% (4) Added ethylene oxide moles: 46 moles on average (5) Added propylene oxide mole: 10 moles on average (6) NMR spectrum A spectrum of " "" H-NMR for polyoxypropylene-polyoxyethylene vitamin E (5) in Figure 6. In this NMR spectrum, when compared to the NMR spectrum of Figure 1, the peak for -OH at 4.1 d disappears while peaks appear for the H of polyethylene oxide - (CH2CH20) m- and for the H of - (CH-CH2-0) n- of polypropylene oxide - (CH (CH3) -CH2-0) nH at 3.5-3.8 d) Also, an H peak of the -OH end of the propylene oxide appears at 3.97 d and a peak is also detected for the polypropylene oxide -CH3 - (CH (CH3) -CH2-0) n- at 1.3 d. The spectrum of Figure 4 is similar in its pattern to that of Figure 2, but larger, because the moles of polyoxyethylene and polyoxypropylene used in this Example were more than the moles of polyoxyethylene and polyoxypropylene used in Example I.

EXAMPLE VI Preparation of polyoxypropylene polyoxyethylene vitamin E (6) The same procedure as in Example III was repeated, with the exception that 120 g (0.29 mol) of natural vitamin E (mixture of β, β, and d-tocopherol were used). ) in place of synthetic vitamin E, to obtain 485 g of polyoxypropylene-polyoxyethylene vitamin E (21 moles of EO and 5 moles of OP on average) as semi-solid phase.

EXAMPLE VII Antioxidant Activity of Polyoxypropylene Polyoxyethylene Vitamin E A study was made of the antioxidant activity of polyoxypropylene polyoxyethylene vitamin E, using linoleic acid. The linoleic acid used was a reagent obtained from Sigma, U.S.A., with a content of 75% linoleic acid and 12.5% linolenic acid 12.5%. The polyoxypropylene polyoxyethylene vitamin E (l) prepared in Example I was added in an amount of 0.5% to linoleic acid, while vitamin E, vitamin E acetate, polyoxyethylene (120E) vitamin E, polyoxyethylene monostearate ( 20OE) sorbitan (T EEN-60) and polyoxyethylene (120E) nonylphenyl ether (Igepal-CO880) as references. These samples were placed in an incubator that was maintained at 40 °. At two and ten days after incubation, the peroxide value was determined for each sample. In more detail, in a 250 ml Erlenmeyer flask, 1.0 g of each of the samples were placed and 10 ml of chloroform was added to dissolve the sample, then 15 ml of glacial acetic acid and 1 ml of saturated potassium iodide solution were added and the flask was capped. After vigorous shaking, the flask was allowed to stand in a dark place for 5 min. Then, 75 ml of distilled water was added to it and vigorously stirred. The free iodine was titrated with a 0.01 N sodium thiosulfate solution, using a starch solution as an indicator. The point at which the solution becomes colorless was considered as the end point. The peroxide value was calculated as follows: POV (eq / kg) = (S - B) xF Sample quantity (g) S: Amount of 0.01 N sodium thiosulfate solution consumed by the sample (mi) B: Amount of 0.01 N sodium thiosulfate solution consumed in the white test tube (mi) F: 0.01 N sodium thiosulfate solution factor The results are summarized in Table 1, below.

TABLE 1 Peroxide Indexes As evident from the data of Table 1, the polyoxypropylene polyoxyethylene vitamin E (1) prepared in Example I, the polyoxypropylene polyoxyethylene vitamin E (3) prepared in Example III and the polyoxypropylene polyoxyethylene vitamin E ( 4) prepared in Example IV are less potent in their antioxidant activity than vitamin E, a physiologically active antioxidant, but show antioxidant activity similar to that of vitamin E acetate, a stable antioxidant derivative of vitamin E, with superiority on polyoxyethylene monostearate (120E), polyoxyethylene (20OE) sorbitan and polyoxyethylene (120E) nonylphenyl ether.

EXAMPLE VIII Surface activity of the polyoxypropylene polyoxyethylene vitamin EA In order to make a review of the surface activity of the novel polyoxypropylene polyoxyethylene vitamin E, the polyoxypropylene polyoxyethylene vitamin E prepared in Example I to VI was analyzed to evaluate surface tension, capacity foaming and foam stability, together with polyoxyethylene (240E) cholesterol and polyoxyethylene (120E) vitamin E. 1. Foaming capacity and foam stability Foaming capacity and foam stability were determined according to a dynamic foam test. First, in a 2 L scale cylinder with an outer diameter of 10 cm, 40 ml of a solution of each 0.1% sample was loaded in water and the solution was stirred at 1,000 rpm. ° for 1 min with an agitator-mixer. The height of the foam layer thus formed was considered as the foaming capacity, while the volume ratio of the foam layer formed immediately after the stirring thereof, which is maintained for three minutes after stirring, was considered as foam stability. The results are given in Table 2, below.

TABLE 2 Foaming capacity and foam stability The data in Table 2 show that the polyoxy-propylene-polyoxyethylene vitamin E (5) with 46 moles of ethylene oxide and 10 moles of propylene oxide on average has a higher foaming capacity and foam stability than polyoxypropylene-polyoxyethylene vitamin E ( 1) and shows almost the same foaming capacity and foam stability as polyoxyethylene (240E) reference cholesterol. 2. Surface tension At 20 °, solutions of the 0.1% samples in water were analyzed to determine the surface tension according to the Nuoy method with the help of a surface tension balance manufactured by Fisher Scientific. The results are presented in Table 3, below.

TABLE 3 Surface tension in 0.1% aqueous solution (20 °) As shown in Table 3, the polyoxypropylene polyoxyethylene vitamin E (5) has a surface tension of 42.5 dynes / cm, which is slightly higher than that of polyoxyethylene (240E) cholesterol. 3. Vesicle Formation In order to examine another property of the surface action of the polyoxypropylene polyoxyethylene vitamin E, vesicles were formed using 5% aqueous solutions of the polyoxypropylene polyoxyethylene vitamin E prepared in Examples III and V. First, the aqueous solutions they were maintained at 25 ° while stirring with a high frequency tip generator, an equal volume of a 2% uranyl acetate solution was added and they were shaken manually. Subsequently, the resulting solution was added dropwise on a carbon-coated copper grid with a size of 200 mesh and dried at room temperature for approximately 20 min. The observation was made with the help of an electron microscope, manufactured by Philips, which operates at 80 KV. The electron microphotographs are shown in Figure 7. As can be seen, closed globular vesicles were formed with a bilayer structure.

EXAMPLE IX Security in living organisms 1. Eye Irritation Test In order to assess the safety of the novel polyoxypropylene-polyoxyethylene vitamin E, a primary irritation test was performed on rabbits as described Draize The polyoxypropylene polyoxyethylene vitamin E (5) prepared in Example V, polyoxyethylene (120E) nonylphenyl ether and polyoxyethylene (20OE) sorbitan monostearate were each diluted with an aqueous solution of % glycerin to give a 10% sample solution.

This test sample was applied in drops to one eye of each of the 6 rabbits, which had a weight of 2 to 3 kg, while the other eye was used as a control. 24 hours later, the average scores were recorded according to the Draize scale for eye injuries. If injuries occurred, the time was extended; otherwise, the observation was suspended. The results are presented in Table 4, below. TABLE 4 Eyes irritation test according to the Draize procedure As seen in Table 4, polyoxypropylene polyoxyethylene vitamin E (5) is a weaker irritant than the other test samples, ie, polyoxyethylene (20OE) sorbitan monostearate, polyoxyethylene (120E) vitamin E, and polyoxyethylene (120E) nonylphenyl ether and therefore, can be used safely in medicines, foods and cosmetics, such as elemental cosmetics, cosmetics for makeup and cosmetics for hair care. The amount that is added of the polyoxypropylene polyoxyethylene vitamin E according to the present invention is dependent on its purposes and the type of materials with which it is to be used, but preferably it is of the order of approximately between 0.05 and 60% by weight. 2. Patch test In order to confirm the non-toxicity of the polyoxypropylene polyoxyethylene vitamin E according to the present invention, a patch test was performed on the human body, according to the Finn Chamber method. All the subjects of the test were women with ages between 15 and 35 years. A sample of material was applied on the upper arm of each of the subjects and a "dermicel" tape was placed in place. Skin irritations were evaluated as a response rate (%) according to an International Contact Dermatitis Research Group (ICDRG) standard after 24 to 48 hours. The results are presented in Table 5, below.

TABLE 5 The data presented in Table 5 show that polyoxypropylenepolyoxyethylene vitamin E does not produce skin irritations and its application is safer than controls, polyoxyethylene (20OE) sorbitan monostearate, polyoxyethylene vitamin E and polyoxyethylene ( 120E) nonylphenyl ether.

INDUSTRIAL APPLICATION As described below, the polyoxypropylene polyoxyethylene vitamin E of the present invention, which can be prepared by the two step addition reaction of the antioxidant and physiologically active vitamin E with ethylene oxide and then with hydrophobic propylene oxide to an appropriate degree, has superior antioxidant activity and presents solubility in water. The curved chain of polyoxypropylene polyoxyethylene vitamin E increases the cross-sectional area of the total molecule, which makes it difficult for the molecule to penetrate the skin. Therefore, its application on the skin is very safe. In addition, polyoxypropylene polyoxyethylene vitamin E has excellent surface activity by forming closed bilayer vesicular structures, in the same way as phospholipids or dialkyl surfactants, so it can be advantageous to use it in the industry

Claims (12)

1. Polyoxypropylene polyoxyethylene vitamin E, represented by the following general formula I: [I] where, Ri is - (OCH2CH2) m- where m is an integer from 0 to 150; CH3 I R2 is H (0-CHCH2) n- where n is an integer from 1 to 200; CH, CH3 I A is -CH2CH- or -CH = C-; B is -CH3 in positions 5-, 7- or 8- of vitamin E; and p is an integer of 1 or 3.

2. A method for preparing polyoxypropylene polyoxyethylene vitamin E, represented by the following general formula I: [I] where, Ri is - (OCH2CH2) m- where m is an integer from 0 to 150; CH3 I R2 is H (0-CHCH2) n- where n is an integer from 1 to 200; CH3 CH3 I I A is -CH2 CH- or -CH = C-; B is -CH3 in the 5-, 7- or 8- position of vitamin E; and p is an integer of 1 or 3, wherein vitamin E represented by the following general formula II: wherein A, B and p are as defined above, is subjected to an addition reaction with ethylene oxide, represented by the following formula III: or [III] in the presence of a catalyst and then with propylene oxide, represented by the following formula IV; / [IV] CHJ-CHJ CHI in the presence of a catalyst.

3. A method according to claim 2, wherein the vitamin E is selected from the group consisting of synthetic vitamin E, natural vitamin E and ester compounds derived therefrom.

4. A method according to claim 3, wherein the synthetic vitamin E is selected from the group consisting of dl-a-tocopherol, dl-β-tocopherol, dl-α-tocopherol and dl-d-tocopherol.

A method according to claim 3, wherein the vitamin E is vitamin E acetate or vitamin E succinate.

6. A method according to claim 2, wherein the polyoxypropylene polyoxyethylene vitamin E has adequate surface activity by selecting m and n of integers that vary from 0 to 150 and from 1 to 200, respectively.

A method according to claim 2, wherein the catalyst is an alkaline catalyst selected from CH30Na, NaOH and KOH or a Lewis acid catalyst selected from BF3, SnCl4 and SbCl5 and used in an amount of 0.02 to 0.8% in weight in each of the stages of polyethoxylation and polypropoxylation.

8. A method according to claim 2, wherein the addition reaction is carried out at a temperature of 135 to 170 °.

9. A method according to claim 2, wherein the addition reaction is carried out at a pressure of 3.5 to 5.5 kg / cm2.

10. A surfactant, comprising the polyoxypropylene polyoxyethylene vitamin E according to claim 1, as an active ingredient.

11. An antioxidant, comprising the polyoxypropylene polyoxyethylene vitamin E according to claim 1, as an active ingredient.

12. A humectant, comprising the polyoxypropylene polyoxyethylene vitamin E according to claim 1, as an active ingredient. SUMMARY A polyoxypropylene polyoxyethylene vitamin E is disclosed, represented by the following formula. It is prepared by submitting vitamin E to polyethoxylation and then to polypropoxylation to an appropriate degree. Vitamin E has superior antioxidant activity and has water solubility. The curved chain of polyoxypropylene polyoxyethylene vitamin E increases the cross-sectional area of the total molecule, which makes it difficult for the molecule to penetrate the skin. Therefore, its application on the skin is very safe. In addition, polyoxypropylene polyoxyethylene vitamin E has an excellent surface activity by the formation of closed bilayer vesicular structures, as do phospholipids or dialkyl surfactants, so it can be advantageous to use it in the cosmetics industry, the food industry and the industry. pharmaceutical -CHj wherein, Ri is - (OCH2CH2) m- where m is an integer from 0 to 150; CH3 I R2 is H (0-CHCH2) n- where n is an integer from 1 to 200; CH3 CH3 I I A is -CH2 CH- or -CH = C-; B is -CH3 in the 5-, 7- or 8- position of vitamin E; and p is an integer of 1 or 3.