KR100453727B1 - Novel polyoxypropylenepolyoxyethylene vitamin E and process for preparation thereof - Google Patents

Abstract

The present invention relates to a novel polyoxypropylene polyoxyethylene (POE-POE) vitamin E and a method for producing the same. Antioxidant biological activity in the preparation of polyoxypropylene polyoxyethylene vitamin E represented by the following general formula (I) Polyoxypropylene polyoxyethylene which addition-polymerized propylene oxide (n = 1-200 mol) to polyoxyethylene vitamin E which did not add ethylene oxide group to the hydroxyl group (OH) of vitamin E, or added 1 mol. Vitamin E has a propylene oxide (PO) chain closer to the chromatin ring of tocopherol, which improves the delocalization of non-covalent electron bands, thereby enhancing the in vivo anti-oxidation ability and the ability to form vesicles. Polyoxyethylene vitamin E obtained by adding ethylene oxide (m = 0 to 150 mol) to the hydroxyl group (OH) of vitamin E A polyoxypropylene polyoxyethylene produced by addition polymerization of propylene oxide (n = 101~200 mol) has the excellent effect that exhibits good yuhwaryeok and antioxidative ability is enhanced hydrophobic and hydrophilic so balanced.

Wherein R ₁ is-(OCH ₂ CH ₂ ) _m- , R ₂ is ego; m is an integer from 0 to 1 when n is an integer from 1 to 200, or n is an integer from 101 to 200 when m is an integer from 0 to 150; A is B is CH _{3 at} the 5-, 7- or 8- position of vitamin E and P is an integer of 1, 3.

Description

Novel polyoxypropylenepolyoxyethylene vitamin E and process for preparation according to novel polyoxypropylene polyoxyethylene vitamin E

The present invention relates to a novel polyoxypropylene polyoxyethylene vitamin E and a method for producing the same. More specifically, the present invention relates to a polyoxypropylene polyoxyethylene vitamin E, a novel amphiphilic substance which is excellent in antioxidant activity, surfactant activity, and skin softening effect and excellent in skin safety, and a method for producing the same.

Surfactants are generally adsorbed on the interface or surface in an aqueous solution to have a property of significantly lowering the interfacial tension or surface tension. Lipids exhibiting surfactant activity in vivo are involved in the biological activity of organs and tissues, and industrially made surfactants are widely used in medicine, food, cosmetics and other industries, depending on their function and use. It can be divided into various agents such as an agent, a foaming agent, an antifoaming agent, an abrasive, a lubricant, a surface treatment agent, and a humectant. Surfactants can be divided into ionic surfactants and nonionic surfactants according to the nature of the hydrophilic group. The ionic surfactants are water-soluble because the hydrophilic groups have ions, and the nonionic surfactants are formed by hydrogen bonding with water. It shows solubility. In vivo in animals, since a large amount of ionic substances are present, it is generally known that nonionic substances have better in vivo compatibility than ionic substances. Therefore, many nonionic surfactants are mainly used in bio-related products. Representative nonionic surfactants are a group of surfactants that do not have an ion group as ionized hydrophilic groups, all of which have -OH groups so that the hydrophilic groups are dissolved in water, and relatively less hydrophilic, but esters (-CO, O-), acidamide in the molecule (-CO.NH-) and ether (-O-) bonds. As the nonionic surfactant, a polyethylene glycol condensation type product is most widely used and important. For example fatty acid polyethylene glycol condensates (Niosol, Myrj), fatty acid amide polyethylene glycol condensates, aliphatic alcohol polyethylene glycol condensates (Leonil, Peregal C), aliphatic amine polyethylene glycol condensates, aliphatic mercaptan polyethylene glycol condensates (Nyon 218), alkylphenol polyethylene glycol condensates (Igepal) and polypropylene glycol polyethylene glycol condensates (Pluronics) and the like. Recently, various types of surfactants having a complicated structure have been developed and used, and the importance of nonionic surfactants has been added.

In general, both ionic and nonionic surfactants are known to make molecules or aggregates of ions called micelles. However, there are many differences between ionic and nonionic surfactants in making such micelles. The ability to make micelles is one of the important properties of surfactants, and it is known that the structure of surfactants greatly affects them, and numerous types of surfactants have been developed and used for practical purposes. The formation of micelles in aqueous solutions by nonionic surfactants can be identified as surface tension, light scattering, interaction with pigments and other studies. Nonionic surfactants are known to cause micelles due to the nature of the alkyl chain in the molecule being released from the aqueous phase at a certain concentration due to the cohesion of water, that is, the basic amphipathic structure.

The inventors have found that it is also the structure of the hydrophobic alkyl group that decisively affects these characteristics of the nonionic surfactant and the properties of the amphiphilic structure, and the intensive study of these characteristic alkyl group structures results in regular dense lipids in vivo. It is thought that vitamin E, which is well inserted into bilayer cell membranes and protects the biofilm from oxidation, can serve as an excellent hydrophobic group when used as a hydrophobic group of a surfactant. Invented and patented polyoxyethylene vitamin E which has excellent skin softening and moisturizing effect and protects living cells from harmful free radicals (Korean Patent No. 083024, US Patent No. 5,235,073, JP No. 10362). As expected, however, polyoxyethylene vitamin E was very well adsorbed to the interface due to its structural characteristics, but showed good surface activity. However, some types of surfactants needed to improve skin safety. In other words, the flat and hard chromane ring part of the hydrophobic part is piled up well, and the phytyl group at the end has a relatively small cross-sectional area and has fluidity. Was thought to cause problems. This safety problem could be solved by adjusting the length of the ethylene oxide chain in the surfactant, that is, by lengthening the length of the polyethylene oxide chain. However, at this time, the hydrophilicity is so large that the function as the desired surfactant is deteriorated. The present inventors first polymerize ethylene oxide (EO) to vitamin E to obtain polyoxyethylene vitamin E, and further polymerize propylene oxide to polyoxyethylene vitamin E again to form vitamin E in a polyoxyethylene chain of suitable length. Invented polyoxypropylene polyoxyethylene vitamin E, a new nonionic amphiphilic substance having antioxidant capacity with excellent hydrophobicity and improved skin safety due to proper size ratio of hydrophobic group to hydrophilic group by having polyoxypropylene chain . (Application No. 98-20705)

However, in the case of the polyoxypropylene polyoxyethylene vitamin E, its structural characteristics have excellent liquid crystal production and form a vesicle and have excellent surface activity and antioxidant properties, but ethylene oxide (EO) is added to vitamin E in a large amount. As the water solubility increases and the antioxidant power decreases, the antioxidant capacity is weaker than that of the vitamin E tocopherol, which is in vivo. In an ongoing study, the inventors have found that the number of moles of propylene oxide (PO) is 2, 5, 10, etc., even if ethylene oxide (EO) is not polymerized (to m = 0) or only 1 mole is added to tocopherol (m = 1). Polyoxypropylene polyoxyethylene vitamin E showed excellent surface activity such as vesicle formation under suitable solvent conditions. When mole number of PO is added when only EO is added to vitamin E without addition polymerization, It was found that the higher the solubility in water, the lower the solubility in water and the better emollient properties.

In addition, the polyoxypropylene polyoxyethylene (POP-POE) of the present inventors of the present invention, polyoxypropylene (POP) of vitamin E has no problem when the polyoxyethylene (POE) is relatively small, but the POP in the vicinity of 150 EO where the POE is relatively large Due to the oxygen atom (O) in PO contained in the structure of the individual PO does not have strong hydrophobicity, even in 100 PO having a relatively large POP, the hydrophobicity was not sufficient, and the function as an excellent emulsifier was insufficient. Therefore, in order to show excellent emulsification, hydrophobicity is required to be improved, which is proposed by Davis JT (Proc. 2nd. Int. Congr. Surface activity, London 1, 426, 1957). HLB) groupnumber: The hydrophilic group has a positive value and the hydrophobic group has a negative value]. Tocopherol is also described as a group number value of -8.65 for EO, 1.3 for EO and -0.125 for PO. However, if the hydrophobicity is too large, proper orientation of the hydrophobic group was required because the orientation property at the interface could be disturbed and the antioxidant power could be reduced. The inventors have found that increasing the length of the added POP hydrophobic group in the patent application to 200 moles of P.O shows that the polyoxypropylenepolyoxyethylene exhibits moderate antioxidant activity, good emulsifying surfactant activity and liquid crystal generation ability.

In view of the above fact, the present inventors adjusted the size of the hydrophobic group POP and the hydrophilic group POE of polyoxypropylene polyoxyethylene (POP-POE) vitamin E by adding the mole number of (EO) of ethylene oxide to 0-1. As a result, polyoxypropylenepolyoxyethylene vitamin E having excellent hydrophobicity and superior antioxidant activity compared to conventional polyoxypropylene polyoxyethylene (POP-POE), which has been applied for at low molecular weight, was prepared. The present invention has been completed by preparing polyoxypropylene polyoxyethylene vitamin E exhibiting excellent emulsification power by adding a mole number of PO to be in the range of 101 to 200 to enhance hydrophobicity in balance with hydrophilicity.

Therefore, the objective of this invention was devised in view of the above fact, and is following General formula (I)

[Wherein R ₁ is-(OCH ₂ CH ₂ ) _m- , R ₂ is ego; m is an integer from 0 to 1 when n is an integer from 1 to 200, or n is an integer from 101 to 200 when m is an integer from 0 to 150; A is Is; B is CH _{3 at} the 5-, 7- or 8- position of vitamin E and P is an integer of 1, 3].

Another object of the present invention is to react vitamin E represented by the following general formula (II) with ethylene oxide (EO) represented by the following general formula (III), and then again to propylene oxide (PO) represented by the following general formula (IV) And a method for producing polyoxypropylene polyoxyethylene vitamin E of the following general formula (I).

[Wherein, R ₁ is-(OCH ₂ CH ₂ ) _m- , R ₂ is ego; when n is an integer from 1 to 200 m is an integer from 0 to 1; Or n is an integer from 101 to 200 when m is an integer from 0 to 150; A is Is; B is CH _{3 at} the 5-, 7- or 8- position of vitamin E and P is an integer of 1, 3].

Another object of the present invention is to provide a skin protectant containing the novel polyoxypropylenepolyoxyethylene vitamin E.

The object of the present invention is not to add ethylene oxide group or 1 mole of hydroxy group (OH) of synthetic vitamin E or natural vitamin E using basic catalyst or Lewis acid catalyst in dry container under anhydrous high pressure condition Polyoxypropylene polyoxyethylene vitamin E was prepared by addition-polymerizing propylene oxide (n = 1 to 200) to the obtained polyoxyethylene vitamin E (m = 0 to 1), and further obtained by adding an ethylene oxide group (m = 0 to 150) Polyoxyethylene vitamin E of polyoxyethylene vitamin E having various molecular weights of different polyoxypropylene polyoxyethylene vitamin E having different molecular weights by addition polymerization from 101 moles or more of propylene oxide to 200 moles (i.e., m = 0 to n = 200) 1 or n = 101 to 200 when m = 0 to 150), and the antioxidative power of the polyoxypropylene polyoxyethylene vitamin E prepared above and the occurrence of red hair due to ultraviolet rays It was achieved by investigating the influence and the surface-active action on melanin formation.

Hereinafter, the configuration and operation of the present invention will be described in detail.

1 is a ¹ H NMR spectrum of the polyoxypropylene polyoxyethylene vitamin E (1) prepared in Example 1. FIG.

2 is a ¹ H NMR spectrum of the polyoxypropylene polyoxyethylene vitamin E (3) prepared in Example 3. FIG.

Figure 3 is a vesicle scanning electron micrograph of the polyoxypropylene polyoxyethylene vitamin E (1) prepared in Example 1.

The present invention comprises the steps of preparing and analyzing a liquid polyoxypropylene (POP5-POE0) vitamin E at room temperature by reacting synthetic vitamin E and propylene oxide in the presence of a catalyst methoxy sodium (CH ₃ ONa); Preparing and analyzing liquid polyoxypropylene [POP (2) -POE (0)] vitamin E at room temperature by reacting with synthetic vitamin E and propylene oxide in the presence of a catalyst potassium hydroxide (KOH); Polyoxyethylene Batamine E is obtained by reacting natural vitamin E with ethylene oxide in the presence of potassium hydroxide (KOH) as a catalyst, followed by propylene oxide in the presence of potassium hydroxide (KOH) as a catalyst. Preparing and analyzing oxyethylene [POP (10) -POE (1)] vitamin E; Synthetic vitamin E, ethylene oxide, propylene oxide and the amount of sodium hydroxide as a catalyst are reacted in the same manner as described above to react polyoxypropylene polyoxyethylene [POP (150) -POE (100), POP (200), which is semi-solid at room temperature. ) -POE (150)] preparing and analyzing the vitamin E; polyoxypropylene polyoxyethylene vitamin E by adding linoleic acid to the prepared new polyoxypropylene polyoxyethylene vitamin E and measuring the peroxide value over time Measuring the antioxidant power of the; The polyoxypropylene polyoxyethylene vitamin E prepared above is applied to human skin, and irradiated with ultraviolet rays, thereby examining the effect of polyoxypropylene polyoxyethylene vitamin E on erythema generation and melanin pigmentation caused by ultraviolet rays.

The POP (n) -POE (m) represents added propylene oxide (average moles) -added ethylene oxide (average moles).

Vitamin E used in the synthesis of polyoxypropylene polyoxyethylene vitamin E of the present invention is extracted from synthetic vitamin E, such as dl-α tocopherol, dl-β tocopherol, dl-γ tocopherol or dl-δ tocopherol, or seeds of plants. Natural vitamin E or esters thereof, and vitamin E esters include vitamin E acetate, vitamin E palmitate, vitamin E succinate and vitamin E linoleate.

CH ₃ ONa, NaOH or KOH is used as the basic catalyst of the present invention, and BF ₃ or SnCl ₄ or SbCl ₅ is used as the Lewis acid catalyst and 0.02 for vitamin E or for polyoxyethylene vitamin E, respectively. It is used in an amount of -0.8% by weight, but it can be used appropriately depending on the reaction conditions.

In the present invention, the reaction temperature is generally 120-180 ° C, preferably 145-160 ° C, and the reaction pressure is generally 1.0-8.0 kg / cm^2,Preferably 3.5-5.5 kg / cm²Hereinafter, specific examples of the present invention will be described in detail with reference to Examples, but the scope of the present invention is not limited to these Examples.

Example 1 Preparation of Polyoxypropylene Polyoxyethylene [POP (5) -POE (0)] Vitamin E (1)

129.2 g (0.30 mol) of synthetic vitamin E (dl α-tocopherol) was added to a 1-liter stainless steel autoclave, and 0.15 g of high-purity methoxy sodium (CH ₃ ONa) was added. It was about 730 mmHg and dehydrated for about 30 minutes, and then 116 g (2.0 mol) of propylene oxide was injected and reacted at 150-155 ° C. for 8 hours to obtain a pale yellow liquid. After the completion of the reaction, the reaction mixture was evacuated three times with nitrogen to remove unreacted propylene oxide, the reaction mixture was cooled to about 30 ° C., and a small amount of citric acid was added to neutralize the alkaline component added to the catalyst and eluted chloroform-methanol (1: 1). Purified with Sephadex LH-50 column chromatography using a solvent, 235.6 g of liquid polyoxypropylene vitamin E (1) was obtained. The analysis results of the liquid product are as follows.

Analysis

(1) Appearance: Light yellow substance which is liquid at room temperature

(2) Elemental analysis result: C ₄₄ H ₇₉ O _{7 as} molecular weight (relative molecular weight)

Calculated Value (%): C: 73.44, H: 10.98, N: 0.00

Found (%): C: 73.21, H: 11.03, N: 0.03

(3) Yield of reaction: 96.1%

(4) Number of moles of added ethylene oxide (average): 0 mol

(5) Number of moles of propylene oxide added (average): 5 moles

(6) NMR (nuclear magnetic resonance) spectrum

The ¹ H NMR spectrum of the polyoxypropylene polyoxyethylene vitamin E (1) prepared in this example is as shown in Figure 1 and compared with the ¹ H NMR spectrum of vitamin E. The ¹ H NMR spectrum of vitamin E shows -CH ₂ -CH ₂ -or -CH ₃ peak at 1.17-1.3δ, -CH ₃ (3) peak of phenyl at 2.8δ and -OH of trimethylphenol at 4.1δ In the ¹ H NMR spectrum of the polyoxypropylene vitamin E (1) obtained in this example of FIG. 1 while the peak appeared, the -OH peak at 4.1δ disappeared and the polypropylene oxide-(CH (CH ₃ ) -CH ₂ -O ) _{n of} H H was a peak is observed in 3.5-3.8δ, got an H peak of the end -OH of propylene oxide appears at 3.97δ, polypropylene oxide _{- (CH (CH 3) -CH} 2 -O) n - in -CH ₃ The peak of was added to 1.3δ.

Example 2 Preparation of Polyoxypropylene Polyoxyethylene [POP (2) -POE (0)] Vitamin E (2)

220 g (0.51 mol) of synthetic vitamin E (dl α-tocopherol) was added to an autoclave of 1 L of double stainless steel, and 0.2 g of high purity potassium hydroxide was added thereto, followed by heating to 75 ° C. to obtain a vacuum of about 750 mmHg. After dehydrating for about 30 minutes, 64 g (1.1 mol) of propylene oxide was indented and reacted with stirring at 135-145 ° C. for about 6 hours to obtain a yellow liquid. After completion of the reaction, the reaction product was evacuated twice with nitrogen to remove unreacted propylene oxide and byproduct 1,4-dioxane, the reaction mixture was cooled to about 30 ° C., and a small amount of citric acid was added to neutralize the alkali component added to the catalyst and not react. Vitamin E was removed with toluene and purified by Sephadex LH-50 column chromatography using chloroform-methanol (1: 1) as eluent to obtain 271.5 g of liquid polyoxypropylene vitamin E (2). The analysis results are as follows.

Analysis

(1) Appearance: Light yellow substance which is liquid at room temperature

(2) Elemental analysis result: As molecular weight (relative molecular weight) C ₃₅ H ₆₁ O ₄

Calculated Value (%): C: 77.06, H: 11.2, N: 0.00

Found (%): C: 76.87, H: 11.36, N: 0.04

(3) Yield of reaction: 95.0%

(4) Number of moles of added ethylene oxide (average): 0 mol

(5) Number of moles of propylene oxide added (average): 2 moles

Example 3 Polyoxypropylene Polyoxyethylene [POP (10) -POE (1)] Preparation of Vitamin E (3 ) 107.7 g of synthetic vitamin E (dl α-tocopherol) in an autoclave of 2 L of double stainless steel ( 0.25 mol), add 0.1 g of high-purity potassium hydroxide (99.9%), and heat to 80 ° C to obtain a vacuum of about 750 mmHg, dehydrate for 40 minutes, and inject 13.2g (0.3 mol) of ethylene oxide into 160- The reaction was completed with stirring at 165 ° C. for about 6 hours. After completion of the reaction, a liquid reaction product was obtained, and then, polyoxyethylene vitamin E obtained in the presence of 0.15 g of KOH (99.9%) was reacted with 174 g (3.0 mol) of propylene oxide at 156-160 ° C. for 7 hours to obtain a pale yellow liquid. After completion of the reaction, the reaction mixture was evacuated three times with nitrogen to remove unreacted ethylene oxide, propylene oxide, and by-product 1,4-dioxane. The reaction mixture was cooled to about 30 ° C., and a small amount of citric acid was added to neutralize the alkaline component added to the catalyst. . Unreacted vitamin E was removed with toluene and purified with Sephadex LH-50 column chromatography using chloroform-methanol (1: 1) as an eluting solvent to obtain 283.1 g of liquid polyoxypropylenepolyoxyethylene vitamin E (3). The analysis results of this liquid product are as follows.

Analysis

(1) Appearance: Light yellow substance which is liquid at room temperature

(2) Elemental Analysis Result: As C ₆₁ H ₁₁₃ O ₂₃ Molecular Weight (relative molecular weight)

Calculated Value (%): C: 60.35, H: 9.32, N: 0.00

Found (%): C: 60.75, H: 9.10, N: 0.03

(3) Yield of reaction: 96.0%

(4) Number of moles of added ethylene oxide (average): 1 mole

(5) Number of moles of propylene oxide added (average): 10 moles

(6) NMR spectrum

The ¹ H NMR spectrum of the polyoxypropylene polyoxyethylene vitamin E (3) obtained in this example is shown in Figure 2 and compared with the ¹ H NMR spectrum of vitamin E. In Figure 2, the -OH peak of 4.1δ seen in vitamin E disappears and the H peak of polyethylene oxide (-CH ₂ -CH ₂ -O) _m -and polypropylene oxide-(CH (CH ₃ ) -CH ₂ -O) _n H The H peak of was found at 3.5-3.8δ, the peak of -OH at the end of propylene oxide was found at 3.97δ, and the peak of -CH ₃ in polypropylene oxide-(CH (CH ₃ ) -CH ₂ -O) _n H The peak was added to 1.3δ.

Example 4 Preparation of Polyoxypropylene Polyoxyethylene [POP (150) -POE (100)] Vitamin E (4)

Into an autoclave of 2 L of double stainless steel, 8.61 g (0.02 mol) of synthetic vitamin E (dl α-tocopherol) was added, followed by 0.2 g of high-purity potassium hydroxide (99.9%), and heated to 75 ° C., and the degree of vacuum was reduced. After dehydrating for about 30 minutes to 750 mmHg, 101.2 g (2.3 mol) of ethylene oxide was injected and reacted with stirring at 160-165 ° C. for about 6 hours. After completion of the reaction, the obtained polyoxyethylene vitamin E was reacted with 200 g (3.45 mol) of propylene oxide at 155 to 160 ° C. for 8 hours in the presence of 0.15 g of KOH (99.9%) to obtain a pale yellow solid. After completion of the reaction, the reaction mixture was evacuated three times with nitrogen to remove unreacted ethylene oxide, propylene oxide, and by-product 1,4-dioxane. The reaction mixture was cooled to about 45 ° C., and a small amount of citric acid was added to neutralize the alkaline component added to the catalyst. . Unreacted vitamin E was removed with toluene and purified with Sephadex LH-50 column chromatography using chloroform-methanol (1: 1) as an eluting solvent to obtain 291.2 g of solid polyoxypropylenepolyoxyethylene vitamin E (4). The analysis results of this liquid product are as follows.

Analysis

(1) Appearance: A pale yellow substance that is semisolid at room temperature.

(2) Elemental analysis: C ₆₇₉ H ₁₃₄₉ O _{252 as} molecular weight (relative molecular weight)

Calculated Value (%): C: 60.23, H: 9.97, N: 0.00

Found (%): C: 60.58, H: 10.02, N: 0.04

(3) Yield of reaction: 94.0%

(4) Number of moles of added ethylene oxide (average): 100 moles

(5) Number of moles of propylene oxide added (average): 150 moles

Example 5 Preparation of Polyoxypropylene Polyoxyethylene [POP (200) -POE (150)] Vitamin E (5)

4.3 g (0.01 mol) of synthetic vitamin E (dl α-tocopherol) was added to a 2-liter stainless steel autoclave, followed by 0.2 g of high purity KOH (99.9%). After dehydration for about 30 minutes, and then 79.2g (1.8 mol) of ethylene oxide was indented and reacted with stirring at 160-165 ℃ for about 6 hours. After the reaction was completed, a solid reaction product was obtained, and the reaction product was reacted with 139.2 g (2.4 mol) of propylene oxide at 155-160 ° C. for 9 hours in the presence of 0.15 g of KOH (99.9%) to obtain a slightly yellow semi-solid. After completion of the reaction, the reaction mixture was evacuated three times with nitrogen to remove unreacted ethylene oxide, propylene oxide, and byproducts 1 and 4-dioxane. The reaction mixture was cooled to about 50 ° C., and a small amount of acetic acid was added to neutralize the alkaline component added to the catalyst. . Unreacted vitamin E was removed with toluene, and then purified by Sephadex LH-50 column chromatography using chloroform-methanol (1: 1) as an eluting solvent to obtain 208.2 g of liquid polyoxypropylenepolyoxyethylene vitamin E (5). The analysis results of this liquid product are as follows.

Analysis

(1) Appearance: A pale yellow substance that is semisolid at room temperature.

(2) Elemental analysis result: C ₉₂ H ₁₈₄₉ O _{352 as} molecular weight (relative molecular weight)

Calculated Value (%): C: 59.84, H: 9.93, N: 0.00

Found (%): C: 60.05, H: 10.34, N: 0.04

(3) Yield of reaction: 93.5%

(4) Number of moles of added ethylene oxide (average): 150 moles

(5) Number of moles of propylene oxide added (average): 200 moles

Example 6 In Vitro Antioxidant Activity of Polyoxypropylene Polyoxyethylene [POP-POE] Vitamin E

The antioxidant power of the novel polyoxypropylene polyoxyethylene vitamin E of the present invention was measured using linoleic acid. Linoleic acid used in the antioxidant test was reagent grade reagent grade 78% linoleic acid and 12.5% linoleic acid.

Vitamin E, Vitamin E Acetate and Pre-Pried Polyoxypropylene Polyoxyethylene Vitamin Es as Controls of the Invention Polyoxypropylenepolyoxyethylene Vitamin Es of Examples 1, 2, 3, 4 and 5 for Antioxidant Testing And the like were added to linoleic acid at a concentration of 0.5%, respectively, and then stored in a thermostat at 40 ° C., and the peroxide value was measured after 2 days and 20 days. In detail, 1.0 g of the sample was placed in a 250 mL Erlenmeyer flask, 10 mL of chloroform was dissolved to dissolve the sample, 15 mL of glacial acetic acid and 1 mL of saturated potassium iodide were added. The cap was shaken vigorously, and left in a dark place for 5 minutes. 75 mL of distilled water was added to the Erlenmeyer flask, which was left to stand again, and the flask was capped and shaken vigorously. The starch solution was used as an indicator, and the free iodine was titrated with 0.01 N sodium thiosulfate solution as the end point. Measured together.

S: 0.01N sodium thiosulfate consumption of sample (mL)

B: 0.01 N sodium thiosulfate consumption in blank test (mL)

As a result of the experiment, as shown in Table 1, polyoxypropylene polyoxyethylene vitamin E (1) prepared in Example 1, polyoxypropylene polyoxyethylene vitamin E (2) prepared in Example 2 and prepared in Example 3 One polyoxypropylenepolyoxyethylene vitamin E (3) exhibited much better antioxidant power than the comparative control polyoxypropylenepolyoxyethylene vitamin Es of the prior invention and was superior to the well-known bioactive antioxidant vitamin E. Examples 1 and 2) or a similar (Example 3) effect and the high molecular weight polyoxypropylene polyoxyethylene vitamin E (4,5) prepared in Examples 4 and 5 is also a comparative control polyoxy of the prior application It showed better antioxidant effect than ethylene polyoxypropylene vitamin E. This is summarized in Table 1.

Peroxide Value of Polyoxypropylene Polyoxyethylene Vitamin E and Control sample 2 days later After 20 days 1. Linoleic Acid (5 ℃) 16.2 16.8 2. Linoleic Acid (40 ℃) 42.6 167.2 3. Linoleic Acid + Vitamin E 23.6 58.9 4. Linoleic Acid + Vitamin E, Acetate 30.8 123.3 5. Linoleic Acid + Polyoxypropylene Polyoxyethylene Vitamin E (1) 20.7 55.6 6. Linoleic Acid + Polyoxypropylene Polyoxyethylene Vitamin E (2) 18.3 53.7 7. Linoleic Acid + Polyoxypropylene Polyoxyethylene Vitamin E (3) 24.2 57.0 8. Linoleic Acid + Polyoxypropylene Polyoxyethylene Vitamin E (4) 38.6 125.6 9. Linoleic acid + polyoxypropylenepolyoxyethylene vitamin E (5) 39.2 131.2 10. Linoleic acid + polyoxypropylene (5) polyoxyethylene (2) vitamin E 28.7 83.2 11. Linoleic acid + polyoxypropylene (5) polyoxyethylene (10) vitamin E 32.8 114.7 12. Linoleic Acid + Polyoxypropylene (100) Polyoxyethylene (150) Vitamin E 40.5 128.3

In particular, when the ethylene oxide group is not added, that is, when m = 0, the number of moles of propylene oxide group n = 2, 5 showed an excellent in vivo antioxidant effect than the vitamin E tocopherol itself can be described as follows.

The free radical scavenging effect by dissociating the hydrogen radicals of the OH groups in the amphiphilic substance with POE or POP added to tocopherol is easier due to the methyl group electron donating effect of PO groups than EO, which is originally hydrophobic. It is believed that hydrogen radicals can be easily generated due to the increase in the delocalization effect of the Chroming-ring electrons when the Chroming and the added groups have the same hydrophobic nature. Therefore, when the more hydrophobic PO is directly polymerized to tocopherol, i.e., when m = 0 or when ethylene oxide (EO) is added to a minimum molar number, i.e., m = 1, the electron donating effect of methyl group and the electron of tocopherol Due to the non-localization synergistic effect of m = 2 it can be seen that the better antioxidant effect.

Example 7 Investigation of the Effect of Polyoxypropylene Polyoxyethylene [POP-POE] Vitamin E on the Erythema and Melanin Pigmentation by UV Light

Polyoxypropylene polyoxyethylene (POP-POE) vitamin E of the present invention was confirmed that the antioxidant properties are superior to the pre-applied POP-POE vitamin E in vitro experiments in the present embodiment in vivo In order to examine the antioxidant and anti-inflammatory activity of the pre-applied POP-POE vitamin E and the polyoxypropylene polyoxyethylene prepared in Examples 1 to 3 were compared.

As shown in Table 2, Test Examples 1, 2, and 3 and Comparative Test Examples 1, 2, 3, and 4, respectively, 0.5 g 4 cm each of 5 males and 5 females of 20 to 30 years of age.²UV light was applied at about 4 MED (minimum erythema dose) to determine the effect on erythema and melanogenesis. The UV irradiator used a German Waldmann UV 800 (Herbert Waldmann Gmbh & Co.) with a Phillips 20W lamp and synthesized the average value for 10 people. The erythema index (Table 3) and melanin It is shown by the melanin index (Table 4). Each index value is a relative value of skin brightness measured with a German Maxameter MX16 (CK Electronic Gmbh) colorimeter on the skin under test. In general, erythema is known to reach the highest after 1 day of ultraviolet irradiation, Comparative Example 1, 2, which is a control group using the pre-applied POP-POE vitamin E and vitamin E derivative vitamin E acetate after the first day The erythema incidence in Test Examples 1, 2, and 3 was less than that in, and 4, and the erythema incidence was less than that in Comparative Test Example 3 using vitamin E. Shrunk. According to the results of Table 3, Test Examples 1, 2, and 3 inhibit erythema development, and thus have an anti-inflammatory effect and an antioxidant effect. In particular, the present invention POP-POE Vitamin E of Test Examples 1, 2, and 3 is a pre-populated POP-POE vitamin As well as E, it can be seen that there is an excellent anti-inflammatory and antioxidant effect than vitamin E, known as a stable bioactive antioxidant.

Unlike erythema, melanin pigments generally increase after 5 days of UV irradiation. According to the results of Table 4, melanin pigments after 5 days and 10 days of UV irradiation were compared with those of Comparative Test Examples 1, 2, and 4 after the initial 1 day. Significantly increased the index, while using Test Examples 1, 2, and 3 were similar after 1, 5, and 10 days of UV irradiation, indicating that melanin formation was inhibited. Vitamin E is known to be effective. The melanin pigmentation difference was less after 1 day, after 5 days, and after 10 days of ultraviolet irradiation than when using. In other words, Test Examples 1, 2, and 3 show melanin pigmentation inhibitory effects superior to Comparative Test Example 3 using vitamin E, which is a stable physiologically active antioxidant, as well as POP-POE vitamin E of the comparative control group.

That is, the present invention POP-POE vitamin E is effective in preventing rash occurs and melanin formation as well as in vitro (in vitro) in vivo (in vivo), vitamin E and the earlier application the POP-POE vitamin E In comparison, it can be seen that there is an excellent effect on anti-inflammatory activity and antioxidant activity.

Test and comparative test composition for the effect test of POP-POE vitamin E on the erythema generation and melanin pigmentation by UV rays (unit weight%) Ingredient Test Example 1 Test Example 2 Test Example 3 Comparative Test Example 1 Comparative Test Example 2 Comparative Test Example 3 Comparative Test Example 4 Polyoxypropylene Polyoxyethylene (1) 2 - - - - - - Polyoxypropylene Polyoxyethylene (2) - 2 - - - - - Polyoxypropylene Polyoxyethylene (3) - - 2 - - - - POP (5) -POE (2) Vitamin E - - - 2 - - - POP (5) -POE (10) Vitamin E - - - - 2 - - Vitamin E - - - - - 2 - Vitamin E Acetate - - - - - - 2 Methyl-paraben 0.1 0.1 0.1 0.1 0.1 0.1 0.1 Propylene glycol 2 2 2 2 2 2 2 ethanol 10 10 10 10 10 10 10 Purified water to 100 to 100 to 100 to 100 to 100 to 100 to 100

* After each test solution is melted, it is manufactured by operating for 5 minutes as a tip-type radio frequency equipment at 50 ℃ and spread on the used part.

Erythema index showing the effect of polyoxyethylene polyoxypropylene vitamin E on erythema development by UV light Measurement date Test Example 1 Test Example 2 Test Example 3 Comparative Test Example 1 Comparative Test Example 2 Comparative Test Example 3 Comparative Test Example 4 1 day after 730 722 728 745 764 751 786 After 5 days 728 720 726 738 754 747 813 10 days later 710 705 713 722 729 723 789

Melanin pigment index showing the effect of polyoxyethylene polyoxypropylene vitamin E on melanin pigmentation by UV rays Measurement date Test Example 1 Test Example 2 Test Example 3 Comparative Test Example 1 Comparative Test Example 2 Comparative Test Example 3 Comparative Test Example 4 1 day after 648 630 657 662 657 665 689 After 5 days 658 645 661 685 698 678 721 10 days later 637 628 642 668 672 658 715

Example 8 Investigation of the Surfactant Activity of Polyoxypropylene Polyoxyethylene (POP-POE) Vitamin E

Foaming force and bubble stability, vesicle formation and emulsification experiment of polyoxypropylenepolyoxyethylene vitamin E prepared in Examples 1 to 5 to investigate the surface active action of the novel polyoxypropylene polyoxyethylene vitamin E of the present invention Was compared with the polyoxypropylene polyoxyethylene vitamin E pre- filed.

Experimental Example 1: Measurement of Bubble Force and Bubble Stability

Bubble strength and bubble stability were performed by the dynamic foam test method. 400cc of 0.1% aqueous solution was put into a 2 l cylinder with a graduated inner diameter of 10cm and the azimixer was rotated for 1 minute at 1000rpm at 20 ° C. The bubble layer volume percentage immediately after was measured as bubble stability. Experimental results As shown in Table 5, the comparatively low molecular weight polyoxypropylene polyoxyethylene vitamin E prepared in Examples 1, 2, and 3 was used as a control group of the pre-populated POP (2) -POE (5), POP ( 5) -POE (10) Compared to vitamin E, it showed very weak foaming power and low foam stability. This indicates that the relatively low molecular weight POP-POE vitamin E of the present invention is hydrophobic than the pre-populated POP-POE vitamin E. On the other hand, POP-POE vitamin E of the present invention of Examples 4 and 5 showed a significant foaming power and bubble stability, and significantly lower foaming power and bubble stability than POP (100) -POE (150) vitamin E of the comparative control group. It was. This also means that the hydrophobicity of the relatively high molecular weight polyoxyethylenepolyoxypropylene vitamin E of the present invention is significantly improved.

Bubble force and bubble stability measurement results sample Bubble force (cc) Bubble stability (%) Polyoxypropylene Polyoxyethylene Vitamin E (1) 56 15 Polyoxypropylene Polyoxyethylene Vitamin E (2) 44 16 Polyoxypropylene Polyoxyethylene Vitamin E (3) 25 10 Polyoxypropylene Polyoxyethylene Vitamin E (4) 247 57 Polyoxypropylene Polyoxyethylene Vitamin E (5) 325 65 POP (2) -POE (5) Vitamin E 85 28 POP (5) -POE (10) Vitamin E 121 35 POP (100) -POE (150) Vitamin E 357 72

Experimental Example 2: vesicle formation experiment

Formation of vesicles using 10% aqueous ethanol solution containing 0.5% of polyoxypropylene-polyoxyethylene vitamin E in order to investigate further surfactant properties of polyoxypropylenepolyoxyethylene vitamin E obtained in the compounds of Examples 1 and 2 of the present invention The experiment was conducted. Since the compounds of the present invention of Examples 1 and 2 are themselves hydrophobic, no vesicles can be formed by aqueous solution alone, and 10% ethanol aqueous solution was used. After stirring a 25 ℃ aqueous solution with a tip type high frequency equipment and mixed with a sample of the same amount of 2% uranyl acetate (aqueous aqueous solution) and shaken by hand, the carbon-coated 200 mesh copper mesh ( The sample was added dropwise onto a copper grid, dried at room temperature for about 20 minutes, and observed with an electron microscope of Philips. The output was 80 KV. As a result, it was surprisingly found that the compounds of Examples 1 and 2 of the present invention formed a clear blocked sphere vesicle. Figure 3 is a vesicle formation picture of the compound of Example 1.

Experimental Example 3: Emulsification Experiment

In order to know exactly the properties of the polyoxyethylene polyoxypropylene vitamin E prepared in Examples 4 and 5 of the present invention as an emulsifier, an emulsification experiment was conducted. As shown in Table 6, oil-in-water formulations with fluid paraffin # 70 (Witco Chem. USA) and polydimethylsiloseine gum and oil (SE 72 and Viscasil 60M, GE Silicone USA), respectively, were formulated as 1 and 2. Indicated. The oil phase containing the emulsifier and the aqueous phase were each heated to 70 ° C. and the oil phase was added to the aqueous phase with homomixing. After emulsification, the mixture was cooled to 30 ° C, filled in a transparent container, stored at 40 ° C, and then checked for stability after 60 days. Emulsification stability is expressed as a percentage of the volume of the total emulsion versus the volume that is not isolated and stable.

Prescription of Oil-in-water Oil Painting NO Ingredients / Prescription One 2 One Liquid Paraffin # 70 60 - 2 Polydimethylsilicone Gum - 40 3 Polydimethylsilicone Oil - 20 4 Emulsifier 5 5 5 Propylene glycol 5 10 6 Purified water to 100 to 100

Stability result (%) of oil-in-water emulsion NO Emulsifier / prescription One 2 One Polyoxyethylene Polyoxypropylene Vitamin E (4) 98 94 2 Polyoxyethylene Polyoxypropylene Vitamin E (5) 93 97 3 POP (100) -POE (150) Vitamin E 78 62 4 POP (100) -POE (100) Vitamin E 72 72

As can be seen in Table 7, the relatively high molecular weight of the present invention POP-POE vitamin E of Examples 4 and 5 used in this experiment is a POP that has been selected as an improved hydrophobicity in the previously patented POP-POE vitamin E Emulsion stability was improved in oil-in-water emulsions with fluid paraffin, silicone gum and oil as oil phase, respectively, than -POE vitamin E.

This shows that hydrophilicity is improved at relatively high moles of ethylene oxide (EO), but hydrophobicity is relatively weak at moles of propylene oxide n = 1 to 100. It can be explained.

As described above in the above Examples and Experimental Examples, the polyoxy obtained by not adding ethylene oxide group or adding 1 mole (m = 0 to 1) to the hydroxyl group (OH) of the antioxidant bioactive vitamin E Polyoxypropylene polyoxyethylene vitamin E obtained by addition polymerization of propylene oxide (n = 1 to 200) to ethylene vitamin E has improved antioxidant capacity in vitro and in vivo than when mole number of ethylene oxy group is 2 or more. In particular, the polyoxypropylene polyoxyethylene vitamin E obtained by moles of ethylene oxide groups from 0 to 1 and propylene oxide groups from 2, 5, and 10 has considerable hydrophilicity to form vesicles. Obtained by adding an ethylene oxide group to the hydroxyl group (OH) of the antioxidant bioactive vitamin E (when m = 0 to 150). Polyoxypropylene polyoxyethylene vitamin E prepared by adding and polymerizing propylene oxide from 101 moles or more to 200 moles of reoxyethylene vitamin E has an excellent effect of excellent emulsification and anti-oxidation properties due to a good balance of hydrophilicity and hydrophobicity. It is a very useful invention in the cosmetic industry, food industry and pharmaceutical industry.

Claims (5)

Polyoxypropylene polyoxyethylene vitamin E represented by the following general formula (I). Wherein R ₁ is-(OCH ₂ CH ₂ ) _m- , R ₂ is ego; m is 0 or 1 when n is an integer from 1 to 200; A is Is; B is CH _{3 at} the 5-, 7- or 8- position of vitamin E and P is 1, 3 integers. Polyoxypropylene polyoxyethylene vitamin E represented by the following general formula (I). Wherein R ₁ is-(OCH ₂ CH ₂ ) _m- , R ₂ is ego; when m is an integer from 0 to 150 n is an integer from 101 to 200; A is Is; B is CH _{3 at} the 5-, 7- or 8- position of vitamin E and P is 1, 3 integers. A melanin pigment production inhibitor comprising the polyoxypropylene polyoxyethylene vitamin E according to claim 1 as an active ingredient. A surfactant comprising the polyoxypropylene polyoxyethylene vitamin E according to claim 2 as an active ingredient. A softener, comprising the polyoxypropylene polyoxyethylene vitamin E according to claim 2 as an active ingredient.