Sodium vitamin E phosphate and method for producing the same

Abstract

This invention provides sodium vitamin E phosphate, which has high water solubility, and a method for producing the same. [Solution] Sodium vitamin E phosphate has a chlorine content of 1000 ppm or less. The method for producing sodium vitamin E phosphate includes a phosphorylation step of phosphorylating vitamin E to obtain vitamin E phosphate ester, a washing step of washing the vitamin E phosphate ester obtained in the phosphorylation step with water, and a neutralization step of sodium chlorideing the vitamin E phosphate ester washed in the washing step. The washing step is repeated until the pH of the aqueous layer separated from the organic layer after washing is 1.4 or higher.

Description

Technical Field

[0001] The present invention relates to sodium vitamin E phosphate (SVEP) and a method for producing the same.

Background Art

[0002] Tocopherols, tocotrienols, and their derivatives are known as vitamin E and have excellent antioxidant effects, so they are expected to have skin whitening effects and effects of improving freckles. Furthermore, the effect is promoted by using it in combination with vitamin C. In particular, since water solubility is improved by derivatization, for example, sodium tocopherol phosphate (STP) is used in aqueous skin lotions and the like.

[0003] In the production process of STP, it is necessary to react tocopherol with phosphorus oxychloride and then perform heating under reflux with sulfuric acid or hydrolysis with water.

[0004] For example, in International Publication No. WO1997 / 014705 (Patent Document 1), after reacting tocopherol with phosphorus oxychloride to produce tocopherol phosphate ester (TP), an aqueous sulfuric acid solution is added thereto and heated under reflux for 4 hours. Further, the organic layer and the aqueous layer are separated, and the organic layer is washed with an aqueous sulfuric acid solution.

[0005] In International Publication No. WO2016 / 186201 (Patent Document 2), after reacting tocopherol with phosphorus oxychloride to produce TP, an aqueous sulfuric acid solution is added thereto and heated under reflux for 3 hours. Further, the organic layer and the aqueous layer are separated, and the organic layer is washed with an aqueous hydrochloric acid solution and water.

Prior Art Documents

Patent Documents

[0006]

Patent Document 1

Patent Document 2

Summary of the Invention

[0007] However, conventional STP (Straightened Thread Processing) products have insufficient water solubility, and sometimes cause clouding when added to water or lotions.

[0008] Furthermore, as described in Patent Documents 1 and 2, the manufacturing method involving heating under reflux with sulfuric acid generates many impurities and significantly reduces the yield. Also, as described in Patent Document 2, even if the organic layer is washed with hydrochloric acid solution and water after adding a 15% by mass sulfuric acid aqueous solution, a large amount of chlorine remains in the final product, STP.

[0009] Therefore, the object of this invention is to provide SVEP having high water solubility and a method for producing the same. [Means for solving the problem]

[0010] The inventors, through diligent research, have found a correlation between the chlorine content in SVEP and its water solubility. Since phosphorus oxychloride is used in the manufacturing process of SVEP, the final SVEP may contain chlorine in the form of sodium chloride. Because sodium chloride has high solubility in water, when SVEP and sodium chloride coexist in an aqueous solution, the sodium chloride dissolves in the water, causing SVEP to precipitate and the aqueous solution to become cloudy. The inventors have found that if the chlorine content in SVEP is below a certain amount, the water solubility of SVEP can be increased and the cloudiness of the aqueous solution can be prevented.

[0011] Based on the above findings, the SVEP according to the present invention has a chlorine content of 1000 ppm or less.

[0012] The inventors also found a correlation between the pH of the washing water used to wash vitamin E phosphate ester (VEP) in the hydrolysis process and the chlorine content in the final obtained SVEP. The organic layer containing VEP, obtained by phosphorylating vitamin E with phosphorus oxychloride, contains hydrogen chloride. If sodium chloride is carried out while hydrogen chloride remains in the organic layer, sodium chloride is produced as a by-product in addition to SVEP. The inventors found that by repeating the washing with water in the process of washing the organic layer with water until the pH of the aqueous layer separated from the organic layer after washing is above a predetermined value, the sodium chloride content in the final obtained SVEP can be reduced, the water solubility of SVEP can be increased, and the turbidity of the aqueous solution can be prevented.

[0013] Based on the above findings, the method for producing SVEP according to the present invention includes a phosphorylation step of phosphorylating vitamin E with phosphorus oxychloride to obtain VEP, a washing step of washing the VEP obtained in the phosphorylation step with water, and a neutralization step of sodium chlorideing the VEP washed in the washing step, and the washing step is repeated until the pH of the aqueous layer separated from the organic layer after washing is 1.4 or higher.

[0014] By doing so, it is possible to provide SVEP with high water solubility. [Modes for carrying out the invention]

[0015] The present invention will be described in detail below with reference to specific examples. However, the present invention is not limited to the embodiments shown below, and various modifications are possible without departing from the technical spirit of the invention.

[0016] The SVEP of the present invention has a chlorine content of 1000 ppm or less. Preferably, the chlorine content of the SVEP is 800 ppm or less, more preferably 400 ppm or less, and even more preferably 200 ppm or less. By doing so, the water solubility of the SVEP can be increased.

[0017] The chlorine content of SVEP can be measured by common methods such as ICP emission spectrometry and ion chromatography.

[0018] For the SVEP of the present invention, the molar number of sodium per mole of VEP (Na / VEP) is preferably less than 1.1, more preferably less than 1.0, and even more preferably less than 0.99, less than 0.98, less than 0.97, less than 0.95, less than 0.93, and less than 0.90. As the molar number of sodium per mole of VEP increases, the water solubility increases and the oil solubility decreases. On the other hand, when the molar number of sodium per mole of VEP decreases, the oil solubility increases and the water solubility decreases. If the molar number of sodium per mole of VEP in SVEP is less than 1.1, it is considered that oil-soluble SVEP and water-soluble SVEP coexist, and SVEP dissolves better in lotion, which is a mixture of water and organic solvent.

[0019] The molar number of sodium in SVEP can be measured by common methods such as ICP emission spectrometry, ion chromatography, atomic absorption spectrometry, and flame luminescence spectrometry. The content of VEP in SVEP and in the organic layer can be determined by detecting with an ultraviolet-visible spectrometer using, for example, a liquid chromatograph.

[0020] <Method for producing SVEP> The SVEP of the present embodiment can be produced, for example, using a production method that performs the following steps 1 to 4.

[0021] <Step 1. Phosphorylation step> VEP is generated by reacting vitamin E with a phosphorylating agent. Then, water is added to the reaction solution containing VEP to dissolve the salt precipitated together with VEP.

[0022] <Step 2. Organic layer washing step> A washing step is performed to remove phosphoric acid and hydrochloric acid from the reaction solution after dissolving the salt.

[0023] <Step 3. Neutralization step> The alkali metal salt of VEP is produced by neutralizing VEP with an alkali metal hydroxide or an alkali metal alkoxide.

[0024] <Step 4. Purification (recrystallization) step> If necessary, the alkali metal salt of VEP is purified.

[0025] In the phosphorylation step (Step 1) for producing VEP, tocopherol or tocotrienol can be used as vitamin E. As tocopherol, α-tocopherol, β-tocopherol, γ-tocopherol, δ-tocopherol can be used, and as tocotrienol, α-tocotrienol, β-tocotrienol, γ-tocotrienol, δ-tocotrienol can be used.

[0026] As the phosphorylating agent, phosphorus oxychloride, trimetaphosphoric acid, polyphosphoric acid, etc. can be used, but from the viewpoints of reactivity and yield, phosphorus oxychloride is preferred. In Step 1, in order to ensure the reaction between vitamin E and the phosphorylating agent, it is preferred to use an excess of the phosphorylating agent with respect to vitamin E.

[0027] As the washing step (Step 2), a method of removing phosphoric acid and hydrochloric acid contained in the reaction solution by washing the organic layer of the reaction solution containing VEP with water having a mass of more than half of the organic layer, preferably repeating the washing 6 times or more, can be mentioned. At this time, by using water or brine containing a weak base such as pyridine, triethylamine, ammonia, etc., it is possible to reduce the number of washing times and shorten the liquid separation time.

[0028] Also, the washing is repeated until the pH of the aqueous layer separated from the organic layer after washing becomes 1.4 or more. The pH of the aqueous layer at this time is preferably 1.4 or more, more preferably 1.6 or more, particularly preferably 2.0 or more, and particularly preferably 2.5 or more. When the pH is low, the washing of the organic layer is insufficient, and the chlorine content contained in the produced SVEP tends to be high.

[0029] In the neutralization step (step 3) for neutralizing VEP, for example, a method can be used in which an alkali metal hydroxide or alkali metal alkoxide dissolved in a solvent is added dropwise to a solution in which VEP is dissolved in a solvent.

[0030] As alkali metal hydroxides, sodium hydroxide and potassium hydroxide can be used, and as alkali metal alkoxides, sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide, potassium t-butoxide, etc. can be used. One or two types of alkali metals can be used, but sodium hydroxide is preferred from the viewpoint of being able to be powdered.

[0031] When performing the purification step (step 4) to recrystallize the alkali metal salt of VEP, it is preferable to purify the alkali metal salt of VEP by crystallization using an organic solvent. In this case, methanol, ethanol, acetone, methyl-t-butyl ether (MTBE), etc., can be used as the organic solvent. It is preferable to use methanol as the organic solvent because it is an easy-to-handle organic solvent.

[0032] The amount of alkali metal hydroxide added to VEP is preferably 1.2 molar equivalents or less, more preferably 1.1 molar equivalents or less, even more preferably 1.05 molar equivalents or less, and particularly preferably 1 molar equivalent or less, from the viewpoint of solubility in topical skin preparations. If the amount exceeds 1.2 molar equivalents, the Na / VEP ratio of the resulting SVEP will exceed 1.1, resulting in poor solubility in topical skin preparations containing organic solvents.

[0033] By doing so, it is possible to provide SVEP that is water-soluble and highly soluble in topical skin preparations.

[0034] <Topical skin preparations> Next, the topical skin preparation of the present invention will be described. The topical skin preparation of this embodiment contains SVEP according to the present invention. Hereinafter, in the topical skin preparation of this embodiment, SVEP means SVEP according to the present invention.

[0035] The topical skin preparation of this embodiment preferably contains 0.01 to 20% by mass of SVEP according to the present invention. When the SVEP content according to the present invention is 0.01% by mass or more, the effects of including SVEP according to the present invention are more easily exhibited. To obtain the effects of including SVEP according to the present invention, it is more preferable to contain 0.03% by mass or more of SVEP according to the present invention, and even more preferable to contain 0.05% by mass or more.

[0036] Furthermore, when the SVEP content according to the present invention is 20% by mass or less, SVEP can be easily and uniformly dissolved and / or dispersed in the topical skin preparation, resulting in a topical skin preparation that is easy to formulate and has excellent productivity. Moreover, when the SVEP content is 20% by mass or less, the salting-out effect by alkali metals in the topical skin preparation can be suppressed. Therefore, a topical skin preparation with excellent stability is obtained. In order to uniformly dissolve and / or disperse SVEP and improve stability, it is more preferable to contain 10% by mass or less of SVEP, and even more preferable to contain 5% by mass or less.

[0037] The topical skin preparation of this embodiment may contain other components in addition to SVEP, such as components commonly used in topical skin preparations. Other components that can be incorporated into the topical skin preparation of this embodiment include, for example, ascorbic acid derivatives, hydrocarbons, natural oils and fats, fatty acids, higher alcohols, alkyl glyceryl ethers, esters, silicone oils, polymers, lower alcohols, polyhydric alcohols, surfactants, UV absorbers, powders and colorants, plant extracts, amino acids and peptides, vitamins and vitamin-like factors, preservatives, antioxidants, chelating agents, humectants, anti-inflammatory agents, pH adjusters, salts, α-hydroxy acids, whitening agents, essential oils, terpenes, fragrances, and water.

[0038] Examples of ascorbic acid derivatives include ascorbic acid-2-phosphate, ascorbic acid-2-glucoside, ascorbic acid-6-palmitic acid, ascorbic acid-2-phosphate-6-palmitic acid, ascorbic acid-2-phosphate-6-hexyldecanoic acid, ascorbic acid-6-tetraisopalmitic acid, ascorbyl palmitate phosphate, isostearyl ascorbyl phosphate, and glyceryl octyl ascorbic acid. Examples of ascorbic acid derivative salts include alkali metal salts and alkaline earth metal salts of the above-mentioned example compounds.

[0039] Examples of hydrocarbons include squalane and mineral oil.

[0040] Examples of natural oils and fats include jojoba oil, olive oil, palm oil, camellia oil, and shea butter.

[0041] Examples of fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, oleic acid, isostearic acid, 12-hydroxystearic acid, undecylenic acid, and coconut oil fatty acids.

[0042] Examples of higher alcohols include isostearyl alcohol, cetanol, stearyl alcohol, behenyl alcohol, and cetostearyl alcohol.

[0043] Examples of alkylglyceryl ethers include batyl alcohol, chymyl alcohol, ceracyl alcohol, and isostearyl glyceryl ether.

[0044] Examples of esters include isopropyl palmitate, octyldodecyl myristate, and isononyl isononanoate.

[0045] Examples of silicone oils include methylpolysiloxane and alkyl-modified silicones.

[0046] Examples of polymers include xanthan gum, hydroxyethylcellulose, sodium polyacrylate, and carboxyvinyl polymer.

[0047] Examples of lower alcohols include ethanol, isopropyl alcohol, 1-butanol, 2-butanol, and benzyl alcohol.

[0048] Examples of polyhydric alcohols include propylene glycol, dipropylene glycol, glycerin, 1,3-butanediol, 1,2-pentanediol, and 1,2-hexanediol.

[0049] Examples of surfactants include anionic surfactants, cationic surfactants, amphoteric surfactants, nonionic surfactants, and natural surfactants.

[0050] Examples of anionic surfactants include sodium stearate, sodium lauryl sulfate, triethanolamine lauryl sulfate, sodium cetyl sulfate, and sodium polyoxyethylene lauryl ether sulfate.

[0051] Examples of cationic surfactants include lauryltrimethylammonium chloride and cetyltrimethylammonium chloride. Examples of amphoteric surfactants include sodium laurylaminopropionate and betaine lauryldimethylaminoacetic acid.

[0052] Examples of nonionic surfactants include polyoxyethylene alkyl ethers, polyoxyethylene hydrogenated castor oil, and sucrose fatty acid esters.

[0053] Examples of natural surfactants include hydrogenated soybean phospholipids, phosphatidylserine, sodium deoxycholate, and sophorolipids.

[0054] Examples of UV absorbers include para-aminobenzoic acid derivatives, cinnamic acid derivatives, urocanic acid derivatives, and benzophenone derivatives.

[0055] Examples of powders and colorants include zinc oxide and titanium oxide.

[0056] Examples of amino acids and peptides include collagen and wheat peptides.

[0057] Examples of vitamins and vitamin-like factors include vitamin A, carotenoids, vitamin B2, vitamin D, fat-soluble vitamin E, ubiquinones, vitamin K, carnitine, ferulic acid, gamma-oryzanol, alpha-lipoic acid, and orotic acid.

[0058] Examples of preservatives include butyl parahydroxybenzoate, propyl parahydroxybenzoate, methyl parahydroxybenzoate, and phenoxyethanol.

[0059] Examples of antioxidants include butylhydroxyanisole, butylhydroxytoluene, propyl gallate, erythorbic acid, sodium erythorbate, parahydroxyanisole, and octyl gallate.

[0060] Examples of chelating agents include EDTA and sodium citrate.

[0061] Examples of moisturizing agents include hyaluronic acid, sodium hyaluronate, sodium chondroitin sulfate, sodium lactate, sodium pyrrolidone carboxylate, betaine, lactic acid bacteria culture solution, yeast extract, and ceramides.

[0062] Examples of anti-inflammatory agents include glycyrrhizic acid, trisodium glycyrrhizate, dipotassium glycyrrhizate, monoammonium glycyrrhizate, β-glycyrrhetinic acid, glyceryl glycyrrhetinate, stearyl glycyrrhetinate, lysozyme chloride, hydrocortisone, and allantoin.

[0063] Examples of pH adjusting agents include sodium hydroxide, potassium hydroxide, triethanolamine, citric acid, and sodium citrate.

[0064] Examples of salts include sodium chloride, potassium chloride, magnesium chloride, and sodium sulfate. Examples of α-hydroxy acids include citric acid, glycolic acid, tartaric acid, and lactic acid.

[0065] Examples of skin whitening agents include arbutin, alpha-arbutin, and placenta extract.

[0066] Examples of terpenes include pinene, terpinene, terpinolene, myrcene, and longifolene.

[0067] The topical skin preparation of this embodiment may be in any dosage form or shape as long as it is used in contact with the skin at the time of application. Preferably, the topical skin preparation of this embodiment is in a dosage form or shape suitable for contact with the skin of the area where the effect of containing SVEP is desired.

[0068] Examples of topical skin preparations include skin milk, skin cream, foundation cream, massage cream, cleansing cream, shaving cream, cleansing foam, lotion, toner, face mask, lipstick, blush, eyeshadow, nail polish, soap, body wash, hand soap, shampoo, conditioner, hair tonic, treatment, hair cream, hair spray, hair growth stimulants, hair tonics, hair dyes, hair styling products, hair removal products, anti-dandruff agents, toothpaste, denture adhesive, mouthwash, permanent wave agents, curling agents, styling products, ointments, poultices, tapes, bath additives, antiperspirants, and sunscreens.

[0069] The dosage form of a topical skin preparation may be solid, liquid, semi-solid, or gas. Specifically, examples include powder, granules, tablets, gels, and foams.

[0070] The topical skin preparation of this embodiment can be used regardless of the user's gender or age. Furthermore, the topical skin preparation of this embodiment may be applied to the skin of animals.

[0071] The topical skin preparation of this embodiment can be manufactured by using SVEP according to the present invention in a predetermined content, and by dissolving, mixing, or dispersing the SVEP according to the present invention in accordance with conventional methods, depending on the dosage form and shape.

[0072] The topical skin preparation of this embodiment contains SVEP according to the present invention, which has excellent water solubility. Therefore, the topical skin preparation of this embodiment is preferably in liquid form, such as a water-based lotion, toner, or cream. In such embodiments, the SVEP of the present invention is easy to formulate and exhibits excellent stability. [Examples]

[0073] The present invention will be explained in more detail by showing specific manufacturing examples and test results of the SVEP.

[0074] <Example 1> <Phosphorylation Process> Solution (A) was prepared by dissolving 23.1 g (0.151 mol) of phosphorus oxychloride, a phosphorylating agent, in 50 mL of methyl-t-butyl ether (MTBE). Separately, solution (B) was prepared by dissolving 50.0 g (0.116 mol) of dl-α-tocopherol in 50 mL of MTBE containing 18.4 g of pyridine.

[0075] A solution (A) containing phosphorus oxychloride was to be mixed dropwise with a solution (B) containing dl-α-tocopherol while maintaining a liquid temperature of 50°C or lower. After the addition was complete, the mixture was stirred for 1 hour to prepare a TP solution. Next, 100 mL of deionized water was added to the TP solution while maintaining a liquid temperature of 40°C or lower, and the mixture was stirred for 30 minutes.

[0076] <Organic layer cleaning process> Subsequently, the solution containing TP was placed in a separatory funnel and separated into an organic layer containing TP and an aqueous layer. After collecting the separated aqueous layer, the remaining organic layer was washed with half the amount of deionized water. This procedure was repeated six times, and after each wash, the pH of the separated wash water and the chlorine content were measured by ion chromatography. The results of the pH measurement and chlorine content measurement of the wash water separated after the sixth wash are shown in Table 1.

[0077] 10 mL was taken from the organic layer, and the MTBE was completely evaporated using an evaporator. Then, 20 mL of 1-propanol was added and completely evaporated again using an evaporator (water bath 45°C, 10 hPa, 60 minutes) to obtain 5.3 g of TP, a yellow viscous solid.

[0078] <Neutralization process> After evaporating the solvent, 20 mL of 1-propanol was added and stirred. A white precipitate formed when an equimolar 5 M NaOH methanol solution was added dropwise to the resulting TP while stirring. After stirring for 1 hour, the precipitate was filtered to obtain white crystals. The obtained crystals were washed with 30 mL of 1-propanol and 30 mL of acetone.

[0079] <Purification process> 500 mL of methanol was added to the obtained crystals and the mixture was stirred at 50°C for 1 hour. After gradually cooling to room temperature, 200 mL of acetone was added dropwise while stirring, and the precipitated crystals were filtered. The obtained crystals were dried at 50°C for 6 hours under vacuum conditions (below 10 hPa). By collecting the dried crystals, 4.0 g of white crystals, which are STP, were obtained.

[0080] <Example 2> In the organic layer washing step of Example 1, an additional washing step was performed, bringing the total number of washing steps to seven. After that, 10 mL of the organic layer was collected and a neutralization step was performed. The rest of the procedure was the same as in Example 1 to obtain the STP.

[0081] <Example 3> In the organic layer washing step of Example 1, washing was performed two additional times, bringing the total number of washings to eight. After that, 10 mL of the organic layer was collected and a neutralization step was performed. The rest of the procedure was the same as in Example 1 to obtain the STP.

[0082] <Example 4> In the organic layer washing step of Example 1, washing was performed an additional three times, bringing the total number of washings to nine. After that, 10 mL of the organic layer was collected and a neutralization step was performed. The rest of the procedure was the same as in Example 1 to obtain the STP.

[0083] <Example 5> In the organic layer washing step of Example 1, washing was performed an additional four times, bringing the total number of washings to 10. After that, 10 mL of the organic layer was collected and a neutralization step was performed. The rest of the procedure was the same as in Example 1 to obtain the STP.

[0084] <Example 6> In the organic layer washing step of Example 1, an additional 6 washes were performed, bringing the total number of washes to 12. After that, 10 mL of the organic layer was collected and a neutralization step was performed. The rest of the procedure was the same as in Example 1 to obtain the STP.

[0085] <Example 7> In the neutralization step of Example 1, STP was obtained in the same manner as in Example 1, except that the amount of 5M-NaOH was increased to 1.4 molar equivalents relative to TP and added dropwise.

[0086] <Example 8> In the neutralization step of Example 1, STP was obtained in the same manner as in Example 1, except that the amount of 5M-NaOH was increased to 1.2 molar equivalents relative to TP and added dropwise.

[0087] <Comparative Example 1> In the organic layer washing step of Example 1, STP was obtained in the same manner as in Example 1, except that the number of washing times was changed to 2 times.

[0088] <Comparative Example 2> In the organic layer washing step of Example 1, STP was obtained in the same manner as in Example 1, except that the number of washing times was changed to 3 times.

[0089] <Comparative Example 3> In the organic layer washing step of Example 1, STP was obtained in the same manner as in Example 1, except that the number of washing times was changed to 4 times.

[0090] <Preparation of Lotion> Lotions containing the respective STPs of each Example and Comparative Example were prepared according to the following formulation. Ethyl alcohol 5.0% by mass 1,3-Butylene glycol 12.0% by mass Glycerin 3.0% by mass STP (STP of each Example and Comparative Example) 1.5% by mass Disodium isostearyl ascorbyl phosphate 0.5% by mass Purified water 78.0% by mass

[0091] <pH Measurement Method> Measurement was carried out using a pH meter manufactured by Horiba, Ltd. In the organic layer washing step, in the washing step of the last number of washing times determined in each Example and Comparative Example, the separated organic layer and aqueous layer were stirred at a speed of 50 rpm or more for 10 minutes (to the extent that the stirring blade contacted the layer interface and the layer interface disappeared) using a stirring blade, then the stirring was stopped and left standing for at least 10 minutes or more. After the separation from the organic layer was completed, the electrode was inserted into the washing water, and the value after 1 minute was measured. The results are shown in Table 1.

[0092] <Measurement of chlorine amount in washing water by ion chromatography> Using an ion chromatograph manufactured by Thermo Fisher Scientific K.K. (column AS22 was used), the chlorine amount contained in the aqueous layer obtained by washing the organic layer was measured. The separated organic layer and aqueous layer in the organic layer washing step were stirred at a speed of 50 rpm or more for 10 minutes (to the extent that the stirring blade contacted the layer interface and the layer interface disappeared) using a stirring blade, then the stirring was stopped and left standing for at least 10 minutes or more. After the separation from the organic layer was completed, the aqueous layer was recovered and used as a measurement sample. The results are shown in Table 1.

[0093] <Measurement of chlorine amount in STP by ion chromatography> Using an ion chromatograph manufactured by Thermo Fisher Scientific K.K. (column AS22 was used), the chlorine amount of a 0.5 mass% aqueous solution of STP was measured and converted to the chlorine amount contained in STP. The results are shown in Table 1.

[0094] <Measurement of sodium amount by ICP> Using a sequential high-frequency plasma emission analyzer (ICPS8100) manufactured by Shimadzu Corporation, the amount of sodium contained in the STP obtained in the Examples and Comparative Examples was measured by ICP emission spectrometry.

[0095] <Measurement of TP amount by HPLC> The content (mass%) of TP was calculated by using liquid chromatography (HPLC), creating a calibration curve using a standard product under the measurement conditions shown below, and analyzing a sample solution (concentration of TP about 1000 ppm (mass basis)) using this calibration curve. (Measurement conditions) Column: Asahipak ODP-50 6D (Shodex (registered trademark)) Eluent: A solution prepared by dissolving ammonium acetate in 1 mass% aqueous methanol to a concentration of 0.1 mol / L Flow rate: 0.5 mL / min Column temperature: 40 °C Detector: PDA 200 - 400 nm

[0096] <Calculation method of Na / TP>[[]]END]] Based on the molar amount of sodium measured by the above ICP and the molar amount of TP calculated from the measurement by HPLC, for each of the STPs prepared in the examples and comparative examples, the amount of sodium (Na / TP) attached per 1 mole of TP was calculated. The results are shown in Table 1.[[]]END]]

[0097] <Haze measurement>[[]]END]] For each of the 0.5 mass% aqueous solutions of the STPs obtained in the examples and comparative examples, the freshly prepared lotion, and the lotion stored for 1 month under refrigeration at 2.5 °C after preparation, they were placed in a quartz cell with an optical path length of 10 mm, and the haze value (%) of the dispersion was measured using a haze meter (NDH 4000) manufactured by Nippon Denshoku Industries Co., Ltd. The results are shown in Table 1.[[]]END]]

[0098]

Table 1

[0099] As shown in Table 1, the STPs of Examples 1-8 all had lower levels of chlorine in both the final wash water and the STP itself compared to Comparative Examples 1-3. In a 0.5% by mass aqueous solution of STP and a lotion immediately after preparation, the STPs of Examples 1-8 showed lower haze values ​​and higher transparency than those of the STPs of Comparative Examples 1-3. In Examples 7-8, the amount of added sodium was increased compared to Examples 1-6 and Comparative Examples 1-3, and despite the number of moles of sodium per mole of TP exceeding 1, the haze values ​​of the 0.5% by mass aqueous solution of STP and the lotion immediately after preparation were lower than those of Comparative Examples 1-3. This confirms that by keeping the chlorine content below a predetermined value, it is possible to obtain STP with high solubility in water, regardless of the presence or absence of residual sodium. On the other hand, in lotions stored for one month at 2.5°C after preparation, the STPs of Examples 1-6 showed lower haze values ​​and maintained a transparent appearance compared to those of the STPs of Examples 7-8. Therefore, it can be said that it is preferable that the number of moles of sodium per mole of TP be less than 1.1.

[0100] The embodiments and examples disclosed herein should be considered in all respects to be illustrative and not restrictive. The scope of the present invention is indicated by the claims rather than by the foregoing description and includes all variations in the meaning and scope equivalent to the claims.

Claims

1. Sodium vitamin E phosphate with a chlorine content of 1000 ppm or less.

2. The vitamin E sodium phosphate according to claim 1, wherein the number of moles of sodium per mole of vitamin E phosphate ester is less than 1.

1.

3. A phosphorylation process to obtain vitamin E phosphate ester by phosphorylating vitamin E with phosphorus oxychloride, A washing step in which the vitamin E phosphate ester obtained in the phosphorylation step is washed with water, The process includes a neutralization step in which the vitamin E phosphate ester washed in the washing step is sodium-chlorinated, The washing step is repeated until the pH of the aqueous layer separated from the organic layer after washing is 1.4 or higher, in a method for producing sodium vitamin E phosphate.

4. The manufacturing method according to claim 3, wherein the neutralization step includes sodium chloride using 1.2 molar equivalents or less of sodium hydroxide relative to the vitamin E phosphate ester.

5. A topical skin preparation containing sodium vitamin E phosphate according to claim 1 or claim 2.

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