JP4717171B2 - Method for producing transparent dispersion containing ceramides - Google Patents

Description

【００５５】
上記のようにして得られたセラミドの分散液は透明であり、実施例１と同様にして調べた分散液の安定性は良好であり、濁り、沈殿などは発生しなかった。
【００５６】
【実施例５〜１０】
実施例１において、ゲル状物を調製する際のポリオキシアルキレングリセリルモノアルキルエステルおよび多価アルコールとして表２に記載する化合物を使用し、セラミドの使用量を変えた以外は同様にしてセラミドを可溶化した。結果を表２に併せて記載する。
【００５７】
なお、以下に示す表２〜４において、「ＡＡ」は「透明で安定である」ことを示し、「ＢＢ」は「安定であるが半透明である」ことを表す。
【００５８】
この結果からモノイソステアリン酸POEグリセリンとモノステアリン酸POEグリセリンの併用で、セラミド類に対する可溶化能力が増大することがわかった。また、モノステアリン酸POEグリコール(25EO)とモノイソステアリン酸POEグリセリンもしくはステアリン酸POEグリセリンの併用でも、同様の傾向が見られる。さらに、多価アルコールの添加により、可溶化能力が増大することがわかった。
【００５９】
【表２】

【００６０】
【実施例１１〜１６】
実施例１において、ゲル状物を調製する際のポリオキシアルキレングリセリルモノアルキルエステルおよび多価アルコールの種類および量を表３に記載するように変えた以外は同様にしてセラミドを可溶化した。結果を表３に併せて記載する。
【００６１】
この結果から、イソステアリン酸POEグリセリンは、単独もしくはモノステアリン酸POEグリセリンまたはモノステアリン酸POEグリコールと併用すると、天然セラミドに対する可溶化力が増大し、安定な透明分散液が得られることがわかった。また、多価アルコールの添加により可溶化能力はさらに増大することがわかった。
【００６２】
【表３】

【００６３】
【実施例１７〜２０】
実施例１において、使用するポリオキシアルキレングリセリルモノアルキルエステルのHLBを表４に示すように代えた以外は同様にしてセラミドの可溶化を行った。結果を表４に示す。
【００６４】
上記表４に示す結果からHLBが１５〜１８の範囲内で可溶化能力がよく、HLBがこの範囲内で天然セラミドは透明で安定に分散することがわかった。
【００６５】
【表４】

[0001]
[Industrial application fields]
The present invention relates to a method for producing a transparent and stable dispersion in which a ceramide such as ceramide or a ceramide-like compound existing in a stratum corneum of living skin is transparently dispersed in an aqueous medium.
[0002]
TECHNICAL BACKGROUND OF THE INVENTION
Ceramide is a compound that exists in the stratum corneum of living skin and plays an important role in constructing and maintaining a lipid barrier necessary for water retention in the living body. This ceramide is an amphiphilic substance and is a compound having a hydrophobic group and a hydrophilic group in the same molecule. In addition to natural ceramide contained in the stratum corneum of living skin, this ceramide includes ceramide containing phytosfigocin as synthetic ceramide, N- (hexadecyloxyhydroxypropyl) -N-hydroxyethylhexadecanamide, N -There are acylsulfifagocin-containing ceramides, sphingomyelin, and phytosphingosine, which are similarly used as ceramides because they also build and maintain lipid barriers necessary for biological moisture retention. Hereinafter, in the present invention, when it is described as “ceramides” without particular limitation, it includes natural ceramide and similar compounds.
[0003]
Such ceramides are used as lipid barrier forming agents in order to retain water in the living body as described above, and therefore it is conceivable to use them in cosmetics.
[0004]
However, these ceramides are insoluble in water, and therefore cosmetics containing ceramides are limited to oils, emulsions or creams. That is, even if a surfactant or the like is added to the ceramides and dispersed in water, the dispersibility in water is poor and even emulsification is considerably difficult. Further, even when emulsified, the emulsification stability is low, and it has been extremely difficult to maintain the emulsified state stably for a long period of time.
[0005]
It is known that when a surfactant is added to an oil agent and water is added to the oil agent, the oil agent forms micelles and emulsifies. At this time, an appropriate surfactant is used and further appropriate solubilization is performed. It is known that very fine micelles can be formed by using an agent, and the liquid becomes transparent when the very fine micelles are stably dispersed in an aqueous medium. This is so-called solubilization of the oil agent.
[0006]
However, ceramides have a lower affinity for water as it is difficult to stably emulsify itself, and a technique for stably solubilizing ceramides has not been clearly established.
[0007]
For example, Japanese Patent Publication No. 9-505065 discloses a cosmetic composition in which phytosfigocin-containing ceramide is solubilized with glycerol C18-C22 monofatty acid ester. It is a very special ceramide, and a stable solubilized product cannot be obtained even if the technique for solubilizing such a special ceramide is applied to other general ceramides.
[0008]
Japanese Patent Application Laid-Open No. 11-130651 discloses a cosmetic with excellent moisturizing effect containing phospholipid, N-acyl phytosphingosine-containing ceramide, and polyhydric alcohol. Even if a technique for solubilizing such a special ceramide is applied to other general ceramides, a stable solubilized product cannot be obtained.
[0009]
Furthermore, Japanese Patent Publication No. 8-18948 discloses an invention of a method for producing an emulsion-type cosmetic by dispersing fats and oils such as ceramide and cholesterol fatty acid ester in an aqueous medium with an emulsifier. However, no specific method for solubilizing ceramides is disclosed.
[0010]
Furthermore, Japanese Patent Publication No. 6-86373 discloses cosmetics containing ceramide and liquid difatty acid glycerin ester. According to the study of the present inventors, such difatty acid glycerin ester was used. Therefore, ceramides cannot be solubilized stably.
[0011]
JP-A-2-78432 discloses an invention of a transparent composition containing an amphiphilic substance, a surfactant, an oil component and water. This publication shows that an amphiphilic substance such as lecithin is used together with a surfactant in solubilizing the oil component in water. The sphingomyelin described here as an amphiphilic substance may be classified into ceramides. However, this publication discloses that an amphiphile is used together with a surfactant when solubilizing the oil component, and a technique for solubilizing the amphiphile is not disclosed.
[0012]
In general, emulsions, creams, and other cosmetics have a strong image of containing a large amount of oil, whereas transparent cosmetics have a clean image. There is a tendency to be preferred. However, ceramides having very good moisturizing performance cannot be made into a stable transparent cosmetic.
[0014]
An object of the present invention is to provide a novel method for producing a stable transparent dispersion containing ceramides.
[0015]
Summary of the Invention
In the method for producing a transparent dispersion containing the ceramides of the present invention, a ceramide and a polyoxyalkylene glyceryl monoalkyl ester are mixed with heating to form a uniform mixture, and the uniform mixture is heated with stirring. It is possible to prepare a gel-like product by adding water, and then solubilize the gel-like product by gradually adding it to a cooled aqueous medium with stirring.
[0017]
In the present invention, when transparently dispersing ceramides in water, using a specific polyoxyalkylene glyceryl monoalkyl ester, hot water is added to a homogeneous mixture containing the ceramides and the polyoxyalkylene glyceryl monoalkyl ester. A semi-transparent gel is prepared, and the gel is put into a cooled aqueous medium to rapidly cool, and the gel is transparently dispersed in the aqueous medium to make ceramides transparent. It is dispersed in an aqueous medium.
[0018]
DETAILED DESCRIPTION OF THE INVENTION
Next, the transparent dispersion containing the ceramides of the present invention will be described along with its production method.
[0019]
In the solubilization of the ceramides of the present invention, a gel-like product is prepared from ceramides and water by a method similar to D-phase emulsification, and the gel-like product is prepared as described above by a method similar to the microemulsion method. The prepared gel-like material is finely dispersed in water while rapidly cooling.
[0020]
The ceramides solubilized in the present invention include natural ceramides, ceramides containing phytosphygosin as synthetic ceramides, N- (hexadecyloxyhydroxypropyl) -N-hydroxyethylhexadecanamide, N-acylsulfurs. There are figosin-containing ceramides, sphingomyelin, and phytosphingosine. The method of the present invention is effective for the ceramide as described above.
[0021]
In the present invention, polyoxyalkylene glyceryl monoalkyl ester is used in order to disperse the ceramides as described above in water and solubilize them.
[0022]
In the polyoxyalkylene glyceryl monoalkyl ester used in the present invention, one of the three hydroxyl groups of glycerin is esterified. The polyoxyalkylene glyceryl monoalkyl ester has a component unit derived from oxyalkylene. In the present invention, the alkyl group forming the ester group preferably has 18 carbon atoms. Examples of the carboxylic acid having an alkyl group having 18 carbon atoms capable of forming an ester with glycerin include stearic acid and isostearic acid. Moreover, as oxyalkylene, ethylene oxide is preferable. The polyoxyalkylene glyceryl monoalkyl ester used in the present invention usually has 10 to 60, preferably 30 to 50, component units derived from this ethylene oxide per molecule.
[0023]
As this polyoxyalkylene glyceryl monoalkyl ester, monoisostearic acid POE (30-50) glycerol and / or monostearic acid PEO (30-50) glycerol is preferably used.
[0024]
In particular, the HLB value of the polyoxyalkylene glyceryl monoalkyl ester used in the present invention is desirably in the range of 15 to 18, preferably 16 to 17. When a plurality of polyoxyalkylene glyceryl monoalkyl esters are used, it is preferable that the HLB values of these compounds are within the above range.
[0025]
This polyoxyalkylene glyceryl monoalkyl ester is usually used in an amount of 100 to 1000 parts by weight, preferably 200 to 500 parts by weight, based on 100 parts by weight of ceramides.
[0026]
At this time, it is preferable to use a polyhydric alcohol together. The polyhydric alcohol used here is ethylene glycol, propylene glycol, 1,3-butylene glycol, diethylene glycol, triethylene glycol, polyethylene glycol, dipropylene glycol, polypropylene glycol, isoprene glycol, glycerin, diglycerin, polyglycerin. And so on. Such polyhydric alcohol is usually used in an amount of 50 to 300 parts by weight, preferably 100 to 200 parts by weight, based on 100 parts by weight of the ceramides.
[0027]
In the ceramides, polyoxyalkylene glyceryl monoalkyl ester is used in the amount described above, and polyhydric alcohol is used in the amount described above, and the mixture is usually stirred at 50 to 95 ° C., preferably 70 to 90 ° C. with stirring. Heat to prepare a uniform mixture of these.
[0028]
Separately from this, 30 to 300 parts by weight, preferably 50 to 150 parts of water are usually prepared for 100 parts by weight of the homogeneous mixture, and this water is usually heated to 50 to 95 ° C., preferably 60 to 90 ° C. To do. In particular, in the present invention, water heated in the range of ± 2.5 ° C., preferably ± 1 ° C., with respect to the temperature of the homogeneous mixture (oil phase) prepared as described above is used.
[0029]
The homogeneous mixture (oil phase) is added little by little while stirring the water thus heated. During this addition, the temperature of the system is usually maintained at 50 to 95 ° C, preferably 70 to 90 ° C.
[0030]
A semitransparent gel-like material can be obtained by adding the homogeneous mixture (oil phase) to the aqueous phase when heated. In this reaction, a D phase is formed with a nonionic sea surface active agent / polyhydric alcohol / water, and an oil phase is added and held under stirring to form a transparent gel emulsion. The reaction is similar to the D-phase emulsification method for producing a W emulsion, but differs from the D-phase emulsification method in that water is added to the oil phase and the transparent gel emulsion is not diluted with water.
[0031]
Apart from the gel phase thus formed, an aqueous phase is prepared. That is, the gel phase is diluted by a method similar to the microemulsion method using the gel phase, and the ceramides are transparently dispersed in water.
[0032]
The aqueous phase used here includes water, polyhydric alcohol as necessary, and other ingredients, for example, natural moisturizing factors such as sodium pyrodonate and sodium lactate, moisturizing ingredients such as sodium hyaluronate, succinic acid and sodium succinate. PH adjusting components such as, anti-inflammatory components such as dipotassium glycyrrhizinate, antiseptic components such as phenoxyethanol, and thickening components such as acrylic acid / alkyl methacrylate copolymers can be blended. When using a polyhydric alcohol here, it is preferable to use the thing similar to the polyhydric alcohol used when preparing a gel-like thing.
[0033]
Such compounds are generally used in amounts of 0.001 to 30 parts by weight per 100 parts by weight of water.
[0034]
In this invention, it cools so that the temperature of this aqueous phase may become the temperature in the range of 0-20 degreeC normally, Preferably 5-15 degreeC. Particularly in the present invention, this aqueous phase is cooled so that the temperature difference from the gel is usually 30 ° C. or higher, preferably 40 ° C. or higher, particularly preferably 50 ° C. or higher.
[0035]
While the water phase thus cooled is vigorously stirred, the above gel-like material is added to the water phase little by little to rapidly cool the gel-like material.
[0036]
This method is similar to the microemulsion method, but in the normal microemulsion method, water is added to a high-temperature gel material and cooled, whereas in the present invention, a large amount of cooled water is heated to a high temperature. This is different in that it is cooled rapidly by adding a small amount of the gel.
[0037]
At this time, the gel-like substance is usually added in an amount of 2 to 20 parts by weight, preferably 5 to 10 parts by weight based on 100 parts by weight of the cooled water. Thus, by adding a gel-like substance to a large excess of water, the gel-like substance can be dispersed in cooled water while rapidly cooling. In addition, since the gel-like material is added little by little to the excessive water phase in this way, the temperature of the aqueous phase hardly increases, but if necessary, the gel-like material may be added while cooling the aqueous phase. .
[0038]
By adding and dispersing a high-temperature gel-like substance little by little with vigorous stirring in the water phase thus cooled, the gel-like substance is transparently dispersed in the aqueous phase.
[0039]
Thus, after adding a gel-like substance to the cooled water and disperse | distributing transparently to an aqueous phase, the pH value of this transparent dispersion liquid is the range of 4-8, if necessary, Preferably it is 4.5-6. Prepare to range. For adjusting the pH value, it is preferable to use a combination of carboxylic acid and carboxylate. Examples of combinations of carboxylic acid and carboxylate used for adjusting the pH value include oxalic acid and sodium oxalate, lactic acid and sodium lactate, citric acid and sodium citrate, hydroxyethane diphosphonic acid, hydroxy Examples include tetrasodium ethanediphosphonate. By adjusting the pH value of the transparent dispersion as described above using such a pH value adjusting agent, the stability of the transparent dispersion is improved.
[0040]
The transparent dispersion of ceramides prepared as described above can contain ceramides in an amount of 0.001 to 10% by weight, preferably 0.1 to 1.0% by weight. Moreover, the transparent liquid in which the ceramides thus prepared are solubilized and dispersed can continue to solubilize the ceramides stably for a long period of time.
[0041]
According to the method of the present invention, it is possible to stably solubilize ceramides that have a low affinity for water and are difficult to emulsify.
[0042]
Thus, the dispersion liquid in which ceramides are transparently dispersed can be effectively used as, for example, cosmetics, skin treatment agents, wet tissue impregnation liquids, and the like.
[0043]
In response to the use of such a transparent dispersion of ceramides, various additives can be added to the transparent dispersion within a range where the stability of the transparent dispersion is not impaired. For example, when used as a skin lotion, this transparent dispersion is added to flavors, dyes, vitamins, moisturizers, antioxidants, UV protection agents, preservatives, thickeners, foaming agents, chelating agents, pH adjustment Agent, rough skin prevention agent, anti-aging agent, whitening agent, hair restorer, anti-inflammatory agent, amino acids and peptides, etc., when used as a skin treatment, hormone agent, antibiotic, bactericidal component, Hair-growth ingredients, anti-inflammatory ingredients, etc. can be blended.
[0044]
【The invention's effect】
According to the present invention, ceramides that have been extremely difficult to solubilize can be solubilized stably using polyoxyalkylene glyceryl monoalkyl ester. Moreover, the transparent dispersion containing ceramides obtained in this way is very stable and maintains a transparent state for a long time.
[0045]
【Example】
Next, the present invention will be described in more detail with reference to examples of the present invention.
[0046]
[Example 1]
Ceramide 0.5 parts by weight, monoisostearic acid POE (40) glycerol (HLB = 17) 1.40 parts by weight, monostearic acid (40) glycerol (HLB = 17) 1.00 parts by weight, 1,3-butylene glycol A uniform mixture was prepared by heating 1.00 parts by weight with stirring to 80 to 85 ° C.
[0047]
Separately, 2.00 parts by weight of purified water was heated to 80 to 85 ° C.
[0048]
The temperature of the homogeneous mixture prepared as described above was maintained at 80 to 85 ° C., and purified water heated to 80 to 85 ° C. was gradually added under strong stirring to prepare a translucent gel.
[0049]
Separately from this, an aqueous solution having the following composition was prepared.
1,3-Butylene glycol ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ ・ 2.00 parts by weight Sodium pyrrolidone sulfonate (50%) ・ ・ ・ 2.00 parts by weight Sodium lactate (50%) ..... 2.00 parts by weight sodium hyaluronate (1%) ..... 1.00 parts by weight glycyrrhizic acid Dipotassium ············ 0.10 parts by weight Phenoxyethanol · ······················································ 0.55 ...... 87.388 parts by weight An aqueous solution having the above composition was cooled to 10 to 15 ° C.
[0050]
While strongly stirring 100 parts by weight of the aqueous solution cooled at 10 to 15 ° C., 6 parts by weight of the gel was added little by little to disperse the gel in the aqueous solution transparently.
[0051]
After the entire amount of the gel-like material was added in this manner, stirring was continued, and 0.01 parts by weight of oxalic acid and 0.002 parts by weight of oxalic acid were added to the dispersion in which the gel-like material was transparently dispersed. The pH value was adjusted to 5.5.
[0052]
In the obtained dispersion, the ceramide was transparently dispersed in the aqueous phase, and was observed after standing at room temperature for 30 days. However, the transparent dispersion became turbid and no precipitation was observed. Had sex.
[0053]
[Examples 2 to 4]
Ceramide was solubilized in the same manner as in Example 1 except that the composition was changed as described in Table 1 below.
[0054]
[Table 1]

[0055]
The dispersion of ceramide obtained as described above was transparent, the stability of the dispersion investigated in the same manner as in Example 1 was good, and no turbidity or precipitation occurred.
[0056]
Examples 5 to 10
In Example 1, ceramides can be used in the same manner except that the polyoxyalkylene glyceryl monoalkyl ester and polyhydric alcohol listed in Table 2 were used in the preparation of the gel and the amount of ceramide used was changed. Solubilized. The results are also shown in Table 2.
[0057]
In Tables 2 to 4 below, “AA” indicates “transparent and stable”, and “BB” indicates “stable but translucent”.
[0058]
From these results, it was found that the combined use of monoisostearic acid POE glycerin and monostearic acid POE glycerin increases the solubilization ability for ceramides. The same tendency is also observed when POE glycol monostearate (25EO) and POE glyceryl monoisostearate or POE glyceryl stearate are used in combination. Furthermore, it was found that the addition of polyhydric alcohol increases the solubilizing ability.
[0059]
[Table 2]

[0060]
Examples 11 to 16
In Example 1, ceramide was solubilized in the same manner except that the types and amounts of polyoxyalkylene glyceryl monoalkyl ester and polyhydric alcohol used in preparing the gel-like product were changed as shown in Table 3. The results are also shown in Table 3.
[0061]
From this result, it was found that POE glycerin isostearate alone or in combination with POE glyceryl monostearate or POE glycol monostearate increases the solubilizing power with respect to natural ceramide, and a stable transparent dispersion can be obtained. It was also found that the solubilization ability was further increased by the addition of polyhydric alcohol.
[0062]
[Table 3]

[0063]
Examples 17 to 20
Ceramide was solubilized in the same manner as in Example 1 except that the HLB of the polyoxyalkylene glyceryl monoalkyl ester used was changed as shown in Table 4. The results are shown in Table 4.
[0064]
From the results shown in Table 4 above, it was found that the solubilization ability was good when the HLB was in the range of 15 to 18, and the natural ceramide was transparent and stably dispersed when the HLB was within this range.
[0065]
[Table 4]

Claims (11)

  Ceramides and polyoxyalkylene glyceryl monoalkyl ester are mixed with heating to form a uniform mixture, and heated water is added to the uniform mixture with stirring to prepare a gel, and then the gel A method for producing a transparent dispersion containing ceramides, characterized in that a product is gradually added to a cooled aqueous medium with stirring and solubilized.   The polyoxyalkylene glyceryl monoalkyl ester is a polyoxyethylene glyceryl monoalkyl ester, and the alkyl group forming the ester is a linear alkyl group having 18 carbon atoms or a branched alkyl group having 18 carbon atoms. The method for producing a transparent dispersion according to claim 1, wherein:   The method for producing a transparent dispersion according to claim 1, wherein the polyoxyethylene of the polyoxyethylene glyceryl monoalkyl ester has 10 to 60 oxyethylene repeating units.   The method for producing a transparent dispersion according to claim 1, wherein the polyoxyalkylene glyceryl monoalkyl ester has an HLB value in the range of 15 to 18.   The method for producing a transparent dispersion according to claim 1, wherein the gelled material contains a polyhydric alcohol.   2. The gel-like product according to claim 1, wherein polyoxyalkylene glyceryl monoalkyl ester is blended in an amount in the range of 100 to 1000 parts by weight with respect to 100 parts by weight of ceramides. Of producing a transparent dispersion liquid.   6. The method for producing a transparent dispersion according to claim 5, wherein polyhydric alcohol is blended in the gel-like material in an amount of 50 to 300 parts by weight with respect to 100 parts by weight of ceramides. .   2. The method for producing a transparent dispersion according to claim 1, wherein the aqueous medium contains a polyhydric alcohol.   The method for producing a transparent dispersion according to claim 1, wherein the ceramide and the polyoxyalkylene glyceryl monoalkyl ester are heated to 50 to 95 ° C when the homogeneous mixture is formed.    The method for producing a transparent dispersion according to claim 1, wherein the temperature of the heated water added to the homogeneous mixture is in the range of 50 to 95 ° C.   The temperature of the aqueous medium to which the gelled material is added is in the range of 0 to 20 ° C, and the difference between the temperature of the aqueous medium and the temperature of the gelled material is 30 ° C or more. The manufacturing method of the transparent dispersion liquid of claim | item 1 item | term.