JP3079531B2 - Oil-in-water type multi-phase emulsion and method for producing the same - Google Patents

Description

Description: FIELD OF THE INVENTION The present invention relates to a novel oil-in-water multi-phase emulsion and a method for producing the same, and more particularly, to disperse two or more oil components independently in an aqueous continuous phase. By emulsifying to prepare an O ₁ + O ₂ +... + O _n / W emulsion, an oil-in-water multiphase emulsion suitable for cosmetics, foods, pharmaceuticals, paints, and the like is provided.

(Conventional technology) Emulsions are originally thermodynamically non-equilibrium systems, but nowadays they are used in a wide range of industrial fields such as cosmetics and pharmaceuticals due to the development of emulsification technology and stabilization technology. became.

More recently, complex emulsions developed from conventional emulsion types such as oil-in-water (O / W) type and water-in-oil (W / O) type, ie, W / O / W type, O / W / O type Attention has also attracted attention to such things as mold emulsions, and the fact is that the mechanism and applications are being actively studied.

(Problems to be Solved by the Invention) However, despite the fact that studies on emulsions have been conducted only to this extent, dispersoids in emulsions such as O / W
At present, little has been studied about the properties of oil droplets in emulsions for their importance.
The reason is that the dispersoid in the emulsion is composed of a thin film of surfactant, so that the union between these dispersoids can be controlled, but the mobility of the oil contained in the dispersoid is reduced. It was technically difficult to control.

On the other hand, various needs are needed for emulsions, such as sustained release and transdermal absorption promotion of inclusions in pharmaceuticals, various feelings in foods, and various skin conditions in cosmetics. It has become Controlling the movement of the oil contained in the dispersoid, in response to the various needs described above, for example, in pharmaceuticals, has both fast-acting and sustained-release properties using the solubility difference of the active ingredient in two types of oils. It is possible to provide a dosage form, and in cosmetics, if the solubility of the physiologically active ingredient in a polar oil is high, it is intensively dissolved in it, and the effect is improved by using another oil to improve the feel. It is also possible to provide a dosage form unique to cosmetics that has both.

The present invention provides, as described above, an oil-in-water emulsion in which two or more types of oils suitable for pharmaceuticals, cosmetics and the like are independently dispersed and emulsified by controlling the mobility of the oil in the oil-in-water emulsion. In other words, it is an object to provide an oil-in-water type multi-phase emulsion and a method for producing the same.

(Means for Solving the Problems) Thus, the present inventor repeated various experimental studies on the mobility of the oil in the oil-in-water emulsion and the components used, and as a result, the mobility of the oil and the surface activity used The existence of a correlation between the amount of the agent and the presence of a water-soluble polymer with high hydration ability in the aqueous phase, which is a continuous phase, can control the movement of oil and stably disperse the oil by type. It has been found that it is possible to make it possible. The present invention is based on such findings.

The present invention is characterized in that a surfactant film is immobilized by a water-soluble polymer and the movement of oil in a dispersoid is controlled, and this principle itself is a completely new one that has never been seen before. .

That is, the present invention is: 1) An oil-in-water type multi-phase emulsion in which two or more types of oil components are independently present in an aqueous continuous phase as an emulsion (excluding a micro-emulsion having a particle size of 0.5 μm or less). The oil-in-water multi-phase emulsion contains a surfactant in an amount of 4% by weight or less, and the water-continuous phase of the oil-in-water multi-phase emulsion contains a natural water-soluble polymer of 0.05 to 10%.
An oil-in-water type multi-phase emulsion characterized by containing 10% by weight.

2) As a first step, a plurality of oil-in-water emulsions obtained by dispersing and emulsifying different kinds of oils, respectively (however,
Excluding a microemulsion having a particle size of 0.5 μm or less), and then, as a second step, mixing a plurality of the oil-in-water emulsions obtained in the above steps to form an oil-in-water multi-phase emulsion, In the oil-in-water multi-phase emulsion, the surfactant is adjusted to be 4% by weight or less, and in the water continuous phase of the oil-in-water multi-phase emulsion, 0.05 to 10% by weight of the natural water-soluble polymer is contained. A method for producing the above-mentioned oil-in-water multi-phase emulsion, characterized in that it is adjusted so as to be contained in a range.

Is provided.

 Hereinafter, the present invention will be described in detail.

The method for producing an oil-in-water emulsion according to the present invention is roughly divided into a first step of preparing a plurality of oil-in-water emulsions in which different types of oil components are respectively dispersed, and a plurality of oil-in-water emulsions obtained in the first step. A second step of mixing the oil-in-water emulsion.

First, in the first step of preparing an oil-in-water emulsion, an oil phase, an aqueous phase, and a surfactant (including a cosurfactant) are mixed, stirred, and emulsified according to a conventional method. Then, a plurality of oil-in-water emulsions in which oil components appropriately selected according to the purpose are dispersed are created.

The oil used here includes liquid oils such as liquid paraffin, squalane, hexadecane, silicone oil, olive oil, jojoba oil, almond oil, 2-ethylhexanoic acid triglyceride, semisolid oils such as petrolatum, lanolin, and ceresin. , Solid paraffin, beeswax, and spermaceous wax, and the like, but are not necessarily limited thereto.

On the other hand, there is no restriction on the type of surfactant as long as an oil-in-water emulsion can be formed, and for example, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene sorbite fatty acid ester, glycerin fatty acid ester, Commonly used surfactants such as glycerin fatty acid ester, polyoxyethylene alkyl ether, polyethylene glycol fatty acid ester, polyoxyethylene polyoxypropylene alkyl ether, and alkyl glycerin ether may be used alone or in combination of two or more. it can. In addition, the same type of surfactant may be used in common for a plurality of oil-in-water emulsions, or conversely, they may be different.

In addition, higher alcohols such as cetanol and stearyl alcohol and higher fatty acids such as stearic acid and palmitic acid may be used as a cosurfactant together with the surfactant.

However, as described later, in the present invention, in order to suppress the transfer of oil between emulsions, the amount of the surfactant (including the cosurfactant) used is determined by the final product after the second step described later, that is, the oil-in-water type. It is desirable to keep the content to 4% by weight or less based on the multi-phase emulsion.

Further, in the present invention, a natural water-soluble polymer is added to the aqueous phase. The natural water-soluble polymer referred to herein is water or an aqueous solvent such as glycerin, propylene glycol,
A natural polymer substance that disperses and swells in 3-butylene glycol and the like to form a highly viscous mucus, specifically, hyaluronic acid, xanthan gum, elastin hydrolyzate, gelatin, collagen hydrolyzate, pectin And sodium alginate, among which hyaluronic acid, xanthan gum and the like having a higher hydration ability are preferable. In addition, when the natural water-soluble polymer is added, it may be added to any one of the plurality of oil-in-water emulsions prepared in the first step, but of course, it may be added to two or all of the products. Absent.

However, the amount of addition may vary depending on the type of the natural water-soluble polymer used because the effect of immobilizing the surfactant film is strong or weak, but is usually based on the final product after the two steps described below. 0.05 to 10% by weight, preferably 0.
A range of 1 to 5% by weight is selected. In the case where hyaluronic acid or xanthan gum having a high hydration ability is used as described above, the effect is sufficiently exerted with an addition amount in the range of 0.05 to 1% by weight.

If the amount is less than 0.05% by weight, the transfer of oil between emulsions cannot be suppressed, which is not preferable. If the amount exceeds 10% by weight, the emulsification system may be broken.

The second step is a step of mixing the plurality of oil-in-water emulsions obtained in the first step. In this step, the plurality of emulsions obtained in the first step may be simply mixed with each other and stirred, but at this time, the emulsion temperature at the time of mixing is preferably as low as possible, and at least the cosurfactant is preferably used. If used, it should be kept below a temperature 5-10 ° C. above its melting point. Of course, in the case of a low-viscosity emulsion that does not use a cosurfactant, it is preferable to mix at room temperature.

In addition, the preparation of the oil-in-water emulsion in the first step and the mixing of the oil-in-water emulsion in the second step may be performed continuously as a series of steps, or the emulsion obtained in the first step may need to be stored once. The mixing in the second step may be performed at any time, and either may be performed.

The oil-in-water multi-phase emulsion finally obtained through the first step and the second step has two or more kinds of different oil components stably dispersed and emulsified in a water continuous phase.

Here, also regarding the point that the oil-in-water type multi-emulsion according to the present invention is stably maintained, the result of evaluating the effect of the surfactant and the water-soluble polymer on the degree of dispersion of the oil serving as the mechanism of action will be described. .

Experiment 1. Effect of Surfactant Concentration on Oil Dispersion (Method) Two types of oil-in-water emulsions were prepared by emulsifying the components shown in Formulas A and B below at a temperature of 60 ° C by a phase inversion method. Thereafter, this was mixed and stirred at a temperature of 45 ° C. to prepare an oil-in-water type multi-phase emulsion. The degree of dispersion was evaluated using a differential calorimeter (DSC), with the melting peak area of hexadecane in the oil-in-water multiphase emulsion immediately after preparation as the standard (100%), and the reduction in the melting area of hexadecane after aging at room temperature. Performed by determining the degree. One day after the measurement, 5
After 4 days, 10 days and 15 days, the results were shown in FIG.

Here, x in Formula A and Formula B is 6.0, 3.0, 1.0
At three points.

As shown in the results in Fig. 1, the degree of decrease in the hexadecane melting peak area decreased with the decrease in the amount of surfactant (6 wt% → 3 wt% → 1 wt%), indicating that the oil-in-water multiphase It became clear that there is a close relationship between the retention of the dispersity of hexadecane in the emulsion and the amount of surfactant.

Experiment 2. Effect of addition of water-soluble polymer on dispersibility of oil (Method) Mix and stir the components shown in Formula C and Formula D below.
After preparing various kinds of emulsions, they were mixed and stirred at room temperature to prepare an oil-in-water type multi-phase emulsion. Evaluation of the degree of dispersion was performed in the same manner as in Experiment 1 using hexadecane as an index. The results are shown in FIG.

As shown in the results of FIG. 2, it was demonstrated that the oil droplets of olive oil and hexadecane dispersed in the aqueous phase to which the water-soluble polymer had been added were independently and stably maintained.

Furthermore, the present inventor evaluated how the mixing temperature in the second step of the production method according to the present invention has an influence on the preparation of the oil-in-water multi-phase emulsion.

Experiment 3. Effect of Mixing Temperature on Oil Dispersion (Method) The components shown in Formulas E and F below were mixed at a temperature of 60 ° C.
Two kinds of oil-in-water emulsions were prepared by emulsification by a phase inversion method. Next, this was mixed and stirred under temperature conditions of 45 ° C, 50 ° C, 70 ° C and 90 ° C to prepare an oil-in-water multi-phase emulsion. Evaluation of the degree of dispersion, using a differential calorimeter, based on the melting peak area of hexadecane in the oil-in-water multiphase emulsion immediately after mixing and prepared at 45 ° C., immediately after prepared under each temperature conditions Ratio of melting peak area of hexadecane in other oil-in-water type multi-phase emulsion (dispersion retention)
I asked. The results are shown in Table 1.

As shown in the results of Table 1, the relationship that the increase in the mixing temperature in the second step lowers the degree of dispersion of the oil became apparent.

(Examples and Effects of the Invention) Examples of the present invention will be described below. In addition, the mixing ratio is weight%
It is.

Example 1. [First step] (A) was heated to 60 ° C., (b) was added thereto with stirring, and (c) was further added thereto, followed by emulsification, followed by cooling to obtain an emulsion G.

(D) was heated to 60 ° C., added with (e) and emulsified, and then cooled to obtain an emulsion H.

(Second step)

Emulsion G and Emulsion H were mixed and stirred at 45 ° C., and cooled to 25 ° C. to obtain an oil-in-water multi-phase emulsion.

Example 2 An oil-in-water multi-phase emulsion was obtained in the same manner as in Example 1 except that xanthan gum was used instead of sodium hymaluronate in Formulation H of Example 1.

Example 3. [First step] (A) is heated to 60 ° C., and (b) is added thereto with stirring, and then (c) is added thereto.
I got

(D) was heated to 60 ° C., and (e) was added thereto while stirring, followed by cooling to obtain an emulsion J.

(Second step)

Emulsion I and Emulsion J were mixed and stirred at 45 ° C and cooled to 25 ° C to obtain an oil-in-water multi-phase emulsion.

Example 4. [First step] (A) was heated to 80 ° C., and (b) was added thereto and dissolved while stirring, and then (c) was further added and cooled to obtain an emulsion K.

(D) is heated to 60 ° C., and (e) is added while stirring,
Further, (f) was added, and finally (g) was added, followed by cooling to obtain an emulsion L.

[Second step] The emulsion K and the emulsion L were mixed and stirred at 45 ° C, and cooled to 25 ° C to obtain an oil-in-water multiphase emulsion.

Example 5. [First step] (A) was heated to 60 ° C., and (b) was added thereto, followed by cooling to obtain an emulsion M.

(C) is heated to 60 ° C., and (d) is added while stirring,
Further, (e) was added, and finally (f) was added, followed by cooling to obtain an emulsion N.

(Second step)

Emulsion M, Emulsion N and Emulsion G obtained in Example 1 were mixed and stirred at 45 ° C., and cooled to 25 ° C. to obtain an oil-in-water multi-phase emulsion.

In order to evaluate the oil-in-water multi-phase emulsion according to the present invention obtained as described above, the degree of dispersion was measured using the oil-in-water multi-phase emulsion obtained in Examples 1 and 2. As a comparative product, a product obtained by removing sodium hyaluronate as a water-soluble polymer from Example 1 (replacement with purified water) was used. The measurement was performed in the same manner as in Experiment 1. FIG. 3 shows the results.

As shown in the results in FIG. 3, it was proved that the oil-in-water type multi-phase emulsion according to the present invention maintained a high degree of dispersion of each oil component in the emulsion even after aging.

[Brief description of the drawings]

FIG. 1 shows the relationship between the number of days over time and the degree of dispersion of the oil when the concentration of the surfactant was changed.
Is 6 wt%, (B) is 3 wt%, and (C) is 1 wt%. FIG. 2 shows the relationship between the aging days and the degree of dispersion of the oil component when using the water-soluble polymer. FIG. 3 shows the relationship between the number of days elapsed and the degree of dispersion of the oil, wherein (D) is Example 1, (E) is Example 2,
(F) is a comparative product.

 ──────────────────────────────────────────────────続 き Continuation of the front page (72) Inventor Hiroyuki Suzuki 27-1 Takashimadai, Kanagawa-ku, Yokohama-shi, Kanagawa Prefecture Inside the Yokohama Research Laboratory, Polar Chemical Industry Co., Ltd. (56) References JP-A-63-150221 (JP, A)

Claims (2)

(57) [Claims] 1. An oil-in-water multiphase emulsion in which two or more kinds of oils are independently present in an aqueous continuous phase as an emulsion (excluding a microemulsion having a particle size of 0.5 μm or less). The surfactant is contained in the oil type multi-phase emulsion so as to be 4% by weight or less, and the water continuous phase of the oil-in-water type multi-phase emulsion contains 0.05 to 10% by weight of a natural water-soluble polymer. An oil-in-water multiphase emulsion characterized by the following. 2. In a first step, a plurality of oil-in-water emulsions (excluding microemulsions having a particle size of 0.5 μm or less) obtained by dispersing and emulsifying different kinds of oils are prepared, and then a second step is carried out. The method comprises mixing a plurality of oil-in-water emulsions obtained in the above steps to form an oil-in-water multi-phase emulsion, wherein the oil-in-water multi-phase emulsion contains 4% by weight or less of a surfactant. And wherein the natural water-soluble polymer is adjusted to be contained in the water continuous phase of the oil-in-water type multi-phase emulsion in the range of 0.05 to 10% by weight, A method for producing the oil-in-water type multiple emulsion according to claim 1.