KR101247803B1 - Solubilizing composition of insoluble material and solubilizing method of the insoluble material using thereof - Google Patents

Abstract

PURPOSE: A solution solubilization composition of an insoluble substance and a method for solublizing the insoluble substance are provided to solubilize the insoluble substance and to improve solubilization efficiency. CONSTITUTION: A solution solubilization composition of an insoluble substance contains mannosylerythritol lipid, a surfactant, and polyol. A method for solubilizing the insoluble substance using the composition comprises: a step of sequentially mixing mannosylerythritol lipid, an insoluble substance, a surfactant, and polyol and preparing a mixture; a step of heating and stirring the mixture. The particle size of micelle of the insoluble substance is 50 nm or less.

Description

Solubilizing composition of insoluble material and solubilizing method of the insoluble material using YOO}

The present invention relates to a solubilizing composition of an aqueous solution of a poorly soluble substance and a method of solubilizing an aqueous solution of a poorly soluble substance using the same. An aqueous solution solubilization composition and a method for solubilizing an aqueous solution of a poorly soluble substance using the same.

In the cosmetic and pharmaceutical industries, methods for solubilizing poorly soluble substances in water have been developed by many researchers. Since the solubilization technology has a great impact on the industry, it is expected that the development of solubilization technology of the poorly soluble substance will be further accelerated in the future.

Hydrophobic poorly soluble materials are characterized by a molecular arrangement that is difficult to solubilize in water due to strong hydrophobic interaction between molecules when there are no or very few hydrophilic groups, or when they are in a position that interferes with molecular arrangement. If the hydrophobic substance can be modified in the molecular arrangement, the poorly soluble substance can be dispersed or solubilized, and the substance that can induce the change in the molecular arrangement is a surfactant.

Surfactants that are usefully used in the cosmetics and pharmaceutical industries are very diverse, and in the past, technologies for nanoparticles were developed under physical conditions by using ultra-high pressure emulsions (Ultrahomogenizer) using synthetic and natural surfactants. Limiting the solubilization of the material and its stability has led to the development of new natural materials and the development of new solubilization systems.

Meanwhile, ceramide is known as a poorly soluble substance well known in the cosmetic industry. Ceramide is a representative skin construct that enhances the barrier function of the skin, and the human skin has various ceramides. Ceramide has a relatively small hydrophilic group and thus shows strong hydrophobic interaction in the skin. Due to this structural feature, ceramide prevents water loss from the human body and prevents influx of harmful ingredients from the skin, thereby exhibiting unique skin barrier function. Therefore, when ceramide is applied to cosmetics, the moisturizing power is increased and the skin protection power is greatly increased, which greatly contributes to the quality improvement of the cosmetics.

However, currently commercially available ceramides have a fatal drawback in that coagulation occurs in cosmetic formulations due to high hydrophobic interactions between molecular chains and eventually separates and precipitates as needle crystals.

In addition, Lutein, Resveratrol, Phylloquinone, Ubiquinone, Oleanolic acid, Bis-ethylhexyloxyphenol methoxyphenyl triazine, Asis Solubilization of hydrophobic, poorly soluble substances such as astaxanthin, rutin, hesperidin and chloramphenicol is a very important technical task in the cosmetic and pharmaceutical industries. New technology development is urgently needed because it is very important factor in maximizing the efficacy and improving the product power.

Many researchers have tried to solve this problem by using self-association and solubilization techniques, but at the present technology level, it can be used at very limited concentration.

As a material used in such a solubilization system, phospholipids (phoshatidylcholine, lecithin), which are natural surfactants, have been used to date, but phospholipids have limitations as solubilization materials due to structural irregularities and specificity of hydrophobic groups. There is a limit that particles cannot be formed at the micro or nano level only by strong pressure.

Therefore, it is necessary to develop a solubilization system capable of solubilizing and stabilizing high hydrophobic poorly soluble materials, and furthermore, there is an urgent demand for the development of new materials capable of realizing nanoparticles without physical pressure.

An object of the present invention has been made to solve the above problems, an object of the present invention is to provide an aqueous solution solubilizing composition of poorly soluble materials and a method of soluble solution of poorly soluble materials using the same.

The aqueous solution solubilizing composition of the poorly water-soluble substance of the present invention for achieving the above object is characterized by comprising (a) mannosylerythritol lipid, (b) surfactant and (c) polyol.

In addition, the aqueous solution soluble method of the poorly soluble substance of the present invention for achieving the above object is (i) preparing a mixture by sequentially mixing mannosyl erythritol lipid, poorly soluble substance, surfactant and polyol and (ii) It characterized in that it comprises the step of stirring the temperature of the mixture.

According to the present invention, it is known to have an excellent effect, but there is an effect that it is possible to solubilize a material having a difficulty in applying a large amount as a poorly soluble material.

In addition, according to the present invention, by improving the solubilization efficiency of various poorly soluble materials that are limited in solubilization, there is an effect that can maximize the effect of the material to which it is applied.

Figure 1 shows the turbidity evaluation value of the ceramide mixed composition solubilized lotion of Examples 1 to 5 prepared in Example 6.
Figure 2 shows the evaluation of the transmittance of the ceramide mixed composition solubilized lotion of Examples 1 to 5 prepared in Example 6.
Figure 3 shows the turbidity evaluation value for the solubilization of the ceramide mixed composition of Example 7 prepared by Example 8.
Figure 4 shows the transmittance evaluation value for the solubilization of the ceramide mixed composition of Example 7 prepared by Example 8.
FIG. 5 shows the results of differential scanning calorimetry differential scanning calorimetry (DSC) evaluation of the mixed composition of Example 7-5 best evaluated in Experiment 2 according to Experimental Example 3. FIG.
Figure 6 shows the turbidity evaluation value of the lotion solubilizing the ceramide mixed composition prepared in Example 9 by Experimental Example 6.
Figure 7 shows the evaluation of the transmittance of the lotion solubilizing the ceramide mixed composition prepared in Example 9 by Experimental Example 6.
Figure 8 shows the turbidity evaluation value of the solubilizer containing the excessively soluble substance finally added to the mixed composition prepared in Example 10.
Figure 9 shows the evaluation of the transmittance of the solubilizing agent containing the excessively soluble substance finally added to the mixed composition prepared in Example 10.

BRIEF DESCRIPTION OF THE DRAWINGS The advantages and features of the present invention, and the manner of achieving them, will be apparent from and elucidated with reference to the embodiments described hereinafter in conjunction with the accompanying drawings. It should be understood, however, that the invention is not limited to the disclosed embodiments, but is capable of many different forms and should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, To fully disclose the scope of the invention to those skilled in the art, and the invention is only defined by the scope of the claims. Like reference numerals refer to like elements throughout.

Hereinafter, an aqueous solution solubilization composition of a poorly soluble substance and a method for soluble solution of a poorly soluble substance using the same will be described in detail.

Aqueous solution solubilization composition of poorly soluble substance

The aqueous solution solubilizing composition of the poorly soluble substance of the present invention is characterized by comprising (a) mannosylerythritol lipid, (b) surfactant and (c) polyol.

Here, the composition is preferably (a) 100 parts by weight of mannosyl erythritol lipid (b) 10 parts by weight to 4500 parts by weight of the surfactant, and (c) 10 parts by weight to 3000 parts by weight of the polyol.

When the composition satisfies the conditions of the above range, it is possible to maximize the activity of the poorly soluble material solubilized by the aqueous solution solubilization composition, it is possible to ensure stability.

If the amount of the surfactant in the composition is less than 10 parts by weight relative to 100 parts by weight of mannosyl erythritol lipid, mannosyl erythritol lipid does not assist in the main action of solubilizing poorly soluble material, so that the size of the particles increases, solubility of the solubility Problem may occur, and if it exceeds 4500 parts by weight, there is a problem that recrystallization may be formed by reducing the solubilization action of mannosylerythrolipid to poorly soluble materials.

In addition, if the content of the polyol in the composition is less than 10 parts by weight relative to 100 parts by weight of mannosyl erythritol lipid, there is a problem that can inhibit the stability of the nanoparticles in the water phase, if more than 3000 parts by weight in poorly soluble material There is a problem that recrystallization can be formed by reducing the solubilization action of mannoserythrolilipide against.

Here, (a) mannosyl erythritol lipid may be represented by the following formula (1).

[Formula 1]

In Formula 1, R ₁ and R ₂ are the same as or different from each other, and are saturated or unsaturated fatty acids having a C ₆ , C ₁₂ or C ₁₄ chain, and R ₃ is an acetyl group.

The (a) mannosyl erythritol lipid is a kind of surfactant produced from the strain Candida sp. SY16 (KCTC 8950P), and is a glycolipid-based surfactant in which fatty acid is bound to mannose erythritol.

In the present invention, mannosylerythritol lipid serves to solubilize the poorly soluble material by mixing with the poorly soluble material to induce rearrangement of the poorly soluble material.

Next, (b) the surfactant is added separately from (a) mannosyl erythritol lipid, and is a material that helps to solubilize mannosyl erythritol lipid, preferably polyoxyethylene hydrogenated castor oil, cetearese , Cetes, glycerin, laureth, oles, polysorbates, steares, amino acid-fatty acid esters, polyoxyethylene stearate may be one or more selected from, but is not limited thereto.

In addition, (c) the polyol is a material that helps to solubilize the (a) mannosyl erythritol lipid as (b) the surfactant, preferably butylene glycol, dipropylene glycol, propylene glycol , Caprylyl glycol, decylene glycol, dipropylene glycol, ethylene glycol, hexylene glycol, polyethylene glycol, glycerin, diglycerin, ethylhexylglycerine, polyglycerine, 1,6- It may be one or more selected from hexanediol, 1,2-hexanediol, 1,2-octanediol, but is not limited thereto.

The poorly soluble substance to which the aqueous solution solubilizing composition of the poorly soluble substance of the present invention can be applied is lutein, resveratrol, phylloquinone, ubiquinone, oleanolic acid, bis-ethylhexyloxyphenol methoxyphenyl triazine, astaxanthin, rutin, At least one selected from hesperidin and chloramphenicol, it may be a poorly water-soluble substance used in cosmetic compositions or pharmaceutical compositions.

Soluble solution of poorly soluble substance

On the other hand, the aqueous solution solubility method of the poorly soluble material of the present invention comprises the steps of (i) mannosyl erythritol lipid, a poorly soluble material, a surfactant and a polyol in order to prepare a mixture, and (ii) the mixture is heated and stirred Characterized in that it comprises a step.

Mannosyl erythritol lipid, a surfactant, a polyol, and the kind of the poorly soluble substance to which it is applied, the specific mixing ratio, etc. which are used for the aqueous solution soluble method of the poorly soluble substance of this invention are as above-mentioned.

Therefore, the contents overlapping with those described above will be omitted or briefly referred to.

According to the solubility method of this invention, (i) mannosyl erythritol lipid, a poorly water-soluble substance, surfactant, and a polyol are mixed sequentially, and the mixture is manufactured.

Mannosyl erythritol lipid, a poorly soluble substance and a co-additive of the above-described composition ratio are sequentially mixed with a surfactant and a polyol. In this case, mannose erythritol lipid, a hydrophobic poorly soluble substance and an auxiliary additive are sequentially added. It is important to prepare the mixture. In addition, the preparation of the mixture in consideration of the composition ratio of each component is very important for the preparation of a solubility containing a transparent and high concentration of poorly soluble material.

Next, (ii) the mixture is heated and stirred. It is preferable that the temperature at the said temperature rising is 40-80 degreeC. If the temperature or less than 40 ℃, the mixing of each raw material is irregular, so that the problem of lowering solubilization capacity may occur, if the temperature exceeds 80 ℃ there is a problem of discoloration and odor.

According to the solubility method of the present invention described above, solubilizers having a high transparency and containing a high concentration of poorly soluble substances can be prepared.

Example

Hereinafter, the present invention will be described in more detail with reference to Examples. However, the scope of the present invention is not limited by this embodiment.

Example  1-5

According to the composition shown in Table 1-5, ceramide and mannosyl erythritol lipid were first mixed, and it heated up at 80 degreeC. After temperature dissolution, the compositions according to Tables 1 to 5 were sequentially added, stirred and cooled to 80 ° C. to prepare a mixed composition containing a poorly soluble material.

Composition table for Example 1 Ingredient (g) 1-1 1-2 1-3 1-4 1-5 1-6 1-7 Ceramide 20 20 20 20 20 20 20 Mannosil erythritol lipid 30 30 30 30 30 30 30 Fiji-60 Hydrogenated Castor Oil - - - - - - - Fiji-40 Hydrogenated Castor Oil - - - - - - - Polysorbate 20 20 20 20 20 20 20 20 Polysorbate 60 - - - - - - - Butylene Glycol 30 - - 20 5 5 10 Dipropylene glycol - 30 - 5 20 5 10 Propylene glycol - - 30 5 5 20 10

Composition table for Example 2 Ingredient (g) 2-1 2-2 2-3 2-4 2-5 2-6 2-7 Ceramide 20 20 20 20 20 20 20 Mannosil erythritol lipid 30 30 30 30 30 30 30 Fiji-60 Hydrogenated Castor Oil - - - - - - - Fiji-40 Hydrogenated Castor Oil - - - - - - - Polysorbate 20 - - - - - - - Polysorbate 60 20 20 20 20 20 20 20 Butylene Glycol 30 - - 20 5 5 10 Dipropylene glycol - 30 - 5 20 5 10 Propylene glycol - - 30 5 5 20 10

Composition table for Example 3 Ingredient (g) 3-1 3-2 3-3 3-4 3-5 3-6 3-7 Ceramide 20 20 20 20 20 20 20 Mannosil erythritol lipid 30 30 30 30 30 30 30 Fiji-60 Hydrogenated Castor Oil 20 20 20 20 20 20 20 Fiji-40 Hydrogenated Castor Oil - - - - - - - Polysorbate 20 - - - - - - - Polysorbate 60 - - - - - - - Butylene Glycol 30 - - 20 5 5 10 Dipropylene glycol - 30 - 5 20 5 10 Propylene glycol - - 30 5 5 20 10

Composition Table for Example 4 Ingredient (g) 4-1 4-2 4-3 4-4 4-5 4-6 4-7 Ceramide 3 20 20 20 20 20 20 20 Mannosil erythritol lipid 30 30 30 30 30 30 30 Fiji-60 Hydrogenated Castor Oil - - - - - - - Fiji-40 Hydrogenated Castor Oil 20 20 20 20 20 20 20 Polysorbate 20 - - - - - - - Polysorbate 60 - - - - - - - Butylene Glycol 30 - - 20 5 5 10 Dipropylene glycol - 30 - 5 20 5 10 Propylene glycol - - 30 5 5 20 10

Composition table for Example 5 Ingredient (g) 5-1 5-2 5-3 5-4 5-5 5-6 5-7 Ceramide 3 20 20 20 20 20 20 20 Mannosil erythritol lipid 30 30 30 30 30 30 30 Fiji-60 Hydrogenated Castor Oil 5 5 5 5 5 5 5 Fiji-40 Hydrogenated Castor Oil 5 5 5 5 5 5 5 Polysorbate 20 5 5 5 5 5 5 5 Polysorbate 60 5 5 5 5 5 5 5 Butylene Glycol 30 - - 20 5 5 10 Dipropylene glycol - 30 - 5 20 5 10 Propylene glycol - - 30 5 5 20 10

Example 6

In Example 6, as in the composition shown in Table 6 below, the mixed composition containing the excess ceramide prepared in Examples 1 to 5 was added to purified water to prepare a solubilized ceramide solubilized finally.

5 wt% of the mixed composition prepared in Examples 1 to 5 was heated to 80 ° C., the purified water heated to 80 ° C. was stirred, and the heated ceramide mixed composition was slowly added to solubilization. By applying 5% by weight of the ceramide mixed composition containing 20% by weight of ceramide, the ceramide content of the final solubilized product was 1.0% by weight.

Composition table for Example 6 ingredient Weight percentage (%) Ceramide Mixture 5 Purified water 95

Experimental Example 1

Experimental Example 1 evaluated the transparency of the ceramide mixed composition solubilized lotion of Examples 1 to 5 prepared in Example 6, the evaluation method is as follows.

(1) Turbidity Assessment Method

The turbidity of the solubilized lotion was measured at 620 nm using a spectrophotometer. High turbidity liquids are cloudy and low turbidity liquids are highly transparent. Turbidity range was measured within (Opical Density) 0.01 ~ 1.0.

(2) Permeability Evaluation Method

The amount of light passing through the solubilized liquid was measured. The light transmittance (T,%) for the liquid was calculated by substituting the equation -log t = A (absorbance, O.D).

The transmittance of light is always less than 1, calculated as T (%) = tx100, and the percent transmittance (T%) ranges from 1 to 100%. The higher the transmittance, the higher the transparency, and the purified water was calculated as 100%. For example, if the light transmittance is 40%, then 60% of the light has not passed through the sample.

(3) Evaluation result

The turbidity evaluation value of the ceramide mixed composition solubilizing lotion of Examples 1 to 5 prepared in Example 6 is shown in FIG. 1, and the transmittance evaluation value is shown in FIG. 2.

Solubility of the Mixed Compositions Prepared in Examples 1, 2, 3, 4, and 5 As in Example 1 In the transparency evaluation of Example 6, the solubilities of the mixed compositions of Example 4-4 were evaluated to have the highest transparency. It became.

Example 7

Example 7 was carried out to investigate the change in transparency according to the change in the content of mannosyl erythritol lipid, and a mixed composition was prepared in the same manner as in Example 1 as shown in Table 7 below.

Ingredient (g) 7-1 7-2 7-3 7-4 7-5 7-6 Ceramide 20 20 20 20 20 20 Mannosil erythritol lipid 5 10 15 20 25 30 Fiji-40 Hydrogenated Castor Oil 45 40 35 30 25 20 Butylene Glycol 20 20 20 20 20 20 Dipropylene glycol 5 5 5 5 5 5 Propylene glycol 5 5 5 5 5 5

Example 8

Example 8 is to prepare a finally solubilized ceramide solubilizing compound by adding a mixed composition prepared according to the change in the content of the mannosyl erythritol lipid in Example 7 in purified water.

The process for preparing a solubilized product containing ceramide is the same as in Example 6.

Experimental Example 2

In Experimental Example 2, the transparency of the solvate of the ceramide mixed composition of Example 7 prepared by Example 8 was evaluated, and the evaluation method is the same as Experimental Example 1.

The turbidity evaluation value for the solubilized product of the ceramide mixed composition of Example 7 prepared by Example 8 is shown in FIG. 3, and the transmittance evaluation value is shown in FIG. 4.

In the evaluation of the solubility of the ceramide mixed composition of Example 7 prepared as in Example 8, as in the result of Experimental Example 2, the solubility of the mixed composition of Example 7-5 was evaluated as having the highest transparency.

Experimental Example 3

In Experimental Example 3, differential scanning calorimetry differential scanning calorimetry (DSC) evaluation of the mixed composition of Example 7-5, which was best evaluated in Experimental Example 2, was shown in FIG.

DSC is a method of measuring the heat ingress of a sample by heating / cooling the sample material. Mannosylerythritol lipid mixed with ceramide changes the melting point of ceramide to 36.2 ° C. as shown in FIG. 5 and the change of the melting point of ceramide suggests that the present invention facilitates solubilization of poorly soluble materials. do.

Experimental Example 4

Particle size analysis was performed for the solubilized compound of Example 7-5 prepared in Example 8.

In the emulsification and solubilization system, the difference in transparency according to the particle size is related to the limit wavelength of visible light. When the size of micelles generated by emulsification and solubilization is larger than the limit wavelength of visible light, light is scattered and milky. It will be transparent.

In general, micelles of 780 ~ 380nm or more, which are the wavelengths of visible light, show milky white color by scattering visible light.However, when the size of the particles decreases, the degree of scattering visible light varies depending on the size of the particles. do. The state change of the appearance caused by the difference in the degree of scattering visible light according to the particle size is shown in Table 8.

Visual discrimination Particle size milk white 1μ (1000nm) or more Blue white 0.1 (100 nm) to 1 μ (1000 nm) Translucent 0.05 (50 nm) to 0.1 μ (100 nm) Transparency 0.05μ (50nm) or less

The average particle size of the solubilizer of the mixed composition of Example 7-5 evaluated by a particle size analyzer of OTSUKA ELECTRONICS was evaluated at a value of 13.4 nanometers (nm). These results indicate that the solubilized ceramide micelle particles have a value below the threshold wavelength of visible light and are in a transparent state when visually judged.

Experimental Example 5

Zeta-Potentiial measurement was carried out for the solubilized compound of Example 7-5 prepared in Example 8. The particles dispersed in the solution are electrically charged negatively or positively by dissociation of the surface polar group and adsorption of ions. Therefore, an electric double layer is formed around the particles because the ions having an excessively opposite sign and the ions having a small amount of the same charge are diffusely distributed around the particles. Such an electric double layer is divided into two parts by a stern plane which exists almost at the interface with the radius of the hydride ion. The inner region is defined as a stern layer and the outer region is defined as a diffusion layer based on the stern plane. On the other hand, the outer layer occupies most of the existing solution in which the cations and anions are respectively balanced.

In general, the zeta potential represents the potential at a slip plane near the interface between the pinned and diffused layers. However, since it is difficult to directly measure the surface potential of particles, information on surface potential is generally discussed in terms of zeta potential values obtained by electrophoretic experiments.

When all the dispersed particles have a large negative or positive charge zeta potential, they tend to repel each other and they do not try to combine with each other. The criterion for dividing the stable or unstable state of experimentally obtained zeta potential is + 30mv or -30mv. As the absolute value increases, the repulsive force between the particles increases, which increases the stability of the particles, while when the zeta potential approaches zero, the particles tend to aggregate. Thus, the zeta potential can be used as a measure of dispersion stability of colloidal particles.

The zeta potential of the solubilized product of the mixed composition of Example 7-5 evaluated by a zeta-potential analyzer manufactured by OTSUKA ELECTRONICS was evaluated at a value of -37.42 (mv). These results indicate that the particles are not aggregated due to the repulsive force between the solubilized ceramide particles and the stability between the particles is high.

Example 9

In Example 9 was prepared a ceramide soluble compound prepared from the ceramide mixed composition of Example 7-5 evaluated in Experimental Example 2, the ceramide mixed composition 0.05 ~ 50% by weight as shown in Table 9 finally the ceramide 0.01 Soluble was prepared containing ~ 10% by weight.

Ingredient (g) 9-1 9-2 9-3 9-4 9-5 9-6 9-7 9-8 9-9 9-10 9-
11 9-
12 9-
13 Ceramide Mixture (20 wt% Ceramide) 0.05 0.1 One 5 10 15 20 25 30 35 40 45 50 Purified water 99.95 99.9 99 95 90 85 80 75 70 65 60 55 50 Total Ceramide Weight% 0.01 0.02 0.2 One 2 3 4 5 6 7 8 9 10

Experimental Example 6

In Experimental Example 6 was evaluated the transparency of the lotion solubilized ceramide mixed composition prepared in Example 9, the evaluation method is the same as Experimental Example 1.

In Experimental Example 6, the turbidity evaluation value of the lotion obtained by solubilizing the ceramide mixed composition prepared in Example 9 is shown in FIG. 6, and the transmittance evaluation value is shown in FIG. 7.

As a result of Experiment 6, the ceramide solubilizer added with 0.05 to 50% by weight of the ceramide mixed composition was evaluated to be more than 99% transparent.

Example 10

With the composition of Table 10, a mixed composition of poorly soluble materials showing an effective effect was prepared. The manufacturing method is the same as in Example 1.

Ingredient (g) 10-1 10-2 10-3 10-4 10-5 10-6 10-7 10-8 10-9 10-10 10-
11 Ceramide 20 Lutein 20 Resveratrol 20 Phylloquinone 20 Ubiquinone 20 Oleanolic acid 20 Bis-ethylhexyloxyphenol methoxyphenyltriazine 20 Astaxanthin 20 Routine 20 Hesperidin 20 Chloramphenicol 20 Mannosil erythritol lipid 25 25 25 25 25 25 25 25 25 25 25 Fiji-40 Hydrogenated Castor Oil 25 25 25 25 25 25 25 25 25 25 25 Butylene Glycol 20 20 20 20 20 20 20 20 20 20 20 Dipropylene glycol 5 5 5 5 5 5 5 5 5 5 5 Propylene glycol 5 5 5 5 5 5 5 5 5 5 5

Experimental Example 7

In Experimental Example 7, the mixed composition prepared in Example 10 was added to purified water to finally prepare a solubility including an excessive amount of poorly soluble material and evaluate transparency. The procedure for preparing a solubility was the same as in Example 6.

The turbidity evaluation value of the solubilizer containing the excessively soluble substance was finally shown in FIG. 8 and the transmittance evaluation value of FIG. 9 was finally added to the mixed composition prepared in Example 10.

According to the present invention as shown in Figures 8 and 9, not only ceramide, but also lutein (Rutein), resveratrol, Phyloquinone, Ubiquinone, Oleanolic acid, bis-ethyl Existing hydrophobic poorly water-soluble materials including hexyloxyphenol methoxyphenyl triazine, astaxanthin, rutin, hesperidin, chlororamphenicol, etc. It was found that it is possible to produce a solubilizer superior to the composition and its preparation method.

Although the present invention has been described in detail through specific examples, it is intended to describe the present invention in detail, and the aqueous solution solubilizing composition of the poorly soluble material and the solubilizing method thereof are not limited thereto. It will be apparent that modifications and improvements are possible by those skilled in the art within the technical idea. All modifications and variations of the present invention fall within the scope of the present invention, and the specific scope of protection of the present invention will be apparent from the following claims.

Claims (13)

(a) mannosylerythritol lipids;
(b) surfactants; And
(c) polyols;
As an aqueous solution solubilization composition of a poorly soluble substance comprising:
The micelle particle size of the poorly soluble substance to be present in the aqueous solution solubilizing composition is 50nm or less, the absolute value of the zeta potential is 30mv or more, aqueous solution solubilizing composition of poorly soluble material.
The method of claim 1,
The composition of (a) 100 parts by weight of the mannosyl erythritol lipid (b) 10 to 4500 parts by weight of the surfactant, (c) a poorly water-soluble material comprising 10 to 3000 parts by weight of the polyol Aqueous solution solubilization composition.
The method of claim 1,
The (a) mannosyl erythritol lipid is an aqueous solution solubilization composition of a poorly soluble material, characterized in that represented by the following formula (1).

[Formula 1]

In Formula 1, R ₁ and R ₂ are the same as or different from each other, and are saturated or unsaturated fatty acids having a C ₆ , C ₁₂ or C ₁₄ chain, and R ₃ is an acetyl group.
The method of claim 1,
The (b) surfactant is selected from polyoxyethylene cured castor oil, ceteares, cethes, glycerin, laureth, oles, polysorbates, steares, amino acid-fatty acid esters, polyoxyethylene stearate An aqueous solution solubilization composition of a poorly water-soluble substance, characterized in that at least one.
The method of claim 1,
The polyol (c) is butylene glycol, dipropylene glycol, propylene glycol, butylene glycol, dipropylene glycol, propylene glycol, caprylyl glycol, decylene glycol, di Propylene glycol, ethylene glycol, hexylene glycol, polyethylene glycol, glycerin, diglycerin, ethylhexylglycerine, polyglycerol, 1,6-hexanediol, 1,2-hexanediol, 1,2 -An aqueous solution solubilization composition of a poorly soluble substance, characterized in that at least one selected from octanediol.
The method of claim 1,
The poorly water-soluble substance is at least one selected from lutein, resveratrol, phylloquinone, ubiquinone, oleanolic acid, bis-ethylhexyloxyphenol methoxyphenyltriazine, astaxanthin, rutin, hesperidin, chloramphenicol, cosmetic composition or medicament An aqueous solution solubilization composition of a poorly soluble substance, characterized in that it is a poorly soluble substance used in the composition for the.
(Iii) sequentially mixing mannosylerythritol lipids, sparingly soluble materials, surfactants and polyols to prepare a mixture; And
(Ii) warming and stirring the mixture;
As an aqueous solution soluble method of poorly soluble substance comprising a,
The micelle particle size of the poorly soluble material present in the aqueous solution is 50nm or less, characterized in that the absolute value of the zeta potential is 30mv or more, aqueous solution soluble method of poorly soluble material.
8. The method of claim 7,
The mixture is 100 parts by weight of mannosyl erythritol lipid, 2 parts by weight to 4000 parts by weight of the poorly soluble material, 10 parts by weight to 4500 parts by weight of the polyol, characterized in that it comprises 10 parts by weight to 3000 parts by weight of polyol A solubility method of an aqueous solution of poorly soluble substance.
8. The method of claim 7,
(A) Mannosyl erythritol lipid soluble method of the aqueous solution of poorly soluble material, characterized in that represented by the following formula (1).
[Formula 1]

In Formula 1, R ₁ and R ₂ are the same as or different from each other, and are saturated or unsaturated fatty acids having a C ₆ , C ₁₂ or C ₁₄ chain, and R ₃ is an acetyl group.
8. The method of claim 7,
The (b) surfactant is selected from polyoxyethylene cured castor oil, ceteares, cethes, glycerin, laureth, oles, polysorbates, steares, amino acid-fatty acid esters, polyoxyethylene stearate Method for soluble in aqueous solution of poorly soluble substances, characterized in that at least one.
8. The method of claim 7,
The polyol (c) is butylene glycol, dipropylene glycol, propylene glycol, butylene glycol, dipropylene glycol, propylene glycol, caprylyl glycol, decylene glycol, di Propylene glycol, ethylene glycol, hexylene glycol, polyethylene glycol, glycerin, diglycerin, ethylhexylglycerine, polyglycerol, 1,6-hexanediol, 1,2-hexanediol, 1,2 -An aqueous solution soluble method of poorly soluble substance, characterized in that at least one selected from octanediol.
8. The method of claim 7,
The poorly water-soluble substance is at least one selected from lutein, resveratrol, phylloquinone, ubiquinone, oleanolic acid, bis-ethylhexyloxyphenol methoxyphenyltriazine, astaxanthin, rutin, hesperidin, chloramphenicol, cosmetic composition or medicament An aqueous solution soluble method of a poorly soluble substance, characterized in that it is a poorly soluble substance used in the composition.
8. The method of claim 7,
The temperature at the time of the temperature increase is 40 ~ 80 ℃ aqueous solution soluble method characterized in that the.

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