KR20200007056A - A surfactant-free type oil-water dispersion composition, surfactant-free type water-oil dispersion composition and the manufacturing method thereof - Google Patents

Abstract

The present invention relates to: a non-surfactant oil-in-water (O/W) dispersion composition comprising a non-polar solvent droplet in a polar solvent, wherein the dispersion composition has a transparency of 90 to 100%; a non-surfactant water-in-oil (W/O) dispersion composition comprising a polar solvent droplet in a non-polar solvent, wherein the dispersion composition has a transparency of 90 to 100%; and manufacturing methods thereof. In the dispersion composition of the present invention, phase separation does not occur even when the use environment is changed.

Description

Non-surfactant oil-water (O / W) dispersion composition, non-surfactant water-oil (W / O) dispersion composition and preparation method thereof {A SURFACTANT-FREE TYPE OIL-WATER DISPERSION COMPOSITION, SURFACTANT-FREE TYPE WATER-OIL DISPERSION COMPOSITION AND THE MANUFACTURING METHOD THEREOF}

The present invention relates to a non-surfactant type oil-water (O / W) dispersion composition, a non-surfactant type water-oil (W / O) dispersion composition, and a method for preparing the same. Is a non-surfactant oil-water (O / W) dispersion composition, a non-surfactant type water-oil (W / O) dispersion composition having excellent dispersion stability and no surfactant. It relates to a manufacturing method.

Common droplets are held together by physical and chemical attraction such as van der Waals forces and surface tension. In order to crush and disperse the droplets present in the solution, there must be a force greater than the above-mentioned attraction force, and a conventional dispersion method such as a ball mill method has a problem in that impurities are included in the dispersion process. Therefore, various methods have been tried to prevent the aggregation of such droplets.

One method is the use of surfactants. In particular, in the case of oil-in-water (O / W) dispersions in which oil is dispersed in water or water-in-water (W / O) dispersions in which water is dispersed in oil, in order to stabilize the dispersion state of the dispersion, additional surfactants necessary for emulsification are added. Sufficient stability can be maintained.

However, the use of a surfactant has the advantage that it can be stabilized through uniform dispersion, but depending on the use of the surfactant, in terms of usability, such as poor stickiness and unpleasant feeling of use, such as stickiness or a large amount of oily residue remaining, In addition to the serious disadvantages, there was a problem that the user causes the rash by the use of a surfactant.

Not only this, in the case of the conventional dispersion, the ultrasonic wave is applied, or the long-term use at high or low temperatures, the degree of dispersion falls, there was a problem that a phase separation phenomenon between water and oil occurs.

Therefore, there is a need for a study on a dispersion liquid in which water and oil can be stably dispersed without using a surfactant and in which phase separation does not occur due to changes in the environment.

Republic of Korea Patent Publication No. 10-2011-0053775 (2011.05.24), nano-powder dispersion device using the focused ultrasound and dispersion method using the same

The present inventors have completed the present invention by confirming that when the droplets of very small size are prepared, excellent dispersibility can be ensured even without using a surfactant.

Accordingly, an object of the present invention is to use a non-surfactant oil-water having good usability, such as spreadability and spreadability without using a surfactant, without causing phase separation even with changes in the use environment, and having an excellent transdermal delivery effect. O / W) dispersion composition or non-surfactant type water-oil (W / O) dispersion composition.

Another object of the present invention to provide a cosmetic composition or a pharmaceutical composition comprising the composition.

In order to achieve the above object, the present invention is a dispersion composition comprising a non-polar solvent droplet in a polar solvent, non-surfactant oil-water (O) having a transparency of 90 to 100% of the dispersion composition. / W) to provide a dispersion composition.

In addition, the present invention comprises the steps of a) impregnating a nonpolar solvent with silica; b) mixing the silica impregnated with the non-polar solvent prepared in step a) with a polar solvent; And c) impinging the silica impregnated with the nonpolar solvent prepared in step b) to generate a nonpolar solvent droplet, thereby including the nonpolar solvent droplet in the polar solvent. Provided are methods for preparing an oil-water (O / W) dispersion composition.

The present invention provides a dispersion composition comprising polar solvent droplets in a nonpolar solvent, wherein the non-surfactant type water-oil (W / O) dispersion composition has a transmittance of 90 to 100%. do.

In addition, the present invention comprises the steps of a) impregnating a polar solvent with silica; b) mixing the silica impregnated with the polar solvent prepared in step a) with a nonpolar solvent; And c) applying polarity to the mixture of silica and nonpolar solvent impregnated with the polar solvent prepared in step b) to produce polar solvent droplets, thereby including the polar solvent droplets in the nonpolar solvent. Provided is a method for preparing a non-surfactant type water-oil (W / O) dispersion composition of the claims.

The dispersion composition of the present invention has the advantage that the phase separation phenomenon does not occur even when the use environment is changed, and when used on the skin without using a surfactant, there is an advantage that the usability such as spreadability and spreadability is good.

In addition, there is an advantage that it is easy to include a poorly soluble material or hardly dispersible material.

In addition, since various active ingredients can be added to the droplets of very small size, when the ingredients having a pharmacological effect are added, the transdermal delivery function through the skin is improved and the absorption rate is excellent, so it can be used for various medical products. have.

In addition, it is possible to deliver a pharmacologically effective component through oral administration and intravenous injection, which can be used in such pharmaceutical products.

Due to these advantages, it can be used in various cosmetic compositions and pharmaceutical compositions.

1 is a photograph of the droplets in the oil-water (O / W) dispersion composition according to an embodiment of the present invention using a CryoTEM (JEMOL JEM-3011HR, FEI Tecnai G2 spirit TWIN) device.
2 is another photograph of droplets in an oil-water (O / W) dispersion composition according to an embodiment of the present invention.
3 to 4 are photographs showing the phase separation characteristics of the oil-water (O / W) dispersion composition according to the embodiment of the present invention.
5 to 7 are photographs showing the temperature stability characteristics of the oil-water (O / W) dispersion composition according to an embodiment of the present invention.

In the present invention, as a dispersion composition containing a polar solvent and a non-polar solvent, when used on the skin without a surfactant, it is not only good usability, such as spreadability and spreadability, but also does not cause phase separation even when the use environment is changed. When the effective ingredient is added, various active ingredients are added to droplets of a very small size to provide a transdermal delivery function through the skin and the like, as well as to improve the performance of intravenous injection or oral administration, thereby providing a dispersion composition having excellent absorption rate.

It will be described in more detail below.

Non-surfactant Oil-Water (O / W) Dispersion Compositions

The non-surfactant oil-water (O / W) dispersion composition referred to herein is a dispersion composition comprising a nonpolar solvent droplet in a polar solvent, wherein the dispersion composition has a transparency of 90 to 100%. It is characterized by. In general, oil-water dispersion compositions include surfactants to prevent phase separation and to facilitate dispersion. However, the use of a surfactant has the advantage that it can be stabilized through uniform dispersion, but depending on the use of the surfactant, in terms of usability, such as poor sticking property and unpleasant feeling of use, such as stickiness or a large amount of oily residue, etc. There was a serious disadvantage.

Thus, the present inventors have completed the present invention by confirming that when the non-polar solvent droplets of very small size are prepared, excellent dispersibility can be ensured even without using a surfactant, and thus the permeability of the dispersion composition is improved.

In the present invention, transparency refers to the degree of transparency of a substance, and the amount of light transmitted through the medium is divided by the amount of incident light. Therefore, the transparent material shows a value close to 100%, the opaque material shows a value close to 0%. In the present invention, the transmittance at UV 650 nm is measured and shown.

The non-surfactant oil-water (O / W) dispersion composition of the present invention comprises a polar solvent.

The polar solvent used in the present invention may be used without particular limitation as long as it is a solvent that can be mixed with water in a conventional sense. Specifically, water, alcohol having 1 to 10 carbon atoms, acetone, and the like may be used.

The non-surfactant oil-water (O / W) dispersion composition of the present invention comprises a nonpolar solvent.

The droplet of the nonpolar solvent used by this invention means the state in which a nonpolar solvent is disperse | distributed in spherical or non-spherical form in a polar solvent. The type of nonpolar solvent used in the present invention is not particularly limited as long as it is a material that can be mixed with oil. Preferably, at least one selected from the group consisting of oil, hexane, chloroform, dichloromethane, ethyl acetate, and the like can be used. Preferably, oil can be used.

The droplets of the nonpolar solvent used in the present invention have a spherical or non-spherical shape. In the present invention, a spherical shape includes not only a perfect sphere having a smooth surface, but also a polyhedron close to a perfect sphere, and is assumed to have a non-spherical shape under the assumption that no droplets of a substantially perfect spherical shape exist.

Therefore, the droplet of the nonpolar solvent used by this invention contains the droplet of sphericity 0.7-1. Here, "spherical degree" is defined as r / R, where R is the diameter of a circle equal to the projection area of the droplet, and r is the diameter of the smallest circle circumscribed on the projection of the droplet. The closer the value of the spherical value to 1, the more complete the shape of the sphere, and the closer to 0 the deviation from the shape of the sphere. Droplets used in the present invention preferably have a spherical degree of 0.7 to 1, which may include a drop having an ellipsoid or a polyhedral shape having a partially protruding portion, and other forms of the drop may also be any form. It may include.

The non-spherical droplets of the droplets of the nonpolar solvent used in the present invention may be represented by ellipses. Therefore, the droplet of the nonpolar solvent used by this invention may contain the elliptical droplet whose average of the long diameter / short diameter ratio is 1-1000, and it is more preferable to exist in the range of 5-100.

In the present invention, the sphericity of the droplet of the non-polar solvent and the ratio of the long diameter / short diameter may be determined by using an electron microscope (N / W) dispersion composition containing a non-surfactant oil-water (O / W) dispersion composition containing the droplet of the non-polar solvent. For example, it is measured using a photograph taken at a magnification (10,000 to 50,000 times) that can be measured using a TEM, and the long diameter is a long rectangle of green drawn to contact the outer edge of the droplet and the smallest area thereof. The length and short diameter of a side are the length of the short side of the rectangle. In addition, the average of a long diameter and a short diameter is an average of 50 or more droplets which randomly selected the measurable droplet on the SEM photograph. The droplet which can be measured on an SEM photograph is, for example, a droplet of 0.01 µm or more at a short diameter in the case of an SEM photograph with a magnification of 10,000 times.

The nonpolar solvent droplets contained in the non-surfactant oil-water (O / W) dispersion composition of the present invention may be those having an average particle diameter of 20 nm or less, preferably those having 15 nm or less, Most preferably, what is 10 nm or less can be used. The average particle diameter may be measured by diffraction experiment, preferably using Small Angle Neutron Scattering (SANS). When the average particle diameter of the non-polar solvent exceeds 20 nm, dispersibility is lowered, and there is a problem in that phase separation occurs. In addition, the lower limit of the droplet average particle diameter of the nonpolar solvent is not particularly limited, but may be about 1 nm or more.

The nonpolar solvent droplet contained in the non-surfactant type oil-water (O / W) dispersion composition of the present invention has a span ΔD in the particle diameter of the long diameter of the droplet in the range of 0.2 to 3, and the span ΔD is It may be calculated according to Equation 1 below.

[Equation 1]

ΔD = (D ₉₀ -D ₁₀ ) / D ₅₀

If the span?

According to the manufacturing method of the non-surfactant type oil-water (O / W) dispersion composition of this invention, the ratio of the particle diameter of a long diameter of 20 nm or less in the nonpolar solvent droplet contained in a composition is 50% or more. If the ratio of the non-polar solvent droplet having a long diameter of 20 nm or less is less than 50%, the dispersibility may be lowered, resulting in a phase separation phenomenon.

The dispersed droplets act on physical and chemical attractive forces, such as van der Waals forces and surface tensions, causing agglomeration. To control this phenomenon, the ΔH of the Gibbs energy acting between the droplets should be adjusted.

However, nano-sized droplets, such as nonpolar solvent droplets, included in the non-surfactant oil-water (O / W) dispersion compositions of the present invention, when thermodynamically at their lowest energy state, It does not self-assemble unless there is an input (see "The role of interparticle and external forces in nanoparticle assembly", Nature Materials 7, 527-538 (2008)).

With this in mind, the inventors of the present invention can control the ΔH of the Gibbs energy by reducing the size of the dispersed droplets to nanoscale, so that the droplets do not aggregate together and are well dispersed. Dispersion is enhanced to prevent phase separation in the same external energy, cryogenic or cryogenic phases.

In addition, the non-polar solvent droplets included in the non-surfactant oil-water (O / W) dispersion composition of the present invention is 0.01 wt% (W / W) to 30 wt% (W / W) based on the total weight of the composition. It may be included, preferably from 0.1% by weight (W / W) to 15% by weight (W / W).

If the weight of the non-polar solvent droplets is less than 0.01% by weight (W / W), there is a problem that the content of the active ingredient is too small, when 30.0% by weight (containing more than W / W) phase inversion (volume inversion) There is a problem that occurs.

In addition, the non-surfactant oil-water (O / W) dispersion composition of the present invention may further include an additive.

The additive may be used without particular limitation so long as it is generally included in the solution of the aqueous phase, and preferably pH adjusting agents, isotonic agents, osmotic stabilizers, excipients or mixtures thereof may be used.

In addition, the non-polar solvent droplets included in the non-surfactant oil-water (O / W) dispersion composition of the present invention may further include an active ingredient. The active ingredient may be used without particular limitation as long as it is a pharmaceutically useful substance or a substance having a medical effect. For example, cyclosporin A, paclitaxel, docetaxel, decusin, meloxycamp, itraconazole, celecoxib, capecitabine , Travo, frost, isoflavone, diclofenac sodium, ginsenoside Rg1, taclolimus, alendronate, latanoprost, bimatoprost, atorvastatin calcium, roschvastatin calcium, entacavir, amphotericin B, omega 3 Or urosodeoxycholic acid; Flavor oils such as eucalyptus oil, lavender oil, lemon oil, sandalwood oil, rosemary oil, chamomile oil, cinnamon oil and orange oil; Alpha bisabolol, vitamin A (retinol), vitamin E, tocopheryl acetate, vitamin D, vitamin F or derivatives thereof; Etc. or a combination thereof may be used.

In addition, the active ingredient may be included in 0.001% by weight (W / W) to 20% by weight (W / W) relative to the non-polar solvent droplets.

Since the non-surfactant type oil-water (O / W) dispersion composition of the present invention contains the active ingredient as described above, it can be used as a cosmetic composition or a pharmaceutical composition.

The non-surfactant oil-water (O / W) dispersion composition of the present invention does not contain ionic bonds with anions present on the skin, as well as non-polar, because it contains no surfactant as mentioned above. This is because the size of the solvent droplet is 20 nm or less, which is significantly smaller than the pores outside the skin (200 nm or more), so that penetration into the skin is easy.

Therefore, when used as the cosmetic composition or pharmaceutical composition, it is possible to deliver a significantly faster and more active ingredients than the conventional composition.

Process for preparing non-surfactant oil-water (O / W) dispersion composition

In addition, the present invention comprises the steps of a) impregnating a nonpolar solvent in silica; b) mixing the silica impregnated with the nonpolar solvent prepared in step a) with the polar solvent; And c) impinging the silica impregnated with the nonpolar solvent prepared in step b) to generate a nonpolar solvent droplet, thereby including the nonpolar solvent droplet in the polar solvent. Provided are methods for preparing an oil-water (O / W) dispersion composition.

Looking at each step of the manufacturing method of the non-surfactant type oil-water (O / W) dispersion composition according to the present invention.

Step a) of the present invention is a step of impregnating silica with a nonpolar solvent.

The non-polar solvent used in step a) is not particularly limited as long as it is a solvent that can be mixed with oil. Preferably, at least one selected from the group consisting of oil, hexane, chloroform, dichloromethane, ethyl acetate, and the like may be used. Preferably, oil can be used.

In addition, in step a), an active ingredient may be further added to the nonpolar solvent. The active ingredient may be used without particular limitation as long as it is a pharmaceutically useful substance or a substance having a medical effect. For example, cyclosporin A, paclitaxel, docetaxel, decusin, meloxycamp, itraconazole, celecoxib, capecitabine , Travo, frost, isoflavone, diclofenac sodium, ginsenoside Rg1, taclolimus, alendronate, latanoprost, bimatoprost, atorvastatin calcium, roschvastatin calcium, entacavir, amphotericin B, omega 3 Or urosodeoxycholic acid; Flavor oils such as eucalyptus oil, lavender oil, lemon oil, sandalwood oil, rosemary oil, chamomile oil, cinnamon oil and orange oil; Alpha bisabolol, vitamin A (retinol), vitamin E, tocopheryl acetate, vitamin D, vitamin F or derivatives thereof; Etc. or a combination thereof may be used.

The silica may have a nano-scale pore size and may be used without particular limitation as long as it can impregnate a nonpolar solvent. Preferably, the pore size in the silica may be 5 to 40 nm based on the particle size. . In this case, there is an advantage that it is easy to adjust the size of the nonpolar solvent droplets described later.

In step b) of the present invention, the non-polar solvent-impregnated silica prepared in step a) is mixed with the polar solvent.

In step b), the silica impregnated with the nonpolar solvent prepared in step a) is filtered and mixed with the polar solvent.

The polar solvent used in the present invention may be used without particular limitation as long as it is a solvent that can be mixed with water in a conventional sense. Specifically, water, alcohol having 1 to 10 carbon atoms, acetone, and the like may be used.

The amount of the polar solvent included at this time is 0.01% by weight (W / W) to 30% by weight (W / W) as compared to the total weight of the non-polar solvent droplets impregnated in the silica and the total weight of the composition in which the polar solvent is added together. / W) may be added, and preferably, the nonpolar solvent droplet may be included in an amount of 0.1 wt% (W / W) to 15 wt% (W / W).

If the weight of the non-polar solvent droplets is less than 0.01% by weight (W / W), there is a problem that the content of the active ingredient is too small, when 30.0% by weight (containing more than W / W) phase inversion (volume inversion) There is a problem that occurs.

Step c) of the present invention is a step of including the non-polar solvent droplet in the polar solvent by impacting the non-polar solvent impregnated silica prepared in step b) to produce a non-polar solvent droplet.

According to the method for producing a non-surfactant oil-water (O / W) dispersion composition of the present invention, after impregnating oil into the pores of silica, the ultrasonic wave or shear stress force is applied to the silica. By applying the nonpolar solvent impregnated into the pores of the silica to form a droplet form, it is possible to obtain a nonpolar solvent droplet of a size smaller than the pore size of the silica. According to the present invention, the size of the non-polar solvent droplets can be adjusted to the nanoscale level.

In the method for producing a non-surfactant oil-water (O / W) dispersion composition of the present invention, the method of applying ultrasonic waves to silica is particularly limited as long as it can remove the nonpolar solvent impregnated into silica. However, preferably, the dispersion apparatus of Korea Patent Registration 10-1157144 may be used.

In addition, in the method for producing a non-surfactant oil-water (O / W) dispersion composition, the method of applying shear stress to silica is not particularly limited as long as it is a method used in the art. Can be used without

According to this method for producing a non-surfactant oil-water (O / W) dispersion composition of the present invention, the particle diameter of the long diameter of the nonpolar solvent droplet has a span ΔD in the range of 0.2 to 3, and the span Δ D may be calculated according to Equation 1 below.

[Equation 1]

ΔD = (D ₉₀ -D ₁₀ ) / D ₅₀

If the span?

Moreover, according to the manufacturing method of the non-surfactant type oil-water (O / W) dispersion composition of this invention, the ratio of the particle diameter of a long diameter of 20 nm or less in the nonpolar solvent droplet contained in a composition is 50% or more. . If the ratio of the non-polar solvent droplet having a long diameter of 20 nm or less is less than 50%, the dispersibility may be lowered, resulting in a phase separation phenomenon.

Non Surfactant Type Water-Oil (W / O) Dispersion Compositions

The non-surfactant type water-oil (W / O) dispersion composition referred to herein is a dispersion composition comprising polar solvent droplets in a nonpolar solvent, wherein the dispersion composition has a transmittance of 90 to 100%. It is characterized by. Typical water-oil dispersion compositions include surfactants to prevent phase separation and to facilitate dispersion. However, the use of a surfactant has the advantage that it can be stabilized through uniform dispersion, but depending on the use of the surfactant, in terms of usability, such as poor sticking property and unpleasant feeling of use, such as stickiness or a large amount of oily residue, etc. There was a serious disadvantage.

Accordingly, the present inventors have completed the present invention by confirming that the preparation of polar solvent droplets of very small size ensures excellent dispersibility even without using a surfactant, thus improving the transparency of the dispersion composition. It was.

The nonsurfactant type water-oil (W / O) dispersion composition of the present invention comprises a nonpolar solvent.

The type of nonpolar solvent used in the present invention is not particularly limited as long as it is a material that can be mixed with oil. Preferably, at least one selected from the group consisting of oil, hexane, chloroform, dichloromethane, ethyl acetate, and the like can be used. Preferably, oil can be used.

The nonsurfactant type water-oil (W / O) dispersion composition of the present invention comprises a nonpolar solvent.

The droplet of the polar solvent used by this invention means the state in which the polar solvent is disperse | distributed in spherical or non-spherical form in a nonpolar solvent.

The polar solvent used in the present invention may be used without particular limitation as long as it is a solvent that can be mixed with water in a conventional sense. Specifically, water, alcohol having 1 to 10 carbon atoms, acetone, and the like may be used.

The droplets of the polar solvent used in the present invention have a spherical or non-spherical shape. In the present invention, a spherical shape includes not only a perfect sphere having a smooth surface, but also a polyhedron close to a perfect sphere, and is assumed to have a non-spherical shape under the assumption that no droplets of a substantially perfect spherical shape exist.

Therefore, the droplet of the polar solvent used by this invention contains the droplet of sphericity 0.7-1. Here, "spherical degree" is defined as r / R, where R is the diameter of a circle equal to the projected area of the droplet and r is the diameter of the smallest circle circumscribed on the projection of the droplet. The closer the value of the spherical value to 1, the more complete the shape of the sphere, and the closer to 0 the deviation from the shape of the sphere. Droplets used in the present invention preferably have a spherical degree of 0.7 to 1, which may include a drop having an ellipsoid or a polyhedral shape having a partially protruding portion, and other forms of the drop may also be any form. It may include.

Aspheric droplets in the droplets of the polar solvent used in the present invention may be represented by ellipses. Accordingly, the droplets of the polar solvent used in the present invention may include elliptical droplets having an average ratio of long diameter / short diameter of 1 to 1000, more preferably in the range of 5 to 100.

In the present invention, the sphericity of the droplets of the polar solvent and the ratio of the long diameter / short diameter may be determined by using an electron microscope (W / O) dispersion composition containing a non-surfactant type water-oil (W / O) dispersion composition containing the droplets of the polar solvent. For example, it is measured using a photograph taken at a magnification (10,000 to 50,000 times) that can be measured using a TEM, and the long diameter is a long rectangle of green drawn to contact the outer edge of the droplet and the smallest area thereof. The length and short diameter of a side are the length of the short side of the rectangle. In addition, the average of a long diameter and a short diameter is an average of 50 or more droplets which randomly selected the measurable droplet on the SEM photograph. The droplet which can be measured on an SEM photograph is, for example, a droplet of 0.01 µm or more at a short diameter in the case of an SEM photograph with a magnification of 10,000 times.

As the polar solvent droplets contained in the non-surfactant type water-oil (W / O) dispersion composition of the present invention, those having an average particle diameter of 20 nm or less may be used, and preferably those having a diameter of 15 nm or less may be used. Most preferably, what is 10 nm or less can be used. The average particle diameter may be measured by diffraction experiment, preferably using Small Angle Neutron Scattering (SANS). When the average particle diameter of the polar solvent exceeds 20 nm, dispersibility is lowered and there is a problem in that phase separation occurs. In addition, the lower limit of the droplet average particle diameter of the polar solvent is not particularly limited, but may be about 1 nm or more.

The polar solvent droplet contained in the non-surfactant type water-oil (W / O) dispersion composition of the present invention has a span ΔD in the particle diameter of the long diameter of the droplet in the range of 0.2 to 3, and the span ΔD is It may be calculated according to Equation 1 below.

 [Equation 1]

ΔD = (D ₉₀ -D ₁₀ ) / D ₅₀

If the span?

In addition, the ratio of the average particle diameter of the long diameter of 20 nm or less in the polar solvent droplet contained in the non-surfactant type water-oil (W / O) dispersion composition of this invention is 50% or more. If the ratio of the particle diameter of the long solvent of the polar solvent droplet is 20 nm or less is lower than 50%, the dispersibility is poor, and there is a problem that phase separation occurs.

The dispersed droplets act on physical and chemical attractive forces, such as van der Waals forces and surface tensions, causing agglomeration. To control this phenomenon, the ΔH of the Gibbs energy acting between the droplets should be adjusted.

However, nano-sized droplets, such as nonpolar solvent droplets, included in the non-surfactant oil-water (O / W) dispersion compositions of the present invention, when thermodynamically at their lowest energy state, It does not self-assemble unless there is an input (see "The role of interparticle and external forces in nanoparticle assembly", Nature Materials 7, 527-538 (2008)).

With this in mind, the inventors of the present invention can control the ΔH of the Gibbs energy by reducing the size of the dispersed droplets to nanoscale, so that the droplets do not aggregate together and are well dispersed. Dispersion is enhanced to prevent phase separation in the same external energy, cryogenic or cryogenic phases.

In addition, the polar solvent droplets included in the non-surfactant type water-oil (W / O) dispersion composition of the present invention is 0.01% by weight (W / W) to 30% by weight (W / W) based on the total weight of the composition. It may be included, preferably from 0.1% by weight (W / W) to 15% by weight (W / W).

If the weight of the polar solvent droplets is less than 0.01% by weight (W / W), there is a problem that the content of the active ingredient is too small, if 30.0% by weight (containing more than W / W phase inversion) There is a problem that occurs.

In addition, the non-surfactant type water-oil (W / O) dispersion composition of the present invention may further include an additive.

The additive may be used without particular limitation so long as it is generally included in the solution of the aqueous phase, and preferably pH adjusting agents, isotonic agents, osmotic stabilizers, excipients or mixtures thereof may be used.

In addition, the polar solvent droplets included in the non-surfactant type water-oil (W / O) dispersion composition of the present invention may further include an active ingredient. The active ingredient may be used without particular limitation as long as it is a pharmaceutically useful substance or a substance having a medical effect, for example, adenosine, arbutin, vitamin C, and hydrophilic derivatives thereof; Vitamin B3, vitamin B5, vitamin H and derivatives thereof; Acetylglucosamine; And peptides; Etc. or a combination thereof may be used.

In addition, the active ingredient may be included in 0.001% by weight (W / W) to 20% by weight (W / W) relative to the polar solvent droplets.

Since the non-surfactant type water-oil (W / O) dispersion composition of the present invention contains the active ingredient as described above, it can be used as a cosmetic composition or a pharmaceutical composition.

Since the non-surfactant type water-oil (W / O) dispersion composition of the present invention does not contain a surfactant as mentioned above, it does not ionic bond with anion present on the skin, but also has polarity. This is because the size of the solvent droplet is 20 nm or less, which is significantly smaller than the pores outside the skin (200 nm or more), so that penetration into the skin is easy.

Therefore, when used as the cosmetic composition or pharmaceutical composition, it is possible to deliver a significantly faster and more active ingredients than the conventional composition.

Process for preparing non-surfactant type water-oil (W / O) dispersion composition

In another aspect, the present invention comprises the steps of a) impregnating a polar solvent with silica; b) mixing the silica impregnated with the polar solvent prepared in step a) with the nonpolar solvent; And c) imparting the polar solvent impregnated with the polar solvent prepared in step b) to generate the polar solvent droplets, thereby including the polar solvent droplets in the non-polar solvent. Provided are methods for preparing a water-oil (W / O) dispersion composition.

Looking at each step of the manufacturing method of the non-surfactant type water-oil (W / O) dispersion composition according to the present invention.

Step a) of the present invention is a step of impregnating a polar solvent with silica.

The polar solvent used in step a) is not particularly limited as long as it is a solvent that can be mixed with oil. Preferably, at least one selected from the group consisting of oil, hexane, chloroform, dichloromethane, ethyl acetate, and the like may be used. Preferably, oil can be used.

In addition, in step a), an active ingredient may be further added to the polar solvent. The active ingredient may be used without particular limitation as long as it is a pharmaceutically useful substance or a substance having a medical effect, for example, adenosine, arbutin, vitamin C, and hydrophilic derivatives thereof; Vitamin B3, vitamin B5, vitamin H and derivatives thereof; Acetylglucosamine; And peptides; Etc. or a combination thereof may be used.

The silica is a nano-scale pore size, as long as it can be impregnated with a polar solvent can be used without particular limitation, preferably, the size of the pores in the silica may be used 5 to 40 nm based on the particle size. . In this case, there is an advantage that it is easy to adjust the size of the polar solvent droplet described later.

Step b) of the present invention is a step of mixing the silica impregnated with the polar solvent prepared in step a) with a nonpolar solvent.

In step b), the silica impregnated with the polar solvent prepared in step a) is filtered and mixed with the nonpolar solvent.

The nonpolar solvent used in the present invention may be used without particular limitation as long as it is a solvent that can be mixed with water in a conventional sense. Specifically, water, alcohol having 1 to 10 carbon atoms, acetone, and the like may be used.

In this case, the amount of the non-polar solvent included in the content of the polar solvent droplets is 0.01% by weight (W / W) to 30% by weight (W) when compared to the total weight of the composition of the droplets of the polar solvent impregnated in the silica and the non-polar solvent. / W) may be added, and preferably, the polar solvent droplet may be included in an amount of 0.1 wt% (W / W) to 15 wt% (W / W).

If the weight of the polar solvent droplets is less than 0.01% by weight (W / W), there is a problem that the content of the active ingredient is too small, if 30.0% by weight (containing more than W / W phase inversion) There is a problem that occurs.

Step c) of the present invention is to include polar solvent droplets in the non-polar solvent by impacting the silica impregnated with the polar solvent prepared in step b) to generate the polar solvent droplets.

According to the manufacturing method of the non-surfactant type water-oil (W / O) dispersion composition of the present invention, after impregnating oil into the pores of silica, ultrasonic waves, shear stress force, etc. are applied to the silica. By applying the polar solvent impregnated in the pores of the silica to form a droplet form, it is possible to obtain a polar solvent droplet of a size smaller than the pore size of the silica. According to the present invention, the size of the polar solvent droplets can be adjusted to the nanoscale level.

In the method for producing a non-surfactant type water-oil (W / O) dispersion composition of the present invention, the method of applying ultrasonic waves to silica is particularly limited as long as it is possible to remove the polar solvent impregnated into silica. However, preferably, the dispersion apparatus of Korea Patent Registration 10-1157144 may be used.

In addition, in the method for producing a non-surfactant water-oil (W / O) dispersion composition, a method of applying shear stress to silica is not particularly limited as long as it is a method used in the art. Can be used without

According to the manufacturing method of the non-surfactant type water-oil (W / O) dispersion composition of this invention, the polarity contained in the non-surfactant type water-oil (W / O) dispersion composition of this invention The solvent droplet may have a span ΔD in the particle diameter of the long diameter of the droplet in a range of 0.2 to 3, and the span ΔD may be calculated according to Equation 1 below.

 [Equation 1]

ΔD = (D ₉₀ -D ₁₀ ) / D ₅₀

If the span?

Moreover, according to the manufacturing method of the non-surfactant type water-oil (W / O) dispersion composition of this invention, the ratio of the particle diameter of long diameter of 20 nm or less in the polar solvent droplet contained in a composition is 50% or more. . If the ratio of the particle diameter of the long solvent of the polar solvent droplet is 20 nm or less is less than 50%, the dispersibility is lowered, and there is a problem that phase separation occurs.

Hereinafter, the production method of the present invention through the embodiment of the present invention in more detail. It is to be understood that the present invention is not limited to these examples.

Example

Preparation of non-surfactant oil-water (O / W) dispersion composition

Example 1

20 g of airgel (JIOS, product name AeroVa) having a pore size of 20 nm or less is heat-treated at 450 ° C. for 2 hours using a furnace (Furnace, JSR, JSMF-45T). After adding 8 g of fragrance oil to 4 g of heat-treated airgel, the fragrance oil is impregnated into the airgel pores using an overhead stirrer (M TOPS®, BL620D). Thereafter, 10 g of the airgel adsorbed with the fragrance oil was added to 100 g of water, and then, using an overhead stirrer, oil droplets contained in the pores in the airgel were separated in the solvent, and the remaining airgel was filtered with a 0.45 um filter to filter the oil-water. Dispersion compositions were prepared. After diluting the water so that the weight ratio (W / W) of the oil droplet and the water is 0.5: 99.5, a photograph taken using a CryoTEM (JEMOL company JEM-3011HR, FEI company Tecnai G2 spirit TWIN) device is shown in FIG. 1. It was. As a result of the scale as shown in the right photograph of FIG. 1, it can be seen that oil droplets having nanoscales all around 10 nm are dispersed.

Example 2

An oil-water dispersion composition was prepared in the same manner as in Example 1 except for aerosil (Evonik, product name R812S) having a pore size of 30 nm or less instead of an airgel (JIOS, product name AeroVa). The volume ratio (V / V) of the oil droplet and water was 0.5: 99.5, and the TEM photograph taken was shown in FIG. 2. As shown in FIG. 2, oil droplets on a nano scale are dispersed.

Comparative Example 1

An oil-water dispersion composition was prepared in the same manner as in Example 1, except that porous silica (ABC NANOTECH, product name Silnos 190) having a pore size of 45 nm or more was used.

Comparative Example 2

The oil-water dispersion composition was prepared by mixing the fragrance oil and water in a volume ratio of 0.5: 99.5, and then adding 5% of a surfactant (TCI, Tween 60).

Preparation of Non Surfactant Type Water-Oil (W / O) Dispersion Compositions

Example 3

20 g of airgel (JIOS, product name AeroVa) having a pore size of 20 nm or less is heat-treated at 450 ° C. for 2 hours using a furnace (Furnace, JSR, JSMF-45T). After adding 8 g of water to 4 g of the heat-treated airgel, water is impregnated into the airgel pores using an overhead stirrer (M TOPS®, BL620D). After that, 10 g of water-adsorbed aerogel was added to 100 g of medium chain triglycerides (MCT) oil, and then water droplets contained in pores in the aerogel were separated in a solvent using an overhead stirrer, and the remaining aerogel was filtered with a 0.45 um filter. Filter to produce a water-oil dispersion composition. The oil was diluted so that the weight ratio (W / W) of the water droplets and the oil was 2.5: 97.5, to prepare a water-oil dispersion composition in which nano-scale water droplets were dispersed.

Example 4

A water-oil dispersion composition in which nano-scale water droplets are dispersed in the same manner as in Example 1 except for aerosil (Evonik, product name R812S) having a pore size of 30 nm or less instead of airgel (JIOS, product name AeroVa). Was prepared. The volume ratio (V / V) of the water droplets and the oil was 0.5: 99.5.

Comparative Example 3

A water-oil dispersion composition was prepared in the same manner as in Example 3, except that porous silica (ABC NANOTECH Co., product name Silnos 190) having a pore size of 45 nm or more was used.

[Comparative Example 4]

Water and oil were mixed at a volume ratio of 0.5: 99.5, and then 5% of a surfactant (TCI, Span 60) was added thereto to prepare a water-oil dispersion composition.

Experimental Example 1: Size Characteristics of Oil Droplets

The particle size of the oil droplets or water in the oil-water dispersion compositions prepared in Examples 1 and 2 and Comparative Examples 1 and 2 and the water-oil dispersion compositions prepared in Examples 3 to 4 and Comparative Examples 3 to 4 was determined by CryoTEM (JEOL Corporation). After photographing using JEM-3011HR, FEI Tecnai G2 spirit TWIN) device, the average particle diameter of the droplets was measured and shown in Table 1.

Droplet average particle diameter (nm) Example 1 10 Example 2 19 Comparative Example 1 Not measurable by phase separation Comparative Example 2 Not measurable by phase separation Example 3 12 Example 4 18 Comparative Example 3 Not measurable by phase separation Comparative Example 4 Not measurable by phase separation

Experimental Example  2: transmittance characteristic

Oil-water dispersion compositions prepared in Examples 1-2 and Comparative Examples 1-2, and water prepared in Examples 3-4 and Comparative Examples 3-4, using a UV-Vis Spectrometer (Evolution 60S from Thermo Scientific) For the oil dispersion composition, 3 mL of each dispersion composition was injected into the device without dilution, and then scanned at UV 700 to 200 nm, and then the transmittance at UV 650 nm was measured. The results are shown in Table 2 below.

650nm transmittance Example 1 100% Example 2 100% Comparative Example 1 55% Comparative Example 2 96% Example 3 100% Example 4 100% Comparative Example 3 43% Comparative Example 4 92%

As shown in Table 2, Examples 1 to 4 exhibited excellent transmittance, and Comparative Example 1 and Comparative Example 3 using porous silica having a pore particle size of 40 nm or more showed significantly lower transmittance.

Experimental Example  3: Phase separation  characteristic

For the oil-water dispersion compositions prepared in Examples 1 and 2 and Comparative Examples 1 and 2 and the water-oil dispersion compositions prepared in Examples 3 and 4 and Comparative Examples 3 to 4, centrifuges (CF of WiseTis®) 10 Set) was used to compare the phase separation characteristics by centrifugation at 13500 rpm for 5 minutes.

As a result, immediately after centrifugation, there was no significant difference from before centrifugation (FIG. 3), and after 5 days as in FIG. 4, Comparative Example 1, Comparative Example 3, and Comparative Example 4 were opaque or layered separation occurred. Examples 1 to 4 confirmed that the phase is stable.

Experimental Example  4: temperature stability characteristics

For the oil-water dispersion compositions prepared in Examples 1 and 2 and Comparative Examples 1 and 2 and the water-oil dispersion compositions prepared in Examples 3 to 4 and Comparative Examples 3 to 4, 4 ° C., 30 ° C., and 45 ° C. The change in appearance of the oil-water dispersion composition prepared after 4 weeks storage under the conditions was observed. Table 3 and FIG. 5 (4 weeks storage at 4 ° C), FIG. 6 (4 weeks storage at 30 ° C), and Storage at 45 ° C. for 4 weeks).

division Stability 4 ℃ 30 ℃ 45 ℃ 1 week 2 weeks 4 Weeks 1 week 2 weeks 4 Weeks 1 week 2 weeks 4 Weeks Example 1 Transparency Transparency Transparency Transparency Transparency Transparency Transparency Transparency Transparency Example 2 Transparency Transparency Transparency Transparency Transparency Transparency Transparency Transparency Transparency Comparative Example 1 opacity opacity opacity opacity opacity opacity opacity opacity opacity Comparative Example 2 opacity opacity opacity opacity opacity opacity opacity opacity opacity Example 3 Transparency Transparency Transparency Transparency Transparency Transparency Transparency Transparency Transparency Example 4 Transparency Transparency Transparency Transparency Transparency Transparency Transparency Transparency Transparency Comparative Example 3 Phase separation Phase separation Phase separation Phase separation Phase separation Phase separation Phase separation Phase separation Phase separation Comparative Example 4 opacity opacity opacity opacity opacity opacity opacity opacity opacity

As a result, as shown in Table 3, Examples 1 to 4 were all transparent in appearance at 4 ℃, 30 ℃, 45 ℃ conditions appeared to be good stability, Comparative Examples 1, 2, 4 was 4 ℃, 30 ℃, All of them were opaque at 45 ° C., and in Comparative Example 3, the layers were separated, and thus, stability was not maintained.

Claims (16)

A non-surfactant oil-water (O / W) dispersion composition comprising non-polar solvent droplets in a polar solvent,
Droplets of the non-polar solvent, the average of the long diameter / short diameter is 1 to 1000,
The droplets of the nonpolar solvent have a sphericity of 0.7 to 1,
Pharmaceutical composition, wherein the dispersion composition has a transmittance of 90 to 100%. The method of claim 1,
The pharmaceutical composition whose average particle diameter of the said nonpolar solvent droplet is 20 nm or less. The method of claim 1,
The non-polar solvent is at least one selected from the group consisting of oil, hexane, chloroform, dichloromethane and ethyl acetate, the pharmaceutical composition. The method of claim 1,
The polar solvent is at least one member selected from the group consisting of water, an alcohol having 1 to 10 carbon atoms, and acetone. The method of claim 1,
Droplets of the non-polar solvent is a pharmaceutical composition comprising 0.01% by weight (W / W) to 30.0% by weight (W / W) relative to the total weight of the composition. The method of claim 1,
Droplets of the non-polar solvent further comprises an active ingredient, the pharmaceutical composition. The method of claim 6,
The active ingredient is cyclosporin A, paclitaxel, docetaxel, decusin, meloxycamp, itraconazole, celecoxib, capecitabine, travo, frost, isoflavone, diclofenac sodium, ginsenoside Rg1, taclolimus, alendronate , Latanoprost, bimatoprost, atorvastatin calcium, rosuvastatin calcium, entecavir, amphotericin B, omega 3, urusodeoxycholic acid, eucalyptus oil, lavender oil, lemon oil, sandalwood oil, rosemary oil , At least one selected from the group consisting of chamomile oil, cinnamon oil, orange oil, alpha bisabolol, vitamin A (retinol), vitamin E, tocopheryl acetate, vitamin D, vitamin F and derivatives thereof. . The method of claim 6,
The active ingredient is 0.001% by weight (W / W) to 20% by weight (W / W) of the non-polar solvent, the pharmaceutical composition. A non-surfactant type water-oil (W / O) dispersion composition comprising polar solvent droplets in a nonpolar solvent,
The droplets of the polar solvent have an average of the long diameter / short diameter of 1 to 1000,
Droplets of the polar solvent, the sphericity is 0.7 to 1,
Pharmaceutical composition, wherein the dispersion composition has a transmittance of 90 to 100%. The method of claim 9,
The pharmaceutical composition whose average particle diameter of the said polar solvent droplet is 20 nm or less. The method of claim 9,
The non-polar solvent is at least one selected from the group consisting of oil, hexane, chloroform, dichloromethane and ethyl acetate, the pharmaceutical composition. The method of claim 9,
The polar solvent is at least one member selected from the group consisting of water, an alcohol having 1 to 10 carbon atoms, and acetone. The method of claim 9,
Droplets of the polar solvent is comprised of 0.01% by weight (W / W) to 30.0% by weight (W / W) relative to the total weight of the composition, the pharmaceutical composition. The method of claim 9,
Droplets of the polar solvent further comprises an active ingredient, a pharmaceutical composition. The method of claim 14,
The active ingredient is any one or more selected from the group consisting of adenosine, arbutin, vitamin C, vitamin B3, vitamin B5, vitamin H, acetylglucosamine, peptides and derivatives thereof. The method of claim 14,
The active ingredient is 0.001% by weight (W / W) to 20% by weight (W / W) of the droplet of the polar solvent, the pharmaceutical composition.

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