KR100861980B1 - Encapsulated composition of a non-water liquid crystalline phase having skin analogue membrane, their cosmetic compositions, and manufacturing method thereof - Google Patents

Abstract

The present invention encapsulates an unstable drug upon contact with water in a highly dense Lamella type non-aqueous liquid crystal phase that does not use water, unlike conventional contracting techniques, thereby promoting the stability of the active ingredient. Designed to have a structure and composition similar to the intercellular lipids of the stratum corneum of the skin, it improves the compatibility with the skin, and when it is used as a concentration of the active ingredient desired in the cosmetics, it is simply stirred to form four petals (Maltese) in the grain interface. Non-aqueous liquid crystalline capsule base composition having a form of (cross), cosmetics using the same and a method for preparing the same, water-soluble polar solvent excluding water 10.0 to 60.0 parts by weight, ceramide 0.1 to 10.0 parts by weight, cholesterol 0.05 to 5.0 Liquid crystal containing 1.0 parts by weight, phospholipid 1.0-40.0 parts by weight and 0.5-7.0 parts by weight of higher alcohols having 16 to 22 carbon atoms Vagina; Oil-soluble active substance portion comprising 0.5 to 20.0 parts by weight of oil, 0.1 to 10.0 parts by weight of oil-soluble active ingredient and 0.01 to 0.5 parts by weight of oil-soluble antioxidant; And a water-soluble active material part including 3.0 to 30.0 parts by weight of water-soluble polar solvent except for water and 0.1 to 10.0 parts by weight of water-soluble active ingredient.

Non-aqueous, skin-like skin, lamellar, multilayer, intercellular lipid, stability, skin barrier restoration

Description

A non-aqueous liquid crystalline capsule base composition having a skin-like film and a cosmetic composition using the same and a method for manufacturing the same {Encapsulated composition of a non-water liquid crystalline phase having skin analogue membrane, their cosmetic compositions, and manufacturing method

FIG. 1 shows a schematic diagram of a real human skin lipid structure (1- (a)) and a schematic diagram of a non-aqueous liquid crystalline capsule base artificially designed in the present invention (1- (b)). Drawings.

Figure 2 is the main material that forms the intercellular lipid of the stratum corneum in the present invention, the phospholipid and the phospholipid to form a non-aqueous lamellar liquid crystal phase in the present invention, it is possible to encapsulate excess oil-soluble and water-soluble substances The lamellar liquid crystal phase has a similar structure and composition to the skin, thereby increasing the miscibility with the skin, resulting in a desirable drug delivery effect and restoring a damaged skin barrier. It is a figure which shows the chemical structures of ceramide and cholesterol to give.

3 is an interfacial liquid crystal formed when lamellar non-aqueous liquid crystal phases prepared by Examples 1, 2, and 3 according to the present invention and Example 2 were applied to water (Example 2 10% + purified water 90%). It is a photograph of the polarization microscope showing.

Figure 4 is a photograph of the transmission electron microscopy (TEM) that can be seen the microstructure of the lamellar non-aqueous liquid crystal phase made by Examples 1, 2, 3 according to the present invention.

FIG. 5 is X-ray diffraction (XRD) photographs for analyzing the structure of lamellar non-aqueous liquid crystal phases prepared by Examples 1, 2, and 3 according to the present invention.

6 is analytical data of differential scanning calorimetry (DSC) to find a proper temperature for injecting a lamellar non-aqueous liquid crystal phase prepared in Examples 1, 2, and 3 into an actual cosmetic.

FIG. 7 is a photograph showing examples 1, Comparative Example 1, and Comparative Example 3 according to the present invention compared with results observed with a polarized microscope of Samples 1, 4, and 6 obtained by dispersing it in water.

FIG. 8 compares drug delivery effects of Samples 3, 5, 10, and 11 into Examples 3, Comparative Examples 2, 7, and 8 according to the present invention. Vitamin C is a diagram shown in Figure 8- (b).

9 is a view showing a comparison of the measurement results of transepidermal water loss (TEWL) for Sample 2 in which Lamellar-type non-aqueous liquid crystal phase according to the present invention was added to water and Sample 2 purchased in the market. to be.

The present invention encapsulates an unstable drug upon contact with water in a highly dense Lamella type non-aqueous liquid crystal phase that does not use water, unlike conventional contracting techniques, thereby promoting the stability of the active ingredient. Designed to have a structure and composition similar to the intercellular lipids of the stratum corneum of the skin, it improves the compatibility with the skin, and when it is used as a concentration of the active ingredient desired in the cosmetics, it is simply stirred to form four petals (Maltese) in the grain interface. The present invention relates to a non-aqueous liquid crystalline capsule base composition having a form of -cross, a cosmetic using the same, and a preparation method thereof. More specifically, without using water to overcome the stability of active reverse degradation, discoloration, discoloration, separation, etc., caused by contact with the highly polar 'water', which is the biggest problem when applying an unstable active substance to cosmetics. To prepare the lamellae non-aqueous liquid crystalline capsule base which encapsulates the water-soluble active ingredient and the oil-soluble active ingredient in high concentration, the lamellae non-aqueous liquid crystalline capsule base has a structure and composition similar to the intercellular lipids of the stratum corneum. Because of its excellent miscibility, it is possible to easily obtain interfacial liquid crystal particles having a skin analogue membrane structure and composition by simple agitation without using any special equipment, and to have excellent drug delivery effect. Moisturizing and atopic dermatitis by restoring damaged or unhealthy skin barrier The present invention relates to a non-aqueous liquid crystalline capsule base composition, cosmetics using the same, and a method for preparing the same, which are effective for alleviating symptoms.

In the cosmetics industry, which is closely related to the skin as well as the pharmaceutical and pharmaceutical fields, research on the structure and components of the skin has been conducted for more than 10 years. Similarly, advances in research on promoting drug delivery are remarkable. Conventional liquid crystal emulsification technology is mostly made of a lamellar liquid crystal as a base material, and emulsified under appropriate conditions with an emulsifier capable of forming a liquid crystal well in the form of an oleosome and one-step applied to cosmetics It can be largely divided into an emulsification method for making petal-shaped cosmetic liquids (Maltese-cross) cosmetics, and they are mainly in the spotlight because they are more effective in encapsulating drugs which are relatively unstable than general emulsions or liposomes. The present inventors also used cosmetics on water-in-oil multi-emulsions using polyprotose-based polymer emulsifiers modified with a lipophilic type and a preparation method thereof (Application No. 2004-74136), a gemini system that stabilizes oil-soluble licorice and promotes transdermal absorption. Oil-based liquid crystal composition containing a surfactant and a method for producing a whitening cosmetic from the same (Application No. 2005-0009997), Skin wrinkle improvement cosmetics containing ursolic acid dissolved in a dissociation constant and Gemini-type surfactant and a method for preparing the same (Application No. 2005-0041143) has been filed. In addition to the stabilization of the drug, in terms of encapsulated usefulness and efficient skin delivery of water-soluble drugs, the structure of the liquid crystal membrane and how similar it is to the intercellular lipid components of the substances that make up the membrane are important factors in cosmetics to achieve a desirable effect. In addition, the present inventors also have a nano-size phospholipid liposome cosmetic and its preparation method (Reg. No. 0530880), nano-sized phospholipid liposome composition and co-zyme Q10 and its preparation method (Reg. No. 0553160), having a skin-like structure and composition Lipid soluble composition for promoting percutaneous absorption of active substance and method for preparing nanoparticle cosmetics using same (Application No. 2005- 0055802), Wrinkle improvement cosmetics with enhanced percutaneous absorption and stabilizing ursolic acid (Application No. 2005- 77819) has been researched and developed and registered and applied for a patent.

In general, the selection of suitable lipids is important for forming lamellae-type liquid crystals, and the polar solvent layer formed between the layers of lamellae has an important effect on the stability of the active substance and its delivery to the skin. . Conventional liquid crystal technology has a multi-layer lamellar structure similar to intercellular lipids, but the lipids are mainly composed of chemically synthesized emulsifiers and fatty acids, In terms of composition, the stability was higher than that of general emulsified products when applied to cosmetics, but it was not very effective in the skin transfer of drugs. In addition, most of them were made of water (H ₂ O) as a polar solvent layer, and many active substances, especially high polar retinol and its derivatives, coenzyme Q10, vitamin C and its derivatives, tocopherol and its derivatives, etc. When contacted with water, there is a problem that the oxidation activity is lowered, the discoloration, malodor and formulation separation occurs. In addition, when the lamellar liquid crystal is applied to the cosmetics, the process is complicated, and the stability of the cosmetics containing the unstable active substance due to the problem of contact with the water is not good. This is very demanding, often at the time of scale-up, and its scope of application is limited to high-viscosity lotions or mainly creams, making it easier to use universally, despite the many advantages of the technology. There is a problem and needs to be improved.

The present invention has been made to solve the problems of the prior art as described above to improve. Accordingly, the present inventors have endeavored to solve the above problems, and as a result of the present invention, in the development of a lamellar non-aqueous liquid crystalline capsule base, the miscibility with interstitial lipids of the skin is poor, and thus the drug delivery and skin barrier restoration are performed. It overcomes the problem of poor effect, and also uses almost water as a polar solvent, encapsulates many unstable active substances in contact with water more stably to apply to cosmetics, complex process and mainly high viscosity cream In order to extend the application limits applicable to formulations only from low-viscosity skins to high-viscosity creams and emulsified tint cosmetics, unstable drugs on contact with water do not use water unlike conventional liquid crystal technology. Encapsulated in) -type non-aqueous liquid crystal phase to stabilize the active ingredient, and this non-aqueous liquid crystal phase Designed to have a structure and composition similar to intercellular lipids, it improves miscibility with the skin, and simply stirs it when used as the concentration of the active ingredient desired in the cosmetics. Non-aqueous liquid crystalline capsule base composition, which easily obtains a cosmetic having a form, enhances skin delivery of the encapsulated active ingredient, and simultaneously restores damaged or defective skin barriers, thereby relieving symptoms of bad dryness and atopic disease, An object of the present invention is to provide a cosmetic and a method of manufacturing the same.

In general, active ingredients exhibiting various activities (moisturizing, whitening, anti-aging, etc.) in cosmetics are very high polarity, and in the case of oil-soluble active ingredients, even in the stability of the raw material itself (active titer, discoloration, deodorization) It is often unstable during storage by various factors such as light and light, and has a property of dissolving in oil, but when applied to cosmetics, its instability is rapidly promoted by interacting with water molecules (H ₂ O). In the case of the water-soluble active ingredient, the stability of the raw material itself is relatively excellent, but when dissolved in water, the stability tends to be very bad. For this reason, the polar layer of the lamellar liquid crystal (Polar layer, C) is lower than that of water to make a multi-layer, highly dense, lamellar non-aqueous liquid crystalline capsule base without using water (FIG. 1). It is possible to properly dissolve lipids and water-soluble active ingredients by using a low molecular polar solvent such as ethanol, ethylene glycol, butylene glycol, propylene glycol, hexylene glycol, glycerin, etc., except for water. . In addition, even if stabilized, the skin barrier function of the skin, that is, to prevent the substance from entering the skin from the outside, and on the contrary to prevent the substance from flowing out from the inside due to the fact that the active ingredients are not effective in penetrating the skin There is difficulty. In order to overcome this problem, Ceramide and Cholesterol, which are mainly constituting intercellular lipids of the stratum corneum of the skin, are used, and they are the main constituents of biological cell membranes. Due to its regularity, the phospholipid that is advantageous for the formation of a lamellar non-aqueous liquid crystal phase is used as the main base material, and the density of the formed lamellar non-aqueous liquid crystal phase is increased to provide a more dense structure. Encapsulating the useful and water-soluble active ingredients in numerous lipophilic (Hydrophobic, A) and hydrophilic (Hydrophilic, C) spaces, respectively, in the dense and rigid multilayer of FIG. It characterized by stabilizing by.

In addition, in the present invention, while forming the lamellar non-aqueous liquid crystalline capsule base as described above, and when applied to the cosmetics to form a stable core (Core), and excellent compatibility with the oil-soluble active ingredient (Compatibility) is a continuous phase Glyceryl trioctanoate, octyldodecyl myristate, isostearyl isostearate, dicaprylcarbonate, capric / caprylic triglycerides, isopropyl palmitate, iso The lipophilic phase of the highly dense lamellar non-aqueous liquid crystals by dissolving excess oil-soluble active ingredients in various types of ester oils and nonpolar oils such as propyl myristate, octyl palmitate, dicaprylcarbonate, neopentylene glycol diheptanoate, etc. It can be encapsulated in a space (region A). In addition, the lamellae non-aqueous liquid crystalline capsule base is dispersed in water making up most of the cosmetics to make a spherical interfacial liquid crystal to prepare the cosmetics, very simple to block the contact with the active component and water in continuous phase with simple stirring. A stable cosmetic can be obtained. In addition, it is characterized by the development of a technology that can relieve the dry skin or atopic symptoms by restoring the skin barrier by replenishing defective intercellular lipids or damaged lipid components remaining after skin transfer of the active ingredient. do.

The non-aqueous liquid crystalline capsule base composition having a skin-like film according to the present invention includes 10.0 to 60.0 parts by weight of water-soluble polar solvent, 0.1 to 10.0 parts by weight of ceramide, 0.05 to 5.0 parts by weight of cholesterol, 1.0 to 40.0 parts by weight of phospholipid, Liquid crystal lipid portion including 0.5 to 7.0 parts by weight of higher alcohol having 16 to 22 carbon atoms; Oil-soluble active substance portion comprising 0.5 to 20.0 parts by weight of oil, 0.1 to 10.0 parts by weight of oil-soluble active ingredient and 0.01 to 0.5 parts by weight of oil-soluble antioxidant; And a water-soluble active material part including 3.0 to 30.0 parts by weight of water-soluble polar solvent except for water and 0.1 to 10.0 parts by weight of water-soluble active ingredient.

In addition, the method for producing a non-aqueous liquid crystalline capsule base composition having a skin-like film according to the present invention, in preparing a base by emulsification using a conventional mixer, (1) 10.0 to 60.0 parts by weight of a water-soluble polar solvent excluding water , Liquid crystal lipids prepared by heating and dissolving 0.1 to 10.0 parts by weight of ceramide, 0.05 to 5.0 parts by weight of cholesterol, 1.0 to 40.0 parts by weight of phospholipid, and 0.5 to 7.0 parts by weight of higher alcohols having 16 to 22 carbon atoms at 75 to 85 ° C. Secondary preparation step; (2) a first cooling step of cooling the liquid crystal lipid part to 55 to 65 ° C. which is a temperature near a phase transition point; (3) 0.5 to 20.0 parts by weight of oil, 0.1 to 10.0 parts by oil-soluble active ingredient and 0.01 to 0.5 parts by weight of oil-soluble antioxidant, warmed to 50 to 60 ℃ dissolution to prepare a useful oil active material portion to prepare a useful oil active material portion; (4) preparing a water-soluble active material part for preparing a water-soluble active material part by heating and dissolving 3.0-30.0 parts by weight of a water-soluble polar solvent except water and 0.1-10.0 parts by weight of a water-soluble active ingredient at 50-60 ° C .; (5) The prepared oil-soluble active material part was prepared at 55 to 65 ° C and stirred with a conventional stirrer to prepare the liquid-crystal lipid part, and homogenized to prepare a oil-soluble active material in the lipophilic part (Hydrophobic region, A region) of the liquid crystal lipid part. Preparing a primary liquid crystal part for encapsulation; (6) The prepared water-soluble active material portion in the primary liquid crystal portion at 55 to 65 ℃ stirred with a conventional stirrer, homogenizing and swelling (Swelling) in the hydrophilic region (H region C region) of the liquid crystal lipid portion Preparing a secondary liquid crystal part encapsulating a water-soluble active material through; And (7) slowly cooling the secondary liquid crystal to 30 to 40 ° C. to solidify lipid chains, thereby making it useful for the multilayer of regular lamellar non-aqueous liquid crystal phases. And a second liquid crystal part stabilizing step of stabilizing the water-soluble active ingredients.

Hereinafter, the present invention will be described in detail.

That is, the present invention compensates for the drawbacks (that is, the active ingredient becomes unstable by water used in the liquid crystal) in the encapsulation of the liquid crystal technology, which has been in the limelight for 10 years. It has a structure very close to the skin analogue membrane, which is not the cell-like composition membrane of interest, and is similar to the components, thus making a non-aqueous liquid crystalline capsule base with a composition having excellent compatibility. This is a technique for encapsulating a drug at a high concentration of 5 times or more of the effective concentration, and to expand it to a variety of basic cosmetics, color cosmetics and the like. First, the present invention encapsulates a drug that is unstable upon contact with water in a highly dense Lamella type non-aqueous liquid crystal phase that does not use water, unlike conventional contracting techniques, to promote the stability of the active ingredient. Although the phase mainly protects the skin from foreign substances and reduces water loss, on the other hand, it is designed to have a structure and composition similar to the intercellular lipids of the stratum corneum, which is a great barrier when delivering drugs to the skin. It improves miscibility, and when it is used as the concentration of active ingredient in cosmetics, it is simply stirred to have a skin-like film structure with four petal-shaped (Maltese-cross) forms on the particle interface, so that percutaneous absorption of active substance ( In addition to promoting transepidermal absorption of drugs, it also restores the skin barrier after drug delivery and is effective for moisturizing and sensitive skin. Non-aqueous liquid phase of the liquid crystal capsules based composition, to a cosmetic preparation, and methods for their preparation using the same. The present invention is a liquid crystalline lipid containing phospholipid, ceramide, cholesterol, and higher alcohols in a polar solvent such as ethanol, ethylene glycol, butylene glycol, propylene glycol, hexylene glycol, glycerin, etc., except for water. To make a wealth, homogeneous by adding the desired oil-soluble active ingredient, oil-soluble oil solvent, and oil-soluble antioxidant mixed with the desired oil-soluble active material, and dissolving the oil-soluble active material, and homogenizing it, and heating and dissolving the polar solvent and water-soluble substance therein. High-density Lamella-type non-aqueous liquid crystal which encapsulates the material part and homogenizes it, then slowly cools it with a normal mixer and slowly cools it by encapsulating the usefulness and the water-soluble active substance in a non-aqueous amount. Obtained a phase encapsulating base so that the inside of the multilayer of the lamellar liquid crystal, that is, the carbonized water of the lipids used It consists of encapsulating the oil-soluble material in the (Hydrocarbon) section with a high concentration of the water-soluble material in a plurality of polar solvent layers formed between these multilayers, and when added to the cosmetics, there is a 'water layer' between the multiple layers. Rather, water exists only in the trauma, which is a continuous phase, so that the active ingredients encapsulated inside are blocked from contacting with water, so the stability is very excellent, and the development of technology that can easily apply the skin-like film liquid crystal technology without a special device It is done.

In describing the configuration of the present invention, repeated description of the same technical configuration and operation as in the prior art will be omitted. In addition, unless there is another definition in the technical terms and scientific terms used herein, it has a meaning commonly understood by those of ordinary skill in the art.

Without using water according to the present invention, a lamella-type non-aqueous liquid crystalline capsule base composition capable of stably encapsulating a water-soluble and oil-soluble drug while having a structure and composition similar to that of skin, has a water-soluble polar solvent 10.0 to 60.0 weight except water A liquid crystal lipid portion including 0.1 to 10.0 parts by weight of ceramide, 0.05 to 5.0 parts by weight of cholesterol, 1.0 to 40.0 parts by weight of phospholipid, and 0.5 to 7.0 parts by weight of higher alcohol having 16 to 22 carbon atoms; Oil-soluble active substance portion comprising 0.5 to 20.0 parts by weight of oil, 0.1 to 10.0 parts by weight of oil-soluble active ingredient and 0.01 to 0.5 parts by weight of oil-soluble antioxidant; And a water-soluble active material portion including 3.0 to 30.0 parts by weight of water-soluble polar solvent and 0.1 to 10.0 parts by weight of water-soluble active ingredient except for water.

The water soluble polar solvent constituting the liquid crystal lipid part is a water soluble polar solvent excluding water, and completely dissolves lipids forming a liquid crystal which is very important in the non-aqueous liquid crystalline capsule base composition having the skin-like film of the present invention, thereby providing a uniform and stable liquid crystal. It is an important material for forming and stabilizing the water-soluble active material in the liquid crystalline capsule base to prevent oxidation, it can be understood to be commonly used in the art as materials with high polarity and low molecular weight. The water-soluble polar solvent is preferably ethylene glycol, butylene glycol, propylene glycol, hexylene glycol, glycerin, 1,2-pentanediol, D-panthenol, dipropylene glycol, diglycerin, diethoxyethyl succinate and It may be selected from the group consisting of two or more of these mixtures. It can be used suitably for the amount of lipids used above. When the water-soluble polar solvent is used in less than 10 parts by weight, after dissolution of the used lipids and liquid crystal formation, there is a problem that the desorption of the lipids occur, if the amount exceeds 60 parts by weight of the polar layer (Polar layer) There is a problem in the stability of the encapsulated drug when applied to the actual cosmetics because the volume is excessively large.

The ceramide constituting the liquid crystal lipid is a main component of the intercellular lipid of the skin, and the non-aqueous liquid crystal has similarity with the skin and plays an important role in delivering water-soluble and oil-soluble active ingredients to the skin and restoring the damaged skin barrier. When the ceramide is used in less than 0.1 parts by weight, there is a problem in that the similarity of the composition and structure between the intercellular lipid and too large, there is a problem that the effect of delivering the drug to the skin, or restore the damaged skin barrier is insignificant On the contrary, if it exceeds 10 parts by weight, there may be a problem in that it is virtually impossible to dissolve with polar solvents and phospholipids, so that the undissolved ones recrystallize.

Cholesterol, which constitutes the liquid crystal lipid portion, imparts membrane fluidity to liquid crystals formed of hard lipids such as ceramide and phospholipid to help the formation of liquid crystal, and also constitutes a major component of intercellular lipid such as ceramide. As the non-aqueous liquid crystal has a similarity with the skin plays an important role in delivering the active ingredient to the skin. When the cholesterol is used in less than 0.05 parts by weight, there may be a problem that the drug delivery is not as smooth as in the case of ceramide, on the contrary, if it exceeds 5 parts by weight, in fact an irregular and bulky structure of cholesterol itself Therefore, there may be a problem in that the density of the liquid crystal is impaired and the stability of the liquid crystal is inhibited.

The ceramide and cholesterol are materials commonly used in the art.

Phospholipid constituting the liquid crystal lipid portion is a material in which a highly polar functional group, such as one phosphate group, and two fatty acids having various chain lengths and chain structures are combined, and have unique multi-orientation characteristics. It is easy to form a dense lamellar (Lamella) type liquid crystal phase, and has excellent compatibility with ceramides, cholesterol and fatty acids, which are important intercellular lipids for drug delivery and skin barrier.

The phospholipid can be used in both saturated and unsaturated type, and the phospholipid is preferably phosphatidylcholin, phosphadidylethanolamine, phosphatidyl inositol, or phosphatidylserine. It may be selected from the group consisting of (Phosphatidylserine) and mixtures of two or more thereof, and more preferably 16 to 30 chain lengths of fatty acids attached to the above-mentioned phosphate group. If the chain length of fatty acids is less than 16, the chain is too short to form a highly dense lamellar non-aqueous liquid crystalline phase. On the contrary, if more than 30 chains are used, the length of the fatty acid is important for liquid crystal formation. There may be problems with regular orientation. In addition, when the phospholipid is used in less than 1 part by weight, there may be a problem that the liquid crystal formation is not good enough to form a lamellar liquid crystal phase, if the amount exceeds 40 parts by weight, there is a problem in dissolving And, too dense there may be a problem that the active ingredient is rather difficult to encapsulate.

The higher alcohol having 16 to 22 carbon atoms constituting the liquid crystal lipid part functions as a material for improving the regularity and density of the liquid crystal in the present invention which does not use water with a unique orientation regularity. May be selected from the group consisting of cetyl alcohol, cetearyl alcohol, stearyl alcohol, behenyl alcohol, batyl alcohol and mixtures of two or more thereof commonly used in the art. Therefore, the capsule-based composition made by the present technology, when applied to cosmetics, in which most of the continuous phase is composed of 'water', the interfacial membrane is very solid like the intercellular lipid of the skin, so that the useful and water-soluble active ingredients encapsulated inside It improves stability by avoiding contact with water molecules in the continuous phase, and also has excellent affinity for intercellular lipids and excellent drug delivery effect, and also improves skin barrier function by replenishing intercellular lipids after drug delivery. You can get the effect. When the higher alcohol is used in less than 0.5 parts by weight, there may be a problem that the above-mentioned effects are insignificant, on the contrary, if the higher alcohol exceeds 7 parts by weight, there may be a problem that the higher alcohol itself is crystallized and detached.

The oil constituting the oil-soluble active material portion is a polar or non-polar oil, and is excellent in dissolution of oil-soluble active ingredients and compatibility with the lipophilic portion of the liquid crystal lipid portion, and acts as a base to facilitate loading in the liquid crystal. The oil may be used in an amount of 0.5 to 20.0 parts by weight in a range that does not interfere with the formation of a highly dense lamellar non-aqueous liquid crystalline phase according to the amount of the oil-soluble active ingredient, and is a non-polar oil including animal and vegetable squalane, mineral oil, isohexadecane; Glyceryl trioctanoate, octyldodecyl myristate, isostearyl isostearate, dicapryl carbonate, neopentylene glycol diheptanoate, cetearyl isonanoate, cetearyl octanoate as polar oils , Capric / caprylic triglyceride, isopropyl palmitate, isopropyl myristate, octyl palmitate or a mixture of two or more thereof. If the oil is used in less than 0.5 parts by weight, there may be a problem in dissolving the oil-soluble active ingredient, on the contrary, when used in excess of 20 parts by weight, the formation of an excessive lipophilic layer in the non-aqueous liquid crystal (Lipophilic layer) There may be a problem in that the oil-soluble active ingredient is detached over time and its stability deteriorates.

The oil-soluble active ingredient constituting the oil-soluble active substance part is oil-soluble, Idebenone, coenzyme Q10, tocopherol and its derivatives, vitamin C oil-soluble derivatives, retinol having excellent effects such as whitening, wrinkles, anti-aging ) And derivatives thereof, oleanolic acid, ursolic acid, diacetyl boldine, oil soluble caviar extract, oil soluble licorice extract, or a mixture of two or more thereof. According to the activity and solubility of each substance, the content can be determined and used. The above range is an example applied in the range in which solubility and efficacy of these physiologically active ingredients can be exerted, and the present invention is limited to the above range. It is not content. Especially preferably, the oil-soluble active ingredient may be used in an amount of 0.1 to 10 parts by weight. When the oil-soluble active ingredient is used in less than 0.1 part by weight, not only the liquid crystal itself due to the low concentration, there may be a problem that can not obtain a desirable skin improvement effect when applied to the cosmetic, on the contrary is used in excess of 10 parts by weight In this case, the liquid crystal structure may be destroyed to stably encapsulate in the non-aqueous liquid crystal, and may be difficult to apply to the cosmetic.

Antioxidant constituting the oil-soluble active substance portion, including the oil-soluble active ingredient and other water-soluble active ingredients contained in the oil-soluble active substance portion to prevent oxidation of the entire capsule base composition according to the present invention, in particular, to maintain the activity of the active ingredient for a long time And increase the storage stability of the product. The antioxidant may be selected from the group consisting of tocopherol and its derivatives, butylated hydroxytoluene, benzophenones, octylmethoxycinnamate, octylsalicylate or mixtures of two or more thereof. However, the antioxidant is not limited to those mentioned above, and it will be obvious to those skilled in the art that an appropriate antioxidant can be purchased or obtained. The antioxidant may preferably be used in an amount of 0.01 to 0.5 parts by weight. When the antioxidant is used in less than 0.01 parts by weight, when preparing the non-aqueous liquid crystal, there may be a problem that can lose its active titer in the heating process, on the contrary when used in excess of 0.5 parts by weight, rather excessive use There may be a problem of discoloration and odor.

The water-soluble active ingredient constituting the water-soluble active substance part is encapsulated and stabilized in the hydrophilic part in the liquid crystal phase, and also has excellent effects such as adenosine, arbutin, vitamin C and its hydrophilic derivatives, vitamin B3, Various hydrophilic vitamins such as vitamin B5 and vitamin H and derivatives thereof, kojic acid and derivatives thereof, acetylglucosamine, yeast extract, water-soluble caviar extract, centella asiatica extract including madecassoside, selenium aspartate, It can be used in the group consisting of various peptide components obtained through various plant extracts and cell cultures or mixtures of two or more thereof, and can be used by setting the content according to the activity and solubility of each substance, and the above range is Examples of applied in the range of solubility and efficacy of the bioactive components , Is not the case of using the present description being limited to the above range. Especially preferably, the water-soluble active ingredient may be used in an amount of 0.1 to 10 parts by weight. When the water-soluble active ingredient is used in less than 0.1 part by weight, not only the liquid crystal itself due to the low concentration, there may be a problem that can not obtain a desirable skin improvement effect when applied to the cosmetics, on the contrary more than 10 parts by weight In this case, the liquid crystal structure may be destroyed to stably encapsulate in the non-aqueous liquid crystal, and may be difficult to apply to the cosmetic.

The water-soluble polar solvent constituting the water-soluble active material portion is the same or similar to the water-soluble polar solvent described in the liquid crystal lipid portion.

In addition, the method for producing a lamellar non-aqueous liquid crystalline capsule base according to the present invention, in preparing the base by emulsification using a conventional mixer, (1) 10.0 to 60.0 parts by weight of water-soluble polar solvent except water, ceramide 0.1 To 10.0 parts by weight, cholesterol 0.05 to 5.0 parts by weight, phospholipids 1.0 to 40.0 parts by weight and 0.5 to 7.0 parts by weight of higher alcohol having 16 to 22 carbon atoms heated to 75 to 85 ℃ dissolved to prepare a liquid crystal lipid part ; (2) a first cooling step of cooling the liquid crystal lipid part to 55 to 65 ° C. which is a temperature near a phase transition point; (3) 0.5 to 20.0 parts by weight of oil, 0.1 to 10.0 parts by oil-soluble active ingredient and 0.01 to 0.5 parts by weight of oil-soluble antioxidant, warmed to 50 to 60 ℃ dissolution to prepare a useful oil active material portion to prepare a useful oil active material portion; (4) preparing a water-soluble active material part for preparing a water-soluble active material part by heating and dissolving 3.0-30.0 parts by weight of a water-soluble polar solvent except water and 0.1-10.0 parts by weight of a water-soluble active ingredient at 50-60 ° C .; (5) The prepared oil-soluble active material part was prepared at 55 to 65 ° C. in the prepared liquid crystal lipid part, stirred with a conventional stirrer, and homogenized to encapsulate the oil-soluble active material in the lipophilic part (Hydrophobic region, A region) of the liquid crystal lipid part. Preparing a primary liquid crystal unit; (6) The prepared water-soluble active material portion in the primary liquid crystal portion at 55 to 65 ℃ stirred with a conventional stirrer, homogenizing and swelling (Swelling) in the hydrophilic region (H region C region) of the liquid crystal lipid portion Preparing a secondary liquid crystal part encapsulating a water-soluble active material through; And (7) gradually cooling the secondary liquid crystal part to 30 to 40 ° C. to solidify the lipid chains to a multilayer of a regular lamellar non-aqueous liquid crystal phase. And a secondary liquid crystal stabilization step of stabilizing the usefulness and water-soluble active ingredients.

Preparation step of the liquid crystal lipid part of (1) is 10.0 to 60.0 parts by weight of water-soluble polar solvent except water, 0.1 to 10.0 parts by weight of ceramide, 0.05 to 5.0 parts by weight of cholesterol, 1.0 to 40.0 parts by weight of phospholipid and 16 to 22 carbon atoms 0.5-7.0 parts by weight of alcohol is dissolved by heating to 75-85 ° C. If the heating temperature is less than 75 ℃, there may be a problem that the dissolution of the lipids of the liquid crystal lipid portion used is not easy, on the contrary, if it exceeds 85 ℃, causing the discoloration and odor caused by oxidation of the lipids There may be a problem.

The primary cooling step of (2) consists of cooling the liquid crystal lipid part to 55 to 65 ° C. which is a temperature near the phase transition point. In the case where the cooling temperature is less than 55 ℃, there may be a problem that the liquid crystal structure is irregular by excessive cooling below the phase transition point, on the contrary, if it exceeds 65 ℃, there may be a problem that the even lipid orientation even by insufficient stirring. have.

The oil-soluble active substance preparation step of (3) comprises 0.5 to 20.0 parts by weight of oil, 0.1 to 10.0 parts by weight of oil-soluble active ingredient, and 0.01 to 0.5 parts by weight of oil-soluble antioxidant to be dissolved by heating to 50 to 60 ° C.

The water-soluble active material part preparation step of (4) consists of dissolving 3.0-30.0 parts by weight of water-soluble polar solvent except water and 0.1-10.0 parts by weight of water-soluble active ingredient at 50 to 60 ° C.

When the heating temperature is less than 50 ° C. in the step of preparing the oil-soluble active material part of step (3) and the step of preparing the water-soluble active material part of step (4), there may be a problem in that the active material is not dissolved well, on the contrary, 60 ° If it exceeds, there may be a problem that the activity of the active material is inhibited by excessive heating.

In the preparing of the primary liquid crystal part of (5), the prepared oil-soluble active material part is added to the prepared liquid crystal lipid part at 55 to 65 ° C., stirred with a conventional stirrer, and homogenized to form a lipophilic part of the liquid crystal lipid part (Hydrophobic region, Encapsulating the oil soluble active substance in region A).

In the preparing of the secondary liquid crystal part of (6), the prepared water-soluble active material part is added to the primary liquid crystal part at 55 to 65 ° C., stirred with a conventional stirrer, and homogenized to form a hydrophilic part of the liquid crystal lipid part (Hydrophilic region, Encapsulating the water-soluble active substance through swelling in the C region.

The preparation of the primary liquid crystal part of (5) and the preparation of the secondary liquid crystal part of (6) are preferably performed at a temperature range of 55 to 65 ° C., which is shown in FIG. 6 of the differential scanning calorimeter (DSC) As shown in the analysis results, the temperature is slightly higher than the phase transition temperature and is added at 55 to 65 ° C in accordance with the solubility of the active ingredient, and at a temperature lower than the above-mentioned temperature, the active ingredient is difficult to stabilize smoothly into the liquid crystal. There may be a problem that the stability itself of the active ingredient deteriorates with high temperature at a temperature higher than the above-mentioned temperature.

In addition, in the stabilizing step of the secondary liquid crystal part of (7), the secondary liquid crystal part is gradually cooled to 30 to 40 ° C. to solidify lipid chains, thereby regular lamellar non-aqueous liquid crystal phase. It consists in stabilizing the oil soluble and water soluble active ingredients in a multi-layer. In the final cooling and stabilization of the secondary liquid crystal part, the cooling temperature is gradually cooled, but stabilized by cooling to 30 to 40 ° C. according to the amount of lipid used and the chain solidification temperature according to the active material. If cooling below the temperature, there may be a problem that the already solidified chains are deformed by shear stress and impair the stability, and when the cooling is terminated beyond the above-mentioned temperature, the solidification of the chains is not sufficiently achieved, so that the active Some of the material may be detached and there may also be a problem that the stability of the formulation is reduced.

Non-aqueous liquid crystalline capsule base composition having a skin-like film obtained according to the present invention as described above,

1) Most active substances with high polarity are unstable when in contact with water, causing problems such as discoloration, odor, and lowering of the titre, which can make it difficult to apply to cosmetics. In the preparation of cosmetics by dispersing in a large part of the water to make a spherical interfacial liquid crystal, a very simple cosmetic can be obtained with a simple stirring to block the contact between the active ingredient and continuous water.

2) Because the liquid crystal phase is important for drug delivery, the structure and composition of intercellular lipids are similar, which can improve drug delivery efficiency with high affinity.

3) It is easy and stable to various cosmetics because lipid components remaining after skin transfer of active ingredient are damaged or replenishing defective intercellular lipids to restore skin barrier and alleviate bad dryness or atopic symptoms. It is a useful technique to apply.

Hereinafter, preferred embodiments and comparative examples of the present invention will be described.

The following examples are intended to illustrate the invention and should not be understood as limiting the scope of the invention.

Example  1 to 3 and Comparative example  1 to 8

To prepare a non-aqueous liquid crystalline capsule base composition having a skin-like film according to the invention in the composition shown in Table 1 and Table 2, the preparation method is as follows.

In a separate dissolution tank, the liquid crystal lipid part was added to the contents shown in Tables 1 and 2 below, warmed to 78 ° C., dissolved, and then cooled to 60 ° C. in a primary manner. The material part was prepared by heating to 58 ° C. to dissolve it, and preparing a water-soluble active material part by adding the water-soluble active material part to a content shown in Table 1 in a separate dissolution bath to dissolve by heating to 60 ° C. The prepared oil-soluble active material was added to the dissolution tank containing the liquid crystal lipid at 60 ° C. and stirred for 10 minutes at a speed of 1,000 rpm using an agitator to make the primary liquid crystal part, while maintaining the temperature at 60 ° C. again. The prepared water-soluble active material part was added and stirred for 10 minutes at a speed of 1,000 rpm using an agitator to make a secondary liquid crystal part. The paddle is slowly cooled to 10 ° C while slowly rotating to stabilize the paddle, thereby loading the oil-soluble active ingredients into the lipophilic part of the liquid crystal and loading the water-soluble active ingredients through the swelling process of the hydrophilic part of the liquid crystal. An aqueous liquid crystalline capsule base composition was obtained.

As a result of observing the obtained non-aqueous liquid crystalline capsule base composition using a polarizing microscope capable of observing the liquid crystal, the density of the liquid crystal was different, but sheet-like light emission due to the birefringence of the lamellar liquid crystal was shown in FIG. As can be confirmed, the electron transmission microscopy of the more detailed structure was able to confirm the lamellar liquid crystal of the multilayer as shown in FIG.

division Ingredients (parts by weight) Example 1 Example 2 Example 3 Comparative Example 1 Comparative Example 2 Comparative Example 3 Comparative Example 4 LCD Propylene glycol 47.95 48.75 47.95 60.45 52.85 38.95 42.95 Ceramide 3.0 3.0 3.0 3.0 0.05 12.0 3.0 cholesterol 2.0 2.0 2.0 2.0 0.01 2.0 7.0 Phospholipids 13.0 13.0 13.0 0.5 13.0 13.0 13.0 Cetearyl Alcohol 2.0 2.0 2.0 2.0 2.0 2.0 2.0 Soluble Active Substance Isostearyl isostearate 6.0 6.0 7.0 7.0 7.0 7.0 7.0 Idebenon 4.0 - - - - - - Coenzyme Q10 - 5.0 - - - - - Retinol - - 3.0 3.0 3.0 3.0 3.0 Oil-soluble antioxidants 0.05 0.05 0.05 0.05 0.05 0.05 0.05 Water soluble active substance Propylene glycol 20.0 20.0 20.0 20.0 20.0 20.0 20.0 Adenosine - 0.2 - - - - - Vitamin c 2.0 - 2.0 2.0 2.0 2.0 2.0 Properties Hardness 56 74 50 10 34 110 14 Liquid crystal formation ◎, 3 ◎, 4 ◎, 3 ×, 1 ◎, 3 ◎, 4 ×, 1 1) propylene glycol; Dowcorning, USA 2) Ceramides; DS-CERAMIDE, Republic of Korea, Doosan Biotech 3) Cholesterol; Cholesterol NF, United States, Solvay 4) Phospholipids: Lecinol (Lecinol S-10, Japan, Nikko Chemical), Lipoid S75-3, Lipoid S100-3, Lipoid S75, Lipoid S100 , Germany, Lipoid company), Emulmetic 920, 930, 950, France, Lucas meyer company 5) Cetearyl alcohol: Lanette O (cetanol: stearyl alcohol = 55: 45), Germany, Cognis 6) Isostearyl isostearate: France, Gattefosse 7) Idebenone: Idebenone, Taiwan 8) Coenzyme Q10: German Carden 9) Retinol : RETINOL 50C, Germany, BASF 10) Antioxidant 1: Dibutyl hydroxytoluene, Japan, Ueno 11) Adenosine: China, World best 12) Vitamin C: Roche, Germany Liquid crystal formation degree: 1) Density: ◎ (very dense), ○ (dense), △ (not dense), × (not very dense) 2) Uniformity: 4 (very uniform), 3 (uniform), 2 (Not uniform), 1 (not very uniform)

division Ingredients (parts by weight) Comparative Example 5 Comparative Example 6 Comparative Example 7 Comparative Example 8 LCD Propylene glycol 49.85 40.95 47.95 47.95 Ceramide 3.0 3.0 3.0 3.0 cholesterol 2.0 2.0 2.0 2.0 Phospholipids 13.0 13.0 13.0 13.0 Cetearyl Alcohol 0.1 9.0 2.0 2.0 Soluble Active Substance Isostearyl isostearate 7.0 7.0 7.0 7.0 Idebenon - - - - Coenzyme Q10 - - - - Retinol 3.0 3.0 3.0 3.0 Oil-soluble antioxidants 0.05 0.05 0.05 0.05 Water soluble active substance Propylene glycol 20.0 20.0 20.0 20.0 Adenosine - - - - Vitamin c 2.0 2.0 2.0 2.0 Properties Hardness 28 300 30 36 Liquid crystal formation ○, 3 ◎, 4 ○, 3 ○, 2 1) propylene glycol; Dowcorning, USA 2) Ceramides; DS-CERAMIDE, Republic of Korea, Doosan Biotech 3) Cholesterol; Cholesterol NF, United States, Solvay 4) Phospholipids: Lecinol (Lecinol S-10, Japan, Nikko Chemical), Lipoid S75-3, Lipoid S100-3, Lipoid S75, Lipoid S100 , Germany, Lipoid company), Emulmetic 920, 930, 950, France, Lucas meyer company 5) Cetearyl alcohol: Lanette O (cetanol: stearyl alcohol = 55: 45), Germany, Cognis 6) Isostearyl isostearate: France, Gattefosse 7) Idebenone: Idebenone, Taiwan 8) Coenzyme Q10: German Carden 9) Retinol : RETINOL 50C, Germany, BASF 10) Antioxidant 1: Dibutyl hydroxytoluene, Japan, Ueno 11) Adenosine: China, World best 12) Vitamin C: Roche, Germany Liquid crystal formation degree: 1) Density: ◎ (very dense), ○ (dense), △ (not dense), × (not very dense) 2) Uniformity: 4 (very uniform), 3 (uniform), 2 (Not uniform), 1 (not very uniform)

The following facts could be confirmed from Table 1 and Table 2 and the analysis results of FIGS. 3, 4, 5 and 6.

In Examples 1 to 3, as shown in FIG. 3, the oil-soluble and water-soluble active ingredients were confirmed to have high density sheet type Lamellar type liquid crystal phases, and thus, all of them had good results in terms of liquid crystal phase uniformity. As a result of observing the microstructure at a further magnification in FIG. 4, the density, that is, the thickness of the liquid crystal was excellent in the order of Example 2> Example 1> Example 3, and the encapsulating material also affected liquid crystal formation. I could see that. In addition, in Examples 1 to 3, the stability of the liquid crystal itself was also 45 ° C. (high temperature), 5 ° C. (low temperature), temperature cycling (circulating temperature −5 (6 hours), 0 ° C. (6 hours), 25 ° C. (6). It was confirmed that good results were obtained for three months at all the temperatures of 3 hours), 40 ° C. (6 hours), and 25 ° C. (room temperature), and the formation of dense and uniform liquid crystals significantly affected the stability of the liquid crystal itself.

However, when the phospholipid is less than the above-mentioned content, respectively, as in Comparative Example 1, the density and uniformity were very poor, and thus it was difficult to see a lamellae liquid crystal. On the contrary, as in Comparative Examples 3 and 4, the ceramide and cholesterol contents were the same. When used in excess of the above-mentioned amount, Comparative Example 3 had good density and uniformity, but did not dissolve completely, and ceramide was recrystallized and precipitated within one week at all storage temperatures, and Comparative Example 4 had cholesterol as mentioned above. Due to its bulky and irregular molecular structure, this branch had very poor density and uniformity, virtually no liquid crystal formation, and very poor stability as in Comparative Example 3. When the cetearyl alcohol is less than the above-mentioned content as in Comparative Example 5, a relatively dense and uniform liquid crystal was obtained, but 45 ° C and temperature circulation (circulation temperature -5 (6 hours), 0 ° C. (6 hours), 25 ° C. (6 hours), 40 ° C. (6 hours) stability had a problem that the stability deteriorated in 2 weeks, on the contrary, in the case of exceeding the above-mentioned content as in Comparative Example 6 , The liquid crystal was excellent in the compactness and uniformity of the liquid crystal, but the liquid crystal was good, but the loaded retinol and vitamin C oozed out in one day at all storage temperature, there was a problem in stabilizing the active ingredients. In addition, even if manufactured to the above-mentioned content, when the temperature of the oil-soluble active material portion and the water-soluble active material portion to the liquid crystal lipid is lower than the above-mentioned temperature as in Comparative Example 7, the uniformity of the liquid crystal is similar, but the density and hardness are inferior When the active ingredients were slightly phase-separated in one week at a high temperature of 45 ° C., and the cooling temperature for stabilizing the liquid crystal formed by secondary cooling as in Comparative Example 8 is lower than the above-mentioned temperature, the density and uniformity of the liquid crystals. In addition, high hardness, such as 45 ℃ due to the drop in both hardness, there was a problem that the stability worsens in the circulation conditions with temperature changes.

When the Examples and Comparative Examples shown in Tables 1 and 2 above are applied to the actual cosmetics, sheet-like lamellar liquid crystal phases are formed as spherical interfacial liquid crystals in the shape of petals (crosses) and encapsulated in the usefulness and water-soluble activity. To determine the degree of stability of the components, 10.0% by weight of each of them was added to 90.0% by weight of water, and by simple stirring, cosmetics (Sample 1 = Example 1 use, Sample 2 = Example 2 use, Sample 3 = Example 3 Use, Sample 4 = Comparative Example 1 Use, Sample 5 = Comparative Example 2 Use, Sample 6 = Comparative Example 3 Use, Sample 7 = Comparative Example 4 Use, Sample 8 = Comparative Example 5 Use, Sample 9 = Comparative Example 6 use, sample 10 = use of Comparative Example 7, sample 11 = use of Comparative Example 8) and the results of the stability observed are shown in Table 3. For the results shown in Table 3, the stability was visually determined by observing the particles with a polarizing microscope (Olympus BX51, Japan, 1,000 times magnification), and the photograph of Sample 2 using Example 2 is shown in FIG. 3.

sample Sample 1 Sample 2 Sample 3 Sample 4 Sample 5 Sample 6 Sample 7 Sample 8 Sample 9 Sample 10 Sample 11 pfi ◎ ◎ ◎ × ◎ ○ × △ ○ △ × pf2 ○ ◎ ○ Prize ○ Prize Prize × Prize × Prize psi 1-2 1-2 1-2 5-20 1-2 3-15 2-10 2-3 3-20 2-3 2-3 ps2 3-4 3-5 3-4 - 3-5 - - 5-20 - 5-20 - pfi; Initial particle formation pf2; Particle formation after 2 months (45 ° C.) psi; Initial particle size (µm) ps2; Particle size (μm) after 2 months (45 ℃) Particle formation; ◎ (uniform multi-layer), ○ (non-uniform multi-layer), △ (uniform single-layer), × (uniform single-layer) phase (phase separation), re (retinol separation)

As shown in the results of Table 3, in order to apply the non-aqueous liquid crystalline capsule-based composition having the skin-like film of the present invention to the base and the color cosmetic which is a continuous phase of water, as in Examples 1 to 3, Density and uniformity are very important, and if the density and uniformity of the initial liquid crystal are poor as in Samples 4 and 7 to which Comparative Examples 1 and 4 are applied, phase separation occurs within two weeks at room temperature within one week at 45 ° C. However, even though the application of cosmetics was not appropriate and the density and uniformity of the liquid crystals were good as in Samples 6 and 9 to which Comparative Examples 3 and 6 were applied, when too much ceramide or higher alcohol was used as shown in FIG. It was confirmed that the crystals were detached and phase separation occurred in one week at 45 ° C., but at about one month at room temperature, resulting in poor stability. In addition, when the ceramide and cholesterol, which acts as if it were an adhesive, such as Sample 5 to which Comparative Example 2 was applied, the stability was relatively good even when observed for 2 months at 45 ° C. However, Sample 8 to which Comparative Example 5 was applied did not form petal-like multilayers when the higher alcohols added to the regularity of the liquid crystal were not formed, polarization was not confirmed, and a single layer was confirmed by a general microscope. Retinol was also detected in the naked eye was confirmed that the stability was not good. Finally, in the case of Samples 10 and 11 to which Comparative Examples 7 and 8 were applied, the same composition as in Example 3 was prepared, but when the above-mentioned active ingredient input temperature and liquid crystal stabilization cooling temperature were not suitable, petal-like multi-film formation was formed. It did not become, it was confirmed that the high temperature stability is not good.

In addition to the stability of the above-mentioned formulations and in particular, the potency integrity of the active ingredient “retinol”, which is unstable when contacted with water, was found in the case of samples 4, 6, 7, 9, and 11 in which phase separation occurred in Table 2. Compared to the initial dose, it was very unstable due to the potency integrity of almost 30% after 2 months at 45 ° C and less than 60% at room temperature. Even though the particles were relatively uniform as shown in Samples 8 and 10, even when multiple films were not formed Similarly, after 2 months at 45 ° C, 37% and 42% of each initial dose and 70% and 65% at room temperature were poor. However, in the case of Sample 3, the multilayer was thinned after 2 months, but was maintained at 93% after 2 months at 45 ° C, and was maintained at 94% after 12 months at room temperature. Blocking was found to be very helpful for retinol stability. The results also showed better titer integrity than retinol in Idebenone of Sample 1 and Coenzyme Q10 of Sample 2, and vitamin C and adenosine, which are used as water-soluble active ingredients, also showed high potency retention of more than 90%. In addition, Example 3 of Table 1 and Table 2, obtained in the samples 3, 5, 10, 11 applying the same composition as Comparative Example 2 and Example 3, the stability was good, but the process was not suitable When the applied cosmetics were actually applied to the skin, the transdermal absorption of the retinol and vitamin C used was checked. Percutaneous absorption, which shows the skin penetration effect of each active ingredient, was measured by dissolution tester (ERWEKA DT800 Dissolution Tester, Germany) in the same amount of 0.1g of samples prepared from samples 3, 5, 10, and 11 (65 years old male, Hans Biomed) was placed in an Enhancer cell (ERWEKA, Germany), filled with 500 ml of pH 7.0 buffer solution with sodium chloride, and the temperature was changed to 37 ° C, similar to the actual human body temperature. The elution amount of each oil-soluble active ingredient was periodically monitored for 12 hours using high performance liquid chromatography (HPLC, Japan, Shimadzu, LC-10VP). As a result, the elution amount of each oil-soluble active substance was measured after about 12 hours, respectively.

When the elution amount of the active ingredient and the elution amount curve with time elapsed after 12 hours of FIG. 8, the elution pattern (Pattern) and the amount of elution were different depending on the usefulness or the type of water solubility. Samples 3 and 5, which formed multi-layered petal-shaped films, showed relatively good elution amount, but had similar structural structure by forming lamellar liquid crystals similar to intercellular lipids, and at the same time, similarity of the composition using phospholipids, ceramides and cholesterol. In the case of sample 3 having a high elution amount of 97% and 94.1% of the initial dose for retinol and vitamin C after 12 hours, the result was very good, and formed a structure similar to the intercellular lipid, but ceramide, In case of different composition due to lack of cholesterol, the amount of elution was relatively low at 64.3% and 57.6%, respectively. In addition, samples 10 and 11, which are similar in composition to the intercellular lipids, but whose structure does not form a lamellar liquid crystal phase, are similar to sample 5, with 59.7%, respectively, for retinol and vitamin C. 56.1%, Sample 11 was 57.2%, 50.3% was low.

Therefore, as mentioned above, the non-aqueous liquid crystalline capsule base of the present invention can encapsulate an unstable high concentration of oil-soluble and water-soluble active ingredients in a highly dense lamellar liquid crystal phase, and when applied to a cosmetic in which the continuous phase is an aqueous phase, about 1 to 3 It forms a uniform petal-shaped interfacial liquid crystal phase of μm, and since water is not present inside the interfacial liquid crystal phase, it is very useful for stabilizing an unstable drug upon contact with water, and the interfacial liquid crystal has a structure and composition similar to that of skin. It was confirmed that this technique is also useful for delivering a stabilized drug to the skin to exhibit efficacy as a desirable cosmetic.

Finally, transepidermal water loss (TE) is used to determine how the barrier function of the skin is improved by ceramide and cholesterol that are oriented on the skin or intercellular lipid after delivery of the drug. Was measured for 9 hours using a TEWAMETER (CK electronics, Germany), and the result obtained is shown in FIG. As shown in Figure 9, after the application of the general cream, the amount of transdermal moisture evaporation was reduced by about 10%, and there was some effect, in comparison, when applying the cosmetics obtained from the sample 2 to approximately 35% of the present invention Non-aqueous liquid crystalline capsule base of skin-like composition was found to be a very effective technique for stabilizing the substance and transferring the active ingredient to the skin and restoring damaged skin barrier.

Therefore, according to the present invention, the present invention is very dense and uniform multilayer using only polar solvents except water for active ingredients that are effective for whitening, wrinkle improvement and anti-aging, which are rapidly unstable due to high polarity when contacted with water. Encapsulated in a non-aqueous liquid crystal phase having a lamellae type dense structure with high concentration, it can be easily applied by simple stirring without special equipment, and the conventional water is used as a technology for extending the scope of application to the base and color cosmetics consisting of water in a continuous phase. Unlike liquid crystals, the lamellar layer and the layer are composed of a solvent, not water, so that the liquid crystal itself has excellent potency preservation of the active ingredient. Since there is no water between the layers, the stability of active substances in cosmetics is excellent. And it may be line. In addition to having a multi-layered structure similar to the skin, it is very similar to the components of intercellular lipids, which are important points for drug penetration, and delivers both useful and water-soluble active ingredients to the skin to obtain a desired skin improvement effect. It is useful, and after the skin penetration of the active ingredient, orientation to damaged or incomplete intercellular lipids with the help of phospholipids used with ceramide and cholesterol, restores the skin barrier function to moisturize and sensitive skin It can be expected to give a differentiating effect to improvement.

Although the present invention has been described in detail only with respect to the described embodiments, it will be apparent to those skilled in the art that various modifications and changes are possible within the technical spirit of the present invention, and such modifications and modifications belong to the appended claims. .

Claims (9)

Group consisting of ethylene glycol, butylene glycol, propylene glycol, hexylene glycol, glycerin, 1,2-pentanediol, D-panthenol, dipropylene glycol, diglycerin, diethoxyethyl succinate, or a mixture of two or more thereof 10.0 to 60.0 parts by weight of a water-soluble polar solvent, 0.1 to 10.0 parts by weight of ceramide, 0.05 to 5.0 parts by weight of cholesterol, 1.0 to 40.0 parts by weight of phospholipids having 16 to 30 chain lengths of fatty acids, and 0.5 to higher alcohols having 16 to 22 carbon atoms. Liquid crystal lipid portion including 7.0 parts by weight; Animal and vegetable squalane, mineral oil, isohexadecane, glyceryl trioctanoate, octyldodecyl myristate, isostearyl isostearate, dicaprylcarbonate, neopentylene glycol diheptanoate, cetearyl isonanono 0.5 to 20.0 parts by weight of oil selected from the group consisting of eight, cetearyloctanoate, capric / caprylic triglyceride, isopropyl palmitate, isopropyl myristate and octyl palmitate or mixtures of two or more thereof 0.01-10.0 parts by weight of active ingredient and oil-soluble antioxidant selected from the group consisting of tocopherol and its derivatives, butylated hydroxytoluene, benzophenones, octylmethoxycinnamate, octylsalicylate or mixtures of two or more thereof Oil-soluble active substance portion comprising 0.5 parts by weight; And ethylene glycol, butylene glycol, propylene glycol, hexylene glycol, glycerin, 1,2-pentanediol, D-panthenol, dipropylene glycol, diglycerin, diethoxyethyl succinate, or a mixture of two or more thereof. A non-aqueous liquid crystalline capsule base composition having a skin-like film, comprising: a water-soluble active substance part including 3.0 to 30.0 parts by weight of a water-soluble polar solvent selected from the group and 0.1 to 10.0 parts by weight of a water-soluble active ingredient. delete The method of claim 1, The phospholipid is a non-aqueous skin layer characterized in that the phospholipid is selected from the group consisting of phosphatidylcholin, phosphadidylethanolamine, phosphatidyl inositol, phosphatidylosine, and phosphatidylserine, or a mixture of two or more thereof. Liquid crystal phase capsule base composition. The method of claim 1, A non-aqueous liquid crystalline capsule base composition having a skin-like film, wherein the higher alcohol is selected from the group consisting of cetyl alcohol, cetearyl alcohol, stearyl alcohol, behenyl alcohol, batyl alcohol or a mixture of two or more thereof. The method of claim 1, The oil-soluble active ingredient is Idebenone, coenzyme Q10, tocopherol and its derivatives, vitamin C oil-soluble derivatives, retinol and its derivatives, oleanolic acid, ursolic acid, diol A non-aqueous liquid crystalline capsule base composition having a skin-like film, which is selected from the group consisting of acetylboldine, oil soluble caviar extract, oil soluble licorice extract, or a mixture of two or more thereof. The method of claim 1, The oil of the oil-soluble active substance part is a non-polar oil, such as animal and vegetable squalane, mineral oil, isohexadecane; Glyceryl trioctanoate, octyldodecyl myristate, isostearyl isostearate, dicapryl carbonate, neopentylene glycol diheptanoate, cetearyl isonanoate, cetearyl octanoate as polar oils And capric / caprylic triglyceride, isopropyl palmitate, isopropyl myristate, octyl palmitate, or a non-aqueous liquid crystalline capsule base composition having a skin-like film, characterized in that the mixture consists of two or more thereof. The method of claim 1, The water-soluble active ingredient constituting the water-soluble active substance portion is adenosine, arbutin, vitamin C and its hydrophilic derivatives, vitamin B3, vitamin B5, hydrophilic vitamins and derivatives thereof of vitamin H, kojic acid and its derivatives, acetyl Glucosamine, yeast extract, water-soluble caviar extract, centella asiatica extract including madecassoside, selenium aspartate or a non-aqueous liquid crystalline capsule base composition having a skin-like film, characterized in that it is selected from the group consisting of two or more thereof. In preparing the base by emulsification using a conventional mixer, (1) ethylene glycol, butylene glycol, propylene glycol, hexylene glycol, glycerin, 1,2-pentanediol, D-panthenol, dipropylene glycol, diglycerin, diethoxyethyl succinate, or mixtures of two or more thereof 10.0 to 60.0 parts by weight of a water-soluble polar solvent selected from the group consisting of, 0.1 to 10.0 parts by weight of ceramide, 0.05 to 5.0 parts by weight of cholesterol, 1.0 to 40.0 parts by weight of phospholipids having 16 to 30 chain lengths of fatty acids and 16 to 22 carbon atoms Preparing a liquid crystal lipid part by heating and dissolving 0.5 to 7.0 parts by weight of alcohol at 75 to 85 ° C .; (2) a first cooling step of cooling the liquid crystal lipid part to 55 to 65 ° C. which is a temperature near a phase transition point; (3) Animal and vegetable squalane, mineral oil, isohexadecane, glyceryl trioctanoate, octyldodecyl myristate, isostearyl isostearate, dicaprylcarbonate, neopentylene glycol diheptanoate, cetearyl 0.5-20.0 weight of oil selected from the group consisting of isononanoate, cetearyloctanoate, capric / caprylic triglyceride, isopropyl palmitate, isopropyl myristate and octyl palmitate or mixtures of two or more thereof Parts, oil-soluble antioxidants selected from the group consisting of 0.1 to 10.0 parts by weight of the active ingredient and tocopherol and its derivatives, butylated hydroxytoluene, benzophenones, octylmethoxycinnamate, octylsalicylate or mixtures of two or more thereof 0.01 to 0.5 parts by weight warmed to 50 to 60 ℃ dissolved by soluble active material Usefulness active material portion preparation step of preparing; (4) ethylene glycol, butylene glycol, propylene glycol, hexylene glycol, glycerin, 1,2-pentanediol, D-panthenol, dipropylene glycol, diglycerin, diethoxyethyl succinate, or mixtures of two or more thereof A water-soluble active material preparation step of preparing a water-soluble active material part by heating and dissolving 3.0-30.0 parts by weight of a water-soluble polar solvent selected from the group consisting of 0.1-10.0 parts by weight of a water-soluble active ingredient at 50-60 ° C .; (5) The prepared oil-soluble active material part was prepared at 55 to 65 ° C. in the prepared liquid crystal lipid part, stirred with a conventional stirrer, and homogenized to encapsulate the oil-soluble active material in the lipophilic part (Hydrophobic region, A region) of the liquid crystal lipid part. Preparing a primary liquid crystal unit; (6) The prepared water-soluble active material portion in the primary liquid crystal portion at 55 to 65 ℃ stirred with a conventional stirrer, homogenizing and swelling (Swelling) in the hydrophilic region (H region C region) of the liquid crystal lipid portion Preparing a secondary liquid crystal part encapsulating a water-soluble active material through; And (7) The secondary liquid crystal part is gradually cooled to 30 to 40 ° C. to solidify lipid chains, thereby making it useful for multi-layers of regular Lamella type non-aqueous liquid crystal phases. Secondary liquid crystal stabilization step of stabilizing the water-soluble active ingredients; Method for producing a non-aqueous liquid crystal phase capsule base composition having a skin-like film, characterized in that consisting of. The composition according to any one of claims 1 and 3 to 7 is applied to the cosmetics in which the continuous phase is a water-phase, skin, lotion, essence, cream, pack, cleansing, makeup base, foundation, sunscreen, lip gloss Cosmetic composition, characterized in that the mixture is made in the usual cosmetic composition for producing.

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