KR100810164B1 - Wrinkle improvement cosmetic composition containing idebenone nanocapsules and preparation method thereof - Google Patents

Abstract

The present invention relates to an anti-wrinkle cosmetic composition containing idebenone nanocapsules and a method for preparing the same, comprising: (a) a core part comprising 0.01-2.0 wt% of idebenone and 1.0-15.0 wt% of an ester polar oil; (b) 2.0-20.0 wt% of nonpolar oil, 2.0-20.0 wt% of polyol, 0.01-1.5 wt% of ceramide, 0.01-1.5 wt% of cholesterol, 0.01-3.0 wt% of fatty acid, 0.01-3.0 wt% of higher alcohol Capsule part containing 0.5% to 6.0% by weight of phospholipids; (c) an outer capsule portion containing 0.01 to 1.0% by weight of anionic phosphorus compound and 0.1 to 5.0% by weight of a polymer emulsifier on the inner capsule part; And (d) anti-wrinkle cosmetic composition containing idebenone nanocapsules comprising water in the core part of (a), the inner capsule part of (b) and the outer capsule part of (c) as the remaining amount, and a preparation method thereof By providing a, it is possible to provide a nano-size wrinkle improvement cosmetic composition that can improve the wrinkle improvement efficiency of idebenone on the skin while stabilizing the idebenone titer for a long time.

Idebenone, Nanocapsules, Cosmetics

Description

Anti-wrinkle cosmetic composition encapsulating idebenone with nano sizes and its manufacturing method

1 is a diagram showing the chemical structural formula of idebenone excellent in anti-aging and brain function and biologically effective in anti-oxidation and wrinkle improvement.

2 is a view showing the chemical structure of ceramide (A), cholesterol (B), stearic acid (C), phospholipid (D) constituting the particle wall (Particle wall) of the nanoparticles of the present invention.

3 is a view showing the chemical structures of the anionic phosphorus compound (A) and the natural emulsifier (B) derived from natural sugars constituting the outer capsule of the present invention.

FIG. 4 is a schematic view schematically showing an idebenone stabilized in nanocapsule particles of an oil-in-water type according to the present invention.

5 is a photograph taken with a real freeze scanning electron microscope (ZeissEM 902A microscope, Germany) of the idebenon nanocapsules prepared according to the present invention (scale bar = 100nm).

6 shows particle sizes of Example 1 (A) and 2 (B) and Comparative Examples 4 (C), 5 (D), 7 (E) and 9 (F) prepared according to the present invention. Data measured and shown.

Figure 7 is a ball showing a simplified method of manufacturing an idebenone nanocapsules according to the present invention.

8 is a simplified diagram (A) and a photo (B) showing the structure of the enhancer cell (Enhencer cell) equipment for measuring the percutaneous absorption of idebenone stabilized in the nanocapsule particles according to the present invention.

9 is a view showing the transdermal absorption of stabilization of idebenone in the nanocapsule particles according to the present invention compared to the control.

10 is a view showing the skin elasticity compared to the control when the wrinkle improvement cosmetic composition according to the invention applied to the actual skin.

11 is a photograph showing the wrinkle improvement effect when the wrinkle improvement cosmetic according to the present invention is used for two months on the actual skin.

The present invention relates to an anti-wrinkle cosmetic composition containing idebenone nanocapsules and a preparation method thereof, and more particularly to non-polar oils, polyols, ceramides, cholesterol, fatty acids, higher alcohols to improve the stability of idebenone The present invention relates to an anti-wrinkle cosmetic composition comprising an idebenone nanocapsule comprising an inner capsule and an outer capsule including an anionic phosphorus compound having a skin-like composition and structure and a polymer emulsifier, and a method for preparing the same.

From the moment humankind was able to perceive and establish a system of culture, human beings have done their best to delay or solve problems with great interest in aging and disease. In particular, skin aging symptoms such as deterioration of skin elasticity, skin peroxidation and fine wrinkles caused by aging are very serious concerns for women and have brought great attention to delays or solutions.

As a matter of fact, to keep their skin younger and younger in recent decades and to have clean and smooth skin that they had in their late teens to early twenties has become a big concern for most women, and their ages are becoming increasingly young, even men As they are beginning to pay attention to improving their skin condition and anti-aging, their interest and demand for not only ingredients that are effective against anti-aging, but also cosmetics containing them have exploded, leading to anti-aging and Wrinkle and elasticity improvement cosmetics occupy a large part of the skincare market.

In general, skin aging is divided into natural aging that is exposed to the outside in conjunction with the physiological effects of the human body and environmental aging promoted by severe air pollution due to environmental pollution, frequent ultraviolet exposure, and free radicals. Among these substances are: IDEBENONE, retinol and its derivatives, adenosine, vitamin C, collagen and various kinds of peptides, proanthocyanidins, epigallocatechins (EGCG), polyphenols such as ursol Acids, triterpenoids including oleanolic acid and the like are known.

In addition, a variety of components extracted from various plants and marine flora and fauna, and combined with them are being used for wrinkle improvement cosmetics.

Idebenone is a ubiquinone-based antioxidant present in living cell membranes and is similar to coenzyme Q10, which is mainly involved in the ETC (Electron Transfer Chain) involved in the production of ATP (Adenosine triphosphate), a cellular energy in mitochondria. Chemical substance with structure, chemical name is 2,3-dimethoxy-5-methyl-6- (10-hydroxydecyl) -1,4-benzoquinone [dimethoxy-5-methyl-6- (10-hydroxy decyl ) -1,4-benzoquinone] and its molecular weight is 338.44, and is known to be a purified yellow crystalline powder material obtained mainly by chemical synthesis (see FIG. 1).

In addition, according to a well-known research paper applied to pharmaceutical or cosmetics, idebenone has been reported to have a very good effect on aging as a medicine and cosmetics. disease, Neuropsychobiology , 1997; Idebenone improves cerebral mitochondrial oxidative metabolism in a patient with MELAs, Neurology , 1996; Oral administration of idebenone, a stimulator of NGF synthesis, Neuroscience letter, 1993; Mitochondrial encephalomyopathy (MELAS), pathological study and successful therapy with coenzym Q10 and idebenone, Journal of Neuroscience , 1989].

In addition, idebenone is involved in ETC (Electron Transfer Chain) related to the production of ATP (Adenosinetriphosphate), a cell energy in mitochondria, and is effective for cell activation. It protects the skin by preventing formation, and medically promotes NGF (Nerve Growth Factor), which is a degenerative neurological disease Alzheimer's disease that is a problem due to aging, cerebrovascular disease (vascular disease) ( Cerebrovascular disease and liver disease have been reported to be effective.

Therefore, Idebenon in the future Research into the development of used cosmetics and pharmaceuticals is actively underway.

However, Idebenone is composed of complex structures such as quinone group, saturated hydrocarbon and hydroxyl group, and has high polarity and low melting point, making it difficult to stabilize in the emulsion system. It is difficult to penetrate the skin, which makes it difficult to apply to cosmetics.

That is, even if idebenone is dissolved once to form emulsified particles, there is a problem in the stability of the formulation and the potency preservation of idebenone due to the inherent characteristics described above when using conventional emulsification techniques and emulsifiers.

Particularly, when idebenone is manufactured as nanocapsule particles, unlike general micro-sized liquid crystals (droplets), the nanoparticles are relatively thin in physical layer and are highly polar materials such as idebenone. It has solubility in the continuous phase around the particles, and the stability is lowered by Ostwald ripening.

In addition, its own Idebenone molecular structure is to pass through the skin formed of keratin (Keratin) consisting of a solid brick-like structure and the intercellular lipid component that attaches the keratin support like Cement. Because of the difficulty, there is a problem in providing the skin with the desired wrinkle improvement effect.

Idebenone was therefore very limited in its use in formulation stability as well as efficient drug delivery into the skin.

Accordingly, the present inventors have attempted to develop a special technology that can effectively deliver the stabilized idebenone into the skin to properly exhibit the effects it has.

The present invention is to develop an anti-wrinkle cosmetic to emulsify the idebenone, and to improve the functional aspect of the cosmetic by nano-encapsulating it.

Accordingly, an object of the present invention is stabilization of Idebenone, which is excellent in antiwrinkle and anti-aging, as an outer capsule composed of an inner capsule composed of ceramide./cholesterol/fatty acid / phospholipid and an anionic phosphorus compound and a polymer emulsifier derived from natural polysaccharides. And double nano encapsulation, to provide a wrinkle improvement cosmetic composition different from the conventional products.

In addition, stabilizing the idebenone in a double capsule while providing a method for producing a wrinkle-improving cosmetics that can be nanonized.

In order to achieve the above object, the present invention (a) a core portion comprising 0.01 to 2.0% by weight of idebenone and 1.0 to 15.0% by weight of an ester polar oil;

(b) 2.0-20.0 wt% of nonpolar oil, 2.0-20.0 wt% of polyol, 0.01-1.5 wt% of ceramide, 0.01-1.5 wt% of cholesterol, 0.01-3.0 wt% of fatty acid, 0.01-3.0 wt% of higher alcohol Capsule part containing 0.5% to 6.0% by weight of phospholipids;

(c) an outer capsule portion containing 0.01 to 1.0% by weight of anionic phosphorus compound and 0.1 to 5.0% by weight of a polymer emulsifier on the inner capsule part; And

(d) water in the core portion of (a), the inner capsule portion of (b) and the outer capsule portion of (c) as the remaining amount;

It provides an anti-wrinkle cosmetic composition containing an idebenone nanocapsule comprising a.

In addition, in order to achieve another object, the present invention (a) 0.01 to 2.0% by weight of idebenone, 1.0 to 15.0% by weight of ester polar oil, 0.01 to 0.5% by weight of an oil-soluble antioxidant to 45 to 50 ℃ 1 Dissolving idebenone by completely dissolving tea and adding 2.0 to 20.0% by weight of nonpolar oil to the lysate, and then warming it to 65 to 75 ° C to stabilize the idebenone soluble portion;

(b) 2.0 to 20.0 wt% polyol, 0.5 to 6.0 wt% phospholipid, 0.01 to 1.5 wt% ceramide, 0.01 to 1.5 wt% cholesterol, 0.01 to 3.0 wt% fatty acid, 0.01 to 3.0 wt% fatty alcohol, anionic phosphorus compound Preparing a lipid dissolving unit to mix 0.01 to 1.0 wt% and warm it to 75 to 85 ° C. to dissolve it;

(c) a step of preparing a capsule stabilizer for dissolving 0.1 to 5.0% by weight of a polymer emulsifier, 0.5 to 15.0% by weight of a moisturizer, 0.01 to 0.5% by weight of a water-soluble antioxidant, and a residual amount of water by heating to 40 to 55 ° C;

(d) The idebenone dissolution portion of (a) and the lipid dissolving portion of (b) are introduced into a normal vacuum emulsification tank and emulsified by stirring at a rotational speed of 2,000 to 3,000 rpm to form a primary nanocapsule phase. step;

(e) a first cooling step of cooling the microcapsule phase of (d) to 40 to 55 ° C; And

(f) mixed by adding the cooled primary microcapsule phase of (e) and the capsule stabilizing unit of (c), and putting it in a conventional high pressure type emulsifier and having a temperature of 40 to 55 ℃ and 600 to 1500 bar Forming a secondary nanocapsule phase formed by stabilizing fine oil-in-water nanoparticles having a particle size of 100 to 300 nm by emulsifying twice to three times under pressure conditions;

It provides a method for producing a wrinkle-improving cosmetic containing an idebenone nano capsule comprising a.

Hereinafter, the present invention will be described in detail.

At this time, if there is no other definition in the technical terms and scientific terms used, it has a meaning commonly understood by those of ordinary skill in the art.

In addition, repeated description of the same technical configuration and operation as in the prior art will be omitted.

The present invention has developed a stabilized idebenone nanocapsule cosmetic composition that can be used in all cosmetic items, from high viscosity creams to very low viscosity lotion or color products, and can improve the stability of idebenone. It is intended to include an inner capsule containing nonpolar oils, polyols, ceramides, cholesterol, fatty acids, higher alcohols, and an outer capsule containing anionic phosphorus compounds and polymer emulsifiers having a skin-like composition and structure.

In particular, the idebenone nanocapsules of the present invention is a method that can easily obtain a cosmetic composition of the nanocapsules containing an idebenone concentration of 80 to 350nm, preferably 100 to 150nm, concentrated concentration of the excess idebenone components to 30 to 80nm It is developed.

That is, the present invention (a) emulsification despite complex structure and high polarity and low melting point (Melting point), such as quinone group, saturated hydrocarbon and hydroxyl group of the idebenone Idebenone, which is difficult to stabilize in the system and does not easily penetrate into the skin, is first dissolved in ester polar oil, which is highly stable in non-polar oil and van der waals in emulsion. An idebenone melted part composition in which the idebenone is first stabilized by using; (b) preparing a lipid dissolving unit comprising ceramide, cholesterol, fatty acid, higher alcohol, anionic phosphorus compound, and polyol in order to achieve the purpose of stabilizing the idebenone dissolution unit composition and promoting transdermal absorption into the skin. , (c) when preparing the oil-in-water emulsion having a nano-size using the prepared edebenone dissolution and lipid dissolving portion, Ostwald due to the reduced inner phase volume due to high polarity and nano-size due to hydroxyl groups In order to suppress the ripening phenomenon, a stabilized idebenone nanocapsule was prepared by adding a capsule stabilizing part including a polymer emulsifier derived from a natural polysaccharide, a water soluble moisturizer, a water soluble antioxidant, and purified water to emulsify (emulsify) It is easy to penetrate the skin and form a stable nano double capsule membrane.

In addition, in the present invention, in order to use the prepared idebenone nanocapsules as cosmetics, a conventional effective amount of preservatives that do not rot cosmetics and a thickener having a viscosity-adjusted amount used according to cosmetic use are used. Effective amounts and amounts of preservatives and thickeners used herein will be omitted as obvious to those skilled in the art.

At this time, Idebenone, an anti-wrinkle active material used in the present invention, is used in an amount of 0.01 to 2.0% by weight based on the total weight of the cosmetic composition, which is less than 0.01% by weight of the wrinkle improvement effect is less than 2.0% by weight. This is because it is difficult to dissolve in non-polar oil when used, and even if dissolved, aggregates to decrease stability.

In addition, in order to dissolve an effective amount of the idebenone in the idebenone dissolution part composition, ester-based polar oils commonly used in the art should use 1.0 to 15.0 wt%, specifically, glyceryl trioctanoate, Octyldodecyl myristate, isostearyl isostearate, dicaprylcarbonate, capric / caprylic triglycerides, isopropyl palmitate, isopropyl myristate or octyl palmitate can be used.

In addition, when obtaining the final secondary nanocapsules, non-polar oil is used in the amount of 2.0 to 20.0% by weight as a material to help prevent the desorption of idebenone, which is less than 2.0% by weight This is because if the amount is insignificant and used in excess of 20% by weight, the above-mentioned effect does not increase in proportion to the excess amount used. Specifically, in the present invention, animal and vegetable squalane, mineral oil, isohexadecane or hydrogenated polyisobutene, hydrogenated polydecene may be used.

In addition, the phospholipid used as the main emulsifier in the lipid dissolving portion may be used both a saturated type and an unsaturated type. In this case, a polar oil for dissolving and stabilizing idebenone and a nonpolar oil for inhibiting desorption thereof. At the same time, phospholipids containing phosphatidylcholin and phosphatidylethanol amine must be used simultaneously to maximize the ease of emulsification while having chemical compatibility. It is desirable to use phospholipids that have a very small content of phosphatic acid that harms them. It is difficult to obtain stable nanoparticles due to the high hydrophilicity and polarity of idebenone to stabilize when phospholipids with little content of phosphatidylcholine and phosphatidylethanolamine are used, and phosphatic acid is difficult to obtain. This is because when the phospholipid containing a large amount is used, there is a problem of inhibiting stability by reacting with the hydroxyl group of the idebenone, which is encapsulated inside the nanoparticles, to change the properties of the idebenone itself.

In addition, when the phospholipid is used less than 0.5% by weight based on the total weight of the cosmetic composition, it is impossible to encapsulate the above-described content of the idebenone dissolved portion in a nano size, and when used in excess of 6.0% by weight, the interface is too thick. Since gelation proceeds, and not spherical nanoparticles, but lamellar liquid crystals are formed, it is preferable to use them within the above-mentioned amounts.

In addition, ceramides, cholesterol, and fatty acids used in the lipid soluble portion of the present invention use compounds of grades commonly used in cosmetics and pharmaceuticals as the main constituents of intercellular lipids. Stearic acid, palmitic acid, oleic acid, linoleic acid or linoleic acid having a chain length of 16 or more may be used (see FIG. 2).

In the lipid lysis portion of the present invention, the intercellular lipid component plays a role in forming the most important capsule membrane for delivering an effective amount of stabilized idebenone to the skin together with phospholipids. In other words, the double capsule membrane of the present invention efficiently wets and penetrates the skin from an appropriate composition similar to intercellular lipids, thereby enhancing the skin penetration efficiency of idebenone and improving the wrinkle improvement effect of idebenone. In addition to doubling, the same role as the intercellular lipids to hold the interface of the nanocapsule particles as if the adhesive to suppress the desorption of idebenone.

In addition, in the present invention, it is preferable to use 0.01-1.5% by weight of ceramide, 0.01-1.5% by weight of cholesterol and 0.01-3.0% by weight of fatty acid, based on the total weight of the cosmetic composition. This is because the nanocapsule membrane itself loses the similarity with the skin composition and thus does not help the transdermal absorption of idebenone, and when used in more than the above contents, it is difficult to dissolve and rather it impairs the stability of the formulation.

In addition, the higher alcohol and the anionic phosphorus compound are desorbed to the outside under conditions such as long-term storage or high temperature in the idebenone nanocapsules cosmetics prepared according to the present invention to lower its own titer or total cosmetics. Used for the purpose of preventing the deterioration of stability.

In the present invention, the higher alcohol (higher alcohol) specifically serves to maintain the idebenone nanocapsules for a long time as described above by improving the density of the particle interface with excellent regularity of chemical structure, 0.01 based on the total weight of the cosmetic composition It is difficult to maintain the effect of the above-mentioned long-term stability if less than the weight%, and if used in excess of 3.0% by weight because the problem occurs that the stability worsens due to excessive interfacial orientation is used within the above-mentioned content range It is preferable. Specifically, in the present invention, cetanol, cetostearyl alcohol, stearyl alcohol, behenyl alcohol, or batyl alcohol which are commonly used as higher alcohols may be used.

Anionic phosphorus compounds provide stability of particles by imparting negative charge and electrostatic repulsive force at the interface of particles to prevent the particles from coalescing between particles. If less than 0.01% by weight is used to give a negative charge is not helpful to the stability, when used in excess of 1% by weight is given a problem of destroying the nanoparticles due to the excessive negative charge, it is mentioned above It is preferred to use within one content range. Specifically, in the present invention, it is preferable to use cetyl phosphate, diecetyl phosphate, diecetyl phosphate or potassium cetyl phosphate used in the art (see FIG. 3A).

In addition, the aforementioned composition ratio of lipids, higher alcohols, and anionic phosphorus compounds is a very important factor in the stability of the wrinkle improvement cosmetics nanoencapsulated idebenone of the present invention, separately in the following Examples and Comparative Examples It will be described in detail.

In addition, the polyol of the lipid dissolving portion is used to dissolve the above-mentioned lipid, specifically, using glycerin, propylene glycol, 1,3-butylene glycol, D-panthenol, 1,2-pentanediol or ethanol It is preferable.

In the present invention, it is preferable to use the emulsifier derived from natural polysaccharide as the polymer emulsifier of the capsule stabilization part. This is because the polymer emulsifier derived from natural polysaccharides gives strong hydration and steric hinderance effects to the nanoparticles, thereby making it stable from ostwald lighting phenomenon.

In the present invention, a polymer emulsifier derived from natural polysaccharides is less than 0.1 wt% based on the total weight of the cosmetic composition, it is difficult to prevent australining, and when used in excess of 5 wt% there is a problem that harms stability due to excessive repulsion and hydration Because of this, it is preferable to use within the above-mentioned content range, specifically, in the present invention, it is preferable to use inulin lauryl carbamate (see FIG. 3B).

In addition, the composition ratio of the polymer emulsifier derived from the above-mentioned natural polysaccharide is a very important factor for the stability of the wrinkle improvement cosmetics nanoencapsulated idebenone of the present invention, will be described in detail in the Examples and Comparative Examples.

In addition, the cosmetic composition nano-encapsulated idebenone according to the present invention can be used in the formulation of the skin, lotion, essence, cream, pack, patch for wrinkle improvement by adjusting the viscosity.

On the other hand, in the present invention will be described a process for producing a cosmetic composition consisting of idebenone nanocapsules by process.

(1) Idebenone melting part manufacturing process

0.01 to 2.0% by weight of idebenone and 1.0 to 15.0% by weight of ester polar oil were completely dissolved by heating at 45 to 50 ° C., and 2.0 to 20.0% by weight of nonpolar oil was added thereto to dissolve Idebenone and 65 to 75. Prepare by dissolving completely by heating to ℃.

At this time, it is preferable to add 0.01 to 0.5% by weight of an oil soluble antioxidant to the idebenone soluble portion to maintain the titer of idebenone more stably.

(2) lipid part melting part manufacturing process

Polyol 2.0-20.0 wt%, phospholipid 0.5-6.0 wt%, ceramide 0.01-1.5 wt%, cholesterol 0.01-1.5 wt%, fatty acid 0.01-3.0 wt%, higher alcohol 0.01-3.0 wt%, anionic phosphorus compound 0.01-1.0 Prepared by warming to 75 to 85 ° C completely dissolved lipid parts, including by weight.

(3) capsule stabilization part manufacturing process

It is prepared by completely dissolving water as a polymer emulsifier derived from natural polysaccharides from 0.1 to 5.0% by weight, a moisturizer from 0.5 to 15.0% by weight, and the remaining amount by heating to 40 to 55 ° C.

At this time, it is preferable to add 0.01 to 0.5% by weight of the water-soluble antioxidant to the capsule stabilization portion to keep the outer capsule more stable.

(4) Primary Nanocapsule Phase Manufacturing Process

The lipid dissolving unit and the dissolving unit of idebenone were introduced into the conventional vacuum emulsification tank and stirred at a rotational speed of 2,000 to 3,000 rpm to emulsify the first to make the idebenone mainly for ceramide / cholesterol / fatty acid / phospholipid / anionic phosphorus compound. Prepare (Micro) size capsules.

(5) primary cooling process

The prepared primary microcapsule phase is stabilized by cooling to 40 to 55 ℃.

(6) secondary nanocapsule phase formation step

The prepared capsule stabilization unit was mixed on the cooled microcapsules and mixed, and this was added to a commercially available high pressure type emulsifier at a temperature of 40 to 55 ° C. and then emulsified twice to three times at a pressure of 600 to 1,500 bar to particles. While producing fine oil-in-water nanoparticles with a size of 100 to 300 nm, Idebenone and polar oils are encapsulated in the innermost layer, and nonpolar oils are encapsulated with ceramide, cholesterol, fatty acids and phospholipids in the innermost phase, and external aqueous phases. An anionic phosphorus compound and a polymer emulsifier derived from a natural polysaccharide form a nanocapsule composed of an external capsule.

In this process, the micro-encapsulated idebenone is nano-sized to be smaller than the skin gap to promote high stability as well as percutaneous absorption to express the effect of improving wrinkles. In this process, the treatment temperature is less than 40 ° C. In this case, it is lower than the solidification temperature of lipids such as phospholipids, ceramides, and higher alcohols, or it is difficult to nanoencapsulate idebenone because the efficiency of emulsification is reduced. Due to the high temperature due to the energy applied in the process, cholesterol, especially idebenone, is desorbed to the outside and crystallized, causing the structure of the nanocapsules to be deformed and failing to form a homogeneous nanosize particle phase. Preference is given to performing within the temperature range.

In addition, the high pressure type emulsifier may be any high pressure type emulsifier known to those skilled in the art and widely commercialized. Purchase and use the machine. However, the high pressure type emulsifier used in the present invention specifically applies a very high pressure in a pressure pump, and passes it through an interaction chamber made of diamond of a hollow fine size such as a pipe to change the high pressure to a high speed, and the interaction It is desirable to have a function of producing nano-sized particles by generating a kind of vacuum phenomenon and crushing effect by collision with a unique structure in the chamber (cavitation).

(7) incremental process

The prepared nanocapsule phase is transferred to a conventional vacuum emulsification tank to prepare a cosmetic composition which maintains a viscosity suitable for a purpose by adding preservatives and thickeners thereto.

In the case of the cosmetic which requires little viscosity, the incremental step may be omitted.

(8) secondary cooling process

The nanocapsules of step (5) or the increased cosmetic composition of step (7) are cooled by cooling to 25 to 30 ° C.

As described above, the present invention is excellent in anti-wrinkle and anti-aging, but has a complex structure, high polarity, precipitation property in the emulsion system, and a quinone group, saturated hydrocarbon and hydroxyl group. Encapsulates idebenone, which has not been used in the past due to its impermeability to the skin, and makes the capsule size smaller than the gap of skin cells by making the size of nano Nano differentiated from conventional products by forming an inner capsule that facilitates transdermal absorption, and an outer capsule that can be stabilized by electrostatic repulsion, steric hinderance and hydration effects. A unique emulsion of size that improves the efficiency of wrinkle improvement of Idebenon on the skin and stabilizes the potency of Idebenon for a long time And it will develop a cosmetic composition that can provide up to a refreshing and moisturizing feeling improvement.

Hereinafter, the present invention will be described in more detail with reference to specific examples. However, the present invention is not limited to the following examples, and it will be apparent to those skilled in the art that various changes or modifications can be made within the spirit and scope of the present invention.

EXAMPLES Preparation of an Anti-Wrinkle Cosmetic Composition Containing Idebenone Nanocapsules According to the Present Invention

One. Idebenon Melting part  Composition preparation

Before elaborating the embodiment in detail, first dissolving idebenone, and maintaining it without aggregation of idebenone to find the optimum stabilization ratio in the preparation of the wrinkle improvement cosmetics as shown in Table 1 The solubility of idebenone was evaluated by varying the composition of the nonpolar oil, and the preparation method thereof is as follows.

First, Idebenone was dissolved by heating the polar oil of Table 1 to around 45 ° C as a solvent, and the nonpolar oil of Table 1 was added thereto and stirred, and then the surfactant solution of Table 1 was added thereto. After stirring, the mixture was left at room temperature for 10 days to check the stability of idebenone on the dissolution part composition.

When dissolving 0.5 g of idebenone in Table 1, instant dissolution in all compositions was very well dissolved without any difficulty, but mixed with a surfactant solution and stirred, and observed after 10 days, the composition 1 and When comparing composition 2, it was found that the use of dicapryl carbonate, which is an ester oil, was superior to the case of non-ester oil such as octyldodecanol.

In addition, when the polar oil dicapryl carbonate and the non-polar oil squalane as in the composition 3 to 5 is used at the same time, the stability is excellent in the case of 1: 1 as in the case of the composition 4, octyl as in the composition 6 to 7 When non-ester oils such as dodecanol were used, it was found that the stability was very low compared to the compositions 4 to 5.

In view of the above results, it can be seen that it is preferable to use ester oil and non-polar oil in a ratio of 1: 1 when preparing an anti-wrinkle cosmetic having nano-encapsulated idebenone.

And the composition ratio of the above-mentioned optimal idebenone melt | dissolution part composition was applied to the Example and comparative example of Table 2 below.

2. Example  1 and 2 and Comparative example  Preparation of 1 to 10 and its physical properties

To prepare a wrinkle-improving cosmetics nano-encapsulated idebenone according to the present invention with the composition shown in Tables 2 and 3, the preparation method is as follows.

In a separate dissolution tank, dissolved in the oil-dissolving tank capable of temperature control and stirring to the content shown in Table 2 by heating and stirring Idebenone at 47 ° C. in polar polar ester oil, adding non-polar oil to the mixture, and heating up to 70 ° C. It was prepared by dissolving uniformly by stirring and dissolving the lipid dissolving unit in the content shown in Table 2 in a vacuum emulsion tank capable of temperature control and stirring. Then, the capsule stabilization unit was added to the content shown in Table 2, and then prepared by heating and dissolving at 52 ° C. in a water soluble tank capable of temperature control and stirring. The idebenone soluble part was added to the lipid soluble part and first emulsified with a homomixer at 2,500 rpm to form a first nanocapsule phase. After cooling it to 50 ° C., the capsule stabilizer was added to maintain a temperature of 50 ° C. After mixing with a paddle, the secondary nanocapsule was double encapsulated with inner capsule and outer capsule by second emulsification by injecting into a high pressure type emulsifier at 50 ° C. and treating it three times at a pressure of 1,000 bar. A phase was formed, and preservatives and thickeners were added thereto to form a desired viscosity, which was then cooled with stirring using a paddle to 28 ° C. to obtain an anti-wrinkle cosmetic having stabilized idebenone.

As a result of photographing the wrinkle-improvement cosmetics obtained by nanoencapsulating idebenone using a conventional optical microscope, it was impossible to observe due to the fine size of 300 nanometers or less, and separately from the particle size analyzer (Sympatec, Germany). NANOPHOX) by the distribution and size of the particles was examined as the average particle size was confirmed that the nano-size was formed to 100 to 300nm.

As a result of particle size analysis by particle size analyzer, Examples 1 and 2 and Comparative Examples 4, 5, 7 and 9 of the present invention have an average particle size of 115, 168, 137, 154, 224 and 192 nm. As a result of observing 6 months at 45 ° C. and 12 months at room temperature, the average particle size of Example 2 in which encapsulated idebenone was 1.0% was increased to about 190 nm, but it was found to be very stable. (See FIG. 5).

From this, the nanocapsules of Examples 1 and 2 form rigid capsules of ceramide, cholesterol, fatty acids, phospholipids, and higher alcohols of idebenone, and are composed of an anionic phosphorus compound and a polymer emulsifier derived from natural polysaccharides. By forming the capsule, it was confirmed that the nano-capsules are easy to penetrate the skin while stabilizing Edebenon.

However, when the amount of idebenone used in the above-mentioned content as in Comparative Example 1 was increased, the average particle size was initially increased even though the stabilizers such as polar oil, nonpolar oil, and phospholipid were increased to dissolve it. It was good to obtain about 300nm, but when about 2 weeks at 45 ℃ Idebenone was detached and precipitated as a yellow band was found to be poor stability.

In the case of using an amount less than the above-mentioned phospholipid content as in Comparative Example 2, although the content of the anionic phosphorus compound and the polymer emulsifier derived from natural polysaccharides was increased, the microparticles of about 3 to 5 μm were initially obtained. The capsule was not formed by the particle size, and when it was passed for 3 weeks at 45 ° C. and for 2 months at room temperature, the oil including idebenone was separated to be visible to the naked eye, indicating that the stability was not good.

In addition, when lipids such as ceramide and cholesterol were used more than the above-mentioned contents as in Comparative Example 3, even after high-pressure emulsifier treatment, a uniform property was not obtained, and the stability was also very poor, and thus the formulation was separated.

And, as in Comparative Example 4, when the content of lipids such as ceramide and cholesterol is less than the above-mentioned content, as mentioned above, nanoparticles similar to those of Examples 1 and 2 were obtained and the stability thereof was also confirmed to be good.

When the content of higher alcohols was lower than the above-mentioned content as in Comparative Example 5, even though the density of the interface was compensated by increasing the content of phospholipid, the initially obtained composition showed the same good condition as in Examples 1 and 2, but 45 When 3 months passed at ℃ ℃ a small amount of idebenone was detached to form a yellow spot, the particles were also found to be slightly larger.

In addition, when the higher alcohol is added in excess of the above-mentioned content as in Comparative Example 6, not only the microparticles of about 4 to 6 μm were obtained immediately after the high-pressure emulsifier treatment, but also the higher alcohol was desorbed into the aqueous phase to obtain a continuous phase. Irrespective of idebenone, irregular lamella was formed, and the appearance was not clean, and creaming occurred after about 1 month at 45 ° C and about 3 months at room temperature. It was confirmed.

When the polymer emulsifier derived from the natural polysaccharide constituting the outer capsule as in Comparative Example 7 is less than the above-mentioned content, good nanoparticles were initially obtained as in Examples 1 to 2, but the hydration effect and steric hindrance effect were insignificant. The particle size increased to 3 to 5 μm after about 1 month at 45 ° C. and about 4 months at room temperature, and excessively increased in the treatment of the high pressure type emulsifier when the content was higher than the above-mentioned content as in Comparative Example 8. On the contrary, the nano-sized particles could not be obtained, and the stability thereof was also poor.

Finally, when the anionic compound imparting a negative charge to the outer capsule is less than the above-mentioned content as in Comparative Example 9, a slightly larger but relatively good nanoparticle was initially obtained than Examples 1 to 2, but the negative charge imparting effect to the interface was obtained. In the case of about 2 months at 45 ° C. and about 5 months at room temperature, the particles grew to 3 to 5 μm. When excessive amounts were added to the above-mentioned content as in Comparative Example 10, excessive negative charge was applied. It was found that no viscosity was formed and the particles were large and heterogeneous and within a few days the formulation separated.

From the results of the above-described examples and comparative examples, it can be seen that the content of phospholipids and higher alcohols constituting the inner capsule is very important when preparing wrinkle-improvement cosmetics nano-encapsulated idebenone. It was found that it is very important to properly assign negative charge or hydration and steric hindrance effect at the interface with the water phase which is a continuous phase in the outer capsule.

In addition, as a result of analyzing the content by high performance liquid chromatography (HPLC, Japan, Shimadzu, LC-10VP), in all the Examples and Comparative Examples, the content of Idebenone is at least 99.5% by weight of the compounding amount. When the titers were analyzed for 6 months at 45 ° C. and 12 months at 25 ° C. (at room temperature), the results were maintained at 96.7% and 95.1% at 45 ° C., respectively, and at 25 ° C. (at room temperature), respectively. It was confirmed that the potency was maintained very stably with 98.3% and 97.2%.

However, even if initially obtained nano-sized particles, in the case of Comparative Example 5, the titer decreased to 72.5% and 75.3% at 45 ° C and 25 ° C (room temperature), respectively, so that higher alcohol increased the density of the interface. In the case of Comparative Example 7, the titer decreased to 75.7% and 80.3% at 45 ° C and 25 ° C (room temperature), respectively, so that the coalescence phenomenon of particles due to the lack of external capsule stabilization effect was maintained. It was found to be an important factor.

In addition, in the case of Comparative Example 9, the titer decreased to 80.3% and 78.1% at 45 ° C and 25 ° C (room temperature), respectively, better than that of Comparative Examples 5 to 7, but it was found that the negative charge is also important to the outer capsule.

However, in Comparative Example 4, the titer was well preserved to 93.6% and 94.8% at 45 ° C. and 25 ° C. (room temperature), respectively, indicating that the effects of ceramide and cholesterol on titer retention were minimal.

In addition, the comparative example in which separation and creaming, etc. occurred during the stability check without forming nanoparticles In case of 1, 2, 3, 6, 8, and 10, the stability of the formulation itself was not good and the potency integrity was also significantly lowered to 60% or less. I could confirm it.

3. According to the present invention Idebenon  Nano Capsule Cosmetics  Of composition Transdermal  Absorption effect

When the cosmetic compositions obtained from Examples 1, 2 and Comparative Examples 3, 4, 7, and 9 are applied to the skin, how much infiltrate isidenon through the intercellular lipids, which is the main point of drug delivery mentioned above. We tried to analyze by measuring transdermal uptake.

At this time, the percutaneous absorption test in the dissolution tester (Dissolution tester, ERWEKA DT800 Dissolution Tester, Germany) 0.2g samples prepared from Examples 1, 2 and Comparative Examples 3, 4, 5, 7, 9, respectively, the actual human skin (Enhancer cell, ERWEKA, Germany) equipped with (65 year old male back, Hans Biomed), filled with 500 ml of a buffer solution prepared at pH 7.0 with sodium chloride, and the temperature was 37 ° C. The elution amount of idebenone periodically for 360 minutes was measured using high performance liquid chromatography (HPLC, Japan, Shimadzu, LC-10VP) (see FIG. 8). This is because, when the cosmetic composition is generally applied to the skin, the average time for which drug delivery can occur efficiently is about 360 minutes.

At this time, the measurement of the dissolution amount is shown in Fig. 9 after about 360 minutes in order to accurately compare with the cosmetic composition of a different composition, the elution amount of idebenone as a percentage (%) of the dissolution amount relative to the initial dose.

As a result, 360 minutes after applying the cosmetic composition, when looking at the percent (%) curve of the dissolution amount compared to the initial dose, Example 1 (= Example 2) = Comparative Example 5> Comparative Example 9> Comparative Example 7> Comparative Example 4> It was found that there was a transdermal absorption effect in the order of Comparative Example 3. Among Examples 1 and 2, 95.4% and (96%) were very good, and in Comparative Example 5, 94.1% showed almost the same efficiency as Idebenone as in Examples. Although it greatly affects the stability, it was found that it did not affect the skin transfer of idebenone.

In Comparative Examples 7, 9, 78.2% and 91.3%, respectively, showed high idebenone transfer efficiency. As such, ceramide, cholesterol, and phospholipids had the same composition, the particle size affected the skin transfer efficiency of idebenone. And it was found.

However, Comparative Example 3 has a very low transfer efficiency of 48.6%, which indicates that when an excess amount of ceramide and cholesterol is used than the above-mentioned amount, it acts as a deterrent to skin transfer of idebenone. 4 was 61.6%, which was similarly low, and it was found that the use of ceramide and cholesterol smaller than the amount mentioned above resulted in lack of similarity in intercellular lipids and composition, resulting in inadequate Idebenone skin transfer. .

Based on the above results, the similarity of the structure and composition with the above-mentioned intercellular lipids is important for producing a cosmetic composition containing idebenone which is chemically unstable and not easily delivered to the skin. The size of the encapsulated particles is also important.

4. According to the invention Idebenon  Nano Capsule Cosmetics  Skin elasticity improvement effect of the composition

Finally, the skin elasticity before and after 1 month of use of the cosmetic using wrinkle improvement cosmetics obtained from the composition of Comparative Example 2 as a control example and a good drug delivery efficiency (Cutometer, Model name MPA 580 , CK Electronic, Germany), it is shown in Figure 10.

In this case, the skin elasticity means that the device pulls the skin back and releases it, and when it is repeated, the closer the value is to '1', the better the skin elasticity is, and the closer to the '0', the skin elasticity is bad.

As a result, as shown in FIG. 10, the elasticity value before use was 0.8309 (A), and the cosmetics obtained from Example 1 rose about 20% to 0.9758 after one month of use (B), and the comparative example was 0.8677. As a result, about 5% was increased (C). That is, when using the idebenone-containing nanocapsules cosmetics of the present invention was found to exhibit an excellent skin elasticity improvement effect.

5. According to the invention Idebenon  Nano Capsule Cosmetics  Wrinkle improvement effect of the composition

In addition, in order to evaluate the wrinkle improvement effect of the present invention, a panel test was carried out by In-vivo for the actual wrinkle improvement effect of 25 volunteers for 8 weeks from an authorized clinical institution [Ellead, Korea], p. When the value (error range) was 0.05% or less, the results were very significant compared to the control group, and a photograph demonstrating the wrinkle improvement effect on one of the volunteers is shown in FIG. 11.

As a result, the present invention was confirmed that not only stabilization of idebenone, but also very effective in improving wrinkles of the skin through the skin delivery.

In addition, a range of modifications, changes, and substitutions may be made to the above disclosure, and in some cases only some of the features of the invention may be used. Accordingly, the appended claims should be construed broadly and in accordance with the spirit and scope of the invention.

As described above, the present invention is excellent in wrinkles and anti-aging, but complex structure composed of quinone group, saturated hydrocarbon and hydroxyl group, high polarity, precipitation in emulsion system Encapsulates idebenone, which has not been used in the past due to sex and skin's impermeability, and manufactures a capsule smaller in size than the gap between skin cells, making the capsule size nano. By forming an inner capsule that facilitates transdermal absorption, and an outer capsule that can be stabilized by electrostatic repulsion, steric hinderance effect and hydration effect, while stabilizing Idebenone titer for a long time It is possible to provide a nano-sized anti-wrinkle cosmetic composition that can improve the efficiency of idebenon wrinkles on the skin to be.

Furthermore, the present invention stabilizes nanodevelopment together with not only idebenone but also all of the above-mentioned emollient oils, thereby minimizing the contact area with the skin, thereby obtaining a superior feeling of use that is completely different from conventional cosmetics. Moisturizing improvement effect is also to be obtained.

Claims (12)

(a) 0.01-2.0% by weight of idebenone and glyceryl trioctanoate, octyldodecyl myristate, isostearyl isostearate, dicaprylcarbonate, capric / caprylic triglycerides, isopropyl palmitate, A core part comprising 1.0 to 15.0 wt% of an ester polar oil selected from the group consisting of isopropyl myristate and octyl palmitate; (b) 2.0 to 20.0% by weight of nonpolar oil, 2.0 to 20.0% by weight of polyol, selected from the group consisting of animal and vegetable squalane, mineral oil, isohexadecane, hydrogenated polyisobutene and hydrogenated polydecene on the core part, and 1.5% by weight, cholesterol 0.01-1.5% by weight, fatty acid 0.01-3.0% by weight, higher alcohols selected from the group consisting of cetanol, cetostearyl alcohol, stearyl alcohol, behenyl alcohol and batyl alcohol and phospholipids Capsule portion containing 0.5 to 6.0% by weight; (c) an external phosphorus containing 0.01 to 1.0% by weight of anionic phosphorus compound selected from the group consisting of cetyl phosphate, diecetyl phosphate, diecetyl phosphate and potassium cetyl phosphate and 0.1 to 5.0% by weight of a polymer emulsifier Capsule portion; And (d) water as the remaining amount in the core part of (a), the inner capsule part of (b) and the outer capsule part of (c); Wrinkle improvement cosmetic composition containing an idebenone nanocapsule comprising a. delete delete The method of claim 1, The phospholipid is a phospholipid improved cosmetic composition, characterized in that the phospholipid comprising phosphatidylcholin (Phosphatidylcholin) and phosphatidylethanolamine (Phosphatidylethanolamine). delete delete The method of claim 1, Wrinkle improvement cosmetic composition, characterized in that the polymer emulsifier is inulin lauryl carbamate. delete The method of claim 1, Wrinkle improvement cosmetic composition, characterized in that the composition further comprises an effective concentration of thickeners and preservatives. delete (a) 0.01-2.0% by weight of idebenone with glyceryl trioctanoate, octyldodecyl myristate, isostearyl isostearate, dicaprylcarbonate, capric / caprylic triglycerides, isopropyl palmitate, 1.0 to 15.0 wt% of ester polar oil selected from the group consisting of isopropyl myristate and octyl palmitate and 0.01 to 0.5 wt% of an oil soluble antioxidant were completely dissolved by primary heating at 45 to 50 ° C. Idebenone is dissolved by adding 2.0 to 20.0% by weight of a nonpolar oil selected from the group consisting of vegetable squalane, mineral oil, isohexadecane, hydrogenated polyisobutene and hydrogenated polydecene, and then it is stabilized by warming it to 65 to 75 ° C. A step of preparing the melt part of the benone; (b) 2.0 to 20.0 weight percent polyol, 0.5 to 6.0 weight percent phospholipid, 0.01 to 1.5 weight percent ceramide, 0.01 to 1.5 weight percent cholesterol, 0.01 to 3.0 weight percent fatty acid, cetanol, cetostearyl alcohol, stearyl alcohol, 0.01 to 3.0% by weight of higher alcohol selected from the group consisting of behenyl alcohol and batyl alcohol, 0.01 to 1.0% by weight of anionic phosphorus compound selected from the group consisting of cetyl phosphate, diecetyl phosphate, dicetyl phosphate and potassium cetyl phosphate Preparing a lipid dissolving unit to dissolve it by heating to 75 to 85 ° C .; (c) 0.1 to 5.0% by weight of a polymer emulsifier, 0.5 to 15.0% by weight of a moisturizer, 0.01 to 0.5% by weight of a water-soluble antioxidant, and the remaining amount of the capsule stabilization part for dissolving by heating the water to 40 to 55 ℃; (d) The idebenone dissolution portion of (a) and the lipid dissolution portion of (b) are introduced into a conventional vacuum emulsion tank, and emulsified by stirring at a rotational speed of 2,000 to 3,000 rpm to form a primary nanocapsule phase. step; (e) a first cooling step of cooling the first nanocapsule phase of (d) to 40 to 55 ° C; And (f) mixed by adding the cooled primary nanocapsule phase of (e) and the capsule stabilizing unit of (c), and putting it in a conventional high pressure type emulsifier and a temperature of 40 to 55 ℃ and 600 to 1500 bar Forming a secondary nanocapsule phase formed by stabilizing fine oil-in-water nanoparticles having a particle size of 100 to 300 nm by emulsifying twice to three times under pressure conditions; Method for producing a wrinkle-improving cosmetics containing idebenone nanocapsules comprising a. The method of claim 11, (g) an incremental step of transferring the secondary nanocapsule phase of (f) to a conventional vacuum emulsifying tank and adding a preservative and a thickener of an effective concentration to prepare a cosmetic having a desired viscosity; And (h) a second cooling step of stabilizing the incremental cosmetic by cooling to 25 ~ 30 ℃; Method for producing a wrinkle improvement cosmetic containing idebenone nanocapsule, characterized in that further comprises.

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