KR20100100202A - Solubilized formulation containing micelle of intercellular lipid ingredients - Google Patents

Abstract

PURPOSE: A solubilization formulation containing micelle formed of ceramide, phosphorlipid, and cholesterol is provided to ensure preservation stability, moisturization, and elasticity. CONSTITUTION: A micelle solubilization formulation composition contains micelle of lipid ingredient The micelle contains 0.1-5 weight% of ceramide, 0.1-5 weight% of phospholipid, and 0.01-2 weight% of cholesterol. The content of the micelle is 0.1-15 weight% based on total weight. The interlipid ingredients is ceramide type 1- type 6, galactosyl ceramide, sphingosine, shipping solitary person, sphinganine, saturated lecithin, unsaturated lecithin, glycerophospholipid, cholesterol, sitosterol, or cholesteryl sulfate.

Description

Solubilized formulation containing micelle of intercellular lipid ingredients

The present invention relates to solubilized formulations containing micelles formed by intercellular lipid components.

Skin barriers that primarily block the penetration of external harmful substances are present in the stratum corneum of the epidermis. The function of this stratum corneum acts as a barrier to prevent the loss of moisture and electrolytes out of the skin, thus preventing the epidermis from drying and providing an environment for normal biochemical metabolism. It protects and prevents bacteria, fungi and viruses from invading the skin.

The structure of the stratum corneum is composed of protein-rich keratinocytes and lipids filling them.In the mid-1970s, Elias et al. This is the source of skin barrier function ( J. Invest . Dermatol . 69: 535-546 (1977)).

These intercellular lipids consist of 50% ceramide, 20-25% cholesterol, 20-25% free fatty acids, 10% cholesterol esters, 1-2% cholesterol sulfate, and contain small amounts of phospholipids. have.

These intercellular lipids are insoluble and not easily hydrated in water.

On the other hand, to date, as a study on the composition containing intercellular lipids, there is a Korean Patent Publication No. 10-2005-0026778 (a cosmetic composition for skin irritation relief containing nanoliposomes of the intercellular lipid component). However, the above technique is not only inconvenient to use a surfactant that stimulates the skin, but also requires the use of a high-pressure homogenizer process, which is useful for preparing nano-level particles, for use in the cosmetic formulation of liposomes having a lamellar structure. The lamellae structure that forms liposomes is quite large in size and has difficulty in being used in cosmetic formulations requiring formulation stability.

Therefore, the technical problem to be achieved by the present invention is to provide a formulation that is superior to the conventional nanoliposome cosmetic composition containing intercellular lipids in terms of improving damaged skin, increasing the moisturizing and softening effect and preservation stability.

In order to achieve the above technical problem, the present invention provides a solubilized formulation composition containing micelles (micelle) of the intercellular lipid component, preferably ceramides and / or derivatives thereof; Phospholipids; And a micelle formed of an intercellular lipid component comprising cholesterol.

Micelle is generally defined as a thermodynamically stable and uniform spherical structure composed of amphiphilic, low molecular weight materials having both hydrophilic and hydrophobic groups at the same time.

In general, an amphiphilic material forming a micelle is typically a surfactant, and a polymer material having a specific molecular structure is also present. When these amphiphiles are dissolved in water or other solvents, the hydrodynamic stability tends to align the hydrophilicity on the surface of the solvent, towards the water, and the hydrophobic chains toward the outside of the surface due to thermodynamic stability. As the concentration is continuously increased, the surface of the solution is saturated with the surfactant, and the surface tension is no longer reduced. In the aqueous solution, the hydrophilic groups of the surfactant are collected to the outside and the hydrophobic groups are collected to form a micelle, which is a ball-shaped association.

The intercellular lipid component of the present invention also has a hydrophilic group and a hydrophobic group, which are characteristics of the amphiphilic molecule, in a molecule, thus playing a role similar to that of a surfactant below a certain concentration. Acting and containing more of the intracellular lipid component, this results in the formation of a double lipid form lamellae. Bilayer lamellar structures, such as liposomes, can typically be used in formulations such as creams, but there are limitations because of the problem of opacity due to suspension for use in solubilizing formulations such as lotion.

Therefore, the present invention confirms that ceramide, a derivative of constituents of intercellular lipids, derivatives and phospholipids have structural affinity, and forms micelles with these components to form cholesterol, free constituents of other intercellular lipids in micelle structure. It is based on the fact that it may contain fatty acids, other poorly soluble substances and the like. Moreover, the present invention is based on the surprising finding that when certain components are contained at a certain concentration, these micelles can be stably maintained in solubilized formulations such as lotion while maintaining the micelle structure.

Therefore, in the present invention, the content of each raw material forming the micelle is preferably 0.1-5% by weight of the total weight of ceramide and its derivatives, 0.1-5% by weight of phospholipids and 0.01-2% by weight of cholesterol, based on the total weight of the composition, More preferably 0.1-2% by weight of ceramide and derivatives thereof, 0.1-2% by weight of phospholipids and 0.01-0.5% by weight of cholesterol, 0.1-1% by weight of ceramide and derivatives thereof, 0.1-1% by weight of phospholipids and 0.01-0.2% by weight of cholesterol is most preferred in terms of formation and stabilization of micelles.

In addition, the content of the micelle in the present invention is preferably 0.1-15% by weight relative to the total weight of the composition in the formation of micelles, stabilization of micelles and the like.

In the present invention, micelles having an average particle diameter of micelles of 1-200 nm are preferred, and more preferred if the average particle diameter of micelles is 100-150 nm. Formulation stability may be dangerous if the average particle diameter of the micelle is greater than 200 nm.

As the intercellular lipid component used for micelle formation of the present invention, various intercellular lipid components known in the art may be used, and preferably, ceramide type 1-type 6, galactosyl ceramide, phytosphingosine and sphingosine and non-ping's and such switch pinggo cannabinoid lipids, saturated lecithin, unsaturated lecithin, a lipid component liver cells with a phospholipid and a glyceride can be contained in micelles are cholesterol, sitosterol, cholesteryl sulfate, C _{10 -40} Fatty alcohols;

The micelle of the present invention may further contain free fatty acid, the free fatty acid is C _10-40 fatty alcohol, the content of which is preferably 0.01-2% by weight based on the total weight of the solubilized raw material.

The micelles of the present invention may also contain oils, flavors or mixtures thereof, the content of which is preferably 0.01-1% by weight relative to the total weight of solubilizing raw materials. Such onil and fragrance may be selected from the group consisting of ester-based synthetic oils, silicone oils such as dimethicone and cyclomethicone-based oils, animal and vegetable oils such as jojoba oil and squalane, and synthetic and natural fragrances. Raw materials known in the art as cosmetically useful poorly soluble materials may be selected.

More preferably, the present invention also provides a micelle solubilized formulation composition characterized in that the micelles are dispersed in a polyol, ie comprising micelles dispersed in a polyol. Dispersing the micelles formed by dispersing the micelles in the polyol not only maintains the stability in the formulation for a longer period of time, but also helps to prevent the growth of lamellar structures.

As the polyol, propylene glycol, dipropylene glycol, 1,3-butylene glycol, pentylene glycol, 1,2-hexanediol, and the like may be used alone or in combination. The amount of the polyol may be 85% based on the total weight of the solubilization raw material. Preference is given to -99% by weight.

The components included in the solubilized formulations of the present invention may include components commonly used in solubilized formulations in addition to micelles formed by intercellular lipid components, and include conventional adjuvants such as stabilizers, solubilizers, vitamins, pigments, and the like. can do.

The micelle solubilization formulation composition according to the present invention is about 40-70 ° C., preferably about 50-55, of polyamide, which is the intracellular lipid component of ceramide / derivative thereof, and the phospholipid and intracellular lipid component contained in micelles. A solubilized raw material is prepared by heating and mixing and dissolving at 60 ° C., and preparing a solubilized raw material by mixing and stirring the solubilized raw material into an aqueous raw material prepared by mixing and dissolving purified water or raw water and polyol.

As described in detail above, the solubilized formulation according to the present invention using the specific component and the specific content of the intercellular lipid component as the micelle forming component does not contain the intercellular lipid component in terms of preservation stability, moisturizing ability and elasticity improvement. It is superior to the comparative formulation. In addition, by using the intercellular lipid component as a forming element of the micelle, not only can solve various difficulties in the manufacturing process, but also contains a micelle formed by the intracellular lipid component, so that a cosmetically useful poorly soluble substance is applied to the skin. It can be solubilized without the use of irritating surfactants.

Hereinafter, examples and the like will be described in detail to help understand the present invention. However, embodiments according to the present invention can be modified in many different forms, the scope of the invention should not be construed as limited to the following examples. Embodiments of the present invention are provided to more fully describe the present invention to those skilled in the art.

<Production of Examples and Comparative Examples>

The composition containing the micelle which stabilized the intercellular lipid component of this invention (Example), and the composition containing no micelle (comparative example) were manufactured with the following composition. Specifically, each formulation was prepared by heating phase A to 50-60 ° C., mixing and dissolving the mixture, stirring the mixture slowly with phase B, and then cooling.

Raw material (unit: weight%) Example 1 Example 2 Comparative Example 1 Comparative Example 2 A Ceramide 0.1 0.1 - - Galactosyl ceramide 0.3 0.6 - - Phospholipids 0.2 0.4 - - cholesterol 0.1 0.2 0.1 Cetearyl Alcohol - 0.2 0.2 - Spices 0.03 0.03 0.03 0.03 Fiji-40 Hydrogenated Castor Oil - - 0.1 0.1 Dipropylene glycol 8.0 8.0 8.0 8.0 B Purified water Balance Balance Balance Balance glycerin 5.0 5.0 5.0 5.0

Experimental Example 1 Measurement of Stability of Formulations

The stability test for the examples of the solubilized formulation containing micelles stabilized intercellular lipid components and their comparative examples was carried out by the following method.

In order to test the stability of the formulations, the formulations were stored in transparent vial containers in 25 ° C., 45 ° C. and 40 ° C. incubators, and subjected to a daily cycling test to carry out stability evaluation. Observation of the storage stability of the formulation was evaluated according to the following criteria and the results are summarized in Table 2. Cycling test means a change in the storage temperature on a daily basis and the specific change conditions are as follows: 6 hours at 1-10 ° C, 6 hours at 25 ° C, 6 hours at 45 ° C, and 4 steps at 45 ° C. 6 hours at 25 ° C.

○: Good, △: Different from the beginning, Ｘ: Suspension becomes severe or transparent

Experiment item Example 1 Example 2 Comparative Example 1 Comparative Example 2 25 ℃ 3 days ○ ○ ○ ○ 1 week ○ ○ Ｘ ○ 3 months ○ ○ Ｘ ○ 45 ℃ 3 days ○ ○ Ｘ ○ 1 week ○ ○ Ｘ ○ 3 months △ ○ Ｘ ○ 40 ℃ 3 days ○ ○ Ｘ ○ 1 week ○ ○ Ｘ ○ 3 months ○ ○ Ｘ ○ Cycling test 3 days ○ ○ ○ ○ 1 week ○ ○ Ｘ ○ 3 months ○ ○ Ｘ ○

As can be seen in Table 2, the Example is stable under all temperature conditions, Comparative Example 1 using a solubilized raw material directly in the formulation without forming micelles as intercellular lipid components, the formulation is unstable at all temperature conditions Could know.

Experimental Example 2 Evaluation of Water Retention Capacity

Five test subjects were evaluated for the water retention of each formulation prepared in Examples 1, 2 and Comparative Example 2 as follows.

Moisture retention was measured by measuring the electrical conductivity of the skin surface using SKICON-200 (IBS). In a constant temperature and humidity room maintained at 25 ° C. and 40% relative humidity, 0.03 g of sample per 16 cm ² of skin was applied, and then the resistance value (moisture loss) over time was measured. However, the average us (micros) was 50 before sample coating.

Experiment item (%) Example 1 Example 2 Comparative Example 2 Short term moisturizing 1.5 hours after application 617 691 204 3 hours after application 378 358 167 Long term moisturizing Apply twice a day for 5 days 25.7 25.2 4.2

As shown in the results of Table 3, it can be seen that the example formulation containing micelles stabilized intercellular lipid component of the present invention has a much better moisture retention ability over time than the formulation of the comparative example.

Experimental Example 3 Evaluation of Elasticity Improvement

For five test subjects, the degree of improvement of elasticity of each formulation prepared in Examples 1, 2 and Comparative Example 2 was evaluated as follows.

Skin elasticity measurement was performed by measuring the elasticity of the skin using a cutometer MPA 580 (CK electronics). After applying 30 ul of sample per 4 cm ^{2 of} skin, the elasticity before and after treatment was measured.

Experiment item (%) Example 1 Example 2 Comparative Example 2 Improved elasticity Day 1 1.04 1.05 1.01 Day 5 6.03 5.99 1.05

As shown in Table 4, it can be seen that the example formulation containing micelles stabilized intercellular lipid component of the present invention has an excellent degree of elasticity improvement compared to the formulation of the comparative example.

Experimental Example 4 Human Skin Patch Test

Twenty adult men and women without skin disease on the test site (Forearm) or back (Back) were subjected to the evaluation of the degree of stimulation of each formulation prepared in Examples 1, 2 and Comparative Example 2.

15 ul of sample was applied to a fin chamber (Finn chamber, 100 × 10, EPITEST, Finland), and then sealed in a test site. The patch was applied for 24 hours, the patch was removed, and the test site was marked with a marking pen. Two hours after patch removal, the test site was observed to observe erythema and edema.

Skin reactions were determined according to the regulations of the International Contact Dermatitis Research Group (ICDRG), and the results are shown in Table 5.

Evaluation criteria and scores of skin reactions

sign score Evaluation standard - 0 No response ± 0.5 Weak erythema + 1.0 Clear erythema ++ 2.0 Severe erythema with edema +++ 3.0 Severe erythema, blisters, edema

Experiment item Example 1 Example 2 Comparative Example 2 Skin Polarity Index (PII) 0.05 0.06 0.08

As can be seen in Table 5, it can be seen that the example formulation containing micelles stabilized intercellular lipid component of the present invention has less skin irritation than the formulation of the comparative example.

Claims (9)

Solubilized formulations containing micelles of intercellular lipid components, Micelles are ceramides, derivatives thereof or mixtures thereof; Phospholipids; And intracellular lipid components, including cholesterol, The content is 0.1-5% by weight of the total weight of ceramide and its derivatives, 0.1-5% by weight of phospholipids and 0.01-2% by weight of cholesterol relative to the total weight of the composition. A micelle solubilized formulation composition characterized by The micelle solubilizing formulation of claim 1, wherein the content of ceramide and its derivatives, phospholipids and cholesterol is 0.1-2 wt%, phospholipid 0.1-2 wt% and cholesterol 0.01-0.5 wt%, respectively, based on the total weight of the composition. Composition. The micelle solubilized formulation composition of claim 1 wherein the content of the micelle is 0.1-15% by weight relative to the total weight of the composition. The micelle solubilized formulation composition according to claim 1, wherein the micelle contains free fatty acid, the free fatty acid is C _10-40 fatty alcohol, and its content is 0.01-2% by weight based on the total weight of the solubilized raw material. The micelle solubilized formulation composition of claim 1, wherein the micelles collect oil, fragrances or mixtures thereof, the content of which is 0.01-1% by weight based on the total weight of the solubilized raw material. The micelle solubilized formulation composition according to claim 1, wherein the micelle is dispersed in a polyol, and the content of the polyol is 85 to 99% by weight based on the total weight of the solubilization raw material. The method of claim 1, wherein the intercellular lipid component is ceramide type 1-type 6, galactosyl ceramide, sphingosine, sipingosine, sphinginine, sphingoidoid lipids, saturated lecithin, unsaturated lecithin, glycerophospholipid Micelle solubilized formulation composition, characterized in that it is selected from the group consisting of, cholesterol, cytosterol, cholesteryl sulfate and mixtures thereof. The method of claim 5, wherein the oyl and fragrance is selected from the group consisting of ester-based synthetic oils, silicone oils such as dimethicone and cyclomethicone-based oils, animal and vegetable oils such as jojoba oil and squalane and synthetic and natural fragrances. Micelle solubilized formulation composition, characterized in that. The micelle solubilized formulation composition according to claim 6, wherein the polyol is at least one selected from the group consisting of propylene glycol, dipropylene glycol, 1,3-butylene glycol, pentylene glycol, and 1,2-hexanediol. .