KR102105210B1 - Cosmetic composition of oil in water emulsion stabilized retinoids derivative - Google Patents

Abstract

The present invention relates to an oil-in-water emulsified cosmetic composition in which the retinoid derivative is stabilized, and more particularly, an oil-in-water emulsified cosmetic composition comprising a retinoid derivative represented by Chemical Formula 1 in the oil phase, octyldodecanol and dipropylene glycol. It is about.

Description

Oil-in-water emulsified cosmetic composition with stabilized retinoid derivatives {COSMETIC COMPOSITION OF OIL IN WATER EMULSION STABILIZED RETINOIDS DERIVATIVE}

The present invention relates to an oil-in-water emulsified cosmetic composition in which a retinoid derivative is stabilized in a formulation in one emulsification process.

Retinoids are derivatives of vitamin A, retinol, retinal, retinoic acid, retinyl acetate, a type of retinyl ester, retinyl propionate, retinyl propionate And retinyl linoleate, retinyl palmitate, and the like.

However, since the retinoid-based compound is very unstable in light, heat, oxygen, and water, stabilization is required for practical use, and a problem of cytotoxicity has been pointed out as a stability in vivo and as a side effect by retinoic acid receptor (RAR). . Accordingly, development of a retinoid derivative having excellent stability, non-toxicity, and non-irritation while maintaining the efficacy of suppressing photoaging has been progressed.

The applicant has developed a new retinoid derivative with excellent collagen synthesis promoting effect, non-irritating, non-toxic, excellent chemical stability, and excellent skin absorption, and has been registered as Korean Patent Registration No. 10-1194337.

Meanwhile, many studies have been conducted on stabilization of retinoid derivatives, and formulations include cosmetic products that stabilize retinoid by forming a large liquid crystal using a surfactant having a high phase transition temperature in order to minimize contact with air and water as much as possible ( Korean Patent Registration No. 10-0258674), stabilized with liposomes (Korean Patent Publication No. 1998-703668), or by using an amphiphilic polymer having self-association prepared by combining a hydrophobic polyester polymer with a hydrophilic polymer There is a stabilizing agent (Korean Patent Publication No. 2004-0062379) using nanoparticles capable of stably collecting soluble bioactive components in water. In addition, a polymer is mainly used as a material capable of trapping retinoids inside, and methods for encapsulating active ingredients using the polymer include interfacial condensation polymerization, spray drying, coacervation, and solvent evaporation.

However, this stabilization method has a disadvantage in that efficiency is low, economical, and time loss occurs because a secondary process of applying the primary agent to the product after manufacture is involved.

Korean Patent Registration No. 10-1194337 See Korean Patent Registration No. 10-0258674 Korean Patent Publication No. 1998-703668 Korean Patent Publication No. 2004-0062379

In order to solve the above-mentioned problems, the present inventors repeatedly studied to stabilize the retinoid derivative directly in the formulation, and as a result, emulsification stability when emulsifying into an oil-in-water type by selecting an appropriate solvent and a mixing ratio using the solubility property of the retinoid derivative It was found that it was excellent, and the present invention was completed.

Accordingly, an object of the present invention is to provide an oil-in-water emulsified cosmetic composition in which a retinoid derivative is stabilized directly in a formulation in one emulsification process.

In order to achieve the above object, the present invention

Retinoid derivative represented by the following formula (1) in the oil phase,

An oil-in-water emulsified cosmetic composition comprising octyldodecanol and dipropylene glycol is provided:

[Formula 1]

(In the above formula,

R ₁ and R ₂ are the same or different from each other, and are hydrogen or a C1 to C6 linear or branched alkyl group.)

According to the present invention, by applying a mixed solvent of octyldodecanol and dipropylene glycol to the oil phase to emulsify the retinoid derivative, it is possible to provide an oil-in-water (O / W) emulsion cosmetic composition having excellent long-term high-temperature stability.

1 is a picture of observing the state after dissolving a retinoid derivative in four types of oil for 1 month at room temperature.
Figure 2 is a picture of observing the state after dissolving a retinoid derivative in four types of polyalcohols for 1 month at room temperature.
Figure 3 is a picture of observing the dissolved state of the retinoid derivative according to the content ratio of octyl dodecanol and dipropylene glycol.
Figure 4 is a graph showing the high temperature stability of the oil-in-water type emulsion cosmetic composition according to the type of solvent in the oil phase.
5 is a graph showing high temperature stability when an oil-in-water emulsification, liposome, and encapsulation of a retinoid derivative.

Hereinafter, the present invention will be described in more detail.

The present invention provides an oil-in-water emulsified cosmetic composition in which a retinoid derivative is directly stabilized in a formulation. In general, the retinoid derivative in the cosmetic composition is stabilized in the form of liposomes or encapsulation, but has a disadvantage of low efficiency and not easy stabilization.

Accordingly, in the present invention, the retinoid derivative is stabilized in the formulation in one emulsification process by selecting and applying a specific solvent to the retinoid derivative in the oil phase.

The retinoid derivative contained as an active ingredient in the composition according to the present invention has the structure of Formula 1 below.

[Formula 1]

(In the above formula,

R ₁ and R ₂ are the same or different from each other, and are hydrogen or a C1 to C6 linear or branched alkyl group.)

More preferably, in the retinoid derivative, R ₁ in Formula ₁ is a methyl group and R ₂ is Hydrogen's 1,5-bis retinami is also 2-methyl pentane.

The retinoid derivative of Formula 1 according to the present invention can be prepared by reacting a compound of Formula 2 with a compound of Formula 3:

[Formula 2]

[Formula 3]

(In the above formula,

Y is hydroxy or halogen,

R ₁ and R ₂ are the same or different from each other, and are hydrogen or a C1 to C6 linear or branched alkyl group.)

In the present invention, the oil phase portion is a component added to form the internal phase of the oil-in-water emulsion composition, and the retinoid derivative is dissolved in a mixed solvent of octyldodecanol and dipropylene glycol and applied to the oil phase portion.

Preferably, octyldodecanol and dipropylene glycol are used in a weight ratio of 1: 1 to 1: 2. If the content of octyldodecanol is less than the above range, the retinoid derivative cannot be effectively dissolved, and the dispersion stability of the oil-in-water emulsion composition is lowered. On the contrary, even if it exceeds the above range, the dispersion stability of the oil-in-water emulsion composition is lowered. Use appropriately within the above range.

The mixed solvent of octyldodecanol and dipropylene glycol is preferably included in an amount of 20 to 30 parts by weight based on 1 part by weight of the retinoid derivative represented by Chemical Formula 1. If the content of the mixed solvent is less than the above range, the retinoid derivative dissolves non-uniformly. On the contrary, if the content of the mixed solvent exceeds the above range, there is a problem that the solubility increase effect is insignificant and the stability of the oil-in-water emulsion composition is lowered.

Preferably, in the oil-in-water emulsifying composition according to the present invention, the oil phase part satisfies the total 100% by weight.

(Iii) 0.1 to 5% by weight of a retinoid derivative represented by Chemical Formula 1,

(Ii) 35 to 60% by weight of octyldodecanol, and

(Iv) 35 to 60% by weight of dipropylene glycol

It includes.

The content of the retinoid derivative is preferably equal to or greater than the minimum to achieve a minimal skin wrinkle improvement effect, and it is preferable that the content of the retinoid derivative is less than or equal to the maximum value in consideration of reduced usability due to excessive addition and applicability to various formulations. . At this time, the content of the retinoid derivative is preferably adjusted appropriately within the above range according to the content of the ingredients contained in the formulation or cosmetic composition.

When the content of the octyldodecanol and the dipropylene glycol is less than the above range, it is difficult to dissolve the retinoid derivative, and it tends to be difficult to impart appropriate softness. In addition, when formulated in excess of the above range, it is difficult to obtain an emulsified cosmetic composition with improved stability, and there is a disadvantage in that it becomes excessively shiny when applied to the skin.

The water phase part included in the cosmetic of the present invention is an ingredient added to form the external phase of the oil-in-water emulsified cosmetic composition, and is added to improve the moisturizing power and improve the feeling of use, and a moisturizer other than water is commonly used.

In addition, if necessary, additives such as water-soluble / soluble bioactive ingredients, preservatives, pH adjusting agents, fatty acids, emulsifiers, surfactants, antioxidants, sunscreens, pigments, dyes, fragrances, stabilizers, etc., as known in the art It can be added, wherein the type and content can be appropriately selected by those skilled in the art.

Preferably, a water-soluble physiologically active ingredient and a moisturizing agent may be included in the aqueous phase, and a useful physiologically active ingredient in the oily phase.

The water-soluble and oil-soluble physiologically active ingredient is not particularly limited in the present invention, and any known active ingredient may be used. For example, as a bioactive component having a whitening effect, an oil-soluble component including oil-soluble licorice, ethyl ascorbyl ether, α-bisabolol, and the like is possible. In addition, as the active ingredient having the effect of improving wrinkles, a useful component such as adenosine is possible. These water-soluble or oil-soluble physiologically active ingredients are used in the total composition in the range of 0 to 10.0% by weight, preferably 0.001 to 10.0% by weight.

Moisturizers that can be used include polyhydric alcohols such as glycerin, erythritol, xylitol, maltitolglycerin, propylene glycol, 1,3-butylene glycol, sorbitol, polyglycerin, polyethylene glycol, 1,2-pentanediol, and isoprene glycol; Ingredients such as amino acid, sodium lactate, sodium pyrrolidone carboxylate, xyloglucan, quinceseed, carrageenan, pectin, met, cadmane, galactan, delmantan sulfate, glycokene, keratan sulfate, chondroitin, mucoy Tin Sulfate, Keratosulfate, Chondroitin, Mucoitin Sulfate, Keratosulfate, Locust Gum, Succinoglucan, Caronym acid, Hyaluronic Acid, Heparan Sulfate, Sodium Hyaluronate, Collagen, Mucopolysaccharide, Chondroitin A water-soluble polymer material that is sulfuric acid; Dimethyl polysiloxane, methyl phenyl siloxane, silicon; Lactobacillus and Bifidobacteria culture supernatant; And one kind selected from the group consisting of and combinations thereof. These moisturizers are used in the range of 0 to 15.0 wt%, preferably 0.5 to 10.0 wt%, in the total composition.

The oil-in-water emulsified cosmetic composition of the present invention includes softening makeup, converging makeup, nutritional makeup, nutrition cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing water, pack, gel, powder, body lotion, It can be formulated with body cream, body oil, and body essence.

The method for preparing the oil-in-water emulsifying composition according to the present invention is not particularly limited, and an emulsifying method commonly used may be used.

Specifically,

S1) preparing an aqueous phase by mixing an emulsifier, a moisturizer, and purified water;

S2) mixing the retinoid derivative, octyldodecanol and dipropylene glycol to prepare an oil phase;

S3) adding and mixing the oil phase to the water phase; And

S4) It is manufactured through a cooling step.

The mixing process of S1), S2), and S3) is performed in a vacuum emulsifying tank capable of temperature control and stirring by a conventional method, and a method of stirring and heating is performed as necessary.

In one example, the aqueous phase is performed by heating to 50 to 80 ° C, preferably 65 to 75 ° C, and the oily phase is heated to 50 to 80 ° C, preferably 65 to 75 ° C so that other components can be sufficiently dissolved in the oil. Perform.

The stirring is carried out for 3 to 10 minutes at a rate of 2000 to 4000 rpm, preferably 3000 rpm, using a homo mixer in a vacuum emulsifying tank.

Hereinafter, preferred embodiments are provided to help understanding of the present invention.

However, the following examples are only provided to more easily understand the present invention, and the contents of the present invention are not limited by the examples.

Experimental example  One: Retinoid  Solubility evaluation of derivatives

0.5 g of 1,5-bis retinamido 2-methyl pentane was added to 10 g of each solvent, heated until uniformly dissolved, cooled, and stored at room temperature for 1 month, and then observed. The results are shown in FIGS. 1 and 2.

1 is a picture of observing the state after dissolving a retinoid derivative in four types of oil for 1 month at room temperature.

Referring to Figure 1, caprylic / capric triglyceride, mineral oil, cetyl ethyl hexanoate is a retinoid derivative is unevenly dissolved or precipitation occurs, unlike octyl dodecanol is uniformly dissolved and after 1 month No precipitation phenomenon occurred.

Figure 2 is a picture of observing the state after dissolving a retinoid derivative in four types of polyalcohols for 1 month at room temperature.

Referring to FIG. 2, in the case of glycerin, butylene glycol, and propylene glycol, the retinoid derivative dissolves non-uniformly, whereas in the case of using dipropylene glycol, dissolution is uniform, and precipitation occurs after 1 month. .

Experimental example  2: Octyldodecanol  According to the content Retinoid  Derivative solubility evaluation

0.5 g of 1,5-bis retinamido 2-methyl pentane was dissolved in 5, 10, and 15 g of octyldodecanol, respectively, and then stored at room temperature for 1 month to observe the state.

As a result, when 5 g of octyldodecanol was used, the retinoid derivative was dissolved non-uniformly, but when 10 g and 15 g were used, both were uniformly dissolved.

Experimental example  3: With octyldodecanol Dipropylene glycol  According to the content ratio Retinoid  Derivative solubility evaluation

Dissolve stability by dissolving 0.5 g of 1,5-bis retinamido 2-methyl pentane in a mixed solvent in which each solvent (total amount of solvent 10 g) is mixed at a content ratio of 1: 3, 1: 1, 3: 1, and then cooled. Observations and results are shown in FIG. 3.

Figure 3 is a picture of observing the dissolved state of the retinoid derivative according to the content ratio of octyl dodecanol and dipropylene glycol.

As shown in FIG. 3, when the content ratio of octyldodecanol and dipropylene glycol is 1: 3, precipitation occurs after 1 month, and when the content ratio is 3: 1, it dissolves unevenly.

Experimental example  4: Retinoid  Determination of high temperature stability of derivatives

To the content shown in Table 1, an emulsifying composition was prepared through the method for preparing the emulsifying composition shown below.

[Emulsifying Composition Manufacturing Method]

1) The water and oil phases are heated to 75 ℃ each.

2) Oil phase 2 is heated to 75 ℃ and uniformly mixed with oil phase 1 heated to the same temperature.

3) Mix with homogenizer 3000 rpm for 5 minutes

4) After increasing and adding, mix for 3 minutes with homogenizer under the same conditions.

5) Slow cooling, defoaming

Division ingredient Content (% by weight) Example 1 Comparative Example 1 Comparative Example 2 Awards Purified water to 100 to 100 to 100 glycerin 5 5 5 Propanediol 5 5 5 Clofenesin Proper Proper Proper Paid 1 Methyl glucose sesquistearate 2 2 2 Cetearyl alcohol One One One Squalane 3 3 3 Caprylic / Capric Triglyceride 2 2 2 Paid 2 Octyldodecanol 2 4 - Dipropylene glycol 2 - 4 Bis-retinamidomethylpentane 0.2 0.2 0.2 Increment Acrylate / C10-30 alkyl acrylate
Cross polymer 0.1 0.1 0.1 Tromethamine 0.1 0.1 0.1 adding Rosemary Leaf Extract 0.1 0.1 0.1 Phenoxyethanol Proper Proper Proper

The contents of the retinoid derivatives of the compositions prepared through Example 1 and Comparative Examples 1 and 2 were confirmed by HPLC analysis, and detailed analysis methods and results are as follows.

The HPLC used for the bis-retinamidomethylpentane analysis was a Waters model 1525 Gradient system, consisting of a 1525 Binary HPLC Pump, 2707 Autosampler, and 2998 Photodiode Array Detector. The analysis was carried out at a flow rate of 1.0 ml / min using 100% methanol as the mobile phase in a Shiseido capcell pak C18 (4.6 mm * 250 mm, 5 µm) column. The bis-retinamidomethylpentane peak area of the test solution and the standard solution was analyzed using Empower 3 Personal Single System Software at 345 nm measurement wavelength with 10 μl each of the test solution and the standard solution.

The method of preparing the test solution and standard solution used in the HPLC analysis method is as follows. At this time, the test solution was prepared with an emulsion composition stored at 45 ° C for 1 month.

The test solution was prepared by precisely weighing about 1.0 g of an emulsifying composition and dispersing it by adding 10 ml of ethanol and dichloromethane mixed solution (1: 1), adding methanol to make 100 ml, and then extracting with ultrasonic filter through a 0.45 μm syringe filter, and the standard solution was bis-retin About 0.0020 g of amidomethylpentane standard was precisely weighed and dissolved in 10 ml of a mixture of ethanol and dichloromethane (1: 1), and then methanol was added to prepare 100 ml.

The bis-retinamidomethylpentane peak area of the test solution and standard solution was analyzed using Empower 3 Personal Single System Software at 345 nm measurement wavelength with 10 μl each of the test solution and standard solution.

The titer result of the retinoid derivative was expressed as a percentage of the average content analyzed three times by the above HPLC analysis method compared to the content of the retinoid derivative added in the composition, and the results are shown in FIG. 4.

Figure 4 is a graph showing the high temperature stability of the oil-in-water type emulsion cosmetic composition according to the type of solvent in the oil phase.

Referring to FIG. 4, the titer of the retinoid derivative is different according to the solvent type, and when a mixed solvent of octyldodecanol and dipropylene glycol is used in the oil phase, the retinoid derivative has the highest high temperature stability.

Experimental example  5: according to the formulation Retinoid  Determination of high temperature stability of derivatives

5-1. Liposome  Formulation preparation

To the content shown in Table 2, after adding to the mixer, uniformly mixed using a homogenizer and using a high pressure microfluidizer (Microfludizer, US Patent 4533254) to prepare a liposome composition containing a retinoid derivative at 1000 atmospheres Did.

ingredient Content (% by weight) Purified water 30 glycerin 50 Lecithin 5 Octyldodecanol 10 Bis-retinamidomethylpentane 5

5-2. Encapsulation  Formulation preparation

To the content shown in Table 3, the retinoid derivative dissolved in octyl dodecanol and the polymethyl methacrylate were uniformly dissolved in 30 mL of the organic solvent ethanol and then added to purified water. When the particles were formed, the organic solvent was removed through a method of evaporation to prepare a capsule formulation containing a retinoid derivative.

ingredient Content (weight (%) Octyldodecanol 5 Bis-retinamidomethylpentane 5 Polymethyl methacrylate 60 Purified water 30

5-3. Liposome  Formulation Department Encapsulation  Preparation of emulsion composition using formulation

Using the prepared liposomes and encapsulation formulations, emulsifying compositions Comparative Examples 3 and 4 were prepared as shown in Table 4 below.

ingredient Content (% by weight) Comparative Example 3 Comparative Example 4 Purified water to 100 to 100 glycerin 5 5 Propanediol 5 5 Clofenesin Proper Proper Methyl glucose sesquistearate 2 2 Cetearyl alcohol One One Squalane 3 3 Caprylic / Capric Triglyceride 2 2 Octyldodecanol - - Dipropylene glycol - - Bis-retinamidomethylpentane - - Acrylate / C10-30 alkyl acrylate
Cross polymer 0.1 0.1 Tromethamine 0.1 0.1 Retinoid liposome 4 - Retinoid encapsulation - 4 Rosemary Leaf Extract 0.1 0.1 Phenoxyethanol Proper Proper

In order to apply the content of the same retinoid derivative as in Example 1, the contents of liposomes and encapsulation agents were determined, and Comparative Examples 3 and 4 were prepared by adding them in an addition process to reduce stabilization inhibitors in the process.

For the compositions prepared through Example 1 and Comparative Examples 3 and 4, the content of the retinoid derivative was confirmed by the HPLC analysis method after storage at 45 ° C. for 1 month, and the analysis results are shown in FIG. 5.

5 is a graph showing high temperature stability when an oil-in-water emulsification, liposome, and encapsulation of a retinoid derivative.

Referring to FIG. 5, when the oil-in-water emulsification, it was confirmed that the titer of the Reynoid derivative is higher than the liposome and encapsulation formulation at a high temperature, so that the oil-in-water emulsion formulation is a method capable of improving the stability of the retinoid derivative.

Claims (6)

Retinoid derivative represented by the following formula (1) in the oil phase,
Contains octyldodecanol and dipropylene glycol,
The oil phase portion so as to satisfy the total 100% by weight
(Iii) 0.1 to 5% by weight of the retinoid derivative,
(Ii) 35 to 60% by weight of octyldodecanol, and
(Iv) 35 to 60% by weight of dipropylene glycol
Including, wherein the octyl dodecanol and dipropylene glycol is a weight ratio of 1: 1 to 1: 2, oil-in-water emulsified cosmetic composition:
[Formula 1]

(In the above formula,
R ₁ and R ₂ are the same or different from each other, and are hydrogen or a C1 to C6 linear or branched alkyl group.) According to claim 1,
R ₁ is a methyl group and R ₂ is Oil-in-water emulsified cosmetic composition characterized by being hydrogen. delete The oil-in-water emulsified cosmetic composition of claim 1, wherein the octyldodecanol and dipropylene glycol are contained in an amount of 20 to 30 parts by weight based on 1 part by weight of the retinoid derivative represented by Chemical Formula 1. delete The composition of claim 1, wherein the composition is softening lotion, converging makeup, nutritional makeup, nutrition cream, massage cream, essence, eye cream, eye essence, cleansing cream, cleansing foam, cleansing water, pack, gel, powder, body lotion, Oil-in-water emulsion cosmetic composition, characterized in that it is any one of the formulations selected from the group consisting of body cream, bodioyl, and body essence.

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