KR20200030217A - Multilamellar vesicle containing LDH with retinal, Method for preparing thereof and Cosmetics composition containing the same - Google Patents

Abstract

The present invention relates to a multilamellar structure containing a retinal-containing layered double hydroxide (LDH), a method for manufacturing the same, and a cosmetic composition including the same. The present invention, specifically, relates to a multilamellar structure comprising a retinal-containing LDH having improved stability and dispersibility of active ingredients and increased skin absorption, by mixing retinaldehyde (retinal), which has an excellent anti-aging effect but is unstable to light and heat, in LDH, coating the mixture with liposomes, and dispersing the same in a multilamellar structure; to a manufacturing method thereof; and to a cosmetic composition including the same.

Description

Multilamellar vesicle containing LDH with retinal, Method for preparing thereof and Cosmetics composition containing the same}

The present invention relates to a multi-lamellar structure including a retinal-containing layered double hydroxide, a method for manufacturing the same, and a cosmetic composition including the same, more specifically, an anti-aging effect is excellent, but layered double retinaldehyde (retinal) which is unstable to light and heat. Multilamellar structure including retinal-containing layered double hydroxide that improves the stability and dispersibility of active ingredients and improves skin absorption by dispersing it in a multilamella structure after mixing it in a layer of hydroxide (Layered-double-hydroxide (LDH)) and coating the liposomes , It relates to a manufacturing method and a cosmetic composition including the same.

Due to the development of functional materials, various functionalization methods to impart higher stability to cosmetic raw materials have been studied. In particular, it is known that these functional materials are not only unstable to light and heat, but also significantly reduce the biological activity of the functional materials by light, heat, and oxygen. Therefore, there is a need to develop technologies for stabilizing various functional cosmetic raw materials.

Retinoic acid, a type of vitamin A, is an excellent anti-aging component, but can cause irritation such as burns, redness and itchiness. In contrast, retinaldehyde (Retinaldehyde) has received a lot of attention because it has an excellent anti-aging effect as well as reducing side effects compared to retinoic acid.

Retinal is one of the vitamin A derivatives, and can have the most similar effect to retinoic acid prescription, and has the advantage of minimizing skin irritation due to less conversion process compared to retinol or other vitamin A forms.

Looking at the process of converting vitamin A derivatives, retinol-> retinal (Retinaldehyde)-> retinoic acid proceeds, but retinol is closer to retinoic acid than retinol, so it improves wrinkles more than retinol. , It has been proved through the paper that it can have more effective effects on improving skin texture. According to Siddharth Mukherjee's paper (Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety) in 2006, when 0.05% of retinal and retinoic acid were applied equally, it showed the same effect on photoaging treatment. There were more patients with side effects when retinoic acid was applied than retinal. In addition, in other studies, it was observed through in vivo tests that retinol had a treatment effect about 20 times lower than retinoic acid.

However, since retinal is also unstable to light and heat and has limitations in use, studies to stabilize the retinal using layered-double-hydroxide and increase the skin absorption rate are actively conducted to solve this. Is becoming.

Layered Double Hydroxide (LDH) is called hydrotalcite and has similar biocompatibility and can be combined with various compounds. In addition, since LDH has an anion exchange ability and an ability to maintain organic and inorganic anions, it is easy to insert and release bioactive molecules, and thus, it is actively used in drug delivery system research. However, LDH has various advantages as a drug carrier, but has a strong cohesive force, so its application range is limited, and it tends to weaken the stability of the formulation.

Therefore, a method of coating liposomes on LDH has been suggested as an alternative, but still shows a phenomenon of aggregation.

Korean Patent Registration No. 10-1882200 discloses a technique for manufacturing a Solid Lipid Nano Particle by mixing LDH synthesized by a co-precipitation method 1: 1 with a nanoemulsion containing an active ingredient, but this uses a mixture prepared as described above. It is a technology for manufacturing multilamellar vesicles and stabilizing retinol over a third time.

Therefore, in the present invention, by improving the stability and dispersibility of the active ingredient by dispersing the liposome-coated LDH mixture in the muramella structure again, the technique of increasing the skin absorption rate was implemented.

Republic of Korea Patent Registration No. 10-1882200

The present invention is to solve the above problems, the first purpose is to mix the retinal in layered double hydroxide (LDH), coat the liposomes and disperse it in a multilamellar structure to improve the stability and dispersibility of the active ingredient and skin It is to provide a multi-lamellar structure including a retinal-containing layered double hydroxide having an increased water absorption rate and a method for manufacturing the same.

In addition, the second object of the present invention is to provide a cosmetic composition containing retinal.

However, the objects of the present invention are not limited to those mentioned above, and other objects not mentioned will be clearly understood by those skilled in the art from the following description.

In order to achieve the above object, a multi-lamellar structure comprising a retinal-containing layered double hydroxide according to the present invention,

Liposome-coated retinal-containing layered double hydroxide (LDH-Liposome);

Phosphatidylcholine;

Hexanediol;

Glycerin (Glycerin);

Medium-chain triglyceride; And

Purified water; characterized in that it comprises a.

In addition, in the multi-lamellar structure comprising the retinal-containing layered double hydroxide according to the present invention,

The liposome-coated retinal-containing layered double hydroxide (LDH-Liposome) is 5 to 50% by weight, phosphatidylcholine is 5 to 30% by weight, hexanediol (Hexanediol) is 0.5 to 5% by weight, and heavy chain triglycerides ( Medium-chain triglyceride) is characterized by containing 5 to 10% by weight.

In addition, in the multi-lamellar structure comprising the retinal-containing layered double hydroxide according to the present invention,

The liposome-coated retinal-containing layered double hydroxide (LDH-Liposome),

Retinal-containing layered double hydroxide (ZnAl-LDH-Retinal);

Hydrogenated lecithin;

Phytosteryl macadamiate;

Medium-chain triglyceride; And

Purified water; characterized in that it comprises a.

In addition, in the multi-lamellar structure comprising the retinal-containing layered double hydroxide according to the present invention,

The retinal-containing layered double hydroxide (ZnAl-LDH-Retinal) is 5 to 20% by weight, hydrogenated lecithin is 0.5 to 50% by weight, phytosteryl macadamiate is 0.1 to 40 Weight%, medium-chain triglyceride (Medium-chain triglyceride) is characterized by containing 2 to 30 weight.

In addition, in the multi-lamellar structure comprising the retinal-containing layered double hydroxide according to the present invention,

The retinal-containing layered double hydroxide (ZnAl-LDH-Retinal),

After dissolving Zn (NO ₃ ) _{2 ·} 6H ₂ O in purified water with Al (NO ₃ ) ₃ · 9H ₂ O, adding the solution to NaOH and Na ₂ CO ₃ and reacting, the mixed solution is filtered. It is characterized by being produced by synthesizing retinal to layered double hydroxide (ZnAl-LDH) produced by washing and drying.

In addition, the multi-lamellar structure containing the retinal-containing layered double hydroxide according to the present invention,

Retinal-containing layered double hydroxides composed of layered double hydroxides (ZnAl-LDH) and retinal; Hydrogenated lecithin; Phytosteryl macadamiate; Medium-chain triglyceride; And purified water; a liposome-coated retinal-containing layered double hydroxide (LDH-Liposome);

Phosphatidylcholine;

Hexanediol;

Glycerin (Glycerin);

Medium-chain triglyceride; And

Purified water; characterized in that it comprises a.

In addition, the present invention provides a cosmetic composition comprising a retinal-containing multilamellar structure.

In addition, the method of manufacturing a multilamellar structure comprising a retinal-containing layered double hydroxide according to the present invention,

(S1) preparing a retinal-containing layered double hydroxide (ZnAl-LDH-Retinal);

(S2) Disperse the medium chain triglyceride and phytosteryl macadamate, disperse the retinal-containing layered double hydroxide (ZnAl-LDH-Retinal) prepared in step S1 in purified water, emulsify with hydrogenate lecithin, and then liposome Preparing a coated retinal-containing layered double hydroxide (LDH-Liposome); And

(S3) The liposome-coated retinal-containing layered double hydroxide (LDH-Liposome) and phosphatidylcholine, hexanediol, glycerin (Glycerin), medium-chain triglyceride prepared in step S2. , And mixing purified water to produce a retinal-containing multilamellar structure (3D liposomal system).

In addition, in the method of manufacturing a multi-lamellar structure comprising a retinal-containing layered double hydroxide according to the present invention,

The retinal-containing layered double hydroxide (ZnAl-LDH-Retinal) of the step S1,

After dissolving Zn (NO ₃ ) _{2 ·} 6H ₂ O in purified water with Al (NO ₃ ) ₃ · 9H ₂ O, adding the solution to NaOH and Na ₂ CO ₃ and reacting, the mixed solution is filtered. It is characterized by being produced by synthesizing retinal to layered double hydroxide (ZnAl-LDH) produced by washing and drying.

The multi-lamellar structure including the retinal-containing layered double hydroxide according to the present invention and the cosmetic composition including the same has an effect of improving stability and dispersibility of an active ingredient and increasing skin absorption.

Figure 1 (a), (b), (c) is a view showing the particle size of the multi-lamellar structure including a retinal-containing layered double hydroxide according to the present invention,
Figures 2 (a), (b), (c) is a diagram showing the zeta potential of a multilamellar structure comprising a retinal-containing layered double hydroxide according to the present invention,
3 (a) shows a retinal-containing layered double hydroxide (ZnAl-LDH-Retinal) and a liposome-coated retinal-containing layered double hydroxide (LDH-Liposome) of a multilamellar structure including a retinal-containing layered double hydroxide according to the present invention. (B) is an enlarged photograph using an electron microscope of a retinol-containing nanoemulsion and a retinol-containing nanoemulsion-LDH composite,
4 is a view showing an XRD analysis of a retinal-containing layered double hydroxide (ZnAl-LDH-Retinal) in a multilamellar structure including a retinal-containing layered double hydroxide according to the present invention;
5 is a view showing FT-IR analysis of retinal-containing layered double hydroxides (ZnAl-LDH-Retinal) in a multilamellar structure including retinal-containing layered double hydroxides according to the present invention;
6 is a view showing the color stability of a liposome-coated retinal-containing layered double hydroxide (LDH-Liposome) and a retinal-containing multilamellar structure (3D liposomal system) in a multilamellar structure including a retinal-containing layered double hydroxide according to the present invention. ,
7 is a view showing a change in retinal content according to a temperature change of a retinal-containing multilamellar structure (3D liposomal system) in a multilamellar structure including a retinal-containing layered double hydroxide according to the present invention;
8 is a view showing the stability according to the temperature of the multi-lamellar structure containing the retinal-containing layered double hydroxide according to the present invention,
9 is a view showing the transdermal absorption rate of a multi-lamellar structure comprising a retinal-containing layered double hydroxide according to the present invention,
10 is a view showing the results of the toxicity test of the multi-lamellar structure containing the retinal-containing layered double hydroxide according to the present invention,
FIG. 11 is a diagram showing the results of a test for synthesis of procollagen when applying a multilamellar structure containing a retinal-containing layered double hydroxide according to the present invention to the skin.

Hereinafter, a detailed description of a preferred embodiment of the present invention will be described with reference to the accompanying drawings. In the following description of the present invention, when it is determined that a detailed description of related known functions or configurations may unnecessarily obscure the subject matter of the present invention, the detailed description will be omitted.

Example 1: Synthesis of retinal-containing layered double hydroxide (ZnAl-LDH-Retinal)

The layered double hydroxide was synthesized as follows by a coprecipitation method at a constant pH.

0.04M of Zn (NO ₃ ) _{2 ·} 6H ₂ O was dissolved in purified water with Al (NO ₃ ) ₃ · 9H ₂ O, and the solution was stirred in a solution of 0.15M NaOH and 0.03M Na ₂ CO ₃ While adding. The reaction was carried out at room temperature for 24 hours while maintaining the pH at 10. The reacted mixed solution was stored in an oven at 70 ° C. for 24 hours, filtered, washed with purified water until the pH became neutral, and dried at 60 ° C. for 24 hours. The white powder produced by drying was identified as ZnAl-LDH.

Retinal was synthesized by co-precipitation using the resulting ZnAl-LDH inorganic matrix, and the LDH synthesized was named ZnAl-LDH-Retinal.

Example 2: Preparation of a liposome-coated retinal-containing layered double hydroxide (LDH-Liposome)

The process of manufacturing a W / O nanoemulsion for producing a liposome-coated retinal-containing layered double hydroxide (LDH-Liposome) using a high pressure homogenizer is as follows.

The components of Table 1 below are classified into compositions belonging to the respective dispersed phases and continuous phases, respectively, put into a container, and dissolved at 50 ° C. After dispersing the medium chain triglyceride (MCT oil) and phytosteryl macadamiate evenly in the continuous phase, and dispersing ZnAl-LDH-Retinal evenly in purified water corresponding to the disperse phase, the hydrogenate lecithin ( Hydrogenated lecithin) was used as emulsifier.

The dispersed phase and the continuous phase were homogenized for 5 times at 1000 bar using a high speed mixer, and then the homogenized solution was cooled and defoamed to prepare a W / O type nanoemulsion containing ZnAl-LDH-Retinal. The liposome-coated retinal-containing layered double hydroxide (LDH) was named LDH-Liposome.

Ingredients % (w / w) ZnAl-LDH-Retinal
Hydrogenated lecithin
Phytosteryl macadamiate
Medium-chain triglyceride, MCT
Distilled water 12
50
10
5
23 Total 100

In the W / O formulation, the content of hydrogenated lecithin is limited to 0.5-50% by weight, and the content of phytosteryl macadamiate is limited to 0.1-40% by weight. The above figures are to ensure that the stability of the formulation is at an appropriate level. Medium-chain triglyceride (Medium-chain triglyceride) is preferably used in 2 to 30% by weight, and if it exceeds the range, affects the stability of the formulation.

Of course, the above-described liposome coating is also capable of O / W production, and the O / W nanoemulsion manufacturing process is as follows.

The components of Table 2 below are classified as compositions belonging to the respective dispersed phases and the continuous phases, respectively, put into containers, and dissolved at 50. After dispersing the medium chain triglyceride (MCT oil) and phytosteryl macadamiate evenly in the disperse phase, and dispersing ZnAl-LDH-Retinal evenly in purified water corresponding to the continuous phase, hydrogenate lecithin ( Hydrogenated lecithin) was used as emulsifier.

The dispersed phase and the continuous phase were homogenized for 5 times at 1000 bar using a high speed mixer, and then the homogenized solution was cooled and defoamed to prepare an O / W type nanoemulsion containing ZnAl-LDH-Retinal.

Ingredients % (w / w) ZnAl-LDH-Retinal
Hydrogenated lecithin
Phytosteryl macadamiate
Medium-chain triglyceride, MCT
Distilled water 12
5
5
10
68 Total 100

In the O / W formulation, an appropriate level of hydrogenated lecithin is limited to 0.5 to 10% by weight, and phytosteryl macadamiate is limited to 0.1 to 10% by weight. Medium-chain triglyceride (2) to 20% by weight of medium-chain triglyceride, which helps skin penetration, is preferred, and it affects formulation stability when the range is exceeded.

Example 3: Formation of a retinal-containing multilamellar structure (3D liposomal system)

The composition of Table 3 below was put in a container, dissolved at 80 ° C., and then mixed for 10 minutes using a homo mixer. Then, using a high pressure homogenizer, homogenized 5 times at 1000 bar, cooled and defoamed to prepare a ZnAl-LDH-Retinal-containing multilamellar vesicle. The resulting multilamellar constructs (MLVs), which are multi-layer carriers, were named 3D liposomal systems.

Ingredients % (w / w) LDH-Liposome
Phosphatidylcholine
Hexanediol
Glycerin
Medium-chain triglyceride, MCT
Distilled water 50
15
2
10
10
13 Total 100

The most basic component of MLVs is Phosphatidylcholine, which has a hydrophilic head portion and an unsaturated fatty acid tail, and when dispersed in the water phase, forms a bilayered vesicle.

The multilamellar structure according to the present invention preferably contains 5-50% by weight of a retinal-containing layered double hydroxide (LDH-Liposome) coated with liposomes. Phosphatidylcholine contains 5 to 30% by weight, and when less than 5% by weight, formation of vesicles is difficult, and when it exceeds 30% by weight, the amount of the active ingredient in the vesicle decreases and the effect decreases. Hexanediol gives a moisturizing and antiseptic effect, and 0.5 to 5% by weight is suitable. When the content is less than 0.5% by weight, the antiseptic effect is reduced, and when it exceeds 5% by weight, the stability of the formulation is affected.

Comparative Example 1: Preparation of retinal-containing nanoemulsion

To prepare a retinal-containing nanoemulsion using a conventional method, the composition of the components shown in Table 4 below is introduced into a container and dissolved at 50 ° C., and then the solution is mixed for 5 minutes using a homo mixer, followed by high pressure. Homogenized using a homogenizer for 5 times at 1000 bar.

Ingredients % (w / w) Retinal
Hydrogenated lecithin
Phytosteryl macadamiate
Medium-chain triglyceride, MCT
Distilled water 12
5
5
10
68 Total 100

Comparative Example 2: Preparation of retinal-containing nanoemulsion-LDH complex

To prepare a retinal-containing nanoemulsion-LDH composite using a conventional method, the composition of the components shown in Table 5 below was introduced into a container and mixed for approximately 10 minutes at 3,000 rpm.

Ingredients % (w / w) Retinal-containing nanoemulsion
Layered double hydroxide 50
50 Total 100

Comparative Example 3: Preparation of retinal-containing multilamellar packets

The composition of the components of Table 6 below is put into a container, dissolved at 80 ° C., mixed for 10 minutes using a homo mixer, then homogenized 5 times at 1000 bar using a high pressure homogenizer, cooled and defoamed to contain retinal. Multilamellar vesicles were prepared.

Ingredients % (w / w) Retinal-containing nanoemulsion-LDH complex
Phosphatidylcholine
Hexanediol
Glycerin
Medium-chain triglyceride, MCT
Distilled water 50
15
2
10
10
13 Total 100

Experimental Example 1: Measurement of particle size and zeta potential

The particle size and zeta potential of ZnAl-LDH-Retinal prepared in Example 1, LDH-Liposome prepared in Example 2, and 3D liposomal system prepared in Example 3 were transferred to ELSZ-1000 (OTSUKA ELECTRONICS Co., LTD). 1 and 2, respectively. Samples were observed after 100-fold dilution with distilled water.

1 and 2, as a result of the measurement, the particle size of the manufactured product was observed with ZnAl-LDH-Retinal (879.2nm), LDH-Liposome (175.6nm), and 3D liposomal system (132.3nm). .

In addition, the zeta potential of the formulation was measured by ZnAl-LDH-Retinal (13.22mV), LDH-Liposome (-46.76mV), and 3D liposomal system (-62.24mV).

That is, it can be seen that as the process of stabilization passes, the particle size decreases and the dispersion degree of the particle increases.

On the other hand, as a result of measuring the particle size of the retinal-containing nanoemulsion and the layered double hydroxide composite, the retinal-containing multilamellar vesicles prepared in Comparative Examples 1, 2, and 3, the particle size was a retinal-containing nanoemulsion. The super-layered double hydroxide composite showed 70 nm, and the retinal-containing multilamellar vesicle showed 210 nm. It can be seen that the particle size is about three times larger during the third stabilization.

In addition, the particle size of the retinal-containing multilamellar vesicle of Comparative Example 3 210 nm, compared with the particle size of the retinal-containing multilamellar structure of Example 3 according to the present invention 132.3nm, it can be seen that a very large difference remains.

In view of the improvement in dispersibility, which is one of the purposes of LDH liposome coating, the size of the particle increases as the particle size increases as the particle size increases. You can see it shrinking. The increase in the size of the particles is likely to result in the formation of entanglement between the particles. Therefore, it can be seen that through this process, uniform dispersion between particles and formulation stability are increased, and it is clear that the difference in skin absorption power remains in the difference in particle size.

Experimental Example 2: SEM observation

Retinal-containing layered double hydroxides (ZnAl-LDH-Retinal) and liposome-coated retinal-containing layered double hydroxides (LDH-Liposome) prepared in Examples 1 and 2, Retinol instead of retinal in Comparative Examples 1 and 2 The containing nanoemulsion and retinol-containing nanoemulsion-LDH complex were observed using an S-4800 (Hitachi) scanning electron microscope, and compared to (a) and (b) of FIG. 3.

As can be seen in Figure 3 (a), both the retinal-containing layered double hydroxide (ZnAl-LDH-Retinal) and the liposome-coated retinal-containing layered double hydroxide (LDH-Liposome) prepared in Examples 1 and 2 are typical circular plates. It was confirmed that the form.

That is, it can be seen that in the comparative example of FIG. 3 (b), LDH and nanoparticles are mixed, whereas in the case of the embodiment, the retinal is stabilized while maintaining the basic structure and characteristics of LDH.

Experimental Example 3: XRD analysis

The powder X-ray diffraction (XRD) pattern for the retinal-containing layered double hydroxide (ZnAl-LDH-Retinal) of Example 1 was measured using a Siemens D5000 diffractometer with CuKα radiation at λ = 1.542 kPa, which is shown in FIG. 4. It is shown in

As shown in Fig. 4, the XRD pattern of retinal-containing layered double hydroxide (ZnAl-LDH-Retinal) shows a characteristic peak of regular layered double hydroxide. The base peaks of the (003), (006) and (009) planes appear at 2θ (2theta) values between 11 ° and 36 °, respectively. The clarity and symmetry of these reflections indicate LDH with high crystallinity, and the layered distance (d003) of LDHs was found to be 0.75 nm.

Experimental Example 4: FT-IR analysis

The Fourier-transform infrared spectroscopy (FT-IR) spectrum for the retinal-containing layered double hydroxide (ZnAl-LDH-Retinal) of Example 1 was observed using IRAffinity-1 (Shimadzu) equipped with a diamond accessory. It was measured in the range of 400-4000 cm ^-1 using 100 scans at 4 cm ^-1 resolution, and is shown in FIG. 5.

As a result, as shown in FIG. 5, the results of analyzing FT-IR of ZnAl-LDH and ZnAl-LDH-Retinal showed similar peaks overall, but in the case of ZnAl-LDH, peaks appeared around 2720 cm ^-1 . , ZnAl-LDH-retinal showed a peak around 3000 cm ^-1 . It can be predicted that in the case of ZnAl-LDH-Retinal, Retinal is intercalated and the aldehyde of the host layer is changed to an alkyl group, and thus interaction between the Retinal and the host layer has occurred.

Intercalation is to stabilize by inserting an active ingredient between the layers of a layered material, and intercalating retinal to ZnAl-LDH to protect the active ingredient from light, oxygen, heat, and the like. The liposome coating improves dispersion stability, controls the release of active ingredients, and encapsulates the LDH mixture in a multilamellar structure to help distribute the active ingredients evenly and efficiently penetrate the skin.

Experimental Example 5: Measurement of color stability

In order to measure the color stability of the LDH-Liposome and 3D liposomal system prepared in Examples 2 and 3, a Chromameter (JS-555, Color Techno System) was used to store the chamber at 25 ° C and 40 ° C and after exposure to sunlight 1 The color stability of LDH-Liposome and 3D liposomal system was examined for months. Color measurements were performed according to the CIE Lab scale.

The color stability results of LDH-Liposome and 3D liposomal system are shown in Fig. 6, and as a result, when the sample is exposed to a natural light source or high temperature (40 ° C), the color intensity of LDH-Liposome changes in color intensity of 3D liposomal system. Appeared bigger than the change. Therefore, it can be seen that the 3D liposome system is more stable at light exposure and high temperature.

Experimental Example 6: Retinaldehyde content observation according to temperature change

In order to measure the change according to the temperature change of the content of retinal (Retinaldehyde) contained in the 3D liposomal system prepared in Example 3, the HPLC (Model 510 Waters USA) analysis method of the conditions in Table 7 below was used. Samples were stored at 25 ° C, 38 ° C, and 45 ° C for 3 weeks.

Column Capcell Pak C18 4.6 ⅹ 250mm Flow rate 1.0 mL / min Detection / Temp UV 254nm / 30? Injection volume 20 Ul Analysis time 30 min Mobile phase 100% Methanol

The measurement results are shown in FIG. 7, and as shown in FIG. 7, the 3D liposomal system was the most stable at 25 ° C and showed a decrease in retinaldehyde at 45 ° C and 50 ° C. A decrease was observed at high temperature, but it was observed that at room temperature, about 50% retinal was still maintained.

Experimental Example 7: Stability measurement

In order to measure the stability of the LDH-Liposome and 3D liposomal system prepared in Examples 2 and 3, LDH- using Turbiscan AGS (Formulation) that can detect stability evolution and quantify global formula changes on a TSI scale The stability of liposome and 3D liposomal system was observed. Samples were scanned at 40 ° C. for 3 days at preset intervals (4 hours). Multiple scattering measurements were used to detect particle or aggregate size changes and particle migration. The measurement results are shown in FIG. 8.

As shown in FIG. 8, it can be seen through the mean value that the 3D liposomal system has smaller particles at a higher temperature than LDH-Liposome.

Experimental Example 8: Measurement of percutaneous absorption

In order to measure the transdermal absorption rate of the LDH-Liposome and 3D liposomal system prepared in Examples 2 and 3, skin penetration was tested using the Franz diffusion cells method. This Franz cell device consists of two main units, the cell cap (donor) and the cell body (receptor), which is divided into membranes and uses artificial skin (Neoderm®, Tego Science). 50 mM phosphate buffer (pH 7.4, 0.1 M NaCl) was added to 5 ml cells, the solution was dispersed at 600 rpm while maintaining the cell temperature at 32 ° C with temperature-controlled water, and the tested solution (50 for each sample Μm) was poured into the donor. The solution was absorbed and diffused in the skin area 0.64 cm ² range. Thereafter, the residue of the skin was washed with ethanol, and the artificial skin was polished with a tip-type homogenizer (Polytron PT 2100, Switzerland). The absorbed retinal was extracted using 4 ml dichloromethane, the extract was filtered through a 0.45 μm nylon membrane, and the content of retinal was detected by HPLC.

The increase in transdermal absorption of retinal was confirmed by the Franz cell method, and the results are shown in FIG. 9.

As shown in FIG. 9, the 3D liposomal system showed a skin absorption rate 1.6 times higher than that of LDH-Liposome, which is the primary liposome.

Experimental Example 9: Toxicity test

Cell viability was determined by MTT [3- (4,5-dimethylthiazolyl-2) -2,5-diphenyltetrazolium bromide] reduction assay. Normal human skin fibroblasts were prepared in a 96-well flat-bottom microtiter plate for 37 hours in a CO ₂ incubator for 24 hours. Cells were treated with 3D liposomal systems of 0.625, 0.3125, 0.16, 0.08, 0.04, 0.020, 0.010, 0.005, 0.0024 and 0.0012%. 10 μL of MTT solution (5 mg / mL) was added to each micro-well. After incubation at 37 ° C for 4 hours, the absorbance value was read at 540 nm with an ELISA reader (Infinite M200, Tecan, Austria), and the results are shown in FIG. 10.

As shown in FIG. 10, as a result of testing the 3D liposomal system for each concentration, synthesis of Procollagen type 1 was confirmed at a concentration at which no toxicity was observed.

Experimental Example 10: Procollagen type 1 synthesis test

Normal human skin fibroblasts were inoculated and cultured in serum-free medium for 24 hours to form a confluent monolayer. Cells were treated with 3D liposomal system of 0.01%, 0.005% and 0.0025%. Procollagen type levels were determined using the Elisa kit (Sigma-Aldrich) and normalized to the volume of the corresponding sample.

The results are shown in FIG. 11, and as shown in FIG. 11, as a result of confirming the synthesis of Procollagen type 1 of the 3D liposomal system, the synthesis of Procollagen type 1 was increased at 0.0025%, 0.005%, and 0.01%.

The 3D liposomal system according to the present invention is identified as a very effective vesicular carrier, as can be seen from the experimental results. Using LDH, it has been confirmed that triple encapsulated retinaldehyde improves stability to external environments such as air, light, and heat, and improves dispersibility, and also enhances skin penetration of retinaldehyde, It is expected to increase procollagen type 1 production and become a promising anti-aging ingredient in the cosmetics industry.

As described above, in the present specification and drawings, preferred embodiments of the present invention have been disclosed, and although specific terms are used, they are merely used in a general sense to easily describe the technical contents of the present invention and to help understand the invention. , It is not intended to limit the scope of the present invention. It is apparent to those skilled in the art to which the present invention pertains that other modified examples based on the technical idea of the present invention can be implemented in addition to the embodiments disclosed herein.

Claims (9)

Liposome-coated retinal-containing layered double hydroxide (LDH-Liposome);
Phosphatidylcholine;
Hexanediol;
Glycerin (Glycerin);
Medium-chain triglyceride; And
Purified water; Multi-lamellar structure comprising a retinal-containing layered double hydroxide, characterized in that it comprises a.
According to claim 1,
The liposome-coated retinal-containing layered double hydroxide (LDH-Liposome) is 5 to 50% by weight, phosphatidylcholine is 5 to 30% by weight, hexanediol (Hexanediol) is 0.5 to 5% by weight, and heavy chain triglycerides ( Medium-chain triglyceride) is a multi-lamellar structure containing a retinal-containing layered double hydroxide, characterized in that it contains 5 to 10% by weight.
According to claim 1,
The liposome-coated retinal-containing layered double hydroxide (LDH-Liposome),
Retinal-containing layered double hydroxide (ZnAl-LDH-Retinal);
Hydrogenated lecithin;
Phytosteryl macadamiate;
Medium-chain triglyceride; And
Purified water; Multi-lamellar structure comprising a retinal-containing layered double hydroxide, characterized in that it comprises a
According to claim 3,
The retinal-containing layered double hydroxide (ZnAl-LDH-Retinal) is 5 to 20% by weight, hydrogenated lecithin is 0.5 to 50% by weight, phytosteryl macadamiate is 0.1 to 40 Weight percent, medium-chain triglyceride (Medium-chain triglyceride) is a multi-lamellar structure containing a retinal-containing layered double hydroxide characterized in that it contains 2 to 30 weight.
According to claim 3,
The retinal-containing layered double hydroxide (ZnAl-LDH-Retinal),
After dissolving Zn (NO ₃ ) _{2 ·} 6H ₂ O in water with Al (NO ₃ ) ₃ · 9H ₂ O, adding the solution to NaOH and Na ₂ CO ₃ and reacting, the mixed solution is filtered. , Multi-lamellar structure including retinal-containing layered double hydroxide, characterized in that it is produced by synthesizing retinal to layered double hydroxide (ZnAl-LDH) produced by washing and drying.
Retinal-containing layered double hydroxides composed of layered double hydroxides (ZnAl-LDH) and retinal; Hydrogenated lecithin; Phytosteryl macadamiate; Medium-chain triglyceride; And purified water; a liposome-coated retinal-containing layered double hydroxide (LDH-Liposome);
Phosphatidylcholine;
Hexanediol;
Glycerin (Glycerin);
Medium-chain triglyceride; And
Purified water; Multi-lamellar structure comprising a retinal-containing layered double hydroxide, characterized in that it comprises a.
A cosmetic composition comprising the retinal-containing multilamellar structure of any one of claims 1 to 6.
(S1) preparing a retinal-containing layered double hydroxide (ZnAl-LDH-Retinal);
(S2) Disperse the medium chain triglyceride and phytosteryl macadamate, disperse the retinal-containing layered double hydroxide (ZnAl-LDH-Retinal) prepared in step S1 in purified water, emulsify with hydrogenate lecithin, and then liposome Preparing a coated retinal-containing layered double hydroxide (LDH-Liposome);
(S3) The liposome-coated retinal-containing layered double hydroxide (LDH-Liposome) and phosphatidylcholine, hexanediol, glycerin (Glycerin), medium-chain triglyceride prepared in step S2. , And mixing purified water to produce a retinal-containing multilamellar structure (3D liposomal system).
The method of claim 8,
The retinal-containing layered double hydroxide (ZnAl-LDH-Retinal) of the step S1,
After dissolving Zn (NO ₃ ) _{2 ·} 6H ₂ O in purified water with Al (NO ₃ ) ₃ · 9H ₂ O, adding the solution to NaOH and Na ₂ CO ₃ and reacting, the mixed solution is filtered. , A method for producing a multilamellar structure including a retinal-containing layered double hydroxide, characterized in that it is produced by synthesizing retinal on the layered double hydroxide (ZnAl-LDH) produced by washing and drying.

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