Method for manufacturing carrier including skin-active substance therein and functional cosmetic composition using same

Abstract

The present invention relates to a method for manufacturing a carrier including a skin-active substance, such as ascorbic acid or glutathione, therein, and to a functional cosmetic composition using same. The present invention includes a method for manufacturing a stable structure that can be composed of at least one hydrophilic region capable of containing a water-soluble skin-active substance and at least one lipid layer capable of separating the hydrophilic region from the outside. The present invention includes a method capable of producing a stable carrier even when employing a skin-active substance acting as a hydrotrope, which alters the dispersion characteristics of a surfactant used in the production of the carrier. When manufacturing a carrier containing a skin-active substance such as ascorbic acid or glutathione, the present invention overcomes difficulties in properly manufacturing the carrier due to a change in phase behavior of a surfactant including hydrogenated lecithin, thereby securing distinction over prior art.

Description

Method for manufacturing a delivery vehicle containing a skin-active substance and a functional cosmetic composition using the same

[0001] The present invention relates to a method for manufacturing a carrier containing a skin-active substance and a functional cosmetic composition using the same. More specifically, the invention relates to a method for manufacturing a carrier containing a skin-active substance such as ascorbic acid or glutathione and a functional cosmetic composition manufactured using the same.

[0002]

[0003] The skin is broadly divided into three layers: the epidermis, dermis, and subcutaneous tissue. Further subdivision reveals that the epidermal layer is classified into the stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and stratum basale; in particular, the stratum corneum is the outermost layer of the skin and is responsible for preventing moisture loss and protecting the skin from harmful external factors.

[0004] The stratum corneum is largely composed of keratinocytes and intercellular lipids forming a lamellar structure. It acts as a protective barrier preventing moisture leakage and the intrusion of harmful substances, while also serving as a barrier that hinders the delivery of skin-activating substances from the epidermal stratum corneum to the dermis. It plays a crucial role in significantly reducing the permeability of these substances. It contains approximately 10–20% moisture. The lamellar layer refers to the structure in which keratinocytes and intercellular lipids are bonded together in a "brick and mortar" fashion. The composition of the lamellar layer consists of 59% keratin, 31–38% natural moisturizing factors (NMF), and 11% intercellular lipids. In particular, the intercellular lipids are composed of ceramides, cholesterol, and fatty acids.

[0005] The granular layer is the layer where natural moisturizing factors and lipids produced in the spinous layer are expelled, and the cells themselves undergo a process of self-lysis in which they become compressed and flattened. It is the layer where the nucleus disappears due to reduced moisture and the stratum corneum process actually begins, and it blocks 80% of ultraviolet rays. Additionally, the granular layer contains filaggrin, a protein known to play an important role in the skin barrier, which is known to have a close influence on skin hydration.

[0006] The stratum spinosum is the thickest layer of the epidermis and contains lymphatic fluid, which is involved in skin circulation and nutrient supply. It is also the layer where Langerhans cells, responsible for skin immunity, exist. It is primarily a region that synthesizes and maintains components necessary for the skin, such as ceramides and moisturizing factors. It is a layer where material exchange occurs between cells to ensure the uniform movement of nutrients, and it contains approximately 70% water.

[0007] The basal layer is located at the bottom of the epidermis and is in contact with the dermis; it consists of a single layer of cuboidal cells, and melanocytes are located there.

[0008] The dermis is a layer closely associated with skin elasticity, with a thickness of about 2 mm. This layer contains collagen, which makes up about 90% of the dermis, elastin, which manages skin elasticity, and hyaluronic acid, which manages skin moisture.

[0009] As such, the skin possesses both hydrophilic and hydrophobic properties and exists in a structure where these hydrophilic and hydrophobic structures alternate. In particular, the hydrophobic layer exhibits properties similar to the structure of a cell membrane and is mainly composed of ceramide, cholesterol, and fatty acids, which poses a problem in that hydrophilic substances have difficulty passing through it. Therefore, despite the great need to deliver active substances such as nutrients to the dermis layer of the skin using a stable skin active substance delivery system having a multilayer structure in which hydrophilic and hydrophobic layers alternate, there is currently no research on this topic.

[0010] The main pathways for active ingredients to penetrate the skin are known to be 1) direct passage through skin cells, 2) passage through the intercellular spaces, or 3) passage through pores. Generally, it is thought that penetration primarily occurs through pores due to their large size, but the actual penetration of active ingredients through the skin is approximately 1%. In reality, it is known that most active ingredients penetrate through the intercellular spaces, and the delivery of skin active ingredients into the skin through the repeated processes of partitioning and diffusion can be explained as follows.

[0011] In the past, it was believed that only liposomes smaller than 100 nm could pass through the gaps between skin cells, as these spaces are very small, ranging from approximately 30 to 60 nm (Journal of controlled release 32:249 (1994)). However, according to a subsequently published paper (Journal of controlled release 59:87–97 (1999)), liposomes smaller than 100 nm fuse to the cell membrane due to cellular tension when passing through the stratum corneum, making it difficult to reach the dermis; conversely, larger liposomes ranging from 500 nm to 1500 nm are capable of reaching the dermis. Although the fundamental mechanism of skin penetration has not yet been fully elucidated, liposomes are believed to be able to pass through narrow gaps because, unlike other micelle structures, their structure is flexible like a water balloon. However, since there is currently no method for manufacturing skin-active substance delivery systems that utilize the stability of these liposomes, there is a great need for their development.

[0012] Various formulations and methods have been developed and researched to promote the absorption of various substances beneficial to skin health. One such method utilizes lipid nanoparticles (LNPs), and research has been conducted on a method to produce nanoparticles containing skin-active substances by utilizing the self-assembly phenomenon of surfactants such as hydrogenated lecithin when dispersed in water. Since lipid nanoparticles can pass through the narrow gaps between keratinocytes, it is believed that material delivery can be achieved more easily when this is utilized compared to cases where it is not.

[0013] Meanwhile, a hydrotrope refers to a substance that has the effect of increasing the water solubility of poorly soluble substances. Representative examples include urea, sodium xylene sulfonate, caffeine, and ascorbic acid, and it has been reported that N,N-diethylnicotinamide has a solubility-enhancing effect on paclitaxel, an anticancer drug with very low water solubility. In addition, poorly soluble substances may include surfactants, which are components of lipid nanoparticles. The effect of the aforementioned hydrotrope may vary depending on various factors, such as the characteristics of the substance itself, the solvent, and the type of surfactant.

[0014] Meanwhile, Korean Registered Patent No. 10-1057283 discloses a method for manufacturing a water-soluble nanoemulsion containing egg yolk lecithin, comprising: a first step of dissolving lecithin paste and ethanol; a second step of mixing purified water and a lecithin ethanol solution; a third step of centrifuging the mixture; a fourth step of mixing the lower layer liquid and purified water after centrifugation; a fifth step of homogenizing the mixture; and a sixth step of filtering the homogenized suspension. However, in Korean Registered Patent No. 10-1057283, there is still a need to develop a method for manufacturing a stable skin-active substance delivery system having a multilayer structure in which a hydrophilic layer and a hydrophobic layer alternately appear by utilizing the stability of liposomes.

[0015]

[0016] The present invention aims to solve the problem that when producing a carrier containing ascorbic acid or glutathione, which are skin active substances, it is difficult to produce it properly due to changes in the phase behavior of surfactants such as hydrogenated lecithin.

[0017] In addition, the present invention aims to provide an optimal content ratio for the production of a carrier containing ascorbic acid or glutathione.

[0018]

[0019] The present invention, for solving the aforementioned problems, provides a method for preparing a carrier comprising ascorbic acid or glutathione and a functional cosmetic composition comprising lipid nanoparticles prepared by said method.

[0020] A method for preparing a carrier comprising ascorbic acid or glutathione according to the present invention comprises the steps of: preparing Phase A by heating 20-30 wt% of polyol, 0.1-1 wt% of hydrated lecithin, and 0.1-1 wt% of lauryl glucoside to 65°C and stirring and dissolving them at 600-1000 RPM for 30 minutes; preparing Phase B by heating 25-65 wt% of water and 10-40 wt% of ascorbic acid or glutathione to 43-47°C and stirring and dissolving them at 600-1000 RPM; slowly adding Phase B to Phase A in a drip manner while stirring continues; stirring a mixture of Phase A and Phase B at 600-1000 RPM at 65°C for 10 minutes; cooling the stirred mixture of Phase A and Phase B to room temperature while continuing stirring at 600-1000 RPM; and cooling the It may include a step of obtaining lipid nanoparticles by probe sonicating a mixture of phase A and phase B.

[0021] To manufacture a suitable carrier, the following points must be considered.

[0022] First, in order to manufacture a suitable carrier, the dispersed phase of the surfactant must form a colloidal dispersed phase.

[0023] To solve this, the present invention uses a surfactant at a concentration higher than the micelle critical concentration.

[0024] Second. The skin-active substance used in the present invention acts as a hydrotrope, which affects the solubility of the surfactant used to manufacture the carrier, thereby causing changes in the phase behavior of the substance. Therefore, if ascorbic acid or glutathione is included, a stable colloidal dispersed phase may not be formed even above the micelle critical concentration. This may result in the failure to manufacture a suitable carrier; for example, the resulting product may exhibit high viscosity, turbidity, or solidify. The influence of the hydrotrope on the dispersed phase varies significantly depending on various factors, such as the characteristics of the substance itself, the solvent, and the surfactant.

[0025] In order to solve this, the present invention uses a hydrotrough skin active substance in a range that does not affect the dispersed phase of hydrogenated lecithin, and the range is 10 to 27% by weight.

[0026] Third, for the manufactured delivery vehicle to promote skin absorption, its size must be at the nanoscale level.

[0027] In this invention, an additional surfactant is used to obtain a nanoscale-level carrier. This surfactant has large hydrophilic groups and small hydrophobic groups compared to hydrogenated lecithin, the basic component, thereby reducing the minimum size that the carrier can achieve.

[0028] In addition, ultrasonic treatment was applied in the present invention. This uniformly mixes hydrogenated lecithin dispersed in a solvent with an additional surfactant to ensure that the carrier containing the skin-active substance achieves a minimum size and makes the size and properties of each carrier similar.

[0029]

[0030] The method for manufacturing a carrier containing skin-active substances such as ascorbic acid or glutathione described in the present invention and the functional cosmetic composition using the same are expected to have the following effects.

[0031] First, it is possible to manufacture a carrier comprising one or more lipid layers that isolate skin-active substances from the outside, so that the carrier can maintain a stable state even under changes in the external environment, including evaporation.

[0032] Second, it is possible to manufacture a delivery vehicle containing one or more lipid layers containing skin-active substances, and since the lipid layers can change shape and pass through the narrow gaps between keratinocytes, the absorption of skin-active substances into the skin becomes easier.

[0033] Third, ultrasonic treatment enables the fabrication of structures at the tens of nanometer scale level containing hydrogenated lecithin and additional surfactants, which has the effect of promoting the skin absorption of particles compared to using conventional processes.

[0034] Fourth, in the method for manufacturing a carrier, since no substances that are toxic or potentially toxic, including organic solvents generally used when dispersing surfactants, are used, a method for manufacturing a carrier that is harmless to the human body can be provided.

[0035]

[0036] FIG. 1 is a manufacturing process flowchart according to one embodiment of the present invention.

[0037] Figure 2 is an electron microscope image of lipid nanoparticles obtained according to one embodiment of the present invention.

[0038] Figure 3 is the result of confirming the dispersed phase of hydrogenated lecithin according to the amount of ascorbic acid used among the skin active substances according to one embodiment of the present invention.

[0039] FIG. 4 is a schematic diagram of a carrier containing only ascorbic acid among skin active substances according to one embodiment of the present invention.

[0040] FIG. 5 is a schematic diagram of a delivery system containing ascorbic acid and glutathione among skin active substances according to one embodiment of the present invention.

[0041]

[0042] The present invention will be described in detail with reference to the attached drawings and embodiments thereof. However, the following embodiments are presented as examples of the present invention, and if it is determined that a detailed description of a technology or configuration well known to those skilled in the art may unnecessarily obscure the essence of the present invention, such detailed description may be omitted, and the present invention is not limited by this. The present invention is capable of various modifications and applications within the scope of the claims set forth below and the equivalent scope interpreted therefrom.

[0043] Furthermore, the terminology used in this specification is used to appropriately describe preferred embodiments of the present invention, and may vary depending on the intent of the user or operator, or the conventions of the field to which the present invention belongs. Accordingly, the definitions of these terms should be based on the content throughout this specification. Throughout the specification, when a part is described as "comprising" a certain component, unless specifically stated otherwise, this means that it may include additional components rather than excluding other components.

[0044] Throughout this specification, '%' used to indicate the concentration of a particular substance is (w / w) % for solid / solid, (w / v) % for solid / liquid, and (v / v) % for liquid / liquid, unless otherwise noted.

[0045]

[0046] The present invention will be explained in more detail below through examples. However, the above examples and experimental examples are presented as illustrative examples of the present invention, and if it is determined that a detailed description of a technology or configuration well known to those skilled in the art may unnecessarily obscure the essence of the present invention, such detailed description may be omitted, and the present invention is not limited by this. The present invention is capable of various modifications and applications within the scope of the claims set forth below and the equivalent scope interpreted therefrom.

[0047]

[0048] <Preparation Example 1>

[0049] Phase A is prepared by stirring and dissolving polyol, hydrolyzed lecithin, and lauryl glucoside, and Phase B is prepared by stirring and dissolving water and ascorbic acid.

[0050] At this time, the above ascorbic acid can be replaced with a skin active substance such as glutathione.

[0051] The mixing ratio of the above Phase A and Phase B is as shown in Table 1 below.

[0052] PhaseRaw material Namewt %RemarksAPolyol24DispersantHydrogenated lecithin0.5Lauryl glucoside0.5Additional surfactantBWater52SolventAscorbic acid23Active cosmetic ingredientTotal 100

[0053]

[0054] <Example 1> Preparation of lipid nanoparticles containing a skin-active substance

[0055] FIG. 1 is a manufacturing process flowchart according to an embodiment of the present invention. With reference to FIG. 1, the manufacturing process according to Example 1 is described in detail as follows.

[0056] Process 1. Place phase A into a suitable glass vial and heat to 65°C while stirring to dissolve (600~1000 RPM, 30 min).

[0057] Process 2. Place phase B into a suitable glass vial and heat to 45°C while stirring to dissolve (600~1000 RPM).

[0058] Process 3. While stirring continues on Phase A, Phase B is slowly added in a drip manner (600~1000 RPM).

[0059] Process 4. Stir phases A and B under the same conditions for 10 minutes.

[0060] Process 5. Cool and stir phases A+B to room temperature (600~1000 RPM).

[0061] Process 6. Probe sonicate phases A and B. If necessary, refrigerate.

[0062] For reference, if Phase A is heated for a long time without proper stirring, the hydrogenated lecithin may denature to brown; therefore, it must be heated while proper stirring is being performed.

[0063] In addition, since ascorbic acid can be destroyed by heat after heating Phase B, it must be used as soon as possible after heating.

[0064] In addition, since the temperature of phases A+B may rise excessively due to probe sonication in process 6 above, ice or the like must be brought into contact with the vial to prevent the temperature from rising.

[0065]

[0066] Figure 2 of the present invention is an electron microscope image of lipid nanoparticles obtained when successfully manufactured according to the above process. Referring to Figure 2, the size of the lipid nanoparticles is approximately 50 to 110 nm (average approximately 60 nm), confirming that spherical structures at the nanoscale level can be successfully fabricated.

[0067]

[0068] Other additives may be introduced to improve the texture or performance of lipid nanoparticles produced in the present invention or cosmetic composition products using them, and it has been confirmed that successful synthesis of lipid nanoparticles is possible in such cases as well. As an example of the above other additives, glutathione, another functional skin active ingredient, can be used.

[0069]

[0070] <Example 2> Confirmation of Dispersed Phase of Hydrogenated Lecithin According to Content of Skin Active Substance

[0071] Ascorbic acid, among the skin active substances, acts as a hydrotrope and affects the solubility of surfactants used for the preparation of carriers, thereby causing changes in the phase behavior of the substance. Therefore, in order to confirm the dispersed phase of hydrogenated lecithin according to the content of ascorbic acid, mixtures of Preparation Examples 2 to 15 were prepared by varying the composition of Phase B containing ascorbic acid of Preparation Example 1, and the compositions are as shown in Table 2 below.

[0072] Water(wt%) Ascorbic acid(wt%) Preparation Example 2741 Preparation Example 3723 Preparation Example 4705 Preparation Example 56510 Preparation Example 66015 Preparation Example 75520 Preparation Example 85421 Preparation Example 95322 Preparation Example 105223 Preparation Example 115124 Preparation Example 125025 Preparation Example 134827 Preparation Example 144728 Preparation Example 154530

[0073]

[0074] The Phase A composition of Preparation Example 1 and the Phase B composition of Preparation Examples 2 to 15 were mixed to prepare a lipid nanoparticle mixture according to the manufacturing process of Example 1, and the degree of suspension of the mixture was visually confirmed. Figure 3 of the present invention is the result of confirming the dispersed phase of hydrogenated lecithin according to the amount of ascorbic acid used according to Example 2.

[0075] Referring to FIG. 3, it can be seen that the mixture prepared with the B-phase compositions of Preparation Examples 5 to 13 has low suspension and the dispersed phase is stably formed. In contrast, it can be seen that the mixture prepared with the B-phase compositions of Preparation Examples 2 to 4 and Preparation Examples 14 to 15 has high suspension of the liquid phase and lipid nanoparticles are not well formed.

[0076] Therefore, the present invention was completed by confirming that the dispersion phase of hydrogenated lecithin is not affected when the ascorbic acid content is 10 to 27 wt%.

[0077] Next, additional experiments were conducted using glutathione, another functional skin active ingredient, when preparing lipid nanoparticles according to the above method (see Table 3 below), and results almost identical to those of ascorbic acid were confirmed (see Fig. 5).

[0078] PhaseRaw material Namewt %RemarksAPolyol24DispersantHydrogenated lecithin0.5Lauryl glucoside0.5Additional surfactantBWater37SolventAscorbic acid23Active cosmetic ingredientGlutathione15AdditivesTotal 100

[0079]

[0080] As described above, specific embodiments of the present invention have been described in detail; however, those skilled in the art who understand the spirit of the present invention will be able to easily propose other inventions that are inferior or other embodiments included within the scope of the spirit of the present invention by adding, changing, or deleting other components within the same spirit. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive. The scope of the present invention is defined by the claims set forth below rather than by the detailed description above, and all modifications or variations derived from the meaning and scope of the claims and equivalent concepts should be interpreted as being included within the scope of the present invention.

Claims

1. A step of preparing Phase A by heating 20~30 wt% of polyol, 0.1~1 wt% of hydrated lecithin, and 0.1~1 wt% of lauryl glucoside to 63~67℃ and stirring and dissolving at 600~1000 RPM for 25~35 minutes; A step of preparing Phase B by heating 25~65wt% of water and 10~40wt% of a skin active substance to 43~47℃ while stirring and dissolving at 600~1000 RPM; A step of slowly adding the above-mentioned B phase in a droplet manner while stirring the above-mentioned A phase continues; A step of stirring a mixture of phases A and B at 600 to 1000 RPM at 63 to 67°C for 8 to 12 minutes; A step of continuously stirring the stirred mixture of phases A and B at 600 to 1000 RPM while cooling it to room temperature; A step of obtaining lipid nanoparticles by sonicating a cooled mixture of phases A and B; A method for manufacturing a delivery vehicle containing a skin-active substance, comprising 2. In Paragraph 1, A method for manufacturing a delivery vehicle containing a skin active substance, characterized in that the skin active substance is one or more of ascorbic acid and glutathione.

3. In Paragraph 1, A method for manufacturing a delivery vehicle containing a skin-active substance, characterized in that the size of the obtained lipid nanoparticles is 50 to 110 nm.

4. In Paragraph 1, A method for manufacturing a carrier containing a skin active substance, characterized in that the carrier containing the skin active substance has low suspension and does not affect the dispersed phase.

5. A cosmetic composition comprising lipid nanoparticles prepared by any one of the methods of paragraphs 1 to 4.

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