KR102283338B1 - Transepidermal delivery system comprising reverse micell - Google Patents

Abstract

The present invention uses a transdermal delivery system including a reverse micelle to pass a skin active material between lipid layers so that it can be effectively delivered to the skin. In addition, bioactive substances that are easily oxidized, poorly soluble substances, antioxidant substances, water-soluble substances, crystalline substances, etc., have low stability and are difficult to penetrate into the skin. Stability, efficacy in the skin, etc. can be improved. In addition, as a non-synthetic fermented product, it is eco-friendly and can be applied to various fields as a natural-derived transdermal delivery system without skin irritation.

Description

Transdermal delivery system comprising reverse micelles {TRANSEPIDERMAL DELIVERY SYSTEM COMPRISING REVERSE MICELL}

The present invention relates to a transdermal delivery system comprising reverse micelles.

This application claims the benefit of priority based on Korean Patent Application No. 2018-0129023 filed on October 26, 2018, and all contents disclosed in the literature of the Korean patent application are incorporated as a part of this specification.

Human skin is largely divided into epidermis, dermis, and subcutaneous fat, and the epidermis is further subdivided into stratum corneum, transparent layer, granular layer, stratum corneum, and basal layer. The stratum corneum, which is the outermost layer of the skin, is composed of a mass of dead keratinocytes, and is mainly composed of keratinocytes composed of protein, and has a structure in which lipids such as ceramide, cholesterol, and free fatty acid fill the spaces between the keratinocytes. This lipid layer prevents the evaporation of moisture from the body and has a health function to protect the body against external invasion, and an aesthetic function to make the skin look shiny and smooth.

There are intrapathway, interpathway, and transcelluar pathways for permeation of substances in the skin. Among them, the interpathway is high for the efficiency of material permeation into the skin. On the other hand, the stratum corneum of the skin is easier to absorb and permeate the hydrophobic material than the hydrophilic material.

Factors affecting the skin absorption of drugs are size, shape, surface charge, lipophilicity, penetration enhancer, form of formulation, and the state of the stratum corneum. In order to allow the active ingredient to pass through the skin naturally, hydrophobicity or a carrier combining hydrophilicity and hydrophobicity should be used. it is common

However, these micelles or liposomes have a limit in absorbing active substances through the lipid layer of the skin. This is because the stratum corneum, which is the outermost layer of the skin, is stacked with keratinocytes and the lipid component between them is structurally easier for a hydrophobic substance to permeate between the keratinocytes rather than a hydrophilic substance.

Reverse micelles mean that nanometer-sized (1-10 nm) round particles are dispersed in an organic solvent by the activity of a surfactant.

On the other hand, the reverse micelle system is an aggregate that is spontaneously arranged so that the hydrophobic part (tail) of the surfactant faces outward and the hydrophilic part (head) faces inward in the environment of a non-polar solvent. It can be dispersed into nano-sized particles.

Therefore, there is a need for a method that can effectively penetrate active ingredients from the skin by applying reverse micelles. In addition, it was attempted to improve stability by capturing active substances that are vulnerable to oxidation and decomposition.

The present invention relates to a transdermal delivery system comprising reverse micelles.

The present invention in order to solve the above problems,

Fermented product formed from Candida bombicola UA-06 (Accession No.: KCTC13855BP, Korea Research Institute of Bioscience and Biotechnology); and

including skin active substances,

The fermented product forms a reverse micelle structure, and the skin active material is entrapped in the reverse micelle structure.

According to one embodiment, the fermented product is a seed culture step of activating Candida bombicola UA-06 microorganisms; and

It may be prepared by a method comprising a fermentation step of fermenting the seed cultured microorganism and vegetable oil.

According to one embodiment, the medium used in the seed culture step may include yeast extract, glycerin, K ₂ HPO ₄ , KH ₂ PO ₄ , NH ₄ NO ₃ and MgSO ₄ .

According to one embodiment, the medium used in the fermentation step is yeast extract, glycerin, K ₂ HPO ₄ , KH ₂ PO ₄ , NH ₄ NO ₃ , MgSO ₄ , glucuronolactone ( glucuronolactone) and vegetable oils.

According to one embodiment, the medium used in the seed culture step is yeast extract 5 to 30 g/L, glycerin 10 to 40 g/L, K ₂ HPO ₄ 10 to 50 g/L, KH ₂ PO ₄ 3 to 15 g/L, NH ₄ NO ₃ 1 to 10 g/L and MgSO ₄ 0.5 to 5 g/L,

The medium used in the fermentation step is 0.5 to 3 g/L of yeast extract, 1 to 20 g/L of glycerin, K ₂ HPO ₄ 10 to 50 g/L, KH ₂ PO ₄ 3 to 15 g/L, NH ₄ NO ₃ 1 to 10 g/L, MgSO ₄ 0.5 to 5 g/L, glucuronolactone 40 to 200 g/L, and vegetable oil 50 to 1000 g/L.

According to one embodiment, the seed culture step is carried out at 15 to 30 ℃, 100 to 500 rpm, 0.5 to 2vvm, aerobic conditions,

The fermentation step may be performed at a temperature of 20 to 35° C. and mixing conditions of 50 to 200 rpm.

According to one embodiment, the seed fermentation step may be terminated at the endpoint of the exponential growth of the bacteria.

According to one embodiment, the vegetable oil is sunflower seed, grape seed, canola, rice germ, olive, soybean, argan, brown rice, perilla, sesame, almond, peanut, corn, red ginseng, avocado, macadamia, coconut, rosehip, vitamin tree seed , shea fruit, oil palm, bergamot fruit, camellia seed, safflower seed, apricot seed, poppy seed, evening primrose seed, castor seed, green tea seed, meadowfoam seed, flax seed and hemp seed.

According to one embodiment, it may further include a purification process step after the fermentation step, wherein the purification step leaves the fermentation product to separate the upper layer and the lower layer, discards the lower layer, _{and adds MgSO 4} and stirs and centrifugation. to remove microorganisms and moisture; and

Using magnesium silicate as a filler in the affinity chromatography column may include recovering the oil from which fatty acids and impurities are removed.

According to one embodiment, a form in which the skin active material is collected in the reverse micelle may be formed.

According to one embodiment, the skin active material is vitamin C, vitamin B, kojic acid, isoflavones, amino acids, peptides, adenosine, proteolytic enzymes and enzymes, arbutin, hyaluronic acid, hydroquinone, ceramide, coenzyme Q10, It may include one or more selected from the group consisting of tetrahydrocurcuminoids, anthocyanins, collagen, retinol, bee saline extract, gardenia extract, turmeric extract and centella asiatica extract.

The specific details of other embodiments according to the present invention are included in the detailed description below.

The present invention uses a transdermal delivery system including a reverse micelle to pass a skin active material through a lipid layer so that it can be effectively delivered to the skin. In addition, physiologically active substances such as active substances that are easily oxidized, poorly soluble substances, antioxidants, and water-soluble substances can be easily grafted into cosmetic formulations, and solubility, emulsification, oxidative stability, and skin efficacy can be improved. In addition, as a fermented product rather than a synthetic product, it is eco-friendly and has no toxicity to skin cells, so it can be applied to various fields as a human-friendly transdermal delivery system.

1 is a photograph showing a thermal stability evaluation result.
2 and 3 are graphs showing the results of measuring the particle size of the reverse micelle.
4 is a photomicrograph of observing reverse micelles.
5 to 7 are graphs showing the measurement results of the amount of skin permeation.

Since the present invention can apply various transformations and can have various embodiments, specific embodiments are illustrated in the drawings and described in detail in the detailed description. However, this is not intended to limit the present invention to specific embodiments, and it should be understood to include all modifications, equivalents and substitutes included in the spirit and scope of the present invention. In describing the present invention, if it is determined that a detailed description of a related known technology may obscure the gist of the present invention, the detailed description thereof will be omitted.

Naturally derived surfactants contain a large amount of ingredients useful for the skin, and among them, bio-surfactants using microorganisms have many advantages.

On the other hand, when the surfactant is at a certain concentration or more, it is common to form a micelle structure in which hydrophobic groups are concentrated in the center of the aqueous phase. Conversely, in the oil phase, a reverse micelle structure is formed in which low molecular weight hydrophilic groups are concentrated in the center. Reverse micelles are more efficient at passing through the lipid layer of the skin than micelles, so they can be applied as a system for stably delivering water-soluble active substances to skin cells through the intercellular space.

Therefore, it is an object of the present invention to provide a transdermal delivery system including such reverse micelles.

Specifically, the present invention

Fermented product formed from Candida bombicola UA-06 (Accession No.: KCTC13855BP, Korea Research Institute of Bioscience and Biotechnology); and

including skin active substances,

The fermented product forms a reverse micelle structure, and the skin active material is entrapped in the reverse micelle structure.

According to one embodiment, the fermented product may include a seed culture step of activating the Candida bombicola UA-06 microorganism and a fermentation step of fermenting the seed cultured microorganism and vegetable oil.

According to one embodiment, the medium used in the seed culture step may include yeast extract, glycerin, K ₂ HPO ₄ , KH ₂ PO ₄ , NH ₄ NO ₃ and MgSO ₄ . Specifically, for example, yeast extract (yeast extract) 5 to 30 g / L, for example 10 g / L, glycerin (glycerin) 10 to 40 g / L, for example 20 g / L, K ₂ HPO ₄ 10 to 50 g / L, eg 25 g/L, KH ₂ PO ₄ 3-15 g/L, eg 7 g/L, NH ₄ NO ₃ 1-10, eg 3 g/L and MgSO ₄ 0.5-5 g/L , for example, 2 g/L. In addition, it may further contain water, specifically, purified water is preferable, for example, purified water using an ion exchange resin may be used.

According to one embodiment, the medium used in the fermentation step is yeast extract, glycerin, K ₂ HPO ₄ , KH ₂ PO ₄ , NH ₄ NO ₃ , MgSO ₄ , glucuronolactone ( glucuronolactone) and vegetable oils. Specifically, for example, yeast extract (yeast extract) 0.5 to 3 g / L, for example 1 g / L, glycerin (glycerin) 1 to 20 g / L, for example 20 g / L, K ₂ HPO ₄ 10 to 50 g / L, eg 25 g/L, KH ₂ PO ₄ 3 to 15 g/L, eg 7 g/L, NH ₄ NO ₃ 1 to 10, eg 3 g/L, MgSO ₄ 0.5 to 5 g/L, eg For example, 2 g/L, glucuronolactone 40 to 200 g/L, for example 100 g/L, and vegetable oil 50 to 1000 g/L, for example 500 g/L. In addition, it may further contain water, specifically, purified water is preferable, for example, purified water using an ion exchange resin may be used.

Specifically, by including glucuronolactone, it is possible to produce an emulsifier with increased hydrophilicity in the form of glucuronolactone-fatty acid, thereby increasing the emulsifying power of the fermented emulsifier or improving the capturing power of hydrophilic active substances. there is.

According to one embodiment, the seed culture step may be performed under 15 to 30 ℃, 100 to 500 rpm, 0.5 to 2vvm, aerobic conditions. In addition, the fermentation step may be carried out at a temperature of 20 to 35° C. and 50 to 200 rpm for 50 to 100 hours, for example, 3 days.

According to one embodiment, the seed fermentation step may be terminated at the endpoint of exponential growth of the bacteria. Specifically, the exponential growth endpoint may be 40 to 120 hours, for example, 50 to 100 hours, for example, the seed fermentation may be terminated at a time point of 60 hours.

According to one embodiment, the vegetable oil is sunflower seed, grape seed, canola (canola), rice germ, olive (olive), soybean, argan (argan), brown rice, perilla, sesame, almond (almond), peanut, corn, red ginseng , avocado, macadamia, coconut, rose hip, shea tree fruit, african oil palm, bergamot fruit, vitamin tree seed, camellia seed From the group consisting of edible or human-friendly oils such as safflower seeds, apricot seeds, poppy seeds, evening primrose seeds, castor seeds, jojoba seeds, green tea seeds, meadowfoam seeds, flax seeds and hemp seeds More than one extracted may be used.

According to one embodiment, it may further include a purification process step after the fermentation step. Specifically, for the removal of moisture and microorganisms, the fermented product is left standing after oil fermentation to separate the hydrophobic portion (fermented product) located in the upper layer and the hydrophilic portion (medium and impurities) located in the lower layer to discard the lower layer, and MgSO ₄ can be added and stirred to remove residual impurities and microorganisms using a centrifuge.

In addition, in order to purify the fatty acids and impurities of the fermented product after the fermentation, a chromatography method may be used. Specifically, by using magnesium silicate as a filler in an affinity chromatography column, fatty acids and impurities can be adsorbed and filtered. However, the fermented product is heated to 50~60℃ before use.

The fermented product included in the present invention includes reverse micelles, in which, in the presence of a hydrophilic lysate, polar groups are oriented inward, hydrophobic groups are oriented toward the outside non-polar solvent side, and a molecular population forming a nearly spherical orientation group. it means.

According to one embodiment, a form in which the skin active material is captured in the reverse micelle may be formed. Specifically, for example, the skin active material is vitamin C, vitamin B, kojic acid, isoflavones, amino acids, peptides, adenosine, proteolytic enzymes and enzymes, arbutin, hyaluronic acid, hydroquinone, ceramide, coenzyme Q10, It may include one or more selected from the group of hydrophilic physiologically active substances such as tetrahydrocurcuminoids, anthocyanins, collagen, retinol, bee saline extract, gardenia extract, turmeric extract and centella asiatica extract.

The lower the interfacial tension of the fermented product, the lower the cohesive force of the molecules, and the lower the cohesive force of the molecules, the better the emulsification ability to be mixed with other phases. This 30 dyne/cm or less, for example, 10 to 30 dyne/cm, for example, may be 20 to 30 dyne/cm.

The transdermal delivery system according to the present invention can effectively penetrate the skin active substances, drugs, etc. into the stratum corneum of the skin, for example, through the interpathway method by including the reverse micelles, thereby improving the transdermal absorption rate and improving the dermatological efficacy. can do it In addition, since a stabilized formulation can be prepared by collecting oxidized substances, water-soluble substances, crystalline substances, and poorly soluble substances with reverse micelles, it can be easily used in cosmetics and pharmaceuticals.

In addition, if a delivery system including reverse micelles is used, skin active substances, drugs, etc. can be easily absorbed through the transdermal route, hair follicles, etc., and thus can be applied to various fields such as cosmetics and pharmaceutical compositions.

Hereinafter, embodiments of the present invention will be described in detail so that those of ordinary skill in the art can easily carry out the present invention. However, the present invention may be embodied in many different forms and is not limited to the embodiments described herein.

manufacturing example

Obtained Candida bombicola UA 06 (Accession No.: KCTC13855BP, Korea Research Institute of Bioscience and Biotechnology).

Candida bombicola UA 06 with yeast extract 10 g/L, glycerin 20 g/L, K ₂ HPO ₄ 25 g/L, KH ₂ PO ₄ 7 g/L, NH ₄ NO ₃ 3 g/ L, MgSO ₄ Inoculated in a medium consisting of 2 g / L and distilled water 933 g / L 20 ℃, 300 rpm, and cultured under aerobic conditions of 1 NL / min (1 vvm). The culture was terminated at 60 hours, the end point of exponential growth, by measuring absorbance at 600 nm with a spectrophotometer (Epoch2, BioTek). The culture solution was centrifuged (16,000 g, 30 minutes) to precipitate the cells and washed several times with a phosphate buffer to obtain the cells.

Fermentation of oil

For oil fermentation, yeast extract 1.0 g/L, glycerin 20 g/L, K ₂ HPO ₄ 25 g/L, KH ₂ PO ₄ 7 g/L, NH ₄ NO ₃ 3 g/L , MgSO ₄ 2 g/L, glucuronolactone 100 g/L, vegetable oil 500 g/L, and distilled water 333 g/L. In a 5 L fermenter, the fermentation broth is mixed at 25°C and 100rpm. prepared. When the temperature of the fermentation broth was 25° C., 2.5 g/L of the cells was added, and fermentation was performed for 3 days. As vegetable oil, sunflower seed oil was used.

refine

After 3 days of fermentation, the remaining enzyme activity with respect to the fermented product was lost at a high temperature of 90° C., the pH was adjusted to 4 to 5 with 1N HCl, and the fermented product was left standing for 6 to 12 hours to obtain an aqueous layer (microorganism and medium) The water layer was removed by separating the oil layer (reverse micellar formation ferment emulsion). In order to remove the moisture remaining in the fermented product, _{20 g/L of MgSO 4} was added, and the mixture was stirred at 50° C. and 300 rpm for 2 hours to obtain a transparent oil layer (reverse micelle-forming fermentation emulsion) after centrifugation. In addition, the fatty acids and impurities of the fermentation emulsion were purified by a column filled with magnesium silicate, and then filtered under reduced pressure with a 0.45 μm filter to completely remove the _{remaining small particles of MgSO 4 to obtain a fermented product containing reverse micelles.}

Examples 1 to 11 and Comparative Example 1

Fermented products including reverse micelles according to Preparation Example were cultured in the fermentation broth medium composition of each Example and Comparative Example according to Table 1. In addition to the vegetable oils described in the Examples, sunflower seeds, grape seeds, canola, rice germ, olive, soybean, argan, brown rice, perilla, sesame, almond, peanut, corn, red ginseng, avocado, macadamia, coconut, rosehip, vitamin tree seed, shea Edible or human-friendly oils such as tree fruit, oil palm, bergamot fruit, camellia seed, safflower seed, apricot seed, poppy seed, evening primrose seed, jojoba seed, castor seed, green tea seed, meadowfoam seed, flax seed, hemp seed, etc. may be included within the scope of the present invention.

Examples 12-29:

A transdermal delivery composition including reverse micelles was prepared with the composition shown in Tables 2 and 3.

The same medium composition as in Example 1 was selected, and the fermented oil containing the reverse micelle-forming emulsifier according to Example 1 was referred to as a carrier oil because it was a skin delivery medium. In the collection method, after mixing and dissolving the active material and the solvent, it was added to a carrier oil heated to 70° C. and stirred until it became transparent. And after cooling to 30 degreeC, it was completed by confirming transparency.

Experimental Example 1: Stability evaluation by temperature

In order to evaluate the stability according to the change of time and temperature conditions for the composition in which the active material is captured, room temperature (15-25 ° C.), low temperature (-5 ° C.), high temperature (50 ℃) and circulation (-5 to 40 ℃) conditions, the stability as time elapsed for 1 month and 3 months was observed.

The evaluation was conducted by checking color and precipitation (transparency) to determine whether the active ingredient was stably captured and whether the material was denatured. When it is not stably collected, the appearance becomes opaque, and precipitation of the active material occurs.

The evaluation results under severe conditions are shown in Table 4, and the evaluation results under normal conditions are shown in Table 5. Cycling conditions were one cycle in which the temperature was changed from -5 to 40° C. for 12 hours. In addition, stability was observed for 3 months under normal conditions and 1 month under severe conditions.

As a result, it is possible to prepare a stable composition by collecting vitamins, amino acids, peptides, plant extracts, antibacterial agents, antioxidants, enzymes, etc. into nanoparticles.

Experimental Example 2: Thermal stability test

Using the examples, the thermal stability of the composition in which the active material was captured by forming reverse micelles was evaluated. As a test method, 150 g of Examples 1, 12, 13, and 16 were weighed in a glass container and heated in a water bath at 90 to 100° C. for 1 hour and 30 minutes. Thereafter, color and odor were compared before heating and when 1 day after heating had elapsed. As a result, color and odor changes before and after heating were not observed in all samples. In addition, Example 1, which is a carrier oil, was similarly tested and compared with the composition in which the active material was collected, and the results are shown in FIG. 1 .

Experimental Example 3: Reverse micelle particle size measurement

Reverse micellar particles of the compositions according to Examples 13 and 19 were measured using a particle size analyzer (ELSZ-1000, Otsuka Electronics). The results are shown in FIGS. 2 and 3, and it was confirmed that the average particle size of 1.4 to 2.2 nm was distributed.

Experimental Example 4: Reverse micelle observation

Reverse micelle formation was observed using a transmission electron microscope (JEM-F200, JEOL) to confirm whether the active material of Example 12 was captured. The sample was pretreated by dropping a drop on a Cu grid coated with carbon, drying it at room temperature for 6 hours, and observed under a microscope.

The micrograph is shown in FIG. 4 . It can be seen that the active material in the oil phase is collected in a nano size to form a round reverse micelle.

Experimental Example 5: Skin penetration test

Artificial skin (Strat-M) was used for skin permeation evaluation of the compositions according to Examples and Comparative Examples. After the donor chamber was covered and clamped, the aqueous phase was filled in a Franz diffusion cell and maintained at 32°C. The permeation test was performed by applying 0.5 ml of each of the prepared Examples and Comparative Examples. In the permeation test, 5.0 ml of the aqueous phase was collected and analyzed by time. Then, it was supplemented with a new aqueous phase. However, as the aqueous phase, a solvent having high solubility of the active substance was used.

In order to analyze the cumulative skin permeation amount, it was measured by HPLC method.

HPLC analysis conditions of Example 12 (tetrahydrocurcumin, tetrahydrocurcumin, THC) are shown in Table 6, and Waters Alliance2690 liquid chromatograph system (Waters, USA) and Waters 2420 detector (Waters, USA) were used. As a column, 5C18-AR-II (4.6 mm I.D. x 150 mm), 4.5 μm (Cosmosil, Japan) was used. In Comparative Example 1, tetrahydrocurcumin (THC) was dissolved in dipropylene glycol at the same concentration as in Example 12. The results are shown in FIG. 5 .

As shown in FIG. 5 , it was confirmed that the cumulative skin permeation amount of Example 12 increased by 4.6 times compared to Comparative Example 1 (control group).

In addition, HPLC analysis of Example 13 (ascorbic acid, Ascorbic acid) was performed, conditions are as shown in Table 7, and a Waters Alliance2690 liquid chromatograph system (Waters, USA) and a UV detector were used. As a column, 5C18-AR-II (4.6mm I.D.x150mm), 4.5 um (Cosmosil, Japan) was used. In Comparative Example 2, ascorbic acid was dissolved in dipropylene glycol at the same concentration as in Example 13. The results are shown in FIG. 6 .

As shown in FIG. 6 , ascorbic acid was not detected in Comparative Example 2, and the cumulative permeation amount of Example 13 was 54 μg/cm ² was confirmed as

In addition, the HPLC analysis conditions of Example 15 (adenosine, adenosine) are shown in Table 8, and a Waters Alliance2690 liquid chromatograph system (Waters, USA) and a UV detector were used. As a column, 5C18-AR-II (4.6 mm I.D. x 150 mm), 4.5 um (Cosmosil, Japan) was used, and the results are shown in FIG. 7 . Comparative Example 3 is obtained by dissolving adenosine in dipropylene glycol at the same concentration as in Example 15. The results are shown in FIG. 6 .

As shown in FIG. 7 , it can be seen that the skin permeability of Example 15 is increased by 16 times compared to Comparative Example 3 (control group).

As a result of the above results, the fermented oil (carrier oil) containing the emulsifier that forms reverse micelles improves the stability of the material because it captures active substances effective for the skin in a nano size, and when applied to the skin, it is mainly used in cosmetics. It can be seen that the skin absorption rate is higher than that of the solvent used, and it acts quickly. Although this is mainly limited to the stratum corneum in skin penetration, the carrier oil can easily and effectively deliver the active substance into the eideraml through the intercellular lipid (lamellar layer) constituting the stratum corneum.

Experimental Example 6: Skin irritation test

In this experiment, the primary skin irritation evaluation was performed for the purpose of skin safety evaluation for Example 13. The evaluation institution was commissioned by the Korea Dermatological Research Institute. Thirty-one subjects were selected and applied on the back for 24 hours, and then at 30 minutes, 24 hours, and 48 hours after the patch was removed, the dermatologist judged the presence or absence of primary skin irritation, respectively. The skin reaction was evaluated based on the International Contact Dermatitis Association (ICDRG) standard and the skin reaction evaluation standard of the American Cosmetics Association (PCPC) (Table 9), and the irritation index was calculated as follows using the skin reaction scores of the subjects. .

After calculating the average irritation index, the Draize Dermal Classification System and the EPA (Environmental Protection Agency) Standard Procedure Dermal Classification System were applied, and the degree of irritation was determined according to the skin irritation result judgment table (Table 10).

Table 11 shows the results according to the standards of Tables 9 and 10.

*Measured 30 minutes after patch removal

As shown in Table 11, Example 13 was judged as a non-irritant material.

Example 30: Cream Formulation 1

A cream formulation including Example 13 was prepared according to the composition of Table 12 below. Specifically, after dispersing the carbomer of the A phase of Table 10, the B phase is added, and the mixture is heated to 70° C. and stirred. Then, the C phase was put into the A + B phase container, and mixed with a homomixer at 3500 rpm for 5 minutes. Phase D was added, mixed with a homomixer at 3500 rpm for 5 minutes, neutralized, cooled and defoamed.

Example 31: Natural Face Oil Formulation

A natural face oil formulation including Example 13 was prepared according to the composition of Table 13 below. Specifically, it was added in the order of phase A in Table 11 and stirred with an azimixer, and then phase B was added to phase A and stirred. After that, the transparency was confirmed and completed.

As can be seen from the above results, the present invention can increase the skin permeability and improve the dermatological efficacy by collecting the effective active material in a nano size by forming a reverse micelle.

Example 32: Cream Formulation 2

A cream formulation including Example 27 was prepared according to the composition of Table 14 below. Specifically, after dispersing the carbomer of phase A in Table 12, the phase B was added, heated to 70° C., and mixed for 1 minute at 3000 rpm with a homomixer. Then, the C phase was put into the A + B phase container and mixed for 1 minute at 3000 rpm with a homomixer. In order, the D phase is put into the A + B + C phase container, and the mixture is emulsified by mixing at 3000 rpm for 10 minutes with a homomixer. Phase E was added and mixed with a homomixer at 3000 rpm for 3 minutes, then phase F was added and homomixed. Finally, it was neutralized to phase G, cooled and depilated to complete.

Therefore, skin permeability can be improved by inclusion of easily oxidized, heat-denatured substances, poorly soluble substances, etc. according to the present invention, and can be applied stably and easily to cosmetic formulations.

The above description is merely illustrative of the technical idea of the present invention, and various modifications and variations are possible without departing from the essential characteristics of the present invention by those skilled in the art to which the present invention pertains. In addition, the embodiments disclosed in the present invention are not intended to limit the technical spirit of the present invention, but to explain, and the scope of the technical spirit of the present invention is not limited by these embodiments. The protection scope of the present invention should be construed by the following claims, and all technical ideas within the equivalent range should be construed as being included in the scope of the present invention.

Claims (10)

Fermented product formed from Candida bombicola UA-06 (Accession No.: KCTC13855BP, Korea Research Institute of Bioscience and Biotechnology); and
including skin active substances,
The fermented product forms a reverse micelle structure, and the skin active material is trapped in the reverse micelle structure,
a seed culture step in which the fermented product activates the C andida bombicola UA-06 microorganism; and
It is prepared by a method comprising a fermentation step of fermenting the seed cultured microorganism and vegetable oil,
Transdermal delivery including reverse micelles, wherein the medium used in the fermentation step includes yeast extract, glycerin, K ₂ HPO ₄ , KH ₂ PO ₄ , NH ₄ NO ₃ , MgSO _{4 , glucuronolactone and vegetable oil} system. delete According to claim 1,
Transdermal containing reverse micelles, wherein the medium used in the seed culture step includes yeast extract, glycerin, K ₂ HPO ₄ , KH ₂ PO ₄ , NH ₄ NO ₃ and MgSO _{4 .} delivery system. delete According to claim 1,
The medium used in the seed culture step is yeast extract 5 to 30 g/L, glycerin 10 to 40 g/L, K ₂ HPO ₄ 10 to 50 g/L, KH ₂ PO ₄ 3 to 15 g/L , NH ₄ NO ₃ 1 to 10 g/L and MgSO ₄ 0.5 to 5 g/L,
The medium used in the fermentation step is yeast extract 0.5 to 3 g/L, glycerin 1 to 20 g/L, K ₂ HPO ₄ 10 to 50 g/L, KH ₂ PO ₄ 3 to 15 g/L, NH ₄ NO ₃ 1 to 10 g/L, MgSO ₄ 0.5 to 5 g/L, glucuronolactone 40 to 200 g/L and vegetable oil 50 to 1000 g/L, including reverse micelles Transdermal delivery system. According to claim 1,
The seed culture step is carried out at 15 to 30 ° C, 100 to 500 rpm, 0.5 to 2 vvm, aerobic conditions,
A transdermal delivery system comprising reverse micelles, wherein the fermentation step is performed at a temperature of 20 to 35° C. and a mixing condition of 50 to 200 rpm. According to claim 1,
The transdermal delivery system comprising reverse micelles, wherein the fermentation step is terminated at the exponential growth endpoint of the bacteria. According to claim 1,
The vegetable oil is sunflower seed, grape seed, canola, rice germ, olive, soybean, argan, brown rice, perilla, sesame, almond, peanut, corn, red ginseng, avocado, macadamia, coconut, rosehip, vitamin tree seed, shea fruit, oil Transdermal delivery system comprising reverse micelles, extracted from the group consisting of palm, bergamot fruit, camellia seed, safflower seed, apricot seed, poppy seed, evening primrose seed, castor seed, green tea seed, meadowfoam seed, flax seed and hemp seed . According to claim 1,
It may further include a purification step after the fermentation step,
The purification step is a step of separating the upper and lower layers by allowing the fermented product to stand, discarding the lower layer _{, adding MgSO 4} , stirring and centrifuging to remove microorganisms and moisture;
A transdermal delivery system comprising reverse micelles, comprising the step of recovering an oil from which fatty acids and impurities have been removed by using magnesium silicate as a filler in an affinity chromatography column. According to claim 1,
The skin active material is vitamin C, vitamin B, kojic acid, isoflavones, amino acids, peptides, adenosine, proteolytic enzymes and enzymes, arbutin, hyaluronic acid, hydroquinone, ceramide, coenzyme Q10, tetrahydrocurcuminoid, Anthocyanin, collagen, retinol, bee parasite extract, gardenia extract, turmeric extract, and a transdermal delivery system comprising at least one selected from the group consisting of centella asiatica extract.

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