KR102576017B1 - Water-dispersible ceramide particles, manufacturing method thereof, and emulsion composition comprising the same - Google Patents

Abstract

Water-dispersible ceramide particles are disclosed. Water-dispersible ceramide particles surround composite particles containing ceramide molecules aggregated in a lamellar laminated structure and higher fatty alcohol molecules having 18 to 22 carbon atoms, and the surface of the composite particle, having a hydrophilic functional group and a hydrophobic functional group on the surface. It includes a cellulose network structure formed of bacterial cellulose nanofibers.

Description

Water-dispersible ceramide particles, manufacturing method thereof, and emulsion composition comprising the same

The present invention relates to water-dispersible ceramide particles with high long-term storage stability, a method for preparing the same, and an emulsion composition comprising the same.

In general, abnormalities in skin barrier function are closely related to the structure and content of intercellular lipids in skin keratinocytes, and when the skin barrier function is weakened due to external factors, various skin diseases occur. In particular, it is known that damage to the skin barrier caused by a decrease in ceramide content, which accounts for about 50% of intercellular lipids, acts as a major factor in dry skin and atopic dermatitis. It is known as an effective method for normalization.

However, ceramide is a poorly soluble substance with a high crystallization tendency due to its structural specificity. It is not completely soluble in the oil phase and is not well soluble in water, making it difficult to use in aqueous phase cosmetics. ), such as formulation stability problems occur. Accordingly, techniques for solubilizing ceramides in various forms have been developed.

As one of the ceramide solubilization technologies, in an attempt to prepare an emulsion formulation containing ceramide, a method of preparing a liquid crystal base in advance and subsequently adding it at the very end of an oil-in-water emulsion has been devised. However, most liquid crystal bases made in this way are in the form of wax or paste with very high hardness at room temperature, so compatibility in the process is not easy, and excessive use of lecithin and high-quality fatty alcohol in the manufacture of liquid crystal bases makes the feeling of use of cosmetics worse. has a downside.

In addition, as a conventional technique, there is a method of stabilizing by preparing ceramide nanoliposomes using high-pressure emulsification technology, which has the advantage of increasing percutaneous absorption, but when the particles become smaller, the attraction between particles becomes stronger and a large amount of ceramide In order to stabilize, the amount of surfactant contained is also increased in proportion to the amount, so that not only the feeling of use is reduced, but also skin irritation may occur.

On the other hand, as another prior art, as an attempt to make a liquid crystal emulsion through an emulsification process, there is a method for preparing a liquid crystal emulsion having a multi-layered lamellar structure composed of a surfactant, ceramide, and a higher fatty alcohol, but such a liquid crystal emulsion is used to stabilize the liquid crystal structure. Since it uses chemical molecules that do not exist in actual skin, there is a limit to expecting a high effect in significantly alleviating or improving the skin barrier function, and long-term use may rather result in deformation of the lamellar structure of the skin barrier. Therefore, there is a need to develop a cosmetic composition in which no synthetic emulsifier is added.

As a means to solve this problem, a non-aqueous ceramide liquid crystal composition containing ceramide and phytosphingosine, which are the most important components of lipids between skin barriers, and glycerin fatty acid ester, which is a sebum component, has been developed. not sufficiently validated. In addition, as a single composition, it is effective in stability and efficacy, but the unit price is relatively high compared to existing water-based compositions due to the use of only solvents other than water, and when used as a second addition to an emulsion formulation, there is a possibility that the liquid crystal structure cannot be maintained, so ceramide stabilization There is a problem of poor marketability as a raw material.

One object of the present invention is to provide water-dispersible ceramide particles having high long-term storage stability.

Another object of the present invention is to provide a method for preparing the water-dispersible ceramide particles.

Another object of the present invention is to provide an emulsion composition comprising the water-dispersible ceramide particles.

Water-dispersible ceramide particles according to an embodiment of the present invention surrounds composite particles including ceramide molecules and higher fatty alcohol molecules having 18 to 22 carbon atoms aggregated with each other in a lamellar laminated structure, and the surface of the composite particles, It includes a cellulose network structure formed of bacterial cellulose nanofibers having a hydrophilic functional group and a hydrophobic functional group on the surface.

In one embodiment, the hydrophilic functional group may include a hydroxy group (-OH) or a carboxyl group ion (COO-), and the hydrophobic functional group may include an alkyl group having 16 to 20 carbon atoms.

In one embodiment, the alkyl group may be grafted onto the surface of the bacterial cellulose nanofiber through an amide bond (-CONH-).

In one embodiment, the ratio of the alkyl group may be 0.08 to 0.64 mmol/g of the total functional groups bonded to the surface of the bacterial cellulose nanofiber.

In one embodiment, the diameter of the water-dispersible ceramide particles may be 0.1 to 100 (μm).

In one embodiment, in the composite particle, the mixing ratio (w / w) of the ceramide molecules and higher fatty alcohol molecules may be 1: 1.5 to 1: 4.

In the method for producing water-dispersible ceramide particles according to an embodiment of the present invention, the first step of preparing a water phase by dispersing bacterial cellulose nanofibers having a hydrophilic functional group and a hydrophobic functional group on the surface in water, ceramide molecules And a second step of preparing an oil phase by mixing higher fatty alcohol molecules having 18 to 22 carbon atoms, a third step of mixing and emulsifying the water phase and the oil phase, and the third step of emulsifying. and a fourth step of cooling the emulsion formed in step.

In one embodiment, the bacterial cellulose nanofibers are subjected to TEMPO oxidation treatment of bacterial cellulose, dispersing the bacterial cellulose nanofibers by applying ultrasonic waves after the TEMPO oxidation treatment, and hydrophobic functional groups in the bacterial cellulose nanofibers It can be prepared by including the step of grafting.

In one embodiment, in the step of TEMPO oxidation treatment, at least some of the hydroxyl groups (-OH) present in the bacterial cellulose may be substituted with carboxyl groups (-COOH).

In one embodiment, the hydrophilic functional group may include a hydroxy group (-OH) or a carboxyl group ion (COO-), and the hydrophobic functional group may include an alkyl group having 16 to 20 carbon atoms.

In one embodiment, the second and third steps may be performed at a temperature of 70 to 90 °C.

In one embodiment, in the third step, a step of sonicating the emulsion formed after emulsification may be further performed.

In one embodiment, the mixing ratio (w / w) of the ceramide molecules and higher fatty alcohol molecules may be 1: 1.5 to 1: 4.

In one embodiment, the concentration of the bacterial cellulose nanofibers may be 0.1 wt% or more and less than 1 wt%.

In one embodiment, based on the concentration of the bacterial cellulose nanofibers of 0.5 wt%, the concentration of the oil phase included in the emulsion may be less than 30 wt%.

In one embodiment, based on the concentration of 0.5 wt% of the bacterial cellulose nanofibers, the concentration of ceramide molecules included in the emulsion may be less than 20 wt%.

On the other hand, the emulsion composition according to an embodiment of the present invention includes a water phase and ceramide particles dispersed in the water phase, and the ceramide particles are ceramide molecules aggregated into a lamellar layered structure with each other and a composite particle comprising higher fatty alcohol molecules having 18 to 22 carbon atoms, and a cellulose network structure formed of bacterial cellulose nanofibers surrounding the surface of the composite particle and having a hydrophilic functional group and a hydrophobic functional group on the surface.

According to the present invention, by stabilizing composite particles containing a high content of ceramide molecules in an aqueous system using a cellulose network structure formed of bacterial cellulose nanofibers having hydrophilic functional groups and hydrophobic functional groups on the surface, change in viscosity or growth of crystals It can be stabilized for a long time in the form dispersed in the aqueous phase without Since the water-dispersible ceramide particles of the present invention prepared in this way contain naturally derived bacterial cellulose nanofibers, there is no skin irritation and no fear of damaging the skin barrier function.

And, according to the present invention, since ceramide particles are prepared using a relatively low concentration of cellulose nanofibers without the introduction of a surfactant, it has low cost and high efficiency effects, and high content of ceramide by particleizing ceramide without containing oil Not only can it contain ceramide, but it can fundamentally block ceramide from migrating from the oil phase to the water phase.

In addition, the water-dispersible ceramide particles of the present invention include composite particles in which ceramide molecules and higher fatty alcohol molecules having 18 to 22 carbon atoms are aggregated in a lamellar layered structure, thereby preventing ceramide molecules located at the interface from being precipitated into the aqueous phase. can In addition, the ceramide particles are easy to use because they are dispersed in the water phase, and since they maintain their structure even in a diluted state, they can be added to the oil-in-water emulsion formulation.

1 is a view for explaining water-dispersible ceramide particles according to an embodiment of the present invention.
Figure 2 (a) is a view for explaining the method of TEMPO oxidation treatment and alkyl chain grafting of bacterial cellulose according to an embodiment of the present invention, (b) - (c) are AFM images of bacterial cellulose before and after TEMPO oxidation treatment , (d) is a UV spectrum of the bacterial cellulose nanofiber to which the alkyl chain is grafted, and (e) is a graph showing the amount of carboxyl groups present on the surface of the bacterial cellulose nanofiber after the alkyl chain grafting.
Figure 3 (a) is a diagram for explaining the dialdehyde cellulose (DAC) conversion process and alkyl chain grafting method of TEMPO oxidation-treated bacterial cellulose (TOBC) according to an embodiment of the present invention, (b) is a view for each Aldehyde and imine FT-IR analysis graph of bacterial cellulose after reaction, (c) is a graph comparing zeta potential of TEMPO oxidation-treated bacterial cellulose (TOBC) and bacterial cellulose nanofibers after alkyl chain grafting.
Figure 4 (a) is a graph of the size change of ceramide particles according to the concentration of bacterial cellulose nanofibers ( _C18 BCNF) grafted with alkyl chains (insert: external image), (b) is a ceramide according to an embodiment of the present invention Optical and polarization images of particles, (c) is a fluorescence image of ceramide particles (green: _C18 BCNF, blue: ceramide and higher fatty alcohol), (d) shows a SEM image of ceramide particles.
5 shows a photograph of the appearance of a mixed solution formed during the manufacture of ceramide particles according to Comparative Example 1 of the present invention.
6 shows the results of thermogravimetric analysis according to the mixing ratio of ceramide and higher fatty alcohol included in the ceramide particles of the present invention.
Figure 7a) is the result of SAXS analysis of ceramide particles according to the type of higher fatty alcohol mixed with ceramide, (b) is a graph of d-spacing length change according to the increase in carbon number of higher fatty alcohol, (c) is mixed with ceramide It shows the results of WAXS analysis of ceramide particles according to the type of higher fatty alcohol to be used.
Figure 8 shows the long-term storage stability results according to the type of higher fatty alcohol mixed with ceramide. ((a) myristyl alcohol, (b) stearyl alcohol, (c) behenyl alcohol)
9 (a) is a photograph of the appearance immediately after preparation of ceramide particles prepared with Comparative Sample 1 (Tween 80) and after gelation after 7 days, (b) is a photograph of appearance after homogenization with Comparative Sample 2 (SLS), (c) Shows an optical microscope image immediately after and 7 days after preparing the ceramide particles prepared with Comparative Sample 3 (Pluronic F127).
10 (a) is a graph showing the size of ceramide particles according to the amount of alkyl chain introduction, (b) is a result of observing the appearance of creaming kinetics according to the amount of alkyl chain introduction, and (c) is a graph showing the size of ceramide particles according to the amount of alkyl chain introduction. This is a graph showing the suspension creaming index (SCI).
Figure 11 (a) is a microscope image showing the size of ceramide particles according to the concentration of ceramide and stearyl alcohol (higher fatty alcohol) mixture (1: 4) (w / w), (b) is ceramide and stearyl alcohol ( Higher fatty alcohol) A graph showing the change in ceramide particle size according to the concentration of the mixed solution (1:4) (w / w), (c) is a graph showing the change in ceramide particle size according to the ceramide mixing ratio (0.5 wt% cellulose nanofiber, 20 wt% higher fatty alcohol), (d) is a graph showing the change in ceramide particle size according to the cellulose nanofiber concentration (based on a mixed solution of 20 wt% ceramide and stearyl alcohol (higher fatty alcohol)).

Hereinafter, embodiments of the present invention will be described in detail with reference to the accompanying drawings. Since the present invention may have various changes and various forms, specific embodiments are illustrated in the drawings and described in detail in the text. However, this is not intended to limit the present invention to a specific form disclosed, and should be understood to include all modifications, equivalents, and substitutes included in the spirit and scope of the present invention.

Terms used in this application are only used to describe specific embodiments and are not intended to limit the present invention. Singular expressions include plural expressions unless the context clearly dictates otherwise. In this application, terms such as "comprise" or "have" are intended to designate that there is a feature, step, operation, component, part, or combination thereof described in the specification, but one or more other features or steps However, it should be understood that it does not preclude the possibility of existence or addition of operations, components, parts, or combinations thereof.

Unless defined otherwise, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention belongs. Terms such as those defined in commonly used dictionaries should be interpreted as having a meaning consistent with the meaning in the context of the related art, and unless explicitly defined in the present application, they should not be interpreted in an ideal or excessively formal meaning. don't

1 is a view for explaining water-dispersible ceramide particles according to an embodiment of the present invention.

Referring to FIG. 1 , the water-dispersible ceramide particle 100 according to an embodiment of the present invention may include a composite particle 110 and a cellulose network structure 120.

The composite particle 110 may include ceramide molecules and higher fatty alcohol molecules having 18 to 22 carbon atoms aggregated in a lamellar laminated structure. The number of carbon atoms of the higher fatty alcohol molecules is a factor that affects the long-term storage stability of the ceramide particles 100. As the number of carbon atoms of the higher fatty alcohol molecules increases, the degree of packing of the lamellar layered structure increases, resulting in better long-term storage stability. However, if the number of carbon atoms is too small, the length between the lamellar layers becomes short, so that sufficient hydrophobic interactions cannot be achieved. Therefore, it is preferable to use higher fatty alcohol molecules having 18 to 22 carbon atoms. For example, stearyl alcohol, behenyl alcohol, and the like can be used as higher fatty alcohol molecules.

In addition, a mixing ratio (w/w) of ceramide molecules and higher fatty alcohol molecules included in the composite particle 110 may be 1:1.5 to 1:4. When the mixing ratio is out of the above-mentioned range and the ratio of ceramide molecules increases, a problem arises in that the ceramide molecules and higher fatty alcohol molecules are not uniformly mixed to form one phase but form various phases.

The cellulose network structure 120 surrounds the surface of the composite particle 110 and is formed of bacterial cellulose nanofibers having a hydrophilic functional group and a hydrophobic functional group on the surface.

Bacterial cellulose nanofibers used in the present invention are naturally-derived materials formed through the cultivation of bacterial species, and have a large surface area, high adsorption energy, high mechanical strength, and form an extremely fine, three-dimensional network structure composed of pure cellulose. As a result, it is known that the elastic modulus is high and the biocompatibility is excellent. Therefore, the ceramide particles 100 of the present invention do not cause skin irritation and do not have to worry about damaging the skin barrier function.

In addition, as the bacterial cellulose nanofiber of the present invention has a hydrophilic functional group and a hydrophobic functional group on the surface, it can promote chemical adsorption to the oil-water interface and induce a hydrophobic interaction between the cellulose nanofibers to obtain a three-dimensional network structure By forming the cellulose network structure 120 at the oil-water interface, crystal growth of ceramide molecules within and between particles can be prevented. Therefore, the ceramide particles 100 of the present invention have an effect of high long-term storage stability.

In one embodiment, the hydrophilic functional group may include a hydroxy group (-OH) or a carboxyl group ion (COO-), and the hydrophobic functional group may include an alkyl group having 16 to 20 carbon atoms. Specifically, the alkyl group may be grafted onto the surface of the bacterial cellulose nanofiber through an amide bond (-CONH-), but is not limited thereto.

In one embodiment, when the hydrophobic functional group includes an alkyl group having 16 to 20 carbon atoms, the ratio of the alkyl group is preferably 0.08 to 0.64 mmol/g of the total functional groups bonded to the surface of the bacterial cellulose nanofiber. If the ratio of alkyl groups is less than 0.08 mmol/g, it is not sufficiently hydrophobic, resulting in poor interfacial adsorption, and if it exceeds 0.64 mmol/g, it becomes too hydrophobic, and the interaction between cellulose nanofibers is greater than adsorption to the oil-water interface, resulting in proper emulsification. I have a problem that I can't perform.

In one embodiment, the diameter of the water-dispersible ceramide particles of the present invention may be 0.1 to 100 (μm).

According to the present invention, by stabilizing the composite particle 110 containing a high content of ceramide molecules in an aqueous system using a cellulose network structure 120 formed of bacterial cellulose nanofibers having a hydrophilic functional group and a hydrophobic functional group on the surface, It can be stabilized for a long time in the form of dispersion in the aqueous phase without change of crystal or growth of crystal.

In addition, the water-dispersible ceramide particles 100 of the present invention include composite particles 110 in which ceramide molecules and higher fatty alcohol molecules having 18 to 22 carbon atoms are aggregated in a lamellar layered structure, so that the ceramide molecules located at the interface are in the aqueous phase. precipitation can be prevented. In addition, the ceramide particles 100 of the present invention are easy to use because they are dispersed in the water phase, and since they maintain their structure even in a diluted state, they have the advantage of being post-added to the oil-in-water emulsion formulation.

On the other hand, in the method for producing water-dispersible ceramide particles according to another embodiment of the present invention, the first step of preparing a water phase by dispersing bacterial cellulose nanofibers having a hydrophilic functional group and a hydrophobic functional group on the surface in water, ceramide A second step of preparing an oil phase by mixing molecules and higher fatty alcohol molecules having 18 to 22 carbon atoms, a third step of mixing and emulsifying the water phase and oil phase, and the A fourth step of cooling the emulsion formed in the third step may be included.

In one embodiment, the bacterial cellulose nanofibers are subjected to TEMPO oxidation treatment of bacterial cellulose, dispersing the bacterial cellulose nanofibers by applying ultrasonic waves after the TEMPO oxidation treatment, and hydrophobic functional groups in the bacterial cellulose nanofibers It can be prepared by including the step of grafting.

Specifically, referring to FIG. 2, since natural bacterial cellulose exists in a bundle form, nanofibrillation may be performed through TEMPO-oxidation to nanofibrillate it. At this time, in the step of TEMPO oxidation treatment, at least some of the hydroxy groups (-OH) present in the bacterial cellulose may be substituted with carboxyl groups (-COOH). Then, ultrasonic waves may be applied to disperse the nanofibers of bacterial cellulose.

Next, a step of grafting a hydrophobic functional group is performed to hydrophobize the surface of the bacterial cellulose nanofiber. In this case, the hydrophobic functional group may include an alkyl group having 16 to 20 carbon atoms, and grafting of the alkyl group is not particularly limited and may be performed by various methods known in the art.

The bacterial cellulose nanofiber having a hydrophilic functional group and a hydrophobic functional group on the surface prepared by the above method includes a hydroxyl group (-OH) or a carboxyl group ion (COO-) as the hydrophilic functional group, and has 16 to 16 carbon atoms as the hydrophobic functional group. 20 alkyl group, thereby promoting chemical adsorption to the oil-water interface and inducing hydrophobic interactions between cellulose nanofibers.

On the other hand, the second step is to prepare an oil phase by mixing ceramide molecules and higher fatty alcohol molecules having 18 to 22 carbon atoms without adding a separate liquid oil, and the oil phase of the liquid phase In order to manufacture, the second step is preferably performed at a high temperature (about 70 to 90 ° C.).

At this time, the mixing ratio (w / w) of the ceramide molecules and higher fatty alcohol molecules mixed in the second step may be 1: 1.5 to 1: 4. When the mixing ratio is out of the above-mentioned range and the ratio of ceramide molecules increases, a problem arises in that the ceramide molecules and higher fatty alcohol molecules are not uniformly mixed to form one phase but form various phases.

The third step is to mix and emulsify the water phase and the oil phase, and may be performed at a high temperature (about 70 to 90° C.). In one embodiment, the water phase and the oil phase may be mixed at a high temperature and then emulsified for about 5 minutes at about 11,000 rpm using a homogenizer.

In addition, in the third step, a step of ultrasonicating the emulsion formed after emulsification may be additionally performed to make the water-dispersible ceramide particles uniform in size and small in size.

Meanwhile, the concentration of the bacterial cellulose nanofibers is preferably 0.1 wt% or more and less than 1 wt% based on the total emulsion content. If it is less than 0.1 wt%, the effect is insignificant because the content of the bacterial cellulose nanofibers is small, and if it is more than 1 wt%, the viscosity is too high, so that emulsification is impossible.

In addition, based on the concentration of the bacterial cellulose nanofibers of 0.5 wt%, the concentration of the oil phase included in the emulsion is preferably less than 30 wt%, and the concentration of ceramide molecules included in the emulsion is 20 wt% It is preferable to be less than This is because when the concentration of the oil phase is 30 wt% or more, gelling occurs and flowability is lost.

According to the present invention, since ceramide particles are prepared using cellulose nanofibers at a relatively low concentration without introducing a surfactant, it has low cost and high efficiency effects, and high content of ceramide is produced by particleizing ceramide without containing oil. Not only can it be contained, but it can fundamentally block ceramide from migrating from the oil phase to the water phase.

On the other hand, the emulsion composition according to another embodiment of the present invention includes a water phase and ceramide particles dispersed in the water phase, and the ceramide particles are ceramide molecules aggregated into a lamellar laminated structure and a composite particle containing higher fatty alcohol molecules having 18 to 22 carbon atoms, and a cellulose network structure formed of bacterial cellulose nanofibers surrounding the surface of the composite particle and having a hydrophilic functional group and a hydrophobic functional group on the surface. .

The emulsion composition of the present invention can be applied to cosmetic compositions. In this case, the cosmetic composition including the emulsion composition may further include additional active ingredients in addition to the ceramide particles.

Hereinafter, in order to aid understanding of the present invention, specific embodiments will be described in detail. However, the following examples are merely some embodiments of the present invention, and the scope of the present invention is not limited to the following examples.

<Example 1: Preparation of surface-modified bacterial cellulose nanofibers with alkyl chains>

By replacing the hydroxyl group (-OH) on the surface of bacterial cellulose with a carboxyl group (-COOH) through the TEMPO oxidation reaction, the bacterial cellulose bundle is nanofibrillated with bacterial cellulose.

Specifically, referring to FIGS. 2(a)-(c), the concentration of bacterial cellulose was diluted to 1%, and TEMPO and NaBr were added, followed by stirring to dissolve completely. Subsequently, NaClO was added to each solution, and an oxidation reaction was performed while maintaining the pH between 10.5 and 10.7 with a 0.5M NaOH solution. After 12 hours, the pH was adjusted to 7 using HCl to terminate the oxidation reaction, and washed with distilled water and ethanol using a centrifuge.

Thereafter, ultrasonic waves were irradiated for 5 minutes using a probe-type ultrasonic irradiator to disperse the bacterial cellulose nanofibers, and ethanol was completely removed by distillation under reduced pressure, and then the concentration of the bacterial cellulose nanofibers was adjusted to 1%.

Then, in order to graft the alkyl chain onto the surface of the TEMPO oxidation-treated bacterial cellulose nanofiber (TOBC), two methods exemplified below were selected and proceeded.

[Method 1]

TEMPO oxidation treatment using 1-ethyl-3-(3-dimethylminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS) as a zero-linker Carboxyl groups of the cellulose nanofibers are reacted with EDC/NHS, and then alkylamine is reacted to graft an alkyl chain to the surface of the cellulose nanofibers through an amide bond. (See Fig. 2(a))

Specifically, after stirring and dissolving EDC and NHS in 0.5 wt% of bacterial cellulose nanofibers for 15 minutes, octadecylamine was dissolved in ethanol at 50° C., added to the mixture, and reacted for 24 hours. In order to remove unreacted substances and salts remaining after the reaction, distilled water and ethanol were used and washed using a centrifugal separator to obtain alkyl cellulose nanofibers grafted with amide bonds.

The alkyl cellulose nanofibers grafted with the amide bond were confirmed by UV analysis, and the degree of alkyl substitution according to the amount of octadecylamine was quantified using a titration method to obtain (d) and (e) of FIG. 2 ) was shown in

2 (d) and (e), the grafting of the alkyl chain (C18) to the cellulose nanofibers showed a strong UV peak at 257 nm, and as the octadecylamine content increased, the carboxy group of the cellulose nanofibers increased. As it is converted to a C18 alkyl chain, the content of the carboxy group decreases.

[Method 2]

TEMPO oxidation-treated bacterial cellulose nanofibers (TOBC) and sodium (meta)periodate were reacted at a weight ratio of 1:1 at 50 °C for 12 hours in a light-blocking state to obtain dialdehyde cellulose nano A fiber (dialdehyde cellulose nanofiber, DAC) was prepared. (See FIG. 3(a)) After the reaction, the mixture was washed with distilled water and ethanol using a centrifuge to remove remaining unreacted substances and salts.

Then, a bacterial cellulose nanofiber ( _C18 BCNF) grafted with an alkyl chain (C18) by Schiff's base bonding is prepared.

Specifically, an ethanol solution in which octadecylamime was dissolved in a 0.5 wt% aqueous solution of dialdehyde cellulose nanofibers was mixed at a volume ratio of 1:1 (v/v) to adjust the pH to 7.5 to 7.8, and then heated to 12 °C at 50 °C. react in time In order to remove unreacted substances and salts remaining after the reaction, distilled water and ethanol were used to wash with a centrifugal separator to obtain alkyl chain-substituted bacterial cellulose nanofibers.

Through FT-IR analysis, it was confirmed whether the reaction was successful by confirming the formation of aldehyde groups and imine peaks before and after the reaction (see FIG. 3b), and as shown in FIG. 3c, the finally prepared bacterial cellulose nanofibers It was confirmed that the zeta potential value of ( _C18 BCNF) was not significantly different from that of TOBC.

<Example 2: Preparation of Ceramide Particles Using Bacterial Cellulose Nanofibers Grafted with Alkyl Chains>

Ceramide particle samples 1a to 4a were prepared in the composition ratios shown in Table 1 below.

Sample 1a Sample 2a Sample 3a Sample 4a Ceramide NP 8 Stearyl alcohol 12 _C18 BCNF 0.1 0.3 0.5 0.7 Water to 100 to 100 to 100 to 100

(Unit: % by weight)

Specifically, the oil phase was prepared by mixing ceramide (Ceramide NP) and higher fatty alcohol, Stearyl alcohol, in the weight ratio of Table 1 above, and completely melting them into a liquid phase at 90 ° C. The water phase was prepared by dispersing the prepared _C18 BCNF (bacterial cellulose nanofiber grafted with an alkyl chain (C18)) in water using a probe-type sonicator. Thereafter, the aqueous phase was heated to 90 ° C., mixed with the oil phase, and then first emulsified at 90 ° C. for 5 minutes at 11,000 rpm using a homogenizer.

Next, the primary emulsion was sonicated for 5 minutes using a probe-type sonicator to make the size uniform and small.

Then, the emulsified emulsion was rapidly cooled using an ice bath. After the temperature dropped, the appearance of the layer separation and color of the ceramide particle suspension was visually checked, and the size of the ceramide particles according to the concentration of _C18 BCNF introduced was measured through optical microscope image analysis. Whether or not crystals of ceramide were formed was observed. (See Figure 4 (a) - (b))

As a result, the diameter of the ceramide particles was measured to be 1 to 10 (μm), ceramide crystals were not observed, and maltase cross was observed inside the ceramide particles. Through this, it was found that the ceramide particles had a multi-laminated structure.

In addition, it was confirmed that the _C18 BCNF film forms a structure surrounding the ceramide particles through scanning electron microscopy (SEM) and fluorescence microscope image analysis shown in FIGS. 4 (c) to (d).

<Comparative Example 1: Preparation of ceramide particles using TEMPO oxidation-treated bacterial cellulose nanofibers>

According to Example 1 of the present invention, since the hydrophilic cellulose nanofibers are partially hydrophobic by grafting an alkyl chain on the surface of the bacterial cellulose nanofibers, the effect of improving the emulsifying power by increasing the adsorption force of the cellulose nanofibers adsorbed to the oil-water interface have

To confirm this, ceramide particles were prepared under the same conditions as in Example 2 using bacterial cellulose nanofibers that were not hydrophobized after TEMPO oxidation treatment of bacterial cellulose.

Specifically, the oil phase was prepared by mixing (20wt%) ceramide (Ceramide NP) and higher fatty alcohol, Stearyl alcohol, in a weight ratio of 1:4 and completely melting them into a liquid phase at 90 ° C. The water phase was prepared by dispersing the prepared TEMPO oxidation-treated cellulose nanofibers in water using a probe-type sonicator. Thereafter, the aqueous phase was heated to 90 ° C., mixed with the oil phase, and then first emulsified at 90 ° C. for 5 minutes at 11,000 rpm using a homogenizer.

As a result, as shown in FIG. 5, unlike the emulsion of Example 2, the mixture was not emulsified even after homogenization and was observed in the form of layer separation.

<Example 3: Heat capacity analysis according to the mixing ratio of ceramide and higher fatty alcohol>

In order to optimize the mixing ratio of ceramide and higher fatty alcohol, ceramide particles were prepared in the same manner as in Example 2 by varying the ratio of ceramide and higher fatty alcohol as shown in Table 2 below, and differential scanning calorimeter (DSC) analysis proceeded. At this time, the prepared ceramide particles were dried in a vacuum oven at 25 ° C. for 24 hours and then analyzed in powder form.

Sample 1 Sample 2 Sample 3 Sample 4 Ceramide NP 4 8 10 12 Myristyl alcohol 16 12 10 8 _C18 BCNF 0.5 Water to 100 to 100 to 100 to 100

(Unit: % by weight)

Referring to FIG. 6 showing the results of thermogravimetric analysis, as the ratio of ceramide increases, the number of endothermic peaks increases. As the weight ratio of ceramide increases, ceramide and higher fatty alcohol are uniformly mixed to form one phase. It means that it does not form and forms various phases. Therefore, the mixing ratio (w/w) of ceramide and higher fatty alcohol is preferably 1:1.5 to 1:4.

<Example 4: Preparation and structural analysis of ceramide particles according to the carbon number of higher fatty alcohol>

In order to analyze the structure of ceramide particles according to the number of carbon atoms of the higher fatty alcohol mixed with ceramide, the types of higher fatty alcohol to be mixed were different (Myristyl alcohol (C ₁₄ OH), Stearyl alcohol ) (C ₁₈ OH), behenyl alcohol (C ₂₂ OH)) SAXS (Small Angle X-ary Scattering) and WAXS (Wide Angle X-ray Scattering) analyzes of the prepared ceramide particles were performed.

Specifically, ceramide particles were prepared in the same manner as in Example 2 according to the composition of Table 3 below, and immediately after preparation, SAXS and WAXS analysis (Pohang Accelerator (Korea), 3 GeV output, Pohang Light Source II (PLS II) within 3 days ) 4C beamline) was conducted.

Sample 1b Sample 2b Sample 3b Ceramide NP 4 Myristyl alcohol (C ₁₄ OH) 16 Stearyl alcohol (C ₁₈ OH) 16 Behenyl alcohol (C ₂₂ OH) 16 _C18 BCNF 0.5 Water to 100 to 100 to 100

(Unit: % by weight)

As a result, in FIG. 7 (a), which is the result of SAXS analysis, it was confirmed that all ceramide particles had a multi-lamellar structure regardless of the carbon number of higher fatty alcohol, and in FIG. 7 (b), the carbon number of higher fatty alcohol increased. It was confirmed that the d-spacing length, which represents the length between multi-lamellae, increased as the number increased.

In addition, referring to FIG. 7(c), which is a result of WAXS analysis, when the carbon number of higher fatty alcohol is 14, the lateral packing of the multi-lamellae shows hexagonal packing, whereas when the number of carbon atoms is 18 or more, orthorhombic packing is shown.

<Example 5: Stability of ceramide particles according to carbon number of higher fatty alcohol>

In order to observe the long-term storage stability of the ceramide particles prepared according to the composition of Table 3, the ceramide particles (Sample 1b - 3b) were observed immediately after preparation and 1 month after polarization microscopy, and the results are shown in Fig. 8 (a)- shown in (c).

Referring to FIG. 8, when a single myristyl alcohol (C14) is mixed (FIG. 8(a)), a plurality of plate-shaped ceramide crystals are observed, whereas stearyl alcohol (C18) ( In the case of FIG. 8 (b)) and behenyl alcohol (C22) (FIG. 8 (c)), it was confirmed that ceramide crystals were not observed, and the size of the initial ceramide particles was maintained.

<Comparative Example 2: Stability of ceramide particles prepared with low molecular and high molecular surfactants>

In the case of preparing ceramide particles using a low-molecular surfactant and a high-molecular surfactant (amphiphilic block polymer), the presence or absence of particle production and long-term storage stability were compared with the ceramide particles prepared according to Example 2 of the present invention.

Specifically, as the surfactant, one type each of a nonionic surfactant and an ionic surfactant having an HLB value of 10 or more was randomly selected, and the polymeric surfactant was selected among hydrophilic triblock copolymers typically used in cosmetic formulations. One type was arbitrarily selected, and ceramide particles were prepared in the same manner as in Example 2 with the composition shown in Table 4 below.

Comparison Sample 1 Comparison Sample 2 Comparison Sample 3 Ceramide NP 4 Stearyl alcohol (C ₁₈ OH) 16 Tween 80 5 SLS 5 Pluronic F127 5 Water to 100 to 100 to 100

(Unit: % by weight)

Referring to FIG. 9 showing the results, in the case of comparative sample 1 (nonionic surfactant) (FIG. 9(a)), nanoparticles of a very small size of 300 to 400 nm were formed immediately after manufacture and the viscosity was very low. However, as a result of observation after a week, gelling was observed and the flowability was lost.

In the case of comparative sample 2 (anionic surfactant) (FIG. 9(b)), when emulsified with a homogenizer, it was not emulsified as in the case of TEMPO oxidized cellulose nanofibers.

In the case of comparative sample 3 (polymer surfactant) (FIG. 9(c)), it had a micro size in a well-dispersed form similar to the suspension made of cellulose nanofibers immediately after preparation, but flocculation between particles over time ), the viscosity increased as the phenomenon worsened.

<Example 6: Preparation and structural analysis of ceramide particles according to the amount of alkyl chain introduction>

Size of ceramide particles prepared with 0.08 mmol/g, 0.16 mmol/g, 0.64 mmol/g, 0.96 mmol/g, 1.28 mmol/g of alkyl chain introduction to analyze the characteristics of ceramide particles according to the amount of alkyl chain introduction was measured through optical microscope image analysis, the appearance of creaming kinetics was observed, and the suspension creaming index (SCI) was measured to show the analysis results in FIG. 10 (a)-(c), respectively. shown

As a result, looking at (a) of FIG. 10, in the case of cellulose nanofibers in which no alkyl chain was introduced, emulsification was not at all, and when grafted with octadecylamine to be introduced, the emulsifying power and particle size depended on the amount of the substituted alkyl chain. You can see that the sizes are different. Additionally, as a result of observing the creaming rate of the prepared ceramide particle suspension, as shown in (b)-(c) of FIG. 10, after 7 days, the amount of octadecylamine introduced was 0.08 mmol/g-0.64 mmol / g, it was confirmed that it was stable without creaming.

<Example 7: Preparation and size analysis of ceramide particles according to the weight ratio of ceramide and cellulose nanofibers>

In order to analyze the characteristics of ceramide particles according to the weight ratio of ceramide and cellulose nanofibers, the concentration of ceramide and stearyl alcohol mixture (1:4 (w / w)) was each 10 wt% based on the cellulose nanofiber concentration of 0.5 wt%. %, 15 wt%, 20 wt%, 25 wt%, 30 wt%, the size of the ceramide particles prepared as 40 wt% was measured through optical microscope image analysis, and the results are shown in FIG. 11 (a) and ( shown in b).

As a result, as shown in (a) of FIG. 11, the size increased as the core content (mixture of ceramide and higher fatty alcohol) of the ceramide particles increased, and at 40 wt% or more, there was no flow due to gelling. The size change was as shown in FIG. 11(b).

In addition, the particle size increased as the ceramide content increased compared to the higher fatty alcohol, whereas the particle size decreased as the content of the alkyl-substituted cellulose nanofibers increased. The results show an increase in size with increasing core content, respectively.

On the other hand, based on the alkyl-substituted cellulose nanofiber concentration of 0.5 wt% and the ceramide and stearyl alcohol mixture concentration of 20 wt%, the weight ratio of ceramide to stearyl alcohol was changed from 20 to 60 wt%. The size of the ceramide particles prepared It was measured through optical microscope image analysis, and the results are shown in FIG. 11 (c).

As a result, the particle size increased linearly as the ceramide content increased compared to the higher fatty alcohol.

In addition, the size of ceramide particles prepared by changing the concentration of alkyl-substituted cellulose nanofibers from 0.1 to 0.7 wt% based on 4 wt% of ceramide and 12 wt% of stearyl alcohol was measured through optical microscope image analysis, The results are shown in (d) of FIG. 11 .

As a result, the particle size decreased as the content of the alkyl-substituted cellulose nanofibers increased.

Although the above has been described with reference to preferred embodiments of the present invention, those skilled in the art can variously modify and change the present invention without departing from the spirit and scope of the present invention described in the claims below. You will understand that you can.

100: water dispersible ceramide particles
110: composite particle 120: cellulose network structure

Claims (17)

composite particles comprising ceramide molecules and higher fatty alcohol molecules having 18 to 22 carbon atoms aggregated into a lamellar layered structure; and
A cellulose network structure formed of bacterial cellulose nanofibers surrounding the surface of the composite particle and having a hydrophilic functional group and a hydrophobic functional group on the surface;
Water-dispersible ceramide particles.
According to claim 1,
The hydrophilic functional group includes a hydroxy group (-OH) or a carboxyl group ion (COO-),
Characterized in that the hydrophobic functional group includes an alkyl group having 16 to 20 carbon atoms,
Water-dispersible ceramide particles.
According to claim 2,
Characterized in that the alkyl group is grafted to the surface of the bacterial cellulose nanofiber through an amide bond (-CONH-),
Water-dispersible ceramide particles.
According to claim 2,
Characterized in that the ratio of the alkyl group is 0.08 to 0.64 mmol / g of the total functional groups bound to the surface of the bacterial cellulose nanofiber,
Water-dispersible ceramide particles.
According to claim 1,
Characterized in that the diameter of the water-dispersible ceramide particles is 0.1 to 100 (㎛),
Water-dispersible ceramide particles.
According to claim 1,
In the composite particle, the mixing ratio (w / w) of the ceramide molecules and higher fatty alcohol molecules is 1: 1.5 to 1: 4, characterized in that
Water-dispersible ceramide particles.
A first step of preparing a water phase by dispersing bacterial cellulose nanofibers having a hydrophilic functional group and a hydrophobic functional group on the surface in water;
A second step of preparing an oil phase by mixing ceramide molecules and higher fatty alcohol molecules having 18 to 22 carbon atoms;
A third step of mixing and emulsifying the water phase and the oil phase; and
A fourth step of cooling the emulsion formed in the third step; including,
Method for producing water-dispersible ceramide particles.
According to claim 7,
The bacterial cellulose nanofibers,
TEMPO oxidation treatment of bacterial cellulose;
dispersing nanofibers of bacterial cellulose by applying ultrasonic waves after the TEMPO oxidation treatment; and
Characterized in that it is prepared by including; grafting a hydrophobic functional group to the bacterial cellulose nanofibers.
Method for producing water-dispersible ceramide particles.
According to claim 8,
In the step of TEMPO oxidation treatment, at least some of the hydroxyl groups (-OH) present in the bacterial cellulose are substituted with carboxyl groups (-COOH),
Method for producing water-dispersible ceramide particles.
According to claim 7,
The hydrophilic functional group includes a hydroxy group (-OH) or a carboxyl group ion (COO-),
Characterized in that the hydrophobic functional group includes an alkyl group having 16 to 20 carbon atoms,
Method for producing water-dispersible ceramide particles.
According to claim 7,
Characterized in that the second and third steps are performed at a temperature of 70 to 90 ° C.
Method for producing water-dispersible ceramide particles.
According to claim 7,
In the third step, ultrasonic treatment of the emulsion formed after emulsification; characterized in that it is further performed,
Method for producing water-dispersible ceramide particles.
According to claim 7,
Characterized in that the mixing ratio (w / w) of the ceramide molecules and higher fatty alcohol molecules is 1: 1.5 to 1: 4,
Method for producing water-dispersible ceramide particles.
According to claim 7,
Characterized in that the concentration of the bacterial cellulose nanofibers is 0.1 wt% or more and less than 1 wt%,
Method for producing water-dispersible ceramide particles.
According to claim 7,
Based on the concentration of 0.5 wt% of the bacterial cellulose nanofibers, the concentration of the oil phase contained in the emulsion is characterized in that less than 30 wt%,
Method for producing water-dispersible ceramide particles.
According to claim 15,
Characterized in that the concentration of ceramide molecules contained in the emulsion is less than 20 wt% based on the concentration of 0.5 wt% of the bacterial cellulose nanofibers,
Method for producing water-dispersible ceramide particles.
water phase; And ceramide particles dispersed in the water phase,
The ceramide particles may include composite particles including ceramide molecules and higher fatty alcohol molecules having 18 to 22 carbon atoms aggregated with each other in a lamellar layered structure; and a cellulose network structure formed of bacterial cellulose nanofibers surrounding the surface of the composite particle and having a hydrophilic functional group and a hydrophobic functional group on the surface.