WO2022181966A1 - Microcapsule comprising multi-component wax and method for manufacturing same - Google Patents

Abstract

The present invention relates to a microcapsule comprising: a shell part comprising a multi-component wax; and an aqueous core part, wherein the multi-component wax changes phase according to temperature change, and the shell part is absent of pores or cracks, and the present invention provides a cosmetic composition and a functional food composition comprising same microcapsule, and a method for manufacturing same.

Description

Microcapsules containing multi-component wax and manufacturing method thereof

It relates to a microcapsule containing a multi-component wax and a method for manufacturing the same.

Emulsions are widely used in cosmetics in the form of lotions or creams to effectively deliver various cosmetic active ingredients to maintain or promote our health and beauty. Emulsions can dissolve both hydrophilic and hydrophobic substances frequently used in cosmetics, and can control the rheological properties of cosmetic formulations without significantly affecting the effectiveness of active ingredients. However, since emulsions are inherently unstable, coalescence of emulsion droplets and bulk phase separation are generally observed over time, even with appropriate emulsifiers.

As a method for avoiding this problem, microcapsules in which a core portion including an active ingredient is encapsulated with a protective shell may be used. This enables efficient storage of sensitive active ingredients such as vitamins, nutrients and therapeutics from oxidation and degradation. As a conventional method for producing microcapsules with such a core-shell structure, multiphase emulsion droplets prepared through bulk emulsification technology are used as templates. Microcapsules prepared by this method generally have high polydispersity and low loading efficiency.

Recent advances in droplet microfluidics have made it possible to fabricate monodisperse multiphase emulsion droplets with high loading efficiencies with precise tunable size, structure and composition. In particular, various water-in-oil-in-water (W/O/W) dual emulsion formulations contain the desired active substance within a solid physical shell to protect and prevent the encapsulated active substance from the surrounding environment. It has been studied as a template for enclosing the aqueous core. For example, using a microfluidic approach to fabricate perfluoropolyether (PFPE)-based microcapsules can improve the retention of encapsulated active materials due to the totipotent nature of the shell. In addition, using thiol-ene photopolymerization, microcapsules with an impermeable membrane for encapsulation and retention of small molecules can be fabricated. Separately, it has also been reported that low molecular weight poly(ethylene glycol) diacrylate (PEGDA) is used as an intermediate step for manufacturing biocompatible PEG-based microcapsules capable of encapsulating hydrophilic and hydrophobic materials at the same time. All these approaches provide some degree of stable storage and biocompatibility of the encapsulated material, but lack the ability to release the material under desired conditions and leave a residue of the shell upon rupture and release, limiting its applicability in cosmetic applications. do.

As a solution to this problem, there is a method of using a thermally reactive phase change material (PCM) as a material of the shell. Capsules with shells containing waxy materials (alkanes and fatty acids) have recently been shown to provide a hermetic function. This means an absolute seal without leakage of the loaded material over a long period of time. In addition, the PMC capsules can melt above the melting temperature designed for on-demand release of the material. However, the size of the existing PMC capsule is in millimeters, and the shape of the capsule cannot be precisely adjusted.

Recently, biocompatible wax-based microcapsules that release support material in response to temperature have been reported. However, in a subsequent study, it was reported that the encapsulated material leaked through the cracks created in the shell during the phase transition process.

Therefore, there is a need for novel temperature-sensitive and biocompatible microcapsule formulations through the study of the properties of the shell. There is also a need for a new approach to simultaneously achieve the hermetic sealing and on-demand release of the encapsulated material for application of these microcapsules to cosmetics or food.

One aspect is a shell portion comprising a multi-component wax; and an aqueous core part; wherein the multi-component wax is characterized in that the phase changes according to temperature change, and the shell part does not have pores or cracks, to provide a microcapsule.

Another aspect is to provide a cosmetic composition comprising the microcapsules.

Another aspect is to provide a functional food composition comprising the microcapsules.

Another aspect is a shell part composed of an oil phase; and a core part composed of an aqueous phase, wherein the shell part comprises a multi-component wax, forming double droplets; and sequentially crystallizing the multi-component wax.

One aspect is a shell portion comprising a multi-component wax; and an aqueous core part;

The multi-component wax is characterized in that the phase changes according to the temperature change,

The shell portion provides a microcapsule that does not have pores or cracks.

The microcapsules have a characteristic of releasing the supported material according to a change in temperature. The microcapsules can be controlled to change phase at a specific temperature. The shell part may include a multi-component wax of a liquid or solid phase change material (PCM). The microcapsules may be melted from a solid phase to a liquid phase as they are heated above a specific temperature (eg, 30 to 40° C.). In addition, as the multi-component wax is cooled below a certain temperature, it may crystallize or solidify from a liquid phase to a solid phase. In addition, since the multi-component wax is sequentially melted or crystallized according to temperature change, there may be no pores or cracks in the shell part. For example, since components having different melting points may be sequentially crystallized during the cooling process, a component having a low melting point may fill initial cracks and pores created by crystallization of a component having a high melting point. As a result, an intact shell without pores or cracks can be created.

The microcapsules may release the compound according to a change in temperature. If the temperature is lower than the melting point of the multi-component wax, the wax may crystallize into a solid, and if it is higher than the melting point, it may be melted into a liquid.

As described above, the microcapsules having the hermetically sealed properties of the material supported on the core and the release properties according to temperature changes can be usefully applied in various fields such as cosmetic compositions, functional food compositions, and the like.

The multi-component wax refers to a wax comprising two or more components. For example, the multi-component wax may be an animal or vegetable fatty acid or an animal or vegetable fatty acid ester. For example, the multi-component wax may be a vegetable wax, specifically palm oil. The animal and vegetable fatty acid ester may be an animal or vegetable fatty acid glyceride. The glyceride may include monoglyceride, diglyceride, lyglyceride and triglyceride. In one embodiment, the multi-component wax may be palm oil. In this case, it may include triglycerides, monoglycerides and diglycerides.

The shell part refers to an external shell part that is a shell part surrounding the core part of the microcapsule structure. The shell part may include a multi-component wax. For example, the multi-component wax may be used in an amount of 50% to 100% by weight, 60% to 100% by weight, 70% to 100% by weight, 80% to 100% by weight, 90% to 100% by weight of the total composition of the shell part. %, 90% to 99% by weight or 95% to 99% by weight. When the multi-component wax is included in the shell part within the composition range, the microcapsule may have sealing properties and temperature response properties.

The core part refers to a part enclosed in the shell part of the microcapsule structure. The core part may be an aqueous core part and may include a hydrophilic material. For example, the hydrophilic material may include a polar material, an acidic material, or a basic material.

The aqueous core part may be in an aqueous solution state. The aqueous solution may contain a water-soluble surfactant to stabilize the water-oil interface. For example, an aqueous solution containing polyethylene glycol (polyethyleneglycol, PEG), polyvinyl alcohol (poly(vinyl alcohol), PVA), polyvinylpyrrolidone (PVP), or a combination thereof may be used.

In this case, the content of the water-soluble surfactant may be 0.1 w/w% to 30 w/w%, 1 w/w% to 20 w/w%, and 3 w/w% to 10 w/w% based on the total aqueous solution. It may be w/w%, and may be 4 w/w% to 6 w/w%. When the surfactant is included in the composition range of the aqueous core part, the interface between water and oil may be stabilized.

The melting point of the multi-component wax may vary depending on the composition of the component. For example, the melting point may be 20 to 50 ℃, 25 to 45 ℃, or 30 to 40 ℃. In addition, the multi-component wax may have a different melting point (or melting point) of each component included. Accordingly, the components may be sequentially melted or cooled during the melting or cooling process. Accordingly, the multi-component wax may be sequentially melted or sequentially crystallized.

The microcapsule may have a diameter of 50 to 500 μm, 100 to 450 μm, 150 to 400 μm, 200 to 350 μm, 250 to 330 μm, 270 to 310 μm, or 275 to 305 μm.

The diameter of the core part may be 50 to 500 μm, 100 to 450 μm, 150 to 400 μm, 200 to 350 μm, 200 to 300 μm, 210 to 250 μm, or 220 to 245 μm.

In one embodiment, the diameter of the microcapsule or the diameter of the core portion can be adjusted by controlling the internal and intermediate flow rates and flow rates. For example, the total flow rate may be between 1500 and 3500 μl/hr, between 2000 and 3000 μl/hr or between 2200 and 2700 μl/hr. Also, the internal flow rate may be 100 to 3000 μl/hr, 300 to 2500 μl/hr, or 500 to 2,000 μl/hr. The flow rate of the external continuous phase may be from 1,000 to 20,000 μl/hr, from 5,000 to 15,000 μl/hr, or from 8,000 to 12,000 μl/hr.

The core part may further include calcium ions. In one embodiment, the calcium ions may be included in the core portion in the form of calcium chloride. In addition, in the case of the microcapsule containing the calcium ion, it may be for heat-induced gelation. When the shell portion of the microcapsule containing the calcium ions is melted at a specific temperature, the calcium ions supported therein may be released. Heat-induced release of calcium ions can induce gelation by reacting with external components. In one embodiment, the heat-induced release of calcium ions may react with sodium alginate solution to form an alginate hydrogel.

The core part may further include ethylenediaminetetraacetic acid (EDTA). In the case of the microcapsule containing the EDTA, it may be for dissolving the hydrogel. The EDTA may reduce the bonding strength of components constituting the structure in the gel. For example, the EDTA can reduce the bond strength of egg box structures. In addition, the EDTA can be used for chelation to decompose or dissolve the preformed alginate hydrogel.

Another aspect provides a cosmetic composition comprising the microcapsules.

The cosmetic composition may include microcapsules in an appropriate amount depending on the purpose of use. For example, the cosmetic composition may include microcapsules in an amount of 0.1 to 100% by weight, 1 to 100% by weight, 10 to 90% by weight, or 50 to 90% by weight.

The microcapsules included in the cosmetic composition may further include an acidic material, for example, a strong acid. For example, the microcapsule may be loaded by compartmentalizing the strong acid in the capsule. An acidic environment is required to maintain the activity of certain cosmetic ingredients, such as vitamin C, but cosmetic ingredients and acidic ingredients may not be compatible. Therefore, the microcapsules can be used for efficient loading and transportation of a wide range of substances without changing the entire cosmetic formulation to acidic acidity in the microcapsules.

In another embodiment, the microcapsules may further include a cosmetically active substance. The cosmetically active substance may have anti-aging, antioxidant, anti-inflammatory, anti-infective, moisturizing, whitening, anti-wrinkle or skin-improving effects. For example, the cosmetically active substance may be niacinamide. The niacinamide may exhibit a whitening effect by inhibiting pigment movement in the basal layer of human skin. Due to this, it can be widely used in cosmetics.

The cosmetic composition is a solution, an ointment for external use, a cream (eg, a nourishing cream, a massage cream, a moisture cream, a hand cream, etc.), a foam, a lotion (eg, a nourishing lotion, a flexible lotion, etc.), a pack, a softening water, an emulsion , makeup bases, essences (eg body essences, etc.), soaps, liquid cleansers, bath products, sunscreen creams, sun oils, suspensions, emulsions, pastes, gels, skins, lotions (eg body lotions, etc.) ), oils (eg body oils, etc.), powders, soaps, surfactant-containing cleansing, oils (eg body oils, etc.), foundations (eg powder foundations, emulsion foundations, wax foundations, etc.) ), may be prepared in a formulation selected from the group consisting of patches and sprays, but is not limited thereto.

The cosmetic composition may further include one or more cosmetically acceptable carriers to be formulated in general skin cosmetics, and as common ingredients, for example, oil, water, surfactant, humectant, lower alcohol, thickener, chelating agent , dyes, preservatives, fragrances, etc. may be appropriately blended, but the present invention is not limited thereto.

The cosmetically acceptable carrier included in the cosmetic composition varies depending on the formulation of the cosmetic composition. When the formulation of the cosmetic composition is an ointment, paste, cream or gel, animal oil, vegetable oil, wax, etc. may be used. When the formulation of the cosmetic composition is a powder or a spray, lactose, talc, silica, etc. may be used, and in particular, in the case of a spray, a propellant may be further included. When the formulation of the cosmetic composition is a solution or emulsion, a solvent, solubilizer, or emulsifier may be used. When the formulation of the cosmetic composition is a suspension, a liquid diluent, suspending agent, etc. may be used. The carrier may be used alone or in combination of two or more.

The cosmetic composition may be used as a transdermal administration method such as directly applied to the skin or sprayed, and the administration route of the composition may be administered through any general route as long as it can reach the target tissue.

The amount of the cosmetic composition used may be appropriately adjusted according to individual differences or formulations such as age, degree of lesion, etc., and may be used for one week to several months by applying a small amount to the skin once to several times a day.

Other details of the microcapsules are as described above.

Another aspect provides a functional food composition comprising the microcapsules. In the case of the multi-component wax, it can be ingested as a component harmless to the human body. Therefore, the microcapsules can also be used for functional foods.

The functional food composition may include microcapsules in an appropriate amount depending on the purpose of use. For example, the functional food composition may include microcapsules in an amount of 0.1 to 100% by weight, 1 to 100% by weight, 10 to 90% by weight, or 50 to 90% by weight.

The functional food composition may further include a functional material having effects such as antioxidant, anticancer, anti-inflammatory, and blood circulation improvement.

In the functional food composition, the food may include both functional health food or health supplement food in a conventional sense. For example, the food is a drink, meat, sausage, bread, biscuit, rice cake, chocolate, candy, snacks, confectionery, pizza, ramen, other noodles, gum, dairy products including ice cream, various soups, beverages, alcoholic beverages and vitamin complexes, dairy products, and dairy products.

Other details of the microcapsules are as described above.

Another aspect is a shell part composed of an oil phase; and a core part composed of an aqueous phase, wherein the shell part comprises a multi-component wax, forming double droplets; and

It provides a method of manufacturing microcapsules comprising a; sequentially crystallizing the multi-component wax.

The method for manufacturing the microcapsule includes forming double droplets, wherein the double droplets include a shell part composed of an oil phase and a core part composed of an aqueous phase, and the shell includes a multi-component wax.

The double droplet forming step is a step of forming a droplet including a wax shell including a multi-component wax of microcapsules. In the double droplet forming step, a double droplet including a wax shell part and an aqueous core part is formed.

The forming of the double droplet may be performed using a microfluidic device. For example, the microfluidic device may consist of two tapered cylindrical glass capillaries each having an inner diameter and an outer diameter. The cylindrical glass capillary may be an injection capillary or a collection capillary. The injection capillary and collection capillary may be hydrophilic or hydrophobic. For example, the injection capillary may be hydrophobic and the collection capillary may be hydrophilic. The two cylindrical glass capillaries may be separately introduced into a square glass capillary from opposite directions to be coaxially aligned.

In one embodiment, the microfluidic device comprises: an outer tube containing a flow of water; an inner tube positioned inside the outer tube and including an oil flow including a multi-component wax; and a small inner tube within the inner tube containing an inner water flow that will constitute the core of the double droplet; and an orifice positioned to face the inner tube containing the oil flow and containing the external water flow.

The step of sequentially crystallizing the multi-component wax may be performed by heating the multi-component wax above a melting point and then collecting and freezing the melted multi-component wax below the melting point. In one embodiment, after heating the multi-component wax to 55° C., the multi-component wax-based droplets may be collected at 17° C. and frozen.

In addition, in the crystallization step, sucrose may be further added to match the osmotic pressure of the inner and outer aqueous phases. This can inhibit water transport through the intermediate stage and prevent rupture of the emulsion droplets before quenching.

The method of manufacturing the microcapsules may further include a droplet forming step. In the droplet forming step, the aqueous phase may be injected through an injection capillary to form an internal droplet. And using multi-component wax as an intermediate step, it can be injected through the interstices of the injection capillary and the square on the same side as the injection capillary. The multi-component wax may be in a molten state. In addition, the intermediate step may be performed using a multi-component wax and a surfactant (eg, Span 80) together. Another aqueous phase can be injected through a square capillary tube opposite to the outer continuous phase to emulsify the homogeneous biphasic fluid into uniform palm oil-based double emulsion droplets. The another aqueous phase may further comprise PVA.

The specific content of the microcapsule is as described above.

According to an embodiment, the microcapsule may not have pores or cracks.

According to one embodiment, the microcapsule may be melted at a defined temperature.

According to one embodiment, the temperature-responsive phase change of the wax material may be utilized to achieve on-demand release of the encapsulated material.

According to one embodiment, the microcapsules may have biocompatibility or edible potential.

According to one embodiment, the microcapsules can be compartmentalized and used for efficient loading and transportation of a wide range of materials.

According to one embodiment, the microcapsule can be efficiently manufactured using the manufacturing method.

A shell part comprising a multi-component wax according to an aspect; and an aqueous core part; wherein the multi-component wax is characterized in that the phase changes according to temperature changes, and the shell part has no pores or cracks, microcapsules, cosmetic compositions or functional food compositions comprising the same, and According to the manufacturing method thereof, the supported material can be transported more efficiently, and there is an effect that the material can be released at a specific temperature.

Figure 1A is a schematic diagram of a glass capillary microfluidic device and temperature control platform used to prepare wax-based microcapsules.

1B and 1C are optical micrographs and fluorescence micrographs of the prepared palm oil-based microcapsules. Scale bar is 200 μm.

1D shows the core and overall capsule diameter distribution of palm oil-based microcapsules.

2 is a graph showing the controllability of the core-shell ratio of palm oil-based microcapsules. The total flow rate of the inner and intermediate stages was kept constant at 2500 μl/hr, and the flow rate of the inner stage was increased from 500 μl/hr to 2,000 μl/hr. The flow rate of the external continuous phase was fixed at 10,000 μl/hr.

3A is a schematic diagram illustrating small molecule (sucrose) permeability experiments for two types of wax layers, eicosane and palm oil, respectively.

Figure 3B shows the osmotic pressure change of the upper aqueous solution with time for the eicosan and palm oil layers.

3C and 3D are electron micrographs showing the surface topology of wax-based microcapsules with eicosan shell and palm oil shell, respectively. Scale bar is 200 μm.

3E and 3F are optical and fluorescence micrographs of palm oil-based microcapsules encapsulating sulforodamine B (red fluorescent dye). Micrographs were taken 4 weeks after preparation. Scale bar is 200 μm.

3G is a series of composite micrographs and schematics showing the release of encapsulated sulforodamine B from microcapsules when heated above the melting point of palm oil. The white dotted circle represents the projected surface area of the molten wax phase at the air-water interface. Scale bar is 200 μm.

Figure 4A is a graph comparing the DSC thermal analysis of palm oil and eicosan with and without a surfactant (Span 80).

Figure 4B is a graph comparing the results of Eicosan microcapsules with or without 1% Span 80.

Figure 4C is a graph comparing the results of palm oil microcapsules with or without 1% Span 80.

5A is an optical micrograph of palm oil-based microcapsules encapsulating fluorescein sodium salt (green fluorescent dye), and FIG. 5B is a fluorescence micrograph. Micrographs were taken 4 weeks after preparation. Scale bar is 200 μm.

6A shows the UV visible spectra of niacinamide solutions at various concentrations (0.2 mM, 0.3 mM and 0.5 mM).

6B shows the UV visible spectrum of a 0.01 mM poly(vinyl alcohol) (PVA) solution.

7A shows the UV visible spectrum showing the temperature-dependent phased release of niacinamide from palm oil-based microcapsules upon heating together with a schematic diagram of each phase.

7B is a schematic and optical micrograph showing the release of hydrochloric acid solution from palm oil-based microcapsules upon heating.

7C is a schematic and photographic representation of palm oil-based microcapsules encapsulating calcium chloride solution for heat-induced gelation.

Figure 7D is a schematic and photographic representation of palm oil-based microcapsules encapsulating an ethylenediaminetetraacetic acid (EDTA) solution for dissolution of a preformed hydrogel.

Figure 7E shows that partial gelation of alginate solution and complete gelation through additional shear occurs with palm oil-based microcapsules encapsulating calcium chloride solution when exposed to body temperature.

7F shows that gelation does not occur in alginate solution for palm oil-based microcapsules without calcium chloride solution.

Hereinafter, the present invention will be described in more detail through examples. However, these examples are for illustrative purposes of the present invention, and the scope of the present invention is not limited to these examples.

ingredient

palm oil (Tm = 30 °C to 40 °C), eicosane (99%, Tm = 38 °C), span® 80, poly (vinyl alcohol) (PVA, 87% to 89% hydrolysis, Mw = 13,000 to 23,000), Sulforodamine B (red fluorescent dye), fluorescein sodium salt (green fluorescent dye), erioglaucine sodium salt (blue dye), sucrose (≥99.5%), hydrochloric acid (35.0 to 37.0%), methyl red (acid indicator), calcium chloride (≥93.0%), sodium alginate, ethylene diamine tetra acetic acid (EDTA) were purchased from Sigma-Aldrich. Niacinamide (Vitamin B3) was purchased from DSM Nutritional Products. 2-[Methoxy(polyethyleneoxy) 9-12 propyl]trimethoxyl silane (hydrophilic treatment) was purchased from Gelest, Inc, and octadecyltriclosilane (90%, hydrophobic treatment) was obtained from ACROS ORGANICS. Glass capillaries were purchased from World Precision Instruments. Purified water (EXL®. 18.2 MΩ·cm at 28°C) was used for all experiments. In the case of microcapsules containing palm oil shell encapsulating the EDTA solution, the pH of the EDTA solution was adjusted to 8.3 before encapsulation because EDTA powder had low solubility in acidic pH conditions.

Experimental method

The osmotic pressure of each fluid used in the experiment was measured with an osmometer (Osmomat 3000D) at room temperature and atmospheric pressure. The thermal properties of the analogs to which eicosan, palm oil and surfactant (Span® 80) were added were analyzed using differential scanning calorimetry (DSC, DSC Q200, TA instrument). In DSC analysis, each sample is heated at a rate of 20 °C min ^-1 to 60 °C under N ₂ , then cooled at a rate of 20 °C min ^-1 to -40 °C, and again at a rate of 10 °C min ^-1 to 60 °C. heated.

The release of niacinamide from microcapsules containing palm oil shells was analyzed using a UV-visible spectrophotometer (UV-1800, Shimadzu). The spectral range of the assay was 400 nm to 200 nm.

The surface topology of wax-based microcapsules was observed using a field emission scanning electron microscope (SEM) (JSM 7800F Prime).

In the preparation of microcapsules containing palm oil shell, the flow rate of each fluid was controlled using a syringe pump (KDS Legato ™ 100).

The formation of palm oil-based emulsion droplets was observed using an inverted microscope (Eclipse Ts2, Nikon) equipped with a high-speed camera (FASTCAM Mini UX50, Photron).

Example 1. Preparation of microcapsules

Microcapsules containing palm oil were prepared using a microfluidic device. A specific manufacturing method is as follows.

(1) glass capillary microfluidic device fabrication

Microcapsules containing palm oil were prepared using a glass capillary microfluidic device with a custom temperature control platform (see Fig. 1A). The glass capillary microfluidic device consists of two tapered cylindrical glass capillaries with inner and outer diameters of 0.58 mm and 1.00 mm, respectively. The two cylindrical glass capillaries, the injection capillary and the collection capillary, have outer diameters of 0.14 mm and 0.66 mm, respectively. The injection capillary (diameter 0.14 mm) was hydrophobically modified using octadecyl trichloro silane. The collection capillary (0.66 mm in diameter) was hydrophilically modified using 2-[methoxy(polyethyleneoxy)propyl]trimethoxy silane. The resulting two cylindrical glass capillaries were individually introduced into square glass capillaries from opposite directions for coaxial alignment.

(2) droplet formation

During droplet formation, an aqueous phase containing 0.5 mM sulforodamine B (red fluorescent dye) was injected through an injection capillary to form an inner droplet. Melted palm oil of Span 80 1% (w/w) was used as an intermediate step, and the palm oil was injected through the gap between the square and the injection capillary on the same side as the injection capillary. Another aqueous phase comprising 10% poly(vinyl alcohol) (PVA) was injected through a square capillary tube opposite the outer continuous phase to emulsify the homogeneous biphasic fluid into uniform palm oil based double emulsion droplets. During droplet formation, the microfluidic device and intermediate stage syringe were heated to 55°C, which is above the melting point of palm oil, using a custom temperature controlled platform and syringe heater. The osmotic pressures of the inner and outer aqueous phases were matched by the addition of sucrose in either stage to inhibit water transport through the intermediate stage and to prevent rupture of the emulsion droplets prior to quenching. The resulting palm oil-based droplets were collected in a quench bath (17° C.), frozen in the molten palm oil phase, and then stored in a refrigerator (1° C.). Microcapsules containing the resulting monodisperse palm oil containing sulforodamine B (red fluorescent dye) in an aqueous core were observed (see FIGS. 1B and 1C ). The average diameters of the core and the entire capsule were 234 μm and 286 μm, with coefficient variation (CV) of 2.38% and 2.07%, respectively (see FIG. 1D ).

Palm oil-based microcapsules having the same size but different core-shell ratios can be manufactured by controlling the flow rates of the inner and middle stages while keeping the sum and the outer stage flow rates constant (see FIG. 2 ). Core diameters, expressed as a function of internal phase flow velocity, show that the overall size of the microcapsules remains the same (457.5 ± 5.6 µm), while the core diameters range from 302.8 ± 27.2 µm to 318.8 ± 5.5 µm, 367.7 ± 7.9 µm, and 386.2 ± increased to 10.7 μm.

The above results indicate that highly uniform palm oil-based microcapsules with tunable core-shell ratio can be successfully produced using droplet microfluidics.

Experimental Example 1. Hermetic sealing performance analysis

To investigate the hermetic sealing performance of the produced palm oil-based microcapsules, we first evaluated the permeability of the palm oil layer to model small molecules and compared the behavior with other types of wax material, eicosane. Eicosan (melting point: 38° C.) having a melting point similar to palm oil was selected as the wax material for the control. In addition, sucrose having a molecular weight (MW) of 342 g·mol ^-1 and a hydrodynamic diameter of 0.9 nm was selected as a small molecule model.

In order to check the low molecular permeability of the two types of wax layers, a 40% sucrose solution was prepared, and 500 μl each was dispensed into two centrifuge tubes. Dissolved eicosane and 130 μl of dissolved palm oil were injected into each tube. Next, the centrifuge tube was quenched to 4° C. to solidify the wax layer. Then 600 μl of deionized water was added on each of the two frozen wax layers. This resulted in two sets of centrifugation tubes in which a 40% sucrose solution and pure deionized water were separated by a layer of frozen wax composed of either eicosane or palm oil with a thickness of 0.0250 mm (see Fig. 3A).

The osmotic pressure of the upper aqueous solution was monitored in these two systems for 2 months. The aqueous solution on the eicosan layer showed a steady increase in osmotic pressure, whereas the aqueous solution on the palm oil layer did not increase the osmotic pressure even after 2 months (see Fig. 3B).

These results indicate that the palm oil layer acts as a good physical barrier and provides a hermetic seal against small molecules such as sucrose.

Experimental Example 2. Confirmation of microcapsule surface topology

Two sets of wax-based microcapsules each containing eicosan or palm oil shell were prepared, and the surface topology of the resulting microcapsules was monitored.

As a result, pores and cracks were present in the eicosan-based microcapsules (see Fig. 3C), whereas no noticeable pores or cracks were observed in the similar microcapsules composed of palm oil (see Fig. 3D).

Eicosan is composed of a single component and exhibits a relatively narrow melting point and thus high crystallinity (see Fig. 4A). Therefore, cracks or pore formation occurred during the cooling process (see FIG. 3C ).

On the other hand, palm oil mainly consists of triglycerides containing various fatty acids and small amounts of monoglycerides and diglycerides. Triglycerides can be further classified into two groups with different melting points as indicated by the two broad peaks appearing in the DSC plot of FIG. 4A. During the cooling process, two groups with different melting points can lead to sequential crystallization, so the group with the lower melting point can fill the initial cracks and pores created by the crystallization of the group with the higher melting point, creating an intact shell without pores or cracks. (See Figure 3D).

Even when Span 80, a surfactant, was added to eicosane and palm oil, the phase transition behavior did not change significantly (see FIGS. 4B and 4C).

These results indicate that the sequential crystallization provided by the multi-component wax material can suppress the formation of pores or cracks during cooling. The use of palm oil as a shell material can have an excellent hermetic sealing effect in microcapsules with a relatively thin shell.

A 250 μm thick palm oil-based microcapsule encapsulating a 0.5 mM sulforodamine B solution (red fluorescent dye, MW=581 g·mol ⁻¹ ) was prepared. It was confirmed that a small fluorescent dye did not leak through the palm oil shell even after culturing for 4 weeks (see FIGS. 3E and 3F ). A similar experiment using a lower molecular weight fluorescent dye molecule, fluorescein sodium salt (green fluorescent dye, MW = 376 g mol ^-1 ), showed that palm oil-based microcapsules maintained sealing performance for at least 4 weeks. was confirmed (see FIGS. 5A and 5B).

Experimental Example 3. Observation of ordered emission behavior according to temperature response phase transition

To understand the release mechanism of palm oil-based microcapsules, palm oil-based microcapsules encapsulated with 0.5 mM sulforodamine B (red fluorescent dye) solution were prepared, and the change of microcapsules was confirmed when the temperature was raised to 55 °C.

Palm oil-based microcapsules were initially located at the air-water interface because of the lower density of palm oil than the aqueous continuous phase. When heat was applied, the phase transition of the palm oil shell occurred asymmetrically, and the melted palm oil began to spread at the air-water interface. Local dilution and rupture of the molten wax-based emulsion droplets were induced, followed by release of a red fluorescent dye into the aqueous continuous phase (see Figure 3G).

Experimental Example 4. Confirmation of cosmetic active agent loading efficiency

The effect of the palm oil-based microcapsules on encapsulation and heat release of cosmetic active substances was confirmed.

Niacinamide (Vitamin B3) was encapsulated in palm oil based microcapsules. 5% PVA was added to the aqueous core to increase the viscosity of the inner phase and prevent backflow during the production of niacinamide encapsulated microcapsules.

In order to determine the amount of niacinamide released upon heating, the UV visible spectrum of niacinamide in various concentrations of deionized water was first observed. Niacinamide exhibited two characteristic peaks at wavelengths of 214 nm and 262 nm, respectively (see FIG. 6A ). Since the peak at 214 nm overlaps the peak of PVA (see Fig. 6B), the peak at 262 nm was selected to analyze the amount of niacinamide released from the microcapsules.

The UV visible spectrum of the niacinamide encapsulated microcapsule suspension showed negligible absorbance at 262 nm before heating, but this peak increased after heating, indicating the heat-induced release of niacinamide from the microcapsules (see Fig. 7A).

In addition, to confirm the thermally induced stepwise release of niacinamide from palm oil-based microcapsules, a two-step heating process including a microcapsule addition step was introduced in the middle.

These results indicate that cosmetic ingredients such as niacinamide can be effectively delivered by utilizing the biocompatibility and temperature response behavior of palm oil-based microcapsules.

Experimental Example 5. Confirmation of strong acid loading efficiency

Palm oil-based microcapsules encapsulated in 0.5 M hydrochloric acid solution and 5% of PVA in an aqueous core (pH 0.79) were prepared and dispersed in an indicator solution (10 mM methyl red in ethanol) at pH 12.58. When the solution becomes acidic (<pH 4.4), the color of the indicator solution changes from yellow to red, allowing visualization of acid release from the microcapsules upon heating.

It was observed that the color of the microcapsule suspension was locally changed from yellow to red when the solution temperature was increased to 55°C. This indicates that there was a thermally induced release of hydrochloric acid from the microcapsules into the continuous phase (see Fig. 7B).

Experimental Example 6. Confirmation of heat-induced gelation and dissolution of preformed hydrogels

Palm oil-based microcapsules can be used for heat-induced gelation and preformed hydrogel dissolution by encapsulating a calcium chloride solution or ethylenediaminetetraacetic acid (EDTA) solution in an aqueous core.

(1) heat-induced gelation

Palm oil-based microcapsules containing 2% calcium chloride solution were dispersed in 5% sodium alginate solution. After that, when heated above the melting point of palm oil, calcium ions are released, and the G block (α-L-glucuronic acid) and calcium ions of the alginate block copolymer are ionically crosslinked to form an egg box structure.

To clearly visualize the heat-induced gelation of the alginate solution by releasing calcium ions from the microcapsules, a star-shaped frame was placed in the sodium alginate solution, and palm oil-based microcapsules containing only calcium ions were added in the frame. After heating, a star-shaped alginate hydrogel was formed (see Fig. 7C).

To confirm the thermally induced release of calcium ions, palm oil-based microcapsules were placed on the hand and applied to the body temperature environment. The alginate solution containing microcapsules containing calcium chloride solution showed complete gelation behavior through partial gelation and additional shear stress when exposed to body temperature (see FIG. 7E ). On the other hand, similar experiments on microcapsules without calcium chloride solution showed no apparent gelation (see Fig. 7F).

After applying shear stress, palm oil does not leave a footprint, so it can be used efficiently in skin care products. These results show that palm oil-based microcapsules are applicable to cosmetics.

(2) Confirmation of heat-induced dissolution of preformed hydrogels by EDTA solution

EDTA can be used to reduce the bond strength and chelate the egg carton structures to degrade the preformed alginate hydrogel.

Two sets of alginic acid hydrogel suspensions with or without microcapsules encapsulating the EDTA solution were prepared and the changes upon heating were compared.

For both suspensions, erioglaucine sodium salt (blue dye) was added to the medium to enhance the visual contrast between the hydrogel and the aqueous continuous phase. It was confirmed that the alginate hydrogel was initially dissolved only in the hydrogel suspension with EDTA encapsulated microcapsules (see FIG. 7D ). Since the chelating reaction generally requires a long time, the hydrogel dissolution was evaluated 3 hours after the application of heat.

Claims (10)

1. a shell part comprising a multi-component wax; and an aqueous core part;

   The multi-component wax is characterized in that the phase changes according to the temperature change,

   The shell portion will have no pores or cracks, microcapsules.
2. The microcapsule of claim 1 , wherein the multi-component wax is palm oil wax.
3. The microcapsule according to claim 1, wherein the multi-component wax is sequentially melted at 30 to 40°C.
4. The microcapsule of claim 3, wherein the component is at least one selected from the group consisting of triglycerides, monoglycerides and diglycerides.
5. The microcapsule of claim 1, wherein the microcapsule has a diameter of 200 to 350 μm.
6. The microcapsule for heat-induced gelation according to claim 1, wherein the core part further comprises calcium ions.
7. The microcapsule for dissolving hydrogel according to claim 1, wherein the core part further comprises EDTA.
8. A cosmetic composition comprising the microcapsules of any one of claims 1 to 7.
9. A functional food composition comprising the microcapsules of any one of claims 1 to 5.
10. a shell part composed of an oil phase; and a core part composed of an aqueous phase, wherein the shell part comprises a multi-component wax, forming double droplets; and

    A method of manufacturing microcapsules comprising a; sequentially crystallizing the multi-component wax.

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