TWI728008B - Composition containing double-layer membrane microcell structure and manufacturing method thereof - Google Patents

Abstract

The present invention provides a double-layer membrane microcell (bicelles) structure composition, which can be safely and simply prepared without using an organic solvent, and has a sense of use as an external agent for skin (permeation, moisturizing, firmness) Excellent, and storage stability is also excellent.

The present invention provides a composition containing a double-layer membrane microcellular structure, which is characterized by containing the following components (a) ~ (e): (a) phospholipids; (b) cholesterol and/or physterol 0.02~1 Mass%; (c) at least one selected from polyoxyethylene cholesteryl ether and/or polyoxyethylene phytosteryl ether with an average added molar number of ethylene oxide of 10-20 Surfactant; (d) a glycol selected from at least one of propylene glycol, dipropylene glycol, and 1,3-butanediol; (e) water; the mass ratio of the aforementioned component (a) to component (c) (a)/(c) is 0.4~2.0, the total of component (a) and component (c) is relative to the content of component (b) The ratio {(a)+(c)}/(b) is 5.0 or more.

Description

Composition containing double-layer membrane microcell structure and manufacturing method thereof

The present invention relates to a composition containing a double-layer membrane microcellular structure using phospholipids suitable for cosmetics or skin external preparations. More specifically, the present invention relates to a composition that does not use an organic solvent but can It is safe and easy to prepare, and has an excellent feeling of use as an external preparation for skin, as well as excellent storage stability.

The double-layer membrane micelle structure is a disc-shaped molecular aggregate formed by covering the end of a double-layer flat membrane composed of long-chain phospholipids with a surfactant such as short-chain phospholipids (Figure 1). The minimal lipid bilayer molecular membrane model has been used in the study of biological membranes. For example, by dissolving membrane proteins in a double-layer membrane micelle structure, it is effective for membrane protein structure analysis using NMR (see Non-Patent Document 1). In addition, it is known that by applying a double-layer membrane microcellular structure, it is known to penetrate into the stratum corneum of pig skin (see Non-Patent Document 2), or penetrate into the stratum corneum of a three-dimensional cultured skin model and affect the layered structure of the stratum corneum. And it has also received attention as a carrier.

As for carriers suitable for skin, micelles, vesicles and the like are known.

The microcellular system can incorporate small amounts in the colloid formed by the aggregation of surfactants. A large amount of oil and a thermodynamically stable balance system. Therefore, it is used when a lipophilic active ingredient is blended into a formulation such as a low-viscosity lotion. However, the micelles may not be able to stably blend effective ingredients with high crystallinity, such as cholesterol or phytosterol, due to the small amount of oil that can be contained, and crystals may be precipitated over time.

Vesicles are closed vesicles with a bilayer molecular membrane structure formed by amphiphilic substances. Because of this specific structure, they can coat various active ingredients. They are also attracting attention as carriers for drug delivery systems, etc. (refer to Patent Literature 1). In addition, when vesicles are applied to the skin, they have high retention in the stratum corneum and can effectively act as active ingredients. Therefore, they are also effective as cosmetics or external skin preparations. Vesicles can stably blend cholesterol or phytol, but because the particle size is larger than that of the double-layered microcellular structure, they have poor permeability and insufficient moisturizing effect.

In addition, the known composition containing the double-layer membrane micelle structure is generally prepared by the Bangham Method. Specifically, the lipid is uniformly dissolved in an organic solvent such as chloroform, the organic solvent is removed by an evaporator to form a thin film, and water is added to disperse it (see Non-Patent Document 3). The preparation by the thin film method is excellent in a small proportion, but because the solvent needs to be removed once, it is not suitable for mass production, and organic solvents such as chloroform are used. Therefore, cosmetics or external skin preparations that contact the human body are prepared. The method of composition is quite bad.

[Prior Technical Literature] [Patent Literature]

[Patent Document 1] Japanese Patent No. 5064717

[Non-Patent Literature]

[Non-Patent Document 1] Hirotaka S, Seketsu F, Jun K, Shigeyuki Y, Hiroshi H and Kazuo T. Langmuir, 19, 9841-9844 (2013)

[Non-Patent Document 2] L. Barbosa-Barros, A. de la Maza, J. Estelrich, AM Linares, M. Feliz, P. Walther, R. Pons, and O. López, Langmuir, 24, 5700-5706( 2008)

[Non-Patent Document 3] Oluwatosin A, Ogunsola Margaret E, Kraeling Sheng Zhong Darrin J, Pochan Robert L. Bronaughd and Srinivasa R. Raghavan, Soft Matter, 8, 10226-10232 (2012)

The subject of the present invention is to provide a composition containing a double-layer membrane microcellular structure, which can be safely and easily prepared without using an organic solvent, and has a feeling of use (penetration, moisturizing, The firmness the next morning) is excellent, and the storage stability is also excellent.

In this case, the inventors devoted themselves to research and found that by combining a surfactant with a specific structure and a phospholipid, cholesterol, and/or phytosterol in a specific ratio, a specific binary Alcohol and purified water can be prepared to obtain a novel double-layer membrane microcellular structure The present invention has been completed, and the composition containing the double-layer membrane micelle structure has excellent usability and storage stability.

That is, the present invention relates to a composition containing a double-membrane microcellular structure, which contains the following components (a) to (e): (a) phospholipids; (b) cholesterol and/or phytosterol; (c) Interfacial activity of at least one selected from polyoxyethylene cholesteryl ether and/or polyoxyethylene phytosteryl ether (polyoxyethylene phytosteryl ether) whose average addition molar number of ethylene oxide is 10-20 Agent; (d) a diol selected from at least one of propylene glycol, dipropylene glycol, and 1,3-butanediol; (e) water; the mass ratio of the aforementioned component (a) to component (c) (a) /(c) is 0.4 to 2.0, and the content mass ratio {(a)+(c)}/(b) of the total of the component (a) and the component (c) to the component (b) is 5.0 or more.

In addition, the present invention relates to the aforementioned composition containing the double-layer membrane micelle structure as a cosmetic or external preparation for the skin. Furthermore, the present invention relates to a method of manufacturing the aforementioned double-layer membrane micelle structure-containing composition. After the component (a), the component (b), and the component (c) are dispersed in the component (d), they are mixed and stirred with the component (e) to prepare.

The composition containing the double-layer membrane microcellular structure of the present invention has excellent storage stability, and has high penetration feeling when applied to the skin, and has excellent qualities of moisturizing feeling and firm feeling the next morning. Therefore, the composition of the present invention is useful as an external preparation for cosmetics or skin And in the lotion formulation, it has very high transparency and can also produce a kind of aesthetics.

[Figure 1] A schematic diagram of the double-layer membrane micelle structure of the present invention.

[Figure 2] Electron micrograph of the composition containing the double-layer membrane micelle structure of the present invention (determination ◎).

[Figure 3] Electron micrograph of the composition containing the double-layer membrane micelle structure of the present invention.

[Figure 4] Electron micrograph of a composition containing multilamellar vesicles.

[The form of implementing the invention]

The present invention will be described in detail below, and in this specification, the numerical range indicated by "~" means a range that includes the numerical values described before and after "~" as the lower limit and the upper limit.

The composition containing the double-layer membrane micelle structure of the present invention contains the component (a) phospholipid, and the component (a) phospholipid is used as the main double-layer molecular membrane structure of the double-layer membrane micelle structure. The phospholipid of the component (a) refers to a structure having glycerol or sphingosine as a central skeleton, a fatty acid and phosphoric acid are bonded, and an alcohol and phosphoric acid are bonded by an ester bond. The fatty acids constituting the phospholipid include saturated and unsaturated carboxylic acids having 7 to 22 carbon atoms, preferably 14 to 20 carbon atoms. As far as the alcohols constituting phospholipids are concerned, most of them contain nitrogen. Examples of such alcohols include choline, ethanolamine, inositol, and serine.

As long as the ingredient (a) of the present invention is general cosmetics or skin The user of the skin external preparation is not particularly limited. For example, soybean phospholipids, hydrogenated soybean phospholipids, egg yolk phospholipids, hydrogenated egg yolk phospholipids, sunflower phospholipids, and hydrogenated sunflower phospholipids can be used as needed. Or two or more, more preferably hydrogenated soybean phospholipid and hydrogenated egg yolk phospholipid.

The content of the component (a) in the present invention is not particularly limited, but is preferably 0.01 to 5 mass% (hereinafter the unit is abbreviated as "%"), and more preferably 0.05 to 3%. Within this range, a composition with more excellent storage stability can be obtained.

The composition containing the double-layer membrane microcellular structure of the present invention contains ingredient (b) cholesterol and/or phytosterol. By containing ingredient (b), the moisturizing feeling and the firmness of the next morning will be improved, and become It is a particularly useful composition for cosmetics or external skin preparations. Component (b) is not particularly limited as long as it is used by cosmetics or external skin preparations, and it can be used in combination of one or two or more as necessary.

The content of component (b) in the present invention is 0.02 to 1%, more preferably 0.05 to 0.5%. When the content of component (b) is less than 0.02%, it lacks moisturizing feeling and firmness the next morning; when the content of component (b) exceeds 1%, crystallization is likely to occur, resulting in poor storage stability.

The composition containing the double-layer membrane microcellular structure of the present invention contains component (c) selected from polyoxyethylene cholesteryl ether and/or polyoxyethylene with an average added molar number of 10-20 ethylene oxide A surfactant of at least one of the phytogenic ethers, component (c) is used as a component constituting the main end of the double-layer membrane micelle structure, and by packing with component (a), Contribute to the stability of the double-layer membrane micelle structure. Ring of component (c) The average number of added moles of oxyethane is 10-20. If it is outside this range, the double-layer membrane micellar structure cannot be formed. Among the component (c), POE(10) cholesteryl ether, POE(10) phytosteryl ether, and POE(20) phytosteryl ether are preferred. For these commercially available products, EMALEX CS-10 (manufactured by Nihon Emulsion Co., Ltd.), NIKKOL BPS-10, BPS-20 (manufactured by Nippon Surfactant Industries Co., Ltd.), etc., can be used in combination of one kind or two or more kinds as necessary.

The content of the component (c) in the present invention is not particularly limited, but is preferably 0.025 to 2.5%, more preferably 0.05 to 2.5%. Within this range, a composition having more excellent storage stability and excellent moisturizing feeling can be obtained.

In the composition containing the double-layer membrane micelle structure of the present invention, the content mass ratio (a)/(c) of component (a) to component (c) is 0.4~2, and component (a) and component ( The content mass ratio {(a)+(c)}/(b) of the total of c) with respect to the component (b) is 5.0 or more. If it is outside this range, a double-layer membrane microcellular structure cannot be formed, or a composition that exhibits sufficient effects as cosmetics or skin external preparations cannot be obtained.

The composition containing the double-layer membrane micelle structure of the present invention contains a component (d) of at least one glycol selected from the group consisting of propylene glycol, dipropylene glycol, and 1,3-butanediol. Component (d) is a solvent for dispersing component (a), component (b), and component (c) in water, and is a component used to prepare a composition with excellent storage stability. These systems can be combined as needed One type or two or more types are used.

The content of the component (d) in the present invention is not particularly limited, but it is 1-40%, and more preferably 10-30%. If in this range Inner, it is not only the storage stability of the composition containing the double-layer membrane microcellular structure, but also the excellent moisturizing effect, so it is preferable.

The composition containing the double-layer membrane micelle structure of the present invention contains the component (e) water, and the component (e) water system is used as a dispersion medium of the double-layer membrane micelle structure together with the component (d). Component (e) is not particularly limited as long as it is used by cosmetics or external skin preparations. For example, in addition to purified water, hard water, soft water, natural water, tap water, sea water, deep ocean water, electrolyzed alkaline ionized water, Electrolysis of acidic ionized water, ionized water, cluster water, or lavender water, rose water, orange flower water and other water derived from plant steam distilled water .

The content of the component (e) in the present invention is not particularly limited, but it is preferably about 50 to 99%.

In addition, within the range that does not interfere with the effects of the present invention and the formation of the double-layer membrane micelle structure, the composition containing the double-layer membrane micelle structure of the present invention can be mixed with general cosmetics or skin external agents. Optional ingredients, specifically oils, alcohols, powders, water-soluble polymers, film-forming agents, surfactants other than the aforementioned ingredients, oil-soluble gelling agents, organic modified clay minerals, resins, UV absorbers can be added Agents, preservatives, antibacterial agents, fragrances, antioxidants, pH adjusters, chelating agents, etc.

The composition system of the present invention containing a double-layer membrane microcellular structure can be manufactured by various methods of manufacturing general cosmetics or skin external preparations, but since the components (a), (b), and (c) Disperse in ingredient (d) and then mix and stir with ingredient (e) to prepare it. It is better for mass production. Specifically, the component (a), the component (b), and the component (c) are dispersed in the component (d) that has been heated to a temperature of, for example, preferably 70°C to 90°C, more preferably about 80°C. The component (e) heated to, for example, preferably a temperature of 70 to 90°C, and more preferably a temperature of about 80°C is added to the solution, mixed and stirred, and then slowly cooled to room temperature. There are no particular limitations on the stirring method during preparation and cooling, but for example, the equipment for dispersing treatment includes a dispersing mixer, a homomixer, a bead mill, etc. Examples of equipment for high-pressure processing include a microfluidizer, etc., but it is more preferable that such processing can be performed under normal pressure.

As described above, the composition containing the double-layer membrane micelle structure of the present invention is obtained. The double-layer membrane micelle structure system can be observed by a transmission electron microscope to confirm its existence and particle size (Figure 2) . The average particle diameter of the double-layer membrane microcell structure of the present invention is preferably 10-60 nm in the long diameter, more preferably 15-40 nm, and preferably 1-10 nm in the short diameter, more preferably 3-8 nm. In the composition of the present invention, there are cases where multi-layered vesicle particles (approximately 50 nm or more concentric images) coexist, but if more than half of the particles in the observation field are double-layered microcellular structures ( Disk-shaped image), will exert its effect as the composition containing the double-layer membrane micelle structure of the present invention. That is, the ratio of the double-layer membrane micelle structure in the present invention is expressed by (number of disc images/number of all particle images) in the observation field of view using an electron microscope, which is 50% or more, preferably 75% Above, more preferably 100%.

The composition system containing the double-layer membrane micelle structure of the present invention can be used directly as cosmetics or external skin preparations, and can also be used in adjusting After preparing the composition containing the double-layer membrane micelle structure, it can be combined with other ingredients to make cosmetics or external skin preparations, which can be used as cosmetics or external skin preparations for various purposes. For example, skin care cosmetics such as lotions, lotions, creams, eye creams, essences, massage creams, facial masks, hand creams, body lotions, body creams, cosmetics such as makeup primers, external liquids, and external use can be exemplified. Gels, creams, ointments, liniments, lotions, poultices, plasters, sprays, aerosols and other skin external preparations. In addition, the method of use includes a method of using hands or fingers, a method of impregnating cotton or non-woven fabric, and the like.

[Example]

Examples are listed below to further illustrate the present invention in detail, but the present invention is not limited to these embodiments.

[Examples 1 to 13 and Comparative Examples 1 to 10: Essence]

According to the following preparation method, the composition of the composition shown in Tables 1 to 3 was prepared.

The confirmation of the double-membrane micellar structure was performed by observation with a transmission electron microscope, and the evaluation was performed based on the following criteria (Figures 2 and 3). In addition, the transmittance (transparency) and storage stability of the composition were evaluated by the following evaluation methods. These compositions were applied to the skin (full face) as an essence, and sensory evaluation was performed according to the following method. The evaluation results are combined and shown in Tables 1 to 3.

(Production method)

1: The classifications (A) to (D) are heated to 80°C for dispersion.

2: Heating classification (E) at 80°C.

3: Add 2 to 1 and mix and stir with a dispersion mixer.

4: Cool 3 to room temperature to obtain the essence (composition containing the double membrane micelle structure).

(Evaluation method 1: Confirmation of double-layer membrane micelle structure)

The formation state of the double-layer membrane micellar structure was observed with a transmission electron microscope, and the following judgment criteria were used to determine the unique disc-shaped image of the double-layer membrane micelle structure.

[Judgment Criteria]

(Evaluation): (judgment)

Most of the disc-shaped images are observed, and the images of multi-layered vesicles are not seen at all (Figure 2): ◎

Some images of multilamellar vesicles were also observed

(Concentric circles) (Picture 3): ○

Almost no disc-shaped image is observed (picture 4): ×

(Evaluation method 2: Penetration rate)

Regarding the transparency of the composition immediately after its manufacture, the transmittance at a wavelength of 700 nm was measured using an ultraviolet-visible spectrophotometer. The measured transmittance is judged using the following judgment criteria.

[Judgment Criteria]

(Evaluation): (judgment)

Penetration rate is above 90%: ◎

The penetration rate is above 85% and less than 90%: ○

The penetration rate is above 80% and less than 85%: △

The penetration rate is less than 80%: ×

(Evaluation method 3: Storage stability)

For each sample, a comparison was made between those stored at a constant temperature of 40°C for 2 months and those stored at 25°C for 2 months. The transparency and the presence or absence of precipitates were visually evaluated, and the following judgment criteria were used for judgment.

[Judgment Criteria]

(Evaluation): (judgment)

No change in appearance: ◎

Slight turbidity is seen in appearance: ○

Obviously turbid in appearance or confirmed to have precipitates: △

Obviously turbid appearance or precipitation: ×

(Evaluation method 4: Sensory evaluation)

Twenty female subjects aged 20 to 49 years used the above-mentioned composition containing the double-layer membrane microcellular structure as an essence for (1) penetration, (2) moisturizing, and (3) the next morning. The feeling of firmness was evaluated based on the following evaluation criteria as the feeling of use. And calculate the average of the evaluation scores of all subjects, and use the following criteria for judgment.

[Evaluation criteria]

(Evaluation): (evaluation score)

Very sensible: 5 points

Feeling a little: 4 points

Normal: 3 points

Not very sensible: 2 points

No feeling: 1 point

[Judgment Criteria]

(Average of evaluation scores of all subjects): (Judgment)

Average score above 4.5: ◎

The average score is 3.5 or more and less than 4.5: ○

The average score is 2.5 or more and less than 3.5: △

The average score is less than 2.5: ×

Judging from the results in Tables 1 to 3, it is clear that Examples 1 to 13 have excellent storage stability, and when applied to the skin as an essence, they will penetrate quickly and have excellent moisturizing effects. Also, observe with an electron microscope The average particle size and ratio of the obtained double-layer membrane micelle structure are 30nm long diameter and 3~5nm short diameter in Example 1, and the ratio is 100%. In Example 6, long diameter 50nm and short diameter 3~5nm are used. 5nm, the ratio is 100%.

On the other hand, Comparative Examples 1 to 7 that did not contain the component (c) or the component (d), and Comparative Examples 8 to 10 in which the content mass ratio of each component was outside the range did not form a bilayer membrane micelle structure.

[Example 14: Toner]

(Production method)

A: The components (1) to (5) are heated and dispersed at 80°C.

B: Component (6) is heated at 80°C.

C: While adding A to B and mixing and stirring, a double-layer membrane micelle structure is formed on the same side, and the mixture is cooled to room temperature.

D: Ingredients (7) to (12) are added and mixed to C to obtain a lotion.

(result)

The lotion of Example 14 is a cosmetic with good storage stability, excellent penetration, and excellent moisturizing effect.

[Example 15: Emulsion]

20. Purified water 10.0

(Note 1) Pemulen TR-2 (manufactured by NOVEON)

(Production method)

A: Heat and melt components (1) to (7) at 80°C.

B: After heating components (8) to (12) at 80°C, they are added to A and emulsified.

C: After cooling B to room temperature.

D: The components (14) to (19) are heated and dispersed at 80°C.

E: The component (20) is heated to 80°C, and mixed and stirred while being added to D to form a double-layer membrane micelle structure.

F: After cooling E, it is added to C, and component (13) is added to obtain an emulsion.

(result)

The emulsion of Example 15 is a cosmetic with good storage stability, excellent penetration, and excellent moisturizing effect.

[Example 16: Cream]

(Production method)

A: Heat and melt components (1) to (6) at 70°C.

B: After heating and dissolving the components (7) and (8) at 70°C, they are added to A and emulsified.

C: After cooling B to room temperature, components (9) to (11) are added.

D: The components (12) to (16) are heated and dispersed at 80°C.

E: Component (17) is heated to 80°C, and D is added while mixing and stirring are performed to form a double-layer membrane micelle structure.

F: After cooling E, it is added to C to obtain a cream.

(result)

The cream of Example 16 is a cosmetic with good storage stability, excellent penetration, and excellent moisturizing effect.

[Example 17: Sheet cosmetics]

(Ingredients) (%)

(Production method)

A: The components (1) to (8) are heated and dispersed at 80°C.

B: Component (9) was heated to 80°C, and A was added while mixing and stirring were performed to form a double-layer membrane micelle structure.

C: After cooling B, the components (10) to (14) are added and the non-woven fabric is impregnated.

D: C was sealed and filled in an aluminum laminated bag-shaped container to obtain a sheet-shaped cosmetic.

(result)

The sheet-shaped cosmetic of Example 17 is a cosmetic with good storage stability, excellent penetration, and excellent moisturizing effect and whitening effect.

[Example 18: Creamy base cosmetics]

(Note 2) KP-549 (60% acrylic-polysiloxane graft copolymer: 40% methyl polytrimethylsiloxane mixture) (manufactured by Shin-Etsu Chemical Co., Ltd.)

(Production method)

A: Disperse the components (1) to (5) with a three-roll mill.

B: Mix the components (6) to (11).

C: Add A to B to emulsify.

D: The components (12) to (16) are heated and dispersed at 80°C.

E: Component (17) is heated to 80°C, and D is added while mixing and stirring are performed to form a double-layer membrane micelle structure.

F: After cooling E, it is added to C to obtain a base makeup before cream makeup.

(result)

The base makeup before cream makeup of Example 6 is a cosmetic with good storage stability, excellent penetration, and excellent moisturizing effect.

[Example 19: Toner]

(Production method)

A: The components (1) to (4) are heated and dispersed at 80°C.

B: The component (5) is heated to 80°C.

C: While adding A to B for mixing and stirring, forming a double Layer the microcellular structure and cool to room temperature.

D: Ingredients (6) to (8) are added and mixed to C to obtain a lotion.

(result)

The double-layer membrane micelle structure of Example 19 was observed by an electron microscope, and its average particle size was 15 nm in the long diameter and 3 to 5 nm in the short diameter, and the ratio of the double-layer membrane micelle structure was 100%. In addition, the lotion of Example 19 is a cosmetic with good storage stability, excellent penetration, and excellent moisturizing effect.

Claims (3)

A composition containing a double-membrane microcellular structure, which contains the following components (a) to (e): (a) phospholipids; (b) cholesterol and/or phytosterol 0.02 to 1% by mass; (c) ) A surfactant selected from at least one of polyoxyethylene cholesteryl ether and/or polyoxyethylene phytosteryl ether (polyoxyethylene phytosteryl ether) whose average addition molar number of ethylene oxide is 10-20; (d) A diol selected from at least one of propylene glycol, dipropylene glycol, and 1,3-butanediol; (e) water; the mass ratio of the aforementioned component (a) to component (c) (a)/( c) is 0.4~2.0, and the total content of component (a) and component (c) relative to the content of component (b) {(a)+(c)}/(b) is 5.0 or more, and the content of component (a) The content ratio is 0.05 to 3% by mass, and the content ratio of component (c) is 0.025 to 2.5% by mass. For example, the composition containing the double-layer membrane micelle structure of claim 1 is a cosmetic or an external preparation for skin. A method for producing a composition containing a double-layered membrane micelle structure as claimed in claim 1, which disperses component (a), component (b), and component (c) in the aforementioned component (d), and then combines with component ( e) Mix and stir to prepare.

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