JP2021046378A - Lipid membrane structure-forming composition and production method thereof, lipid membrane structure-containing composition and production method thereof, cosmetics containing lipid membrane structure-containing composition, and skin external preparation - Google Patents

Abstract

To provide means allowing simple formation of a fine lipid membrane structure.SOLUTION: A lipid membrane structure-forming composition contains (A) a hydrogenated phospholipid with an acid value of 5 mgKOH/g or more, and (B) a compound represented by the formula 1 in the figure, where the content of the (B) component is greater than 100 pts.mass based on 100 pts.mass of the (A) component. In the formula 1, R is a substituted or unsubstituted C2-6 alkyl group, or a substituted or unsubstituted C3-6 cycloalkyl group; X is -O-, -C(=O)O-, or -O-C(=O)-; and n is 0 or 1.SELECTED DRAWING: None

Description

The present invention relates to a composition for forming a lipid membrane structure and a method for producing the same, a composition containing a lipid membrane structure and a method for producing the same, and the composition containing the lipid membrane structure. Concerning cosmetics and external preparations for skin, which are made by blending substances.

Lipid membrane structures such as liposomes and bicells have skin care effects such as moisturizing and improving skin quality, and can contain active ingredients, and are therefore useful in cosmetic applications and external preparations for skin. Phospholipids are mainly used as raw materials for lipid membrane structures in the above applications because they are naturally derived and highly safe. Of these, hydrogenated phospholipids in which hydrogen atoms are added to unsaturated carbon bonds of phospholipids are preferably used because they are not easily deteriorated by oxidation.

So far, techniques for forming lipid membrane structures using hydrogenated phospholipids have been studied. For example, in Patent Document 1, a composition in which ceramides, branched alcohols, etc. are mixed with hydrogenated phospholipids is prepared and dispersed in a large excess of water to improve the flexibility and storage stability of the lipid membrane. It has been described that high liposomes can be obtained. Patent Document 2 describes that an oil-soluble composition containing a hydrogenated phospholipid, a glycol compound, and a fat-soluble compound is mixed with a water-soluble composition to form a multilayer liposome, and then treated by a conversion process. It is described that fine monolayer liposomes can be obtained.

Japanese Unexamined Patent Publication No. 2011-32230 Special Table 2012-504620

For cosmetics and external preparations for skin, a fine lipid film structure (for example, with an average particle size of 200 nm or less) is required from the viewpoints of penetration into the skin, expression of the effect of the contained active ingredient, storage stability, and the like. .. However, since the hydrogenated phospholipid has a higher phase transition temperature than the non-hydrogenated phospholipid, it is difficult to form a fine lipid film structure. In fact, in the technique for forming a lipid membrane structure using hydrogenated phospholipids as described in Patent Documents 1 and 2, a fine (for example, an average particle diameter of 200 nm or less) lipid membrane structure is formed. In order to make it possible, it was necessary to use a miniaturization means such as a microfluidizer.

Therefore, an object of the present invention is to provide a means capable of easily forming a fine lipid membrane structure.

The present inventors have conducted diligent research in order to solve the above problems. As a result, they have found that the above-mentioned problems can be achieved by a composition for forming a lipid membrane structure containing a hydrogenated phospholipid having an acid value of 5 mgKOH / g or more and a polyol compound having a specific structure in a specific ratio. The present invention has been completed.

According to the present invention, a fine lipid membrane structure can be easily formed.

It is a photograph which observed the lipid membrane structure formed by using the composition for forming a lipid membrane structure of an Example by a cryo-electron microscope (Cryo-TEM).

The composition for forming a lipid membrane structure according to the present invention contains (A) a hydrogenated phospholipid having an acid value of 5 mgKOH / g or more, and (B) a compound represented by the following formula 1, as described in (B). ) The content of the component exceeds 100 parts by mass with respect to 100 parts by mass of the component (A).

In the above formula 1,
R is a substituted or unsubstituted alkyl group having 2 to 6 carbon atoms or a substituted or unsubstituted cycloalkyl group having 3 to 6 carbon atoms.
X is −O−, −C (= O) O− or −OC (= O) −,
n is 0 or 1.

According to the composition for forming a lipid membrane structure according to the present invention, it is possible to form a fine lipid membrane structure (for example, an average particle size of 200 nm or less) without requiring a miniaturization means such as a microfluidizer. it can.

As described above, lipid membrane structures such as liposomes and bicelles are useful in cosmetic applications and skin external preparation applications. In the above applications, a fine lipid membrane structure (for example, an average particle size of 200 nm or less) is required from the viewpoints of penetration into the skin, expression of the effect of the contained active ingredient, storage stability, and the like. Phospholipids are mainly used as raw materials for lipid membrane structures in the above applications because they are naturally derived and highly safe. Of these, hydrogenated phospholipids are preferably used because they are not easily deteriorated by oxidation. However, compared to non-hydrogenated phospholipids, hydrogenated phospholipids have a higher phase transition temperature and their physical properties are significantly different between the two. Therefore, in the techniques described in Patent Documents 1 and 2, it is possible to easily form a fine (for example, an average particle size of 200 nm or less) lipid film structure using hydrogenated phospholipids having a high phase transition temperature. It was difficult.

Therefore, the present inventors have diligently studied a means for easily forming a fine lipid membrane structure using hydrogenated phospholipids. As a result, surprisingly, (A) a hydrogenated phospholipid having an acid value of 5 mgKOH / g or more and (B) a polyol compound represented by the above formula 1 were added to 100 parts by mass of the component (A). By blending the component (B) so as to exceed 100 parts by mass to prepare a composition for forming a lipid film structure and dispersing it in the aqueous phase, fine (B) can be obtained without the need for micronization means. For example, it has been found that a lipid film structure (with an average particle size of 200 nm or less) can be formed.

Preferred embodiments of the present invention will be described. The present invention is not limited to the following embodiments.

In addition, in this specification, a "lipid membrane structure" means a particle having a lamellar (lipid bilayer) structure in which lipid molecules are arranged with hydrophilic groups facing outward and hydrophobic groups facing each other. Specific forms thereof include those described in the section <Lipid Membrane Structure-Containing Composition> described later. Further, in the present specification, regarding the lipid membrane structure-containing composition prepared by using the composition for forming a lipid membrane structure, a dynamic light scattering measuring device, more specifically, a Zetasizer Nano ZSP (Marvern Instruments) If the average particle size can be measured using (manufactured by the company), it is assumed that a lipid membrane structure is formed.

In the present specification, "x to y" indicating a range includes x and y and means "x or more and y or less". Unless otherwise specified, operations and measurements of physical properties shall be performed under the conditions of room temperature (20 to 25 ° C.) / relative humidity of 40 to 50% RH.

<Composition for forming lipid membrane structure>
Hereinafter, the components and production method of the composition for forming a lipid membrane structure according to the present invention (hereinafter, also referred to as “lipid membrane structure forming agent” or “forming agent”) will be described.

[(A) component]
The lipid membrane structure-forming agent of the present invention contains a hydrogenated phospholipid having an acid value of 5 mgKOH / g or more as the component (A). The component (A) may be one or more hydrogenated phospholipids having an acid value of 5 mgKOH / g or more, one or more hydrogenated phospholipids having an acid value of less than 5 mgKOH / g, and one or more hydrogenated phospholipids. A hydrogenated phospholipid having an acid value of 5 mgKOH / g or more may be combined to have an acid value of 5 mgKOH / g or more.

The hydrogenated phospholipid can be obtained by adding a hydrogen atom to the unsaturated carbon bond of the phospholipid by a conventionally known method. The origin of the phospholipid is not particularly limited, but lecithin is particularly preferable because it is naturally derived and can be suitably used for cosmetics and external preparations for skin. Therefore, in one embodiment of the present invention, the component (A) is hydrogenated lecithin. The lecithin may be derived from soybean, egg yolk, rapeseed, sunflower, corn, etc., and is preferably derived from plants such as soybean, rapeseed, sunflower, and corn, and is easily available. It is more preferable that it is derived from soybean from the viewpoint of sex and quality stability.

The acid value of the component (A) is 5 mgKOH / g or more. When a hydrogenated phospholipid having an acid value of less than 5 mgKOH / g is used, a fine lipid membrane structure cannot be formed even when combined with the component (B) (Comparative Example 2-1 (a) described later). ~ 2-1 (c)). From the viewpoint of obtaining a finer lipid membrane structure, the acid value of the component (A) is preferably 12 mgKOH / g or more, more preferably 15 mgKOH / g or more, still more preferably 17 mgKOH / g or more. Even more preferably, it is 20 mgKOH / g or more, and particularly preferably 22 mgKOH / g or more. Further, although not particularly limited, the acid value of the component (A) is, for example, 70 mgKOH / g or less, 60 mgKOH / g or less, 50 mgKOH / g or less, or 40 mgKOH / g or less. By appropriately selecting the type of phospholipid, a hydrogenated phospholipid having a desired acid value can be obtained. The acid value of component (A) shall be the value measured in accordance with "Quasi-drug Raw Material Standards 2006 General Test Method 27. Acid Value Measurement Method".

As the component (A), either a synthetic product or a commercially available product may be used. Examples of commercially available products include NIKKOL (registered trademark) Resinol S-10 and S-10 PLUS manufactured by Nikko Chemicals Co., Ltd., EMALEX (registered trademark) SLP manufactured by Nippon Emulsion Co., Ltd., and SLP manufactured by Tsuji Oil Co., Ltd. -White H and the like can be mentioned. These may be used alone or in combination of two or more.

The content of the component (A) in the lipid membrane structure forming agent of the present invention is preferably 5 to 40% by mass, more preferably 10 to 20% by mass.

[(B) component]
The lipid membrane structure forming agent of the present invention contains the compound represented by the following formula 1 as the component (B). The component (B) may be only one kind or two or more kinds.

In the above formula 1, R is a substituted or unsubstituted alkyl group having 2 to 6 carbon atoms or a substituted or unsubstituted cycloalkyl group having 3 to 6 carbon atoms.

The alkyl group having 2 to 6 carbon atoms may be linear or branched. Examples of alkyl groups having 2 to 6 carbon atoms include ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, n-pentyl group, and iso-amyl. Group, tert-pentyl group, neopentyl group, n-hexyl group, 3-methylpentane-2-yl group, 3-methylpentane-3-yl group, 4-methylpentyl group, 4-methylpentane-2-yl group Groups, 1,3-dimethylbutyl group, 3,3-dimethylbutyl group, 3,3-dimethylbutane-2-yl group and the like can be mentioned. Alkyl groups having 2 to 6 carbon atoms are preferably linear. That is, the alkyl group having 2 to 6 carbon atoms is preferably a group selected from the group consisting of an ethyl group, an n-propyl group, an n-butyl group, an n-pentyl group and an n-hexyl group.

Examples of the cycloalkyl group having 3 to 6 carbon atoms are a cyclopropyl group, a cyclobutyl group, a cyclopentyl group and a cyclohexyl group, and a cyclohexyl group is preferable.

Substituents that can be present in the alkyl group having 2 to 6 carbon atoms and the cycloalkyl group having 3 to 6 carbon atoms are not particularly limited as long as the effects of the present invention are exhibited. Examples of the substituent include a halogen atom, an acyl group, an alkyl group, an aryl group, an alkoxyl group, a nitro group, an amino group, a cyano group and the like. However, the alkyl group having 2 to 6 carbon atoms is not substituted with the alkyl group.

In the above formula 1, X is −O−, −C (= O) O− or −OC (= O) −, preferably −O−. Further, in the above formula 1, n is 0 or 1. In the above formula 1, when X is −O− and n is 1, the number of carbon atoms of the alkyl group as R is preferably 4 or more.

The component (B) is at least one selected from the group consisting of, for example, 1,2-pentanediol, 1,2-hexanediol, 1,2-heptanediol, 1,2-octanediol, cyclohexylglycerin and hexylglycerin. It is preferably a seed.

In particular, when 1,2-hexanediol, 1,2-heptanediol, and hexylglycerin are used as the component (B), an extremely fine lipid membrane structure can be formed. At this time, the lipid membrane structure is considered to form a bicell. Since the bicell has a disk-shaped (disk) single-layer lamellar structure, it has excellent permeability to the stratum corneum as compared with liposomes having a similar particle size. Therefore, from the viewpoint of obtaining a lipid membrane structure having high permeability of the fat-soluble component, at least selected from the group consisting of 1,2-hexanediol, 1,2-heptanediol and hexylglycerin as the component (B). It is preferable to use one type.

The component (B) may be either a synthetic product or a commercially available product.

The content of the component (B) in the lipid membrane structure forming agent of the present invention is preferably 30 to 90% by mass, more preferably 40 to 80% by mass, and even more preferably 50 to 70% by mass. is there.

In the lipid membrane structure forming agent of the present invention, the content of the component (B) exceeds 100 parts by mass with respect to 100 parts by mass of the component (A). When the content of the component (B) is 100 parts by mass or less with respect to 100 parts by mass of the component (A), a fine lipid membrane structure cannot be formed (Comparative Examples 1-1 and 1-described later). 2). Further, the content of the component (B) is preferably 150 parts by mass or more with respect to 100 parts by mass of the component (A). When the amount is 150 parts by mass or more, the component (A) is more easily dissolved or dispersed in the lipid membrane structure forming agent. By using the lipid membrane structure forming agent, it is possible to form a lipid membrane structure having excellent dispersibility in the aqueous phase. Further, from the viewpoint of obtaining a finer lipid membrane structure, the content of the component (B) is preferably 200 parts by mass or more, more preferably 250 parts by mass or more with respect to 100 parts by mass of the component (A). It is more preferably 300 parts by mass or more, further preferably 350 parts by mass or more, and particularly preferably 400 parts by mass or more. On the other hand, the upper limit of the content of the component (B) with respect to 100 parts by mass of the component (A) is not particularly limited, but even if it exceeds 2000 parts by mass, the solubility of the component (A) in the lipid membrane structure forming agent or It has no effect on decentralization and is simply uneconomical. Therefore, the content of the component (B) is preferably 2000 parts by mass or less with respect to 100 parts by mass of the component (A). Therefore, according to a preferred embodiment of the present invention, the content of the component (B) is preferably 150 to 2000 parts by mass with respect to 100 parts by mass of the component (A).

[Component (C)]
The lipid membrane structure forming agent of the present invention may further contain water as the component (C). When the component (A) having a high acid value is used, the lipid film structure forming agent having better solubility or dispersibility of the component (A) can be obtained by using the component (B) and the component (C) together. it can. By using the lipid membrane structure forming agent, it is possible to form a lipid membrane structure having excellent dispersibility in the aqueous phase. In addition, the component (C) has a role of assisting the compounding of the following component (D) (basic compound) and component (E) (acidic compound) into the lipid membrane structure forming agent. Specifically, the component (D) and / or the component (E) is previously dissolved in the component (C) and then mixed with the components (A) and (B) to form the component (D) and / or the component (D). The component (E) can be easily blended with the lipid membrane structure forming agent.

As the component (C), water having few impurities is preferable, and for example, water purified from normal water by a system such as purified water in which ion exchange, distillation, reverse osmosis, ultrafiltration, etc. are used alone or in combination is preferable. ..

The content of the component (C) in the lipid membrane structure forming agent of the present invention is preferably 0.5 to 70% by mass, more preferably 5 to 60% by mass, and even more preferably 15 to 50% by mass. %, Especially preferably 20 to 40% by mass.

Further, in the lipid membrane structure forming agent of the present invention, the mass ratio of the component (B) and the component (C) is preferably 100: 1 to 1: 3, and more preferably 9: 1 to 1: 2. Yes, and even more preferably 6: 1 to 1: 1.

[(D) component]
The lipid membrane structure forming agent of the present invention may further contain a basic compound as a component (D) in addition to the above components (A) and (B). When the component (A) having a high acid value is used, the lipid film structure forming agent having more excellent solubility or dispersibility of the component (A) can be obtained by containing the component (D). By using the lipid membrane structure forming agent, the dispersibility of the lipid membrane structure in the aqueous phase can be enhanced. The component (D) may be only one type or two or more types.

Examples of the component (D) include inorganic bases such as sodium hydroxide, potassium hydroxide and ammonia; basic amino acids such as arginine, lysine and histidine; ethanolamine, diethanolamine, triethanolamine and 2-amino-2-methyl. Examples thereof include amine compounds such as -1,3-propanediol (AMPD) and 2-amino-2-hydroxymethyl-1,3-propanediol (tromethamine). Of these, arginine is preferable.

As the component (D), either a synthetic product or a commercially available product may be used.

The content of the component (D) in the lipid membrane structure forming agent of the present invention is preferably 0.01 to 2% by mass, more preferably 0.02 to 1% by mass.

In the lipid membrane structure forming agent of the present invention, the content of the component (D) is preferably 0.05 to 10 parts by mass, more preferably 0.1 to 1 part by mass with respect to 100 parts by mass of the component (A). 5 parts by mass.

[(E) component]
The lipid membrane structure forming agent of the present invention may contain an acidic compound as the component (E) in addition to the above components (A) and (B). By containing the component (E), a lipid membrane structure-forming agent having more excellent solubility or dispersibility of the component (A) can be obtained. By using the lipid membrane structure forming agent, the dispersibility of the lipid membrane structure in the aqueous phase can be enhanced. The component (E) may be only one kind or two or more kinds.

Examples of the component (E) include inorganic acids such as hydrochloric acid, sulfuric acid, nitrate, phosphoric acid and carbonic acid; acetic acid, formic acid, propionic acid, butyric acid, citric acid, lactic acid, succinic acid, malic acid, tartaric acid and pyrrolidone carboxylic acid ( PCA), gluconic acid, benzoic acid, ethylenediamine tetraacetic acid (EDTA), etidroic acid, organic acids such as phytic acid and the like can be mentioned. Of these, an organic acid is preferable from the viewpoint of obtaining a lipid membrane structure-forming agent having more excellent solubility or dispersibility of the component (A).

Above all, from the viewpoint that a lipid film structure forming agent having better solubility or dispersibility of the component (A) can be obtained, a lipid film structure having excellent dispersibility in an aqueous phase using the lipid film structure forming agent. From the viewpoint of forming the above, and from the viewpoint of enhancing the storage stability of the lipid film structure forming agent and the lipid film structure-containing composition using the lipid film structure forming agent, the component (E) has a chelating action. It is preferably an organic acid having. The component (A) may have a property of easily binding to a metal ion. In this case, by adding an organic acid having a chelating action as the component (E), metal ions in the lipid film structure forming agent are captured, the storage stability of the lipid film structure forming agent is enhanced, and ( A) component becomes easier to dissolve or disperse, and a lipid film structure forming agent having better solubility or dispersibility of component (A) can be obtained. It is presumed that the lipid membrane structure having excellent dispersibility in the aqueous phase and storage stability can be formed by using the forming agent. As the organic acid having a chelating action, for example, citric acid, ethylenediaminetetraacetic acid (EDTA) and etidronic acid are preferable, and ethylenediaminetetraacetic acid (EDTA) is more preferable.

As the component (E), either a synthetic product or a commercially available product may be used.

In the lipid membrane structure forming agent of the present invention, the content of the component (E) (in terms of free acid) is preferably 0.02 to 4% by mass, more preferably 0.04 to 2% by mass.

In the lipid membrane structure forming agent of the present invention, the content of the component (E) (in terms of free acid) is preferably 0.1 to 20 parts by mass with respect to 100 parts by mass of the component (A), more preferably. Is 0.2 to 10 parts by mass.

From the viewpoint of increasing the solubility of both the component (D) and the component (E) in the lipid membrane structure forming agent and keeping the pH of the forming agent at the time of aqueous phase dispersion within a predetermined range, the lipid membrane structure of the present invention. The forming agent preferably contains both the component (D) and the component (E). Such a lipid membrane structure forming agent may be obtained by adding the component (D) and the component (E) separately, or by adding the salt of the component (D) and the component (E). You may.

The salt of the component (D) and the component (E) is not particularly limited, and is, for example, lysine hydrochloride; sodium citrate salt such as trisodium citrate; sodium phosphate salt such as disodium hydrogen phosphate; benzoate. Sodium; Examples thereof include sodium ethylenediaminetetraacetate such as trisodium ethylenediaminetetraacetate (EDTA-3Na).

When the lipid membrane structure forming agent contains the component (D) and the component (E), the mass ratio of the component (D) and the component (E) is preferably 1: 0.1 to 1: 4, and more. It is preferably 1: 0.2 to 1: 2.

In the lipid membrane structure forming agent of the present invention, the total content of the component (D) and the component (E) is preferably 0.05 to 4% by mass, more preferably 0.1 to 2% by mass. ..

[(F) component]
The lipid membrane structure forming agent of the present invention may further contain a fat-soluble compound as a component (F) in addition to the above components (A) and (B). When the component (A) having a high acid value is used, the lipid film structure forming agent having better solubility or dispersibility of the component (A) can be obtained by using the component (B) and the component (F) in combination. it can. By using the lipid membrane structure forming agent, it is possible to form a lipid membrane structure having excellent dispersibility in the aqueous phase and high storage stability. Further, by using the component (F) in combination with the component (D) and / or the component (E), a finer lipid membrane structure can be formed (Table 5 described later). The component (F) may be only one type or two or more types.

Examples of the component (F) include phytosterols, cholesterol, sterols such as di (phytosteryl / octyldodecyl) lauroyl glutamate, phytosteryl oleate, and phytosteryl glucoside; Triterpenes such as (mixtures of asiatic acid, madecacinic acid and asiaticoside); fat-soluble vitamins such as retinol, hydrogenated retinol, cholecalciferol, tocopherol, ascorbic acid ester; carotenoids such as astaxanthin and β-carotene; ubiquinone and the like Co-enzymes; hydrocarbons such as limonene, vaseline, squalane; ceramide EOS, ceramide NG (ceramide 2), ceramide NP (ceramide 3), ceramide AP (ceramide 6II), ceramide EOP (ceramide 1), dihydroxylignocelloylphyto Examples thereof include ceramides such as sphingosine, celebroside, sphingoliglycolide, and cetyl PG hydroxyethyl palmitamide; and polyphenols such as tetrahydrodiferloylmethane and pterostilben. Above all, by combining the component (F), the component (A) and the component (B), the solubility of the component (A) and the component (F) is mutually enhanced, and the solubility of the component (A) is further improved. F) From the viewpoint that the components can be easily blended and a lipid film structure-forming agent having good storage stability can be obtained, and the storage stability of the lipid film structure-containing composition using the lipid film structure-forming agent. From the viewpoint of enhancing, the components (F) are phytosterols, cholesterol, γ-oryzanol, glycyrrhizinic acid, ursolic acid, tuboxa extract (mixture of asiatic acid, madecasinic acid and asiaticoside), hydrogenated retinol, tocopherol, astaxanthin, ubiquinone, and ceramide. It is preferably at least one selected from the group consisting of NG, ceramide NP, ceramide AP, ceramide EOP, tetrahydrodiferloylmethane and pterostilben.

As the component (F), either a synthetic product or a commercially available product may be used. Examples of commercially available products include phytosterol-SKP manufactured by Tama Biochemical Co., Ltd., TECA manufactured by Bayer Co., Ltd., dl-α-tocopherol manufactured by DSM Co., Ltd., NIKKOL (registered trademark) Retinol H10 manufactured by Nikko Chemicals Co., Ltd., and NIKKOL. (Registered Trademarks) VC-IP, Squalane, Astaxanthin-20C manufactured by Oryza Yuka Co., Ltd., γ-Oryzanol, Kaneka Coenzyme Q10 manufactured by Kaneka Corporation, CERAMIDE2 manufactured by Crowda Japan Co., Ltd., manufactured by Sabinsa Japan Corporation Examples thereof include 90% ursolic acid, rust white, and ptero white.

The content of the component (F) in the lipid membrane structure forming agent of the present invention is preferably 0.001 to 12% by mass, more preferably 0.01 to 10% by mass, and even more preferably 0. It is 1 to 8% by mass, and particularly preferably 1 to 6% by mass.

Further, in the lipid membrane structure forming agent of the present invention, the content of the component (F) is preferably 0.005 to 60 parts by mass with respect to 100 parts by mass of the component (A), and more preferably 0. It is 05 to 50 parts by mass, still more preferably 0.5 to 40 parts by mass, and particularly preferably 5 to 30 parts by mass.

[Other ingredients]
The lipid membrane structure forming agent of the present invention may further contain components (other components) other than the above components (A) to (F). Other components are not particularly limited, and are not particularly limited, and are oil agents, surfactants, moisturizers, whitening agents, coloring materials, alcohols, amino acids, sugars, vitamins, viscosity modifiers, polymers, coloring agents, powders, and ultraviolet absorption. Examples include agents, preservatives, antibacterial agents, antioxidants, fragrances, cosmetological ingredients, electrolytes, fibers, plant extracts and the like. These may be used alone or in combination of two or more. For example, by blending a beauty ingredient such as a moisturizer or a whitening agent with a lipid membrane structure forming agent and dispersing the forming agent in the aqueous phase, a lipid membrane structure containing the beauty ingredient can be formed. In forming the lipid membrane structure containing the beauty ingredient, the timing of blending the beauty ingredient is not particularly limited. For example, a lipid membrane structure-forming agent containing a component other than the beauty component is stored after preparation, and when preparing the lipid membrane structure-containing composition, the beauty component is added to the above-mentioned forming agent and uniformly dissolved. A lipid membrane structure containing a cosmetological ingredient may be formed by dispersing the lipid film in the aqueous phase. For this reason, the forming agent not only simplifies the production of individual cosmetics and external preparations for skin, but also differs by arbitrarily changing the contained beauty ingredients by stocking the forming agent in advance. Product groups can be easily created.

From the viewpoint of obtaining a finer lipid membrane structure, the pH when the composition for forming the lipid membrane structure is dispersed in the aqueous phase is preferably 4.0 or more, more preferably 5.0 or more. It is even more preferably 7.0 or more, and even more preferably 8.0 or more. On the other hand, from the viewpoint of obtaining a lipid membrane structure having a uniform particle size (that is, a highly uniform lipid membrane structure-containing composition), when the composition for forming a lipid membrane structure is dispersed in the aqueous phase. The pH is preferably 10.0 or less, more preferably 9.5 or less, and even more preferably 9.0 or less. Therefore, the composition for forming a lipid membrane structure according to a preferred embodiment of the present invention has a pH of 4.0 to 10.0 when dispersed in the aqueous phase. Here, the "pH when the lipid membrane structure forming composition is dispersed in the aqueous phase" is the pH of the product obtained by dispersing the lipid membrane structure forming composition in the aqueous phase. Means, and is measured by the method described in Examples described later. That is, 100 mL of purified water is added to a 200 mL beaker to prepare an aqueous phase. The aqueous phase is heated to 80 ° C. and stirred at 100 rpm, and the above-prepared lipid membrane structure forming agent at 80 ° C. is added. After completion of the addition, the mixture is stirred at 80 ° C. for 2 minutes to prepare a lipid membrane structure-containing composition. The prepared lipid membrane structure-containing composition is naturally cooled to room temperature (25 ° C.), and the pH at 25 ° C. is measured using a pH meter (HM-25R manufactured by Toa Decay Co., Ltd.) by a glass electrode method.

<Method for producing a composition for forming a lipid membrane structure>
The present invention is selected from the group consisting of the above-mentioned (A) component, (B) component, and, if necessary, the above-mentioned (C) component, (D) component, (E) component, and (F) component. A method for producing a composition for forming a lipid film structure (lipid film structure forming agent), which comprises mixing seeds or more (mixing step), is also provided, and at this time, the content of the component (B) is determined. It exceeds 100 parts by mass with respect to 100 parts by mass of the component (A). In the production method, in addition to the above-mentioned components (A) to (F), the components described in the above-mentioned [Other components] may be further mixed. Preferred embodiments of each component are as described above.

In the production method, each component may be mixed all at once or sequentially. When each component is mixed sequentially, the order is not particularly limited. For example, when a lipid membrane structure forming agent is produced using the components (A), (B) and (C), the component (A) and the component (B) are mixed and then the component (C) is added. After mixing the components (A) and (C), the component (B) may be added and mixed, or the component (B) and (C) may be mixed with the component (A). ) Components may be added at the same time (for example, a mixed solvent of the component (B) and the component (C) may be added) and mixed. Further, for example, when a lipid membrane structure forming agent is produced by using the component (C), the component (D) and / or the component (E) in addition to the above components (A) and (B), (C) ), (D) and / or (E) may be added separately or the mixture may be added after premixing. Further, for example, in addition to the above-mentioned components (A), (B), and (F), a component (C), a component (D) and / or a component (E) is used to prepare a lipid membrane structure forming agent. In the case of production, the order of addition of the component (F) is not particularly limited. For example, after mixing the components (A), (B) and (F), the components (C), (D) and / or (E) may be added simultaneously or sequentially. Alternatively, in addition to the components (A) and (B), the components (C), (D) and / or (E) are mixed simultaneously or sequentially, and then the component (F) is finally added. You may. Further, when the lipid membrane structure forming agent is produced using the components described in the above [other components], the order of addition of the components described in the above [other components] is not particularly limited, and for example, the solubility is increased. It can be appropriately selected accordingly. For example, if it is fat-soluble, it may be added at the same time as the component (F) is added, or it may be added at the end. Alternatively, if it is water-soluble, it may be added at the same time as the component (C), the component (D) and / or the component (E) is added, or it may be added last.

In the production method, the mixing temperature is not particularly limited, but is preferably 25 to 120 ° C, more preferably 40 to 100 ° C, and even more preferably 60 to 90 ° C. The mixing time is also not particularly limited, but is preferably 10 to 60 minutes. The mixing method is not particularly limited, but since a high mechanical shearing force is not required, a known mixing means such as a magnetic stirrer (for example, a hot stirrer), a paddle mixer, a propeller mixer, or a planetary mixer is used. be able to.

In the production method, in addition to the above mixing step, other steps such as purification (for example, filtration etc.), cooling, storage and the like may be appropriately performed. For example, when a mixture of the components (A) and (B) is prepared, the mixture is cooled and stored, and then the lipid membrane structure-containing composition is prepared, the mixture is optionally added ( A composition for forming a lipid membrane structure may be obtained by blending a component C), a component (D), a component (E) and / or a component (F).

<Use of composition for forming lipid membrane structure>
According to the composition for forming a lipid membrane structure according to the present invention, a fine lipid membrane structure can be spontaneously formed without a substantial mechanical shearing force, and at that time, a water-soluble component or a fat can be formed. It can contain soluble components. From this, not only can the manufacturing cost in the manufacturing factory be reduced, but also in the store such as a cosmetics specialty store, a lipid film structure-containing composition containing any water-soluble or fat-soluble beauty ingredient based on counseling can be obtained. A system for preparing blended cosmetics and external preparations for skin as needed is also possible, and widespread use of lipid membrane structures can be expected.

<Lipid membrane structure-containing composition>
The present invention also provides a lipid membrane structure-containing composition using the above-mentioned lipid membrane structure forming composition (lipid membrane structure forming agent).

The morphology of the lipid membrane structure is not particularly limited as long as it has a lamellar (lipid bilayer) structure in which the lipid molecules are arranged with the hydrophilic groups facing outward and the hydrophobic groups facing inward. Examples include bicelle and α-gel. The lipid membrane structure may be a single-layer lamellar structure called uni-lamellar or single lamellar, or may be a multi-layer (2 to 10-layer) lamellar structure called oligo lamellar, and has a larger number of layers. It may be a multi-lamellar structure, or a mixture of these. The lipid membrane structure is preferably a monolayer lamellar structure. The single-layer lamellar structure has a fine particle size and is excellent in compound encapsulation efficiency and permeability. The fact that the lipid membrane structure is a single-layer lamellar structure can be confirmed by using, for example, cryo-electron microscopy (Cryo-TEM). In one embodiment of the invention, the lipid membrane structure is preferably monolayer lamella liposomes. Since the monolayer lamella liposome has a fine particle size and a high internal aqueous phase volume, it is excellent in encapsulation efficiency and permeability of a water-soluble compound. Therefore, it is useful in cosmetics and skin external preparations containing water-soluble beauty ingredients. Further, in one embodiment of the present invention, the lipid membrane structure is preferably bicell. Bisel is a fine disk-shaped single-layer lamellar structure having a thickness of 3 to 10 nm and a diameter of 15 to 100 nm, and is excellent in encapsulation efficiency and permeability of fat-soluble components. Therefore, it is useful in cosmetics and skin external preparations containing fat-soluble beauty ingredients. In the lipid membrane structure-containing composition according to the present invention, only one of monolayer lamellar liposomes and bicelle may be present, or these two may be mixed.

The upper limit of the average particle size of the lipid membrane structure is preferably 200 nm or less, more preferably 140 nm or less, and even more preferably 90 nm or less from the viewpoint of dispersibility, storage stability, and skin permeability. Is. The lower limit of the average particle size of the lipid membrane structure is not particularly limited, but is, for example, 20 nm or more from the viewpoint of the formation efficiency of the single-layer lamellar structure.

The upper limit of the polydispersity index (PDI) of the lipid membrane structure is preferably 0.80 or less, more preferably 0.50 or less, from the viewpoint of dispersibility, storage stability, and skin permeability. , More preferably 0.40 or less, even more preferably 0.30 or less, particularly preferably 0.25 or less, and most preferably 0.20 or less. The lower limit of the polydispersity index (PDI) of the lipid membrane structure is not particularly limited, but is, for example, 0.01 or more.

The average particle size and polydisperse index (PDI) of the lipid film structure were determined by a cumulant analysis using a dynamic light scattering measuring device (Zetasizer Nano ZSP manufactured by Malvern Instruments) (Z-). Average) and Multivariance Index (PDI) shall be adopted. The definitions of the average particle size and the polydisperse index used here shall be in accordance with the description in "JIS Z8826: 2005 Particle Size Analysis-Photon Correlation Method".

The concentration of the lipid membrane structure in the lipid membrane structure-containing composition of the present invention is preferably 0.0001% by mass or more, more preferably 0.01% by mass, from the viewpoint of obtaining the skin care effect of the lipid membrane structure. The above is more preferably 1% by mass or more. On the other hand, the upper limit of the concentration is not particularly limited, but is, for example, less than 5% by mass.

The pH of the lipid membrane structure-containing composition is preferably 4.0 to 10.0. Specifically, the pH measured by a pH meter (HM-25R manufactured by Toa Decay Co., Ltd.) by the glass electrode method shall be adopted.

<Method for producing lipid membrane structure-containing composition>
The method for producing the lipid membrane structure-containing composition of the present invention is not particularly limited, and may be a method of adding a large excess of water to the above-mentioned lipid membrane structure-forming agent, or a large excess of water. However, the method of adding the above-mentioned lipid membrane structure forming agent may be used. The latter method is preferable from the viewpoint of improving the dispersibility of the lipid membrane structure. Therefore, the method for producing a lipid membrane structure-containing composition according to an embodiment of the present invention includes dispersing the above-mentioned composition for forming a lipid membrane structure in the aqueous phase.

More specifically, the method for producing the lipid membrane structure-containing composition according to the embodiment of the present invention comprises the above-mentioned components (A) and (B), and if necessary, components (C) and (D). ) Component, (E) component and (F) component are mixed to obtain a composition for forming a lipid membrane structure (forming agent preparation step), and the lipid membrane structure is described. Dispersing the body-forming composition in the aqueous phase (dispersion step), and the content of the component (B) exceeds 100 parts by mass with respect to 100 parts by mass of the component (A). .. Since the preferred embodiment of the forming agent preparation step is the same as the embodiment described in the above <Method for producing a composition for forming a lipid membrane structure>, the description thereof will be omitted here.

Dispersion of the lipid film structure forming agent in the aqueous phase is performed because the lipid film structure forming agent spontaneously forms a fine lipid film structure even if there is no substantial mechanical shearing force. May be added without stirring (the lipid film structure forming agent is added to the aqueous phase), or may be carried out while stirring the aqueous phase. At this time, the stirring conditions are not particularly limited, but for example, the stirring is performed at a rotation speed of 10 to 300 rpm using a known stirring means. Further, the lipid membrane structure forming agent may be added all at once, may be added in divided portions, or may be sequentially added at an arbitrary addition rate using a known dropping means.

It is preferable to use water with few impurities for the aqueous phase, for example, water purified from normal water by a system such as purified water in which ion exchange, distillation, reverse osmosis or ultrafiltration is used alone or in combination. Is preferably used. Further, the aqueous phase may further contain components other than water as long as the lipid membrane structure can be formed. Such components include, for example, oils, surfactants, moisturizers, whitening agents, coloring materials, alcohols, amino acids, sugars, vitamins, viscosity modifiers, polymers, coloring agents, powders, UV absorbers, etc. Preservatives, antibacterial agents, antioxidants, fragrances, cosmetological ingredients, electrolytes, fibers, plant extracts and the like can be mentioned.

In the dispersion step, the temperature of the aqueous phase is preferably 25 to 100 ° C, more preferably 40 to 95 ° C, and even more preferably 60 to 90 ° C.

In the dispersion step, the temperature of the lipid membrane structure forming agent to be dispersed is preferably 25 to 120 ° C, more preferably 40 to 100 ° C, and even more preferably 60 to 90 ° C.

In the method for producing a lipid membrane structure-containing composition according to the present invention, in addition to the above-mentioned forming agent preparation step and dispersion step, other steps such as purification (for example, filtration), cooling, and storage may be further performed. Good.

<Use of lipid membrane structure-containing composition>
The lipid membrane structure-containing composition of the present invention can be used as a cosmetic or an external preparation for skin, and can be moisturized by blending the composition containing the lipid membrane structure with a cosmetic or an external preparation for skin. It is possible to impart skin care effects such as improvement of skin quality. Therefore, one embodiment of the present invention is a cosmetic containing the above-mentioned lipid membrane structure-containing composition. Moreover, one embodiment of the present invention is a skin external preparation containing a lipid membrane structure-containing composition.

The form of the cosmetic or external preparation for skin of the present invention is not particularly limited as long as the lipid film structure is stably blended, but is in the form of lotion, gel, emulsion, cream, shampoo, and facial cleanser. And so on. From the viewpoint of utilizing the fine (for example, average particle size of 200 nm or less) lipid membrane structure of the present invention, the transparency of the appearance, the permeation feeling at the time of application, and the high stability, the lipid membrane structure It is preferably blended into a low-viscosity lotion, which is difficult to blend.

In addition to the above-mentioned lipid membrane structure-containing composition, the cosmetic or skin external preparation of the present invention further contains ingredients usually used in the cosmetic or skin external preparation as long as the effects of the present invention are not impaired. You may. Such ingredients include oils, surfactants, moisturizers, whitening agents, coloring materials, alcohols, amino acids, vitamins, viscosity regulators, polymers, colorants, powders, UV absorbers, preservatives, antibacterial agents. Agents, antioxidants, fragrances, cosmetological ingredients, electrolytes, pH regulators, fibers, water, plant extracts, etc., but are not limited thereto.

The concentration of the lipid membrane structure in the cosmetics and skin external preparations containing the lipid membrane structure-containing composition of the present invention is preferably 0.0001% by mass or more from the viewpoint of obtaining the skin care effect of the lipid membrane structure. It is more preferably 0.01% by mass or more, and further preferably 1% by mass or more. On the other hand, the upper limit of the concentration is not particularly limited, but is, for example, less than 5% by mass.

The effects of the present invention will be described with reference to the following examples and comparative examples. However, the technical scope of the present invention is not limited to the following examples. In the following examples, the operation was performed at room temperature (20 to 25 ° C.) unless otherwise specified. Unless otherwise specified, "%" and "parts" mean "mass%" and "parts by mass", respectively.

<Preparation of lipid membrane structure-containing composition>
A lipid membrane structure-containing composition was prepared by the following method. For hydrogenated lecithin, obtain commercially available hydrogenated lecithin derived from soybeans having different acid values (acid value 0.3 to 30.8 mgKOH / g) and mix them at a ratio so as to obtain a desired acid value. Prepared by

[Example 1-1]
To a 100 mL beaker, 20 parts by mass of hydrogenated lecithin (acid value 23.5 mgKOH / g) and 40 parts by mass of 1,2-pentanediol were added, and the mixture was stirred at 80 ° C. for 20 minutes using a hot stirrer to form a lipid film structure. A forming agent was prepared. Next, 100 mL of purified water was added to a 200 mL beaker to prepare an aqueous phase. The aqueous phase was heated to 80 ° C. and stirred at 100 rpm, and the above-prepared lipid membrane structure forming agent at 80 ° C. was added. After completion of the addition, the mixture was stirred at 80 ° C. for 2 minutes to prepare a lipid membrane structure-containing composition.

[Examples 1-2 to 1-4, Comparative Examples 1-1 to 1-2]
Examples except that the addition amounts of hydrogenated lecithin (acid value 23.5 mgKOH / g) and 1,2-pentanediol were changed to the addition amounts (parts by mass) shown in Table 1 below in Example 1-1. A lipid film structure-containing composition was prepared in the same manner as in 1-1.

[Examples 2-1 (a) to 2-6 (a), Comparative Example 2-1 (a)]
To a 100 mL beaker, 15 parts by mass of hydrogenated lecithin and 60 parts by mass of 1,2-pentanediol having the acid value (unit: mgKOH / g) shown in Table 2A were added to prepare a lipid film structure forming agent. Using the lipid membrane structure forming agent, a lipid membrane structure-containing composition was prepared in the same manner as in Example 1-1.

[Examples 2-1 (b) to 2-6 (b), Comparative Example 2-1 (b)]
To a 100 mL beaker, 15 parts by mass of hydrogenated lecithin and 60 parts by mass of 1,2-pentanediol having the acid values (unit: mgKOH / g) shown in Table 2B were added, and a hot stirrer was used at 80 ° C. for 20 minutes. After stirring, 25 parts by mass of purified water heated to 80 ° C. was added, and the mixture was stirred at 80 ° C. for 5 minutes using a hot stirrer to prepare a lipid film structure forming agent. Using the lipid membrane structure forming agent, a lipid membrane structure-containing composition was prepared in the same manner as in Example 1-1.

[Example 2-4 (b) Modification 1]
In a 100 mL beaker, 15 parts by mass of hydrogenated lecithin (acid value 23.1 mgKOH / g), 60 parts by mass of 1,2-pentanediol and 25 parts by mass of purified water were simultaneously added (60 parts by mass of 1,2-pentanediol and purified water). It was added (as a mixed solvent of 25 parts by mass) and stirred at 80 ° C. for 30 minutes using a hot stirrer to prepare a lipid film structure forming agent. Using the lipid membrane structure forming agent, a lipid membrane structure-containing composition was prepared in the same manner as in Example 1-1.

[Example 2-4 (b) Modification 2]
To a 100 mL beaker, 15 parts by mass of hydrogenated lecithin (acid value 23.1 mgKOH / g) and 25 parts by mass of purified water were added, and the mixture was stirred at 80 ° C. for 20 minutes using a hot stirrer, and then 1,2-pentanediol 60. A part by mass was added, and the mixture was stirred at 80 ° C. for 20 minutes using a hot stirrer to prepare a lipid film structure forming agent. Using the lipid membrane structure forming agent, a lipid membrane structure-containing composition was prepared in the same manner as in Example 1-1.

[Examples 2-1 (c) to 2-6 (c), Comparative Example 2-1 (c)]
To a 100 mL beaker, 15 parts by mass of hydrogenated lecithin and 60 parts by mass of 1,2-pentanediol having the acid value (unit: mgKOH / g) shown in Table 2C were added, and a hot stirrer was used at 80 ° C. for 20 minutes. After stirring, an aqueous solution prepared by mixing 24.4 parts by mass of purified water, 0.45 parts by mass of arginine and 0.15 parts by mass of citric acid was added by heating to 80 ° C., and added at 80 ° C. using a hot stirrer. The mixture was stirred for 5 minutes to prepare a lipid film structure forming agent. Using the lipid membrane structure forming agent, a lipid membrane structure-containing composition was prepared in the same manner as in Example 1-1.

[Examples 3-1 to 3-5, Comparative Examples 3-1 to 3-7]
To a 100 mL beaker, 15 parts by mass of hydrogenated lecithin (acid value 23.1 mgKOH / g) and 60 parts by mass of the B component or B'component shown in Table 3 were added, and the mixture was stirred at 80 ° C. for 20 minutes using a hot stirrer. After that, 25 parts by mass of purified water was added, and the mixture was stirred at 80 ° C. for 5 minutes using a hot stirrer to prepare a lipid film structure forming agent. Using the lipid membrane structure forming agent, a lipid membrane structure-containing composition was prepared in the same manner as in Example 1-1. In Comparative Examples 3-1 to 3-2, the lipid membrane structure-forming agent was prepared and gelled into a paste at a temperature of 80 ° C., and the lipid membrane structure was contained using these lipid membrane structure-forming agents. The composition was inferior in dispersibility. Further, in Comparative Examples 3-3 to 3-7, it was difficult to prepare the lipid membrane structure-containing composition because a large amount of precipitates were generated when the lipid membrane structure forming agent was prepared.

[Examples 4-1 to 4-12]
To a 100 mL beaker, 15 parts by mass of hydrogenated lecithin (acid value 23.1 mgKOH / g) and 60 parts by mass of 1,2-pentanediol were added, and the mixture was stirred at 80 ° C. for 20 minutes using a hot stirrer, and then Table 4-. An aqueous solution prepared by mixing purified water, D component and E component (or a salt of D component and E component) in the amounts described in 1 and 4-2 is added, and the mixture is stirred at 80 ° C. for 5 minutes using a hot stirrer. , A lipid film structure forming agent was prepared. Using the lipid membrane structure forming agent, a lipid membrane structure-containing composition was prepared in the same manner as in Example 1-1.

[Examples 5-1 (a) to 5-6 (a)]
To a 100 mL beaker, add hydrogenated lecithin (acid value 23.1 mgKOH / g), 1,2-pentanediol, and the F component shown in Table 5 in the amounts shown in Table 5, and use a hot stirrer. After stirring at 80 ° C. for 20 minutes, purified water was added in the amount shown in Table 5, and the mixture was stirred at 80 ° C. for 5 minutes using a hot stirrer to prepare a lipid film structure forming agent. Using the lipid membrane structure forming agent, a lipid membrane structure-containing composition was prepared in the same manner as in Example 1-1.

[Examples 5-1 (b) to 5-6 (b)]
To a 100 mL beaker, add hydrogenated lecithin (acid value 23.1 mgKOH / g), 1,2-pentanediol, and the F component shown in Table 5 in the amounts shown in Table 5, and use a hot stirrer. After stirring at 80 ° C. for 20 minutes, an aqueous solution containing purified water, arginine and citric acid mixed in the amounts shown in Table 5 is added, and the mixture is stirred at 80 ° C. for 5 minutes using a hot stirrer to form a lipid film structure. The agent was prepared. Using the lipid membrane structure forming agent, a lipid membrane structure-containing composition was prepared in the same manner as in Example 1-1.

[Examples 6-1 to 6-7]
To a 100 mL beaker, 15 parts by mass of hydrogenated lecithin (acid value 23.1 mgKOH / g) and 60 parts by mass of 1,2-pentanediol were added, and the mixture was stirred at 80 ° C. for 20 minutes using a hot stirrer, and then shown in Table 6. Purified water, an aqueous solution obtained by mixing the D component and the E component in the stated amounts were added, and the mixture was stirred at 80 ° C. for 5 minutes using a hot stirrer to prepare a lipid film structure forming agent. Next, 100 mL of purified water was added to a 200 mL beaker to prepare an aqueous phase. The aqueous phase was heated to 80 ° C. and stirred at 100 rpm, and the above-prepared lipid membrane structure forming agent at 80 ° C. was added. After completion of the addition, the mixture was stirred at 80 ° C. for 2 minutes to prepare a lipid membrane structure-containing composition. The prepared lipid membrane structure-containing composition was naturally cooled to room temperature (25 ° C.), and the pH at 25 ° C. was measured using a pH meter (HM-25R manufactured by Toa Decay Co., Ltd.) by a glass electrode method. .. The measured pH is shown in Table 6 below.

<Evaluation of composition>
[Appearance (lipid membrane structure forming agent)]
The above-prepared lipid membrane structure-forming agent was visually observed at 80 ° C. in a glass bottle container having a diameter of 3.7 cm, and judged based on the following criteria (if ◎ or ○, there is a problem in actual use. No):
⊚: Uniformly transparent liquid ◯: Not transparent but uniform liquid Δ: Gelled in paste form ×: Precipitates are observed.

[Appearance (lipid membrane structure-containing composition)]
The prepared lipid membrane structure-containing composition was visually observed at 25 ° C. in a glass bottle container having a diameter of 3.7 cm, and judged based on the following criteria (if ◎ or ○, the lipid membrane structure was determined. Good body dispersibility):
⊚: The characters on the opposite side of the container are visible and transparent to translucent liquid. ○: The characters on the opposite side of the container are not visible, but the liquid is uniform. ×: Separation and precipitation are observed.

Further, the lipid membrane structure-containing composition was stored at 25 ° C. for 1 month, and the appearance was observed and judged in the same manner as described above.

[Average particle size / polydispersity index]
The prepared lipid membrane structure-containing composition was subjected to cumulant analysis using a dynamic light scattering measuring device (Zetasizer Nano ZSP manufactured by Malvern Instruments), and the average particle size and polydispersion index (PDI) of the lipid membrane structure were analyzed. ) Was measured.

[Cryo-TEM observation]
The lipid membrane structure-containing composition prepared in Example 4-1 was subjected to Cryo-TEM observation using a transmission electron microscope (H-7650 manufactured by Hitachi High-Technologies Corporation). As a result, the ring-shaped image showed a monolayer lamellar liposome structure, and the rod-shaped image showed a bicell structure, confirming the formation of a lipid membrane structure having a monolayer lamellar structure (FIG. 1).

The results are shown in the table below.

As shown in Table 1 above, hydrogenated lecithin having an acid value of 5 mgKOH / g or more, which is a component (A), and 1,2-pentanediol, which is a component (B), are added to 100 parts by mass of the component (A). On the other hand, the component (B) could be mixed so as to exceed 100 parts by mass to prepare a homogeneous liquid lipid film structure forming agent. When the lipid membrane structure forming agent is dispersed in the aqueous phase, a fine lipid membrane structure-containing composition having an average particle size of 200 nm or less can be prepared without the need for a microfluidizer or other micronizing means. did it. In addition, the prepared lipid membrane structure-containing composition maintained stability (excellent appearance) even after storage at 25 ° C. for 1 month (Examples 1-1 to 1-4). In the lipid membrane structure forming agent prepared by blending 200 parts by mass of the component (B) with 100 parts by mass of the component (A), the average particle size at the time of aqueous phase dispersion is preferably 110 nm or less, which is a preferable translucent. A lipid membrane structure-containing composition having an appearance could be prepared (Example 1-1). Further, in the lipid membrane structure forming agent prepared by blending 400 parts by mass or more of the component (B) with respect to 100 parts by mass of the component (A), the average particle size at the time of aqueous phase dispersion is extremely 50 nm or less. A lipid membrane structure-containing composition having a highly transparent appearance could be prepared (Examples 1-2 to 1-4).

On the other hand, when a lipid membrane structure forming agent blended so that the content of the component (B) is 100 parts by mass or less with respect to 100 parts by mass of the component (A), the average particles of the lipid membrane structure formed are used. The diameter exceeded 200 nm, and a fine lipid membrane structure could not be obtained (Comparative Examples 1-1 to 1-2).

As shown in Table 2A above, a hydrogenated lecithin having an acid value of 5 mgKOH / g or more, which is a component (A), and 1,2-pentanediol, which is a component (B), are mixed to prepare a lipid film structure forming agent. When dispersed in the aqueous phase, a lipid film structure having an average particle diameter of 90 nm or less could be formed without the need for miniaturization means such as a microfluidizer (Examples 2-1 (a) and 2). -6 (a)). Further, as shown in Tables 2A to C, when hydrogenated lecithin having an acid value of 15.0 mgKOH / g, 20.0 mgKOH / g or 23.1 mgKOH / g was used, water as a component (C), and further. By further blending the component (D) arginine and the component (E) citric acid to prepare a lipid film structure forming agent, a lipid film structure forming agent having a better appearance when melted by heating can be obtained. I was able to get it. Further, by using the forming agent, the dispersibility of the lipid membrane structure in the aqueous phase was improved, and a lipid membrane structure-containing composition having a more excellent appearance could be obtained.

On the other hand, as shown in Tables 2A to C, when hydrogenated lecithin that does not correspond to the component (A) is used, the average particle size of the formed lipid membrane structure exceeds 200 nm, and the fine lipid membrane structure is formed. It was not obtained (Comparative Examples 2-1 (a) to (c)).

In Table 3 above, the component (B) was examined. When the polyol compound corresponding to the component (B) was used, a lipid membrane structure having an average particle size of 200 nm or less could be formed in each case (Examples 2-4 (b), 3-1 to 3- 5). In particular, when 1,2-hexanediol, 1,2-heptanediol, and hexylglycerin were used, an extremely fine lipid membrane structure (with an average particle size of 30 nm or less) could be formed (Example 3). -1, 3-2, 3-5).

On the other hand, when a polyol compound or ethanol that does not correspond to the component (B) is used, precipitation or gelation occurs at the time when the lipid membrane structure forming agent is prepared, and it is difficult to form the lipid membrane structure. Even if it could be formed, the average particle size exceeded 200 nm (Comparative Examples 3-1 to 3-7).

In Tables 4-1 and 4-2 above, the types of component (D) and component (E) were examined. When citric acid is used as the component (E), a lipid film structure having an average particle size of 90 nm or less can be obtained regardless of which basic compound is used at a blending amount that equalizes the ion equivalents as the component (D). It was able to be formed (Examples 4-1 to 4-8, 4-10). Further, when etidronic acid was used as the component (E) (Example 4-9), citric acid was used as the component (E) in an amount having the same ion equivalent (Example 4-8). In comparison with the above, the lipid film structure tended to become finer.

When sodium hydroxide is combined as the component (D) and citric acid is used as the component (E), both components are mixed separately (Example 4-8) and when they are mixed as salts of both components (when they are mixed as salts of both components (Example 4-8). No difference in average particle size, particle size distribution and dispersibility of the lipid film structure was observed between Examples 4-10).

From the above results, by using the lipid membrane structure forming agent according to the present invention, it was possible to form a fine lipid membrane structure (with an average particle size of 200 nm or less) without requiring a miniaturization means.

In Table 5 above, the types of component (F) were examined. When any fat-soluble compound is used as the component (F), the average particle size is the same as when the component (F) is not used, when hydrogenated lecithin having a certain acid value corresponding to the component (A) is used. A lipid film structure having a diameter of 200 nm or less could be formed. In particular, when coenzyme Q-10 (ubiquinone) was used, the average particle size of the lipid membrane structure was 41 nm to 55 nm, and an extremely fine lipid membrane structure could be formed (Example 5-5 (Example 5-5 (Example 5-5)). a), (b)). Further, in addition to the component (F), the component (D) arginine and the component (E) citric acid are further blended to prepare a lipid membrane structure forming agent, whereby the lipid membrane structure at the time of aqueous phase dispersion is prepared. A lipid membrane structure having a smaller average particle size of the body and a smaller polydispersity index of the lipid membrane structure and a more uniform particle size was obtained, and the storage stability of the lipid membrane structure-containing composition was improved. ..

In Table 6 above, the pH when the composition for forming a lipid membrane structure was dispersed in the aqueous phase (pH of the composition containing the lipid membrane structure immediately after preparation) was examined. In either case, a lipid membrane structure having an average particle size of 200 nm or less can be formed, and the prepared lipid membrane structure-containing composition maintains stability (excellent appearance) even after storage at 25 ° C. for 1 month. Was there. Specifically, a fine lipid membrane structure-containing composition having an average particle size of 91 nm or less could be prepared in the pH range of 4.0 to 10.0 (Examples 6-1 to 6-7). Above all, in the pH range of 5.0 to 7.0, a finer lipid membrane structure-containing composition having an average particle size of 58 nm to 61 nm could be prepared (Examples 6-2 to 6-4). Further, a finer lipid membrane structure-containing composition having an average particle size of 43 nm or less could be prepared in the pH range of 8.0 to 10.0 (Examples 6-5 to 6-7). In addition, a highly homogeneous lipid membrane structure-containing composition (with a lipid membrane structure polydispersion index of 0.40 or less) could be prepared in the pH range of 4.0 to 10.0 (Example 6-1). ~ 6-7). Further, in the pH range of 4.0 to 9.5, a more uniform lipid membrane structure-containing composition (with a polydispersion index of the lipid membrane structure of 0.25 or less) could be prepared (Example 6-). 1-6-6). Further, in the pH range of 4.0 to 9.0, a lipid membrane structure-containing composition having higher uniformity (the polydispersion index of the lipid membrane structure was 0.20 or less) could be prepared (Example 6-). 1-6-5).

Claims (15)

It contains (A) a hydrogenated phospholipid having an acid value of 5 mgKOH / g or more and (B) a compound represented by the following formula 1, and the content of the component (B) is 100 mass by mass of the component (A). Composition for forming a lipid film structure, which exceeds 100 parts by mass with respect to parts:

In the above formula 1,
R is a substituted or unsubstituted alkyl group having 2 to 6 carbon atoms or a substituted or unsubstituted cycloalkyl group having 3 to 6 carbon atoms.
X is −O−, −C (= O) O− or −OC (= O) −,
n is 0 or 1. The component (B) is at least one selected from the group consisting of 1,2-pentanediol, 1,2-hexanediol, 1,2-heptanediol, 1,2-octanediol, cyclohexylglycerin and hexylglycerin. The composition for forming a lipid film structure according to claim 1. The composition for forming a lipid membrane structure according to claim 1 or 2, wherein the content of the component (B) is 150 to 2000 parts by mass with respect to 100 parts by mass of the component (A). (C) The composition for forming a lipid membrane structure according to any one of claims 1 to 3, further containing water. The composition for forming a lipid membrane structure according to any one of claims 1 to 4, further containing at least one of (D) a basic compound and (E) an acidic compound. (F) The composition for forming a lipid membrane structure according to any one of claims 1 to 5, further containing a fat-soluble compound. The composition for forming a lipid membrane structure according to claim 5 or 6, wherein the component (E) is contained and the component (E) is an organic acid. The composition for forming a lipid membrane structure according to any one of claims 1 to 7, wherein the pH when dispersed in the aqueous phase is 4.0 to 10.0. (A) Hydrogenated phospholipids with an acid value of 5 mgKOH / g or more, (B) compounds represented by the following formula 1, and if necessary, (C) water, (D) basic compounds, (E) acidic compounds and It has a mixture of one or more selected from the group consisting of (F) fat-soluble compounds, and the content of the component (B) is 100 parts by mass with respect to 100 parts by mass of the component (A). Method for producing a composition for forming a lipid film structure:

In the above formula 1,
R is a substituted or unsubstituted alkyl group having 2 to 6 carbon atoms or a substituted or unsubstituted cycloalkyl group having 3 to 6 carbon atoms.
X is −O−, −C (= O) O− or −OC (= O) −,
n is 0 or 1. A lipid membrane structure-containing composition comprising the composition for forming a lipid membrane structure according to any one of claims 1 to 8. The lipid membrane structure-containing composition according to claim 10, wherein the lipid membrane structure is a monolayer lamellar structure. A method for producing a lipid membrane structure-containing composition, which comprises dispersing the lipid membrane structure-forming composition according to any one of claims 1 to 8 in an aqueous phase. (A) Hydrogenated phospholipids with an acid value of 5 mgKOH / g or more, (B) compounds represented by the following formula 1, and if necessary, (C) water, (D) basic compounds, (E) acidic compounds and (F) To obtain a composition for forming a lipid film structure by mixing one or more selected from the group consisting of fat-soluble compounds,
Dispersing the composition for forming a lipid membrane structure in the aqueous phase and
A method for producing a lipid membrane structure-containing composition, wherein the content of the component (B) exceeds 100 parts by mass with respect to 100 parts by mass of the component (A).

In the above formula 1,
R is a substituted or unsubstituted alkyl group having 2 to 6 carbon atoms or a substituted or unsubstituted cycloalkyl group having 3 to 6 carbon atoms.
X is −O−, −C (= O) O− or −OC (= O) −,
n is 0 or 1. A cosmetic comprising the lipid membrane structure-containing composition according to claim 10 or 11. An external preparation for skin containing the lipid membrane structure-containing composition according to claim 10 or 11.

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