JP7680844B2 - Cosmetics - Google Patents

Description

The present invention relates to a cosmetic product that provides a long-lasting cool sensation.

In order to provide a comfortable feeling during use, cosmetics containing functional ingredients such as cooling or warming ingredients have been developed.
One technique for providing a cooling sensation when cosmetics are applied to the skin involves combining a volatile ingredient such as alcohol with a sugar alcohol, taking advantage of the cooling sensation produced when the alcohol evaporates and the heat absorption properties of the sugar alcohol.
For example, Patent Document 1 discloses that an O/W cosmetic containing xylitol, ethanol, liquid oil, and a polymer having a hydrocarbon group with 10 to 30 carbon atoms and a carboxyl group in the molecule in specific ratios is a cosmetic that is non-sticky, has a fresh feel to the touch, and provides a long-lasting cool and refreshing sensation (Patent Document 1).
Menthol has long been used in cosmetics because it stimulates the skin's receptors that cause a cooling sensation, but adding only a small amount of menthol does not maintain the cooling sensation, and adding a large amount to maintain the cooling sensation can cause problems, such as a strong menthol odor or excessive cooling sensation or skin pain or irritation due to receptor stimulation.
In this situation, various technical proposals have been made to impart a cooling sensation to the skin and scalp and to sustain this effect.
For example, a technology for cosmetics containing menthol and borneol has been disclosed that even when a large amount of menthol is blended, the borneol reduces the skin irritation caused by menthol, and a strong cooling sensation is exerted, and the exerted cooling sensation is also excellent in durability (Patent Document 2).
In addition, it has been disclosed that an emulsion composition containing a sugar alcohol, menthol, an oily component that is liquid at room temperature, a nonionic surfactant, and water, and having an emulsion particle size of 400 nm or less, provides a cooling sensation when applied to the skin, and again provides a cooling sensation when the skin sweats (Patent Document 3).
Furthermore, it has been disclosed that when a skin cosmetic composition containing 0.1 to 3.0% by mass of a menthol derivative and silicone oil further contains water-insoluble spherical powder having a particle size of 1 μm to 100 μm, the skin cosmetic composition has an excellent cooling sensation effect and the duration of the effect is excellent (Patent Document 4).
However, even with these techniques, fully satisfactory results have not been obtained.
Furthermore, when a large amount of ethanol is blended, although a temporary cooling sensation is obtained due to the evaporation of the ethanol, the distinctive ethanol odor is unpopular, and there are problems in that the cooling sensation does not last long.
In recent years, there has been an increasing trend towards cosmetics that emphasize safety to the skin, and techniques have been disclosed that effectively maintain a cooling sensation even when a smaller amount of menthol is blended.
For example, it has been disclosed that when a cosmetic preparation containing water contains xylitol and two or more powders having different properties together with menthol or a menthol derivative, the cooling sensation observed immediately after application is sustained for a long period of time even when the amount of menthol or a menthol derivative blended is reduced (Patent Document 5).

On the other hand, as a method for sustaining the function of a functional ingredient, there is a method of retaining the functional ingredient inside a nanocapsule and utilizing its sustained release property. Examples of nanocapsules contained in cosmetics include micelles of surfactants, vesicles (niosomes) of surfactants, and vesicles (liposomes) formed by phospholipids. Of these, liposomes have stability issues, such as the structure of phospholipids changing over time and forming sediments. The present inventor has been researching niosomes and has disclosed a technology for niosomes with superior stability (Patent Document 6, Patent Document 7). In the course of this research, the inventor created menthol complex niosomes (particles) in which menthol or a menthol derivative is retained in the inner aqueous phase or membrane of the niosome, and discovered that when the complex niosome particles are incorporated into a cosmetic, there is no skin irritation, the cooling sensation is improved without increasing the amount of menthol incorporated, and the cooling sensation is sustained, and a cosmetic with excellent stability is obtained, thus completing the present invention.

JP 2011-162448 A JP 2004-18411 A JP 2014-201525 A JP 2001-226252 A Patent No. 6470999 Patent application No. 2020-004942 Patent application No. 2020-004874

The objective of the present invention is to obtain a cosmetic preparation that has a long-lasting cooling sensation due to menthol or a menthol derivative, is non-irritating to the skin, and has excellent stability.

The present invention relates to a cosmetic preparation containing (A) a sorbitan fatty acid and/or glyceryl isostearate, (B) a polyoxyethylene hydrogenated castor oil having an average degree of polymerization of the polyoxyethylene chain of 60 to 100, (C) one or more selected from dipropylene glycol, pentylene glycol, 1,3-butylene glycol, and propylene glycol, (D) menthol and/or a menthol derivative, and (E) water. When (D) menthol and/or menthol derivatives, which are poorly soluble in water as they are, are dissolved in one or more solvents selected from (C) dipropylene glycol, pentylene glycol, 1,3-butylene glycol, and propylene glycol, and further mixed and dissolved with surfactants (A) and (B), and the mixture is added to (E) water, (D) menthol and/or menthol derivatives become particles (hereinafter referred to as menthol complex niosomes) together with surfactants (A) and (B) and are dispersed in (E) water, and the obtained composition (menthol complex niosome aqueous dispersion) becomes a cosmetic with excellent stability without separation or crystal floating even after storage for one month under various temperature ranges (50°C, 40°C, 25°C, 5°C, cycle). The particle size of the menthol complex niosomes of the present invention is 80 to 150 nm, and the appearance of the cosmetic, which is the menthol complex niosome aqueous dispersion, appears cloudy when placed in a transparent container. The menthol complex niosome (particle) of the present invention obtained with a composition substantially free of oil is extremely stable even after long-term storage. Even if salts such as dipotassium glycyrrhizinate and sodium ascorbate are further added to the cosmetic, which is a menthol complex niosome (particle) aqueous dispersion, according to the purpose, the menthol complex niosome (particle) is stable. In other words, the cosmetic of the present invention is a cosmetic with excellent stability without separation or crystal floating. The menthol complex niosome aqueous dispersion of the present invention may be further prepared by adding optional components to prepare a desired cosmetic, or the composition of the present invention (menthol complex niosome, menthol complex niosome aqueous dispersion) may be blended as an additive to any cosmetic (lotion, milky lotion, cream, gel, etc.) prepared in advance. Compositions obtained by either method are included in the scope of the cosmetic of the present invention. Compared to a cosmetic in which menthol or a menthol derivative is dissolved in a solvent such as ethanol and the solution is directly blended, the cosmetic of the present invention not only does not have skin irritation or irritating odor due to ethanol immediately after application, but also the cooling sensation due to menthol or a menthol derivative felt after application lasts for a long time.
The present invention has the following configuration.
(1) A cosmetic preparation containing the following (A) to (E):
(A) fatty acid sorbitan and/or glyceryl isostearate; (B) polyoxyethylene hydrogenated castor oil having an average degree of polymerization of the polyoxyethylene chain of 60 to 100; (C) one or more selected from dipropylene glycol, pentylene glycol, and propylene glycol; (D) menthol and/or a menthol derivative; and (E) water. (2) The cosmetic according to (1), wherein (A) fatty acid sorbitan includes one or more selected from sorbitan sesquiisostearate, sorbitan sesquioleate, and sorbitan oleate.
(3) The cosmetic according to (1) or (2), in which the content ratio of (A) fatty acid sorbitan and/or glyceryl isostearate and (B) polyoxyethylene hydrogenated castor oil having an average degree of polymerization of polyoxyethylene chains of 60 to 100 is 1:4 to 3:2.
(4) The cosmetic according to any one of (1) to (3), wherein the total content of (A) fatty acid sorbitan and/or glyceryl isostearate, and (B) polyoxyethylene hydrogenated castor oil having an average degree of polymerization of polyoxyethylene chains of 60 to 100 is 0.5 to 2 mass% per cosmetic.
(5) The cosmetic according to any one of (1) to (4), wherein the content of (D) menthol and/or a menthol derivative is 0.05 to 0.2% by mass per cosmetic.
(6) The cosmetic preparation according to any one of (1) to (5), having a viscosity of 100 mPa·s or less as measured using a Brookfield type viscometer (No. 1 rotor, 60 rpm, 30 seconds, 25° C.).
(7) A cosmetic preparation according to any one of (1) to (6), which is substantially free of oil.
(8) A cosmetic preparation according to any one of (1) to (7), which is substantially free of ethanol.

The cosmetic of the present invention containing menthol complexed niosomes (particles) in which menthol and/or menthol derivatives are complexed with niosomes has a longer cooling sensation felt immediately after application compared to a cosmetic in which menthol and/or menthol derivatives are dissolved in a solvent such as ethanol and the solution is directly blended. By adopting the configuration of the present invention, menthol and/or menthol derivatives can be stably blended into the cosmetic without blending ethanol, which is the first choice as a solvent for menthol, so there is no irritating odor due to ethanol immediately after application or irritating feeling on the skin, which were problems in the prior art. In addition, the cosmetic has good temperature stability and is excellent in storage stability without separation or crystal floating even after storage for one month under various temperature ranges (50°C, 40°C, 25°C, 5°C, cycle).
The viscosity of the dispersion of menthol complex niosome (particle) in which menthol and/or menthol derivative is complexed with a surfactant and dispersed in water is 100 mPa·s or less when measured using a B-type viscometer (No. 1 rotor, 30 rpm, 30 seconds, 25°C). The menthol complex niosome (particle) aqueous dispersion is stable without the addition of a thickener for stabilization, and can be used as it is as a cosmetic such as a lotion. In addition, since it is cloudy, it is optimal as a luxurious lotion. Furthermore, the stability of the menthol complex niosome (particle) is maintained even if it contains electrolytes that are preferably added to cosmetics, such as sodium chloride, magnesium sulfate, dipotassium glycyrrhizinate, magnesium ascorbate, and sodium citrate, so that any beauty ingredient can be added to make a cosmetic without repeating excessive storage stability tests. In this way, the composition of the present invention allows for relatively free variation of the formulation, which reduces costs when designing the formulation.

1 is a graph showing the results of a sensory evaluation of cooling sensation in Example 1 and Comparative Example 1. 1 is a graph showing the results of a sensory evaluation of cooling sensation in Example 2 and Comparative Example 3. This is a graph showing the results of storing the lotion of Example 2 at 5°C, 25°C, 40°C, and 50°C in a cycle (-5°C to 45°C) and measuring the average particle size of niosomes by dynamic light scattering after a predetermined number of days.

The components of the cosmetic of the present invention will be described below.
<Component A: Fatty acid sorbitan and/or glyceryl isostearate>
Sorbitan fatty acids, also known as sorbitan fatty acids, are esters of sorbitan and fatty acids and are used as food emulsifiers, cosmetics, and industrial surfactants, either alone or in combination with other surfactants.
Examples of fatty acid sorbitan used in the present invention include sorbitan sesquiisostearate, sorbitan sesquioleate, and sorbitan oleate. Sorbitan sesquiisostearate and sorbitan sesquioleate are preferred, and sorbitan sesquioleate is more preferred. Examples of commercially available sorbitan sesquiisostearate include Cosmol 182V (manufactured by Nisshin Oillio Group, Ltd., HLB 4), NIKKOL SS-15V (manufactured by Nikko Chemicals, HLB 4.2), and EMALEX SP15-150 (manufactured by Nippon Emulsion Co., Ltd., HLB 6). Commercially available sorbitan sesquioleate products include Cosmol 82 (manufactured by Nisshin Oillio Group, Ltd., HLB 5), NIKKOL SO-15V (manufactured by Nikko Chemicals, HLB 4), and Rheodol AO-15V (manufactured by Kao Corporation, HLB 4.7). Commercially available sorbitan oleate products include Rheodol AO-10V (manufactured by Kao Corporation, HLB 4.3), NIKKOL SO-10V (manufactured by Nikko Chemicals, HLB 4.3), and EMALEX SPO-100 (manufactured by Nippon Emulsion Co., Ltd., HLB 8).
An example of a commercially available glyceryl isostearate product is EMALEX GWIS-100EX (manufactured by Nippon Emulsion Co., Ltd., HLB 6).
The alkyl group of the fatty acid sorbitan and/or glyceryl isostearate is preferably a fatty acid having a branched or unsaturated bond, since it enhances the fluidity of the membrane of the formed niosome particle. High fluidity of the membrane enhances the permeability into the skin. In other words, it is preferable because it effectively penetrates into the skin and enhances the effect of feeling a cooling sensation.
The fatty acid sorbitan and/or glyceryl isostearate may be contained alone or in combination of two or more kinds.
In the cosmetic of the present invention, the fatty acid sorbitan and/or glyceryl isostearate is contained in a total amount of 0.01 to 5 mass %, preferably 0.05 to 1 mass %, and particularly preferably 0.2 to 1 mass %, based on the total amount of the cosmetic.

<Component B: Polyoxyethylene hydrogenated castor oil having an average polymerization degree of polyoxyethylene chain of 60 to 100>
The polyoxyethylene hydrogenated castor oil in the present invention contains one having an average degree of polymerization of polyoxyethylene chains of 60 to 100, preferably 80 to 100, and more preferably 80. Two or more types of polyoxyethylene hydrogenated castor oils having polyethylene chains with different chain lengths can be used in combination.
Specific examples include PEG-100 hydrogenated castor oil, PEG-80 hydrogenated castor oil, and PEG-60 hydrogenated castor oil. Commercially available PEG-100 hydrogenated castor oils include NIKKOL HCO-100 (manufactured by Nikko Chemicals, HLB 16.5) and EMALEX HC-100 (manufactured by Nippon Emulsion, HLB 15). Commercially available PEG-80 hydrogenated castor oils include NIKKOL HCO-80 (manufactured by Nikko Chemicals, HLB 15) and EMALEX HC-80 (manufactured by Nippon Emulsion, HLB 15). Examples of commercially available PEG-60 hydrogenated castor oil include NIKKOL HCO-60 (manufactured by Nikko Chemicals Co., Ltd., HLB 14) and EMALEX HC-60 (manufactured by Nippon Emulsion Co., Ltd., HLB 14).
The content of polyoxyethylene hydrogenated castor oil in the cosmetic of the present invention is 0.05 to 5% by mass, preferably 0.1 to 2% by mass, and particularly preferably 0.4 to 1% by mass.

The (A) fatty acid sorbitan and/or glyceryl isostearate and (B) polyoxyethylene hydrogenated castor oil having an average degree of polymerization of polyoxyethylene chains of 60 to 100 of the present invention are preferably contained in a total amount of 1 to 2% by mass relative to the total amount of the cosmetic. This range is preferable because it does not cause stickiness. In addition, when forming a niosome complex with (D) menthol and/or a menthol derivative, which will be described later, the total amount of surfactants (A) and (B) is preferably 10 to 11 times the content (mass %) of (D) menthol and/or a menthol derivative.

The content ratio of (A) fatty acid sorbitan and/or glyceryl isostearate to (B) polyoxyethylene hydrogenated castor oil with an average degree of polymerization of the polyoxyethylene chain of 60 to 100 is preferably 1:4 to 3:2. Outside this range, the particle size varies, aggregation is more likely to occur, and the stability of the cosmetic composition is more likely to decrease. The content ratio (A):(B) is preferably 1:4 to 3:2, more preferably 2:3 to 3:2, and most preferably 1:1, which is the most stable.

<Component C: dipropylene glycol, pentylene glycol, 1,3-butylene glycol, propylene glycol>
The component (C) of the present invention is at least one selected from dipropylene glycol (display name: DPG), pentylene glycol, 1,3-butylene glycol, and propylene glycol, and is blended for the purpose of dissolving the surfactants (A) and (B) and the below-described (D) menthol and/or a menthol derivative.
Most of the (C) component becomes a dispersion medium together with (E) water after preparation, but it is considered that a part of the (C) component is also contained in the inner aqueous phase and membrane of the formed menthol complex niosome (particle). Considering safety (low irritation) to the skin, dipropylene glycol, pentylene glycol, and 1,3-butylene glycol are preferred. The total content of the (C) component is preferably 1.5 to 19% by mass, more preferably 3 to 12% by mass, and even more preferably 5 to 10% by mass, based on the total amount of the cosmetic.

<Component D: Menthol and/or Menthol Derivative>
Examples of menthol used in the present invention include l-menthol, dl-menthol, and peppermint oil. Examples of menthol derivatives include menthol esters such as menthyl PCA, menthyl lactate, and menthyl acetate. It is preferable to blend menthol and/or a menthol derivative in an amount of 0.05 to 0.2% by mass, and more preferably 0.1 to 0.15% by mass, based on the total amount of the cosmetic. A range of 0.05 to 0.2% by mass is preferable because the irritating odor specific to menthol and/or a menthol derivative is not noticeable when applied to the skin.

(E) Water The cosmetic of the present invention is a cosmetic in which menthol complex niosomes (particles) are dispersed in (E) water, and contains the same. In the present invention, (E) water is essential. The blending amount of water may be appropriately set, but when the (E) water dispersion of menthol complex niosomes (particles) is used as a cosmetic as it is, it is preferably 50% by mass or more, more preferably 70% by mass or more, based on the total amount of the cosmetic.

(Production method)
Menthol complex niosome aqueous dispersion (D) Menthol and/or menthol derivative is dissolved in one or more solvents selected from (C) dipropylene glycol, pentylene glycol, 1,3-butylene glycol, and propylene glycol, and further mixed with surfactants (A) and (B) to dissolve everything, and the mixture is added to (E) water, and (D) menthol and/or menthol derivative becomes menthol and/or menthol derivative complex niosome (particle) together with surfactants (A) and (B), and is dispersed in (E) water to become menthol complex niosome (particle) aqueous dispersion. (D), (C), (A), and (B) may be heated and mixed at once, and then added to (E) heated in a separate container. The heating temperature is preferably 80 to 90°C, more preferably 85 to 90°C. As an example, menthol complex niosome (particle) is formed by stirring with a paddle mixer at 20 to 40 rpm when preparing 500 liters.
In the menthol complex niosome aqueous dispersion of the present invention, it is considered that about 33% of (D) menthol and/or menthol derivative is present in the inner aqueous phase or membrane of the menthol complex niosome (particle), and about 67% is dispersed in water.
Cosmetics The menthol complex niosome aqueous dispersion can be used as it is as a cosmetic, but depending on the purpose, any component that can be further blended in a cosmetic may be added to the menthol complex niosome aqueous dispersion to make a cosmetic. An appropriate amount of the menthol complex niosome aqueous dispersion of the present invention may be contained in any cosmetic prepared in advance. The content of the menthol complex niosome aqueous dispersion per total amount of the cosmetic may be appropriately set depending on the purpose, but is 0.01 to 100% by mass.

(viscosity)
When the aqueous dispersion of menthol composite niosomes (particles) is measured using a B-type viscometer (No. 1 rotor, 30 rpm, 30 seconds, 25° C.), the viscosity is 100 mPa·s or less.

(Particle size)
The measurement was performed using a particle size distribution meter (ELSZ-1000, manufactured by Otsuka Electronics).
When the blending amount of menthol and/or menthol derivative was 0.1% by mass and the total amount of surfactants A and B was 1% by mass, the size (particle diameter) of the menthol composite niosome was in the range of 80 to 150 nm. Since the particle diameter was about 100 nm, the aqueous dispersion of the menthol composite niosome (particle) appeared cloudy.

(optional ingredient)
The menthol and/or menthol derivative complex niosome aqueous dispersion (cosmetic) of the present invention can contain ingredients that can be added to cosmetics within a range that does not impair the effects of the present invention. For example, polyhydric alcohols, sugars, sugar alcohols, preservatives, sequestering agents, medicinal ingredients, fragrances, etc. can be included.
The menthol complex niosome aqueous dispersion (cosmetic) of the present invention has high salt resistance. Therefore, ingredients (salts) that can be normally incorporated into cosmetics can be safely incorporated without frequent confirmation of stability. In particular, ingredients that have been confirmed to be stable when incorporated include sodium chloride, magnesium sulfate, dipotassium glycyrrhizinate, sodium hyaluronate, magnesium ascorbyl phosphate, and sodium citrate.

Considering the stability of the menthol complex niosomes (particles), it is important to first form the menthol complex niosomes (particles) with the compositions (A) to (E), prepare an aqueous dispersion of the menthol complex niosomes, and then add any optional ingredients.

In addition, when preparing the menthol complex niosome aqueous dispersion of the present invention, it is preferable that the oil is substantially not contained. In the present invention, substantially no oil is added means that the amount is 0.1 mass% or less with respect to the total amount of the composition. If an optional oil is further added to the compositions (A) to (D), when the dissolved matter (A + B + C + D + optional oil) is dispersed in water (E), the surfactant is insufficient, and oil droplets other than the niosome particles of the present invention are formed, or the amount of menthol dispersed in water increases, which increases the possibility of inhibiting efficient formation of the menthol derivative complex niosome (A + B + C + D). And, if the amount of menthol and/or menthol derivative present in the external aqueous phase increases, there is a risk that the duration of the cooling sensation will decrease.
In addition, when it is desired to prepare a cosmetic composition containing oil as an optional component, a stable emulsion or cream can be prepared by adding the menthol complexed niosome aqueous dispersion of the present invention to a separately prepared emulsion or cream.

The menthol complex niosome aqueous dispersion of the present invention has low viscosity, so that when it is used as a cosmetic, it is most suitable for a lotion.In addition, since niosomes are vesicle particles in which surfactants are associated by hydrophobic interaction, when niosomes are blended into a cosmetic, it is preferable to use a formulation in which no other substances that contribute to hydrophobic interaction exist, and from this viewpoint, it is considered that a lotion in which most of the blended ingredients are aqueous ingredients is most suitable.
When the menthol complex niosome aqueous dispersion of the present invention is added as an additive component to a separately prepared cosmetic, the cosmetic is not limited in its formulation, and may be a viscous lotion, milky lotion, cream, gel, etc. It may also be a skin cosmetic or hair cosmetic. When the cosmetic of the present invention is added to another cosmetic to prepare a cosmetic, the menthol complex niosome aqueous dispersion may be contained in an amount of 0.1 to 100% by mass relative to the total amount of the cosmetic.

In the present invention, long-term stability (excellent stability over time) refers to a state in which no precipitation or separation occurs when visually observed one month after storage at various temperatures (5°C, 25°C, 40°C, 50°C, cycle (-5°C to 45°C)) from preparation, and further, the particle size of the dispersed niosome particles does not change by more than ±10%.

In the cosmetic of the present invention, (D) menthol and/or menthol derivatives are considered to be present in an amount of about 33% in the internal aqueous phase or membrane of menthol complex niosomes (particles) composed of (A) fatty acid sorbitan and/or glyceryl isostearate, (B) polyoxyethylene hydrogenated castor oil having an average degree of polymerization of polyoxyethylene chains of 60 to 100, (C) one or more selected from dipropylene glycol, pentylene glycol, 1,3-butylene glycol, and propylene glycol, (D) menthol and/or menthol derivatives, and (E) water.

In the present invention, approximately 33% of the menthol complex niosomes (particles) do not easily disintegrate in the composition and have excellent temperature stability, making sustained release possible, and it is believed that this sustained release property sustains the cooling sensation. The cooling sensation immediately after application is believed to be due to approximately 67% of free menthol that was not incorporated into the internal aqueous phase or membrane of the menthol complex niosomes (particles).

On the other hand, in conventional cosmetics in which ethanol is selected as a solvent for menthol and ethanol is highly blended at about 6 to 10% by mass relative to the total amount of the cosmetic, a temporary strong cooling sensation may be felt due to the evaporation of ethanol immediately after application. However, tests have revealed that after the ethanol has evaporated, the cooling sensation of the menthol and/or menthol derivatives blended at the same time as the cooling ingredient tends to become less noticeable. Therefore, a high blend of ethanol is not preferred because it tends to require an increase in the amount of menthol and/or menthol derivatives blended. In the present invention, it is preferable to limit the ethanol content to 5% by mass or less, preferably 3% by mass or less, and more preferably 1% by mass or less. Most preferably, the cosmetic is substantially free of ethanol. In the present invention, substantially free of ethanol means 0.1% by mass to 0% by mass.

When the inventors tested the amount of ethanol required to solubilize menthol with ethanol, the amount of ethanol required to mix 0.1 g of menthol with water was 10% by mass. When the amount of ethanol was less than 10% by mass, crystal precipitation was observed after adding to water, and the mixture could not be stably mixed. Therefore, in the tests shown below, a composition in which menthol was solubilized with the minimum amount of ethanol was used as a comparative example.

The present invention will be described in detail below with reference to examples and comparative examples.
Conventionally, when menthol and/or menthol derivatives, which are cooling sensation ingredients, are blended in cosmetics, they are generally blended after solubilization with ethanol or after solubilization with micelles. Therefore, in the following tests, the aqueous dispersion of the composite niosome (particle) of menthol and/or menthol derivatives (hereinafter, sometimes simply referred to as menthol composite niosome) of the present invention is used as an example, and the conventional methods (micelle solubilized menthol, ethanol solubilized menthol) are used as comparative examples.

A menthol complex niosome aqueous dispersion (Example 1), a micelle solubilized product of menthol (Comparative Example 1), and a solubilized product of menthol with ethanol (Comparative Example 2) were prepared as follows.
The obtained test product was measured and evaluated for average particle size (number), menthol quantification, sensory evaluation (cooling sensation immediately after application, duration of cooling sensation), and stability over time.In addition, since the appearance of Comparative Example 2 was completely transparent due to ethanol, it was predicted that the particle size was very small, so the particle size was not measured.In addition, the menthol quantification was performed to confirm the presence or absence of influence due to the different preparation method depending on the test product, and to confirm the amount of menthol in the niosome of the present invention.

Table 1 shows the compositions of the test products (Example 1, Comparative Examples 1 and 2). The units of numbers are mass %. In the table, "niosome", "micelle", and "free" indicate the simplified method of blending menthol. In this test, "free" was solubilized with ethanol. The following commercially available products were used for the components in the composition table.

・Sorbitan sesquioleate: Cosmol 82 (Nisshin Oillio Group, Ltd.)
・PEG-40 hydrogenated castor oil: EMALEX HC-40 (Nihon Emulsion Co., Ltd.)
・PEG-60 hydrogenated castor oil: EMALEX HC-60 (Nihon Emulsion Co., Ltd.)
・PEG-80 hydrogenated castor oil: EMALEX HC-80 (Nihon Emulsion Co., Ltd.)
・PEG-100 hydrogenated castor oil: EMALEX HC-100 (Nihon Emulsion Co., Ltd.)
・Dipropylene glycol (DPG): DPG-FC (AGC Co., Ltd.)
・1,3-Butylene glycol (BG): 1,3-butylene glycol (UK) (Daicel Corporation)
・Pentylene glycol: Hydrolite-5 (Symrise Co., Ltd.)
・Menthol: L-menthol (Kobayashi Kei Co., Ltd.)
・PCA Menthyl: QUESTICE LIQUID CQ U/A (Givaudan Co., Ltd.)
・Ethylhexylglycerin: ADEKA NOL GE-RF (ADEKA Corporation)
Ethanol: Fermented alcohol 95% Grade 1 (ethanol): (Daiichi Alcohol Co., Ltd.)
・Glycerin: Concentrated glycerin for cosmetics (Lion Corporation)
Diglycerin: Diglycerin 801 (Sakamoto Pharmaceutical Co., Ltd.)
・Betaine: Aminocoat (Nippon Beet Sugar Co., Ltd.)

Preparation of test samples
The preparation methods for the cases of complexing menthol with niosome, solubilizing menthol in micelles, and solubilizing menthol in ethanol are as follows.

1. Complexation of menthol with niosomes (Example 1)
0.5 g of sorbitan sesquioleate, 0.5 g of PEG-80 hydrogenated castor oil, and 0.1 g of menthol were dissolved in 5 g of dipropylene glycol (DPG) by heating at 85° C. Next, 93.9 g of water was heated to 85° C., and the above solution was added dropwise while stirring (propeller: 200 rpm). Then, the mixture was cooled to 30° C. in an ice bath.

2. Solubilization of menthol by micelles (Comparative Example 1)
1 g of polyoxyethylene hydrogenated castor oil and 0.1 g of menthol were dissolved in 5 g of DPG by heating at 85° C. Next, 93.9 g of water was heated to 85° C., and the above solution was added dropwise while stirring (propeller: 200 rpm). Then, the mixture was cooled to 30° C. in an ice bath.

3. Solubilization of menthol with ethanol (Comparative Example 2)
5 g of DPG was dissolved in 84.9 g of water. 0.1 g of menthol was dissolved in 10 g of ethanol, and the solution was gradually added to the DPG aqueous solution with stirring (propeller: 200 rpm).

<Average particle size (number)>
The test samples (Example 1, Comparative Example 1) were stored at 25°C for one day, and the particle size of the composite niosomes and the particle size of the micelles were measured using a particle size distribution meter (ELSZ-1000: manufactured by Otsuka Electronics Co., Ltd.). Comparative Example 2 was not measured because no particles were present. The results are shown in Table 2.

The average particle size of Example 1 was 103.4 nm, and that of Comparative Example 1 was 20.4 nm. When visually observed, the cosmetic of Example 1 containing menthol-complexed niosomes was uniformly cloudy. The cosmetic of Comparative Example 1 containing menthol as micelles was transparent.

Quantitative Analysis of Menthol
The quantification of menthol was carried out in order to: 1. confirm the influence of different preparation methods depending on the test product; and 2. confirm the amount of menthol contained in the menthol complex niosome of the present invention.

1. Confirmation of the influence of different preparation methods When preparing the test products, Example 1 and Comparative Example 1 include a process of heating menthol, so there is a possibility that menthol may sublimate and cause a difference between the amount added during preparation and the content when made into a cosmetic. Therefore, it was confirmed whether the menthol content when made into a cosmetic differs depending on the preparation method. That is, the amount of menthol contained in Example 1, Comparative Example 1, and Comparative Example 2 was quantified by HPLC and evaluated to confirm the presence or absence of a difference due to the preparation method. Note that Comparative Example 2, in which menthol was solubilized with ethanol, is a preparation method in which menthol is added at room temperature without heating, and is therefore the comparison subject of this test.

2. Confirmation of the amount of menthol contained in the menthol complexed niosomes In Example 1 containing the niosome complexed material, in order to know the niosome complexing rate of menthol, the niosome complexed material (particles) was separated and removed by ultracentrifugation (55,000 rpm, 30 minutes), and the amount of menthol present in the external aqueous phase outside the niosomes and not complexed with the niosomes was quantified.

(Quantitative method)
Each sample was precisely weighed out at 0.25 g, and acetone was added to make up to 5 ml. This was filtered through a membrane filter (PTFE, pore size: 0.45 μm) to obtain a measurement sample. Furthermore, 0.05 g of a standard menthol sample was weighed out, and made up to 50 ml with acetone. This liquid was diluted with ethanol to 10, 20, 50, and 100 ppm, and filtered through a membrane filter (pore size: 0.45 μm) to obtain a standard sample. The measurement sample was evaluated by HPLC, and the amount of menthol contained in the measurement sample was determined by comparison with the standard sample.
Table 3 shows the results of quantification of the menthol content by HPLC (actual measurement value). In the table, "niosome", "micelle", and "free" indicate the simplified blending method of menthol. In this test, "free" is solubilized with ethanol. "After ultracentrifugation" means that the outer aqueous phase (the part from which niosome was removed) after ultracentrifugation of Example 1 (niosome) in this test is measured.

(Result 1)
The quantitative value of menthol in the menthol complex niosome aqueous dispersion (Example 1) was 0.09% by mass, the quantitative value of menthol in the menthol-solubilized micelle aqueous dispersion (Comparative Example 1) was 0.1% by mass, and the quantitative value of menthol in the comparative example 2 (ethanol solubilized menthol) used for comparison was 0.1% by mass. The amount of menthol added during preparation was 0.1% by mass, so only Example 1 had a value that was reduced by 0.01% by mass.
(Consideration)
The measured menthol content in both Comparative Example 2 and Comparative Example 1 was 0.1% by mass, which was the same amount as the amount added during preparation. On the other hand, the quantitative value for Example 1 was 0.09% by mass, which was 0.01% by mass lower than the amount of 0.1% by mass added during preparation. In Comparative Example 1, in which menthol was heated and blended in the same manner as in Example 1, the quantitative value was 0.1% by mass, which was the same amount as the amount added during preparation, so it was inferred that there was no effect of heating. The fact that the value for Example 1 was measured to be slightly lower at 0.09% by mass was not due to menthol sublimating during the heating process, but was simply due to mechanical error of the analysis device. It was determined that there was no difference in the menthol content depending on the preparation method.

(Result 2)
Niosomes (particles) were separated from the menthol-complexed niosome dispersion (Example 1) by ultracentrifugation, and the quantitative value of menthol present in the aqueous phase outside the niosomes (particles) (Example 1 (after ultracentrifugation)) was 0.06% by mass.
(Consideration)
The quantitative value of menthol in the external aqueous phase obtained by removing menthol complexed niosomes (particles) by ultracentrifugation in Example 1 was 0.06% by mass. The quantitative value of menthol contained in the menthol complexed niosome aqueous dispersion (Example 1) before ultracentrifugation was 0.09% by mass, and the difference was calculated to find that the amount of menthol complexed in the niosomes was 0.03% by mass, and the complexation rate was found to be about 33%. It was considered that about 33% of menthol was complexed in the niosome membrane or in the internal aqueous phase.

<Sensory evaluation>
A sensory evaluation was carried out for a total of three types of systems, namely, a case where menthol and niosome were composited (Example 1), a case where menthol was solubilized in micelles (Comparative Example 1), and a case where menthol was solubilized with ethanol (Comparative Example 2), with the case where menthol was solubilized with ethanol (Comparative Example 2) as the standard.
Five men and women with excellent sensory evaluation skills engaged in cosmetics development evaluated the cooling sensation immediately after application and the duration of the cooling sensation.
A drop was dispensed from the eye dropper bottle onto the inside of the forearm, spread with a finger, and the cooling sensation felt immediately after application was evaluated as the "evaluation immediately after application," and the cooling sensation felt 30 minutes after application was evaluated as the "evaluation of duration." The cooling sensation was evaluated by each person giving a score according to the following criteria, and the sum and average of the scores of the five people was used as the sensory evaluation result of the cooling sensation.
The sensory evaluation score was 7-level scale from -3 to 3, with -3 being the clear deterioration in cooling sensation of the test products (Example 1, Comparative Example 1) compared with the reference product (Comparative Example 2), -2 being the deterioration, -1 being the deterioration but only a slight difference, 0 being the absence of difference, 1 being the improvement in cooling sensation but only a slight difference, 2 being the improvement, and 3 being the clear improvement. For example, a score of 0 means that there is no difference from Comparative Example 2. The results are shown in FIG. 1.

(result)
<Cool sensation immediately after application>
The sensory evaluation of the cooling sensation of Example 1 was 1.2 on average, and no significant increase in the intensity of the cooling sensation was confirmed, when the evaluation was based on Comparative Example 2. The score of Comparative Example 1 was also less than 1, and no increase in the intensity of the cooling sensation was confirmed.
This shows that no matter how menthol is incorporated into the cosmetic (composite niosome, micelle, or free (dissolved in ethanol)), there is no difference in the cooling sensation immediately after application.
(Consideration)
Initially, in Example 1, there was a concern that the amount of menthol that directly contacts the skin and acts immediately after application would decrease due to the nanoencapsulation of menthol, and the strength of the cooling sensation would decrease.However, the strength of the cooling sensation immediately after application was not significantly different in either the case where menthol was complexed with niosomes (Example 1) or the case where it was solubilized in micelles (Comparative Example 1) from the case where it was blended in free form (dissolved in ethanol) without encapsulation (Comparative Example 2).The reason for this result is that when niosomes or micelles are used, not all menthol is encapsulated, and most of the menthol added during preparation is present in a state distributed outside the niosomes or micelles.In order to confirm this, as described above, the menthol in the niosome aqueous dispersion of Example 1 and the external aqueous phase excluding niosome particles were quantified, and the amount of menthol complexed with niosomes was calculated from the difference, and the result was 33% by mass.This result was not inconsistent with the consideration of this test.
Therefore, it was found that the cosmetic composition of the present invention, which contains menthol nanoencapsulated as niosome composite particles, can provide a cooling sensation at the same level as that obtained by the conventional method of dissolving menthol in ethanol and incorporating it, by allowing the menthol present in the external aqueous phase (approximately 67% in the example of this test system) to act directly on the skin, even immediately after application.
In the evaluation immediately after application, the average score of the sensory evaluation of Example 1 (niosome) was 1.2, which was slightly higher than that of Comparative Example 2 (standard: 0). Although Comparative Example 2 contained 100% free menthol and had a large amount of direct contact with the skin, it did not feel as cool as Example 1 (composite niosome) containing about 67% free menthol. This was thought to be because the temporary strong cooling sensation caused by the evaporation of ethanol made it difficult to feel the cooling sensation of menthol felt after the evaporation of ethanol.

<Cooling sensation 30 minutes after application (sustained cooling sensation)>
In the case where menthol was compounded with niosomes (Example 1), the average score exceeded 2, indicating that a longer-lasting cooling sensation was obtained than in Comparative Example 2, where menthol was dissolved in ethanol and blended free. In the case of micelles (Comparative Example 1), the average score was below 1, indicating that there was almost no difference in the evaluation results from the ethanol solubilized material (Comparative Example 2), and no sustained cooling sensation was observed.
(Consideration)
In the case where menthol was compounded with niosomes (Example 1), a longer-lasting cooling sensation was obtained than in Comparative Example 2 in which menthol was dissolved in ethanol and blended in free form. This was considered to be the result of a part of menthol (approximately 33% by mass in this test system) being retained in the internal aqueous phase of the niosomes, and the sustained release property working to enhance the duration of the cooling sensation.
On the other hand, in the case of micelles (Comparative Example 1), the evaluation results showed almost no difference from the ethanol solubilized material (Comparative Example 2), and the cooling sensation was not sustained. The reason for this is unclear in detail, but it is thought that in the case of Comparative Example 1 (micelles), menthol is solubilized not in the micelle core or palisade but between the micelles, that is, it is solubilized in the same state as when it was blended in free form in Comparative Example 2.
Other possible explanations include the following. Niosomes contain hydrophobic surfactants, while micelles are formed only with hydrophilic surfactants. Therefore, the polarity of the hydrophobic field is lower in niosomes. And since menthol is a relatively hydrophobic substance, it is predicted to be strongly oriented in the hydrophobic field of niosomes, which have low polarity. As a result, it was thought that the sustained release function and the sensory evaluation score improved only when menthol was complexed with niosomes.
(summary)
From the above results, it was determined that only when menthol is complexed with niosomes can the sustained release effect be achieved and a long-lasting cooling sensation be obtained.

<Stability over time>
<Stability>
The prepared cosmetic was filled in a glass bottle with a screw cap at 50 ml, and stored in a thermostatic chamber at 50° C. for one month. After the storage period, the bottle was taken out and visually evaluated for occurrence of separation or precipitation. If separation or precipitation occurred, it was marked with "X." If no separation or precipitation occurred, the average particle size of the niosome particles was measured, and the state in which the particle size did not change by ±10% or more when the average particle size immediately after preparation was taken as 100% was marked with "O." If the particle size changed by ±10% or more when the average particle size immediately after preparation was taken as 100%, it was marked with "△." These marks are shown in the lower part of Table 1.
In this test, there was no evaluation of "x" in which separation or precipitation occurred. In addition, for Comparative Example 2 (free), since it was transparent even after time had passed, it was evaluated as "good" without measuring the particle size.

(result)
Example 1 (menthol complex niosome) was evaluated as "good", Comparative Example 1 (micelle) was evaluated as "good", and Comparative Example 2 (free) was evaluated as "good". Comparative Example 1 (micelle) was evaluated as "good" because a change in particle size of ±10% or more was observed over time when the average particle size immediately after preparation was taken as 100%.
It was thought that capsules could be incorporated into cosmetics in the hope of achieving sustained release effects, but it was confirmed that the "micelles" that were the first choice for incorporating menthol as capsules had stability problems. It was confirmed that the niosomes of the present invention were superior in terms of stability.

Next, compositions further containing optional ingredients often incorporated in cosmetics were tested in the same manner. Toners (Example 2, Comparative Example 3, Comparative Example 4) having the compositions shown in Table 4 were prepared by a conventional method, and a sensory evaluation test of cooling sensation was carried out in the same manner as in the above test, with Comparative Example 4 (free; dissolved in ethanol) as the standard. Example 2 is a complex niosome-containing toner, Comparative Example 3 is a micelle-solubilized toner, and Comparative Example 4 is an ethanol-solubilized toner. The sensory evaluation results are shown in Figure 2.
The stability tests were carried out as follows.

(preparation)
Glycerin, diglycerin, and betaine were added to the remaining water, and the temperature was raised to 85°C (A). Next, sorbitan sesquioleate, PEG-80 hydrogenated castor oil, DPG, pentylene glycol, ethylhexylglycerin, and menthol were weighed, and the temperature was raised to 85°C to dissolve uniformly (B). While stirring the former solution (A) (propeller: 200 rpm), the latter solution (B) was gradually added. Then, it was immediately cooled to 30°C in an ice bath. Glycerin, diglycerin, and betaine were prepared by including them in A, since they are water-soluble. Ethylhexylglycerin was prepared by including them in B, taking into consideration its solubility.

<Stability>
The lotion of Example 2 was stored at 5°C, 25°C, 40°C, 50°C, and cycle (-5°C to 45°C), and the average particle size of the niosomes was measured by dynamic light scattering after a certain number of days. The measuring device used was ELSZ-1000 manufactured by Otsuka Electronics. In addition, the presence or absence of separation or precipitation was visually observed. The particle size results of Example 2 are shown in Figure 3.

(Sensory evaluation results)
There was almost no difference in the cooling sensation immediately after application between Example 2, Comparative Example 3, and Comparative Example 4 (standard). With respect to the cooling sensation 30 minutes after application, Example 2 was rated as having a stronger cooling sensation than Comparative Example 4 (standard), and Comparative Example 3 was rated as having a cooling sensation at the same level as Comparative Example 4 (standard).
It was determined that the cosmetic preparation containing the menthol complex niosome of the present invention has excellent durability of cool sensation.
(Consideration)
In the case where menthol-complexed niosomes (Example 2) and menthol-solubilized micelles (Comparative Example 4) were blended in a lotion formulation containing optional ingredients, no significant difference was confirmed in the initial cooling sensation intensity compared to the lotion containing free menthol (Comparative Example 5), as in the above test results. On the other hand, it was confirmed that the duration of the cooling sensation was significantly increased in the menthol-complexed niosomes (Example 2). Taking this result into account in combination with the stability results described below, it was considered that the state in which menthol was retained in the inner aqueous phase or membrane of the niosomes was stably maintained even in the lotion formulation containing optional ingredients.

(Stability results)
The size of the menthol complex niosome particles showed almost no change in the average particle size even after storage for one month at each temperature range (5°C, 25°C, 40°C, 50°C, cycle (-5°C to 45°C)). Furthermore, the polydispersity index showed a value of about 0.1 in all measurements, which means that the particles were dispersed relatively uniformly. Furthermore, the lotion of Example 2 was visually observed, but no separation or floating of crystals was observed.
From the above results, it was concluded that the menthol complexed niosome can maintain its stability even in a lotion containing optional ingredients such as those in Example 2.

(safety)
Menthol is a toxic component, albeit in small amounts. Therefore, a commonly performed cytotoxicity test was conducted on the cosmetics of Example 1 (menthol complex niosomes) and Comparative Example 1 (micelle solubilization). As a comparison for Example 1, empty niosomes not containing menthol were used, and as a comparison for Comparative Example 1, empty micelles not containing menthol were used.
When compared with the above comparison targets, Example 1 showed almost no change in cytotoxicity, while Comparative Example 1 showed high cytotoxicity. In the case of Example 1, menthol was held in the membrane of the niosome or in the inner aqueous phase, and the amount of menthol that directly contacted the cells was reduced, which is thought to have suppressed the increase in cytotoxicity. Taking into account the test results so far, the composite niosome of the present invention is expected to have a greater effect of reducing skin irritation than a micelle or free formulation. And no one complained of skin irritation in either Example 1 or Example 2.

<Examples 3 to 13, Comparative Examples 5 and 6>
The compositions of the cosmetics of Examples 3 to 13 and the cosmetics of Comparative Examples 5 to 6 are shown in Table 5. The units of numbers are mass %. The cosmetics were prepared in the same manner as in Example 1, and a sensory evaluation test was conducted (N=1) to visually confirm the stability at each temperature range and to check the durability of the cooling sensation.

The cosmetics of Examples 3 to 13, which have the composition of the present invention, had the same stability as Example 1, which was previously tested. The duration of the cool sensation was also at the same level as Example 1. Comparative Examples 5 and 6 had stability problems, with precipitation occurring.

As described above, it has been clarified that the cosmetic preparation containing the composite niosome (particle) of menthol and/or menthol derivative of the present invention not only provides a cooling sensation immediately after application, but also has excellent durability of the cooling sensation, excellent storage stability, and is a hypoallergenic cosmetic preparation.
Cosmetics having the constitution of the present invention are shown below. All formulation examples were excellent in the duration of the cool sensation and in the storage stability.

Formulation Example 1: Lotion (% by mass)
1. Water remainder 2. BG 1.5
3. Glycerin 3
4. DPG 5
5. Glyceryl isostearate 0.5
6. PEG-80 hydrogenated castor oil 0.5
7. Methylgluceth-10 2.25
8. Betaine 1.5
9. Raffinose 0.5
10. Diglycerin 0.1
11. Pentylene glycol 1.75
12. Ethylhexylglycerin 0.07
13. Menthol 0.05
14. Citric acid 0.04
15. Sodium citrate 0.13

Components 1, 2, 3, 7, 8, 9, and 10 were mixed by heating, and components 4, 5, 6, 11, 12, and 13 were added by heating and dissolving, and the mixture was cooled to room temperature to obtain an aqueous solution in which niosome particles were formed. Components 14 and 15, which are salts, were further added to obtain a lotion. The lotion of Formulation Example 1 had a sustained cooling sensation of menthol. It was also evaluated to have an excellent feeling when used. There was no problem with storage stability.

Claims (6)

A cosmetic composition comprising the following (A) to (E), wherein the content ratio of (A) to (B) is 1:4 to 3:2, and the content of ethanol is 5 mass% or less relative to the total amount of the composition.
(A) fatty acid sorbitan and/or glyceryl isostearate; (B) polyoxyethylene hydrogenated castor oil having an average degree of polymerization of the polyoxyethylene chain of 60 to 100; (C) one or more selected from dipropylene glycol, pentylene glycol, 1,3-butylene glycol, and propylene glycol; (D) menthol and/or a menthol derivative containing any one of menthyl PCA, menthyl lactate, and menthyl acetate; (E) water. 2. The cosmetic composition according to claim 1, wherein the fatty acid sorbitan (A) comprises at least one selected from the group consisting of sorbitan sesquiisostearate, sorbitan sesquioleate, and sorbitan oleate. The cosmetic composition according to claim 1 or 2, wherein the total content of (A) fatty acid sorbitan and/or glyceryl isostearate, and (B) polyoxyethylene hydrogenated castor oil having an average degree of polymerization of polyoxyethylene chains of 60 to 100 is 0.5 to 2 mass% per cosmetic. The cosmetic composition according to any one of claims 1 to 3, wherein the content of (D) menthol and/or a menthol derivative containing any one of menthyl PCA, menthyl lactate, and menthyl acetate is 0.05 to 0.2% by mass per cosmetic composition. The cosmetic composition according to any one of claims 1 to 4, which has a viscosity of 100 mPa·s or less as measured using a B-type viscometer (No. 1 rotor, 60 rpm, 30 seconds, 25°C). The cosmetic composition according to any one of claims 1 to 5, wherein the content of oil excluding (D) is 0.1 mass% or less based on the total amount of the composition.

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