Method for dispersing poorly water-soluble substances in an aqueous solvent, and method for exposing aquatic organisms to poorly water-soluble substances.

Abstract

To provide a novel technique for dispersing a water-insoluble substance or exposing the water-insoluble substance to an aquatic organism.SOLUTION: The present invention provides a method for dispersing a water-insoluble substance in an aqueous solvent or a method for exposing the water-insoluble substance to an aquatic organism, including a preparation step for preparing an oil-in-water emulsion composition that includes (A) at least one selected from polyoxyethylene hydrogenated castor oils with an HLB of 10-15 and (B) at least one selected from polyoxyethylene sorbitol fatty acid esters with an HLB of 10-15, and (C) a water-insoluble substance, and a dispersion step for dispersing the oil-in-water emulsion composition in an aqueous solvent.SELECTED DRAWING: None

Description

Technical Field

[0001] The present technology relates to a method for dispersing poorly water-soluble substances in an aqueous solvent and a method for exposing poorly water-soluble substances to aquatic organisms.

Background Art

[0002] Currently, newly developed cosmetics and the like may contain poorly water-soluble substances that are extremely poorly soluble in aqueous solvents. In the development process of cosmetics and the like, it is required to disperse poorly water-soluble substances in an aqueous solvent and examine the effects on aquatic organisms and the like in approaching environmental problems and the like.

[0003] Here, as a technique for dispersing poorly water-soluble substances, for example, Patent Document 1 discloses a solubilization method for poorly water-soluble substances, which comprises pulverizing a cyclodextrin and one or more selected from cyclodextrin and their derivatives and a water-insoluble substance using a pulverizing medium. Further, Patent Document 2 discloses a method for producing a solubilized product of a poorly water-soluble compound, which comprises a step of adding a solution containing a poorly water-soluble compound to an aqueous phase containing a solubilizing agent for solubilizing the poorly water-soluble compound in a mass 50 times or less the mass of the poorly water-soluble compound. Furthermore, Patent Document 3 discloses a solubilization composition for a poorly water-soluble substance, which contains (A) a polyglycerol fatty acid ester composed of an unsaturated and / or branched fatty acid having 18 carbon atoms, the degree of polymerization of the constituent polyglycerol being 5 to 20 and the HLB value being 13 or more, (B) a polyglycerol fatty acid ester composed of a fatty acid having 10 to 14 carbon atoms, the degree of polymerization of the constituent polyglycerol being 5 to 20 and the HLB value being 13 or more, (C) an ester oil composed of a fatty acid having 10 or less carbon atoms and an alcohol having 9 or less carbon atoms, and (D) a polyhydric alcohol, and these are blended in a predetermined weight ratio.

[0004] Furthermore, when exposing corals, which are aquatic organisms, to poorly water-soluble substances, Non-Patent Document 1 discloses the use of methanol as a solvent (solubilizer) to disperse the poorly water-soluble substances, and Non-Patent Document 2 discloses the use of dimethyl sulfoxide (DMSO) as a solvent (solubilizer) to disperse the poorly water-soluble substances. [Prior art documents] [Patent Documents]

[0005] [Patent Document 1] Japanese Patent Publication No. 2021-123554 [Patent Document 2] Japanese Patent Publication No. 2020-152674 [Patent Document 3] Japanese Patent Publication No. 2022-60041 [Non-patent literature]

[0006] [Non-Patent Document 1] Photochemical response of the scleractinian coral Stylophora pistillata to some sunscreen ingredients, Coral Reefs, volume 38, pp.109-122 (2019) [Non-Patent Document 2] Toxicopathological Effects of the Sunscreen UV Filter, Oxybenzone (Benzophenone-3), on Coral Planulae and Cultured Primary Cells and Its Environmental Contamination in Hawaii and the US Virgin Islands, Archives of Environmental Contamination and Toxicology, volume 70, pp.265-288 (2016) [Overview of the project] [Problems that the invention aims to solve]

[0007] However, the development of technologies for dispersing poorly water-soluble substances is still insufficient. Poorly water-soluble substances, which have low solubility in polar solvents such as methanol and DMSO, require the use of large amounts of solvent. Furthermore, their low solubilizing power makes it difficult to uniformly disperse them in aqueous solvents.

[0008] Therefore, the primary objective of this technology is to provide a novel technique for dispersing or exposing poorly water-soluble substances to aquatic organisms. [Means for solving the problem]

[0009] The inventors of this application conducted extensive experimental studies on techniques for dispersing or exposing poorly water-soluble substances to aquatic organisms. They discovered that dispersibility in aqueous solvents is improved by preparing an oil-in-water emulsion composition containing specific components and then dispersing it, thus completing this technology.

[0010] In other words, this technology provides a method for dispersing a poorly water-soluble substance in an aqueous solvent, comprising: a preparation step of first preparing an oil-in-water emulsion composition containing (A) one or more selected from polyoxyethylene hydrogenated castor oil with an HLB of 10 to 15, (B) one or more selected from polyoxyethylene sorbitol fatty acid esters with an HLB of 10 to 15, and (C) a poorly water-soluble substance; and a dispersion step of dispersing the oil-in-water emulsion composition in an aqueous solvent. Furthermore, this technology also provides a method for exposing aquatic organisms to poorly water-soluble substances, comprising a preparation step of preparing an oil-in-water emulsion composition containing (A) one or more selected from polyoxyethylene hydrogenated castor oil with HLB 10 to 15, (B) one or more selected from polyoxyethylene sorbitic fatty acid esters with HLB 10 to 15, and (C) a poorly water-soluble substance, and a dispersion step of dispersing the oil-in-water emulsion composition in an aqueous solvent in which aquatic organisms live. In this technology, component (C) may be one or more selected from ultraviolet absorbers, zinc oxide, and titanium dioxide. In this technology, the mass ratio of component (A) and component (B) to component (C) may be A:B:C = 0.1 to 5:0.01 to 5:1. In this technology, if component (C) contains a solid oil and / or powder, the oil-in-water emulsion composition may further contain component (D), an ester oil that is liquid at 25°C (excluding component (C)). In this case, the molecular weight of component (D) may be 200 to 500. Also, in this case, the content of component (D) may be 1 to 20% by mass relative to component (C). In this technology, in the dispersion step, component (C) may be dispersed in the aqueous solvent such that its theoretical concentration in the aqueous solvent is 0.0001 to 20 ppm. In this technology, the salt concentration of the aqueous solvent may be 1.0 to 5.0% by mass percentage. In this technology, if component (C) is a liquid oil, the oil-in-water emulsion composition may consist of components (A) to (C) and water. In this technology, if component (C) includes solid oil and / or powder, the oil-in-water emulsion composition may consist of components (A) to (D) and water. In this technology, during the dispersion step, the temperature of the aqueous solvent may be set to 15-30°C, and a stream of water may be applied to the aqueous solvent. The dispersion method relating to this technology may be used to evaluate its impact on aquatic organisms. The exposure method related to this technology may further include an evaluation step to assess its effects on aquatic organisms. [Effects of the Invention]

[0011] This technology provides a novel method for dispersing or exposing poorly water-soluble substances to aquatic organisms. The effects of this technology are not limited to those described herein, but may include any of the effects described in this specification. [Modes for carrying out the invention]

[0012] Hereinafter, preferred embodiments for implementing the present technology will be described. The embodiments described below show typical embodiments of the present technology, and the scope of the present technology is not limited only to these embodiments. In this specification, "X to Y" indicating a range includes X and Y and means "X or more and Y or less".

[0013] 1. Method for dispersing poorly water-soluble substances in an aqueous solvent The dispersion method according to the present technology performs at least a preparation step and a dispersion step. Further, if necessary, other steps may be performed as long as the effects of the present technology are not impaired. Hereinafter, each step will be described in detail.

[0014] (1) Preparation step The preparation step is a step of preparing an oil-in-water type emulsion composition containing (A) one or more selected from polyoxyethylene hydrogenated castor oil having an HLB of 10 to 15, (B) one or more selected from polyoxyethylene sorbitol fatty acid esters having an HLB of 10 to 15, and (C) a poorly water-soluble substance.

[0015] (1-1) Component (A) Component (A) contributes to the emulsification of component (C). As component (A), those obtained by adding ethylene oxide to hydrogenated castor oil obtained by hydrogenating castor oil can be used as long as their HLB is between 10 and 15. Among them, those in which 20 to 80 of ethylene oxide is mainly added to hydrogenated castor oil are preferred. Specifically, for example, PEG-20 hydrogenated castor oil (HLB: 10.5), PEG-30 hydrogenated castor oil (HLB: 11.0), PEG-40 hydrogenated castor oil (HLB: 12.5), PEG-50 hydrogenated castor oil (HLB: 13.5), PEG-60 hydrogenated castor oil (HLB: 14.0), PEG-80 hydrogenated castor oil (HLB: 15.0), etc. can be mentioned, and if necessary, one or more of them can be used in combination. Also, in this technology, it is possible to use commercial products as component (A), for example, NIKKOL HCO-20, 30, 40, 50, 60, 80 (manufactured by Nikko Chemicals Co., Ltd., etc.) can be mentioned.

[0016] The content of component (A) in the oil-in-water emulsion composition is preferably at least 0.001% by mass, more preferably at least 0.01% by mass, still more preferably at least 0.1% by mass as the lower limit, and preferably at most 10% by mass, more preferably at most 5% by mass, still more preferably at most 3% by mass as the upper limit. Also, the content of component (A) in the oil-in-water emulsion composition is preferably 0.001 to 10% by mass, more preferably 0.01 to 5% by mass, still more preferably 0.1 to 3% by mass.

[0017] (1-2) Component (B) Component (B), along with component (A), contributes to the emulsification of component (C). Component (B) can be any sorbitol esterified with a fatty acid after adding ethylene oxide, provided its HLB is between 10 and 15. Among these, polyoxyethylene sorbitic tetraoleate, obtained by esterifying sorbitol esterified with oleic acid, is particularly preferred. Specifically, examples include sorbitic tetraoleate sorbeth-30 (HLB: 11.5), sorbitic tetraoleate sorbeth-40 (HLB: 12.5), and sorbitic tetraoleate sorbeth-60 (HLB: 14.0), and one or more of these can be used in combination as needed. Furthermore, this technology allows the use of commercially available products as component (B), such as NIKKOL GO-430NV, 440V, and 460V (all manufactured by Nikko Chemicals Co., Ltd.).

[0018] The content of component (B) in the oil-in-water emulsion composition is preferably 0.001% by mass or more, more preferably 0.01% by mass or more, and still preferably 0.1% by mass or more, with an upper limit of 10% by mass or less, more preferably 5% by mass or less, and still preferably 3% by mass or less. Furthermore, the content of component (B) in the oil-in-water emulsion composition is preferably 0.001 to 10% by mass, more preferably 0.01 to 5% by mass, and still preferably 0.1 to 3% by mass.

[0019] In an oil-in-water emulsion composition, the mass ratio of component (A) to component (B) is preferably 0.2 to 100, more preferably 0.2 to 50, and even more preferably 0.2 to 10.

[0020] (1-3) Component (C) Component (C) refers to a substance with low solubility in aqueous solvents. Specifically, it refers to a substance whose solubility in aqueous solvents at 25°C is "slightly soluble" (30 mL or more but less than 100 mL of aqueous solvent is required to dissolve 1 g or 1 mL of solute), "slightly soluble" (100 mL or more but less than 1000 mL of solvent), "very soluble" (1000 mL or more but less than 10000 mL of solvent), or "almost insoluble" (10000 mL or more of solvent or no solubility).

[0021] Component (C) can specifically be a poorly water-soluble substance commonly used in cosmetics. More specifically, examples include UV absorbers containing solid oils that are solid at 25°C and liquid oils that are liquid at 25°C, powders, etc. In this invention, "liquid" refers to a substance that has fluidity at room temperature (25°C) and atmospheric pressure, and "solid" refers to a substance that exhibits semi-solid to solid properties at room temperature (25°C) and atmospheric pressure, with a melting point of 25°C or higher. Semi-solid refers to a substance with a melting point of 25°C or higher but that has not completely solidified at 25°C, and solid refers to a substance with a melting point of 25°C or higher that has completely solidified at 25°C.

[0022] Examples of UV absorbers include cinnamic acid-based UV absorbers, triazine-based UV absorbers, benzoylmethane-based UV absorbers, salicylic acid-based UV absorbers, benzoic acid-based UV absorbers, benzophenone-based UV absorbers, UV absorbers having sulfonic acid groups, and other organic UV absorbers. One or more of these can be used in combination as needed.

[0023] Examples of cinnamic acid-based UV absorbers include 2-ethylhexyl paramethoxycinnamate (OMC), glyceryl mono-2-ethylhexanoate diparamethoxycinnamate, methyl 2,5-diisopropylcinnamate, 2-ethoxyethyl paramethoxycinnamate, methylbis(trimethylsiloxy)silylisopentyl trimethoxycinnamate, and isopropyl paramethoxycinnamate / diisopropyl cinnamic acid ester mixtures. Examples of triazine-based UV absorbers include 2,4,6-tris[4-(2-ethylhexyloxycarbonyl)anilino]-1,3,5-triazine and bis(ethylhexyloxyphenol)methoxyphenyltriazine (BEMT). Examples of benzoylmethane-based UV absorbers include 4-isopropyldibenzoylmethane and 4-tert-butyl-4'-methoxydibenzoylmethane.

[0024] Examples of salicylic acid-based UV absorbers include ethylene glycol salicylate, 2-ethylhexyl salicylate, butyloctyl salicylate, benzyl salicylate, and homomenthyl salicylate (homosalate). Examples of benzoic acid-based UV absorbers include diethylaminohydroxybenzoyl hexyl benzoate (DHHB), para-aminobenzoic acid, ethyldihydroxypropyl para-aminobenzoic acid, octyldimethyl para-aminobenzoic acid, amyl para-dimethylaminobenzoate, 2-ethylhexyl para-dimethylaminobenzoate, and glyceryl para-aminobenzoate. Examples of benzophenone-based UV absorbers include 4-(2-β-glucopyranosiloxy)propoxy-2-hydroxybenzophenone, dihydroxydimethoxybenzophenone, sodium dihydroxydimethoxybenzophenone disulfonate, 2-hydroxy-4-methoxybenzophenone (oxybenzone-3) (BP-3), 2-hydroxy-4-methoxybenzophenone-5-sulfate, 2,2'-dihydroxy-4-methoxybenzophenone, 2,4-dihydroxybenzophenone, 2,2',4,4'-tetrahydroxybenzophenone, 2,2'-dihydroxy-4,4'-dimethoxybenzophenone, and 2-hydroxy-4-N-octoxybenzophenone.

[0025] Examples of UV absorbers having a sulfonic acid group include hydroxymethoxybenzophenone sulfonic acid, phenylbenzimidazole sulfonic acid, phenyldibenzimidazole tetrasulfonic acid, and terephthalylidene dicamphor sulfonic acid. Other UV absorbers include, for example, octocrylene; dimethicone diethyl benzalmalonate (polysilicone-15) (PS-15); 2-ethylhexyl dimethoxybenzylidene dioxoimidazolidinepropionate; copolymer (polyester-8) in which the ends of a copolymer of adipic acid and neopentyl glycol are encapsulated with octyldodecanol or cyanodiphenylpropenoic acid; 1-(3,4-dimethoxyphenyl)-4,4-dimethyl-1,3-pentanedione; cinoxate; methyl-o-aminobenzoate, 3-(4-methylbenzylidene)camphor; methylenebisbenzotriazolyltetramethylbutylphenol; drometrizole trisiloxane, etc.

[0026] The powder is not particularly limited in terms of shape, particle size, particle structure, etc., as long as it is a powder commonly used in cosmetics. Specifically, for example, inorganic powders (e.g., talc, kaolin, mica, sericite, muscovite, phlogopite, synthetic mica, rose mica, biotite, lithium mica, calcined mica, calcined talc, vermiculite, magnesium carbonate, calcium carbonate, aluminum silicate, barium silicate, calcium silicate, magnesium silicate, strontium silicate, tungstate metal salts, magnesium, silica, fuming silica, zeolite, glass, barium sulfate, calcined calcium sulfate (calcined gypsum), calcium phosphate, fluorine apatite, hydroxyapatite, ceramic powder, metal soaps (e.g., zinc myristate, calcium palmitate, aluminum stearate, etc.), boron nitride, etc.); organic powders (e.g., polyamide resin powder (nylon powder), polyethylene powder, polymethyl methacrylate powder, polystyrene powder, styrene-acrylic acid copolymer resin powder, benzoguanamine resin powder, poly Polytetrafluoroethylene powder, cellulose powder, silicone resin powder, silk powder, wool powder, urethane powder, etc.); inorganic white pigments (e.g., titanium dioxide, zinc oxide, etc.); inorganic red pigments (e.g., iron oxide (red iron oxide), iron titanate, etc.); inorganic brown pigments (e.g., γ-iron oxide, etc.), inorganic yellow pigments (e.g., yellow iron oxide, yellow ochre, etc.), inorganic black pigments (e.g., black iron oxide, carbon black, lower titanium dioxide, etc.), inorganic purple pigments (e.g., manganese violet, cobalt violet, etc.); inorganic green pigments (e.g., chromium oxide, chromium hydroxide, cobalt titanate, etc.); inorganic blue pigments (e.g., ultramarine, Prussian blue, etc.); pearl pigments (e.g., titanium dioxide coated mica, titanium dioxide coated bismuth oxychloride, titanium dioxide coated talc, colored titanium dioxide coated mica, bismuth oxychloride, fish scale foil, etc.); metal powder pigments (e.g., aluminum powder, copper powder, etc.);Examples of organic pigments include zirconium, barium, or aluminum lake (e.g., Red 201, Red 202, Red 204, Red 205, Red 220, Red 226, Red 228, Red 405, Orange 203, Orange 204, Yellow 205, Yellow 401, and Blue 404, as well as Red 3, Red 104, Red 106, Red 227, Red 230, Red 401, Red 505, Orange 205, Yellow 4, Yellow 5, Yellow 202, Yellow 203, Green 3, and Blue 1); natural pigments (e.g., chlorophyll, β-carotene); wax powders (e.g., carnauba wax powder); starch powders (e.g., corn starch powder, rice starch powder), etc.), and one or more of these can be used in combination as needed.

[0027] Furthermore, the powder may be surface-treated using conventionally known methods with silicone compounds, silane treatments, fluorine compounds, metal soaps, collagen, hydrocarbons, higher fatty acids, lecithin, higher alcohols, esters, waxes, amino acids, surfactants, etc., or further compounded with these. Such surface treatment agents are not particularly limited as long as they are commonly used in cosmetics, quasi-drugs, pharmaceuticals, etc., but examples include silicone treatment agents, silane coupling agents, fluorine treatment agents, organic titanate treatment agents, fatty acid treatment agents, lecithin treatment agents, amino acid treatment agents, acylated amino acid treatment agents, etc.

[0028] Examples of silicone treatment agents include chain-like silicones such as low-molecular-weight dimethylpolysiloxane, high-molecular-weight dimethylpolysiloxane, and methylphenylpolysiloxane; modified silicones such as amino-modified silicones, alkyl-modified silicones, and alkoxy-modified silicones; silicone resins such as trimethylsiloxysilicate and acrylic-silicone graft copolymers; silicone rubbers; partially or fully crosslinked organopolysiloxanes; silylation agents; silane coupling agents; and, as necessary, one or more of these can be used in combination.

[0029] While not particularly limited, trialkoxyalkylsilanes are preferred as silane coupling agents. Triakoxyalkylsilanes are compounds in which three alkoxy groups and one alkyl group are bonded to a silicon atom. These alkoxy groups react with hydroxyl groups and other elements on the powder surface, thereby chemically modifying the powder surface. In the trialkoxyalkylsilane, the alkoxy groups are preferably alkoxy groups having 1 to 3 carbon atoms, such as methoxy, ethoxy, and propoxy. In the trialkoxyalkylsilane, the alkyl group is preferably an alkyl group having 6 to 18 carbon atoms, such as hexyl, octyl, decyl, and octadecyl groups. Examples of such trialkoxyalkylsilanes include trimethoxyhexylsilane, trimethoxyoctylsilane, trimethoxydecylsilane, trimethoxyoctadecylsilane, triethoxyhexylsilane, triethoxyoctylsilane (OTS), triethoxydecylsilane, and triethoxyoctadecylsilane.

[0030] Examples of organic titanate treatment agents include alkyl titanates such as long-chain carboxylic acid type, pyrophosphate type, phosphorous acid type, and amino acid type, with alkyl titanates having an alkyl group with 8 to 24 carbon atoms being preferred. Examples of such alkyl titanates include isopropyl triisostearoyl titanate (ITT), isopropyl trioctanoyl titanate, isopropyl dimethacrylate isostearoyl titanate, isopropyl isostearoyl diacrylic titanate, and diisostearoylethylene titanate as long-chain carboxylic acid type alkyl titanates, and tetraisopropyl bis(dioctyl phosphite) titanate and tetraoctyl bis(ditridecyl) as pyrophosphate type alkyl titanates. Examples include phosphite titanate, tetra(2,2-diallyloxymethyl-1-butyl)bis(ditridecylphosphite) titanate, phosphite-type alkyl titanates include isopropyl tri(dioctyl pyrophosphate) titanate, bis(dioctyl pyrophosphate) oxyacetate titanate, bis(dioctyl pyrophosphate) ethylene titanate, and amino acid-type alkyl titanates include isopropyl tri(N-amidoethyl-aminoethyl) titanate.

[0031] Examples of fatty acid treatment agents include fatty acids and their metal salts. Among these, fatty acids with 12 to 18 carbon atoms are preferred from the viewpoint of redispersibility of component (A), etc. Examples of their salts include calcium, magnesium, zinc, and aluminum.

[0032] Examples of amino acid processing agents include proline, hydroxyproline, alanine, glycine, sarcosine, lysine, aspartic acid, and glutamic acid, and their salts are included.

[0033] While there are no particular limitations on the acylated amino acid treatment agent, fatty acids with 6 to 23 carbon atoms constituting the acyl group are preferred, and fatty acids with 8 to 20 carbon atoms are more preferred. Among these, stearoyl glutamic acid, lauroyl aspartic acid, dilauroyl glutamic acid lysine, and lauroyl lysine are particularly preferred.

[0034] In this technology, it is preferable to use one or more selected from ultraviolet absorbers, zinc oxide, and titanium dioxide as component (C). Furthermore, in this technology, commercially available products can also be used as component (C).

[0035] The mass ratio of components (A) and (B) to component (C) is not particularly limited, but it is preferably A:B:C = 0.1~5:0.01~5:1, more preferably A:B:C = 0.3~3:0.05~3:1, and even more preferably A:B:C = 0.5~2:0.1~2:1. Compared to dispersion using methanol or DMSO as a solubilizer, the dispersion method according to this technology requires a small amount of components (A) and (B) relative to component (C). Therefore, when dispersed in an aqueous solvent for exposure to aquatic organisms, the effect of the solubilizer on aquatic organisms can be reduced, and costs can be reduced and experimental procedures can be kept from becoming complicated.

[0036] (1-4)Water The oil-in-water emulsion composition prepared in this process contains water as an essential component. The water used is not particularly limited, as long as it is water commonly used in cosmetics. Specifically, examples include purified water, hot spring water, deep-sea water, and steam-distilled water from plants. One or more of these can be used in combination as needed.

[0037] When component (C) is a liquid oil that is liquid at 25°C, the oil-in-water emulsion composition prepared in this step preferably consists of components (A) to (C) and water.

[0038] (1-5) Component (D) In this technology, if component (C) contains solid oil and / or powder, it is preferable that the oil-in-water emulsion composition further contains component (D), an ester oil that is liquid at 25°C (excluding component (C)). By including component (D), component (D) functions as a solvent or dispersion medium for component (C), improving the solubility or dispersibility of component (C).

[0039] Component (D) is an ester consisting of a linear or branched fatty acid and a linear or branched monohydric or polyhydric alcohol. Specifically, for example, octyldodecyl myristate, isocetyl myristate, glyceryl tri-2-ethylhexanoate (triethylhexanone), glyceryl triisostearate, propylene glycol isostearate, diethylhexyl sebacate, trimethylpropane tri-2-ethylhexanoate, di-2-ethylhexyl succinate, di(caprylic / capric acid)propylene glycol, 2-ethylhexyl 2-cyano-3,3-diphenylacrylate, tri(caprylic / capric acid)glyceryl, trimethylolpropane trioctanoate, glyceryl tricaprylate, ethylene glycol dioctanoate, glyceryl dimyristate, diethylene glycol dilaurate, pentaerythritol tetra-2-ethylhexanoate, glyceryl monostearate diacetate, diisostearyl malate, alkyl benzoate (C 12 ~C 15 Examples of suitable materials include octyldodecyl lactate, propylene glycol monostearate, propylene glycol oleate, oleyl lactate, propylene glycol dicaprate, diisopropyl sebacate, ethylene glycol monostearate, diethylene glycol dicaprate, neopentyl glycol dicaprate, neopentyl glycol di2-ethylhexanoate, coconut oil fatty acid glyceryl, glyceryl dilaurate, glyceryl sesquioleate, ethylene glycol monooleate, cetyl lactate, diethyl sebacate, methyl castor oil fatty acid, ethylene glycol palmitate, polyethylene glycol dilaurate, and tripropylene glycol dipivalate. One or more of these can be used in combination as needed.

[0040] In this technology, among these, component (D) is glyceryl tri-2-ethylhexanoate, di(caprylic / capric acid) propylene glycol, propylene glycol dicaprate, diisopropyl sebacate, di-2-ethylhexyl succinate, and alkyl benzoate (C 12 ~C 15 Preferably one or more selected from ), including propylene glycol dicaprate and / or alkyl benzoate (C 12 ~C 15 ) is more preferable. Furthermore, in this technology, it is also possible to use a commercially available product as component (D).

[0041] The molecular weight of component (D) is preferably 200 to 500. By setting the molecular weight to 200 to 500, the solubility or dispersibility of component (C) can be further improved.

[0042] The IOB value of component (D) is preferably 0.1 to 0.5, and more preferably 0.14 to 0.4. Setting the IOB value to 0.1 to 0.5 can further improve the solubility or dispersibility of component (C). In this specification, the IOB value refers to the ratio of the inorganic value to the organic value, i.e., "inorganic value / organic value".

[0043] The content of component (D) is preferably 1 to 20% by mass relative to component (C), and more preferably 1.5 to 15% by mass. By including 1 to 20% by mass relative to component (C), component (D) can function efficiently as a solvent or dispersion medium for component (C).

[0044] When component (C) contains solid oil and / or powder that is solid at 25°C, the oil-in-water emulsion composition prepared in this step preferably consists of components (A) to (D) and water.

[0045] (1-6) Others In this process, the oil-in-water emulsion composition may contain other components besides components (A) to (D), such as humectants, colorfastness inhibitors, antioxidants, defoamers, cosmetic ingredients, preservatives, fragrances, and cooling agents, as long as they do not impair the effects of this technology.

[0046] The method for producing the oil-in-water emulsion composition of the present invention is not particularly limited, but one example is as follows. Mix components (A) to (C) or components (A) to (D) uniformly. Heating may be done if desired. Heating to approximately 65-75°C is preferable. Next, a portion of the water is added to the above mixture and emulsified. Heating may be performed at this stage if desired. Heating to approximately 65-75°C is preferable. The amount of water used for emulsification in this step is preferably 5-60 times the total mass of components (A)-(C) or components (A)-(D). The remaining water and any other components added as desired are further mixed into the emulsion.

[0047] The average particle size of the emulsion droplets in the oil-in-water emulsion composition of the present invention is preferably 10 to 500 nm, more preferably 50 to 300 nm, and even more preferably 60 to 150 nm. By setting the average particle size of the emulsion droplets within the above range, the stability over time under harsh conditions (salinity concentration) of the aqueous solvent described later is improved, and component (C) can be uniformly dispersed in the aqueous solvent. Furthermore, when used to evaluate the effects on aquatic organisms described later, the stability over time is also improved in the habitat of aquatic organisms, and component (C) can be uniformly dispersed, allowing for appropriate evaluation of the effects on aquatic organisms. The average particle size of the emulsion droplets can be measured using a particle size distribution analyzer that measures by laser diffraction and scattering (for example, a submicron particle analyzer N5 manufactured by BECKMAN COULTER).

[0048] (2) Dispersion process The dispersion step is the process of dispersing the oil-in-water emulsion composition prepared in the preparation step into an aqueous solvent. In this technology, since an oil-in-water emulsion composition containing component (C), which is a poorly water-soluble substance, is prepared first and then dispersed in an aqueous solvent, it is not necessary to use a large amount of solvent (solubilizer), and component (C) can be uniformly dispersed in the aqueous solvent.

[0049] The dispersion method is not particularly limited; for example, the oil-in-water emulsion composition can be dropped into a container holding an aqueous solvent to reach the desired concentration. Examples of containers holding an aqueous solvent include water tanks and other similar vessels.

[0050] Examples of aqueous solvents include water, saline solution, seawater, and buffered aqueous solutions (e.g., phosphate-buffered saline (PBS)). The salt concentration of the aqueous solvent is not particularly limited, but may be 1.0-5.0% by mass percentage, 2.0-4.0%, or around 3.1-3.8%. The dispersion method according to this technology exhibits excellent temporal stability of the oil-in-water emulsion composition even under harsh conditions of a salt concentration of 1.0-5.0% by mass percentage, and can uniformly disperse component (C), meaning it can be implemented even under conditions close to the salinity of seawater.

[0051] In this process, the theoretical concentration of component (C) in the aqueous solvent can be appropriately set depending on the purpose. In this specification, the theoretical concentration is the concentration estimated from the amount of oil-in-water emulsion composition dropped (dispersed), and the theoretical concentration of component (C) is preferably 0.0001 to 20 ppm, and more preferably 0.001 to 15 ppm. Setting the theoretical concentration of component (C) in the aqueous solvent to 0.0001 to 20 ppm is more preferable because, when the dispersion method according to this technology is used to evaluate the effects on aquatic organisms described later, it is possible to evaluate within an appropriate concentration range, that is, a concentration range to which aquatic organisms may be exposed in their habitat.

[0052] The temperature of the water-soluble solvent is not particularly limited, but it is preferably 15 to 30°C. Furthermore, it is preferable to apply a water flow to the water-soluble solvent using conventionally known methods such as a screw. This allows the dispersion method according to this technology to be used to evaluate the effects on aquatic organisms, as described later, as it can more closely resemble the habitat of aquatic organisms and enable a more appropriate evaluation. The flow rate when applying the water flow can be, for example, 1000 to 3000 L / h (hours) if the container size is 50 to 55 L.

[0053] (3) Applications of methods for dispersing poorly water-soluble substances in aqueous solvents The dispersion method relating to this technology can be used for a wide range of applications, but it is particularly useful for evaluating the impact on aquatic organisms. In this specification, aquatic organisms refer to organisms that inhabit water, water surfaces, watersides, etc. Specifically, examples include fish such as medaka, reptiles such as turtles, vertebrates including amphibians such as frogs and newts; protochordates such as sea squirts; echinoderms such as sea urchins and sea cucumbers; arthropods such as shrimp, crabs and insects; annelids such as polychaetes and ragworms; mollusks such as shellfish, squid and octopuses; cnidarians such as jellyfish, sea anemones and corals; sponges such as sponges; seaweeds such as cyanobacteria, green algae, cephaloalgae, and red algae; seagrasses such as eelgrass; plants such as rice; and single-celled organisms such as paramecium and rotifers.

[0054] In this technology, among these, coelenterates are preferred as aquatic organisms, and among coelenterates, corals are particularly preferred, as their effects from environmental stress have become a problem in recent years. Corals are very delicate animals, and there have been reports that certain types of poorly water-soluble substances released into the ocean can cause serious damage to them.

[0055] 2. Methods for exposing aquatic organisms to poorly water-soluble substances The exposure method related to this technology involves at least a preparation step and a dispersion step. Furthermore, other steps, such as an evaluation step, may be performed as needed, provided that they do not impair the effectiveness of this technology. Each step will be described in detail below.

[0056] (1) Preparation process In the exposure method related to this technology, the preparation process is the same as described above, so it will not be explained here.

[0057] (2) Dispersion process The dispersion step is a process of dispersing the oil-in-water emulsion composition prepared in the preparation step described above into an aqueous solvent in which aquatic organisms live.

[0058] The dispersion method is not particularly limited; for example, the oil-in-water emulsion composition can be dropped into a container holding aquatic organisms and an aqueous solvent to the desired concentration, and stirred as necessary. Examples of containers holding aquatic organisms and aqueous solvents include aquariums. Other than the presence of aquatic organisms in the aqueous solvent, the details are the same as described above and are therefore omitted here.

[0059] (3) Evaluation process The exposure method related to this technology may include a step to evaluate the effects on aquatic organisms, if necessary.

[0060] There are no particular limitations on the evaluation method; evaluation criteria can be appropriately created according to the characteristics of the aquatic organisms in question, and it can be determined whether component (C) dispersed in the aqueous solvent has a positive effect, a negative effect, or no effect at all on the aquatic organisms.

[0061] Specifically, for example, if coral is selected as an aquatic organism, it is known that coral bleaching occurs when stress (e.g., water temperature, light, ultraviolet rays, water quality, etc.) causes the symbiotic zooxanthellae (substances that give coral its appearance color) to be washed away. Coral bleaching can be evaluated by visually checking whether or not this phenomenon has occurred. In addition to bleaching, other conditions such as growth inhibition, larval deficiency, destruction, reduction, death, black band disease, white syndrome, and tumors (skeletal malformations) can also be evaluated by visually checking. Furthermore, in addition to visual inspection, evaluation can also be performed by using conventionally known measuring instruments to measure weight, photosynthetic activity, etc.

[0062] Furthermore, the present invention may also employ the following configuration. <1> A preparation step to prepare an oil-in-water emulsion composition containing (A) one or more selected from polyoxyethylene hydrogenated castor oil with HLB 10 to 15, (B) one or more selected from polyoxyethylene sorbitol fatty acid esters with HLB 10 to 15, and (C) a poorly water-soluble substance. A dispersion step of dispersing the oil-in-water emulsion composition in an aqueous solvent, This is a method for dispersing poorly water-soluble substances in an aqueous solvent. <2> A preparation step to prepare an oil-in-water emulsion composition containing (A) one or more selected from polyoxyethylene hydrogenated castor oil with HLB 10 to 15, (B) one or more selected from polyoxyethylene sorbitol fatty acid esters with HLB 10 to 15, and (C) a poorly water-soluble substance. A dispersion step of dispersing the oil-in-water emulsion composition in an aqueous solvent in which aquatic organisms inhabit, This is a method for exposing aquatic organisms to poorly water-soluble substances. <3> The method according to (1) or (2), wherein component (C) is one or more selected from ultraviolet absorbers, zinc oxide, and titanium dioxide. <4> The method according to any one of <1> to <3>, wherein the mass ratio of component (A) and component (B) to component (C) is A:B:C = 0.1 to 5:0.01 to 5:1. <5> If component (C) contains a solid oil and / or powder, the oil-in-water emulsion composition further contains component (D) a liquid ester oil at 25°C (excluding component (C)), wherein the method is one of any one of <1> to <4>. <6> The method according to <5>, wherein the molecular weight of component (D) is 200 to 500. <7> The method according to <5> or <6>, wherein the content of component (D) is 1 to 20% by mass relative to component (C). <8> The method according to any one of (1) to (7), wherein the dispersion step involves dispersing the component (C) in the aqueous solvent so that its theoretical concentration in the aqueous solvent is 0.0001 to 20 ppm. <9> The method according to any one of (1) to (8), wherein the salt concentration of the aqueous solvent is 1.0 to 5.0% by mass percentage. <10> If component (C) is a liquid oil, the oil-in-water emulsion composition is a method according to any one of <1> to <4>, <8>, and <9>, comprising components (A) to (C) and water. <11> If component (C) contains solid oil and / or powder, the oil-in-water emulsion composition is a method according to any one of <5> to <7>, comprising components (A) to (D) and water. <12> The method according to any one of (1) to (11), wherein the dispersion step involves setting the temperature of the aqueous solvent to 15 to 30°C and further applying a stream of water to the aqueous solvent. [Examples]

[0063] The present technology will be described in more detail below based on the following examples. The examples described below are representative examples of the present technology and should not be interpreted as narrowing the scope of the present technology. In Tables 1-3 below, unless otherwise specified, the unit is "mass%".

[0064] <Experimental Example 1> In Experimental Example 1, the dispersibility of each component (C) shown in Table 1 below was evaluated.

[0065] (1) Experimental method First, each component was blended in the amounts shown in Table 1 below, and an oil-in-water emulsion composition was prepared using the preparation method described below. Next, the oil-in-water emulsion composition was dropped into seawater (approximately 52 L) to achieve the theoretical concentration of component (C) in aqueous solvent shown in Table 1 below, and a water flow was generated using a screw to disperse the mixture at a flow rate of 1000 to 3000 L / h (hours). After one hour, the concentration of component (C) in the seawater was measured by high-performance liquid chromatography (HPLC) under the following conditions, referring to J.Soc.Cosmet.Chem.Jpn., Vol.47, No.1 33-37 (2013). Sample solution preparation: After extracting the oil phase from collected seawater, dissolve it in tetrahydrofuran (THF) for HPLC. HPLC equipment: Waters Alliance 2695 Detector: Photo Diode Array (PDA) detector 2996 Column: Develosil C30-UG-5 Mobile phase: THF / 1% phosphoric acid solution = 70 / 30 Detection wavelength: 310nm

[0066] (2) Details of the method for preparing an oil-in-water emulsion composition I: Components (A) to (C) or components (A) to (D) were mixed and stirred at 70°C. II: Purified water was added to I at 70°C and mixed uniformly to obtain an oil-in-water emulsion composition.

[0067] (3) Experimental results The experimental results are shown in Table 1 below. In the evaluation of "dispersibility of poorly water-soluble substances," a ratio of the detected concentration of component (C) in the aqueous solvent after one hour to the theoretical concentration of component (C) in the aqueous solvent (= recovery rate) of 50% or more was judged as passing (○), and a recovery rate of less than 50% was judged as failing (×).

[0068] [Table 1] *1: Although not measured, it was confirmed that the recovery rate was 50% or higher even when the theoretical concentration of component (C) was 0.01 ppm. Furthermore, it was confirmed that the recovery rate was 90% or higher when the theoretical concentration of component (C) was 10 ppm, so it is inferred that the recovery rate is 50% or higher even when the theoretical concentration of component (C) is 1 ppm, which is within the range of 0.01 ppm and 10 ppm. *2: Although not measured, as with the other examples, it was visually confirmed that the solution remained uniformly cloudy even after one hour, suggesting good dispersibility. *3: Although component (C) was in powder form and therefore could not be measured by HPLC, no sedimentation of the powder was observed even after one hour of dropping, and it was visually confirmed that the mixture was uniformly cloudy, similar to the other examples.

[0069] (4) Discussion The preparation step involves preparing an oil-in-water emulsion composition containing (A) one or more selected from polyoxyethylene hydrogenated castor oil with HLB 10-15, (B) one or more selected from polyoxyethylene sorbitic fatty acid esters with HLB 10-15, and (C) a poorly water-soluble substance. The dispersion step involves dispersing the oil-in-water emulsion composition in an aqueous solvent. It was confirmed that the poorly water-soluble substance remained well dispersed even after one hour of dropping. Furthermore, it was inferred that the composition could be used to evaluate its effects on aquatic organisms by dispersing it in an aqueous solvent where aquatic organisms live.

[0070] <Experimental Example 2> In Experimental Example 2, the effects of each component (C) shown in Table 2 below on aquatic organisms were evaluated.

[0071] (1) Experimental method First, as in Experimental Example 1, an oil-in-water emulsion composition was prepared by blending each component in the amounts shown in Table 2 below. Next, the oil-in-water emulsion composition was dropped into a tank (approximately 52 L) filled with seawater containing colony pieces of Acropora tenuis, each approximately 5 cm in length, to achieve the theoretical concentration of component (C) in the aqueous solvent shown in Table 2 below, and dispersed. The temperature in the tank was maintained at 15-30°C, and a water flow was applied using a screw to achieve a flow rate of 1000-3000 L / h (hour). The condition of the coral was then evaluated after one week. The details of the preparation method for the oil-in-water emulsion composition are the same as in Experimental Example 1, so the explanation is omitted here.

[0072] (2) Experimental results The experimental results are shown in Table 2 below. For the evaluation of the "condition of the coral after one week," n=6 colony fragments were evaluated. A sample was judged as passing (○) if no coral bleaching was observed after one week, and failing (×) if any coral bleaching was observed in any part of the sample after one week.

[0073] [Table 2]

[0074] (3) Consideration It was confirmed that aquatic organisms can be exposed to poorly water-soluble substances by performing a preparation step of preparing an oil-in-water emulsion composition containing (A) one or more selected from polyoxyethylene hydrogenated castor oil with HLB 10 to 15, (B) one or more selected from polyoxyethylene sorbitic fatty acid esters with HLB 10 to 15, and (C) a poorly water-soluble substance, and a dispersion step of dispersing the oil-in-water emulsion composition in an aqueous solvent in which aquatic organisms live. Furthermore, it was confirmed that the effects on aquatic organisms can be appropriately evaluated as a result of exposing them to poorly water-soluble substances.

[0075] <Experimental Example 3> In Experimental Example 3, the dispersibility was evaluated when methanol and DMSO, which are conventional solvents (solubilizers), were used.

[0076] (1) Experimental method First, each component (C) was dissolved in the solvents (solubilizers) shown in Table 3 below, and then dropped into seawater (approximately 52 L). A water flow was generated using a screw to maintain a flow rate of 1000-3000 L / h (hour) to disperse the components. After one hour, the concentration of component (C) in the seawater was measured by high-performance liquid chromatography (HPLC) under the following conditions, referring to J.Soc.Cosmet.Chem.Jpn., Vol.47, No.1 33-37 (2013). Sample solution preparation: After extracting the oil phase from collected seawater, dissolve it in tetrahydrofuran (THF) for HPLC. HPLC equipment: Waters Alliance 2695 Detector: Photo Diode Array (PDA) detector 2996 Column: Develosil C30-UG-5 Mobile phase: THF / 1% phosphoric acid solution = 70 / 30 Detection wavelength: 310nm

[0077] (2) Results The experimental results are shown in Table 3 below. In the evaluation of "dispersibility of poorly water-soluble substances," a ratio of the detected concentration of component (C) in the aqueous solvent after one hour to the theoretical concentration of component (C) in the aqueous solvent (=recovery rate) of 50% or more was judged as passing (○), and a recovery rate of less than 50% was judged as failing (×).

[0078] [Table 3] *4: It was confirmed that an excessive amount of solubilizer is required for poorly water-soluble substances. *5: Although component (C) was in powder form and therefore could not be measured by HPLC, it was confirmed that the poorly water-soluble substance settled at the bottom of the tank, and the supernatant seawater was clear.

[0079] (3) Consideration In Comparative Examples 1-4, compared to Examples 1-8 described above, the amount of solubilizer for poorly water-soluble substances was excessive, and the solubilizing power of the solvent was low, making uniform dispersion of poorly water-soluble substances in aqueous solvents difficult. Similarly, it was confirmed that dispersion of powders was impossible. In contrast, this technology exhibits excellent dispersibility of poorly water-soluble substances in aqueous solvents, thereby increasing the reliability of the results of exposure experiments with aquatic organisms. Furthermore, because the content of components (A) and (B) relative to component (C), which is a poorly water-soluble substance, is small, the effect of the solubilizer on aquatic organisms can be reduced, and it was found that costs can be reduced and experimental procedures can be prevented from becoming complicated. In addition, it was found that powders, which were impossible with conventional technology, can now be dispersed or exposed to aquatic organisms.

Claims

1. A preparation step to prepare an oil-in-water emulsion composition containing (A) one or more selected from polyoxyethylene hydrogenated castor oil with an HLB of 10 to 15, (B) one or more selected from polyoxyethylene sorbitol fatty acid esters with an HLB of 10 to 15, and (C) a poorly water-soluble substance. A dispersion step of dispersing the oil-in-water emulsion composition in an aqueous solvent, Perform A method for dispersing a poorly water-soluble substance in an aqueous solvent, wherein component (C) is one or more selected from ultraviolet absorbers, zinc oxide, and titanium dioxide.

2. A preparation step to prepare an oil-in-water emulsion composition containing (A) one or more selected from polyoxyethylene hydrogenated castor oil with an HLB of 10 to 15, (B) one or more selected from polyoxyethylene sorbitol fatty acid esters with an HLB of 10 to 15, and (C) a poorly water-soluble substance. A dispersion step of dispersing the oil-in-water emulsion composition in an aqueous solvent in which aquatic organisms inhabit, Perform A method for exposing aquatic organisms to poorly water-soluble substances, wherein component (C) is one or more selected from ultraviolet absorbers, zinc oxide, and titanium dioxide.

3. The method according to claim 1 or 2, wherein the mass ratio of component (A) and component (B) to component (C) is A:B:C = 0.1 to 5:0.01 to 5:

1.

4. If component (C) contains solid oil and / or powder, the oil-in-water emulsion composition further contains component (D) a liquid ester oil at 25°C (excluding component (C)). The method according to claim 1 or 2, comprising )

5. The method according to claim 4, wherein the molecular weight of component (D) is 200 to 500.

6. The method according to claim 4, wherein the content of component (D) is 1 to 20% by mass relative to component (C).

7. The method according to claim 1 or 2, wherein in the dispersion step, the component (C) in the aqueous solvent is dispersed in the aqueous solvent such that the theoretical concentration of the component in the aqueous solvent is 0.0001 to 20 ppm.

8. The method according to claim 1 or 2, wherein the salt concentration of the aqueous solvent is 1.0 to 5.0% by mass percentage.

9. The method according to claim 1 or 2, wherein, when component (C) is a liquid oil, the oil-in-water emulsion composition comprises components (A) to (C) and water.

10. The method according to claim 4, wherein, if component (C) includes a solid oil and / or powder, the oil-in-water emulsion composition comprises components (A) to (D) and water.

11. The method according to claim 1 or 2, wherein in the dispersion step, the temperature of the aqueous solvent is set to 15 to 30°C, and a stream of water is further applied to the aqueous solvent.

12. The method according to claim 1, used for evaluating the impact on aquatic organisms.

13. The method according to claim 2, further comprising an evaluation step to evaluate the impact on aquatic organisms.

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