Method for producing liquid dispersion

Abstract

To produce a liquid dispersion excellent in storage stability obtained by dispersing an oil phase containing a phospholipid in an aqueous phase.SOLUTION: A method for producing an oil-in-water type liquid dispersion includes: a confluence step of each flowing a liquid oil phase containing a phospholipid, sterol and non-sterol oil solution, and a liquid aqueous phase containing water, and converging these; and a pore flow step of flowing a fluid obtained by converging the oil phase and the aqueous phase by the confluence step to pores. A temperature of a confluent fluid of the oil phase and the aqueous phase in the pore flow step after flowing to the pores is lower than a temperature of the oil phase before converging with the aqueous phase in the confluence step, and a difference obtained by subtracting a melting temperature of the oil phase from a temperature of the confluent fluid of the oil phase and the aqueous phase after flowing to the pores is 5°C or lower.SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a method for producing a dispersion liquid.

Background Art

[0002] A method for producing a dispersion liquid using a phospholipid is known. For example, Patent Document 1 discloses a method for producing a lecithin-sterol complex by removing an organic solvent from a solution in which lecithin and sterol of a phospholipid are uniformly dissolved in an organic solvent by spray drying or the like to simultaneously precipitate lecithin and sterol, and dispersing it in water. Patent Document 2 discloses a method for producing a nanoemulsion in which an oil phase in which a phospholipid is dissolved in ethanol and an aqueous phase of physiological saline are mixed using a micromixer, and then the obtained dispersion liquid is dialyzed with physiological saline to remove ethanol.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0004] In a dispersion liquid in which an oil phase containing a phospholipid is dispersed in an aqueous phase, there is a problem that the average particle size of the oil phase increases during storage. The method disclosed in Patent Document 1 is to disperse the spray-dried product in water, and the method disclosed in Patent Document 2 is to produce a nanoemulsion, but the storage stability of the dispersion liquid is not considered.

[0005] An object of the present invention is to produce a dispersion liquid having excellent storage stability in which an oil phase containing a phospholipid is dispersed in an aqueous phase.

Means for Solving the Problems

[0006] The present invention relates to a method for producing an oil-in-water dispersion, comprising a confluence step of flowing a liquid oil phase containing a phospholipid, sterols, and a non-sterol oil agent and a liquid water phase containing water, respectively, and then confluencing them, and a pore flow step of flowing the fluid obtained by confluencing the oil phase and the water phase in the confluence step through pores. In the pore flow step, the temperature of the confluent fluid of the oil phase and the water phase after flowing through the pores is lower than the temperature of the oil phase before confluence with the water phase in the confluence step, and the difference obtained by subtracting the dissolution temperature of the oil phase from the temperature of the confluent fluid of the oil phase and the water phase after flowing through the pores is 5°C or less.

Advantages of the Invention

[0007] According to the present invention, a fluid obtained by confluencing an oil phase containing a phospholipid, sterols, and a non-sterol oil agent and a water phase containing water is flowed through pores, and after the oil phase is refined by the shearing force, it is cooled, whereby a dispersion excellent in storage stability in which the oil phase containing a phospholipid is dispersed in the water phase can be produced.

Brief Description of the Drawings

[0008]

Figure 1

Figure 2

Figure 3

Embodiments for Carrying Out the Invention

[0009] Hereinafter, embodiments will be described in detail.

[0010] The method for producing an emulsion according to the embodiment is for producing an oil-in-water emulsion, and includes a merging step of flowing a liquid oil phase containing a phospholipid, sterols, and a non-sterol oil agent and a liquid water phase containing water, respectively, and merging them, and a pore flow step of flowing the fluid obtained by merging the oil phase and the water phase in the merging step through pores. Then, the temperature of the merged fluid of the oil phase and the water phase (i.e., the emulsion) after flowing through the pores in the pore flow step is lower than the temperature of the oil phase before merging with the water phase in the merging step, and the difference obtained by subtracting the dissolution temperature of the oil phase from the temperature of the merged fluid of the oil phase and the water phase (emulsion) after flowing through the pores is 5°C or less.

[0011] According to the method for producing an emulsion according to the embodiment, a fluid obtained by merging an oil phase containing a phospholipid, sterols, and a non-sterol oil agent and a water phase containing water is caused to flow through pores, and after the oil phase is refined by the shearing force, it is rapidly cooled, whereby an emulsion excellent in storage stability in which the oil phase containing a phospholipid is dispersed in the water phase can be produced.

[0012] This is considered to be because when the oil phase is dispersed in the water phase and rapidly cooled at the same time, the phospholipid having surface activity is precipitated around the non-sterol oil agent finely dispersed in the water phase, and the oil phase is stabilized, so that in the process of storage, an increase in the average particle size of the oil phase due to coalescence or the like is suppressed. Also, at that time, since sterols are mixed in the non-sterol oil agent, the affinity of the phospholipid for the non-sterol oil agent is enhanced, and the phospholipid is more likely to precipitate around the non-sterol oil agent, so that further excellent storage stability is promoted.

[0013] <Oil phase> The oil phase contains a phospholipid. The phospholipid is an amphiphilic substance having a phosphate ester moiety, and includes glycerophospholipid and sphingophospholipid. From the viewpoint of producing an emulsion with high storage stability, the phospholipid preferably contains glycerophospholipid.

[0014] In glycerophospholipids, fatty acids are ester - bonded to the glycerol backbone in the hydrophobic part, and alcohol is phospho - ester - bonded in the hydrophilic part. From the viewpoint of producing a dispersion with high storage stability, this alcohol preferably contains one or more of choline, ethanolamine, inositol, and serine.

[0015] Examples of glycerophospholipids include phosphatidylcholine, phosphatidylethanolamine, etc. Glycerophospholipids preferably contain one or more of these, and from the viewpoint of producing a dispersion with high storage stability, it is more preferable to contain phosphatidylcholine. In phosphatidylcholine, choline is phospho - ester - bonded as the hydrophilic part of the glycerophospholipid, and it has a structure in which two fatty acids are ester - bonded to the glycerol backbone as the hydrophobic part.

[0016] In sphingophospholipids, fatty acids are amide - bonded to the sphingosine backbone in the hydrophobic part, and alcohol is phospho - ester - bonded in the hydrophilic part. From the viewpoint of producing a dispersion with high storage stability, this alcohol preferably contains choline and / or ethanolamine.

[0017] Generally, as phospholipids, for example, lecithin, its hydrogenated product hydrogenated lecithin, etc. are used. Examples of lecithin include natural lecithins such as soybean phospholipid, rapeseed phospholipid, egg yolk phospholipid, etc. Examples of hydrogenated lecithin include hydrogenated soybean phospholipid, hydrogenated rapeseed phospholipid, hydrogenated egg yolk phospholipid, etc. Phospholipids preferably contain one or more of these, and from the viewpoint of producing a dispersion with high storage stability, it is more preferable to contain hydrogenated lecithin, and even more preferable to contain hydrogenated soybean phospholipid. Hydrogenated soybean lecithin contains phosphatidylcholine as a main component.

[0018] The content A of phospholipids in the oil phase is preferably 0.5% by mass or more, more preferably 1% by mass or more, still more preferably 2% by mass or more, from the viewpoint of producing a dispersion with high storage stability, and preferably 20% by mass or less, more preferably 10% by mass or less, still more preferably 5% by mass or less, from the viewpoint of production cost. The content A of phospholipids in the oil phase is preferably 0.5% by mass or more and 20% by mass or less, more preferably 1% by mass or more and 10% by mass or less, still more preferably 2% by mass or more and 5% by mass or less.

[0019] When phosphatidylcholine is included as the phospholipid, the preferred content of phosphatidylcholine in the oil phase and in the dispersion is the same as the content of the above phospholipids.

[0020] The oil phase contains sterols. Examples of sterols include animal-derived sterols, plant-derived sterols, etc. Examples of animal-derived sterols include cholesterol, dihydrocholesterol, cholesteryl succinate, etc. Examples of plant-derived sterols include sitosterol, stigmasterol, campesterol, etc. The sterols preferably contain one or more of these, and more preferably contain animal-derived sterols, and still more preferably contain cholesterol, from the viewpoint of producing a dispersion with high storage stability.

[0021] The content B of sterols in the oil phase is preferably 0.1% by mass or more, more preferably 0.4% by mass or more, still more preferably 0.8% by mass or more, from the viewpoint of producing a dispersion with high storage stability, and preferably 10% by mass or less, more preferably 5% by mass or less, still more preferably 3% by mass or less, from the viewpoint of production cost. The content B of sterols in the oil phase is preferably 0.1% by mass or more and 10% by mass or less, more preferably 0.4% by mass or more and 5% by mass or less, still more preferably 0.8% by mass or more and 3% by mass or less, from the above viewpoints.

[0022] When the sterols contain cholesterol, the preferred contents of cholesterol in the oil phase and in the dispersion are the same as the contents of the above-mentioned sterols.

[0023] From the viewpoint of producing a dispersion with high storage stability, the mass ratio (B / A) of the content B of sterols to the content A of phospholipids in the oil phase is preferably 0.05 or more, more preferably 0.1 or more, still more preferably 0.2 or more, and from the same viewpoint, is preferably 2 or less, more preferably 1 or less, still more preferably 0.6 or less. From the above viewpoints, the mass ratio (B / A) of the content B of sterols to the content A of phospholipids in the oil phase is preferably 0.05 or more and 2 or less, more preferably 0.1 or more and 1 or less, still more preferably 0.2 or more and 0.6 or less.

[0024] The oil phase contains a non-sterol oil agent. From the viewpoint of reducing the dissolution temperature of the oil phase and producing a dispersion with high storage stability, this non-sterol oil agent preferably contains a liquid oil that is liquid at 20°C. It is considered that when the non-sterol oil agent contains a liquid oil, phospholipids are likely to precipitate around the finely dispersed non-sterol oil agent in the aqueous phase.

[0025] Examples of the non-sterol oil agent include ester oils, higher alcohols, hydrocarbon oils, silicone oils, fluorine oils, and the like.

[0026] Examples of the ester oil include fatty acid glycerides such as neopentyl glycol di-fatty acid ester, ethylene glycol di-fatty acid ester, fatty acid diglyceride, and fatty acid triglyceride. The ester oil preferably contains one or more of these, and from the viewpoint of producing a dispersion with high storage stability, it is more preferable to contain fatty acid triglyceride.

[0027] From the perspective of producing a dispersion with high storage stability, the fatty acid in the ester oil is preferably a monocarboxylic acid having a carboxy group attached to a saturated or unsaturated straight-chain or branched-chain hydrocarbon chain. From the same perspective, the number of carbon atoms in the hydrocarbon chain of this fatty acid is preferably 5 or more, more preferably 7 or more, preferably 21 or less, more preferably 17 or less, and even more preferably 11 or less.

[0028] From the perspective of producing a dispersion with high storage stability, the ester oil preferably contains a triglyceride of a fatty acid having one or more branched-chain alkyl groups with 5 to 21 carbon atoms, more preferably contains a triglyceride of a fatty acid having one or more branched-chain alkyl groups with 5 to 11 carbon atoms, and even more preferably contains glyceryl tri(2-ethylhexanoate).

[0029] From the perspective of producing a dispersion with high storage stability, the number of carbon atoms in the higher alcohol is preferably 8 or more and 22 or less, more preferably 12 or more and 22 or less. Specific higher alcohols for liquid oils include, for example, 2-ethylhexanol, oleyl alcohol, 2-octyldodecan-1-ol, etc. Specific higher alcohols for solid fats include, for example, myristyl alcohol, cetyl alcohol, cetostearyl alcohol, stearyl alcohol, etc. The higher alcohol preferably contains one or more of these.

[0030] Examples of hydrocarbon oils include paraffin, squalene, squalane, etc. The hydrocarbon oil may be a straight-chain or branched-chain hydrocarbon, a saturated or unsaturated hydrocarbon, or a cyclic hydrocarbon.

[0031] Examples of silicone oils include dimethylpolysiloxane, methylpolysiloxane, methylphenylpolysiloxane, octamethylcyclotetrasiloxane.

[0032] The non-steroidal oil agent preferably contains one or more of these, and more preferably contains an ester oil from the viewpoint of producing a dispersion having high storage stability.

[0033] From the viewpoint of increasing the content of the non-steroidal oil agent in the dispersion, the content C of the non-steroidal oil agent in the oil phase is preferably 1% by mass or more, more preferably 3% by mass or more, still more preferably 10% by mass or more. From the viewpoint of producing a dispersion having high storage stability, it is preferably 30% by mass or less, more preferably 20% by mass or less, still more preferably 15% by mass or less. The content C of the non-steroidal oil agent in the oil phase is preferably 1% by mass or more and 30% by mass or less, more preferably 3% by mass or more and 20% by mass or less, still more preferably 5% by mass or more and 15% by mass or less from the above viewpoints.

[0034] From the viewpoint of increasing the content C of the non-steroidal oil agent, the mass ratio (C / A) of the content C of the non-steroidal oil agent to the content A of the phospholipid in the oil phase is preferably 0.1 or more, more preferably 1 or more, still more preferably 2 or more. From the viewpoint of producing a dispersion having high storage stability, it is preferably 15 or less, more preferably 10 or less, still more preferably 7 or less. The mass ratio (C / A) of the content C of the non-steroidal oil agent to the content A of the phospholipid in the oil phase is preferably 0.1 or more and 15 or less, more preferably 1 or more and 10 or less, still more preferably 2 or more and 7 or less from the above viewpoints.

[0035] From the viewpoint of producing a dispersion having high storage stability, the mass ratio (B / C) of the content B of the sterol to the content C of the non-steroidal oil agent in the oil phase is preferably 0.01 or more, more preferably 0.03 or more, still more preferably 0.05 or more. From the same viewpoint, it is preferably 0.5 or less, more preferably 0.3 or less, still more preferably 0.2 or less. The mass ratio (B / C) of the content B of the sterol to the content C of the non-steroidal oil agent in the oil phase is preferably 0.01 or more and 0.5 or less, more preferably 0.03 or more and 0.3 or less, still more preferably 0.05 or more and 0.2 or less from the above viewpoints.

[0036] The oil phase preferably contains a water-soluble solvent from the viewpoint of dissolving a non-steroidal oil agent and producing a dispersion with high storage stability. The dissolution amount of the water-soluble solvent in 100 g of water at 20°C is preferably 50 g or more, more preferably 100 g or more.

[0037] Examples of the water-soluble solvent include alcohols, ketones, ethers, etc. Examples of the alcohols include monohydric alcohols, dihydric alcohols, trihydric alcohols, etc. The number of carbon atoms of the alcohols is preferably 2 or more and 12 or less, more preferably 2 or more and 6 or less. The water-soluble solvent preferably contains one or more of these, more preferably contains one or more of the alcohols from the viewpoint of producing a dispersion with high storage stability, still more preferably contains one or more of the dihydric alcohols, still more preferably contains one or more of the dihydric alcohols having 2 or more and 12 or less carbon atoms, and still more preferably contains dipropylene glycol.

[0038] From the viewpoint of producing a dispersion with high storage stability, the content D of the water-soluble solvent in the oil phase is preferably 50% by mass or more, more preferably 70% by mass or more, still more preferably 80% by mass or more, and from the same viewpoint, is preferably 99% by mass or less, more preferably 95% by mass or less, still more preferably 90% by mass or less. From the above viewpoints, the content D of the water-soluble solvent in the oil phase is preferably 50% by mass or more and 99% by mass or less, more preferably 70% by mass or more and 95% by mass or less, still more preferably 80% by mass or more and 90% by mass or less.

[0039] The mass ratio (D / A) of the content D of the water-soluble solvent to the content A of the phospholipid in the oil phase is preferably 5 or more, more preferably 10 or more, still more preferably 15 or more, from the viewpoint of producing a dispersion with high storage stability, and preferably 100 or less, more preferably 60 or less, still more preferably 40 or less, from the same viewpoint. The mass ratio (D / A) of the content D of the water-soluble solvent to the content A of the phospholipid in the oil phase is preferably 5 or more and 100 or less, more preferably 10 or more and 60 or less, still more preferably 15 or more and 40 or less, from the above viewpoints.

[0040] The oil phase may further contain, for example, cosmetic ingredients such as ultraviolet absorbers, vitamins, preservatives, pigments, fragrances, and medicinal components.

[0041] The melting temperature of the oil phase is preferably 0 °C or higher, more preferably 10 °C or higher, still more preferably 15 °C or higher, from the viewpoint of making the oil phase flow and producing a dispersion with high storage stability, and preferably 50 °C or lower, more preferably 45 °C or lower, still more preferably 40 °C or lower, from the viewpoint of producing a dispersion with high storage stability. The melting temperature of the oil phase is preferably 0 °C or higher and 50 °C or lower, more preferably 10 °C or higher and 45 °C or lower, still more preferably 15 °C or higher and 40 °C or lower, from the above viewpoints. Here, the "melting temperature of the oil phase" in the present application is the lowest temperature among the temperatures at which the appearance becomes clear without turbidity when left standing at a predetermined constant temperature for one day. The melting temperature of the oil phase is determined by the method described in the examples below.

[0042] <aqueous phase> The main component of the aqueous phase is water. The aqueous phase may be composed of only water, or may be an aqueous solution containing water-soluble components such as salts other than water, pH adjusters, water-soluble solvents, and preservatives. Examples of the salt include sodium monohydrogen phosphate and potassium dihydrogen phosphate. Examples of the preservative include ethylene glycol monophenyl ether and methyl paraoxybenzoate.

[0043] It is preferable that neither the oil phase nor the water phase, and thus the dispersion to be produced, substantially contains a surfactant other than phospholipids from the viewpoint of depositing phospholipids around non-steroidal oils. In the method for producing a dispersion according to the embodiment, only phospholipids are used as the surfactant, and a dispersion excellent in storage stability can be easily produced without using a surfactant other than phospholipids. Here, in the present application, "substantially does not contain a surfactant other than phospholipids" means that the content of the surfactant other than phospholipids in the oil phase, water phase or dispersion is 0.5% by mass or less. In this case, the content of the surfactant other than phospholipids in the oil phase, water phase or dispersion is preferably 0.5% by mass or less, more preferably 0.1% by mass or less, still more preferably 0.01% by mass or less, and even more preferably 0% by mass. When the surfactant other than phospholipids contains a salt, the content of the surfactant other than phospholipids includes the content of the salt.

[0044] Surfactants other than phospholipids are anionic surfactants, cationic surfactants, nonionic surfactants, amphoteric surfactants, etc. having a hydrocarbon group with 8 to 24 carbon atoms.

[0045] Examples of anionic surfactants having a hydrocarbon group with 8 to 24 carbon atoms include fatty acid salts with 8 to 24 carbon atoms such as sodium laurate, potassium laurate, and potassium palmitate; polyoxyethylene alkyl ether carboxylates such as sodium polyoxyethylene tridecyl ether acetate; alkyl phosphates such as potassium lauryl phosphate, sodium lauryl phosphate, arginine lauryl phosphate, potassium myristyl phosphate, sodium myristyl phosphate, arginine myristyl phosphate, potassium palmityl phosphate, sodium palmityl phosphate, and arginine palmityl phosphate; polyoxyethylene alkyl ether phosphates such as sodium polyoxyethylene oleyl ether phosphate and sodium polyoxyethylene stearyl ether phosphate; alkyl sulfate esters such as sodium lauryl sulfate and potassium lauryl sulfate; polyoxyethylene alkyl ether sulfate esters such as potassium polyoxyethylene lauryl sulfate, sodium polyoxyethylene lauryl sulfate, and triethanolamine polyoxyethylene lauryl sulfate; acylated amino acid salts such as sodium lauroyl sarcosinate, monosodium N-lauroyl glutamate, disodium N-stearoyl glutamate, monosodium N-myristoyl-L-glutamate, triethanolamine N-lauroyl glycine, potassium N-coconut oil fatty acid acyl glycine, triethanolamine N-lauroyl-β-alanine, and triethanolamine N-stearoyl-β-alanine; fatty acid amide sulfonates such as sodium N-myristoyl-N-methyl taurate and sodium N-stearoyl-N-methyl taurate; and sulfosuccinates such as sodium di-2-ethylhexyl sulfosuccinate, etc.

[0046] Examples of amphoteric surfactants having a hydrocarbon group with 8 to 24 carbon atoms include betaine-based amphoteric surfactants such as lauryldimethylaminoacetic acid betaine, lauroyl amidobetaine, and lauryl sulfobetaine.

[0047] Examples of nonionic surfactants having a hydrocarbon group with 8 to 24 carbon atoms include sorbitan fatty acid esters such as sorbitan monostearate; polyglycerin fatty acid esters such as glycerin fatty acid ester and polyglyceryl monoisostearate; polyoxyethylene fatty acid esters such as propylene glycol fatty acid ester and polyethylene glycol monolaurate; sucrose fatty acid esters; polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monostearate, polyoxyethylene sorbitan monostearate, and polyoxyethylene coconut oil fatty acid sorbitan; polyoxyethylene alkyl ethers; polyoxyethylene sorbitol fatty acid esters; polyoxyethylene glycerin fatty acid esters; polyoxyethylene propylene glycol fatty acid esters; polyoxyethylene castor oil; polyoxyethylene hydrogenated castor oil; polyoxyethylene hydrogenated castor oil fatty acid esters; alkyl polyglucosides; polyoxyalkylene-modified silicones such as polyoxyethylene-methylpolysiloxane copolymers, etc.

[0048] Examples of cationic surfactants having a hydrocarbon group with 8 to 24 carbon atoms include tertiary amine compounds and quaternary ammonium salts. As the tertiary amine compound, those formed into salts with organic acids and / or inorganic acids can be used. Examples include alkyltrimethylammonium salts such as octyltrimethylammonium, decyltrimethylammonium chloride, lauryltrimethylammonium chloride, and tetradecyltrimethylammonium chloride; and dialkyldimethylammonium salts such as didecyldimethylammonium chloride and distearyldimethylammonium chloride.

[0049] <Dispersion liquid> The content A of phospholipids in the dispersion to be produced is preferably 0.05% by mass or more, more preferably 0.1% by mass or more, still more preferably 0.3% by mass or more, from the viewpoint of producing a dispersion with high storage stability, and is preferably 5% by mass or less, more preferably 3% by mass or less, still more preferably 1% by mass or less, from the viewpoint of production cost. The content of phospholipids in the dispersion to be produced is preferably 0.05% by mass or more and 5% by mass or less, more preferably 0.1% by mass or more and 3% by mass or less, still more preferably 0.3% by mass or more and 1% by mass or less, from the above viewpoints.

[0050] The content B of sterols in the dispersion to be produced is preferably 0.01% by mass or more, more preferably 0.05% by mass or more, still more preferably 0.1% by mass or more, from the viewpoint of producing a dispersion with high storage stability, and is preferably 3% by mass or less, more preferably 2% by mass or less, still more preferably 1% by mass or less, from the viewpoint of production cost. The content of sterols in the dispersion to be produced is preferably 0.01% by mass or more and 3% by mass or less, more preferably 0.05% by mass or more and 2% by mass or less, still more preferably 0.1% by mass or more and 1% by mass or less, from the above viewpoints.

[0051] The mass ratio (B / A) of the content B of sterols to the content A of phospholipids in the dispersion to be produced is preferably 0.05 or more, more preferably 0.1 or more, still more preferably 0.2 or more, from the viewpoint of producing a dispersion with high storage stability, and is preferably 2 or less, more preferably 1 or less, still more preferably 0.6 or less, from the same viewpoint. The mass ratio (B / A) of the content B of sterols to the content A of phospholipids in the dispersion is preferably 0.05 or more and 2 or less, more preferably 0.1 or more and 1 or less, still more preferably 0.2 or more and 0.6 or less, from the above viewpoints.

[0052] The content C of the non-steroidal oil agent in the dispersion to be produced is preferably 0.1% by mass or more, more preferably 0.5% by mass or more, still more preferably 1% by mass or more, from the viewpoint of increasing the content of the non-steroidal oil agent in the dispersion, and is preferably 10% by mass or less, more preferably 5% by mass or less, still more preferably 3% by mass or less, from the viewpoint of producing a dispersion with high storage stability. The content of the non-steroidal oil agent in the dispersion to be produced is preferably 0.1% by mass or more and 10% by mass or less, more preferably 0.5% by mass or more and 5% by mass or less, still more preferably 1% by mass or more and 3% by mass or less, from the above viewpoints.

[0053] The mass ratio (C / A) of the content C of the non-steroidal oil agent to the content A of the phospholipid in the dispersion to be produced is preferably 0.1 or more, more preferably 1 or more, still more preferably 2 or more, from the viewpoint of increasing the content C of the non-steroidal oil agent, and is preferably 15 or less, more preferably 10 or less, still more preferably 7 or less, from the viewpoint of producing a dispersion with high storage stability. The mass ratio (C / A) of the content C of the non-steroidal oil agent to the content A of the phospholipid in the dispersion is preferably 0.1 or more and 15 or less, more preferably 1 or more and 10 or less, still more preferably 2 or more and 7 or less, from the above viewpoints.

[0054] The mass ratio (B / C) of the content B of the sterol to the content C of the non-steroidal oil agent in the dispersion to be produced is preferably 0.01 or more, more preferably 0.03 or more, still more preferably 0.05 or more, from the viewpoint of producing a dispersion with high storage stability, and is preferably 0.5 or less, more preferably 0.3 or less, still more preferably 0.2 or less, from the same viewpoint. The mass ratio (B / C) of the content B of the sterol to the content C of the non-steroidal oil agent in the dispersion to be produced is preferably 0.01 or more and 0.5 or less, more preferably 0.03 or more and 0.3 or less, still more preferably 0.05 or more and 0.2 or less, from the above viewpoints.

[0055] The content D of the water-soluble solvent in the dispersion to be produced is preferably 3% by mass or more, more preferably 5% by mass or more, still more preferably 10% by mass or more, from the viewpoint of producing a dispersion with high storage stability. From the same viewpoint, it is preferably 40% by mass or less, more preferably 20% by mass or less, still more preferably 15% by mass or less. The content of the water-soluble solvent in the dispersion to be produced is preferably 3% by mass or more and 40% by mass or less, more preferably 5% by mass or more and 20% by mass or less, still more preferably 10% by mass or more and 15% by mass or less, from the above viewpoints.

[0056] The mass ratio (D / A) of the content D of the water-soluble solvent to the content A of the phospholipid in the dispersion to be produced is preferably 5 or more, more preferably 10 or more, still more preferably 15 or more, from the viewpoint of producing a dispersion with high storage stability. From the same viewpoint, it is preferably 100 or less, more preferably 60 or less, still more preferably 40 or less. The mass ratio (D / A) of the content D of the water-soluble solvent to the content A of the phospholipid in the dispersion to be produced is preferably 5 or more and 100 or less, more preferably 10 or more and 60 or less, still more preferably 15 or more and 40 or less, from the above viewpoints.

[0057] <Manufacturing method> The method for producing an oil-in-water type dispersion of the present invention is a method for producing an oil-in-water type dispersion in which a liquid oil phase containing a phospholipid, a sterol, and a non-sterol oil agent and a liquid water phase containing water are each caused to flow and a fluid obtained by combining them is passed through pores, the temperature of the combined fluid after passing through the pores is lower than the temperature of the oil phase before it combines with the water phase, and the difference obtained by subtracting the dissolution temperature of the oil phase from the temperature of the combined fluid after passing through the pores is 5°C or less.

[0058] Figure 1 shows an example of a micromixer 10 used for mixing an oil phase and a water phase.

[0059] This micromixer 10 includes a liquid supply section 11, a constriction mixing section 12 on the downstream side thereof, and a mixed liquid outflow section 13 on the further downstream side.

[0060] The liquid supply unit 11 has a double-tube structure in which a small-diameter tube 112 is introduced into a large-diameter tube 111 and they are coaxially provided. The gap between the large-diameter tube 111 and the small-diameter tube 112 is configured as a first liquid flow path P1 through which a first liquid L1 flows. The inside of the small-diameter tube 112 is configured as a second liquid flow path P2 through which a second liquid L2 flows. A first liquid inlet portion 111a provided at the upstream end of the large-diameter tube 111 is connected to a first liquid supply source (not shown). The small-diameter tube 112 is connected to a second liquid supply source (not shown).

[0061] The inside of the downstream end portion of the large-diameter tube 111 is formed in a bowl shape, and the outside of the downstream end portion of the small-diameter tube 112 is formed in a hemispherical shape, and the gap between them constitutes a part of the first liquid flow path P1. The downstream end portion of the second liquid flow path P2 inside the small-diameter tube 112 is formed in a conical hole shape that tapers toward the downstream side. A second liquid outflow hole 112a extending in the axial direction, that is, along the flow direction of the second liquid L2, is formed at the downstream end of the small-diameter tube 112. The second liquid outflow hole 112a communicates the first liquid flow path P1 and the second liquid flow path P2.

[0062] In the contraction mixing unit 12, a pore 121 extending coaxially with the second liquid outflow hole 112a, that is, along the flow direction of the second liquid L2, is formed. The pore 121 communicates the liquid supply unit 11 and the mixed liquid outflow unit 13.

[0063] The inner diameter d of the pores 121 is preferably 0.03 mm or more, more preferably 0.05 mm or more, still more preferably 0.1 mm or more, from the viewpoint of obtaining high productivity, and preferably 20 mm or less, more preferably 10 mm or less, still more preferably 7 mm or less, still more preferably 5 mm or less, still more preferably 3 mm or less, still more preferably 1 mm or less, from the viewpoint of obtaining high miscibility. The inner diameter d of the pores 121 is preferably 0.03 mm or more and 20 mm or less, more preferably 0.05 mm or more and 10 mm or less, still more preferably 0.1 mm or more and 7 mm or less. The inner diameter d of the pores 121 is preferably smaller than the inner diameter D of the second liquid outflow holes 112a. When the flow path cross-sectional shapes of the pores 121 and / or the second liquid outflow holes 112a are non-circular, the inner diameters d and D thereof are hydraulic diameters.

[0064] The length l of the pores 121 is preferably 0.05 mm or more, more preferably 0.1 mm or more, still more preferably 0.3 mm or more, from the viewpoint of obtaining high miscibility, and preferably 30 mm or less, more preferably 15 mm or less, still more preferably 10 mm or less, still more preferably 5 mm or less, still more preferably 1 mm or less, from the viewpoint of obtaining high productivity.

[0065] The ratio (l / d) of the length l of the pores 121 to the inner diameter d is preferably 0.10 or more, more preferably 0.50 or more, still more preferably 1 or more, from the viewpoint of high miscibility, and preferably 10 or less, more preferably 5 or less, still more preferably 3 or less, from the viewpoint of high productivity.

[0066] Inside the mixed liquid outflow part 13, a mixed liquid flow path P3 is formed which expands in a conical hole shape toward the downstream side and then continues in a cylindrical hole shape. The mixed liquid outflow part 13 is connected to a mixed liquid recovery part (not shown).

[0067] In this micromixer 10, in the liquid supply unit 11, the first liquid L1 flows through the first liquid flow path P1 toward the downstream side, and the second liquid L2 flows through the second liquid flow path P2 toward the downstream side. The first liquid L1 and the second liquid L2 merge near the outlet of the second liquid outlet hole 112a such that the first liquid L1 surrounds the second liquid L2 flowing out from the second liquid outlet hole 112a from all around. The merged product of the first liquid L1 and the second liquid L2 is mixed by flowing through the pores 121 in the constriction mixing unit 12. The mixed liquid L3 of the first liquid L1 and the second liquid L2 flowing out from the pores 121 flows out into the mixed liquid flow path P3 in the mixed liquid outlet unit 13.

[0068] In the method for producing a dispersion according to the embodiment, this micromixer 10 is used, and one of the liquid oil phase and the liquid water phase is used as the first liquid L1 and the other is used as the second liquid L2. The oil phase and the water phase flow and merge in the micromixer 10 (merging step), and then, their merged product flows through the pores 121 (pore flow step). At this time, the oil phase and the water phase are mixed and emulsified to form an oil-in-water type dispersion in which the oil phase is dispersed in the water phase. From the viewpoint of producing a dispersion with high stability over time, it is preferable that the oil phase is the first liquid L1 and the water phase is the second liquid L2, and they merge such that the oil phase surrounds the water phase from all around.

[0069] The inlet temperature of the oil phase to the micromixer 10, that is, the temperature of the oil phase before merging with the water phase, is preferably equal to or higher than the dissolution temperature of the oil phase from the viewpoint of flowing the oil phase and producing a dispersion with high storage stability. Specifically, it is preferably 30°C or higher, more preferably 35°C or higher, still more preferably 40°C or higher, and from the viewpoint of producing a dispersion with high storage stability, it is preferably 120°C or lower, more preferably 100°C or lower, still more preferably 90°C or lower, and still more preferably 85°C or lower. The temperature of the oil phase before merging with the water phase is preferably 30°C or higher and 120°C or lower, more preferably 35°C or higher and 100°C or lower, still more preferably 40°C or higher and 90°C or lower from the above viewpoints.

[0070] The inlet temperature of the aqueous phase to the micromixer 10, that is, the temperature of the aqueous phase before it merges with the oil phase, is preferably 0 °C or higher, more preferably 1 °C or higher, still more preferably 2 °C or higher, from the viewpoint of flowing the aqueous phase and producing a dispersion with high storage stability, and is lower than the temperature of the oil phase, preferably 60 °C or lower, more preferably 50 °C or lower, still more preferably 40 °C or lower, from the viewpoint of cooling the oil phase and producing a dispersion with high storage stability. The temperature of the aqueous phase before it merges with the oil phase is preferably 0 °C or higher and 60 °C or lower, more preferably 1 °C or higher and 50 °C or lower, still more preferably 2 °C or higher and 40 °C or lower, from the above viewpoints.

[0071] The total flow rate of the merged fluid of the oil phase and the aqueous phase that have merged in the micromixer 10 is preferably 10 g / min or higher, more preferably 50 g / min or higher, still more preferably 100 g / min or higher, from the viewpoint of producing a dispersion with high storage stability, and is preferably 500000 g / min or lower, more preferably 400000 g / min or lower, still more preferably 200000 g / min or lower, still more preferably 100000 g / min or lower, particularly preferably 50000 g / min or lower, even more particularly preferably 25000 g / min or lower, from the same viewpoint.

[0072] The content of the oil phase in the total flow rate is preferably more than 0% by mass, more preferably 3% by mass or higher, still more preferably 10% by mass or higher, from the viewpoint of increasing the oil phase content in the dispersion to be produced, and is preferably 30% by mass or lower, more preferably 20% by mass or lower, still more preferably 15% by mass or lower, from the viewpoint of producing a dispersion with high storage stability.

[0073] The outlet temperature of the dispersion flowing out from the micromixer 10, that is, the temperature of the combined fluid (dispersion) of the oil phase and the water phase after flowing through the pores 121 and flowing out into the mixed liquid flow path P3, is lower than the temperature of the oil phase before it merges with the water phase. Specifically, from the viewpoint of cooling the oil phase and producing a dispersion with high storage stability, the temperature of the combined fluid (dispersion) of the oil phase and the water phase after flowing through the pores 121 is preferably 0 °C or higher, more preferably 5 °C or higher, still more preferably 10 °C or higher. From the same viewpoint, it is preferably 60 °C or lower, more preferably 50 °C or lower, still more preferably 45 °C or lower. From the above viewpoints, the temperature of the combined fluid (dispersion) of the oil phase and the water phase after flowing through the pores 121 is preferably 0 °C or higher and 60 °C or lower, more preferably 5 °C or higher and 50 °C or lower, still more preferably 10 °C or higher and 45 °C or lower.

[0074] The difference obtained by subtracting the temperature of the combined fluid (dispersion) of the oil phase and the water phase after flowing through the pores 121 (i.e., the outlet temperature of the dispersion flowing out from the micromixer 10) from the temperature of the oil phase before it merges with the water phase (i.e., the inlet temperature of the oil phase to the micromixer 10) is preferably 5 °C or higher, more preferably 10 °C or higher, still more preferably 15 °C or higher, even more preferably 16 °C or higher from the viewpoint of depositing phospholipids at the interface between the oil phase and the water phase and stabilizing the oil phase in the dispersion. From the viewpoint of ease of production, it is preferably 90 °C or lower, more preferably 80 °C or lower, still more preferably 70 °C or lower. From the above viewpoints, the difference obtained by subtracting the temperature of the combined fluid (dispersion) of the oil phase and the water phase after flowing through the pores 121 from the temperature of the oil phase before it merges with the water phase is preferably 5 °C or higher and 90 °C or lower, more preferably 10 °C or higher and 80 °C or lower, still more preferably 15 °C or higher and 70 °C or lower, even more preferably 16 °C or higher and 70 °C or lower.

[0075] The difference obtained by subtracting the melting temperature of the oil phase from the temperature of the combined fluid (dispersion) of the oil phase and the aqueous phase after passing through the pores 121 is 5°C or lower, and from the viewpoint of depositing a trace amount of phospholipid at the interface between the oil phase and the aqueous phase, rapidly stabilizing the oil phase in the dispersion, and producing a dispersion with high storage stability, it is preferably 3°C or lower, more preferably 0°C or lower, still more preferably -5°C or lower, and even more preferably -10°C or lower. From the viewpoint of ease of production, it may be -35°C or higher. That the difference obtained by subtracting the melting temperature of the oil phase from the temperature of the combined fluid (dispersion) is -5°C or lower means that the temperature of the combined fluid (dispersion) is cooled to 5°C or lower lower than the melting temperature of the oil phase. The same applies to -10°C or lower. Thereby, it is considered that phospholipids are likely to precipitate and the oil phase is stabilized.

[0076] From the viewpoint of producing a dispersion with high stability over time, the average particle diameter of the oil phase in the dispersion after production recovered from the micromixer 10 is preferably 100 nm or less, more preferably 95 nm or less, still more preferably 90 nm or less, and the lower limit is preferably 10 nm or more. Here, this average particle diameter is the cumulant diameter measured by the photon correlation method (dynamic light scattering method).

[0077] The rate of change in particle diameter from the average particle diameter of the oil phase in the dispersion at the time of production to the average particle diameter of the oil phase in the dispersion stored statically in a 40°C atmosphere for 1 month or more after production is preferably less than 10%, more preferably 5% or less, still more preferably 3% or less. Here, the rate of change in particle diameter is calculated based on the following formula. Rate of change in particle diameter [%] = {(Average particle diameter of the oil phase after static storage - Average particle diameter of the oil phase at the time of production) / Average particle diameter of the oil phase at the time of production} × 100

[0078] The shear rate (shear rate in the pores 10 of the micromixer) when flowing a fluid obtained by combining a liquid oil phase and an aqueous phase containing water and an acid through the pores is preferably 3000 s -1 or more, more preferably 5000 s -1 or more, more preferably 10,000 s -1The above, and from the viewpoint of reducing the device load, it is preferably 300,000 s -1 or less, more preferably 200,000 s -1 or less, still more preferably 100,000 s -1 or less. This shear rate is calculated by dividing the linear velocity of the confluent fluid by the inner diameter of the nozzle (linear velocity / inner diameter of the nozzle). The linear velocity is obtained by flow rate / pore area.

[0079] In the above embodiment, the micromixer 10 having a double-tube structure is used, but it is not particularly limited thereto, and micromixers 20 and 30 having a T-tube structure as shown in FIGS. 2 and 3 may also be used.

[0080] In the micromixer 20 having the T-tube structure shown in FIG. 2, one side of the main pipe is configured as the first liquid supply part 21 and the other side is configured as the second liquid supply part 22, and their interiors are respectively configured as the first liquid flow path P1 and the second liquid flow path P2. The tip flow side part of the branch pipe is configured as the mixed liquid outflow part 23, and its interior is configured as the mixed liquid flow path P3. Fine holes 24 are formed inside the base end side part of the branch pipe. The fine holes 24 communicate the first liquid flow path P1 and the second liquid flow path P2 with the mixed liquid flow path P3. In this micromixer 20, the first liquid L1 flowing through the first liquid flow path P1 of the first liquid supply part 21 and the second liquid L2 flowing through the second liquid flow path P2 of the second liquid supply part 22 collide head-on and merge, and their confluent product flows through the fine holes 24 extending in a direction orthogonal to the flow directions of the first liquid L1 and the second liquid L2 and is mixed.

[0081] In the micromixer 30 having a T-shaped tube structure shown in FIG. 3, one side of the main tube is configured as the first liquid supply section 31 and the branch tube is configured as the second liquid supply section 32, and their interiors are respectively configured as the first liquid flow path P1 and the second liquid flow path P2. The tip-side portion on the other side of the main tube is configured as the mixed liquid outflow section 33, and its interior is configured as the mixed liquid flow path P3. Pores 34 are formed inside the base-end side portion on the other side of the main tube. The pores 34 communicate the first liquid flow path P1 and the second liquid flow path P2 with the mixed liquid flow path P3. In this micromixer 30, the first liquid L1 flowing through the first liquid flow path P1 of the first liquid supply section 31 collides with and merges with the second liquid L2 flowing through the second liquid flow path P2 of the second liquid supply section 22 from the orthogonal direction thereto, and the merged product thereof flows through the pores 34 extending in the flowing direction of the first liquid L1 and is mixed.

[0082] The present invention includes the following aspects.

[0083] 〔1〕A merging step of flowing a liquid oil phase containing a phospholipid, sterols, and a non-sterol oil agent and a liquid water phase containing water, respectively, and merging them; A pore flow step of flowing the fluid obtained by merging the oil phase and the water phase in the merging step through pores; A method for producing an oil-in-water type dispersion liquid, comprising: The temperature of the merged fluid of the oil phase and the water phase after flowing through the pores in the pore flow step is lower than the temperature of the oil phase before merging with the water phase in the merging step, and the difference obtained by subtracting the dissolution temperature of the oil phase from the temperature of the merged fluid of the oil phase and the water phase after flowing through the pores is 5°C or less.

[0084] 〔2〕The production method according to 〔1〕, wherein the difference obtained by subtracting the dissolution temperature of the oil phase from the temperature of the merged fluid of the oil phase and the water phase after flowing through the pores is 0°C or less.

[0085] 〔3〕The method for producing the dispersion according to 〔1〕or〔2〕, wherein the difference obtained by subtracting the dissolution temperature of the oil phase from the temperature of the combined fluid of the oil phase and the aqueous phase after passing through the pores is -5°C or lower.

[0086] 〔4〕The method for producing the dispersion according to any one of 〔1〕to〔3〕, wherein the difference obtained by subtracting the temperature of the combined fluid of the oil phase and the aqueous phase after passing through the pores from the temperature of the oil phase before merging with the aqueous phase is 5°C or higher.

[0087] 〔5〕The method for producing the dispersion according to any one of 〔1〕to〔4〕, wherein the difference obtained by subtracting the temperature of the combined fluid of the oil phase and the aqueous phase after passing through the pores from the temperature of the oil phase before merging with the aqueous phase is 5°C or higher, and the difference obtained by subtracting the dissolution temperature of the oil phase from the temperature of the combined fluid of the oil phase and the aqueous phase after passing through the pores is -5°C or lower.

[0088] 〔6〕The method for producing the dispersion according to any one of 〔1〕to〔5〕, wherein the dispersion substantially does not contain surfactants other than phospholipids.

[0089] 〔7〕The method for producing the dispersion according to any one of 〔1〕to〔6〕, wherein the non-steroidal oil agent contains a liquid oil that is liquid at 20°C.

[0090] 〔8〕The method for producing the dispersion according to any one of 〔1〕to〔7〕, wherein the mass ratio of the content of the sterols to the content of the phospholipids in the oil phase is 0.05 or more and 2 or less.

[0091] 〔9〕The method for producing the dispersion according to any one of 〔1〕to〔8〕, wherein the mass ratio of the content of the non-steroidal oil agent to the content of the phospholipids in the oil phase is 15 or less.

[0092] 〔10〕The method for producing the dispersion according to any one of 〔1〕to〔9〕, wherein the mass ratio of the content of the sterols to the content of the non-steroidal oil agent in the oil phase is 0.01 or more.

[0093] 〔11〕The method for producing the dispersion according to any one of 〔1〕to 〔10〕, wherein the phospholipid contains hydrogenated lecithin.

[0094] 〔12〕The method for producing the dispersion according to any one of 〔1〕to 〔11〕, wherein the non-steroidal oil agent contains a triglyceride of a fatty acid having a branched alkyl group with 5 to 21 carbon atoms.

[0095] 〔13〕The method for producing the dispersion according to any one of 〔1〕to 〔12〕, wherein the sterols contain cholesterol.

[0096] 〔14〕The method for producing the dispersion according to any one of 〔1〕to 〔13〕, wherein the inner diameter of the pores is 0.03 mm or more and 20 mm or less.

Examples

[0097] (Dispersion production apparatus) A micromixer having the same structure as that shown in FIG. 1 was prepared. In Example 1 and Comparative Example 1, the inner diameter of the pores of the micromixer was 0.4 mm, the length was 1 mm, and the ratio of the length to the inner diameter was 2.5. In Examples 2 to 10 and Comparative Examples 2 to 3, the inner diameter of the pores of the micromixer was 0.6 mm, the length was 1.5 mm, and the ratio of the length to the inner diameter was 2.5. In Example 14, the inner diameter of the pores of the micromixer was 4.0 mm, the length was 10 mm, and the ratio of the length to the inner diameter was 2.5. In Example 15, the inner diameter of the pores of the micromixer was 4.5 mm, the length was 11.25 mm, and the ratio of the length to the inner diameter was 2.5. Then, the first liquid inlet of the large-diameter tube of this micromixer was connected to an oil-phase storage tank via an oil-phase supply line, the small-diameter tube was connected to an aqueous-phase storage tank via an aqueous-phase supply line, and the mixed liquid outlet was connected to a dispersion recovery tank via a dispersion recovery line to construct a dispersion production apparatus.

[0098] A heat exchanger for controlling the temperature of the oil phase supplied to the micromixer was provided at the connection part between the oil phase supply line and the micromixer. Similarly, a heat exchanger for controlling the temperature of the aqueous phase supplied to the micromixer was provided at the connection part between the aqueous phase supply line and the micromixer. A temperature sensor for measuring the temperature of the dispersion obtained by mixing the oil phase and the aqueous phase in the micromixer was provided at the connection part between the dispersion recovery line and the micromixer.

[0099] (Oil phase and aqueous phase) As Oil Phase 1, a mixed solution prepared by mixing hydrogenated soybean phospholipid (COATSOME NC-21, manufactured by NOF Corporation, phospholipid content 90% by mass), cholesterol (Cholesterol JSQI, manufactured by Nippon Seika Chemical Co., Ltd.), glyceryl tri-2-ethylhexanoate (T.I.O, manufactured by Nisshin Oillio Group, Ltd.) and dipropylene glycol (DPG-RF, manufactured by ADEKA Corporation) in the composition shown in Table 1A was prepared.

[0100] Oil Phase 1 was charged into a transparent screw tube and placed in a thermostatic bath. Visual appearance inspection was performed while varying the temperature by 1°C per day when it was left standing at a constant temperature for 1 day. The lowest temperature at which the liquid was clear and had no turbidity in appearance was 25°C. Therefore, the dissolution temperature of this Oil Phase 1 is 25°C.

[0101] As Oil Phase 2, a mixed solution having the composition shown in Table 1B was prepared. The dissolution temperature of Oil Phase 2 measured in the same manner as Oil Phase 1 was 36°C.

[0102]

Table 1A

[0103]

Table 1B

[0104] As Aqueous Phase 1, deionized water was prepared.

[0105] As the aqueous phase 2, a mixed solution prepared by mixing disodium hydrogen orthophosphate dodecahydrate (monosodium hydrogen phosphate, manufactured by Taihei Chemical Industry Co., Ltd.), potassium dihydrogen phosphate (monopotassium phosphate, manufactured by Yoneyama Chemical Industry Co., Ltd.), ethylene glycol monophenyl ether (Hysorb EPH, manufactured by Toho Chemical Industry Co., Ltd.) and deionized water in the composition shown in Table 2 was prepared.

[0106]

Table 2

[0107] (Evaluation method of dispersion liquid) <Average particle size of oil phase> Regarding the dispersion liquid during production, the cumulant diameter of the oil phase was measured by the photon correlation method (dynamic light scattering method) using a particle size distribution measuring device (ELS-Z, manufactured by Otsuka Electronics Co., Ltd.), and it was taken as the average particle size of the oil phase in the dispersion liquid during production. The measurement conditions were: temperature 25°C, angle between the incident light and the detector 90°, number of integrations 100 times, and the refractive index of water (1.333) was input as the refractive index of the dispersion solvent. For the measurement sample, the dispersion liquid was weighed into a screw tube (No. 5, manufactured by Maruemu Co., Ltd.), water was added so that the solid content concentration became 2×10 -4 mass%, and the mixture was stirred at 25°C and used.

[0108] <Rate of change in particle size> Regarding the prepared dispersion liquid, the average particle size of the oil phase was measured when it was left standing and stored in an atmosphere at 40°C for a predetermined period after production. Then, the rate of change in particle size from the average particle size of the oil phase in the dispersion liquid during production was calculated based on the following formula. Rate of change in particle size [%] = {(Average particle size of the oil phase after standing storage - Average particle size of the oil phase during production) / Average particle size of the oil phase during production} × 100

[0109] (Operation and results) <Example 1 and Comparative Example 1> In Example 1 and Comparative Example 1, the oil phase 1 was charged into an oil phase storage tank, and the liquid temperature was adjusted to 80°C. The aqueous phase 1 was charged into an aqueous phase storage tank, and the liquid temperature was maintained at room temperature. Then, the oil phase 1 and the aqueous phase 1 were supplied to a micromixer to produce a dispersion. At this time, the flow rate was controlled so that the total flow rate was 120 g / min and the composition was as shown in Table 3. Further, as shown in Table 4, the inlet temperature of the oil phase 1 to the micromixer, which was the temperature of the oil phase 1 before merging with the aqueous phase 1, was controlled by a heat exchanger provided in the oil phase supply line. The inlet temperature of the aqueous phase 1 to the micromixer, which was the temperature of the aqueous phase 1 before merging with the oil phase 1, was controlled by a heat exchanger provided in the aqueous phase supply line. The outlet temperature of the dispersion flowing out from the micromixer, which was the temperature of the merged fluid of the oil phase 1 and the aqueous phase 1 after flowing through the pores, was measured by a temperature sensor provided in the dispersion recovery line.

[0110]

Table 3

[0111]

Table 4

[0112] For each of Example 1 and Comparative Example 1, Table 4 shows the rate of change in particle size from the time of production of the average particle size of the oil phase in the dispersion that was allowed to stand and stored in a 40°C atmosphere for 1.5 months after production.

[0113] <Examples 2 to 9 and Comparative Examples 2 to 3> In Examples 2 to 9 and Comparative Examples 2 to 3, the oil phase 2 having the composition shown in Table 1B and the aqueous phase 2 having the composition shown in Table 2 were used. A dispersion was produced in the same manner as in Example 1, except that the flow rate was controlled so that the total flow rate was 170 g / min and the composition was as shown in Table 5, and the temperature settings shown in Table 6 were made.

[0114]

Table 5

[0115]

Table 6

[0116] For each of Examples 2 to 9 and Comparative Examples 2 to 3, Table 6 shows the rate of change in the particle size of the oil phase from the production time in the dispersion liquid that was allowed to stand and stored in a 40°C atmosphere for 1.5 months after production.

[0117] <Examples 10 and 11> In Examples 10 and 11, an oil phase 2 having the composition shown in Table 1B and an aqueous phase 2 having the composition shown in Table 2 were used. The total flow rate was controlled to be 1100 kg / h and the composition shown in Table 5, and a dispersion liquid was produced in the same manner as in Example 1 except that the temperature settings shown in Table 7 were performed.

[0118]

Table 7

[0119] For each of Examples 10 and 11, Table 7 shows the rate of change in the particle size of the oil phase from the production time in the dispersion liquid that was allowed to stand and stored in a 40°C atmosphere for 3 months after production.

[0120] <Comparative Example 4> Similar to Example 1, an oil phase 1 having the composition shown in Table 1A and an aqueous phase 1 of deionized water were prepared. The temperature of the oil phase 1 was controlled to 80°C and the temperature of the aqueous phase 1 was controlled to 40°C. After mixing them, pre-emulsification was carried out by mixing at a rotation speed of 8000 r / min for 15 minutes using a homomixer (manufactured by Primix Corporation, TK Robomix). Then, the pre-emulsion was put into a nanomizer (manufactured by Yoshida Kikai Kogyo Co., Ltd., NM2-L200), which is a high-pressure emulsifier, and carried out under the conditions of a discharge pressure of 100 MPa and 5 passes. Table 8 shows the particle size at the time of production and the rate of change in the particle size after 1 month at 40°C.

[0121] (Discussion) In Examples 1 to 7, 10, and 11, where the difference obtained by subtracting the temperature of the confluent fluid after passing through the pores from the temperature of the oil phase before merging with the aqueous phase is 5°C or more and the difference obtained by subtracting the dissolution temperature of the oil phase from the temperature of the confluent fluid after passing through the pores is -5°C or less, it can be seen that the particle size change rate is remarkably excellent.

[0122] In Comparative Example 2, there is no difference between the temperature of the oil phase before merging with the aqueous phase and the temperature of the confluent fluid after passing through the pores. In Comparative Example 3, the temperature of the confluent fluid after passing through the pores is 11°C higher than the dissolution temperature of the oil phase. It is considered that this is because the stabilization of the oil phase by phospholipids did not proceed.

[0123]

Table 8

Industrial Applicability

[0124] The present invention is useful in the technical field of a method for producing a dispersion.

Explanation of Signs

[0125] 10, 20, 30 micromixer 11 liquid supply section 111 large-diameter pipe 111a first liquid inflow section 112 small-diameter pipe 112a second liquid outflow hole 12 constriction mixing section 121, 24, 34 pores 13, 23, 33 mixed liquid outflow section 21, 31 first liquid supply section 22, 32 second liquid supply section L1 first liquid L2 second liquid L3 mixed liquid P1 first liquid flow path P2 second liquid flow path P3 mixed liquid flow path

Claims

1. A confluence step of flowing a liquid oil phase containing a phospholipid, sterols, and a non-sterol oil agent and a liquid aqueous phase containing water, respectively, and then confluencing them; A pore flow step of flowing the fluid obtained by confluencing the oil phase and the aqueous phase in the confluence step through pores; A method for producing an oil-in-water dispersion, comprising: The temperature of the confluent fluid of the oil phase and the aqueous phase after flowing through the pores in the pore flow step is lower than the temperature of the oil phase before confluencing with the aqueous phase in the confluence step, and the difference obtained by subtracting the dissolution temperature of the oil phase from the temperature of the confluent fluid of the oil phase and the aqueous phase after flowing through the pores is 5°C or less. A method for producing a dispersion.

2. The method for producing a dispersion according to claim 1, wherein the difference obtained by subtracting the dissolution temperature of the oil phase from the temperature of the confluent fluid of the oil phase and the aqueous phase after flowing through the pores is 0°C or less.

3. The method for producing a dispersion according to claim 1 or 2, wherein the difference obtained by subtracting the dissolution temperature of the oil phase from the temperature of the confluent fluid of the oil phase and the aqueous phase after flowing through the pores is -5°C or less.

4. The method for producing a dispersion according to any one of claims 1 to 3, wherein the difference obtained by subtracting the temperature of the confluent fluid of the oil phase and the aqueous phase after flowing through the pores from the temperature of the oil phase before confluencing with the aqueous phase is 5°C or more.

5. The method for producing a dispersion according to any one of claims 1 to 4, wherein the difference obtained by subtracting the temperature of the confluent fluid of the oil phase and the aqueous phase after flowing through the pores from the temperature of the oil phase before confluencing with the aqueous phase is 5°C or more, and the difference obtained by subtracting the dissolution temperature of the oil phase from the temperature of the confluent fluid of the oil phase and the aqueous phase after flowing through the pores is -5°C or less.

6. The method for producing a dispersion according to any one of claims 1 to 5, wherein the dispersion substantially does not contain a surfactant other than phospholipids.

7. The method for producing a dispersion according to any one of claims 1 to 6, wherein the non-sterol oil agent contains a liquid oil that is liquid at 20°C.

8. The method for producing a dispersion according to any one of claims 1 to 7, wherein the mass ratio of the content of sterols to the content of phospholipids in the oil phase is 0.05 or more and 2 or less.

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