Microcapsules

Abstract

To provide microcapsules having a small mean particle diameter and high biological safety.SOLUTION: A microcapsule is composed of gelatin, an anionic polymer, a polyvalent metal salt, and a nonionic surfactant with a HLB value of 12 or more, and includes a core material.SELECTED DRAWING: None

Description

[Technical Field]

[0001] The present invention relates to a microcapsule and a method for producing the same. [Background technology]

[0002] Microcapsules are constructed by enclosing a target component as a core substance within a wall material. One method for manufacturing microcapsules is to apply the coacervation method. Furthermore, there are two types of coacervation methods: simple coacervation, in which the wall material is made of only one type of polymer, and complex coacervation, in which the wall material is made of two or more types of polymer. In the complex coacervation method, the wall material is made of anionic polymers and cationic polymers. The complex coacervation method is suitable for manufacturing microcapsules with strong wall materials.

[0003] When producing microcapsules using the complex coacervation method, a crosslinking agent is usually applied to the wall material encapsulating the core substance, thereby crosslinking the components of the wall material to improve the strength of the microcapsules. However, during this process, aggregation or coalescence of the microcapsules and the wall material components during their formation tends to increase the particle size of the final microcapsules. Such microcapsules with large particle sizes can be easily visually recognized, which can limit their applications.

[0004] On the other hand, formaldehyde, glutaraldehyde, etc. are well known as crosslinking agents, and it has been disclosed that by using these, small microcapsules having an average particle size of, for example, 20 μm or less can be produced (see Patent Document 1). [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Special Publication No. 2015-518031 Summary of the Invention [Problem to be solved by the invention]

[0006] However, because these crosslinking agents (formaldehyde, glutaraldehyde, etc.) are highly toxic, the microcapsules obtained using these crosslinking agents have low safety for living organisms, and therefore cannot be used for purposes such as skin contact (e.g., topical preparations, cosmetics, etc.), let alone for consumption.

[0007] An object of the present invention is to provide microcapsules that have a small average particle size and are highly safe for living organisms. [Means for solving the problem]

[0008] A first aspect of the present invention is a microcapsule comprising gelatin, an anionic polymer, a polyvalent metal salt, and a nonionic surfactant having an HLB value of 12 or more, and encapsulating a core substance.

[0009] A second aspect of the present invention includes a step of preparing an emulsion by mixing gelatin and a core substance in the presence of water, a step of preparing a mixed solution (A) by mixing an anionic polymer and the emulsion in the presence of water, a step of preparing an acidic mixed solution (1B) by mixing the mixed solution (A) with an acid, a step of preparing a mixed solution (1B) by mixing the mixed solution (1B) with water, and a step of preparing a mixed solution (1C) by mixing the mixed solution (1C) with an acid having an HLB value of 1. The method for producing microcapsules includes the steps of: preparing a mixed solution (1D) by mixing two or more nonionic surfactants; cooling the mixed solution (1D) to a temperature of 10°C or less; mixing the cooled mixed solution (1D) with a polyvalent metal salt to prepare a mixed solution (1E); and mixing the mixed solution (1E) with a base to prepare an aqueous dispersion of microcapsules having an adjusted pH. A third aspect of the present invention is a method for producing a emulsion by mixing gelatin and a core substance in the presence of water, a method for producing a mixed liquid (A) by mixing an anionic polymer and the emulsion in the presence of water, a method for producing a mixed liquid (2B) by mixing the mixed liquid (A) with water, a method for producing an acidic mixed liquid (2C) by mixing the mixed liquid (2B) with an acid, and a method for producing an acidic mixed liquid (2C) by mixing the mixed liquid (2C) with an anionic polymer having an HLB value of 1. The method for producing microcapsules includes the steps of: preparing a mixed solution (2D) by mixing two or more nonionic surfactants; cooling the mixed solution (2D) until its temperature reaches 10°C or less; mixing the cooled mixed solution (2D) with a polyvalent metal salt to prepare a mixed solution (2E); and mixing the mixed solution (2E) with a base to prepare an aqueous dispersion of microcapsules with an adjusted pH. [Effects of the Invention]

[0010] According to the present invention, microcapsules having a small average particle size and high safety to living organisms are provided. DETAILED DESCRIPTION OF THE INVENTION

[0011] <<Microcapsules>> The microcapsules according to one embodiment of the present invention are composed of gelatin, an anionic polymer, a polyvalent metal salt, and a nonionic surfactant with an HLB (Hydrophilic-Lipophilic Balance) value of 12 or more, and encapsulate a core substance.

[0012] The microcapsules of this embodiment are highly safe for living organisms because they are produced without the use of highly toxic components such as formaldehyde and glutaraldehyde. Furthermore, the average particle size of the microcapsules of this embodiment is small. The reason why the microcapsules of this embodiment have a small average particle size and are highly safe for living organisms is because a nonionic surfactant with an HLB value of 12 or more is used in their production. By using a nonionic surfactant with an HLB value of 12 or more, microcapsules with a small average particle size can be obtained using a polyvalent metal salt without using components such as formaldehyde and glutaraldehyde.

[0013] In this specification, a "nonionic surfactant having an HLB value of 12 or more" may be simply referred to as a "nonionic surfactant."

[0014] The microcapsules of this embodiment are highly safe for living organisms and are therefore particularly suitable for use in applications that come into contact with the skin (for example, topical preparations, cosmetics, etc.).

[0015] The microcapsules of this embodiment are configured by encapsulating a core substance within a wall material. The microcapsules can be produced by applying a complex coacervation method, as described below. The gelatin and the anionic polymer are components constituting the wall material of the microcapsules (sometimes abbreviated as "wall material components" in this specification), and form the wall material by a complex coacervation method.

[0016] ◎Wall materials and wall material components As described above, the wall material is composed of the gelatin and the anionic polymer, and the polyvalent metal salt contributes to maintaining the strong structure of the wall material.

[0017] <Gelatin> The gelatin, together with the anionic polymer, serves as a wall component of the microcapsules. The gelatin that constitutes the wall material is a cationic polymer that has cationic moieties in its molecules.

[0018] As the gelatin, conventional gelatin such as that derived from animal bones or skin can be used. The molecular weight of the gelatin may be, for example, 20,000 to 9,000,000.

[0019] Gelatin is an amphoteric polymer that can be either cationic or anionic, and is therefore used after being cationized by the action of an acid, as will be described later.

[0020] The gelatin constituting the microcapsules may be of one type or two or more types, and when two or more types are used, the combination and ratio thereof can be selected arbitrarily.

[0021] <Anionic polymer> The anionic polymer is a polymer having an anionic moiety in its molecule, and serves as a wall material component of the microcapsules together with gelatin.

[0022] The anionic polymer is not particularly limited as long as it is a polymer having an anionic group. Examples of anionic polymers include polymers having groups in which acid groups are dissociated (anionized), such as groups in which carboxy groups (-C(=O)-OH) are dissociated (anionized), i.e., carboxylate anions (-C(=O)-O - ) is preferred. In one molecule of an anionic polymer, some or all of the anionic groups may form a salt together with a cation.

[0023] In an anionic polymer, the cation forming a salt with the anionic group (anionized group) is preferably a metal ion. The metal ion may be either a monovalent metal ion or a metal ion with a valence of two or more (a polyvalent metal ion), but is preferably a monovalent metal ion.

[0024] Examples of the monovalent metal ions include sodium ions (Na + ), potassium ions (K + ), lithium ion (Li + ) and other alkali metal ions. Examples of the polyvalent metal ions include calcium ions (Ca 2+ ), magnesium ions (Mg 2+ ) and other alkaline earth metal ions.

[0025] Examples of anionic polymers include gum arabic, sodium alginate, sodium carboxymethylcellulose, xanthan gum, and pectin.

[0026] The molecular weight of the anionic polymer is not particularly limited and may be, for example, 20,000 to 50,000,000. The molecular weight of the anionic polymer may vary depending on the type of anionic polymer. For example, the molecular weight of gum arabic may be 200,000 to 2,000,000, the molecular weight of sodium alginate may be 40,000 to 4,000,000, the molecular weight of sodium carboxymethylcellulose may be 20,000 to 400,000, the molecular weight of xanthan gum may be 2,000,000 to 50,000,000, and the molecular weight of pectin may be 50,000 to 360,000.

[0027] The anionic polymer constituting the microcapsules may be of only one type, or may be of two or more types, and when two or more types are used, the combination and ratio thereof can be selected arbitrarily.

[0028] In the microcapsules, the content of the anionic polymer is preferably 10 to 1000 parts by mass with respect to 100 parts by mass of the gelatin content. For example, it may be any of 10 to 700 parts by mass, 10 to 400 parts by mass, 10 to 150 parts by mass, and 10 to 70 parts by mass, or any of 300 to 1000 parts by mass, 600 to 1000 parts by mass, and 800 to 1000 parts by mass, or may be 300 to 700 parts by mass. When the content of the anionic polymer is within such a range, the amount of the anionic polymer or gelatin that does not contribute to the composition of the wall material can be reduced.

[0029] <Nonionic surfactant with an HLB value of 12 or more> By including a nonionic surfactant with an HLB value of 12 or more in the microcapsules, aggregation and coalescence of the microcapsules themselves are suppressed, and aggregation and coalescence of the wall material components in the process of forming the microcapsules are also suppressed. Furthermore, the average particle diameter of the microcapsules becomes smaller. It is presumed that part or all of the nonionic surfactant adheres to the wall material in the microcapsules, particularly to the surface on the outer side of the wall material (in other words, the side opposite to the side enclosing the core material of the wall material).

[0030] The HLB value of the nonionic surfactant may be 12 or more. For example, it may be any of 12.5 or more, 14 or more, 15.5 or more, and 17 or more. The upper limit value of the HLB value of the nonionic surfactant is not particularly limited. The HLB value of the nonionic surfactant may be, for example, any of 19 or less, 18 or less, 16.5 or less, 15 or less, and 13.5 or less.

[0031] The HLB value of the nonionic surfactant may be within a range set by any combination of any of the above-mentioned lower limits and any of the above-mentioned upper limits. For example, in one embodiment, the HLB value of the nonionic surfactant may be any of 12 to 19, 12.5 to 19, 14 to 19, 15.5 to 19, and 17 to 19, or any of 12 to 18, 12 to 16.5, 12 to 15, and 12 to 13.5, or any of 12.5 to 18 and 14 to 16.5.

[0032] In this specification, unless otherwise specified, the "HLB value" is a value calculated by the Griffin method.

[0033] The nonionic surfactant is not particularly limited as long as it has an HLB value of 12 or more. Examples of nonionic surfactants include polyoxyethylene polyoxypropylene block polymers, polyoxyalkylene styrenated phenyl ethers, and polyoxyalkylene alkyl ethers.

[0034] Examples of the polyoxyethylene polyoxypropylene block polymer include those represented by the following general formula (G3): HO-(CH2CH2O) m2 -(CH2CH(CH3)O) n2 -(CH2CH2O) l2 -H (G3) (In general formula (G3), m2, n2 and l2 each independently represent an integer of 2 or more.)

[0035] Examples of the polyoxyalkylene styrenated phenyl ether include polyoxyethylene styrenated phenyl ether. Examples of the polyoxyalkylene alkyl ether include polyoxyethylene alkyl ether.

[0036] The nonionic surfactant constituting the microcapsules may be of only one type, or may be of two or more types, and when two or more types are used, the combination and ratio thereof can be selected arbitrarily.

[0037] In the microcapsules, the content of the nonionic surfactant may be, for example, 3 to 25 parts by mass, 5 to 20 parts by mass, or 7 to 16 parts by mass, relative to 100 parts by mass of the total content of gelatin and anionic polymer. When the content of the nonionic surfactant is equal to or greater than the lower limit, aggregation and coalescence of the microcapsules and the wall material components in the process of forming the microcapsules are further suppressed, and the average particle size of the microcapsules becomes smaller. When the content of the nonionic surfactant is equal to or less than the upper limit, excessive use of the nonionic surfactant is suppressed.

[0038] <Polyvalent metal salts> The microcapsules contain the polyvalent metal salt, making the wall material thereof strong. It is presumed that part or all of the polyvalent metal salt contributes to binding the wall material components together in the microcapsules. More specifically, it is presumed that the polyvalent metal ions in the polyvalent metal salt are interposed between different sites in one molecule of the wall material component, connecting these sites together through electrical attraction, or are interposed between two molecules of the wall material component, connecting these two molecules together through electrical attraction. In other words, it is presumed that the polyvalent metal salt exhibits the same effect as known crosslinking agents, and in this specification, such polyvalent metal salts are sometimes referred to as crosslinking agents.

[0039] The polyvalent metal salt is not particularly limited as long as it contains a metal ion with a valence of two or more (polyvalent metal ion) as a constituent component. For example, the polyvalent metal salt may be either a polyvalent metal inorganic salt or a polyvalent metal organic salt. The polyvalent metal salt may be either a hydrate or a non-hydrate.

[0040] Examples of the polyvalent metal inorganic salts include sulfates such as aluminum sulfate (Al2(SO4)3), zirconium sulfate (Zr(SO4)2), calcium sulfate (CaSO4), magnesium sulfate (MgSO4), aluminum potassium sulfate (potassium alum, AlK(SO4)2), and aluminum ammonium sulfate (ammonium alum, AlNH4(SO4)3); hydrochlorides such as calcium chloride (CaCl2), magnesium chloride (MgCl2), aluminum chloride (AlCl3), barium chloride (BaCl2), and zinc chloride (ZnCl2); and nitrates such as calcium nitrate (Ca(NO3)2).

[0041] Examples of the polyvalent metal organic salt include acetates such as magnesium acetate ((CH3COO)2Mg) and calcium acetate ((CH3COO)2Ca).

[0042] Examples of the polyvalent metal salts include aluminum salts (Al salts), zirconium salts (Zr salts), calcium salts (Ca salts), magnesium salts (Mg salts), barium salts (Ba salts), and zinc salts (Zn salts), regardless of whether they are inorganic or organic salts of polyvalent metals.

[0043] The polyvalent metal salt constituting the microcapsules may be of only one type or of two or more types, and when two or more types are used, the combination and ratio thereof can be selected arbitrarily.

[0044] In the microcapsules, the content of the polyvalent metal salt may be any of 30 to 95 parts by mass, 40 to 85 parts by mass, and 50 to 75 parts by mass, relative to 100 parts by mass of the total content of gelatin and anionic polymer. When the content of the polyvalent metal salt is equal to or greater than the lower limit, the wall material of the microcapsules becomes stronger. When the content of the polyvalent metal salt is equal to or less than the upper limit, excessive use of the polyvalent metal salt is suppressed.

[0045] <Cationic polymers other than gelatin> The wall material in the microcapsules may be composed of a cationic polymer other than gelatin (which may be referred to as "other cationic polymer" in this specification) as long as the effects of the present invention are not impaired.

[0046] The other cationic polymer is not particularly limited. Examples of the other cationic polymer include chitosan, casein, polyethyleneimine, cation-modified polyvinyl alcohol, and the like.

[0047] The other cationic polymer constituting the microcapsules may be only one kind or two or more kinds. In the case of two or more kinds, their combinations and ratios can be arbitrarily selected.

[0048] In the microcapsules, the content of the other cationic polymer is preferably 5 parts by mass or less, more preferably 3 parts by mass or less, still more preferably 1 part by mass or less, and particularly preferably 0 part by mass (that is, the microcapsules do not contain the other cationic polymer) with respect to 100 parts by mass of the gelatin content. When the content of the other cationic polymer is below the above upper limit value, the average particle diameter of the microcapsules becomes smaller, and the stability of the microcapsules is further improved. Also, the wall material is formed better.

[0049] <Nonionic surfactant with HLB value less than 12> The microcapsules may be composed of a nonionic surfactant with an HLB value less than 12 (which may be referred to as "other nonionic surfactant" in this specification) as long as the effects of the present invention are not impaired.

[0050] The other nonionic surfactant is not particularly limited. Examples of the other nonionic surfactants include those similar to the nonionic surfactants listed above as nonionic surfactants having an HLB value of 12 or more, except that the HLB value is less than 12. That is, more specific examples of the other nonionic surfactants include polyoxyethylene polyoxypropylene block polymers; polyoxyalkylene styrenated phenyl ethers such as polyoxyethylene styrenated phenyl ethers; and polyoxyalkylene alkyl ethers such as polyoxyethylene alkyl ethers.

[0051] The other nonionic surfactants constituting the microcapsules may be one type only, or two or more types, and when there are two or more types, the combination and ratio thereof can be selected arbitrarily.

[0052] In the microcapsules, the content of the other nonionic surfactant is preferably 5 parts by mass or less, more preferably 3 parts by mass or less, even more preferably 1 part by mass or less, and particularly preferably 0 part by mass (i.e., the microcapsules do not contain the other nonionic surfactant) relative to 100 parts by mass of the content of the nonionic surfactant having an HLB value of 12 or more. When the content of the other nonionic surfactant is equal to or less than the upper limit, the average particle size of the microcapsules becomes smaller, and the stability of the microcapsules is further improved.

[0053] In the microcapsules, the ratio of the total content of gelatin, anionic polymer, polyvalent metal salt, and nonionic surfactant with an HLB value of 12 or more to the total content of components other than the core substance (([gelatin content] + [anionic polymer content] + [polyvalent metal salt content] + [nonionic surfactant content with an HLB value of 12 or more]) / [total content of components other than the core substance] × 100) is 100% by mass or less, and is not particularly limited as long as the effects of the present invention are not impaired, but is preferably 90% by mass or more, more preferably 94% by mass or more, and even more preferably 98% by mass or more. When this ratio is equal to or greater than the lower limit, the average particle size of the microcapsules becomes smaller and the stability of the microcapsules is further improved. In addition, the wall material is formed more satisfactorily.

[0054] ◎Core substance The core substance is not particularly limited and can be selected arbitrarily depending on the purpose. The core substance is preferably liquid at room temperature, more preferably oily at room temperature. In this specification, "room temperature" means a temperature that is neither particularly cold nor hot, that is, an ordinary temperature, and examples thereof include temperatures of 15 to 25°C.

[0055] The core substance may be, for example, either an organic compound or an inorganic compound, but is preferably an organic compound.

[0056] Examples of the core substance include fragrances, insecticides, insect repellents, insect repellents, cosmetics, deodorants, medicines, disinfectants, other chemical reactants, etc. The chemical reactants are components that react with specific chemical substances to inhibit the action of the chemical substances, and do not fall under any of the following categories: fragrances, insecticides, insect repellents, insect repellents, cosmetics, deodorants, medicines, and disinfectants. The microcapsules are highly safe for living organisms, and therefore, when the core substance is a component suitable for use in living organisms, the excellent effects of the microcapsules are more pronounced.

[0057] The core substance constituting the microcapsules (in other words, encapsulated in the wall material) may be of only one type, or of two or more types, and if there are two or more types, the combination and ratio thereof can be selected arbitrarily.

[0058] In the microcapsules, the content of the core material may be, for example, 400 to 1200 parts by mass or 600 to 1000 parts by mass per 100 parts by mass of the gelatin content. Microcapsules with a core material content in such a range have better quality and can be produced more easily.

[0059] The average particle size of the microcapsules is preferably 20 μm or less, more preferably 17 μm or less, and may be, for example, any one of 14 μm or less, 11 μm or less, and 8 μm or less. There is no particular lower limit to the average particle size of the microcapsules. For example, microcapsules with an average particle size of 4 μm or more can be more easily produced.

[0060] In this specification, unless otherwise specified, the term "average particle size" refers to the median diameter of the volume particle size distribution of particles measured using a particle size distribution analyzer.

[0061] The microcapsules can be made to have sustained release properties, in which the encapsulated core substance is gradually released to the outside over time, and such microcapsules can maintain the action of the core substance for a long period of time.

[0062] The microcapsules can be produced by complex coacervation, as described below. The microcapsules of the present embodiment produced in this manner have stronger walls than microcapsules produced by simple coacervation.

[0063] <<Microcapsule manufacturing method>> ◇Manufacturing method (1) A method for producing microcapsules according to one embodiment of the present invention (sometimes referred to herein as "production method (1)") comprises the steps of: mixing gelatin and a core substance in the presence of water to prepare an emulsion (sometimes referred to herein as "emulsification step"); a step of preparing a mixed liquid (A) by mixing an anionic polymer and the emulsion in the presence of water (sometimes referred to as an "emulsion mixing step" in this specification); a step of preparing an acidic mixed solution (1B) by mixing the mixed solution (A) with an acid (sometimes referred to as an "acidification (1) step" in this specification); a step of preparing a mixed liquid (1C) by mixing the mixed liquid (1B) with water (sometimes referred to herein as a "water mixing (1) step"); a step of preparing a mixed solution (1D) by mixing the mixed solution (1C) with a nonionic surfactant having an HLB value of 12 or more (sometimes referred to in this specification as a "surfactant mixing (1) step"); a step of cooling the mixed solution (1D) until its temperature reaches 10°C or less (sometimes referred to as "cooling (1) step" in this specification); a step of preparing a mixed solution (1E) by mixing the cooled mixed solution (1D) with a polyvalent metal salt (sometimes referred to in this specification as a "polyvalent metal salt mixing (1) step"); The method includes a step of preparing an aqueous dispersion of microcapsules having an adjusted pH by mixing the mixed solution (1E) with a base (sometimes referred to in this specification as the "base mixing (1) step").

[0064] The production method (1) is a method for producing microcapsules by applying the complex coacervation method, and by this method, the above-mentioned microcapsules of the present invention can be produced satisfactorily.

[0065] <Emulsification process> In the emulsification step, gelatin and a core substance are mixed in the presence of water to prepare an emulsion. The emulsion contains gelatin, water, and a core substance.

[0066] The gelatin and core substance used in the emulsification step have been described above, and detailed description thereof will be omitted here.

[0067] The gelatin and core substance used in the emulsification step may each be one type only, or two or more types. When two or more types are used, the combination and ratio thereof can be selected arbitrarily.

[0068] In the emulsification step, for example, gelatin, water, and a core substance may be blended, or an aqueous gelatin solution and a core substance may be blended. When an aqueous gelatin solution is blended, water may or may not be blended separately in addition to the water in the aqueous gelatin solution.

[0069] In the emulsification step, the order in which gelatin, water, and a core substance are mixed is not particularly limited, and the order in which the gelatin aqueous solution, a core substance, and, if necessary, water are mixed is also not particularly limited.

[0070] In the emulsification step, it is preferable to blend the gelatin aqueous solution, the core substance, and, if necessary, water, which allows the preparation of a more uniform emulsion.

[0071] The gelatin concentration of the aqueous gelatin solution used in the emulsification step is preferably 3 to 20% by mass, and more preferably 5 to 10% by mass.

[0072] The water used in the emulsification step and the aqueous gelatin solution may both be heated. By heating the water or the aqueous gelatin solution, a more uniform emulsion can be prepared. The heating temperature of the water and gelatin aqueous solution is preferably 40 to 75° C., more preferably 40 to 60° C. When the heating temperature is equal to or higher than the lower limit, the heating effect is more pronounced. When the heating temperature is equal to or lower than the upper limit, the effect of suppressing adverse effects caused by heating, such as deterioration of gelatin or core substances, is more enhanced.

[0073] When the aqueous gelatin solution and the core substance are blended, the core substance may be added to the aqueous gelatin solution, or the aqueous gelatin solution may be added to the core substance. When a liquid core substance is added to the aqueous gelatin solution, the core substance may be added to the aqueous gelatin solution all at once or dropwise. When the aqueous gelatin solution is added to the core substance, the aqueous gelatin solution may be added to the core substance all at once or dropwise.

[0074] In the emulsification step, the amount of water used is preferably 8 to 20 times, and more preferably 10 to 16 times, the mass of the gelatin used. When the amount of water used is equal to or greater than the lower limit, the effects of using water are enhanced, such as the ability to prepare an emulsion with higher uniformity. When the amount of water used is equal to or less than the upper limit, excessive use of water is suppressed. Here, the amount of water used refers to the amount of water when gelatin, water, and a core substance are combined; it refers to the amount of water in the aqueous gelatin solution when a gelatin aqueous solution and a core substance are combined without additional water; and it refers to the total amount of water in the aqueous gelatin solution and the additional water when a gelatin aqueous solution, a core substance, and additional water are combined.

[0075] In the emulsification step, the amount of the core material used is preferably 4 to 12 times, and more preferably 6 to 10 times, the amount of gelatin used. When the amount of the core material used is within this range, microcapsules of better quality can be obtained.

[0076] In the emulsification step, other components that do not fall into the category of gelatin, water, or a core substance (sometimes referred to in this specification as "other component (01)") may be mixed in as long as the effects of the present invention are not impaired.

[0077] The other component (01) is not particularly limited and can be selected arbitrarily depending on the purpose. The other component (01) used in the emulsification step may be one type only, or two or more types, and when two or more types are used, the combination and ratio thereof can be selected arbitrarily.

[0078] In the emulsification step, the amount of the other component (01) used is not particularly limited and can be adjusted appropriately depending on the type of the other component (01). Usually, in the emulsification step, the ratio of the amount of other component (01) used to the total amount of gelatin, water, and core substance used ([amount of other component (01) used] / ([amount of gelatin used]+[amount of water used]+[amount of core substance used])×100) is preferably 10% by mass or less, more preferably 5% by mass or less, even more preferably 3% by mass or less, and particularly preferably 1% by mass or less. Here, the amount of water used is as explained above.

[0079] In the emulsification step, the mixing of gelatin, a core substance, and, if necessary, other component (01) in the presence of water is preferably carried out at a temperature of 15 to 75°C, more preferably at a temperature of 18 to 60°C.

[0080] The method for mixing gelatin, a core substance, and, if necessary, other component (01) in the presence of water is not particularly limited, and examples thereof include a method in which these components are mixed by rotating a stirring means such as a stirring bar or a stirring blade. The stirring speed of the stirring means may be, for example, but is not limited to, either 5,000 to 15,000 rpm or 7,500 to 12,500 rpm. For example, such a stirring speed is particularly suitable when the amount of gelatin used is 5 to 15 g. However, the amount of gelatin used is not limited to this. Furthermore, such a stirring speed is preferably applied at least in this step after the gelatin, core substance, and, if necessary, other component (01) have all been mixed in the presence of water.

[0081] In the emulsification step, when the remaining components are added to any of the gelatin or gelatin aqueous solution, the core substance, separately water as needed, and other component (01) as needed, the remaining components may be added while stirring any of the components to be added, or the remaining components may be added without stirring any of the components to be added, and after all the components have been blended, the blend may be stirred.

[0082] In the emulsification step, after blending all the components (gelatin or gelatin aqueous solution, core substance, water if necessary, and other component (01) if necessary), the resulting blend is stirred for preferably 1 to 30 minutes, more preferably 1 to 10 minutes.

[0083] In the emulsification step, for example, it is preferable to prepare an emulsion by adding the core substance alone to a heated aqueous gelatin solution, and it is also possible to prepare an emulsion by adding the core substance alone at room temperature to a heated aqueous gelatin solution.

[0084] <Emulsion mixing process> In the emulsion mixing step, an anionic polymer and the emulsion are mixed in the presence of water to prepare a mixed liquid (A). The mixed liquid (A) contains an anionic polymer, gelatin, water, and a core substance.

[0085] The anionic polymer used in the emulsion mixing step has been described above, and detailed description thereof will be omitted here.

[0086] The anionic polymer used in the emulsion mixing step may be one type only, or two or more types. When two or more types are used, the combination and ratio thereof can be selected arbitrarily.

[0087] In the emulsion mixing step, for example, an anionic polymer, water, and the emulsion may be mixed together, or an aqueous anionic polymer solution and the emulsion may be mixed together. When an aqueous anionic polymer solution is mixed, water may or may not be added separately in addition to the water in the aqueous anionic polymer solution.

[0088] In the emulsion mixing step, the order in which the anionic polymer, water, and the emulsion are mixed is not particularly limited, and the order in which the anionic polymer aqueous solution, the emulsion, and, if necessary, water are mixed is also not particularly limited.

[0089] In the emulsion mixing step, it is preferable to mix the anionic polymer aqueous solution, the emulsion, and, if necessary, water, separately, in order to prepare a more uniform mixed solution (A).

[0090] The concentration of the anionic polymer in the aqueous anionic polymer solution used in the emulsion mixing step is preferably 3 to 20% by mass, more preferably 5 to 10% by mass.

[0091] The water used in the emulsion mixing step and the aqueous anionic polymer solution may both be heated. By heating the water or the aqueous anionic polymer solution, a more uniform mixed solution (A) can be prepared. The heating temperature of the water and anionic polymer aqueous solution is preferably 40 to 75° C., more preferably 40 to 60° C. When the heating temperature is equal to or higher than the lower limit, the heating effect is more pronounced. When the heating temperature is equal to or lower than the upper limit, the effect of suppressing adverse effects caused by heating, such as deterioration of the anionic polymer, gelatin, or core substance, is more enhanced.

[0092] When the anionic polymer aqueous solution and the emulsion are mixed together, the emulsion may be added to the anionic polymer aqueous solution, or the anionic polymer aqueous solution may be added to the emulsion. When the emulsion is added to the anionic polymer aqueous solution, the emulsion may be added to the anionic polymer aqueous solution all at once or may be added dropwise.When the anionic polymer aqueous solution is added to the emulsion, the anionic polymer aqueous solution may be added to the emulsion all at once or may be added dropwise.

[0093] In the emulsion mixing step, the amount of water used is preferably 8 to 20 times by mass, and more preferably 10 to 16 times by mass, the amount of anionic polymer used. When the amount of water used is equal to or greater than the lower limit, the effects of using water are enhanced, such as the ability to prepare a more uniform mixed liquid (A). When the amount of water used is equal to or less than the upper limit, excessive use of water is suppressed. Here, the amount of water used refers to the amount of water when an anionic polymer, water, and the emulsion are blended together; it refers to the amount of water in the anionic polymer aqueous solution when an anionic polymer aqueous solution and the emulsion are blended together without adding additional water; and it refers to the total amount of water in the anionic polymer aqueous solution and the additional water when an anionic polymer aqueous solution, the emulsion, and additional water are blended together.

[0094] In the emulsion mixing step, the amount of the anionic polymer used is preferably 0.1 to 10 times by mass the amount of gelatin in the emulsion, and may be, for example, any of 0.1 to 7 times by mass, 0.1 to 4 times by mass, 0.1 to 1.5 times by mass, and 0.1 to 0.7 times by mass, or any of 3 to 10 times by mass, 6 to 10 times by mass, and 8 to 10 times by mass, or may be 3 to 7 times by mass. By using an anionic polymer in such a range, the amount of anionic polymer or gelatin that does not contribute to the formation of the wall material can be reduced.

[0095] In the emulsion mixing step, other components that do not fall under any of the anionic polymer, gelatin, water, and core substance (sometimes referred to in this specification as "other component (02)") may be mixed within a range that does not impair the effects of the present invention.

[0096] The other component (02) is not particularly limited and can be selected arbitrarily depending on the purpose. The other component (02) used in the emulsion mixing step may be one type only, or two or more types, and when two or more types are used, the combination and ratio thereof can be selected arbitrarily.

[0097] In the emulsion mixing step, the amount of the other component (02) used is not particularly limited and can be adjusted appropriately depending on the type of the other component (02). Usually, in the emulsion mixing step, the ratio of the amount of other component (02) used to the total amount of anionic polymer, water, and the emulsion used ([amount of other component (02) used] / ([amount of anionic polymer used]+[amount of water used]+[amount of the emulsion used])×100) is preferably 10% by mass or less, more preferably 5% by mass or less, even more preferably 3% by mass or less, and particularly preferably 1% by mass or less. Here, the amount of water used is as explained above.

[0098] In the emulsion mixing step, the anionic polymer, the emulsion, and, if necessary, other component (02) are mixed in the presence of water at a temperature of preferably 30 to 75°C, more preferably 40 to 60°C.

[0099] The method for mixing the anionic polymer, the emulsion, and, if necessary, other component (02) in the presence of water is not particularly limited, and may be the same as or different from the method for mixing the gelatin, the core substance, and, if necessary, other component (01) in the presence of water in the above-mentioned emulsification step.

[0100] In the emulsion mixing step, when adding the remaining components to any of the components to be added, namely, the anionic polymer or the anionic polymer aqueous solution, the emulsion, water as needed, and other components (02) as needed, the remaining components may be added while stirring the components to be added, or the remaining components may be added without stirring the components to be added, and after all the components have been blended, the blend may be stirred.

[0101] In the emulsion mixing step, after blending all of the components (anionic polymer or anionic polymer aqueous solution, the emulsion, water if necessary, and other components (02) if necessary), the resulting blend is stirred for a time period of preferably 1 to 30 minutes, more preferably 1 to 10 minutes.

[0102] In the emulsion mixing step, for example, the mixed solution (A) is preferably prepared by adding the emulsion alone to a heated aqueous anionic polymer solution, or the mixed solution (A) may be prepared by adding the emulsion alone at 25°C or higher to a heated aqueous anionic polymer solution.

[0103] <Acidification (1) step> In the acidification (1) step, the mixed solution (A) is mixed with an acid to prepare an acidic mixed solution (1B). The gelatin in the mixed solution (A) does not have any cationic groups and therefore cannot be considered a cationic polymer, or even if it has cationic groups, the number of groups is so small that it does not have sufficient properties as a cationic polymer. In contrast, the gelatin in the mixed solution (1B) has a sufficiently large number of cationic groups due to the action of the acid, and is in a state where it has sufficient properties as a cationic polymer, and is clearly a cationic polymer. That is, the mixed liquid (1B) contains gelatin (cationic polymer), an anionic polymer, water, and a core substance.

[0104] The pH of the mixed solution (1B) obtained in the acidification (1) step is not particularly limited as long as the gelatin can stably form a wall material together with the anionic polymer in the end, but is preferably 2 to 5, and more preferably 2 to 4. When the pH of the mixed solution (1B) is equal to or less than the upper limit, the gelatin can more stably form a wall material together with the anionic polymer. When the pH is equal to or more than the lower limit, an excessive decrease in the pH of the mixed solution (1B) can be avoided.

[0105] The acid used in the acidification (1) step is not particularly limited, and may be, for example, either an inorganic acid or an organic acid. Examples of the inorganic acid include hydrochloric acid (HCl), sulfuric acid (H2SO4), nitric acid (HNO3), and phosphoric acid (H3PO4). Examples of the organic acid include citric acid (HOOCCH2C(COOH)(OH)CH2COOH) and acetic acid (CH3COOH).

[0106] The acid used in the acidification (1) step may be one kind or two or more kinds, and when two or more kinds are used, the combination and ratio thereof can be selected arbitrarily.

[0107] In the acidification step (1), the acid may be added alone or as an aqueous solution. The use of an aqueous acid solution makes it easier to prepare the mixed solution (1B) with an adjusted pH.

[0108] The acid concentration of the aqueous acid solution used in the acidification (1) step can be adjusted appropriately depending on the type of acid, but is preferably 10 to 70% by mass, more preferably 30 to 60% by mass.

[0109] When the aqueous acid solution and the mixed liquid (A) are mixed, it is preferable to add the aqueous acid solution to the mixed liquid (A), and the aqueous acid solution may be added to the mixed liquid (A) all at once or dropwise. When the acid is not added as an aqueous solution, it is preferable to add the acid to the mixed liquid (A), and the acid may be added to the mixed liquid (A) all at once, or may be added dropwise or in portions.

[0110] In the acidification (1) step, other components that do not fall into any of the categories of gelatin, anionic polymer, core substance, and acid (sometimes referred to in this specification as "other components (03)") may be mixed within a range that does not impair the effects of the present invention.

[0111] The other component (03) is not particularly limited and can be selected arbitrarily depending on the purpose, and may be, for example, water. The other component (03) used in the acidification (1) step may be one kind or two or more kinds, and when two or more kinds are used, the combination and ratio thereof can be selected arbitrarily.

[0112] In the acidification (1) step, the amount of the other component (03) used is not particularly limited and can be adjusted appropriately depending on the type of the other component (03). Usually, in the acidification (1) step, the ratio of the amount of the other component (03) used to the total amount of the mixed solution (A) and the acid used ([amount of the other component (03) used] / ([amount of the mixed solution (A) used]+[amount of the acid used])×100) is preferably 10% by mass or less, more preferably 5% by mass or less, even more preferably 3% by mass or less, and particularly preferably 1% by mass or less. Here, the amount of acid used refers to the amount of acid when the acid is not added as an aqueous solution. When the acid is added as an aqueous solution, the amount of acid is the amount of acid in the aqueous acid solution.

[0113] In the acidification (1) step, when the mixed solution (A), the acid or the aqueous acid solution, and, if necessary, other component (03) are mixed, the mixing is preferably carried out at a temperature of 30 to 75°C, more preferably at a temperature of 40 to 60°C.

[0114] The method for mixing the mixed solution (A), the acid or aqueous acid solution, and, if necessary, the other component (03) is not particularly limited, and may be the same as or different from the method for mixing the gelatin, the core substance, and, if necessary, the other component (01) in the presence of water in the above-mentioned emulsification step.

[0115] In the acidification (1) step, when adding the remaining components to any of the components to be added, namely, the mixed solution (A), the acid or aqueous acid solution, and, if necessary, other components (03), the remaining components may be added while stirring the components to be added, or the remaining components may be added without stirring the components to be added, and after all the components have been blended, the blend may be stirred.

[0116] In the acidification (1) step, after all components (mixture (A), acid or aqueous acid solution, and, if necessary, other component (03)) are mixed, the resulting mixture may be stirred for, for example, 1 to 10 minutes.

[0117] In the acidification (1) step, for example, it is preferable to prepare the acidic mixed solution (1B) by adding or dropping an acid aqueous solution to the mixed solution (A), and it is more preferable to prepare the acidic mixed solution (1B) by dropping an acid aqueous solution to the mixed solution (A). The addition or dropwise addition of the aqueous acid solution to the mixed liquid (A) is preferably carried out at a temperature of 30 to 75°C, more preferably at a temperature of 40 to 60°C.

[0118] <Water mixing (1) process> In the water mixing (1) step, the mixed liquid (1B) is mixed with water to prepare a mixed liquid (1C). The mixed solution (1C) contains more water than the mixed solution (1B), which promotes the formation of a wall material from gelatin and anionic polymer. The mixed liquid (1C) contains gelatin (cationic polymer), an anionic polymer, water, and a core substance.

[0119] The water used in the water mixing step (1) may be heated. The water is preferably heated to a temperature of 40 to 75°C, more preferably 40 to 60°C.

[0120] The amount of water used in the water mixing step (1) is preferably 8 to 14 times by mass, more preferably 10 to 12 times by mass, the total amount of gelatin and anionic polymer in the mixed solution (1B). When the amount of water used is equal to or greater than the lower limit, the effect of using water is more pronounced. When the amount of water used is equal to or less than the upper limit, excessive use of water is suppressed.

[0121] In the water mixing step (1), water may be added to the mixed liquid (1B), or the mixed liquid (1B) may be added to water. When water is added to the mixed liquid (1B), water may be added to the mixed liquid (1B) all at once or may be added dropwise. When the mixed liquid (1B) is added to water, the mixed liquid (1B) may be added to water all at once or may be added dropwise.

[0122] In the water mixing step (1), the other component (03) may be mixed in as long as the effects of the present invention are not impaired. The other component (03) used in the water mixing step (1) may be the same as or different from the other component (03) used in the acidification step (1). The other component (03) used in the water mixing step (1) may be one type or two or more types, and when two or more types are used, the combination and ratio thereof can be selected arbitrarily.

[0123] In the water mixing step (1), the amount of the other component (03) used is not particularly limited and can be adjusted appropriately depending on the type of the other component (03). Usually, in the water mixing step (1), the ratio of the amount of other component (03) used to the total amount of mixed solution (1B) and water used ([amount of other component (03) used] / ([amount of mixed solution (1B) used]+[amount of water used])×100) is preferably 10% by mass or less, more preferably 5% by mass or less, even more preferably 3% by mass or less, and particularly preferably 1% by mass or less.

[0124] In the water mixing step (1), the mixed liquid (1B), water, and, if necessary, other component (03) are mixed preferably at a temperature of 30 to 75°C, more preferably at a temperature of 40 to 60°C.

[0125] The method for mixing the mixed liquid (1B), water, and, if necessary, other component (03) is not particularly limited, and may be the same as or different from the method for mixing gelatin, a core substance, and, if necessary, other component (01) in the presence of water in the emulsification step described above.

[0126] In the water mixing step (1), when adding the remaining components to any of the components to be added, namely the mixed liquid (1B), water, and, if necessary, other components (03), the remaining components may be added while stirring the components to be added, or the remaining components may be added without stirring the components to be added, and after all the components have been blended, the blend may be stirred.

[0127] In the water mixing (1) step, after all components (mixed liquid (1B), water, and, if necessary, other components (03)) have been mixed, the resulting mixture is stirred for preferably 1 to 30 minutes, more preferably 1 to 10 minutes.

[0128] In the water mixing step (1), for example, it is preferable to prepare a mixed liquid (1C) by adding heated water (hot water) to the mixed liquid (1B), and the mixed liquid (1C) may also be prepared by adding heated water to the mixed liquid (1B) at 25°C or higher.

[0129] <Surfactant mixing step (1)> In the surfactant mixing step (1), the mixed solution (1C) is mixed with a nonionic surfactant having an HLB value of 12 or more to prepare a mixed solution (1D). In the mixed solution (1D), the action of the nonionic surfactant inhibits aggregation and coalescence of the wall material components in the process of forming the target microcapsules.Furthermore, the action of the nonionic surfactant inhibits aggregation and coalescence of the final microcapsules themselves, thereby reducing the average particle size of the microcapsules. The mixed liquid (1D) contains gelatin (cationic polymer), an anionic polymer, water, a core substance, and the nonionic surfactant.

[0130] The nonionic surfactant having an HLB value of 12 or more used in the surfactant mixing step (1) has been described above, and detailed description thereof will be omitted here.

[0131] The nonionic surfactant used in the surfactant mixing step (1) may be one type only, or two or more types. When two or more types are used, the combination and ratio thereof can be selected arbitrarily.

[0132] In the surfactant mixing step (1), the amount of the nonionic surfactant used is preferably 0.03 to 0.25 times by mass, more preferably 0.05 to 0.2 times by mass, and even more preferably 0.07 to 0.16 times by mass, relative to the total amount of gelatin and anionic polymer in the mixed solution (1C). When the amount of the nonionic surfactant used is equal to or greater than the lower limit, aggregation and coalescence of the wall material components during the formation of the target microcapsules are further suppressed. Furthermore, aggregation and coalescence of the final microcapsules themselves are further suppressed, resulting in a smaller average particle size of the microcapsules. When the amount of the nonionic surfactant used is equal to or less than the upper limit, excessive use of the nonionic surfactant is suppressed. In the microcapsules, the content of the nonionic surfactant may be, for example, 3 to 25 parts by mass, 5 to 20 parts by mass, or 7 to 16 parts by mass, relative to 100 parts by mass of the total content of gelatin and anionic polymer. When the content of the nonionic surfactant is equal to or greater than the lower limit, aggregation and coalescence of the microcapsules and the wall material components in the process of forming the microcapsules are further suppressed, and the average particle size of the microcapsules becomes smaller. When the content of the nonionic surfactant is equal to or less than the upper limit, excessive use of the nonionic surfactant is suppressed.

[0133] In the surfactant mixing step (1), other components that do not fall into any of the categories of gelatin, anionic polymer, core substance, acid, and nonionic surfactant (sometimes referred to in this specification as "other components (04)") may be mixed within a range that does not impair the effects of the present invention.

[0134] The other component (04) is not particularly limited and can be selected arbitrarily depending on the purpose. The other component (04) used in the surfactant mixing step (1) may be one type or two or more types, and when two or more types are used, the combination and ratio thereof can be selected arbitrarily.

[0135] In the surfactant mixing step (1), the amount of the other component (04) used is not particularly limited and can be adjusted appropriately depending on the type of the other component (04). Usually, in the surfactant mixing step (1), the ratio of the amount of other component (04) used to the total amount of the mixed solution (1C) and the nonionic surfactant used ([amount of other component (04) used] / ([amount of mixed solution (1C) used]+[amount of the nonionic surfactant used])×100) is preferably 10% by mass or less, more preferably 5% by mass or less, even more preferably 3% by mass or less, and particularly preferably 1% by mass or less.

[0136] In the surfactant mixing step (1), the mixed solution (1C), the nonionic surfactant, and, if necessary, other component (04) are mixed preferably at a temperature of 30 to 75°C, more preferably at a temperature of 40 to 60°C.

[0137] The method for mixing the mixed liquid (1C), the nonionic surfactant, and, if necessary, other component (04), is not particularly limited, and may be the same as or different from the method for mixing gelatin, a core substance, and, if necessary, other component (01) in the presence of water in the above-mentioned emulsification step.

[0138] In the surfactant mixing step (1), when adding the remaining components to any of the components to be added, namely, the mixed solution (1C), the nonionic surfactant, and, if necessary, other components (04), the remaining components may be added while stirring the components to be added, or the remaining components may be added without stirring the components to be added, and after all the components have been blended, the blend may be stirred.

[0139] In the surfactant mixing step (1), after all components (mixed liquid (1C), the nonionic surfactant, and, if necessary, other components (04)) have been mixed, the resulting mixture is stirred for a time period of preferably 1 to 30 minutes, more preferably 1 to 10 minutes.

[0140] In the surfactant mixing step (1), it is preferable to prepare a mixed solution (1D) by adding the nonionic surfactant to a heated mixed solution (1C).

[0141] <Cooling (1) process> In the cooling (1) step, the mixed liquid (1D) is cooled to a temperature of 10°C or lower. By cooling the mixed liquid (1D), precipitation of the wall material encapsulating the core substance is promoted in the mixed liquid (1D).

[0142] The temperature of the mixed liquid (1D) during cooling is preferably 0 to 10°C, more preferably 2 to 9°C. When the temperature is equal to or less than the upper limit, the cooling effect of the mixed liquid (1D) can be more pronounced. When the temperature is equal to or more than the lower limit, excessive cooling of the mixed liquid (1D) can be suppressed.

[0143] The cooling rate of the mixed liquid (1D) is not particularly limited, but is preferably 0.2 to 2.0°C / min, and more preferably 0.3 to 1.0°C / min. When the cooling rate is within this range, the cooling effect of the mixed liquid (1D) can be more pronounced.

[0144] <Polyvalent metal salt mixing step (1)> In the polyvalent metal salt mixing step (1), the cooled mixed solution (1D) is mixed with a polyvalent metal salt to prepare a mixed solution (1E). By carrying out this step, the desired microcapsules having a small average particle size can be obtained as an aqueous dispersion. In the mixed solution (1E), the wall material components are bound together by the action of the polyvalent metal ions (cations) in the polyvalent metal salt, forming microcapsules with strong walls. The action of the polyvalent metal ions at this time is as described above. That is, the mixed liquid (1E) contains the desired microcapsules.

[0145] The polyvalent metal salt used in the polyvalent metal salt mixing step (1) has been explained above, and detailed explanation thereof will be omitted here.

[0146] The polyvalent metal salt used in the polyvalent metal salt mixing step (1) may be one kind or two or more kinds, and when two or more kinds are used, the combination and ratio thereof can be selected arbitrarily.

[0147] In the polyvalent metal salt mixing step (1), the polyvalent metal salt may be added alone, but it is preferable to add it as an aqueous solution. By using an aqueous solution of the polyvalent metal salt, microcapsules with a more stable structure can be obtained.

[0148] The concentration of the polyvalent metal salt in the aqueous polyvalent metal salt solution used in the polyvalent metal salt mixing step (1) can be adjusted appropriately depending on the type of polyvalent metal salt, but is preferably 10 to 40% by mass, more preferably 15 to 25% by mass.

[0149] When the aqueous solution of a polyvalent metal salt is mixed with the mixed liquid (1D), it is preferable to add the aqueous solution of a polyvalent metal salt to the mixed liquid (1D), and the aqueous solution of a polyvalent metal salt may be added to the mixed liquid (1D) all at once or dropwise. When the polyvalent metal salt is not added as an aqueous solution, it is preferable to add the polyvalent metal salt to the mixed liquid (1D), and the polyvalent metal salt may be added to the mixed liquid (1D) all at once or in portions.

[0150] The polyvalent metal salt mixing step (1) is usually carried out immediately following the cooling step (1). Therefore, the temperature of the mixed liquid (1D) at the start of the polyvalent metal salt mixing step (1) is the same as the temperature of the mixed liquid (1D) at the end of the cooling step (1).

[0151] In the polyvalent metal salt mixing step (1), the amount of polyvalent metal salt used is preferably 0.3 to 0.95 times by mass, more preferably 0.4 to 0.85 times by mass, and even more preferably 0.5 to 0.75 times by mass, relative to the total amount of gelatin and anionic polymer in the cooled mixed solution (1D). When the amount of polyvalent metal salt used is equal to or greater than the lower limit, the wall material of the microcapsules becomes stronger. When the amount of polyvalent metal salt used is equal to or less than the upper limit, excessive use of the polyvalent metal salt is suppressed.

[0152] In the polyvalent metal salt mixing step (1), other components that do not fall into any of the categories of gelatin, anionic polymer, core substance, acid, nonionic surfactant, and polyvalent metal salt (sometimes referred to in this specification as "other components (05)") may be mixed within a range that does not impair the effects of the present invention.

[0153] The other component (05) is not particularly limited and can be selected arbitrarily depending on the purpose. The other component (05) used in the polyvalent metal salt mixing step (1) may be one type or two or more types, and when two or more types are used, the combination and ratio thereof can be selected arbitrarily.

[0154] In the polyvalent metal salt mixing step (1), when the mixed solution (1D), the polyvalent metal salt or the aqueous solution of the polyvalent metal salt, and, if necessary, other components (05) are mixed, the mixing is preferably carried out at a temperature of 0 to 10° C., more preferably at a temperature of 2 to 9° C. By mixing at such a temperature, microcapsules with a more stable structure can be obtained. The temperature range during mixing in the polyvalent metal salt mixing step (1) may or may not match the temperature range of the mixed liquid (1D) in the cooling step (1).

[0155] The method for mixing the mixed liquid (1D), the polyvalent metal salt or the aqueous solution of the polyvalent metal salt, and, if necessary, the other component (05), is not particularly limited, and may be the same as or different from the method for mixing the gelatin, the core substance, and, if necessary, the other component (01) in the presence of water in the above-mentioned emulsification step.

[0156] In the polyvalent metal salt mixing step (1), when adding the remaining components to any of the components to be added, namely, the mixed solution (1D), the polyvalent metal salt or the aqueous solution of the polyvalent metal salt, and, if necessary, other components (05), the remaining components may be added while stirring the components to be added, or the remaining components may be added without stirring the components to be added, and after all the components have been mixed, the mixture may be stirred.

[0157] In the polyvalent metal salt mixing step (1), after all components (mixed liquid (1D), polyvalent metal salt or polyvalent metal salt aqueous solution, and, if necessary, other component (05)) are mixed, the resulting mixture is stirred for preferably 1 to 30 minutes, more preferably 1 to 10 minutes.

[0158] In the polyvalent metal salt mixing step (1), for example, it is preferable to prepare the mixed solution (1E) by adding an aqueous solution of a polyvalent metal salt to the mixed solution (1D), and it is more preferable to prepare the mixed solution (1E) by adding the aqueous solution of a polyvalent metal salt to the mixed solution (1D) while maintaining the temperature of the mixed solution (1D) constant.

[0159] <Base mixing step (1)> In the base mixing step (1), the mixed solution (1E) is mixed with a base to prepare an aqueous dispersion of microcapsules with an adjusted pH. The microcapsules obtained in the base mixing step (1) have a more stable structure in the aqueous dispersion.

[0160] The pH of the aqueous dispersion of microcapsules obtained in the base mixing step (1) is not particularly limited as long as the microcapsules can be stably present.

[0161] The base used in the base mixing step (1) is not particularly limited, and may be, for example, either an inorganic base or an organic base. Examples of the inorganic base include alkali metal hydroxides such as sodium hydroxide (NaOH), potassium hydroxide (KOH), and lithium hydroxide (LiOH); alkali metal carbonates such as sodium carbonate (Na2CO3), potassium carbonate (K2CO3), and lithium carbonate (Li2CO3); and alkali metal bicarbonates such as sodium bicarbonate (NaHCO3), and potassium bicarbonate (KHCO3). Examples of the organic base include alkylamines such as triethylamine ((CH3CH2)3N).

[0162] The base used in the base mixing step (1) may be one kind or two or more kinds, and when two or more kinds are used, the combination and ratio thereof can be selected arbitrarily.

[0163] In the base mixing step (1), the base may be added alone or as an aqueous solution. By using an aqueous base solution, an aqueous dispersion of microcapsules with an adjusted pH can be more easily prepared.

[0164] The concentration of the base in the aqueous base solution used in the base mixing step (1) can be adjusted appropriately depending on the type of base, but is preferably 10 to 40% by mass, more preferably 15 to 25% by mass.

[0165] When the aqueous base solution and the mixed solution (1E) are mixed, it is preferable to add the aqueous base solution to the mixed solution (1E), and the aqueous base solution may be added to the mixed solution (1E) all at once or dropwise. When the base is not added as an aqueous solution, it is preferable to add the base to the mixed solution (1E), and the base may be added to the mixed solution (1E) all at once, or may be added dropwise or in portions.

[0166] In the base mixing step (1), when the mixed solution (1E) and the base or the aqueous base solution are mixed, the mixing is preferably carried out at a temperature of 0 to 10°C, more preferably at a temperature of 2 to 9°C.

[0167] The method for mixing the mixed solution (1E) with the base or aqueous base solution is not particularly limited, and may be the same as or different from the method for mixing the gelatin, the core substance, and, if necessary, other component (01) in the presence of water in the above-mentioned emulsification step.

[0168] In the base mixing (1) step, when the remaining components are added to either the mixed solution (1E) or the base or the aqueous base solution, the remaining components may be added while stirring the components to be added, or the remaining components may be added without stirring the components to be added, so that all the components are blended and then the blend is stirred.

[0169] In the base mixing (1) step, after blending all the components (mixed solution (1E) and the base or aqueous base solution), the time for stirring the resulting blend is, for example, preferably 1 to 8 hours, more preferably 2 to 6 hours. When the time is equal to or greater than the lower limit, the effect of using the base is more pronounced. When the time is equal to or less than the upper limit, the time required for the base mixing (1) step can be prevented from being excessively long.

[0170] When stirring the mixture obtained after blending all the components in this manner, the mixture is preferably stirred at a temperature of 15 to 40°C, more preferably at a temperature of 18 to 30°C, or may be stirred at normal temperature (e.g., room temperature).

[0171] In the base mixing (1) step, for example, it is preferable to prepare an aqueous dispersion of microcapsules by adding or dropping an aqueous base solution to the mixed liquid (1E), and it is more preferable to prepare an aqueous dispersion of microcapsules by dropping an aqueous base solution to the mixed liquid (1E). The addition or dropwise addition of the aqueous base solution to the mixed solution (1E) is preferably carried out at a temperature of 0 to 10°C, more preferably at a temperature of 2 to 9°C.

[0172] <Other process (1)> The production method (1) may include other steps (sometimes referred to as "other steps (1)" in this specification) that do not fall under any of the above-mentioned emulsification step, emulsion mixing step, acidification (1) step, water mixing (1) step, surfactant mixing (1) step, cooling (1) step, polyvalent metal salt mixing (1) step, and base mixing (1) step, as long as the effects of the present invention are not impaired. The type of other step (1), the number of other steps (1), and the timing of performing other step (1) can be selected arbitrarily depending on the purpose, and are not particularly limited.

[0173] The microcapsules obtained by production method (1) may be used as an aqueous dispersion as is, or the aqueous dispersion obtained after performing known post-treatments, purification, etc. may be used as is, or the microcapsules may be used as a single substance by removing the dispersion medium after performing known post-treatments, purification, etc. as necessary.

[0174] ◇Manufacturing method (2) A method for producing microcapsules according to one embodiment of the present invention (sometimes referred to herein as "production method (2)") includes the steps of: preparing an emulsion by mixing gelatin and a core substance in the presence of water (emulsification step); a step of preparing a mixed liquid (A) by mixing an anionic polymer and the emulsion in the presence of water (emulsion mixing step); a step of preparing a mixed liquid (2B) by mixing the mixed liquid (A) with water (sometimes referred to as a "water mixing (2) step" in this specification); a step of preparing an acidic mixed solution (2C) by mixing the mixed solution (2B) with an acid (sometimes referred to as an "acidification (2) step" in this specification); a step of preparing a mixed solution (2D) by mixing the mixed solution (2C) with a nonionic surfactant having an HLB value of 12 or more (sometimes referred to in this specification as a "surfactant mixing (2) step"); a step of cooling the mixed liquid (2D) until its temperature becomes 10°C or less (sometimes referred to as a "cooling (2) step" in this specification); a step of preparing a mixed solution (2E) by mixing the cooled mixed solution (2D) with a polyvalent metal salt (sometimes referred to in this specification as a "polyvalent metal salt mixing (2) step"); The method includes a step of preparing an aqueous dispersion of microcapsules having an adjusted pH by mixing the mixed solution (2E) with a base (sometimes referred to in this specification as the "base mixing (2) step"). The above-mentioned microcapsules of the present invention can be successfully produced by the production method (2).

[0175] The production method (2) is also a method for producing microcapsules to which the complex coacervation method is applied, and this method can satisfactorily produce the above-mentioned microcapsules of the present invention. The production method (2) corresponds to the above-mentioned production method (1) in which the order of the "acidification (1) step" and the "water mixing (1) step" is reversed.

[0176] <Emulsification process, emulsion mixing process> The emulsification step and emulsion mixing step in production method (2) are the same as the emulsification step and emulsion mixing step in production method (1). That is, production methods (1) and (2) are the same up to the emulsion mixing step.

[0177] <Water mixing (2) process> In the water mixing (2) step, the mixed liquid (A) and water are mixed to prepare a mixed liquid (2B). By preparing the mixed solution (2B), the mixed solution (2C) obtained in the acidification (2) step described below contains more water than the mixed solution (A), which promotes the formation of a wall material from gelatin and anionic polymer. The mixed liquid (2B) contains an anionic polymer, gelatin, water, and a core substance.

[0178] The water used in the water mixing step (2) may be heated. The water is preferably heated to a temperature of 40 to 75°C, more preferably 40 to 60°C.

[0179] The amount of water used in the water mixing step (2) is preferably 8 to 14 times by mass, more preferably 10 to 12 times by mass, the total amount of gelatin and anionic polymer in the mixed solution (A). When the amount of water used is equal to or greater than the lower limit, the effect of using water is more pronounced. When the amount of water used is equal to or less than the upper limit, excessive use of water is suppressed.

[0180] In the water mixing step (2), water may be added to the mixed liquid (A), or the mixed liquid (A) may be added to water. When water is added to the mixed liquid (A), water may be added to the mixed liquid (A) all at once or may be added dropwise. When the mixed liquid (A) is added to water, the mixed liquid (A) may be added to water all at once or may be added dropwise.

[0181] In the water mixing step (2), the other component (02) may be mixed in as long as the effects of the present invention are not impaired. The other component (02) used in the water mixing step (2) may be the same as or different from the other component (02) used in the emulsion mixing step. The other component (02) used in the water mixing step (2) may be one type or two or more types, and when two or more types are used, the combination and ratio thereof can be selected arbitrarily.

[0182] In the water mixing step (2), the amount of the other component (02) used is not particularly limited and can be adjusted appropriately depending on the type of the other component (02). Usually, in the water mixing step (2), the ratio of the amount of other component (02) used to the total amount of mixed solution (A) and water used ([amount of other component (02) used] / ([amount of mixed solution (A) used]+[amount of water used])×100) is preferably 10% by mass or less, more preferably 5% by mass or less, even more preferably 3% by mass or less, and particularly preferably 1% by mass or less.

[0183] In the water mixing step (2), the mixed liquid (A), water, and, if necessary, other components (02) are mixed preferably at a temperature of 30 to 75°C, more preferably at a temperature of 40 to 60°C.

[0184] The method for mixing the mixed liquid (A), water, and, if necessary, other component (02) is not particularly limited, and may be the same as or different from the method for mixing gelatin, a core substance, and, if necessary, other component (01) in the presence of water in the above-mentioned emulsification step.

[0185] In the water mixing (2) step, when adding the remaining components to any of the components to be added, namely the mixed liquid (A), water, and, if necessary, other components (02), the remaining components may be added while stirring the components to be added, or the remaining components may be added without stirring the components to be added, and after all the components have been blended, the blend may be stirred.

[0186] In the water mixing (2) step, after all components (mixed liquid (A), water, and, if necessary, other components (02)) are mixed, the resulting mixture is stirred for a time period of preferably 1 to 30 minutes, more preferably 1 to 10 minutes.

[0187] In the water mixing (2) step, for example, it is preferable to prepare the mixed liquid (2B) by adding heated water (hot water) to the mixed liquid (A), and the mixed liquid (2B) may also be prepared by adding heated water to the mixed liquid (A) at 25°C or higher.

[0188] <Acidification (2) step> In the acidification (2) step, the mixed solution (2B) is mixed with an acid to prepare an acidic mixed solution (2C). The mixed solution (2C) obtained here may be the same as the mixed solution (1C) obtained in the water mixing (1) step of the production method (1). The gelatin in the mixed solution (2B) does not have any cationic groups and therefore cannot be considered a cationic polymer, or even if it does have cationic groups, the number of groups is so small that it does not have sufficient properties as a cationic polymer. In contrast, the gelatin in the mixed solution (2C) has a sufficiently large number of cationic groups due to the action of the acid, and is in a state where it has sufficient properties as a cationic polymer, and is clearly a cationic polymer. That is, the mixed liquid (2C) contains gelatin (cationic polymer), an anionic polymer, water, and a core substance.

[0189] The pH of the mixed solution (2C) obtained in the acidification (2) step is not particularly limited as long as the gelatin can stably form a wall material together with the anionic polymer in the end, but is preferably 2 to 5, and more preferably 2 to 4. When the pH of the mixed solution (2C) is equal to or less than the upper limit, the gelatin can more stably form a wall material together with the anionic polymer. When the pH is equal to or more than the lower limit, an excessive decrease in the pH of the mixed solution (2C) can be avoided.

[0190] The acid used in the acidification (2) step may be the same as the acid used in the acidification (1) step in the production method (1).

[0191] The acid used in the acidification (2) step may be one kind or two or more kinds, and when two or more kinds are used, the combination and ratio thereof can be selected arbitrarily.

[0192] In the acidification step (2), the acid may be added alone or as an aqueous solution. The use of an aqueous acid solution makes it easier to prepare a mixed solution (2C) with an adjusted pH.

[0193] The acid concentration of the aqueous acid solution used in the acidification (2) step can be adjusted appropriately depending on the type of acid, but is preferably 30 to 70% by mass, more preferably 40 to 60% by mass.

[0194] When the aqueous acid solution and the mixed liquid (2B) are mixed, it is preferable to add the aqueous acid solution to the mixed liquid (2B), and the aqueous acid solution may be added to the mixed liquid (2B) all at once or dropwise. When the acid is not added as an aqueous solution, it is preferable to add the acid to the mixed liquid (2B). The acid may be added to the mixed liquid (2B) all at once, or may be added dropwise or in portions.

[0195] In the acidification step (2), the other component (03) may be mixed in as long as the effect of the present invention is not impaired. The other component (03) used in the acidification (2) step may be one kind or two or more kinds, and when two or more kinds are used, the combination and ratio thereof can be selected arbitrarily.

[0196] In the acidification (2) step, the amount of the other component (03) used is not particularly limited and can be adjusted appropriately depending on the type of the other component (03). Usually, in the acidification (2) step, the ratio of the amount of the other component (03) used to the total amount of the mixed solution (2B) and the acid or aqueous acid solution used ([amount of the other component (03) used] / ([amount of the mixed solution (2B) used]+[amount of the acid or aqueous acid solution used])×100) is preferably 10% by mass or less, more preferably 5% by mass or less, even more preferably 3% by mass or less, and particularly preferably 1% by mass or less.

[0197] In the acidification (2) step, when the mixed solution (2B), the acid or the aqueous acid solution, and, if necessary, other component (03) are mixed, the mixing is preferably carried out at a temperature of 30 to 75°C, more preferably at a temperature of 40 to 60°C, or may be carried out at normal temperature (e.g., room temperature).

[0198] The method for mixing the mixed liquid (2B), the acid or aqueous acid solution, and, if necessary, the other component (03) is not particularly limited, and may be the same as or different from the method for mixing the gelatin, the core substance, and, if necessary, the other component (01) in the presence of water in the above-mentioned emulsification step.

[0199] In the acidification (2) step, when adding the remaining components to any of the components to be added, namely, the mixed solution (2B), the acid or aqueous acid solution, and, if necessary, other components (03), the remaining components may be added while stirring the components to be added, or the remaining components may be added without stirring the components to be added, and after all the components have been blended, the blend may be stirred.

[0200] In the acidification (2) step, after all components (mixed liquid (2B), acid or aqueous acid solution, and, if necessary, other component (03)) are mixed, the resulting mixture may be stirred for, for example, 1 to 10 minutes.

[0201] In the acidification (2) step, for example, it is preferable to prepare the acidic mixed solution (2C) by adding or dropping an acid aqueous solution to the mixed solution (2B), and it is more preferable to prepare the acidic mixed solution (2C) by dropping an acid aqueous solution to the mixed solution (2B). The addition or dropwise addition of the aqueous acid solution to the mixed liquid (2B) is preferably carried out at a temperature of 30 to 75°C, more preferably at a temperature of 40 to 60°C.

[0202] <Surfactant mixing step (2)> In the surfactant mixing step (2), the mixed liquid (2C) is mixed with a nonionic surfactant having an HLB value of 12 or more to prepare a mixed liquid (2D). The mixed liquid (2D) obtained here may be the same as the mixed liquid (1D) obtained in the surfactant mixing (1) step of the production method (1). In the mixed solution (2D), the action of the nonionic surfactant inhibits aggregation and coalescence of the wall material components in the process of forming the desired microcapsules, and further inhibits aggregation and coalescence of the final microcapsules themselves, thereby reducing the average particle size of the microcapsules. The mixed liquid (2D) contains gelatin (cationic polymer), an anionic polymer, water, a core substance, and the nonionic surfactant.

[0203] The surfactant mixing step (2) is the same as the surfactant mixing step (1) in the production method (1) except that the mixed solution (2C) is used instead of the mixed solution (1C). For example, in this step, the amount of nonionic surfactant used relative to the total amount of gelatin and anionic polymer in the mixed solution (2C) can be the same as the amount of nonionic surfactant used relative to the total amount of gelatin and anionic polymer in the mixed solution (1C) in the surfactant mixing (1) step. In the surfactant mixing step (2), the same effect as in the surfactant mixing step (1) can be obtained.

[0204] <Cooling (2) process> In the cooling (2) step, the mixed liquid (2D) is cooled to a temperature of 10°C or lower. The cooled mixed liquid (2D) obtained here may be the same as the cooled mixed liquid (1D) obtained in the cooling (1) step of the production method (1). By cooling the mixed liquid (2D), precipitation of the wall material encapsulating the core substance is promoted in the mixed liquid (2D).

[0205] The cooling (2) step is the same as the cooling (1) step in the production method (1) except that the mixed liquid (2D) is used instead of the mixed liquid (1D). In the cooling (2) step, the same effect as in the cooling (1) step can be obtained.

[0206] <Polyvalent metal salt mixing step (2)> In the polyvalent metal salt mixing step (2), the cooled mixed liquid (2D) is mixed with a polyvalent metal salt. By carrying out this step, the desired microcapsules having a small average particle size can be obtained as an aqueous dispersion. The aqueous dispersion of microcapsules obtained here may be the same as the aqueous dispersion of microcapsules obtained in the polyvalent metal salt mixing step (1) of the production method (1). In the mixed solution (2D) (sometimes referred to herein as "mixed solution (2E)") after mixing the polyvalent metal salt, the wall material components are bound together by the action of the polyvalent metal ions in the polyvalent metal salt, forming microcapsules with strong walls. The action of the polyvalent metal ions at this time is as described above. That is, the mixed liquid (2E) contains the target microcapsules.

[0207] The polyvalent metal salt mixing step (2) is the same as the polyvalent metal salt mixing step (1) in the production method (1), except that the cooled mixed solution (2D) is used instead of the cooled mixed solution (1D). For example, in this step, the amount of polyvalent metal salt used relative to the total amount of gelatin and anionic polymer in the mixed solution (2D) after cooling can be the same as the amount of polyvalent metal salt used relative to the total amount of gelatin and anionic polymer in the mixed solution (1D) after cooling in the polyvalent metal salt mixing (1) step. In the polyvalent metal salt mixing step (2), the same effects as in the polyvalent metal salt mixing step (1) can be obtained.

[0208] <Base mixing step (2)> In the base mixing step (2), the mixed solution (2E) is mixed with a base to prepare an aqueous dispersion of microcapsules with an adjusted pH. The microcapsules obtained in the base mixing step (2) have a more stable structure in the aqueous dispersion. The aqueous dispersion of microcapsules obtained here may be the same as the aqueous dispersion of microcapsules obtained in the base mixing step (1) of the production method (1).

[0209] The pH of the aqueous dispersion of microcapsules obtained in the base mixing step (2) is not particularly limited as long as the microcapsules can be stably present.

[0210] The base mixing step (2) is the same as the base mixing step (1) in the production method (1) except that the mixed solution (2E) is used instead of the mixed solution (1E). In the base mixing step (2), the same effect as in the base mixing step (1) can be obtained.

[0211] <Other process (2)> The production method (2) may include other steps (sometimes referred to as "other steps (2)" in this specification) that do not fall under any of the above-mentioned emulsification step, emulsion mixing step, water mixing (2) step, acidification (2) step, surfactant mixing (2) step, cooling (2) step, polyvalent metal salt mixing (2) step, and base mixing (2) step, as long as the effects of the present invention are not impaired. The type of other step (2), the number of other steps (2), and the timing of performing other step (2) can be selected arbitrarily depending on the purpose, and are not particularly limited.

[0212] The microcapsules obtained by production method (2) may be used as an aqueous dispersion as is, or the aqueous dispersion obtained after performing known post-treatments, purification, etc. may be used as is, or the microcapsules may be used as a single substance by removing the dispersion medium after performing known post-treatments, purification, etc. as necessary. [Example]

[0213] The present invention will be described in more detail below with reference to specific examples, although the present invention is not limited to the examples shown below.

[0214] The nonionic surfactants used in the following examples and comparative examples are shown in Table 1.

[0215] [Table 1]

[0216] [Example 1] <<Microcapsule manufacturing>> An aqueous solution (130 g) of 7% by mass gelatin ("Type A" manufactured by MP Biomedicals) was heated to 50°C, and dioctyl sebacate (manufactured by Toyokuni Oil Essential Oils) (70 g) at room temperature (23°C) was added to this aqueous solution. An emulsion was then produced by stirring at a stirring speed of 10,000 rpm at room temperature for 3 minutes using an emulsifier (manufactured by Primix) (emulsification process).

[0217] An aqueous solution (130 g) of gum arabic (manufactured by Nacalai Tesque) with a concentration of 7% by mass was heated to 50°C, and the entire amount of the emulsion obtained above was added to this aqueous solution. The mixture was stirred for 2 minutes while maintaining the temperature at 50°C, thereby preparing a mixed solution (A) (emulsion mixing process).

[0218] Next, under the condition of 50°C, an aqueous solution of citric acid (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) with a concentration of 50% by mass was added dropwise to the mixed solution (A) while stirring it, and the mixture was stirred for 2 minutes to adjust the pH of the mixed solution (A) to 3.8, thereby preparing an acidic mixed solution (1B) (acidification (1) step).

[0219] Next, while stirring the mixed solution (1B) at 50°C, distilled water (200 g) at a temperature of 50°C was added thereto, and the mixture was stirred for 2 minutes while maintaining the temperature at 50°C to prepare the mixed solution (1C) (water mixing (1) step).

[0220] Next, while stirring the mixed solution (1C) at 50°C, nonionic surfactant (Z)-1 (2 g) was added thereto, and the mixture was stirred for 2 minutes while maintaining the temperature at 50°C to prepare mixed solution (1D) (surfactant mixing (1) step).

[0221] Next, the resulting mixed liquid (1D) was cooled with stirring at a cooling rate of 0.5°C / min until its temperature reached 5°C (cooling (1) step).

[0222] Next, to the mixed solution (1D) being stirred at a temperature of 5°C, an aqueous solution (50 g) of aluminum sulfate (Al2(SO4)3, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) with a concentration of 20% by mass was added, and the mixture was stirred for 2 minutes at a temperature of 5°C to prepare mixed solution (1E) (polyvalent metal salt mixing (1) step).

[0223] Next, while stirring the mixed solution (1E) at 5°C, an aqueous solution (50 g) of sodium hydroxide (manufactured by Kanto Chemical Co., Ltd.) with a concentration of 20% by mass was added dropwise to the mixed solution (1E) to adjust the pH of the mixed solution (1E) to 5.0, and then the mixed solution (1E) after the pH adjustment was stirred at room temperature for 4 hours to prepare an aqueous dispersion of microcapsules (base mixing (1) step). As a result of the above, a microcapsule was obtained as an aqueous dispersion, the wall component of which contained gelatin and gum arabic, and further contained aluminum sulfate and a polyoxyethylene polyoxypropylene block polymer with an HLB value of 16.2, and encapsulated dioctyl sebacate as a core material.

[0224] <<Evaluation of Microcapsules>> <Evaluation of the degree of microcapsule formation> The appearance of the product in the aqueous dispersion obtained above was observed using a scanning electron microscope (SEM, JEOL Ltd., "JSM-6700F") to confirm the degree of wall formation, and the degree of microcapsule formation was evaluated according to the following criteria. The results are shown in Table 2. [Evaluation criteria] A: The wall material is formed normally and the microcapsules are produced normally. B: The wall material is not formed normally and no microcapsules are produced.

[0225] <Measurement of the average particle size of microcapsules> The average particle size of the microcapsules was measured using a particle size distribution analyzer (Sysmex Corporation, "CDA-1000X") and the aqueous dispersion obtained above. The results are shown in Table 2.

[0226] <Safety classification of microcapsules> The safety of the obtained microcapsules to living organisms was classified according to the following criteria based on the raw materials used to manufacture the wall material. The results are shown in Table 2. [Classification criteria] A: The raw materials used to manufacture the wall material do not contain any substances that are highly toxic to living organisms, making the microcapsules highly safe for living organisms. B: The raw materials used to manufacture the wall material are highly toxic to living organisms, making the microcapsules less safe for living organisms.

[0227] <<Production and evaluation of microcapsules>> [Example 2] Microcapsules were produced and evaluated in the same manner as in Example 1, except that the same amount (parts by mass) of nonionic surfactant (Z)-2 was used instead of nonionic surfactant (Z)-1. The results are shown in Table 2.

[0228] In Table 2, a "-" in the "Raw Materials" column means that the raw material is not used. Furthermore, among the raw materials, components that do not fall into the category of gelatin, anionic polymers, or nonionic surfactants (e.g., crosslinking agents) are listed as "additives" in Table 2.

[0229] [Example 3] Microcapsules were produced and evaluated in the same manner as in Example 1, except that the same amount (parts by mass) of nonionic surfactant (Z)-3 was used instead of nonionic surfactant (Z)-1. The results are shown in Table 2.

[0230] [Example 4] Microcapsules were produced and evaluated in the same manner as in Example 1, except that the same amount (parts by mass) of nonionic surfactant (Z)-4 was used instead of nonionic surfactant (Z)-1. The results are shown in Table 2.

[0231] [Example 5] Microcapsules were produced and evaluated in the same manner as in Example 1, except that sodium alginate (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) was used in place of gum arabic in an amount half that of the gum arabic (parts by mass). The results are shown in Table 2.

[0232] [Example 6] Microcapsules were produced and evaluated in the same manner as in Example 1, except that half the amount (parts by mass) of carboxymethylcellulose sodium (manufactured by Daiichi Kogyo Seiyaku Co., Ltd.) was used instead of gum arabic. The results are shown in Table 2.

[0233] [Example 7] Microcapsules were produced and evaluated in the same manner as in Example 1, except that the same amount (parts by mass) of aluminum potassium sulfate (AlK(SO) Fujifilm Wako Pure Chemical Industries, Ltd.) was used instead of aluminum sulfate. The results are shown in Table 2.

[0234] [Example 8] Microcapsules were produced and evaluated in the same manner as in Example 1, except that the same amount (parts by mass) of aluminum ammonium sulfate (AlNH4(SO4)3, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) was used instead of aluminum sulfate. The results are shown in Table 2.

[0235] [Example 9] Microcapsules were produced and evaluated in the same manner as in Example 1, except that the same amount (parts by mass) of calcium chloride (CaCl, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) was used instead of aluminum sulfate. The results are shown in Table 2.

[0236] [Example 10] Microcapsules were produced and evaluated in the same manner as in Example 1, except that the same amount (parts by mass) of magnesium sulfate (MgSO4, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) was used instead of aluminum sulfate. The results are shown in Table 2.

[0237] [Example 11] Microcapsules were produced and evaluated in the same manner as in Example 1, except that the same amount (parts by mass) of zirconium sulfate (Zr(SO4)2, manufactured by Mitsuwa Chemical Co., Ltd.) was used instead of aluminum sulfate. The results are shown in Table 2.

[0238] [Example 12] <<Microcapsule manufacturing>> A mixed liquid (A) was prepared in the same manner as in Example 1 (emulsification step to emulsion mixing step).

[0239] Next, while stirring the mixed solution (A) at 50°C, distilled water (200 g) at a temperature of 50°C was added thereto, and the mixture was stirred for 2 minutes while maintaining the temperature at 50°C to prepare a mixed solution (2B) (water mixing (2) step).

[0240] Next, under the condition of 50°C, while stirring the mixed solution (2B), an aqueous solution of citric acid (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) with a concentration of 50% by mass was added dropwise thereto, and the mixture was stirred for 2 minutes to adjust the pH of the mixed solution (2B) to 3.8, thereby preparing an acidic mixed solution (2C) (acidification (2) step).

[0241] Next, while stirring the mixed solution (2C) at 50°C, nonionic surfactant (Z)-1 (2 g) was added thereto, and the mixture was stirred for 2 minutes while maintaining the temperature at 50°C to prepare mixed solution (2D) (surfactant mixing (2) step).

[0242] Next, the resulting mixed liquid (2D) was cooled with stirring at a cooling rate of 0.5°C / min until its temperature reached 5°C (cooling (2) step).

[0243] Next, to the mixed solution (2D) being stirred at a temperature of 5°C, an aqueous solution (50 g) of aluminum sulfate (Al2(SO4)3, manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) with a concentration of 20% by mass was added, and the mixture was stirred for 2 minutes at a temperature of 5°C to prepare a mixed solution (2E) (polyvalent metal salt mixing (2) step).

[0244] Next, while stirring the mixed solution (2E) at 5°C, an aqueous solution (50 g) of sodium hydroxide (manufactured by Kanto Chemical Co., Ltd.) with a concentration of 20% by mass was added dropwise to the mixed solution (2E) to adjust the pH of the mixed solution (2E) to 5.0, and then the pH-adjusted mixed solution (2E) was stirred at room temperature for 4 hours to prepare an aqueous dispersion of microcapsules (base mixing (2) process). As a result of the above, a microcapsule was obtained as an aqueous dispersion, the wall component of which contained gelatin and gum arabic, and further contained aluminum sulfate and a polyoxyethylene polyoxypropylene block polymer with an HLB value of 16.2, and encapsulated dioctyl sebacate as a core material.

[0245] <<Evaluation of Microcapsules>> The microcapsules obtained above were evaluated in the same manner as in Example 1. The results are shown in Table 2.

[0246] <<Production and evaluation of microcapsules>> [Comparative Example 1] Microcapsules were produced and evaluated in the same manner as in Example 1, except that the nonionic surfactant (Z)-1 was not used. The results are shown in Table 2. The production method in this comparative example is listed as "Modification 1" in Table 2.

[0247] Comparative Example 2 Microcapsules were produced and evaluated in the same manner as in Example 1, except that the same amount (parts by mass) of nonionic surfactant (Z)-5 was used instead of nonionic surfactant (Z)-1. The results are shown in Table 2. The production method in this comparative example is listed as "Variation 2" in Table 2.

[0248] Comparative Example 3 Microcapsules were produced and evaluated in the same manner as in Example 1, except that the same amount (parts by mass) of nonionic surfactant (Z)-6 was used instead of nonionic surfactant (Z)-1. The results are shown in Table 2. The production method in this comparative example is listed as "Variation 2" in Table 2.

[0249] Comparative Example 4 Microcapsules were produced and evaluated in the same manner as in Example 1, except that the same amount (parts by mass) of nonionic surfactant (Z)-7 was used instead of nonionic surfactant (Z)-1. The results are shown in Table 2. The production method in this comparative example is listed as "Variation 2" in Table 2.

[0250] Comparative Example 5 Microcapsules were produced and evaluated in the same manner as in Example 1, except that instead of adding an aqueous solution of aluminum sulfate, 8 g of an aqueous solution of formaldehyde (manufactured by Kanto Chemical Co., Ltd.) with a concentration of 37% by mass was added, resulting in 3 g of formaldehyde. The results are shown in Table 2. The production method in this comparative example is listed in Table 2 as "Modification 3."

[0251] Comparative Example 6 Microcapsules were produced and evaluated in the same manner as in Example 1, except that the same amount (parts by mass) of tannic acid was used instead of aluminum sulfate. The results are shown in Table 2. The production method in this comparative example is listed as "Modification 3" in Table 2.

[0252] Comparative Example 7 Microcapsules were produced and evaluated in the same manner as in Example 1, except that the same amount (parts by mass) of transglutaminase was used instead of aluminum sulfate. The results are shown in Table 2. The production method in this comparative example is listed as "Modification 3" in Table 2.

[0253] [Comparative Example 8] <<Microcapsule manufacturing>> An aqueous solution (130 g) of 7% by mass gelatin ("Type A" manufactured by MP Biomedicals) was heated to 50°C, and dioctyl sebacate (manufactured by Toyokuni Oil Refining Co., Ltd.) (70 g) and nonionic surfactant (Z)-1 (2 g) were added to this aqueous solution at room temperature (23°C). An emulsion was then produced by stirring the mixture at a stirring speed of 10,000 rpm at room temperature for 3 minutes using an emulsifier (manufactured by Primix Corporation).

[0254] An aqueous solution (130 g) of gum arabic (manufactured by Nacalai Tesque) with a concentration of 7% by mass was heated to 50°C, and the entire amount of the emulsion obtained above was added to this aqueous solution. The mixture was stirred for 2 minutes while maintaining the temperature at 50°C to prepare a mixed solution (A01).

[0255] Next, while stirring the mixed solution (A01) at 50°C, an aqueous solution of citric acid (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) with a concentration of 50% by mass was added dropwise thereto, followed by stirring for 2 minutes, and the pH of the mixed solution (A01) was adjusted to 3.8 to prepare an acidic mixed solution (1B01).

[0256] Next, while stirring the mixed solution (1B01) at 50°C, distilled water (200 g) at a temperature of 50°C was added thereto, and the mixture was stirred for 2 minutes while maintaining the temperature at 50°C to prepare a mixed solution (1C01).

[0257] Next, the resulting mixed liquid (1C01) was cooled to a temperature of 5°C at a cooling rate of 0.5°C / min while stirring.

[0258] Microcapsules were produced in the same manner as in Example 1, except that the mixed solution (1C01) stirred at 5° C. was used instead of the mixed solution (1D) stirred at 5° C. The production method in this comparative example is shown as “Modification 4” in Table 2.

[0259] <<Evaluation of Microcapsules>> The microcapsules obtained above were evaluated in the same manner as in Example 1. The results are shown in Table 2.

[0260] Comparative Example 9 <<Microcapsule manufacturing>> A mixed liquid (A) was prepared in the same manner as in Example 1 (emulsification step to emulsion mixing step).

[0261] Next, while stirring the mixed solution (A) at 50°C, nonionic surfactant (Z)-1 (2 g) was added thereto, and the mixture was stirred for 2 minutes while maintaining the temperature at 50°C to prepare mixed solution (1B02).

[0262] Next, while stirring the mixed solution (1B02) at 50°C, an aqueous solution of citric acid (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) with a concentration of 50% by mass was added dropwise thereto, followed by stirring for 2 minutes, and the pH of the mixed solution (1B02) was adjusted to 3.8, thereby producing an acidic mixed solution (1C02).

[0263] Next, while stirring the mixed solution (1C02) at 50°C, distilled water (200 g) at a temperature of 50°C was added thereto, and the mixture was stirred for 2 minutes while maintaining the temperature at 50°C to prepare a mixed solution (1D01).

[0264] Microcapsules were produced in the same manner as in Example 1, except that this acidic mixed solution (1D01) was used instead of the mixed solution (1D). The production method in this comparative example is shown in Table 2 as "Modification 5."

[0265] <<Evaluation of Microcapsules>> The microcapsules obtained above were evaluated in the same manner as in Example 1. The results are shown in Table 2.

[0266] [Comparative Example 10] <<Microcapsule manufacturing>> A mixed solution (1C) was prepared in the same manner as in Example 1 (water mixing (1) step).

[0267] Next, the resulting mixed liquid (1C) was cooled to a temperature of 5°C at a cooling rate of 0.5°C / min while stirring.

[0268] Next, nonionic surfactant (Z)-1 (2 g) was added to the mixed solution (1C) under stirring at a temperature of 5° C. to prepare a mixed solution (1E03).

[0269] Next, to this mixed solution (1E03) being stirred at a temperature of 5°C, an aqueous solution (50 g) of aluminum sulfate (manufactured by Fujifilm Wako Pure Chemical Industries, Ltd.) with a concentration of 20% by mass was added, and the mixture was stirred for 2 minutes at a temperature of 5°C to produce a mixed solution (1F03).

[0270] Microcapsules were produced in the same manner as in Example 1, except that this mixed solution (1F03) was used instead of the mixed solution (1E). The production method in this comparative example is shown as "Modification 6" in Table 2.

[0271] <<Evaluation of Microcapsules>> The microcapsules obtained above were evaluated in the same manner as in Example 1. The results are shown in Table 2.

[0272] [Table 2]

[0273] As is clear from the above results, in Examples 1 to 12, wall materials were formed normally, microcapsules were produced normally, and the average particle size was 16 μm or less (6 to 16 μm), which was sufficiently small. In Examples 1 to 12, no highly toxic substances to living organisms were used as raw materials for the wall materials, and the microcapsules were highly safe for living organisms. In Examples 1 to 12, the HLB values ​​of the nonionic surfactants were 12.8 or more (12.8 to 18.7), which was sufficiently large. In addition, in Examples 1 to 12, polyvalent metal salts were used.

[0274] In contrast to this, in Comparative Examples 1 to 4, 6, and 8 to 10, the wall material was formed normally and the microcapsules were produced normally, but the average particle size was large, at 31 μm or more. In Comparative Example 1, no nonionic surfactant was used. In Comparative Examples 2 to 4, a nonionic surfactant was used, but its HLB value was small, at 10.5 or less. In Comparative Example 6, no polyvalent metal salt was used. In Comparative Examples 8 to 10, a nonionic surfactant with a sufficiently large HLB value of 16.2 was used, but the timing of using the nonionic surfactant during the production of microcapsules was inappropriate.

[0275] In Comparative Example 5, the wall material was formed normally, the microcapsules were produced normally, and the average particle diameter was 9 μm, which was sufficiently small. However, formaldehyde, which is highly toxic to living organisms, was used as a raw material for manufacturing the wall material, and the safety of the microcapsules to living organisms was low.

[0276] In Comparative Example 7, the wall material was not formed normally, and no microcapsules were produced. Therefore, the average particle size of the microcapsules could not be measured. Thus, although microcapsules could not be produced in Comparative Example 7, the safety of the microcapsules was classified as "B" based on the raw materials used to produce the wall material. In Comparative Example 7, no polyvalent metal salt was used. [Industrial Applicability]

[0277] The present invention can be used as microcapsules for skin contact (for example, topical preparations, cosmetics, etc.).

Claims

[Claim 1] A microcapsule containing a core substance, the microcapsule comprising a cationic polymer, an anionic polymer, a polyvalent metal salt, and a nonionic surfactant having an HLB value of 12 or more, the wall material of the microcapsules is composed of the cationic polymer and the anionic polymer; The microcapsules contain at least gelatin as the cationic polymer, The average particle size of the microcapsules is 20 μm or less, The microcapsules are for skin contact.

Images