JP5241480B2 - Method for producing nanoparticles - Google Patents

Description

  The present invention relates to a method for producing nanoparticles and the nanoparticles.

  Fatty acids are very important substances for human beings, both nutritionally and physiologically. For example, lipids containing DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid) are used for the prevention of cardiovascular diseases. Recently, lipids containing palmitoleic acid have the effect of increasing the amount of antibacterial fatty acids in the epidermis (see, for example, Patent Document 1), and lipids containing DGLA (dihomo-γ-linolenic acid) Reported to have an action to improve disease (for example, see Patent Document 2), and a lipid containing α-linolenic acid to promote maturation of corneocytes (for example, see Patent Document 3). Has been. And when providing the fatty acid which has such a function as an external preparation applied to skin, hair, or mucous membrane, or an oral administration agent, the method of making it into a dispersion liquid is generally used.

  When a functional substance such as a fatty acid is used as the dispersion, creaming and aggregation can be effectively avoided as the particle size is smaller. Therefore, in order to obtain a stable dispersion, the nano-sizing is effective. For these reasons, for example, Patent Documents 4 to 7 and Non-Patent Document 1 disclose nano-size functional substances.

  Specifically, Patent Document 4 discloses that nanoparticles are obtained by homogenizing an aqueous solution containing a polyglycerin fatty acid ester and tocopherol at a high pressure of 200 MPa.

  In Patent Document 5, a mixture of polyglycerin fatty acid ester and polyoxyethylene nonionic surfactant in a large amount of polyglycerin fatty acid ester and polyoxyethylene-based nonionic surfactant and a mixture of a large amount of polyhydric alcohol such as glycerin is mixed with water. It is disclosed that nanoparticles can be obtained by simple stirring without using high-pressure emulsification.

  Patent Document 6 discloses that nanoparticles mixed with lecithin, surfactant, and ethanol are mixed with water to obtain nanoparticles by simple stirring without using high-pressure emulsification. Yes.

  Patent Document 7 discloses that calcium stearate nanoparticles are obtained by mixing stearic acid dissolved in benzene with a surfactant solution, and dropping an aqueous calcium chloride solution and an aqueous sodium hydroxide solution thereto. Yes.

Non-Patent Document 1 discloses that fatty acid nanoparticles are obtained by dissolving a fatty acid in subcritical water and then reducing the pressure while mixing it with an aqueous surfactant solution.
JP-T-2004-504044 WO2006 / 085687A1 JP 2004-35456 A JP 2004-175664 A JP 2004-277375 A JP 11-335261 A JP 2005-306972 A Journal of Colloid and Interface Science 278 (2004) 192-197

  The objective of this invention is providing the manufacturing method of the nanoparticle which can prepare the nanoparticle dispersion liquid of the stable fatty acid easily without using an organic solvent, and the nanoparticle.

The method for producing nanoparticles of the present invention is a method for producing nanoparticles by preparing a nanoparticle dispersion in the absence of an organic solvent,
Step 1 of mixing an aqueous solution of component (A) that is a fatty acid and / or fatty acid salt having 10 to 36 carbon atoms and component (B) that is a surfactant;
Step 2 of mixing the liquid obtained in Step 1 above with the component (C) that is an acid and / or the component (D) that is a divalent to trivalent metal salt;
including.

  The nanoparticles of the present invention are produced by the method for producing nanoparticles of the present invention.

  According to the present invention, by preparing a nanoparticle dispersion in the absence of an organic solvent by the method including steps 1 and 2, deterioration of stability over time is suppressed, and the nanoparticles are reduced in size and stabilized. A fatty acid nanoparticle dispersion can be easily prepared.

  Hereinafter, embodiments will be described in detail.

  The method for producing nanoparticles according to this embodiment includes at least the following steps 1 and 2, and produces nanoparticles by preparing a nanoparticle dispersion in the absence of an organic solvent. According to this method for producing nanoparticles, by preparing a nanoparticle dispersion in the absence of an organic solvent by a method comprising the following steps 1 and 2, deterioration of stability over time is suppressed and nanoparticles are produced. A stable dispersion of fatty acid nanoparticles with a reduced particle size can be easily prepared.

  Here, an organic solvent is not used in the method for producing nanoparticles, but the organic solvent is a liquid organic compound capable of dissolving a solid, a gas, or a liquid, for example, methanol, ethanol, acetone. , Propanol, butanol and the like.

(Process 1)
In step 1, an aqueous solution of component (A) that is a fatty acid and / or fatty acid salt having 10 to 36 carbon atoms and component (B) that is a surfactant are mixed.

  (A) A component is a C10-C36 fatty acid and / or fatty acid salt.

  Examples of the fatty acid having 10 to 36 carbon atoms include lauric acid (C12), myristic acid (C14), palmitic acid (C16), stearic acid (C18), arachidic acid (C20), behenic acid (C22), and lignoceric acid. (C24), serotic acid (C26), montanic acid (C28), palmitoleic acid (C16), oleic acid (C18), erucic acid (C22), linoleic acid (C18), linolenic acid (C18), docosahexaenoic acid (C22) ), Eicosapentaenoic acid (C20), isostearic acid (C18) and the like. Examples of fatty acids having a melting point of 50 ° C. or higher include myristic acid, palmitic acid, stearic acid, arachidic acid, behenic acid, lignoceric acid, serotic acid, and montanic acid.

  Examples of the fatty acid salt include fatty acid potassium, fatty acid sodium, fatty acid triethanolamine, and fatty acid ammonium. Of these, fatty acid potassium and sodium fatty acid are preferred, and fatty acid potassium is preferred for obtaining fatty acid nanoparticles having a smaller particle size and a higher concentration.

  The fatty acid salt may be obtained by treating a fatty acid having 10 to 36 carbon atoms with an alkali agent. Examples of the alkali in that case include potassium hydroxide, sodium hydroxide, potassium carbonate, sodium carbonate, triethanolamine and the like. Of these, potassium hydroxide and sodium hydroxide are preferable, and potassium hydroxide is particularly preferable.

  The component (A) may be a single type or a plurality of types of fatty acids, may be a single type or a plurality of types of fatty acid salts, and may be a single type or a plurality of types of fatty acids and a single type or It may be a combination with a plurality of types of fatty acid salts.

  The amount of the component (A) is preferably such that the content in the prepared nanoparticle dispersion is 0.1% by mass or more, and more preferably 0.5% by mass or more. On the other hand, since the amount of fatty acid in the nanoparticle dispersion is limited to the amount of saturated solubility, the amount of the component (A) is such that the content in the prepared nanoparticle dispersion is 20% by mass or less. Is preferable, and the amount of 10% by mass or less is more preferable. In addition, since the solubility is increased by heating, in the case of a fatty acid having a melting point of 50 ° C. or higher, the aqueous solution is preferably heated to the melting point or higher in order to obtain high-concentration fatty acid nanoparticles.

  The component (B) is a surfactant other than the component (A).

  The surfactant is preferably a nonionic surfactant, an anionic surfactant, or an amphoteric surfactant from the viewpoint of dispersing the fatty acid in nano size. Specifically, examples of the nonionic active agent include polyglycerin fatty acid ester, sucrose fatty acid ester, polyoxyethylene alkyl ether, polyoxyethylene sorbitan fatty acid ester and the like. Examples of the anionic activator include polyoxyethylene alkyl ether sulfate, polyoxyethylene alkyl acetate, polyoxyethylene alkyl ether phosphate, N-acyl taurine salt, N-acyl amino acid salt and the like. Examples of zwitterionic activators include alkyl betaines, amine oxides, imidazolinium betaines, and enzymatically decomposed lecithins. Of these, those having an alkyl chain length of 12 carbon atoms are particularly preferred.

  The surfactant may be only one or a plurality of nonionic surfactants, may be only a single species or a plurality of anionic surfactants, and may be a single species or a plurality of species. These zwitterionic surfactants may be used alone, or a combination thereof.

  The blending amount of the surfactant is preferably such that the mass ratio of the (B) component to the (A) component is such that the mass of the (B) component / the mass of the (A) component = 0.1 to 5.0. An amount of 5 to 3.0 is more preferable.

  The mixing means of the aqueous solution of component (A) and the component (B) is not particularly limited, and examples thereof include known stirring means such as stirring blades such as a propeller, turbine, disper, and anchor, and a stirrer. . The mixing temperature is preferably equal to or higher than the melting point of the component (A), for example, preferably 40 to 100 ° C, and more preferably 50 to 90 ° C.

  In this step 1, from the viewpoint of reducing the particle size of the fatty acid, the mixing temperature of the aqueous solution of the component (A) and the component (B) is the higher of the melting point of the component (A) or the temperature exceeding 40 ° C. It is preferable to rapidly cool the liquid obtained by mixing them to 20 to 40 ° C. In that case, the cooling means is not particularly limited, and for example, a known method using a double-tube countercurrent cooling device or the like can be used. The cooling rate is preferably 5 ° C./second or more, and more preferably 10 ° C./second or more.

  In addition, in this process 1, you may mix a thickener, antiseptic | preservative, a coloring agent, a disintegration inhibitor, antioxidant, etc. other than (A) component and (B) component.

(Process 2)
In Step 2, the liquid obtained in Step 1 is mixed with the component (C) that is an acid and / or the component (D) that is a divalent to trivalent metal salt. This produces a nanoparticle dispersion of the fatty acid.

  Component (C) is an acid.

  Examples of the acid include hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, citric acid, lactic acid, malic acid, fumaric acid, succinic acid and the like. Of these, hydrochloric acid and citric acid are preferable.

  Component (C) may be a single species or a plurality of species. When blending only the component (C), the blending amount is from the viewpoint of the stability of the nanoparticle dispersion, the number of moles of acidic hydrogen in the component (C) / the number of moles of the component (A) = 0.8-3. An amount that becomes 0.9 to 1.5 is more preferable.

  Component (D) is a divalent to trivalent metal salt.

  Examples of the divalent metal salt include calcium salts such as calcium chloride, calcium lactate and calcium sulfate; zinc salts such as zinc chloride, zinc acetate and zinc sulfate; copper salts such as copper chloride and copper sulfate. Examples of the trivalent metal salt include iron salts such as iron chloride and iron sulfate. Of these, calcium chloride, calcium lactate and zinc chloride are preferred.

  The component (D) may be only a single species or a plurality of types of divalent metal salts, may be a single species or a plurality of types of trivalent metal salts, and may be a single species or a plurality of species. A combination of a divalent metal salt of a species and a single species or a plurality of trivalent metal salts may be used.

  When blending only the component (D), the blending amount is the number of moles of the metal (D) component / number of moles of the component (A) in the case of a divalent metal salt from the viewpoint of the stability of the nanoparticle dispersion. = 0.4 to 1.5 is preferable, and an amount of 0.45 to 0.75 is more preferable. In the case of a trivalent metal salt, the number of moles of metal contained in the component (D) / (A) The amount of the number of moles of the component = 0.27 to 1.0 is preferable, and the amount of 0.3 to 0.5 is more preferable.

  Only one of the component (C) and the component (D) may be used, or both of them may be used.

  The mixing means of the liquid obtained in step 1 and the component (C) and / or the component (D) is not particularly limited. For example, a stirring blade or a stirrer such as a propeller, a turbine, a disper, or an anchor is used. Well-known means such as a stationary mixer and a micromixer provided can be used. For example, the mixing temperature is preferably 20 to 40 ° C, and more preferably 25 to 35 ° C. When the liquid is rapidly cooled to 20 to 40 ° C. in Step 1, since the liquid becomes unstable, it is preferable to mix the component (C) and / or the component (D) immediately after the rapid cooling.

  In Step 2, in addition to the component (C) and / or the component (D), a thickener, an antiseptic, a colorant, an anti-collapse agent, an antioxidant, and the like may be mixed.

(Process 3)
In the method for producing nanoparticles according to the present embodiment, when the component (D) is mixed in Step 2, as Step 3, the liquid (nanoparticle dispersion) obtained in Step 2 and monovalent to trivalent basicity are used. You may mix the (E) component which is a salt.

  The component (E) is a monovalent to trivalent basic salt.

  Examples of the component (E) include hydrogen carbonates such as sodium hydrogen carbonate and potassium hydrogen carbonate; hydrogen phosphates such as sodium hydrogen phosphate and potassium hydrogen phosphate; carbonates such as sodium carbonate and potassium carbonate; Examples thereof include phosphates such as sodium and potassium phosphate. Of these, carbonates and phosphates are preferred.

  The amount of component (E) is preferably such that the number of moles of component (E) / number of moles of component (D) = 0.05 to 0.5, from the viewpoint of the stability of the nanoparticle dispersion. An amount of 0.1 to 0.3 is more preferable.

  The mixing means of the liquid obtained in step 2 and the component (E) is not particularly limited. For example, a stationary mixer equipped with a stirring blade or a stirrer such as a propeller, a turbine, a disper, or an anchor, Well-known means, such as a micro mixer, are mentioned. For example, the mixing temperature is preferably 20 to 40 ° C, and more preferably 25 to 35 ° C.

  In Step 3, in addition to the component (E), a thickener, an antiseptic, a colorant, a disintegration inhibitor, an antioxidant, and the like may be mixed.

(Nanoparticle dispersion)
The nanoparticle dispersion prepared through the above steps preferably has a fatty acid nanoparticle concentration of 0.1 to 20% by mass, preferably 0.5 to 10% by mass. This can be controlled by setting the amount of component (A) in step 1.

  The nanoparticle dispersion liquid preferably has a dynamic scattering diameter measured by a dynamic scattering method of nanoparticles of 1 to 250 nm, and more preferably 5 to 200 nm. This can be controlled by the type of component (A), the type and amount of component (B), the amount of component (C) and / or component (D). In order to obtain finer nanoparticles, it is preferable that the surfactant (B) component contains a large number of surfactants having 12 alkyl chains.

  Nanoparticle dispersions are products that can be used as pharmaceutical compositions, such as cosmetics, soaps, body soaps, facial cleansers, bath preparations, lotions, lotions, shampoos, rinses, and toothpastes that are applied to skin, hair and mucous membranes. , Dental rinses, poultices, adhesives and other external preparations; oral administration agents and the like.

(Dispersion preparation)
Dispersions of the following Examples 1 to 13 and Comparative Examples 1 and 2 were prepared. Each configuration is also shown in Table 1.

<Example 1>
1.0g of behenic acid-containing fatty acid (trade name: LUNAC BA, 85% by mass of behenic acid, neutralization value = 166, manufactured by Kao Corporation) as component (A) while stirring with 37.8g of ion-exchanged water using a stirrer piece Then, 0.157 g of potassium hydroxide was added and the mixture was stirred and mixed at 85 ° C. for 30 minutes. Next, while continuing stirring to this aqueous solution, 1.0 g of decaglycerin lauric acid ester (trade name: Ryoto Polyglycerin L-7D, HLB = 17, manufactured by Mitsubishi Chemical Foods Co., Ltd.) was added as component (B) for 3 minutes. Stir and mix. Then, while continuing stirring to this aqueous solution, 10.0 g of 0.31N hydrochloric acid was added as component (C), and immediately from 85 ° C. to room temperature (25 ° C.) in a passage time of 5 seconds by a double tube countercurrent cooling device. The solution was rapidly cooled to obtain a dispersion of fatty acid nanoparticles. This nanoparticle dispersion was designated as Example 1. The pH of Example 1 was 2. The pH was measured at 25 ° C. using a pH meter (manufactured by HORIBA, Ltd., model number: D-53) (same as Example 2 and below).

  In addition, the density | concentration of (A) component is 2.00 mass%. The mass ratio of the component (B) to the component (A) is the mass of the component (B) / the mass of the component (A) = 1.00. The number of moles of acidic hydrogen contained in component (C) / number of moles of component (A) = 1.0.

<Example 2>
1.0g of behenic acid-containing fatty acid (trade name: LUNAC BA, 85% by mass of behenic acid, neutralization value = 166, manufactured by Kao Corporation) as component (A) while stirring with 37.8g of ion-exchanged water using a stirrer piece Then, 0.157 g of potassium hydroxide was added and the mixture was stirred and mixed at 85 ° C. for 30 minutes. Next, while continuing stirring to this aqueous solution, 1.0 g of decaglycerin lauric acid ester (trade name: Ryoto Polyglycerin L-7D, HLB = 17, manufactured by Mitsubishi Chemical Foods Co., Ltd.) was added as component (B) for 3 minutes. Immediately after stirring and mixing, the mixture was rapidly cooled from 85 ° C. to room temperature (25 ° C.) with a double tube countercurrent cooling device with a passage time of 5 seconds. Then, while continuing stirring to this aqueous solution, 10.0 g of 0.31N hydrochloric acid was added as component (C) to obtain a nanoparticle dispersion of fatty acid. This nanoparticle dispersion was designated as Example 2. The pH of Example 2 was 1.8.

  In addition, the density | concentration of (A) component is 2.00 mass%. The mass ratio of the component (B) to the component (A) is the mass of the component (B) / the mass of the component (A) = 1.00. The number of moles of acidic hydrogen contained in component (C) / number of moles of component (A) = 1.0.

<Example 3>
A fatty acid nanoparticle dispersion was obtained in the same manner as in Example 2 except that the amount of ion-exchanged water was 38.3 g and the amount of decaglycerin laurate was 0.5 g. This nanoparticle dispersion was designated as Example 3. The pH of Example 3 was 2.3.

  In addition, the density | concentration of (A) component is 2.00 mass%. The mass ratio of the (B) component to the (A) component is the mass of the (B) component / the mass of the (A) component = 0.50. The number of moles of acidic hydrogen contained in component (C) / number of moles of component (A) = 1.0.

<Example 4>
A fatty acid nanoparticle dispersion was obtained in the same manner as in Example 2 except that the amount of ion-exchanged water was 35.8 g and the amount of decaglycerin laurate was 3.0 g. This nanoparticle dispersion was designated as Example 4. The pH of Example 4 was 2.2.

  In addition, the density | concentration of (A) component is 2.00 mass%. The mass ratio of the (B) component to the (A) component is (B) component mass / (A) component mass = 3.00. The number of moles of acidic hydrogen contained in component (C) / number of moles of component (A) = 1.0.

<Example 5>
A fatty acid nanoparticle dispersion was obtained in the same manner as in Example 2 except that decaglycerin laurate was added and then rapidly cooled to 11 ° C. This nanoparticle dispersion was designated as Example 5. The pH of Example 5 was 2.1.

  In addition, the density | concentration of (A) component is 2.00 mass%. The mass ratio of the component (B) to the component (A) is the mass of the component (B) / the mass of the component (A) = 1.00. The number of moles of acidic hydrogen contained in component (C) / number of moles of component (A) = 1.0.

<Example 6>
(B) Instead of decaglycerin laurate as a component, sucrose laurate (trade name: Ryoto Sugar Ester L-1695, HLB = 16, manufactured by Mitsubishi Chemical Foods) was used, and 0.31N hydrochloric acid was used. A fatty acid nanoparticle dispersion was obtained in the same manner as in Example 2 except that 9.5 g was used. This nanoparticle dispersion was designated as Example 6. The pH of Example 6 was 4.8.

  In addition, the density | concentration of (A) component is 2.02 mass%. The mass ratio of the component (B) to the component (A) is the mass of the component (B) / the mass of the component (A) = 1.00. The number of moles of acidic hydrogen contained in component (C) / number of moles of component (A) = 0.95.

<Example 7>
The amount of ion-exchanged water is 33.5 g, the amount of behenic acid is 3.0 g, the amount of potassium hydroxide is 0.457 g, the amount of decaglycerin laurate is 3.0 g, and 0.93N hydrochloric acid is used for neutralization. A fatty acid nanoparticle dispersion was obtained in the same manner as in Example 2 except that 0.0 g was used. This nanoparticle dispersion was designated as Example 7. The pH of Example 7 was 2.2.

  In addition, the density | concentration of (A) component is 6.00 mass%. The mass ratio of the component (B) to the component (A) is the mass of the component (B) / the mass of the component (A) = 1.00. The number of moles of acidic hydrogen contained in component (C) / number of moles of component (A) = 1.0.

<Example 8>
A fatty acid nanoparticle dispersion was obtained in the same manner as in Example 2 except that the amount of ion-exchanged water was 37.9 g, and 0.106 g of sodium hydroxide was used instead of potassium hydroxide. This nanoparticle dispersion was designated as Example 8. The pH of Example 8 was 1.8.

  In addition, the density | concentration of (A) component is 2.00 mass%. The mass ratio of the component (B) to the component (A) is the mass of the component (B) / the mass of the component (A) = 1.00. The number of moles of acidic hydrogen contained in component (C) / number of moles of component (A) = 1.0.

<Example 9>
A fatty acid nanoparticle dispersion was obtained in the same manner as in Example 2 except that a 0.10N aqueous citric acid solution was used as the component (C) instead of hydrochloric acid. This nanoparticle dispersion was designated as Example 9. The pH of Example 9 was 5.3.

  In addition, the density | concentration of (A) component is 2.00 mass%. The mass ratio of the component (B) to the component (A) is the mass of the component (B) / the mass of the component (A) = 1.00. The number of moles of acidic hydrogen contained in component (C) / number of moles of component (A) = 0.96.

<Example 10>
The amount of potassium hydroxide was 0.166 g, and the fatty acid solution was the same as in Example 2 except that 5.0 g of a 0.31N calcium chloride aqueous solution was used as the component (D) instead of hydrochloric acid as the component (C). A nanoparticle dispersion was obtained. This nanoparticle dispersion was designated as Example 10. The pH of Example 10 was 5.3.

  In addition, the density | concentration of (A) component is 2.22 mass%. The mass ratio of the component (B) to the component (A) is the mass of the component (B) / the mass of the component (A) = 1.00. The number of moles of metal in component (D) / number of moles of component (A) = 0.50.

<Example 11>
(B) Nanoparticle dispersion of fatty acid in the same manner as in Example 2, except that sodium N-lauroylmethyl taurate (trade name: NIKKO LMT manufactured by Nikko Chemicals Co., Ltd.) was used instead of decaglycerin laurate. Got. This nanoparticle dispersion was designated as Example 11. The pH of Example 11 was 2.3.

  In addition, the density | concentration of (A) component is 2.00 mass%. The mass ratio of the component (B) to the component (A) is the mass of the component (B) / the mass of the component (A) = 1.00. The number of moles of acidic hydrogen contained in component (C) / number of moles of component (A) = 1.0.

<Example 12>
(B) Nanoparticle dispersion of fatty acid in the same manner as in Example 10 except that sodium N-lauroylmethyl taurate (trade name: NIKKO LMT manufactured by Nikko Chemicals) was used in place of decaglycerin laurate Got. This nanoparticle dispersion was designated as Example 12. The pH of Example 12 was 6.9.

  In addition, the density | concentration of (A) component is 2.22 mass%. The mass ratio of the component (B) to the component (A) is the mass of the component (B) / the mass of the component (A) = 1.00. The number of moles of metal in component (D) / number of moles of component (A) = 0.5.

<Example 13>
Example: Except for adding 0.31N calcium chloride aqueous solution as component (D) and then adding 1.25 g of 0.31N sodium carbonate aqueous solution as component (E) and stirring for 60 minutes while continuing stirring. In the same manner as in Example 12, a fatty acid nanoparticle dispersion was obtained. This nanoparticle dispersion was designated as Example 13. The pH of Example 13 was 10.5.

  In addition, the density | concentration of (A) component is 2.16 mass%. The mass ratio of the component (B) to the component (A) is the mass of the component (B) / the mass of the component (A) = 1.00. The number of moles of metal in component (D) / number of moles of component (A) = 0.50. The number of moles of component (E) / number of moles of component (D) = 0.25.

<Comparative Example 1>
While stirring with 378.0 g of ion-exchanged water using a stirrer piece, 1.57 g of potassium hydroxide and 100.0 g of 0.31N hydrochloric acid as component (C) were added and stirred and mixed at 85 ° C. for 5 minutes. Next, 10.0 g of a behenic acid-containing fatty acid (trade name: Lunac BA, 85% by weight of behenic acid, neutralization value = 166) was added as component (A) while continuing to stir the aqueous solution. Stir and mix for a minute. Then, this aqueous solution was stirred at 8000 rpm for 1 minute using a TK homomixer (manufactured by Primix) and immediately cooled rapidly from 85 ° C. to room temperature (25 ° C.) with a double tube countercurrent cooling device in 5 seconds. A fatty acid dispersion was obtained. This dispersion was designated as Comparative Example 1.

  In addition, the density | concentration of (A) component is 1.95 mass%. The mass ratio of the component (B) to the component (A) is the mass of the component (B) / the mass of the component (A) = 1.00. The number of moles of acidic hydrogen contained in component (C) / number of moles of component (A) = 1.0.

<Comparative example 2>
While stirring with 29.8 g of ion-exchanged water using a stirrer piece, behenic acid-containing fatty acid (product name: Lunac BA, containing 85% by mass of behenic acid, neutralization value = 166) as component (A) 1.0 g Then, 0.157 g of potassium hydroxide was added and the mixture was stirred and mixed at 85 ° C. for 30 minutes. Next, while continuing stirring to this aqueous solution, 1.0 g of decaglycerin lauric acid ester (trade name: Ryoto Polyglycerin L-7D, HLB = 17, manufactured by Mitsubishi Chemical Foods Co., Ltd.) was added as component (B) for 3 minutes. Stir and mix. After cooling this solution to 70 ° C., 8.0 g of ethanol was added with stirring using a stirrer piece, and the mixture was stirred and mixed for 3 minutes. Rapid cooling to room temperature (25 ° C.). Then, while continuing stirring to this aqueous solution, 10.0 g of 0.31N hydrochloric acid was added as component (C) to obtain a nanoparticle dispersion of fatty acid. This nanoparticle dispersion was designated as Comparative Example 2. The pH of Comparative Example 2 was 2.0.

  In addition, the density | concentration of (A) component is 2.00 mass%. The mass ratio of the component (B) to the component (A) is the mass of the component (B) / the mass of the component (A) = 1.00. The number of moles of acidic hydrogen contained in component (C) / number of moles of component (A) = 1.0.

(Test evaluation method)
<Dynamic scattering diameter>
About each of Examples 1-13 and Comparative Examples 1-2, the dynamic scattering diameter was measured using the dynamic scattering particle size distribution measuring apparatus (Otsuka Electronics Co., Ltd. model number: DLS-Z2).

<Liquid stability>
About each of Examples 1-13 and Comparative Examples 1-2, the external appearance 12 hours after the manufacture was visually evaluated.

(Test evaluation results)
The test results are shown in Table 1.

  The dynamic scattering diameter is 160 nm for Example 1, 38 nm for Example 2, 76 nm for Example 3, 20 nm for Example 4, 90 nm for Example 5, 38 nm for Example 6, 45 nm for Example 7, and Example. 8 is 45 nm, Example 9 is 29 nm, Example 10 is 71 nm, Example 11 is 18 nm, Example 12 is 18 nm, Example 13 is 17 nm, Comparative Example 1 is 1500 nm, and Comparative Example 2 is 354 nm. there were.

  In Examples 1 to 13, the liquid stability was stable while maintaining a bluish and transparent appearance until 12 hours from the beginning of production, whereas in Comparative Example 1, the liquid stability was cloudy from the beginning of production. After a time, creaming was confirmed on the liquid surface, and in Comparative Example 2, it was cloudy from the beginning of production, and remained cloudy after 12 hours.

  From the results of Examples 1 and 2, it can be seen that significantly fine fatty acid nanoparticles can be obtained by rapid cooling before mixing the hydrochloric acid of component (C).

  From the result of Examples 2-4, it turns out that the nanoparticle of a fine fatty acid is obtained, so that there are many compounding quantities of (B) component surfactant.

  From the results of Examples 2 and 8, it is understood that finer fatty acid nanoparticles can be obtained when the fatty acid salt is made of potassium salt than when it is made of sodium salt.

  From the results of Example 2 and Comparative Example 2, it can be seen that the presence of the organic solvent ethanol increases the particle size of the fatty acid and significantly deteriorates the stability.

  The present invention is useful for a method for producing nanoparticles and the nanoparticles.

Claims (5)

A method of producing nanoparticles by preparing a nanoparticle dispersion in the absence of an organic solvent,
Step 1 of mixing an aqueous solution of component (A) that is a fatty acid and / or fatty acid salt having 10 to 36 carbon atoms and component (B) that is a surfactant;
A liquid obtained in the step 1, a divalent to trivalent metal salt and the component (D), and step 2 of mixing,
A method for producing nanoparticles comprising
In the step 1, a method for producing nanoparticles, wherein a liquid obtained by mixing an aqueous solution of the component (A) and the component (B) is rapidly cooled to 20 to 40 ° C. at a cooling rate of 5 ° C./second or more .   The nano of Claim 1 which further includes the process 3 which mixes the liquid obtained by mixing the (D) component at the said process 2, and the (E) component which is a monovalent to trivalent basic salt. Particle production method.   The method for producing nanoparticles according to claim 1 or 2, wherein the fatty acid salt of the component (A) is obtained by treating a fatty acid having 10 to 36 carbon atoms with an alkali agent. The content of the component (A) in the prepared nanoparticle dispersion is 0.1 to 20% by mass, and the mass ratio of the component (B) to the component (A) is the mass of the component (B) / (A). The method for producing nanoparticles according to any one of claims 1 to 3 , wherein the mass of the component = 0.1 to 5.0. Dynamic scattering size measured by a dynamic scattering method of nanoparticles produced is 1 to 250 nm, method for producing nanoparticles according to any one of claims 1-4.