JP2005028559A - Nanocapsule - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide simple and low cost nanosized particles having excellent stability and high safety which consists of water and/or liquid matrix, a surfactant dissolved/dispersed in it, and a fat-soluble material, its application, and a manufacturing method. <P>SOLUTION: The simple and low cost nanosized particles having excellent stability, and high safety can be manufactured by the materials consisting of one kind or more simple substance of water and/or liquid matrix or its complex, one kind or more simple substance of the surfactant dissolved/dispersed in it or its complex, and one kind or more simple substance of the fat-soluble material or its complex. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

Detailed Description of the Invention

The present invention relates to a nanocapsule having good stability and high safety composed of water and / or a liquid matrix, a surfactant dissolved and dispersed therein, and a fat-soluble substance, its use, and a method for using the same.

Conventionally, as a method for obtaining nano-sized microcapsules, a method of blending organic silicic acid, a method of blending metal soap, and the like are known.

German patent DE 19846660 discloses nano-sized or mixed oxide particles surrounded by organosilicon groups covalently bonded to the oxide particles. Expensive because the components are used in the prepolymer.

DE 198464659 teaches the use of acryloxyalkylsilanes to make nano-sized capsule particles with reactive radiation curable groups.

However, in the method of blending organosilicic acid, it is necessary to blend a large amount of these components for gelation, and there are problems such as poor extensibility, low safety, and skin irritation. In addition, the nanocapsules were liable to collapse and the stability was not sufficient. As described above, none of the conventional nanocapsule compositions was sufficiently satisfactory. In addition, these nano-sized fine particles according to the prior art tend to agglomerate easily, and are difficult to diffuse and apply to a single layer. In order to use them as industrial raw materials, treatments such as pulverization, re-dispersion, and re-dissolution are necessary. There was a problem that processing was extremely complicated and difficult to handle, and the performance of nano-sized particles could not be fully demonstrated.

Problems to be solved by the invention

An object of the present invention is to provide a stable and high-safety simple and inexpensive structure with a low degree of secondary aggregation, comprising water and / or a liquid matrix, a surfactant dissolved and dispersed therein, and a fat-soluble substance. It is to provide a nanocapsule, its use, and production method.

Problems to be solved by the invention

The present invention has good stability, high safety, and can contain a large amount of fat-soluble substances in capsules, and can be used for pharmaceuticals, pharmaceutical raw materials, cosmetics, cosmetic raw materials, external preparations, iontophoretic compositions, vibrations. Introduction composition, electromagnetic wave introduction composition, thermal introduction composition, electrolytic introduction composition, food, food additive, functional food, feed, feed additive, anti-aging agent, antioxidant, antioxidant It is an object of the present invention to provide a nano-sized capsule composition suitable for use in the above, its use, and usage.

Means for solving the problem

As a result of intensive studies to solve the above problems, the present inventors have found that nanocapsules can be prepared by water-dispersing a combination of a surfactant, a non-aqueous matrix, and a fat-soluble component. . Further, the present inventors have found that the nanocapsules have extremely good stability and high safety, and have completed the present invention.

That is, the present invention relates to the following matters.

Claim 1

  From one or more simple substances of water and / or a liquid matrix or a composite thereof, one or more simple substances of a surfactant dissolved or dispersed therein or a composite thereof, and one or more simple substances of a fat-soluble substance or a composite thereof. Composition for raw material for producing nanocapsules

Claim 2

  A nanocapsule production raw material composition according to claim 1 formed by dispersing in water in a range of 1 micrometer or less, preferably in the range of 999 nanometers to 1 nanometer, more preferably in the range of 300 nanometers to 10 nanometers. Nanocapsules with average particle size in the range

Claim 3

  The nanocapsule according to claim 2, wherein the surfactant according to claim 1 is one or a mixture selected from surfactin, a derivative thereof and a salt thereof.

Claim 4

  The nanocapsule according to claim 2, wherein the water and / or liquid matrix according to claim 1 is one or a mixture selected from glycerin and its derivatives and salts thereof.

Claim 5

  The fat-soluble substance of claim 1 is an antioxidant substance, preferably an antioxidant substance having a radical scavenging effect such as singlet oxygen, hydroxy radical, NO radical, lipid peroxide, more specifically vitamin C, A fat-soluble substance selected from vitamin E, vitamin A, coenzyme, lipoic acid, polyphenol, fullerene, tar dye, fat-soluble conductive substance, fat-soluble magnetic substance, fat-soluble pigment, fat-soluble dye, or the like, or The nanocapsule according to claim 2, wherein the nanocapsule is an antioxidant derivative or provitamin which is one or more of a fat-soluble derivative, a complex with a fat-soluble substance, or a complex with a fat-soluble substance.

Claim 6

  The nanocapsule according to claim 2 is used for pharmaceuticals, pharmaceutical raw materials, cosmetics, cosmetic raw materials, external preparations, ion introduction compositions, vibration introduction compositions, electromagnetic wave introduction compositions, heat introduction compositions, and electrolytic introduction compositions. Products, foods, food additives, functional foods, feeds, feed additives, antioxidants, antioxidants, antioxidants, paints, toners, ink jet inks, inkjet printed circuit boards, and photosensitive particles for photographic films The use according to claim 2, which is one or more of a simple substance or a mixture

Claim 7

  A method for enhancing the effect of the use according to claim 6 by introducing the nanocapsule according to claim 2 by one or more single methods or a mixing method selected from ion introduction, vibration introduction, electromagnetic wave introduction, heat introduction, and electrolysis introduction.

Claim 8

  A method for producing fine emulsified particles having an average particle diameter of less than 1000 nm dispersed in water and an aqueous solvent by subjecting the composition for raw material for producing nanocapsules of claim 1 to impact deformation at a shear rate of at least 15 / s.

Claim 9

  The method according to claim 9, wherein the shear deformation is performed using at least one dispersion device selected from the group consisting of a static mixer, a jet dispersator, a microporous filter, a microfluidizer, and a Manton-Gaulin homogenizer nozzle. .

Hereinafter, the present invention will be described in detail.
In the present invention, the water of claim 1 is purified water having a pH of 1 to 13, ion exchange water, distilled water, natural water, alkali ion water, acid water, electrolytic ion water, negative ion water, strong acid water, strong alkali water. Any water that can dissolve 50% by weight or more of HCl as an equivalent solvent may be used.

The liquid matrix of the present invention and claim 1 is a polyhydric alcohol, glycerin, ethanol, propanol, isopropanol, gelling agent, glycerin, methyl laurate, lauryl alcohol, glycerol monolaurate, oleic acid, oleyl alcohol, monooleic acid Glycerol, glycerol dioleate and glycerol trioleate, nicotinic acid, 2-pyrazinecarboxylic acid, sinapinic acid (3,5-dimethoxy-4-hydroxycinnamic acid), 2,5-dihydroxybenzoic acid, 5-methoxysalicylic acid, Examples include α-cyano-4-hydroxycinnamic acid, 3-hydroxypicolinic acid, diaminonaphthalene, 2- (4-hydroxyphenylazo) benzoic acid, disranol, succinic acid, and 5- (trifluoromethyl) uracil. Among these, as polyhydric alcohol, for example, propylene glycol, dipropylene glycol, polypropylene glycol, glycerin, diglycerin, polyglycerin, ethylene glycol, diethylene glycol, polyethylene glycol, 1,3-butanediol, sorbitol, maltitol, erythritol, Pentaerythritol, glucose, saccharose, maltose, xylose, trehalose and the like can be exemplified, and these may be used alone or in combination of two or more.

  Of these, preferred are trihydric or higher polyhydric alcohols such as glycerin, diglycerin, polyglycerin, sorbitol, maltitol, erythritol, pentaerythritol, glucose, saccharose, maltose, xylose, trehalose, and particularly preferred is glycerin. Sorbitol.

  Any surfactant can be used as the surfactant of the present invention and claim 1 as long as it can prepare a composition for a raw material for producing nanocapsules, and an anionic surfactant having a lipopeptide structure is particularly suitable. ing. Specific examples of the surfactant that can be used in the present invention include anionic, cationic, nonionic and amphoteric active agents. In the present invention, nonionic surfactants can be used. Examples of the anionic surfactant that can be used at this time include fatty acid soaps such as sodium stearate and triethanolamine palmitate, alkyl ether carboxylic acids and salts thereof, carboxylates such as condensation of amino acids and fatty acids, and alkyl sulfonic acids. Alkene sulfonate, fatty acid ester sulfonate, fatty acid amide sulfonate, alkyl sulfonate and its formalin condensate sulfonate, alkyl sulfate ester, secondary higher alcohol sulfate ester, alkyl and Allyl ether sulfate ester, fatty acid ester sulfate ester salt, fatty acid alkylolamide sulfate ester salt, sulfuric acid ester salt such as funnel oil, alkyl phosphate, ether phosphate, alkyl allyl ether phosphate, amide phosphate N-acyl Examples of cationic surfactants such as mino acid-based surfactants include amine salts such as alkylamine salts, polyamines and aminoalcohol fatty acid derivatives, alkyl quaternary ammonium salts, aromatic quaternary ammonium salts, pyridium salts, imidazolium salts, etc. Nonionic surfactants include sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, propylene glycol fatty acid ester, polyethylene glycol fatty acid ester, sucrose fatty acid ester, polyoxyethylene alkyl ether, polyoxypropylene alkyl ether, Polyoxyethylene alkyl phenyl ether, polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, polyoxyethylene sorbitol fatty acid ester, poly Xylethylene glycerin fatty acid ester, polyoxyethylene propylene glycol fatty acid ester, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene phytostanol ether, polyoxyethylene phytosterol ether, polyoxyethylene cholestanol ether, polyoxyethylene Cholesteryl ether, polyoxyalkylene-modified organopolysiloxane, polyoxyalkylene / alkyl co-modified organopolysiloxane, alkanolamide, sugar ether, sugar amide, etc .; amphoteric surfactants include betaine, aminocarboxylate, imidazoline derivatives, etc. Other surfactant components include 12-hydroxy aluminum stearate, zinc stearate, aluminum stearate , Calcium stearate, magnesium stearate, zinc myristate, magnesium myristate, zinc cetyl phosphate, calcium cetyl phosphate, sodium cetyl phosphate, zinc laurate, zinc undecylenate, but are not limited thereto.

  Examples of the anionic surfactant having a lipopeptide structure include surfactin, its related compounds, and / or salts thereof.

  The content of the surfactant of the present invention is not particularly limited, but preferably the total amount of the composition (in the present invention, “the total amount of the composition” means the total amount of surfactant, water and / or liquid matrix, and fat-soluble substance). The same shall apply hereinafter.) 0.01 to 45% by mass, and more preferably 0.1 to 20% by mass. When the amount of the surfactant is less than 0.01% by mass, nanocapsules cannot be sufficiently produced, and when the amount exceeds 45% by mass, the viscosity becomes too high.

The fat-soluble substance of the present invention and claim 1 is preferably liquid or pasty at 1 atm 25 ° C., and preferably liquid oil. The fat-soluble substance of claim 1 is preferably an antioxidant, and is an antioxidant having a radical scavenging effect such as singlet oxygen, hydroxy radical, NO radical, lipid peroxide, and more preferably vitamin C, vitamin E, vitamin A, a single substance or a mixture of fat-soluble substances or fat-soluble derivatives selected from coenzyme, fullerene, lipoic acid, and polyphenol.

  Examples of the fat-soluble substance of the present invention and claim 1 include, for example, hydrocarbons, higher alcohol esters, higher fatty acid esters, triglycerides, silicone oils, higher alcohols, higher fatty acids, animal and vegetable oils, cholesterol fatty acids Examples include esters, sterols, sterol esters, polyphenols, fullerenes, tars, tar dyes, fat-soluble conductive substances, fat-soluble magnetic substances, fat-soluble pigments, fat-soluble dyes, and the like. Ascorbic acid isopalmitic acid, ascorbic acid-2-phosphate-6-palmitate, ascorbic acid-2-phosphate-6-isopalmitate, ascorbic acid-6-palmitate, ascorbic acid-2,6-dipalmitate, ascorbic acid-6 Stearate, retinol, retinoic acid, retino Lupalmitate, retinoic acid palmitate, retinoic acid isopalmitate, retinoic acid stearate, retinol stearate, astaxanthin, lutein, lycopene, β-carotene, α-carotene, α-tocopherol, β-tocopherol, γ-tocopherol, dimethylglycine γ-tocopherol, dimethylglycine-α-tocopherol Ubiquinone, coenzyme A, tocotrienol, mineral oil, liquid paraffin, squalane, isopropyl palmitate, isopropyl myristate, isooctyl myristate, isotridecyl myristate, octadecyl myristate, octyldodecyl myristate, isostearyl cholesteryl ester, 2-ethylhexanoic acid Triglyceride, cetyl 2-ethylhexanoate, sunflower oil, oil Ove oil, jojoba oil, camellia oil, grape seed oil, avocado oil, macadamia nut oil, almond oil, rice germ oil, clove oil, orange oil, spruce oil, octamethyltrisiloxane, decamethyltetrasiloxane, methylpolysiloxane Dimethyl silicone oil such as highly polymerized methylpolysiloxane; cyclic silicone oil such as octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane, methylcyclopolysiloxane, methylpolycyclosiloxane; polyether-modified silicone oil And methylphenyl silicone oil such as methylphenylpolysiloxane. These may be used alone or in combination of two or more.

（ピグメントレッド１２３，Ｃ．Ｉ．Ｎｏ．７１１４５）、トルイジンレッドＢ（Ｃ．Ｉ．ピグメン

イエローＧ（Ｃ．Ｉ．ピグメントイエロー１）、ピグメントスカーレット（Ｃ．Ｉ．ピグメントレッド６０）、Ａｕｒｉｃ Ｂｒｏｗｎ（Ｃ．Ｉ．ピグメントブラウン６）等が含まれる。本発明のインキの配合に有用な他の典型的な顔料は、フタロシアニンブルー（Ｃ．Ｉ．７４２６０）、フタロシアニングリーン（Ｃ．Ｉ．７４２６０）、Ｈａｎｚａ
イエロー３Ｇ（Ｃ．Ｉ．１１６７０）、ジアゾイエローＧＲ（Ｃ．Ｉ．２１１００）、パーマネントレッド４Ｒ（Ｃ．Ｉ．１２３３５）、ブリリアントカーミン６Ｂ（Ｃ．Ｉ．１５８５０）及びキナクリドンレッド（Ｃ．Ｉ．４６５００）である。これらの顔料、色素で脂溶性特性が低い場合は、前記記載の脂溶性物質に０．１〜９５％重量の含量で分散した組成物を使用することもできる。Representative fat-soluble pigments and fat-soluble dyes described above that can be used in the present invention include:

(Pigment Red 123, CI No. 71145), Toluidine Red B (CI Pigment)

Yellow G (CI Pigment Yellow 1), Pigment Scarlet (CI Pigment Red 60), Auric Brown (CI Pigment Brown 6), and the like are included. Other typical pigments useful in formulating the inks of the present invention are phthalocyanine blue (CI. 74260), phthalocyanine green (CI. 74260), Hanza.
Yellow 3G (C.I. 11670), Diazo Yellow GR (C.I. 21100), Permanent Red 4R (C.I. 12335), Brilliant Carmine 6B (C.I. 15850) and Quinacridone Red (C.I. 46500). When these pigments and dyes have low fat-soluble properties, it is also possible to use a composition dispersed in the above-described fat-soluble substance at a content of 0.1 to 95% by weight.

  Content of 0.1 to 95% by weight of lipid-soluble conductive substances, lipid-soluble magnetic substances, and nano-sized metal or metal oxide fine particles as fat-soluble pigments in claim 5 of the present invention. It is also possible to use oily compositions of metals or metal oxides dispersed in The metals and metal oxides that can be used at this time are suitable for the production of magnetic ink jet inks, for example. Fine particle size oxides such as silica, alumina, titania and the like may also be selected. In addition, finely ground metal particles such as copper, iron, steel, aluminum and alloys can be selected for suitable applications.

  Particularly preferred pigments for use in the present invention, the fat-soluble pigment of claim 5 and the fat-soluble dyes, are C.I. I. Pigment red 122, C.I. I. Pigment yellow 74 and C.I. I. Pigment Blue 15. The present invention is particularly advantageous when used for color pigments. The amount of the pigment contained in the nanocapsule is usually 10 to 50% by weight with respect to the total composition. More preferably, the amount of pigment is in the range of 10-25% by weight.

  A polymer electrolyte can also be used as the fat-soluble conductive substances and the fat-soluble magnetic substances according to claim 5, and is preferably a polymer carboxylate. This salt may be a sodium salt, potassium salt, lithium salt or ammonium salt of carboxylic acid.

  The polymeric carboxylates that can be used in the present invention are in particular the salts of the following polymers: polyacrylic acid, acrylic acid-acrylonitrile copolymer, potassium acrylate-acrylonitrile copolymer, vinyl acetate-acrylic acid ester copolymer and acrylic acid- Acrylic resins such as alkyl acrylate copolymers, styrene-acrylic acid copolymers, styrene-methacrylic acid copolymers, styrene-methacrylic acid-acrylic acid alkyl ester copolymers, styrene-α-methylstyrene-acrylic acid copolymers and styrene-α-methyl. Styrene acrylic resins such as styrene-acrylic acid-alkyl acrylate ester copolymers; styrene-maleic acid copolymers, styrene-maleic anhydride copolymers; vinylnaphthalene-acrylic Vinyl acetate resins such as lauric acid copolymers, vinyl acetate-ethylene copolymers, vinyl acetate-fatty acid vinyl ethylene copolymers, vinyl acetate-maleic acid ester copolymers, vinyl oxalate-crotonic acid copolymers and vinyl acetate-acrylic acid copolymers; and optional Salt of polyester or cellulose polymer.

  Surfactants suitable as polyelectrolytes include, for example, polymeric alkyl sulfates, polymeric alcohol sulfate salts, condensation products of polymeric fatty acids and amino acids, sulfosuccinates, naphthanates, and liquid fatty oil sulfates. Anionic surfactants such as salts and alkyl allyl sulfates; cationic surfactants such as quaternary ammonium salts, sulfonium salts and phosphonium: and such as polyoxyethylene alkyl esters, sorbitan alkyl esters and polyoxyethylene sorbitan alkyl esters Nonionic surfactants. Suitable amounts of polyelectrolyte range from about 0.05 to 10% by weight, preferably 0.1 to 3% by weight, based on the total composition.

  The preferable content of the fat-soluble substance in the composition for producing nanocapsules of the present invention is 1 to 99.9% by mass, and more preferably 50 to 95% by mass with respect to the total amount of the composition.

  The preferred content of water and / or liquid matrix in the composition for producing nanocapsules according to claim 1 of the present invention is 0.01 to 43% by mass, and 0.05 to 39% by mass with respect to the total amount of the composition. Is more preferable, and 0.1-36 mass% is further more preferable.

  In the composition for raw material for producing nanocapsules of the present invention, for example, an anionic surfactant having a lipopeptide structure is dissolved in polyhydric alcohol and / or water, and a fat-soluble substance is added little by little while stirring. It can prepare by. When polyhydric alcohol and water are used in combination, water may be added after adding the fat-soluble substance.

  The fat-soluble substance may be added in predetermined amounts (divided addition) or continuously (continuous addition). In the case of divided addition, an amount of 60% by mass or less, preferably 30% by mass or less, more preferably 10% by mass or less of the amount of polyhydric alcohol and / or water already added is added at one time and stirred. And make it uniform. Add the required amount by repeating it. In the case of continuous addition, the addition rate is 60% by mass / min or less, preferably 30% by mass / min or less, more preferably 10% by mass / min or less of the amount of polyhydric alcohol and / or water already added. .

In addition, when adding other components, it may be added before adding the fat-soluble substance, dissolved or dispersed in the fat-soluble substance, or added after the total amount of the fat-soluble substance is added. Any method may be used even if it is added during the addition of the fat-soluble substance. The polyhydric alcohol and / or water may be added in the total amount at first, or a part of the added amount may be used first and the rest may be added later.
The average particle diameter of the nanocapsules according to the present invention and claim 2 has an average particle diameter in the range of 1 micrometer or less, preferably in the range of 999 nanometers to 1 nanometer, more preferably in the range of 700 nanometers to 10 nanometers. Any nanocapsule may be used.

で示される化合物、またはこの化合物を２種以上含有する組成物である。上記一般式（Ｉ）において、Ｘは、ロイシン、イソロイシン、バリン、グリシン、セリン、アラニン、トレオニン、アスパラギン、グルタミン、アスパラギン酸、グルタミン酸、リジン、アルギニン、システイン、メチオニン、フェニルアラニン、チロシン、トリプトファン、ヒスチジン、プロリン、４−ヒドロキシプロリン及びホモセリンからなる群から選ばれるアミノ酸残基を表わす。好ましいＸはロイシン、イソロイシンまたはバリンである。The surfactin of the present invention, claim 3 and derivatives thereof and salts thereof are represented by the general formula (I)

Or a composition containing two or more of these compounds. In the general formula (I), X is leucine, isoleucine, valine, glycine, serine, alanine, threonine, asparagine, glutamine, aspartic acid, glutamic acid, lysine, arginine, cysteine, methionine, phenylalanine, tyrosine, tryptophan, histidine, It represents an amino acid residue selected from the group consisting of proline, 4-hydroxyproline and homoserine. Preferred X is leucine, isoleucine or valine.

R is a normal alkyl group having 8 to 14 carbon atoms, an isoalkyl group having 8 to 14 carbon atoms, or an anteisoalkyl group having 8 to 14 carbon atoms. The normal alkyl group is a straight chain alkyl group, the isoalkyl group is usually a structure consisting of (CH ₃ ) ₂ CH— (CH ₂ ) _n —, and the anteisoalkyl group is usually CH ₃ —CH ₂ —CH (CH ₃ ) —. it is made of the structure - _{(CH 2) n.} Surfactin-related compounds refer to compounds in which the amino acid of the above general formula (I) is replaced with another amino acid. Specific examples include, but are not limited to, those in which the second L-leucine, the fourth L-valine, the sixth D-leucine and the like are replaced with other amino acids. Hereinafter, “surfactin and / or its related compounds” may be referred to as “surfactin”.

Surfactin is usually produced by prokaryotes. As prokaryotes, Bacillus subtilis IAM1213 strain, IAM1069 strain, IAM1259 strain, IAM1260 strain, IFO3035 strain, ATCC21332 strain and the like are generally used.
Surfactin can be easily obtained by culturing and purifying the microorganism. The purification is performed, for example, by acidifying the culture solution by adding hydrochloric acid or the like, filtering the precipitated surfactin, dissolving it in an organic solvent such as methanol, and thereafter performing ultrafiltration, activated carbon treatment, crystallization, etc. The Precipitation by addition of acid may be replaced by precipitation by addition of calcium salt (Biochem. Bioph. Res. Commun., 31 : 488-494 (1968)). Surfactin can be used in the same manner as that produced by prokaryotic organisms such as the aforementioned Bacillus microorganisms, as well as those obtained by other production methods such as chemical synthesis. Surfactin can be used as an inorganic salt or an organic salt as can be seen from the above general formula (I). Any metal can be used as the counter ion as long as it forms a salt with surfactin, including alkali metals such as sodium, potassium and lithium, alkaline earth metals such as calcium and magnesium.

Examples of organic salts include trimethylamine, triethylamine, tributylamine, monoethanolamine, diethanolamine, triethanolamine, lysine, arginine, choline and the like.

Among these, sodium, potassium, monoethanolamine, diethanolamine, triethanolamine, lysine and arginine are preferable, and sodium is particularly preferable. Surfactin sodium salt can be used as surfactin sodium sold by Showa Denko Co., Ltd. under the trade name Aminofect (registered trademark of Showa Denko KK).

Anionic surfactants having a lipopeptide structure such as surfactin, its analogs, and / or their salts are very mild to the skin. Surfactin, its related compounds, and / or their salts are hypoallergenic to the skin, because surfactin and its related compounds are complex cyclic compounds and bulky, and are considered to be due to their low skin permeability. It is done. It is also considered that surfactin, its related compounds, and / or their salts reduce the irritation of the irritating substance due to the masking effect surrounding the skin irritating substance. In the present invention, a salt of surfactin and / or a salt of a related compound of surfactin is preferably used, and a composition for a raw material for producing nanocapsules having extremely low skin irritation is provided.

  Applications of the nanocapsules of the present invention include pharmaceuticals, pharmaceutical raw materials, cosmetics, cosmetic raw materials, external preparations, ion introduction compositions, vibration introduction compositions, electromagnetic wave introduction compositions, heat introduction compositions, and electrolysis introduction compositions. In the case of foods, food additives, functional foods, feeds, feed additives, anti-aging agents, antioxidants and antioxidants, the fat-soluble substances of the present invention and claim 1 are preferably anti-fouling substances. More preferably, it is an antioxidant having radical scavenging effects such as singlet oxygen, hydroxy radical, NO radical, lipid peroxide, and more specifically vitamin C, vitamin E, vitamin A, coenzyme, Antioxidant derivative or provita which is one or more of a fat-soluble substance or a fat-soluble derivative selected from fullerene, lipoic acid and polyphenol It may be a down. The fullerene used in the present invention may be Cn (n is the number of carbon atoms constituting the fullerene), preferably n is an integer of 60 to 1,000,000, preferably C60 and C70. The fullerene used in the present invention may be an ester derivative of fullerene and a derivative in which fullerene is bonded by one or more oxygen molecules, or a metal salt selected from alkali metals and alkaline earth metals. It may be a composite selected from water-soluble polymers such as These antioxidant substances are desirably fat-soluble substances, but may not be fat-soluble alone, for example, fat-soluble derivatives, or complexes with fat-soluble substances, or complexes with fat-soluble substances. It may be a dispersion of a fat-soluble substance by taking the form of one or more simple substances or a mixture thereof.

  Applications of the nanocapsules of the present invention include pharmaceuticals, pharmaceutical raw materials, cosmetics, cosmetic raw materials, external preparations, ion introduction compositions, vibration introduction compositions, electromagnetic wave introduction compositions, heat introduction compositions, and electrolysis introductions. It may be one or more simple substances or mixtures selected from compositions, foods, food additives, functional foods, feeds, feed additives, antioxidants, antioxidants and antioxidants.

  Applications of the nanocapsules of the present invention include pharmaceuticals, pharmaceutical raw materials, cosmetics, cosmetic raw materials, external preparations, ion introduction compositions, vibration introduction compositions, electromagnetic wave introduction compositions, thermal introduction compositions, and electrolysis introduction compositions. Of fat-soluble substances having physiological activity in the case of one or more simple substances or mixtures selected from foods, foods, food additives, functional foods, feeds, feed additives, antioxidants, antioxidants, antioxidants The addition amount may be added in the range of 0.005% to 90% by weight with respect to the total weight of the final preparation. This is because it becomes difficult to produce capsules when it is 90% or more, and the effect is lowered when it is 0.005% or less.

  Applications of the nanocapsules of the present invention include pharmaceuticals, pharmaceutical raw materials, cosmetics, cosmetic raw materials, external preparations, ion introduction compositions, vibration introduction compositions, electromagnetic wave introduction compositions, thermal introduction compositions, and electrolysis introduction compositions. Food, food additives, functional foods, feed, feed additives, anti-aging agents, antioxidants, antioxidants, antioxidants, one or more selected from a single substance or mixture is added to humans or organisms Depending on the type of fat-soluble substance having physiological activity, nanocapsules containing the manifestation of the effect of the fat-soluble substance having physiological activity may be administered, applied, and added within the physiologically acceptable range. Specifically, the amount of nanocapsules may be 300 ppb to 10 g / day in terms of 1 kg body weight or a living organism.

  Applications of the nanocapsules of the present invention include pharmaceuticals, pharmaceutical raw materials, cosmetics, cosmetic raw materials, external preparations, ion introduction compositions, vibration introduction compositions, electromagnetic wave introduction compositions, thermal introduction compositions, and electrolysis introduction compositions. In the case of one or more simple substances or mixtures selected from foods, foods, food additives, functional foods, feeds, feed additives, antioxidants, antioxidants and antioxidants, the following physiologically acceptable Can be formulated in dosage form.

In order to formulate and stabilize the nanocapsules of the present invention and claim 2, the pH may be 1 to 13.

In addition, the use of the nanocapsule of the present invention includes pharmaceuticals, pharmaceutical raw materials, cosmetics, cosmetic raw materials, external preparations, ion introduction compositions, vibration introduction compositions, electromagnetic wave introduction compositions, thermal introduction compositions, electrolytic introductions. In the case of one or more simple substances or mixtures selected from compositions for foods, foods, food additives, functional foods, feeds, feed additives, antioxidants, antioxidants, antioxidants, their specific effects As whitening, pigmentation improvement, acne treatment, wrinkle improvement, rough skin improvement, oily skin improvement, dry skin improvement, pore reduction, scar treatment, red face treatment, hair loss treatment, hair growth promotion Can have a therapeutic effect on burn treatment, skin sterilization, skin mite killing, skin texture improvement.

Moreover, although the density | concentration of the nanocapsule of this invention required in order to acquire these effects changes with the density | concentrations etc. of a nanocapsule or its clathrate, what is necessary is just 0.1 ppm-100% weight. With this 100% weight, the original nanocapsule itself of claim 2 can be formulated as a final preparation. However, considering the usability, the concentration of nanocapsules in the preparation is preferably 0.001 to 50% by weight. At this concentration, the nanocapsule of claim 2 is added to the body in an amount of 0.01 mg to 10 g per square centimeter of skin area when applied to the skin, and 0 or less per 60 kg of body weight when administered by oral or injection. It may be from 0.01 mg to 100 g.

The nanocapsules of the present invention can be prepared by blending with various forms of bases in accordance with conventional methods. For example, selecting various forms such as liquid, emulsion, cream, powder, ointment, dispersed liquid, multilayer, paste, gel, solid, powder, pellet, granule, capsule, etc. Can do.

The nanocapsules of the present invention can also be prepared by blending with various forms of bases known as compositions for external use according to a conventional method. For example, basic cosmetics such as milky lotion, cream, lotion, cosmetic liquid, pack, oil, nail care product, lip balm, hair restorer, hair nourishing agent, bathing agent, antiperspirant, facial cleanser such as shampoo, rinse, and whole body cleanser , Foundation, white powder, makeup cosmetics such as makeup base, ointments, dispersions, etc., liquid, multilayer, emulsion, paste, gel, solid, powder, granule Various forms such as a shape can be selected.

In addition, the composition containing the nanocapsules of the present invention and the complex of the antioxidant substance according to claim 5 are components used for various preparations in addition to the above-mentioned components, as long as the effects of the present invention are not impaired. That is, water (purified water, hot spring water, deep layer water, etc.), oil agent, surfactant, metal soap, gelling agent, powder, alcohol, water-soluble polymer, film forming agent, resin, clathrate compound, moisturizer , Antibacterial agents, fragrances, deodorants, salts, pH adjusters, refreshing agents, animal / microbe-derived extracts, plant extracts, vitamins, amino acids, nucleic acids, hormones, cell activators, blood circulation promoters, convergence 1 type or 2 types or more of additives, anti-seborrheic agents, active oxygen scavengers, keratolytic agents, enzymes, etc. are added in the range of 0.001 to 90% by weight, more preferably in the range of 0.01 to 50% by weight. can do.

The oil agent that can be added to the composition containing the nanocapsules of the present invention described above and the complex of the antioxidant substance according to claim 5 are natural oils if used in normal cosmetics. , Hydrocarbons, waxes, fatty acids, higher alcohols, ester oils, silicone oils, fluorine oils, regardless of whether they are synthetic oils or solid, semi-solid, liquid Any oil agent can be used. For example, hydrocarbons such as ozokerite, squalane, squalene, ceresin, paraffin, paraffin wax, liquid paraffin, pristane, polyisobutylene, microcrystalline wax, petroleum jelly, waxes such as beeswax, carnauba wax, candelilla wax, whale wax, beef fat , Beef leg fat, beef bone fat, hardened beef fat, hardened oil, turtle oil, pork fat, horse fat, mink oil, liver oil, egg yolk oil and other animal oils, lanolin, liquid lanolin, reduced lanolin, lanolin alcohol, hard lanolin, acetic acid Lanolin derivatives such as lanolin, lanolin fatty acid isopropyl, phospholipid, phosphadylcholine, POE lanolin alcohol ether, POE lanolin alcohol acetate, lanolin fatty acid polyethylene glycol, POE hydrogenated lanolin alcohol ether, lauric Fatty acids such as acid, myristic acid, palmitic acid, stearic acid, behenic acid, undecylenic acid, oleic acid, linoleic acid, arachidonic acid, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), isostearic acid, 12-hydroxystearic acid Lauryl alcohol, myristyl alcohol, palmityl alcohol, stearyl alcohol, behenyl alcohol, hexadecyl alcohol, oleyl alcohol, isostearyl alcohol, hexyl decanol, octyldodecanol, cetostearyl alcohol-2-decyltetradecinol, cholesterol, phytosterol , Sitosterol, lanosterol, POE cholesterol ether, monostearyl glycerol ether (batyl alcohol), etc. Coal, diisobutyl adipate, 2-hexyldecyl adipate, di-2-heptylundecyl adipate, N-alkyl glycol monoisostearate, isocetyl isostearate, trimethylolpropane triisostearate, ethylene di-2-ethylhexanoate Glycol-2-ethylhexanoate cetyl, tri-2-ethylhexanoate trimethylolpropane, tetra-2-ethylhexanoate pentaerythritol, cetyl octoate, octyldodecyl gum ester, oleic oleate, octyldodecyl oleate, oleic acid Decyl, neopentyl glycol dicaprate, triethyl citrate, 2-ethylhexyl succinate, amyl acetate, ethyl acetate, butyl acetate, isocetyl stearate, butyl stearate, Diisopropyl sebacate, di-2-ethylhexyl sebacate, cetyl lactate, myristyl lactate, isopropyl palmitate, 2-ethylhexyl palmitate, 2-hexyldecyl palmitate, 2-heptyl undecyl palmitate, cholesteryl 12-hydroxystearylate, Dipentaerythritol fatty acid ester, isopropyl myristate, octyldodecyl myristate, 2-hexyldecyl myristate, myristyl myristate, hexyldecyl dimethyloctanoate, ethyl laurate, hexyl laurate, 2-octyl N-lauroyl-L-glutamate Ester oil such as dodecyl ester, diisostearyl malate, acetoglyceride, triisooctanoic acid glyceride, triisostearic acid glyceride, Glyceride oil such as glyceride of lysopalmitic acid, glyceride of tri-2-ethylhexanoic acid, glyceride of monostearic acid, glyceride of di-2-heptylundecanoic acid, glyceride of trimyristic acid, dimethylpolysiloxane, methylphenylpolysiloxane, methylhydrogen Higher alkoxy-modified silicones such as polysiloxane, octamethylcyclotetrasiloxane, decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane, tetramethyltetrahydrogencyclotetrasiloxane, stearoxysilicone, higher fatty acid-modified silicone, silicone resin, silicone rubber Silicone oil such as silicone resin, perfluoropolyether, perfluorodecalin, perfluorooctane Motokei oil and the like.

Surfactants that can be added to the composition containing the nanocapsules of the present invention and the antioxidant complex of claim 5 include anionic, cationic, nonionic and amphoteric active agents. Then, a nonionic surfactant can be used.
Examples of the anionic surfactant that can be added to the composite comprising the nanocapsule of the present invention and the antioxidant substance of claim 5 include fatty acid soaps such as sodium stearate and triethanolamine palmitate, and alkyl ether carboxylic acids. And salts thereof, carboxylates such as condensation of amino acids and fatty acids, alkyl sulfonic acids, alkene sulfonates, sulfonates of fatty acid esters, sulfonates of fatty acid amides, sulfonates of alkyl sulfonates and their formalin condensates Salts, alkyl sulfates, secondary higher alcohol sulfates, alkyl and allyl ether sulfates, fatty acid ester sulfates, fatty acid alkylolamide sulfates, sulfate oils such as funnel oil, alkyl phosphorus Acid salt, ether phosphate, Kill allyl ether phosphate, amide phosphate, N-acyl amino acid type activator, etc .; cationic surfactants include alkylamine salts, amine salts such as polyamine and amino alcohol fatty acid derivatives, alkyl quaternary ammonium salts, aromatic Non-ionic surfactants include sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, propylene glycol fatty acid ester, polyethylene glycol fatty acid ester, sucrose fatty acid ester , Polyoxyethylene alkyl ether, polyoxypropylene alkyl ether, polyoxyethylene alkyl phenyl ether, polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester Polyoxyethylene sorbitol fatty acid ester, polyoxyethylene glycerin fatty acid ester, polyoxyethylene propylene glycol fatty acid ester, polyoxyethylene castor oil, polyoxyethylene hydrogenated castor oil, polyoxyethylene phytostanol ether, polyoxyethylene phytosterol ether, Polyoxyethylene cholestanol ether, polyoxyethylene cholesteryl ether, polyoxyalkylene-modified organopolysiloxane, polyoxyalkylene / alkyl co-modified organopolysiloxane, alkanolamide, sugar ether, sugar amide, etc .; as an amphoteric surfactant, betaine , Aminocarboxylates, imidazoline derivatives, and the like, but are not limited thereto.

Metal soaps that can be added to the composite comprising the nanocapsules of the present invention and the antioxidant complex of claim 5 include 12-hydroxy aluminum stearate, zinc stearate, aluminum stearate, calcium stearate, magnesium stearate Zinc myristate, magnesium myristate, zinc cetyl phosphate, calcium cetyl phosphate, sodium cetyl phosphate, zinc laurate, zinc undecylenate and the like.

Examples of the gelling agent that can be added to the composite comprising the nanocapsule of the present invention and the antioxidant substance of claim 5 include amino acids such as N-lauroyl-L-glutamic acid and α, γ-di-n-butylamine. Derivatives, dextrin palmitate, dextrin stearate, dextrin fatty acid ester such as dextrin 2-ethylhexanoic acid palmitate, sucrose fatty acid ester such as sucrose palmitate, sucrose stearate, monobenzylidene sorbitol, di Examples include benzylidene derivatives of sorbitol such as benzylidene sorbitol, organically modified clay minerals such as dimethylbenzyl dodecyl ammonium montmorillonite clay and dimethyl dioctadecyl ammonium montmorillonite clay.

As a complex of the powder that can be added to the composition containing the nanocapsules of the present invention and the antioxidant substance of claim 5, the shape (spherical, needle-like, Any one can be used regardless of the plate shape, etc.), particle size (smoke, fine particles, pigment grade, etc.) and particle structure (porous, nonporous, etc.). Examples of inorganic powders that can be added to the capsule-containing composition include magnesium oxide, barium sulfate, calcium sulfate, magnesium sulfate, calcium carbonate, magnesium carbonate, talc, synthetic mica, mica, kaolin, sericite, muscovite, and synthetic mica. , Phlogopite, red mica, biotite, lithia mica, silicic acid, anhydrous silicic acid, aluminum silicate, magnesium silicate, magnesium aluminum silicate, calcium silicate, silicic acid Lithium, strontium silicate, metal tungstate, hydroxyapatite, vermiculite, hydrite, montmorillonite, zeolite, ceramic powder, dicalcium phosphate, alumina, aluminum hydroxide, boron nitride, boron nitride, etc .; As organic powder, polyamide Powder, polyester powder, polyethylene powder, polypropylene powder, polystyrene powder, polyurethane, benzoguanamine powder, polymethylbenzoguanamine powder, tetrafluoroethylene powder, polymethyl methacrylate powder, cellulose, silk powder, nylon powder, 12 nylon, 6 nylon, styrene Acrylic acid copolymer, divinylbenzene / styrene copolymer, vinyl resin, urea resin Phenolic resin, fluororesin, silicon resin, acrylic resin, melamine resin, epoxy resin, polycarbonate resin, microcrystalline fiber powder, lauroyl lysine, etc .; As colored pigments, inorganic red pigments such as iron oxide, iron hydroxide, and iron titanate , Inorganic brown pigments such as γ-iron oxide, inorganic yellow pigments such as yellow iron oxide and loess, inorganic black pigments such as black iron oxide and carbon black, inorganic purple pigments such as manganese violet and cobalt violet, chromium hydroxide Inorganic green pigments such as chromium oxide, cobalt oxide and cobalt titanate, inorganic blue pigments such as bituminous and ultramarine blue, tar dyes raked, natural dyes raked, and composites of these powders Composite powders, etc .; pearl pigments include titanium oxide-coated mica, titanium oxide-coated mica, bismuth oxychloride, titanium oxide Covered bismuth oxychloride, titanium oxide coated talc, fish scale foil, titanium oxide coated colored mica, etc .; as metal powder pigment, aluminum powder, copper powder, stainless steel powder, etc .; as tar pigment, red No. 3, red No. 104, red 106, Red 201, Red 202, Red 204, Red 205, Red 220, Red 226, Red 227, Red 228, Red 230, Red 401, Red 505, Yellow 4 Yellow No. 5, Yellow No. 202, Yellow No. 203, Yellow No. 204, Yellow No. 401, Blue No. 1, Blue No. 2, Blue No. 201, Blue No. 404, Green No. 3, Green No. 201, Green No. 204, Green No. 205, Orange No. 201, Orange No. 203, Orange No. 204, Orange No. 206, Orange No. 207, etc .; natural pigments include carminic acid and lacaic acid Carthamine, brazilin, a powder selected from crocin, or composite of these powder, oil, silicone, or fluorine compound may be a powder was subjected to surface treatment.

Examples of alcohols that can be added as a composite of the composition containing the nanocapsules of the present invention and the antioxidant substance of claim 5 include lower alcohols such as ethanol and isopropanol, glycerin, diglycerin, ethylene glycol, diethylene glycol, and triethylene. Examples include glycols, propylene glycol, dipropylene glycol, 1,3-butylene glycol, sorbitol, erythritol, maltitol, maltose, xylitol, xylose, trehalose, inositol, glucose, mannitol, and polyhydric alcohols such as polyethylene glycol.

The water-soluble polymer that can be added as a composite of the composition containing the nanocapsules of the present invention and the antioxidant substance of claim 5 is mucos selected from chondroitin sulfate, hyaluronic acid, mucin, dermatan sulfate, heparin and keratan sulfate. Polysaccharides and salts thereof, plant polymers such as gum arabic, tragacanth, galactan, carob gum, guar gum, caraya gum, carrageenan, pectin, agar, quince seed, algae colloid, tant gum, locust bean gum, galactomannan, xanthan gum, dextran, Microbial polymers such as succinoglucan and pullulan, animal polymers such as collagen, casein, albumin and gelatin; starch polymers such as starch, carboxymethyl starch and methylhydroxypropyl starch; Loose, ethylcellulose, methylhydroxypropylcellulose, carboxymethylcellulose, hydroxymethylcellulose, hydroxypropylcellulose, nitrocellulose, sodium cellulose sulfate, sodium carboxymethylcellulose, crystalline cellulose, cellulose-based cellulose polymer, sodium alginate, propylene glycol alginate, etc. Alginate polymer, polyvinyl methyl ether, carboxyvinyl polymer, vinyl polymer such as alkyl-modified carboxyvinyl polymer, polyoxyethylene polymer, polyoxyethylene polyoxypropylene copolymer polymer, sodium polyacrylate, poly Acrylic polymers such as ethyl acrylate and polyacrylamide, polyethyleneimine Cationic polymers, bentonite, laponite, and inorganic water-soluble polymers such as hectorite. Also included are film forming agents such as polyvinyl alcohol and polyvinyl pyrrolidone.

Antibacterial agents that can be added to the composition containing the nanocapsules of the present invention include benzoic acid, sodium benzoate, salicylic acid, carboxylic acid, sorbic acid, potassium sorbate, p-hydroxybenzoic acid ester, parachlorometacresol, hexachlorophene, chloride Benzalkonium, chlorhexidine chloride, trichlorocarbanilide, photosensitizer, bis (2-pyridylthio-1-oxide) zinc, pentadiol, iturin, surfactin, polyglycine, ethanol, phenoxyethanol, isopropylmethylphenol and the like can be mentioned.

PH adjusters that can be added to the composition containing the nanocapsules of the present invention include lactic acid, citric acid, glycolic acid, succinic acid, tartaric acid, malic acid, potassium carbonate, sodium bicarbonate, ammonium bicarbonate, etc. Examples thereof include L-menthol and camphor.

Examples of animal-derived and microorganism-derived extracts that can be added to the composition containing the nanocapsules of the present invention include blood extracts such as pigs and cows, serum deproteinized extracts, spleen extracts, avian egg components, Chicken crown extract, fish extract, squid ink, chitin, chitosan, shell extract, shell extract, royal jelly, silk protein and its degradation product or derivatives thereof, hemoglobin or its degradation product, milk, casein and its derivatives or their derivatives Degradation products, lactoferrin or degradation products thereof, collagen and derivatives thereof or hydrolysis products thereof, elastin and derivatives thereof or hydrolysis products thereof, keratin and derivatives thereof or degradation products thereof, mammals, birds, fish, soft bodies Extracts from animals such as animals, crustaceans, shellfish, insects; yeast metabolites, fermentation metabolites, yeast extracts, milk Fungal extract, extracts from microorganisms such as bifidobacteria extract.

Natural extracts that can be added to the composition containing the nanocapsules of the present invention include glabrizine, glabrene, liquiritin, isoliquiritin and licorice extract containing these, placenta extract, carotenoids and animal and plant extracts containing these, Neo agarobiose, agarose oligosaccharide, asparagus extract, ibukitorano extract, pea extract, age extract, ougon extract, onionis extract, seaweed extract, raspberry extract, cucumber extract, caquette extract , Scallop extract, plant oil containing linoleic acid, saicin extract, hawthorn extract, sampens extract, shirayuri extract, peonies extract, sempukuka extract, sohakuhi extract, soybean extract, tea extract, toki Extract, molasses extract, beechlen extract Beech extract, grape seed extract, flow demanita extract, hop extract, micaika extract, mokka extract, yukinoshita extract, yokuinin extract and rahan fruit extract, asparagus, akane, red grape, akamegashiwa, akebi, Asa, morning glory, azuki bean, asenyak, achacha, amacha eel, itadori, fig, ginkgo, ylang ylang, moray eel, ume, cormorant, walrus, mandarin orange, prairie moth, shrimp, enju, pea, plantain, okra, ogurma, minced oak , Oysters, persimmons, cashews, cashews, valerian, calla lilies, quince, guarana, kyoto, chrysanthemum, catalpa, scallop, gymnema sylvesta, goldfish, guava, wolfberry, kudzu, camphor, chestnut Ketou, gecko, keihi, gosho strawberries, pepper, coffee, sesame seeds, colombo, sasanqua, salamander, saffron, cherry blossom, pomegranate, sandscon, sunpens, zion, shobu, watermelon, stevia, plum, swan, pear, psyllium, Horseshoe, horseradish, buffalo, buffalo, seri, senega, senna, daiou, daidai, tamarind, taranki, dandelion, chicory, clove, dung beetle, chorei, primrose, clover, communis, tsuruna, teuchigurumi, tougan, tochua, toruo Natsumikan, Nanten, Nigaki, Yarrow, Pineapple, Hibiscus, Papaya, Basil, Lotus, Hadakamugi, Hagi, Peanut, Hikikoshi, Hishi, Piss Tachio, Hiba, Himematsutake, Peacock, Biwa, Japanese dandelion, Fushinoki, Fujibakama, Blueberry, Bowfish, Physalis, Hoonoki, Bokeh, Maikai, Mao, Mango, Mannentake, Mishimasaiko, Misohagi, Mitsuba, Mimosa, Meriron, Memoron Examples include gross benoly, moroheiya, sprout, yakchi, yakusou, cornflower, palm, yashajitsu, mistletoe, willow, pokeweed, bayberry, quail, mugwort, rye, orchid, longan, apple, litchi and forsythia.

Examples of vitamins include vitamin Fs such as linolenic acid and its derivatives; vitamin Ks such as phytonadione, menaquinone, menadione and menadiol; vitamins P such as eriocitrin and hesperidin; other biotin, carcinine, ferulic acid and the like It is done.

Amino acids that can be added to the composition containing the nanocapsules of the present invention include glycine, alanine, valine, isoleucine, serine, threonine, aspartic acid, glutamic acid, asparagine, glutamine, lysine, hydroxylysine, arginine, cystine, methionine, Examples include amino acids such as phenylalanine, tyrosine, proline, hydroxyproline, ortinin, citrulline, and theanine, and derivatives thereof, salts thereof, amino acid derivatives such as pyrrolidone carboxylic acid, and derivatives thereof. Examples of nucleic acid-related substances include deoxyribonucleic acid and salts thereof, adenylic acid derivatives selected from adenosine triphosphate, adenosine diphosphate and adenosine monophosphate and salts thereof, ribonucleic acid and salts thereof, cyclic AMP, and cyclic GMP Examples of the flavin adenine nucleotide, guanine, adenine, cytosine, thymine, xanthine and their derivatives caffeine, theophylline, and salts and hormones thereof include estradiol, etenyl estradiol and the like. Examples of the enzyme include lipase and papain.

As a blood circulation promoter that can be added to the composition containing the nanocapsule of the present invention, nonyl acid wallenylamide, capsaicin, gingerone, cantalis tincture, ictamol, α-borneol, inositol hexanicotinate, cyclandrate, cinnarizine, trazoline, Examples of skin astringents such as acetylcholine, verapamil, cephalanthin, and γ-oryzanol include tannic acid, and examples of antiseborrheic agents include sulfur and thianthol.

When the composition for producing nanocapsules is used for cosmetics, the following optional components can be blended.

Examples of such components include hydrocarbons such as petrolatum and microcrystalline wax; esters such as octyldodecyl myristate and isopropyl myristate; glyceryl triisooctanoate and triglycerides such as olive oil; methylphenylpolysiloxane, methyl Silicone oils such as polysiloxane; higher alcohols such as cetanol and behenyl alcohol; fatty acids such as stearic acid and oleic acid; polyhydric alcohols such as glycerin, 1,3-butanediol, and propylene glycol; ethanol, isopropyl alcohol, etc. Lower alcohols: nonionic surfactants, anionic surfactants, cationic surfactants, amphoteric surfactants, thickeners, UV absorbers, antioxidants, emollients, emulsifiers, solubilizers, anti Inflammatory agent Humectants, preservatives, germicides, pH adjusting agents, dyes, perfumes, powders such as water and the like.

Furthermore, in the composition containing the nanocapsule of the present invention, the existing raw material specifications or the raw materials described in the official document are added to a general concentration, for example, preferably the total amount of the composition containing the nanocapsule of the present invention. It can also be added at 100 ppm to 90% by weight. Examples of the raw materials described in the above-mentioned existing raw material standards or official documents include, for example, the 14th revised Japanese Pharmacopoeia, edited by the Japan Standards Association, issued by Jiho Co., Ltd., issued in April 2001. Commentary on the second edition of the standards, edited by the Japanese Official Church, 1984 (Pharmaceutical Daily Report), Standards for Ingredients for Cosmetic Ingredients, Supervised by the Pharmaceutical Affairs Bureau, Ministry of Health and Welfare, 1993 (Pharmaceutical Daily Report), Supplement for Standards for Ingredients for Cosmetic Ingredients, Ministry of Health and Welfare Supervised by the Pharmaceutical Affairs Bureau Screening Division, 1993 (Pharmaceutical Daily Report), Permit Cosmetics Permit Standard, Ministry of Health and Welfare Pharmacy Screening Division Supervision, 1993 (Pharmaceutical Daily Report), and International Cosmetic Ingredient Dictionary 2002 Ninth Edition Vol. All raw materials described in 1-4, by CTFA, cosmetic raw material dictionary 1991 (Nikko Chemicals) and the like can be used.

The nanocapsule of the present invention can further enhance the effect of the application of claim 6 by introducing it by one or more single methods or mixing methods selected from ion introduction, vibration introduction, electromagnetic wave introduction, heat introduction, and electrolysis introduction. it can.

The nanocapsule production method of the present invention and claim 2 may be formed by dispersing the composition of claim 1 in water, and the nanocapsule of claim 2 of the present invention is impact resistant. One composition for producing nanocapsules can be produced by subjecting it to shear deformation. With respect to impact resistance, the nanocapsules of claim 2 can be easily produced by colliding a water flow at a certain pressure or higher against the composition for producing nanocapsules of claim 1, but the particle size distribution range is narrowed. When the purpose or the average particle size of the nanocapsule particles is set to 200 nm or less, it is preferable to use an apparatus for applying shear deformation. More preferably, when the composition for nanocapsule production raw material is subjected to shear deformation at a shear rate of at least 15 / s, fine emulsion particles having an average particle diameter of less than 1000 nm dispersed in water and an aqueous solvent can be produced. The water flow at a constant pressure here does not require a special pressurizing device, and a pressure of about the water pressure of tap water is sufficient. Or the shear rate of the grade which mixes the composition for nanocapsule manufacture raw materials of Claim 1 stored in the tank, and water with a normal stirrer may be sufficient.
Specific examples of the apparatus for applying shear deformation include a stirrer, a stirrer mill, a stirrer mixer, a homomixer, a screw mixer, and a drill mixer, and more preferably a static mixer, a jet displacer, a microporous filter, and a microfluidizer. And at least one disperser selected from the group consisting of Manton-Gaulin homogenizer nozzles.

A jet dispersator that dissipates pressure energy into a small volume object in a depressurizing nozzle can be used as the nanocapsule manufacturing apparatus of the present invention. Examples of other suitable static dispersion devices include microporous filters, microporous glass filters, microfluidizers and Manton-Gaulin homogenizer nozzles. A jet dispagator is a preferred device.

Thus, one important feature of the present invention is that the shear deformation by the method of the present invention reduces the average particle size of nanocapsules (denoted herein as “d _w ”) and the width of the particle size distribution. (expressed as "d _{w /} d _n", as used herein, wherein d _n is the number average particle size) consists in that it becomes narrower. When applying a speed shear deformation disclosed in the present invention according to the methods of the present invention, d _w and d _{w /} d _n is based on the value obtained by the method without shearing stresses above the speed at least 20%, Preferably it is reduced by 30%.

This shear stress is applied after the phase inversion is completed. The jet displacer has a depressurizing nozzle in which the available pressure energy is dissipated in the smallest possible volume in the dispersion region, which is used to obtain a high volumetric specific dispersion force.

Examples of suitable static mixers include those available from Sulzer, Winterthur, Switzerland / Germany (commercially identified SMX). The common point of all static mixers is that the fluid flow in the tube is constantly separated, rearranged, combined and redistributed by internal components. The static mixer is thereby operated in a manner similar to a jet dispersator, i.e. the available pressure energy is dissipated in the static mixer.

The volumetric flow rate at which the polymer solution containing the nanocapsule particles is transferred through the shearing device is high, and a pressure drop of between 0.01 and 500 bar, preferably between 0.5 and 50 bar appears. An operating pressure of 0.5 to 50 bar can be generated with a relatively simple and inexpensive pump. The shear rate (velocity gradient, shear rate) in the shearing apparatus is high, at least 100 / s, preferably 1000 to 20000000 / s, most preferably 35000 to 1500,000 / s. This shear rate is set by the pressure drop.

EXAMPLES Hereinafter, although an Example demonstrates this invention further in detail, this invention is not limited to these Examples at all. The glycerin listed below was used with a content of 98% by mass or more. As Surfactin sodium, Aminofect (registered trademark of Showa Denko KK) manufactured by Showa Denko KK was used. % Is% by weight.

Example 1: Composition for raw material for producing nanocapsules Dissolve 1 part by weight of surfactin sodium in 20 parts by weight of glycerin, add 2 parts by weight of squalane to this and stir until uniform to create a composition for raw materials for producing nanocapsules. did.

Example 2:
2 parts by mass of squalane was added to the composition for raw material for producing nanocapsules of Example 1 and stirred until uniform. This operation was repeated 4 times. Next, 4 parts by mass of squalane was added and stirred until uniform. This operation was repeated 5 times. Next, 6 parts by mass of squalane was added and stirred until uniform. This operation was repeated three times. Next, 8 parts by mass of squalane was added and stirred until uniform. This operation was repeated 4 times to obtain a composition for raw material for producing nanocapsules. The final composition was 80 parts by weight of squalane, 20 parts by weight of glycerin, and 1 part by weight of surfactin sodium.

Example 3: Raw material composition for nanocapsules Surfactin sodium was added and dissolved in glycerin according to the following formulation, and an oil mixture having the following composition was added little by little while stirring. Further, water and 1,3-butanediol were slowly added while stirring, and finally the oil mixture 60%, glycerin 23%, 1,3-butanediol 13%, and water 3%. A raw material composition for nanocapsules of surfactin sodium 1% was obtained.

(Composition of oil mixture)
Each of the following fat-soluble substances was mixed by 0.5% by weight, and finally squalane was added as a residue to make 100% by weight.
Ascorbic acid isopalmitic acid, ascorbic acid-2-phosphate-6-palmitate, ascorbic acid-2-phosphate-6-isopalmitate, ascorbic acid-6-palmitate, ascorbic acid-2, 6-dipalmitate, ascorbic acid-6 Stearate, retinol, retinoic acid, retinol palmitate, retinoic acid palmitate, retinoic acid isopalmitate, retinoic acid stearate, retinol stearate, astaxanthin, lutein, lycopene, β-carotene, α-carotene, α-tocopherol, β-tocopherol, γ-tocopherol , Dimethylglycine gamma tocopherol, dimethylglycine alpha tocopherol, ubiquinone, coenzyme A, tocotrienol, mineral oil, liquid paraffin, squalene, palmitic Isopropyl acid, isopropyl myristate, isooctyl myristate, isotridecyl myristate, octadecyl myristate, octyldodecyl myristate, rice germ oil, mineral oil, liquid paraffin, isostearyl cholesteryl ester, 2-ethylhexanoic acid triglyceride, 2-ethylhexane Cetyl acid, sunflower oil, olive oil, jojoba oil, camellia oil, grape seed oil, avocado oil, macadamia nut oil, almond oil, rice germ oil, clove oil, orange oil, spruce oil, octamethyltrisiloxane, decamethyltetrasiloxane , Methylpolysiloxane, octamethylcyclotetrasiloxane, picnojanol, coenzyme A, decamethylcyclopentasiloxane, dodecamethylcyclohexasiloxane, methyl Ropolysiloxane, methylpolycyclosiloxane, methylphenylpolysiloxane

Example 4: Water-dispersed nanocapsules Surfactin sodium was dissolved in glycerin according to the following formulation A, and a fat-soluble substance was added little by little while stirring to prepare a gel.
The gel of the formulation A was heated to 80 ° C., the formulation B solution dissolved by heating to 80 ° C. was added, and the mixture was homogenized with a homomixer at 5000 rpm for 5 minutes. Further, the arginine aqueous solution of Formulation C was added with stirring, the mixture was cooled with paddle stirring, the stirring was stopped at 40 ° C. or lower, and the mixture was allowed to stand. It was 300 nm when the average particle diameter of the nanocapsule was measured.

Formula A
16% fat-soluble mixture, 4% glycerin, 0.2% surfactin sodium
The fat-soluble mixture was mixed according to the following formulation.
Ascorbic acid isopalmitic acid, ascorbic acid-2-phosphate-6-palmitate, ascorbic acid-2-phosphate-6-isopalmitate, ascorbic acid-6-palmitate, ascorbic acid-2, 6-dipalmitate, ascorbic acid-6 Stearate, retinol, retinoic acid, retinol palmitate, retinoic acid palmitate, retinoic acid isopalmitate, retinoic acid stearate, retinol stearate, astaxanthin, lutein, lycopene, β-carotene, α-carotene, α-tocopherol, β-tocopherol, γ-tocopherol , Dimethylglycine γ-tocopherol, dimethylglycine α-tocopherol, ubiquinone, coenzyme A, tocotrienol 1% each, and squalene added as a residue. And the.

Formula B
Red No. 3 0.001%, behenyl alcohol 2%, and stearic acid 0.5%

Formula C
L-Arginine 0.1%
Water balance

Example 5: Water-dispersed nanocapsules Surfactin sodium was dissolved in glycerin according to the following formulation A, and the following fat-soluble substances were added little by little while stirring to prepare a gel.

Formula A
The following fat-soluble mixture 16%, glycerin 4%, surfactin sodium 0.2%. The composition of the fat-soluble mixture is as follows.
Ascorbic acid isopalmitic acid, ascorbic acid-2-phosphate-6-palmitate, ascorbic acid-2-phosphate-6-isopalmitate, ascorbic acid-6-palmitate, ascorbic acid-2, 6-dipalmitate, ascorbic acid-6 Stearate, retinol, retinoic acid, retinol palmitate, retinoic acid palmitate, retinoic acid isopalmitate, retinoic acid stearate, retinol stearate, astaxanthin, lutein, lycopene, beta carotene, alpha carotene, alpha tocopherol, beta tocopherol, gamma tocopherol , Dimethylglycine γ-tocopherol, dimethylglycine α-tocopherol, ubiquinone, coenzyme A, tocotrienol 1% each, and squalene added as a residue. And the.

Formula B
2% behenyl alcohol and 0.5% stearic acid

Water balance

  The gel of formulation A was heated to 80 ° C., and the formulation B solution dissolved by heating to 80 ° C. was added, and the mixture was homogenized by stirring at 5000 rpm for 5 minutes with a homomixer. Further, the arginine aqueous solution of Formulation C was added while stirring, and the mixture was cooled while stirring with a paddle. It was 350 nm when the average particle diameter of the nanocapsule was measured.

  This nanocapsule for pigmentation treatment and wrinkle removal medicine, pharmaceutical raw material, cosmetic, cosmetic raw material, food, food additive, external preparation, iontophoretic composition, vibration introducing composition, electromagnetic wave introducing composition, Composition for introducing heat, composition for electrolytic introduction, functional food, whitening as anti-aging agent, improvement of pigmentation, treatment of acne, improvement of wrinkles, improvement of rough skin, improvement of oily skin, improvement of dry skin, pores Twice a day for 100 men and women, including placebo suffering from shrinkage, scar treatment, red face treatment, hair loss treatment, hair growth promotion, burn treatment, skin sterilization, skin mite killing, skin texture improvement ( When 5 CC) was applied to the affected area and applied externally for 60 days, the lesion was clearly improved after 60 days compared to the beginning of use. In addition, about the ion introducing device, the vibration introducing device, the electromagnetic wave introducing device, the heat introducing device, and the electrolytic introducing device, commercially available products were used.

  Moreover, when this capsule is added at 0.5% concentration as an antioxidant component of feed, feed additives, antioxidants, and antioxidants, the lifespan of each product can be doubled and excellent antioxidant effect It was confirmed that can be demonstrated.

Example 6 Nanocapsules Made of Water Dispersion In the following formulation A, surfactin sodium is dissolved in glycerin, and the following fat-soluble substances are added little by little while stirring to prepare the raw material for producing nanocapsules according to claim 1 of the present invention. did.

Formula A
The composition of the following fat-soluble mixture 16%, glycerin 4%, surfactin sodium 0.2% fat-soluble mixture is as follows.
Ascorbic acid isopalmitic acid, ascorbic acid-2-phosphate-6-palmitate, ascorbic acid-2-phosphate-6-isopalmitate, ascorbic acid-6-palmitate, ascorbic acid-2, 6-dipalmitate, ascorbic acid-6 Stearate, retinol, retinoic acid, retinol palmitate, retinoic acid palmitate, retinoic acid isopalmitate, retinoic acid stearate, retinol stearate, astaxanthin, lutein, lycopene, β-carotene, α-carotene, α-tocopherol, β-tocopherol, γ-tocopherol , Dimethylglycine γ-tocopherol, dimethylglycine α-tocopherol, ubiquinone, coenzyme A, tocotrienol 1% each, and squalene added as a residue. And the.

Formula B
2% behenyl alcohol and 0.5% stearic acid

Water balance

The raw material for producing nanocapsules of formulation A was heated to 80 ° C., and the formulation B solution dissolved by heating to 80 ° C. was added, and the mixture was homogenized by stirring at 5000 rpm for 5 minutes. Further, the AB mixture and water (remainder) were sheared and mixed uniformly with a static mixer, a jet dispersator, a microporous filter, a microfluidizer and a Manton-Gaulin homogenizer nozzle, and naturally cooled to room temperature.
When the average particle size of the nanocapsules dispersed by the respective shear deformation methods was measured, they were static mixer 234 nm, jet dispersator 217 nm, microporous filter 210 nm, microfluidizer 94 nm, and Manton-Gaulin homogenizer nozzle 153 nm.

Example 7:
Emulsion Surfactin sodium was dissolved in glycerin with the following formulation A, and squalane was added little by little with stirring to prepare a gel. The gel of formulation A was heated to 70 ° C., the formulation B solution dissolved by heating to 70 ° C. was added, and the mixture was homogenized by stirring at 5000 rpm for 5 minutes with a homomixer. Further, water was added in an amount of Formulation C with stirring, and the mixture was cooled with paddle stirring.

Formula A
Squalane 16% Glycerin 4% Surfactin sodium 1%

Formula B
Stearic acid 0.5% behenyl alcohol 2% Preservative

Formula C
Arginine 0.1%
Water balance

Example 8: Water-dispersed nanocapsules Surfactin sodium was dissolved in glycerin according to the following formulation A, and the following fat-soluble substances were added little by little while stirring to prepare a gel.

Formula A
The following fat-soluble mixture 16%, glycerin 4%, surfactin sodium 0.2%. The composition of the fat-soluble mixture is as follows.
10% of Red No. 3 and 1% of α-tocopherol were mixed, and palmitic acid was added as a residue to make 100%.

Formula B
2% behenyl alcohol and 0.5% stearic acid

Water balance

  The gel of formulation A was heated to 80 ° C., and the formulation B solution dissolved by heating to 80 ° C. was added, and the mixture was homogenized by stirring at 5000 rpm for 5 minutes with a homomixer. Further, the arginine aqueous solution of Formulation C was added while stirring, and the mixture was cooled while stirring with a paddle. It was 345 nm when the average particle diameter of the nanocapsule was measured.

  Using these nanocapsules as coloring materials, pharmaceuticals, pharmaceutical raw materials, cosmetics, cosmetic raw materials, foods, food additives, external preparations, ion introduction compositions, vibration introduction compositions, electromagnetic wave introduction compositions, heat introduction compositions, Composition for electrolytic introduction, functional food, anti-aging agent, feed, feed additive, antioxidant, antioxidant, paint, toner, ink for ink jet, ink for inkjet printed circuit board, dye for photosensitive particle for photographic film When added at a concentration of 0.5%, the life until the dye of each product fades can be extended by a factor of three, and the dye particles are fine, so the resolution is excellent and the nano-sized dye particles have high stability. Confirmed that could be.

Example 9: Water-dispersed nanocapsules Surfactin sodium was dissolved in glycerin according to the following formulation A, and the following fat-soluble substances were added little by little while stirring to prepare a gel.

Formula A
The following fat-soluble mixture 16%, glycerin 4%, surfactin sodium 0.2%. The composition of the fat-soluble mixture is as follows.
5% magnetic iron powder having an average particle diameter of 100 nm and 1% each of α-tocopherol were mixed, and palmitic acid was added as a residue and mixed to 100%, and kneaded well to obtain a uniform magnetic iron powder-dispersed fat-soluble mixture.

Formula B
2% behenyl alcohol and 0.5% stearic acid

Water balance

  The gel of formulation A was heated to 80 ° C., and the formulation B solution dissolved by heating to 80 ° C. was added, and the mixture was homogenized by stirring at 5000 rpm for 5 minutes with a homomixer. Further, the arginine aqueous solution of Formulation C was added while stirring, and the mixture was cooled while stirring with a paddle. It was 345 nm when the average particle diameter of the nanocapsule was measured.

  This nanocapsule is used as a magnetic material for pharmaceuticals, cosmetics, vibration-introducing compositions, electromagnetic wave-introducing compositions, heat-introducing compositions, electrolytic-introducing compositions, paints, toners, ink-jet inks, and magnetic memory materials. When added to a normal binder at a concentration of 5% as particles, the particles are fine and the secondary agglomeration of the powder is unlikely to occur, so the storage density is improved 3 times, creating a storage medium with high stability and high storage density I confirmed that I can do it.

Example 10: Water-dispersed nanocapsules Surfactin sodium was dissolved in glycerin according to the following formulation A, and the following fat-soluble substances were added little by little while stirring to prepare a gel.

Formula A
The following fat-soluble mixture 16%, glycerin 4%, surfactin sodium 0.2%. The composition of the fat-soluble mixture is as follows. Conductive fullerene (1,3 butylene glycol complex of 1: 1 mixture of C60 and C70) and 1% each of α-tocopherol are mixed, and palmitic acid is added as the residue to make 100%, and kneaded well and uniform A conductive particle-dispersed fat-soluble mixture was obtained.

Formula B
2% behenyl alcohol and 0.5% stearic acid

Water balance

  The gel of formulation A was heated to 80 ° C., and the formulation B solution dissolved by heating to 80 ° C. was added, and the mixture was homogenized by stirring at 5000 rpm for 5 minutes with a homomixer. Further, the arginine aqueous solution of Formulation C was added while stirring, and the mixture was cooled while stirring with a paddle. It was 2915 nm when the average particle diameter of the nanocapsule was measured.

  Using this nanocapsule as a conductive material for pharmaceuticals, cosmetics, composition for introducing vibration, composition for introducing electromagnetic waves, composition for introducing heat, composition for introducing electrolysis, paint, toner, ink for ink jet, for magnetic memory material, When added to a normal matrix at a concentration of 5% as a conductive material for a pirinta substrate, fine particles are less likely to cause secondary agglomeration of the powder, so finer wiring can be printed and the wiring density is doubled. It was confirmed that a printed board with a low disconnection rate and a high wiring density could be created.

The invention's effect

According to the present invention, one or more simple substances of water and / or a liquid matrix or a composite thereof, one or more simple substances of a surfactant dissolved or dispersed therein or a composite thereof, and one or more of a fat-soluble substance. By producing nanocapsules from a raw material composed of a single substance or a composite thereof, it is possible to produce nanocapsules with good stability, high safety, simple and inexpensive, and capable of supplying nanocapsules that can be used in a wide range of applications. .

Claims (9)

  From one or more simple substances of water and / or a liquid matrix or a composite thereof, one or more simple substances of a surfactant dissolved or dispersed therein or a composite thereof, and one or more simple substances of a fat-soluble substance or a composite thereof. Composition for raw material for producing nanocapsules   A nanocapsule production raw material composition according to claim 1 formed by dispersing in water in a range of 1 micrometer or less, preferably in the range of 999 nanometers to 1 nanometer, more preferably in the range of 300 nanometers to 10 nanometers. Nanocapsules with average particle size in the range   The nanocapsule according to claim 2, wherein the surfactant according to claim 1 is one or a mixture selected from surfactin, a derivative thereof and a salt thereof.   The nanocapsule according to claim 2, wherein the water and / or liquid matrix according to claim 1 is one or a mixture selected from glycerin and derivatives thereof and salts thereof.   The fat-soluble substance of claim 1 is an antioxidant substance, preferably an antioxidant substance having a radical scavenging effect such as singlet oxygen, hydroxy radical, NO radical, lipid peroxide, more specifically vitamin C, A fat-soluble substance selected from vitamin E, vitamin A, coenzyme, lipoic acid, polyphenol, fullerene, tar dye, fat-soluble conductive substance, fat-soluble magnetic substance, fat-soluble pigment, fat-soluble dye, or the like, or The nanocapsule according to claim 2, wherein the nanocapsule is an antioxidant derivative or provitamin which is one or more of a fat-soluble derivative, a complex with a fat-soluble substance, or a complex with a fat-soluble substance.   The nanocapsule according to claim 2 is used for pharmaceuticals, pharmaceutical raw materials, cosmetics, cosmetic raw materials, external preparations, ion introduction compositions, vibration introduction compositions, electromagnetic wave introduction compositions, heat introduction compositions, and electrolytic introduction compositions. Products, foods, food additives, functional foods, feeds, feed additives, antioxidants, antioxidants, antioxidants, paints, toners, ink jet inks, inkjet printed circuit boards, and photosensitive particles for photographic films The use according to claim 2, which is one or more of a simple substance or a mixture   A method for enhancing the effect of the use according to claim 6 by introducing the nanocapsule according to claim 2 by one or more single methods or a mixing method selected from ion introduction, vibration introduction, electromagnetic wave introduction, heat introduction, and electrolysis introduction.   A method for producing fine emulsified particles having an average particle diameter of less than 1000 nm dispersed in water and an aqueous solvent by subjecting the composition for raw material for producing nanocapsules of claim 1 to impact deformation at a shear rate of at least 15 / s.   The method according to claim 9, wherein the shear deformation is performed using at least one dispersion device selected from the group consisting of a static mixer, a jet dispersator, a microporous filter, a microfluidizer, and a Manton-Gaulin homogenizer nozzle. .