JP2006137684A - Method for preparing liposome precursor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method for preparing a high quality liposome precursor containing ubiquinone Q10 with high efficiency, a liposome using the same, and a cosmetic and a health food which contain the liposome precursor or the liposome. <P>SOLUTION: The method for preparing the liposome precursor containing ubiquinone Q10 comprises drying an organic solvent solution obtained by uniformly dissolving a phospholipid and ubiquinone Q10 in an organic solvent by the CRUX(R) method to obtain a powdered liposome precursor. The liposome uses the liposome precursor, and the cosmetic and the health food contain the liposome precursor or the liposome. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

The present invention relates to a method for producing a ubiquinone Q10-containing liposome precursor, a liposome using the same, and a cosmetic and health food containing the liposome.

Ubiquinone Q10 is also called ubidecalenone, coenzyme Q10, vitamin Q, etc., and exists as a physiologically active component in vivo. In recent years, not only for pharmaceutical and health food applications,
In cosmetic applications, blending has been attempted as it has effects such as cell activation, pigmentation prevention, antioxidant and wrinkle prevention. As a cosmetic application, JP-A 61-
289029.
Ubiquinone Q10 is a fat-soluble compound and is emulsified with a surfactant in order to disperse it in water. However, heavy use of the surfactant is not preferable from the viewpoint of safety to living bodies, skin, and the like.
It is known to form a liposome as a means for solubilizing a fat-soluble component. Since liposomes are composed of phospholipids, etc., they have high biocompatibility and are excellent in safety, and unstable substances such as ubiquinone are encapsulated in the liposome particles, which is preferable.
Ubiquinone Q10-containing liposomes are known from JP-A 58-8010. However, in the production method disclosed here, a thin-film liposome precursor is obtained by a rotary evaporator method, dispersed in a solvent, and then fractionated by a Sephadex column is further filtered to obtain a liposome. Therefore, the operation was very complicated, and the yield was very low and the economy was poor. There has been a demand for a method for producing ubiquinone Q10-containing liposomes that are easy to operate and have high yield and high quality.
In addition, the powdered liposome precursor is easily dispersed by dispersing it in a polyhydric alcohol aqueous solution or the like, and since it is powdery, it has high temporal stability and is useful for producing liposomes. Spray drying, freeze drying, etc. are known as methods for producing powdered liposome precursors, but the powder obtained by spray drying is hard and poorly dispersible, and is expensive in freeze drying. , And the drying rate is slow and the economy is poor.
JP 58-8010 A JP-A-01-222291 JP 2002-540718 A

A method for producing a high-quality ubiquinone Q10-containing liposome precursor with high efficiency, a liposome using the same, and a cosmetic and a health food containing the liposome precursor or the liposome.

As a result of intensive studies to solve the above problems, the present inventors have found that phospholipid and ubiquinone Q1.
A method for producing a ubiquinone Q10-containing liposome precursor in which an organic solvent solution in which 0 is uniformly dissolved in an organic solvent is dried by a cracks method to obtain a powdered liposome precursor, and a liposome using the same and the liposome precursor or Cosmetics and health foods containing the liposomes are provided.

Provided is a ubiquinone Q10-containing liposome precursor having a high efficiency and high quality, having a small particle size and excellent stability over time, and a cosmetic and health food containing the liposome precursor or the liposome. It comes out.

It is known that ubiquinone Q10 used in the present invention exists in vivo and acts as a coenzyme for mitochondrial energy metabolism enzymes. These can be obtained by extraction from a living body, but commercially available products produced by fermentation methods, organic synthesis methods, and the like can also be used.
Ubiquinone Q10 can be contained in an amount of about 0.01 to 30% by weight, preferably 1 to 20% by weight, more preferably 5 to 15% by weight, based on the liposome precursor. This is because if the amount of ubiquinone Q10 is small, stable liposomes are easily obtained, but the addition efficiency is poor, and if it is too large, the stability of the liposomes is poor.

As the phospholipid used in the present invention, any known phospholipid can be used, and specific examples thereof include, for example, soybean reticin, egg yolk lecithin, dipartoyl phosphatidylcholine, distearoyl phosphatidylcholine, dioleyl phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol. And phospholipids such as sphingomyelin and phosphatidylinositol and those obtained by hydrogenating natural phospholipids such as hydrogenated lecithin. Natural products are obtained as a mixture of phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidic acid and the like. By purifying these with a solvent such as acetone, the content of phosphatidylcholine can be increased. Phosphatidylcholine can also be obtained by an organic synthesis method in which phospholipase is allowed to act on fatty acid and glycerylphosphorylcholine. These fatty acids include lauric acid, myristic acid, palmitic acid, stearic acid, isostearic acid, behenic acid,
Examples include higher fatty acids such as undecylenic acid, 12-hydroxystearic acid, palmitoleic acid, oleic acid, linoleic acid, linolenic acid, erucic acid, docosahexaenoic acid, icosapentaenoic acid, isohexadecanoic acid, anteisopentadecanoic acid, animal and vegetable oil fatty acids it can.
As the phospholipid of the present invention, those having a low iodine value such as hydrogenated lecithin are preferable because of their excellent oxidation stability, color and odor. In particular, an iodine value of 5 or less is preferable. In addition, lecithin having a high phosphatidylcholine content purified with a solvent or the like is preferable. These phospholipids can be used in combination of two or more. In particular, it is preferable to use in combination with a positively or negatively charged phospholipid in order to impart charge to the liposome particles.
As a phospholipid, it can be used 1-1000 times by weight ratio with respect to ubiquinone Q10, Preferably it is 4-50 times. More preferably, it is 5 to 10 times.

The organic solvent used in the present invention is not particularly limited as long as it can dissolve both phospholipid and ubiquinone Q10 at the same time. However, considering the ease of dissolution and drying property, ubiquinone Q1.
Organic solvents having a boiling point higher than 0 and lower than 100 ° C. are preferred. Specifically, for example, hydrocarbons such as pentane, hexane, heptane and cyclohexane, halogen hydrocarbons such as methylene chloride and chloroform, aromatic hydrocarbons such as benzene and toluene,
Examples include lower alcohols such as methanol and ethanol, and esters such as methyl acetate and ethyl acetate. An organic solvent can be used individually or in combination of 2 or more types. The amount of the organic solvent used is not particularly limited and may be appropriately selected from a wide range depending on the solubility of the lipid in the organic solvent. However, considering the applicability to an industrial scale, etc. -10
About 0 times by weight, preferably about 5 to 50 times by weight.

Examples of sterols used in the present invention include cholesterol, dihydrocholesterol, lanosterol, dihydrolanosterol, sitosterol, campesterol, stigmasterol, brassicasterol, ergosterol, and a mixture thereof, phytosterol, and hydrogenated phytosterol. it can. Sterols can be used alone or in combination of two or more. Among these, cholesterol, sitosterol, and phytosterol are preferable. Cholesterol is particularly preferable because of its high effect on liposome stability. The amount of sterol used is about 0.01 to 0.3 times by weight, preferably 0.02 to 0.2 times by weight, more preferably 0.02 to 0.1 times by weight relative to the phospholipid.

The method for producing the powdered liposome precursor of the present invention can be easily obtained with a particle size of 50 to 180 nm when used as a liposome solution without using a surfactant other than phospholipid and sterol. Are preferably free of a surfactant. In addition to the above-described compounds, the above-mentioned organic solvent solution may contain fats and oils, antioxidants, physiologically active substances, surfactants, and the like.

The drying method by the cracks method of this invention can be implemented according to the flow sheet shown in FIG.
First, an organic solvent solution of phospholipid and ubiquinone Q10 is prepared. For example, a stock tank (
Phospholipid and ubiquinone Q10 may be added to 1) together with an organic solvent and dissolved uniformly.
You may heat as needed at the time of melt | dissolution.
Next, the solution in the stock solution tank (1) is preheated by a preheater (not shown) as necessary,
It is supplied to the heating tube (2) at a constant speed. Although the supply method is not particularly limited, for example, it may be supplied at a constant speed using a pump or the like. The supply rate can be appropriately selected from a wide range according to the flow rate of the mixture of the heated steam and the solid content described later and the diameter of the heating pipe (2).
It may be about 00 l / h, more preferably about 5 to 50 l / h. Although not shown, the heating tube (2) can be heated from the outside by, for example, heating with steam, hot water heating, electric heating, or the like. The heating temperature is not particularly limited as long as it is higher than the boiling point of the organic solvent to be used, but is usually about 5 to 100 ° C., more preferably 5 to 5 than the boiling point of the organic solvent.
What is necessary is just to raise about 0 degreeC.
By heating, the organic solvent in the solution supplied into the heating tube (2) is heated and evaporated, so that the solution is a mixture of heated vapor, phospholipid and ubiquinone Q10 (hereinafter referred to as “solid content”). become. At this time, a slight amount of organic solvent remains in the solid content. The temperature of the solid content at this time is preferably 40 to 90 ° C, more preferably 50 to 80 ° C. By setting the temperature to such a level, the powdered liposome precursor obtained is less agglomerated.
Next, the heated vapor and solid content mixture is introduced from the outlet of the heating tube (2) into the vacuum chamber (3) in a reduced pressure state. By the introduction, a slight amount of the organic solvent remaining in the solid content is instantaneously evaporated, and the organic solvent does not substantially remain in the solid content.
The degree of vacuum in the vacuum chamber (3) is usually about 40 kPa or less, preferably about 0.6 to 40 kPa, more preferably about 0.6 to 13 kPa. Thereby, the mixture of the heated steam and the solid content is introduced into the vacuum chamber (3) at a speed of about 1/10 or more, preferably 100 m / sec or more, more preferably about the speed of sound. . Degree of vacuum is 40kP
When the temperature is lower than a, the inside of the heating tube (2) is clogged, the residual amount of the organic solvent in the obtained powder is increased or the particle size of the powder is increased, the hydration property is reduced, or the raw material loss There will be more. What is necessary is just to connect the vacuum pump (7) for making a vacuum chamber (3) into a vacuum state to a vacuum chamber (3) via a condenser (4), for example.
The solid content instantly vacuum-dried as described above is recovered, for example, in the container (6) below the vacuum chamber (3). In this way, the ubiquinone Q10-containing liposome precursor of the present invention can be obtained in powder form. The particle size of the powder is usually about 100 to 2000 μm, and it can be made smaller by applying this to a pulverizer. On the other hand, the vapor of the evaporated organic solvent is liquefied in the condenser (4), stored in the recovery tank (5), and recovered.
In the present invention, as an apparatus for instant vacuum drying of a solution as shown in FIG.
Commercially available instantaneous vacuum drying systems such as “Crax” (manufactured by Hosokawa Micron Corporation) can be used. According to this apparatus, since the time for which the components are heated is as short as about 30 seconds to 2 minutes, it is convenient for ubiquinone Q10 which is unstable to heat.
The thus obtained powdered ubiquinone Q10-containing liposome precursor is desirably hermetically preserved with an inert gas such as nitrogen, carbon dioxide, or argon gas.

The liposome of the present invention is dispersed by adding the above-mentioned powdered ubiquinone Q10-containing liposome precursor to an aqueous solution. Dispersion can be easily performed without vigorous stirring or heating.
Subsequently, a fine liposome solution can be obtained by monodispersing with a disperser such as a homogenizer or a disper mixer. The liposome liquid can be further sized with a high-pressure filter such as an extruder. The particle size of the liposome is preferably about 50 to 180 nm. This is because the liposome liquid becomes transparent and the stability with time increases with a particle size of this level. Moreover, when it is contained in health foods, it is known that the absorbability from the intestinal tract is significantly improved if the particle size is small. Moreover, when preparing the above-mentioned liposome solution, physiologically active ingredients such as vitamins can be added and encapsulated in the liposome. When preparing the liposome solution, it is preferable to contain a polyhydric alcohol such as glycerin, 1,3-butylene glycol or propylene glycol in the aqueous solution.

The amount of the ubiquinone Q10-containing liposome in the cosmetic of the present invention may be added as about 0.0001 to 1% by weight as ubiquinone Q10 with respect to the entire cosmetic.

In the cosmetic of the present invention, water and additive components blended in the cosmetic and skin external preparations as necessary, such as oil bases, surfactants, alcohols, humectants, polymers, thickeners, and gels Agents, antioxidants, antiseptics, bactericides, chelating agents, pH adjusters / acids / alkalis, UV absorbers, whitening agents, solvents, exfoliating / dissolving agents, antipruritics, anti-inflammatory agents, antiperspirants, cooling agents , Antihistamines, astringents, stimulants, hair growth agents / blood circulation promoters, reducing agents / oxidants, polymer powders, hydroxy acids,
Vitamins and derivatives thereof, saccharides and derivatives thereof, organic acids, enzymes, nucleic acids, hormones, inorganic powders, fragrances, pigments and the like can be blended.

Examples of these additive components include oil bases such as cetanol, myristyl alcohol, oleyl alcohol, lauryl alcohol, cetostearyl alcohol, stearyl alcohol, aralkyl alcohol, behenyl alcohol, jojoba alcohol, chimyl alcohol, batyl alcohol, hexyl decanol. , Isostearyl alcohol, 2
-Higher alcohols such as octyldodecanol and dimer diol; lauric acid, myristic acid, palmitic acid, stearic acid, isostearic acid, behenic acid, undecylenic acid,
12-hydroxystearic acid, palmitooleic acid, oleic acid, linoleic acid, linolenic acid, erucic acid, docosahexaenoic acid, eicosapentaenoic acid, isohexadecanoic acid,
Higher fatty acids such as anteisohenicosanoic acid, long-chain branched fatty acid, dimer acid, hydrogenated dimer acid, and metal soaps such as aluminum salts, calcium salts, magnesium salts, zinc salts, potassium salts, and amides Nitrogen-containing derivatives; liquid paraffin, heavy liquid isoparaffin, α-olefin oligomer, polyisobutene, hydrogenated polyisobutene, polybutene, squalane, squalene, petroleum jelly, solid paraffin and other carbides; candelilla wax, carnauba wax, rice Waxes such as wax, wax, beeswax, montan wax, ozokerite, ceresin, paraffin wax, microcrystalline wax, petrolatum, Fischer-Tropsch wax, polyethylene wax, ethylene-propylene copolymer; Shea oil, palm oil, palm kernel oil, safflower oil, olive oil, castor oil, avocado oil, sesame oil, tea oil, evening primrose oil, wheat germ oil, macadamia nut oil,
Hazelnut oil, cucumber oil, rosehip oil, meadow foam oil, persic oil, tea tree oil, mint oil, corn oil, rapeseed oil, sunflower oil, wheat germ oil, linseed oil, cottonseed oil, soybean oil, peanut oil, rice bran oil, Cacao butter, shea butter, hydrogenated palm oil,
Vegetable oils such as hydrogenated castor oil, jojoba oil, hydrogenated jojoba oil; animal fats such as beef tallow, milk fat, horse fat, egg yolk oil, mink oil, turtle oil; whale wax, lanolin, orange luffy oil, etc. Animal waxes: liquid lanolin, reduced lanolin, adsorbed purified lanolin, lanolin acetate,
Acetic acid liquid lanolin, hydroxy lanolin, polyoxyethylene lanolin, lanolin fatty acid, hard lanolin fatty acid, lanolin alcohol, lanolin alcohol acetate, acetic acid (cetyl
Lanolins such as lanolinyl ester; phospholipids such as phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, sphingomyelin, phosphatidic acid, lysolecithin; phospholipid derivatives such as hydrogenated soybean phospholipid, hydrogenated egg yolk phospholipid; cholesterol, Sterols such as dihydrocholesterol, lanosterol, dihydrolanosterol, phytosterol; cholesteryl acetate, cholesteryl nonanoate,
Cholesteryl stearate, cholesteryl isostearate, cholesteryl oleate,
N-lauroyl-L-glutamate di (cholesteryl / behenyl / octyldodecyl),
N-lauroyl-L-glutamate di (cholesteryl / octyldodecyl), N-lauroyl-L-glutamate di (phytosteryl / behenyl / octyldodecyl), N-lauroyl-L-glutamate di (phytosteryl / octyldodecyl), 12-hydroxy Sterol esters such as cholesteryl stearate, macadamia nut oil fatty acid cholesteryl, macadamia nut oil fatty acid phytosteryl, phytosteryl isostearate, soft lanolin fatty acid cholesteryl, hard lanolin fatty acid cholesteryl, long chain branched fatty acid cholesteryl, long chain α-hydroxy fatty acid cholesteryl; ethyl oleate , Ethyl avocado fatty acid, isopropyl myristate, isopropyl palmitate, octyl palmitate, isoisostearate Lower alcohol fatty acid esters such as propyl, lanolin fatty acid isopropyl, diethyl sebacate, diisopropyl sebacate, dioctyl sebacate, diisopropyl adipate, dioctyl succinate; octyldodecyl myristate, hexyldecyl myristate, octyldodecyl isostearate, palmitic acid Octyldodecyl, cetyl octoate, hexyldecyl octoate, isotridecyl isononanoate, isononyl isononanoate, octyl isononanoate, isotridecyl isononanoate,
Isodecyl neopentanoate, isotridecyl neopentanoate, isostearyl neopentanoate, octyldodecyl neodecanoate, oleyl oleate, octyldodecyl oleate, octyldodecyl ricinoleate, lanolin fatty acid octyldodecyl, hexyldecyl dimethyloctanoate, octyldodecyl erucate, isostearic acid Higher alcohol fatty acid esters such as hydrogenated castor oil; oxyacid esters such as cetyl lactate, diisostearyl malate, hydrogenated castor oil monoisostearate; glyceryl trioctanoate, glyceryl trioleate, glyceryl triisostearate, tri ( Caprylic acid / Capric acid)
Glyceryl, tri (caprylic acid / capric acid / myristic acid / stearic acid) glyceryl, hydrogenated rosin glyceryl (hydrogenated ester gum), neopentyl glycol dioctanoate, 2-butyl-2-ethyl-1,3-propane dioctanoate Diol, propylene glycol dioleate, pentaerythrityl tetraoctanoate, hydrogenated rosin pentaerythrityl, (hydroxystearic acid / stearic acid / rosinic acid) dipentaerythrityl, diglyceryl diisostearate, polyglyceryl tetraisostearate, polyglyceryl nonaisostearate-10 , Polyhydric alcohol fatty acid esters such as deca (erucic acid / isostearic acid / ricinoleic acid) polyglyceryl-8; diisopropyl linoleic acid diisopropyl, dimer Linoleic acid diisostearyl, dimerdilinoleic di (
Isostearyl / phytosteryl), dimer linoleic acid (phytosteryl / behenyl), dimer linoleic acid (phytosteryl / isostearyl / cetyl / stearyl / behenyl), dimer dilinoleate dimer dilinoleyl, diisostearate dimer dilinoleyl, dimer stearic acid Dimer acid or dimer diol derivatives such as merlinoleyl hydrogenated rosin condensate, dimer linoleic acid hydrogenated castor oil, hydroxyalkyl dimer linoleyl ether; coconut oil fatty acid monoethanolamide, coconut oil fatty acid diethanolamide, lauric acid mono Fatty acid alkanolamides such as ethanolamide, lauric acid diethanolamide, palmitic acid monoethanolamide, palmitic acid diethanolamide, etc .; low viscosity dimethylpolysiloxane Sun, high viscosity dimethylpolysiloxane, cyclic dimethylsiloxane (decamethylcyclopentasiloxane), methylphenylpolysiloxane, diphenylpolysiloxane, silicone resin, silicone rubber, aminopropyl dimethicone and amodimethicone Siloxane, polyether-modified polysiloxane, polyglycerin-modified polysiloxane, sugar-modified polysiloxane,
Examples include silicones such as alkyl-modified polysiloxane, fatty acid-modified polysiloxane, and fluorine-modified polysiloxane; fluorine-based oils such as perfluorodecane, perfluorooctane, and perfluoropolyether.

Surfactants include fatty acid salts, alkyl sulfate esters, alkyl benzene sulfonates, polyoxyethylene alkyl sulfates, polyoxyethylene fatty amine sulfates, acyl N-methyl taurates, alkyl phosphate esters, alkyl ether phosphates. Anionic surfactants such as acid ester salts and N-acyl amino acid salts; polyoxyethylene alkyl ether, polyoxyethylene alkyl phenyl ether, polyoxyethylene alkyl ether sorbitan fatty acid partial ester, polyoxyethylene hydrogenated castor oil, polyvalent Nonionic surfactants such as alcohol fatty acid partial esters, polyglycerin fatty acid esters, polyoxyethylene fatty acid esters, alkyldimethylamine oxides, alkyl polyglycosides, alkyl glucosides; Rutrimethylammonium chloride, alkyltrimethylammonium bromide, dialkyldimethylammonium chloride, ethyl sulfate long chain branched fatty acid (12-31) aminopropylethyldimethylammonium, ethyl lanolin sulfate fatty acid aminopropylethyldimethylammonium, short chain polyoxyethylene alkylamine and Cationic surfactants such as salts or quaternary salts thereof, benzalkonium chloride; fatty acid amidoamines and salts thereof; alkyldimethylaminoacetic acid betaine, alkylamidodimethylaminoacetic acid betaine, 2-alkyl-N-carboxy-N-hydroxy Amphoteric surfactants such as imidazolinium betaine; polyvinyl alcohol, sodium alginate, starch derivatives, tragacanth gum, acrylic acid / methacrylic acid Polymeric surfactants such as alkyl copolymer; and the like can be exemplified.

Examples of humectants include propylene glycol, glycerin, 1,3-butanediol, 3-
Polyhydric alcohols such as methyl-1,3-butanediol, sodium hyaluronate, citrate, urea, lactic acid bacteria culture solution, yeast extract, eggshell membrane protein, submandibular gland mucin, hypotaurine, sesameignan glycoside, Betaine, chondroitin sulfate, glutathione, polyethylene glycol, sorbitol, carbitol, sodium lactate, sodium 2-pyrrolidone-5-carboxylate, albumin, trimethylglycine; collagen, gelatin, elastin, collagen degrading peptide, elastin degrading peptide, keratin degrading peptide Protein peptides such as conchiolin degrading peptides, silk proteolytic peptides, soybean proteolytic peptides, wheat proteolytic peptides, casein degrading peptides, acylated peptides and their derivatives; arginine, serine, glycine Emissions, threonine, glutamic acid, cysteine, methionine, leucine, amino acids such as tryptophan; placental extract, Earasuchin, collagen,
Aloe extract, Hamamelis water, loofah water, chamomile extract, licorice extract, comfrey extract and other animal / plant extract components, natural ceramide (types 1, 2, 3, 4, 5, 6), hydroxyceramide, pseudoceramide And ceramides such as glycosphingolipids.

Polymers, thickeners and gelling agents include guar gum, locust bean gum, queens seed, carrageenan, galactan, gum arabic, tara gum, tamarind, fur celerin, karaya gum, troarooi, cara gum, tragacanth gum, pectin, alginic acid and its salts , Mannan, starch, xanthan gum, dextran, succinoglucan,
Curdlan, hyaluronic acid and salts thereof, xanthan gum, pullulan, gellan gum, chitin, chitosan, agar, chondroitin sulfate, casein, gelatin, albumin, methylcellulose, ethylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, carboxymethylcellulose and salts thereof, methylhydroxy Propylcellulose,
Cationized cellulose, soluble starch, carboxymethyl starch, methyl starch,
Alginate propylene glycol ester, polyvinyl alcohol, polyvinyl pyrrolidone, polyoxyethylene-polyoxypropylene copolymer, polyvinyl acetate partial saponification product, maleic acid copolymer, polyacrylic acid ester copolymer, carboxyvinyl polymer,
Polyacrylic acid and its salts, acrylic acid / methacrylic acid ester copolymer, amphoteric methacrylic acid ester copolymer, acrylic acid / methacrylic acid alkyl copolymer, diallyldimethylammonium chloride / acrylamide copolymer, acrylic acid / Diallyldimethylammonium chloride / acrylamide copolymer, acrylic acid / cationized methacrylic acid ester copolymer, acrylic acid / cationized methacrylic acid amide copolymer, chloromethacrylic acid choline ester polymer, cationized guar gum, nitrocellulose And 12-hydroxystearic acid and salts thereof, dextrin fatty acid ester, silicic anhydride, metal soap, organically modified clay mineral, sucrose fatty acid ester, fructooligosaccharide fatty acid ester and the like.

Examples of the antioxidant include BHT, BHA, propyl gallate, vitamin E (tocopherol) and / or its derivative, vitamin C (ascorbic acid) and / or its derivative, sulfite, bisulfite and the like. . Examples of preservatives include phenols, phenoxyethanol, hydroxybenzoic acid and salts thereof, 1,2-pentanediol, 1,2-hexanediol, halogenated bisphenols, acid amides, quaternary ammonium salts and the like. it can. Examples of the bactericides include trichlorocarbanide, zinc pyrithione, benzalkonium chloride, benzethonium chloride, chlorhexidine, halocarban, hinokitiol, phenol, isopropylphenol, and photosensitizers. Examples of chelating agents include edetate, phytic acid, phosphonic acids, sodium oxalate, polyamino acids and the like. pH adjusters / acids / alkalis include citric acid, lactic acid, glycolic acid, succinic acid, acetic acid, hydrochloric acid, monoethanolamine, diethanolamine, triethanolamine, isopropanolamine, arginine, sodium hydroxide, potassium hydroxide, aqueous ammonia Examples thereof include guanidine carbonate and the like.

Examples of ultraviolet absorbers include benzophenone derivatives such as oxybenzone, paraaminobenzoic acid derivatives, paramethoxycinnamic acid derivatives, salicylic acid derivatives, ferulic acid and its derivatives, derivatives such as urocanic acid and ethyl urocanate, butylmethoxybenzoylmethane,
Examples include octyl triazone, 2- (2′-hydroxy-5′-methylphenyl) benzotriazole, ferulic acid, methyl anthranilate, rutin and derivatives thereof. As whitening agents, arbutin, ascorbic acid, ascorbic acid glucoside, ascorbic acid phosphate ester salt, ascorbic acid branched fatty acid ester, ascorbic acid alkyl ether and other ascorbic acid derivatives, kojic acid, glutathione, ellagic acid, placenta extract, oryzanol, Examples include plant extracts such as butylresorcinol and chamomile extract.

Examples of the solvents include lower alcohols such as ethanol and 2-propanol; acetone, ethyl acetate, ethylene glycol monoethyl ether, toluene and the like.

Examples of the exfoliating / dissolving agent include salicylic acid, sulfur, resorcin, selenium sulfide, pyridoxine and the like. Examples of the antipruritic agent include diphenhydramine hydrochloride, chlorpheniramine maleate, camphor and the like. Examples of the anti-inflammatory agent include glycyrrhizic acid and its derivatives, guaiazulene, hydrocortisone acetate, prednisone and the like. Examples of the antiperspirant include chlorohydroxyaluminum, aluminum chloride, zinc oxide, and zinc paraphenol sulfonate. Examples of the refreshing agent include menthol and methyl salicylate. As an antihistamine,
Examples thereof include diphedramine hydrochloride, chlorpheniramine maleate, glycyrrhetinic acid derivatives and the like. Examples of the astringent include citric acid, tartaric acid, lactic acid, aluminum sulfate / potassium sulfate, and tannic acid. Examples of the stimulant include cantalis tincture, ginger tincture, chili pepper tincture, benzyl nicotinate and the like.
Plant extracts and tinctures such as assembly extract, chili pepper tincture, ginger tincture, cantalis tincture, etc. as cephalanthin, vitamin E and its derivatives, γ-oryzanol, nicotinic acid and nicotinic acid benzyl ester And derivatives thereof, allantoin, photosensitive element 301, photosensitive element 401, pentadecanoic acid monoglyceride, flavonol derivative, minoxidil and the like.

Examples of the reducing agent include thioglycolic acid, cysteine, cysteamine and the like. Examples of the oxidizing agent include aqueous hydrogen peroxide, ammonium persulfate, and sodium bromate.

Examples of the polymer powder include starch, nylon powder, polyethylene powder, polymethyl methacrylate, polyethylene terephthalate / polymethyl methacrylate laminate powder, polyethylene terephthalate / aluminum / epoxy laminate powder, and the like, and these asserted powders. be able to.

Examples of α-hydroxy acids and derivatives thereof include lactic acid, glycolic acid, fruit acid, hydroxycapric acid, long chain α-hydroxy fatty acid, long chain α-hydroxy fatty acid cholesteryl and the like.

Vitamins and their derivatives include vitamin A, vitamin B group, vitamin D, vitamin E, pantothenic acid, biotin and the like; ascorbyl stearate, ascorbyl palmitate, ascorbyl dipalmitate, ascorbyl magnesium phosphate, ascorbine Examples thereof include vitamin derivatives such as sodium acid, tocopherol nicotinate, tocopherol acetate, tocopherol linoleate, and tocopherol ferulate.

Examples of sugars and derivatives thereof include cyclodextrin, β-glucan, chitin, chitosan, glucose, trehalose, pectin, arabinogalactan, dextrin, dextran, glucosylethyl methacrylate polymer or copolymer, and the like. . Examples of organic acids include acetic acid, propionic acid, citric acid, abietic acid, tartaric acid and the like.

Examples of enzymes include lysozyme chloride, papain, pancreatin, protease, and the like. Examples of nucleic acids include adenosine triphosphate disodium. Examples of hormones include estradiol, estrone, ethinyl estradiol, cortisone, hydrocortisone, prednisone and the like.

Inorganic powders include mica, talc, kaolin, montmorillonite, sericite, kaolinite, calcium carbonate, bengara, yellow iron oxide, black iron oxide, ultramarine, bitumen, carbon black, titanium dioxide, zinc oxide, alumina, silica. , Fumed silica (ultrafine silica), mica titanium, fish scale foil, boron nitride, photochromic pigment, synthetic fluorine phlogopite, fine particle composite powder, gold, aluminum and other inorganic powders and hydrophobic treatment Examples of such powders can be given.

Examples of the fragrance include limonene, linanol, citral, β-ionone, benzyl benzoate, indole, eugenol, auranthiol, geraniol, rilal, damascon, benzyl acetate, jasmine lactone, galac solid, essential oil and the like.

Natural pigments such as β-carotene, calsamine, rutin, cochineal, chlorophyll; legal pigments, basic dyes, lakes, organic pigments; p-phenylenediamine, toluene
Examples thereof include intermediates of oxidative dyes such as 2,5-diamine, m-phenylenediamine, o-, m-, or p-aminophenol and resorcin.

In addition, other components used in known cosmetics, pharmaceuticals, foods and the like can be appropriately blended as long as the effects of the present invention are not impaired.

The cosmetic of the present invention can be produced according to a usual method, and includes cosmetics for hair, basic cosmetics, makeup cosmetics, aromatic cosmetics, body cosmetics and the like.

Cosmetics for hair include oil shampoo, cream shampoo, conditioning shampoo, dandruff shampoo, hair color shampoo, shampoo with integrated rinse, shampoo, rinse, treatment, hair pack, hair foam, hair mousse, hair spray, hair mist, Hair wax, hair gel, water grease, set lotion, color lotion, hair tonic, hair liquid, pomade, tic, hair cream, hair blow, split hair coat, hair oil, permanent wave agent, straight permanent agent, oxidative hair dye, hair Illustrate bleach, hair color pre-treatment, hair color after-treatment, perm pre-treatment, perm after-treatment, hair nail polish, hair restorer, etc. It can be.

As basic cosmetics, cleansing foam, cleansing powder, facial cleansing powder, cleansing cream, cleansing milk, cleansing lotion, cleansing gel, cleansing oil, cleansing mask, etc .; soft lotion, astringent lotion, cleansing lotion,
Skin lotion such as multi-layered lotion; emollient lotion, moisture lotion, milky lotion, nourishing lotion, nourishing milk, skin moisture, moisturizer emulsion, massage lotion, cleansing lotion, protect emulsion, sun protect, sun protector, UV Care milk, sunscreen, makeup lotion, horny smoother, elbow lotion, hand lotion, body lotion, etc .; emollient cream, nourishing cream, nourishing cream, vanishing cream, moisture cream, night cream, massage cream, cleansing cream, makeup Cream, base cream, pre-makeup cream, sunscreen cream, sun Cream, hair removal cream, deodorant cream, shaving cream, keratin softening cream, etc .; gels such as cleansing gel, moisture gel, etc .: soap such as cosmetic soap, transparent soap, medicated soap, liquid soap, shaving soap, synthetic cosmetic soap Packs and masks such as peel-off packs, powder packs, washing packs, oil packs and cleansing masks; essences such as moisturizing essences, whitening essences, and UV protection essences.

Examples of makeup cosmetics include white powder, dusting powder, foundations, lipsticks, lip gloss, blusher, eyeliner, mascara, eye shadow, eyebrow, eyebrow, nail enamel, enamel remover, and nail treatment. .

Examples of aromatic cosmetics include perfume, perfume, parfum, eau de parfum, eau de toilette, eau de cologne, perfume, fragrance powder, perfume soap, body lotion, bath oil and the like.

Body cosmetics such as body shampoos; deodorant lotions, deodorant powders, deodorant sprays, deodorant sticks and other deodorant cosmetics; decoloring agents, hair removal / hair removal agents; bathing agents; insect repellents An example is a repeller.

In addition, oil-in-water (O / W) type, water-in-oil (W / O) type, W / O / W type, O / W as dosage forms
/ O type emulsified cosmetics, oily cosmetics, solid cosmetics, liquid cosmetics, kneaded cosmetics, sticky cosmetics, volatile oily cosmetics, powdery cosmetics, jelly cosmetics, gels It can be used in dosage forms such as cosmetics, pasty cosmetics, emulsified polymer cosmetics, sheet cosmetics, mist cosmetics, and spray cosmetics.

Moreover, it can be used as a skin external preparation in dosage forms such as an ointment, a patch, a lotion, a liniment, and a liquid coating agent.

EXAMPLES Hereinafter, although this invention is demonstrated in detail using an Example, this invention is not limited to these Examples.

Example 1
As the instantaneous vacuum drying device shown in FIG. 1, a device commercially available under the trade name “CRUX 8B type” [
The powdered liposome precursor of the present invention was manufactured using Hosokawa Micron Co., Ltd. (hereinafter referred to as “Crax System”).
Hydrogenated soybean lecithin 780 g, cholesterol 100 g, ubiquinone Q10 12
0 g was dissolved in 10 l of chloroform. This lipid solution was put into the stock solution tank (1) of the CRAX system, and supplied to the heating tube (2) at a liquid feed amount of about 20 l / h. At this time, the heating tube (
The temperature of the heat exchanger provided outside 2) was set to 70 ° C., and the degree of vacuum in the vacuum chamber (3) connected to the outlet of the heating tube (2) was set to 5 to 10 kPa. The mixture of chloroform vapor and lipid formed in the heating tube (2) flowed into the vacuum chamber (3) at a speed of 1/10 or more of the speed of sound. Forty minutes after starting to supply the lipid solution to the heating tube (2), 950 g of ubiquinone Q10-containing liposome precursor in the form of a fine yellow powder was obtained. (Raw material recovery rate 95%).

Comparative Example 1
78 g of hydrogenated soybean lecithin, 10 g of cholesterol, and 12 g of ubiquinone Q10 were dissolved in 400 ml of tert-butanol. This lipid solution was put in a freezing bottle, immersed in a −70 ° C. refrigerant and frozen, and lyophilized at a vacuum of 0.013 kPa using a freeze dryer FLEXI-DRY (manufactured by FTS SYSTEM INC.). Drying was carried out all day and night to obtain 90 g of yellow fine powder. (Raw material recovery rate 90%).

Example 2 Ubiquinone Q10-containing liposome 1 g of ubiquinone Q10-containing liposome precursor of Example 1 was added to 80 g of water, 5 g of glycerin,
After adding 7.5 g of 1,3-butylene glycol, 0.1 g of phenoxyethanol, and 0.1 g of methylparaben and heating to 50 ° C., the mixture was heated to 50 ° C. to 70 ° C. for 20 minutes with Heidolph DIAX 900 (manufactured by Heidorf Japan). The mixture was stirred while the temperature was raised to obtain a yellow transparent liposome solution.

Comparative Example 2
A slightly turbid yellow liposome solution was obtained in the same manner as in Example 2 except that the ubiquinone Q10-containing liposome precursor of Example 1 was changed to the precursor of Comparative Example 1.

Example 3 Lotion (a) To 93.7 g of the liposome solution of Example 2, (b) 2.55 g of 2% xanthan gum aqueous solution
2% carboxyvinyl polymer aqueous solution adjusted to pH 6.5, 0.5 g, 2% sodium hyaluronate aqueous solution 0.25 g, and water 3 g were added and uniformly dispersed 6.3 g.
The mixture was stirred for 5 minutes with K.HOMOMIXER (manufactured by Tokushu Kika Kogyo Co., Ltd.) to obtain a yellow transparent lotion.
When this lotion was applied to the skin, it stretched well as a slippery, dry and moisturized and had high moisture retention.

Comparative Example 3 Lotion Toner A slightly cloudy yellow lotion was obtained in the same manner as in Example 3 except that the liposome solution of Example 2 was changed to the liposome solution of Comparative Example 2.

Evaluation Method Turbidity After diluting the lotion obtained in Example 3 and Comparative Example 3 four times with water as an index of the obtained lotion, a spectrophotometer HITACHI U-3310 Spectrophometer (Hitachi, Ltd.) The transmittance at 600 nm was measured.

The particle size of the liposome contained in the particle size lotion was measured using a particle size distribution analyzer ZETASIZER NANO-ZS (MALVERN INSTALLMENTS LIMITED).
The appearance change was observed by leaving the time-dependent lotion at 50 ° C. for 2 weeks.
The results are shown in Table 1.

表１から本発明のクラックス乾燥法は平均粒子径の小さいものが得られ、経時安定性も優
れ、透明性もあるので、透明な化粧料にも適用でき、凍結乾燥法に比べて優れていること
がわかる。

From Table 1, the cracks drying method of the present invention is obtained with a small average particle size, and is excellent in stability over time and transparency, so that it can be applied to transparent cosmetics and is superior to freeze drying methods. I understand that.

Example 4 Lotion Toner lotion having the following formulation was prepared. It has excellent moisturizing feeling and provides a smooth feeling while keeping the skin soft and fresh and moist, and these effects last for a long time.
Component Blending amount (% by weight)
--------------------------------
A
Citric acid 0.01
Sodium citrate 0.1
Sodium pyrrolidonecarboxylate 1.0
1,3-butylene glycol 3.0
Purified water Amount B totaling 100
Polyoxyethylene hydrogenated castor oil 0.2
Preservative Appropriate amount Ceramide 3 0.01
Ethanol 10.0
C
Liposome solution of Example 2 15.0
--------------------------------
(Preparation method)
Both A and B are heated and dissolved at 50 ° C., and B is gradually added to A while stirring and solubilized. Cool to 30 ° C with stirring, add C and mix uniformly.

Example 5 Cosmetic liquid A cosmetic liquid having the following formulation was prepared. A moisturizing effect is high, and a feeling of use such as a smooth feeling while keeping the skin soft and fresh and moist is obtained, and these effects last for a long time.
Component Blending amount (% by weight)
--------------------------------
A
(HEMA glucoside / ethyltrimonium methacrylate chloride)
Copolymer (10%) (Nippon Seika) 20.0
Xanthan gum 0.4
Carbomer 0.1
1,3-butylene glycol 10.0
Hyaluronic acid Na 0.05
Purified water Amount B totaling 100
Hydroxide K (1% aqueous solution) 2.5
Purified water 10.0
C
Liposome solution of Example 2 20.0
Glycyrrhizic acid 2K 0.2
Purified water 5.0
D
Preservative appropriate amount PEG-40 hydrogenated castor oil 0.2
Squalane 0.1
Purified water 5.0
(Preparation method)
A to D are dissolved at room temperature. Slowly add B to A with stirring to give a viscous liquid, then C,
Add D, make uniform, and leave.

Example 6 Emulsion An emulsion having the following formulation was prepared. Elongation has a moist feeling, and the feeling of use such as keeping skin moisture and keeping freshness is obtained, and these effects last for a long time.
Component Blending amount (% by weight)
--------------------------------
Plandool-G (Nippon Seika) 1.0
Liposome precursor of Example 1 0.2
Ceramide 2 0.01
Stearic acid 2.0
Vaseline 3.0
Cetyl alcohol 1.0
Sorbitan monooleate 2.0
Polyethylene glycol 1500 3.0
1,3-butylene glycol 3.0
Glycerin 3.0
Maltose 1.0
Sorbitol 1.0
Triethanolamine 1.0
Perfume, preservatives Appropriate amount of purified water Amount to be 100 in total
(Preparation method)
Polyethylene glycol 1500, 1,3-butylene glycol and triethanolamine are added to purified water and heated to 80 ° C. and dissolved (aqueous phase). The other components are mixed and dissolved by heating at 80 ° C. (oil phase). The oil phase is gradually added and pre-emulsified while stirring in this aqueous phase. Further, the mixture is uniformly emulsified with an emulsifier and cooled to room temperature.

Example 7 Anti-aging cream An anti-aging cream having the following formulation was prepared. This cream was glossy, stretched well, and excellent in the effect of giving a moist feeling.
Component Blending amount (% by weight)
--------------------------------
A
Plandool-S (Nippon Seika) 10.0
Liposome precursor of Example 1 0.2
Cetyl octanoate 1.0
Trioctanoin 1.0
Batyl isostearate 2.0
PEG-60 glyceryl isostearate 1.5
Jojoba oil 0.5
Hydrogenated jojoba oil 1.0
Squalane 0.5
Hydrogenated palm oil 3.7
Ceramide 2 0.1
Ceramide 3 0.1
Lauroyl sarcosine isopropyl 0.5
Retinol 0.1
Oil soluble licorice extract 0.5
Oil-soluble chamomile extract 0.5
Ethylparaben 0.2
Stearyl alcohol 3.5
Glyceryl stearate (SE) 1.0
Steerless-6 1.5
Distearic acid PEG-8 1.0
Cetanol 1.0
Dimethicone 1.0
Polyether-modified silicone 0.5
Tocopherol 0.2
B
Nishi-Hayanagi Extract 0.05
Peach leaf extract 0.05
Persimmon leaf extract 0.05
Eggshell membrane extract 0.05
C
Arbutin 3.0
Ascorbyl phosphate Mg 1.0
Glycyrrhizic acid 2K 0.05
Glycyrrhetinic acid 0.05
Allantoin 0.05
Tranexamic acid 0.02
β-cyclodextrin 0.5
Serine 0.1
Alanine 0.1
Arginine 0.1
Betaine 0.1
Pyrrolidone carboxylic acid 0.1
Chondroitin sulfate Na 0.01
EDTA-3Na 0.1
Polyglutamic acid (Ichimaru Falcos, Bio PGA solution) 0.1
White jellyfish polysaccharide 0.1
Glycerin 1.0
Diglycerin 1.0
Polyglycerin-10 0.2
Trehalose 0.5
Sulfite Na 0.05
Bisulfite Na 0.05
1,2-hexanediol 0.5
1,2-pentanediol 0.5
BG 5.0
Citric acid 0.05
Fumaric acid 0.05
Hydroxyl K Appropriate amount of purified water Total amount of 100 ---------------------------
(Preparation method)
A was heated to about 80 ° C. and dissolved uniformly (A). C was heated to about 80 ° C. and dissolved (
C). While stirring with a homomixer at about 80 ° C., C was gradually added to A, mixed uniformly after emulsification, cooled to about 40 ° C., B was added and mixed uniformly.

Example 8 Moisture Pack A moisture pack having the following formulation was prepared. The moisturizing effect is enhanced, the skin is softened, moisturized and an excellent cleaning action is obtained.
Component Blending amount (% by weight)
--------------------------------
A
Polyvinyl alcohol 13.0
1,3-butylene glycol 3.0
Alginic acid K 0.5
(Styrene / vinyl pyrrolidone) copolymer 1.5
B
Plandool-G (Nippon Seika) 0.3
Liposome solution of Example 2 20.0
PCA Glyceres-25 isostearate 1.5
Denatured alcohol 8.0
PEG / PPG-5 / 30 copolymer 1.0
Ores-10 phosphate DEA 1.0
Glycyrrhizic acid 2K 0.05
Tocopherol 0.1
Methylparaben 0.2
Hyaluronic acid Na 0.05
Na chloride 0.3
Purified water Total amount of 100 --------------------------------
(Preparation method)
A is warmed and swollen at 50 ° C. Slowly add B to A with stirring and mix evenly. Cool with stirring, stop stirring at 30-25 ° C. and let stand.

Example 9 Sunscreen A sunscreen having the following formulation was prepared. There were effects such as a high UV prevention effect and whitening suppression.
Component Blending amount (% by weight)
--------------------------------
A
Quaternium-18 hectorite 1.0
B
Cyclomethicone 13.7
Diphenyl dimethicone 1.0
Liposome solution of Example 2 10.0
Dicaprylyl carbonate 1.0
Plandool-G (Nippon Seika) 1.0
Dimethicone copolyol 5.5
YOFCO MAS (Nippon Seika) 2.0
Octyl rearzone 0.5
Sodium dihydroxydimethoxybenzophenone disulfonate
0.5
Dihydroxybenzophenone 0.5
1- (3,4-Dimethoxyphenyl) -4,4-dimethyl-1,3-pentanedione 0.5
2-methoxyhexyl dimethoxybenzylidenedioxoimidazolidinepropionate 0.5
Tetrahydroxybenzophenone 0.5
Terephthalylidene dicamphulsulfonic acid 0.5
Methyl bis (trimethylsiloxy) silylisopentyl trimethoxycinnamate 0.5
Drometrizol trisiloxane 0.5
Amyl paradimethylaminobenzoate 0.5
C
Titanium oxide 3.9
Zinc oxide 2.1
D
Stearic acid Al 0.7
Hydroxide Al 0.5
Isononyl isononanoate 5.0
E
Trimethylsiloxysilicic acid 1.2
Dimethicone 0.8
Methicone 0.1
Stearyl glycyrrhetinate 0.02
Sorbitan sesquioleate 2.0
Tocopherol 0.02
F
Na chloride 1.0
Methylparaben 0.15
Purified water Total amount of 100 --------------------------------
(Preparation method)
Add A to B and stir. Further, C is added and dispersed using a roller mill. D is heated and melted and added to the mixture of A, B, and C, and E is further added to about 70 ° C. F is warmed and slowly added to the mixture of A to E with stirring and emulsified. Cool with stirring to 40-35 ° C
Stop stirring and leave it alone.

Example 10 Powder Bath Agent A powder bath agent having the following formulation was prepared. The foaming property was good, the skin was moist after bathing, and the bathing effect and moisture retention were excellent.
Component Blending amount (parts by weight)
--------------------------------
Sodium carbonate 20.0
Sodium bicarbonate 22.0
Sodium sulfate 15.0
Succinic acid 20.0
Fumaric acid 22.0
Silica anhydride 0.8
Liposome precursor of Example 1 0.2
Perfume Trace amount Dye Trace amount ---------------------------
The above powders were put into a kneader and mixed by stirring.

Provided is a ubiquinone Q10-containing liposome precursor having a high efficiency and high quality, having a small particle size and excellent stability over time, and a cosmetic and health food containing the liposome precursor or the liposome. It comes out.

FIG. 1 is a flow sheet showing an example of the method of the present invention. (1) Stock solution tank, (2) Heating tube, (3) Vacuum chamber, (4) Condenser (5) Solvent recovery tank, (6) Powder recovery container, (7) Vacuum pump

Claims (6)

Method for producing ubiquinone Q10-containing liposome precursor, wherein a powdered liposome precursor is obtained by drying an organic solvent solution in which phospholipid and ubiquinone Q10 are uniformly dissolved in an organic solvent by a cracks method A method for producing a liposome precursor, wherein the organic solvent solution of claim 1 contains a sterol Liposomes using liposome precursors obtained by the method for producing liposome precursors according to claim 1-2 The liposome according to claim 3, wherein the liposome has an average particle size of 50 to 180 nm. A cosmetic comprising the liposome precursor obtained by the production method of claim 1 or claim 2, or the liposome of claim 3 or claim 4. The liposome precursor obtained by the production method of claim 1 or claim 2, or claim 3 or claim 4.
Health food containing liposomes

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