WO2020036266A1 - Nanoliposome preparation method using horse oil and nanodiamonds and composition thereof - Google Patents

Nanoliposome preparation method using horse oil and nanodiamonds and composition thereof Download PDF

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WO2020036266A1
WO2020036266A1 PCT/KR2018/016045 KR2018016045W WO2020036266A1 WO 2020036266 A1 WO2020036266 A1 WO 2020036266A1 KR 2018016045 W KR2018016045 W KR 2018016045W WO 2020036266 A1 WO2020036266 A1 WO 2020036266A1
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oil
solution
aqueous solution
nanodiamonds
liposome
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French (fr)
Korean (ko)
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이강현
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이강현
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/02—Inorganic compounds
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/24—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
    • A61K8/14—Liposomes; Vesicles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/98—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/98—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin
    • A61K8/981—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution of animal origin of mammals or bird
    • A61K8/986—Milk; Derivatives thereof, e.g. butter
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/10—Dispersions; Emulsions
    • A61K9/127—Liposomes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
    • A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
    • A61K2800/56—Compounds, absorbed onto or entrapped into a solid carrier, e.g. encapsulated perfumes, inclusion compounds, sustained release forms

Definitions

  • the present invention relates to a liposome preparation method using horse oil and nanodiamonds and to a composition comprising the prepared liposomes.
  • Liposomes are small spheres with a phospholipid bilayer structure in which amphiphilic phospholipids are self-arranged by hydrophobic forces in the water phase.
  • the advantages of using liposomes as drug carriers for medicines and cosmetics are listed: (a) It consists of a biological component called phospholipids, which can be degraded and not toxic in vivo, and (b) Liposomes that contain both water-soluble or fat-soluble components. It can be collected into (c) the size and shape characteristics of the liposomes according to the preparation method, surface charge, lipid composition, etc. can be varied, and (d) easily prepared without chemical bonding between the inclusion material and liposomes.
  • Horse oil is rich in unsaturated fatty acids since horse oil has long been known to be beneficial for the prevention of fine lines and aging. It has been used for a long time in skin care as a folk remedy. Horse oil, for example, is known to be very effective for burns because it helps to soothe inflammation and remove heat.It contains a large amount of palmitoleic acid, a powerful antibacterial agent that is an important ingredient in sebum that protects human skin. It is known to form a natural protective film of the skin to give a high moisturizing effect of the skin. In addition, it contains a large amount of vitamin E, which stimulates blood circulation, so that the oil itself can be a great cosmetic product and is also used in skin care products.
  • horse oil is the closest ingredient to sebum. Since the composition of fatty acids, oil and moisture balance is almost the same, it has high affinity with human skin and contains about 60% of unsaturated fatty acid, which can supply unsaturated fatty acid to skin. Known as a substance.
  • the present invention is to provide a nano liposome having a long-lasting physiological activity by releasing a functional material over a long period of time using nanodiamonds has a remarkably long pharmacological action and a method for producing the same.
  • the present invention provides a method for preparing a nanoliposome by emulsifying horse oil and nanodiamonds through lecithin to form nanoliposomes, wherein the aqueous phase preparation step comprises preparing an aqueous solution containing nanodiamonds and a functional component; An oil phase preparation step of preparing an oil phase solution containing horse oil and phospholipids; And a liposome preparation step of mixing and stirring the aqueous solution and the oily solution to form nanoliposomes.
  • the aqueous solution preparation step is characterized in that the functional plant extract physiologically active ingredient is added to the purified water together with the nanodiamond and warmed to 80 ⁇ 100 °C and dissolved.
  • the nanodiamond is characterized in that the powder of 1 ⁇ 100nm size having a defective graphene structure made by the explosion method of carbon.
  • the aqueous phase manufacturing step is characterized in that the step of preparing a water phase solution containing the nanodiamond 1 to 5 ppm aqueous solution in the range of 10 to 50% by weight based on the total weight of the mixture of the aqueous phase solution and the oil phase solution.
  • the oil phase manufacturing step is characterized in that the step of dissolving horse oil in phospholipids while heating 80 ⁇ 100 °C.
  • the oil phase preparation step may include the horse oil in the range of 20 to 40% by weight based on the total weight of the mixture of the aqueous solution and the oil solution, and the phospholipid 1.5 to 1.5 based on the total weight of the mixture of the aqueous solution and the oil solution Including the range of 3.5% by weight characterized in that the step of producing an oil solution.
  • the liposome manufacturing step is characterized in that the step of forming a nano liposome by stirring while adding the oily solution to the aqueous solution, and repeatedly processing using a microfluidizer when the temperature after the stirring is 40 °C or less. .
  • the liposome manufacturing step is stirred for 30 minutes to 60 minutes while pouring the oily solution to the aqueous solution, when the temperature is 40 °C or less using a microfluidizer 2 to 5 times at 20,000 to 30,000psi pressure It is characterized by the step of forming a nano-liposomes by repeated processing.
  • the present invention is a nanoliposome prepared by emulsifying the aqueous solution containing the defective nanodiamond and the oily solution containing horse oil and phospholipid, the functional plant extract bioactive component is bound to the defective portion of the nanodiamond It provides nanoliposomes included.
  • the nanoliposome is characterized in that it comprises an oil phase shell consisting of a phospholipid surrounding the water core, including the nanodiamond is bound to a defective portion of the functional plant extract bioactive components.
  • the present invention provides a pharmaceutical composition
  • a pharmaceutical composition comprising a nanoliposome contained in the water core as an active ingredient in a state in which the functional plant extract physiologically active component is bound to a defective portion of the nanodiamond.
  • the present invention provides a cosmetic composition
  • a cosmetic composition comprising a nanoliposome contained in the water core as an active ingredient in a state in which the functional plant extract physiologically active component is bound to a defective portion of nanodiamonds.
  • the present invention emulsifies horse oil and nanodiamonds through vegetable lecithin, and then prepares nano liposomes using a microfluidizer, so that the surface desorption of physiologically active substances is made in small amounts over a long time. It is possible to provide a liposome composition that can provide physiological activity.
  • Figure 1 shows the configuration of the nano liposomes according to an embodiment of the present invention.
  • the termcomprise comprises, and configure means to include the referenced article, step, or group of articles, and step, and any other article It is not meant to exclude a stage or group of things or a group of stages.
  • the method for preparing nanoliposomes is a method for preparing nanoliposomes using a microfluidizer after emulsifying horse oil and nanodiamonds with vegetable lecithin, and more specifically, nanodiamonds and functional components.
  • the aqueous phase preparation step (S10) is a step of preparing an aqueous phase solution containing nanodiamonds and functional components, adding a functional plant extract physiologically active component to the purified water with nanodiamonds and warming and dissolving at 80 ⁇ 100 °C to be.
  • the aqueous solution is a part that forms a continuous phase in making the nanoliposomes
  • water is essentially included, and preservatives such as methylparaben may be included in the aqueous solution.
  • the water may be included in the range of 30 to 80% by weight based on the total weight of the mixture of the aqueous solution and the oil solution. If the content of water is less than 30% by weight may not be good emulsification, when more than 80% by weight may lower the particle density.
  • the functional plant extract physiologically active ingredient alone means a component extracted from a plant as a functional ingredient capable of exhibiting a desired physiological activity or itself in combination with a carrier having no activity.
  • the nanodiamond is a powder of 1 ⁇ 100nm size having a defective graphene structure made by the explosion method of carbon, in the form of grain aggregate in which nanoparticles are agglomerated with each other, and have abrasion resistance, heat resistance, chemical resistance and substance adsorption properties. have.
  • the nanodiamond has a stable structure even under the high temperature and high pressure conditions of the microfluidizer.
  • the nanodiamond contains at least 80% as a constituent in which carbon is bonded to amorphous carbon, diamond, and diamond, and at least 5% in the form of an oxygen bonder. It also contains up to 10% impurities such as Si, S, Cu and Fe. Since the amorphous carbon component is removed by heating to a high temperature, it can be removed by high temperature and high pressure treatment using a microfluidizer in a step to be described later, and the main component may be composed of diamond.
  • the defects of the nanodiamonds have a size in the range of 30 to 300 mm 3 and the average size is 100 to 150 mm 3. Such defects are mainly distributed on the outer surface constituted by a collection of nanoparticles rather than the inside.
  • the specific surface area of nanodiamonds is recommended to use 500 ⁇ 600m 2 / g.
  • the functional plant extract bioactive component When the nanodiamond is added while the functional plant extract bioactive component is dissolved in purified water and stirred, the functional plant extract bioactive component is adsorbed to the surface defect structure of the nanodiamond.
  • the plant extraction component is not resistant to high temperature and high pressure, all of the liposomes are destroyed at the manufacturing stage using a microfluidizer.
  • the present invention uses nanodiamonds to produce nanoliposomes that are susceptible to high temperature and high pressure. It is possible.
  • the nanodiamond may be included in the range of 10 to 50% by weight of the nanodiamond 1-5 ppm aqueous solution based on the total weight of the mixture of the aqueous solution and the oil solution.
  • the nanodiamond 2 to 3 ppm aqueous solution is preferably included in the range of 20 to 30% by weight.
  • the aqueous solution may further contain 1.3 butylene glycol (1.3 butylene glycol) for the skin moisturizing effect.
  • the aqueous solution In order to prepare the aqueous solution, it is heated and dissolved at 80 to 100 ° C., but when heated to less than 80 ° C., the lecithin or added aqueous solution may not be completely dissolved, and may not be easily emulsified. In this case, there is a problem in forming liposomes because the water evaporates in the aqueous solution. Preferably heated to 90 ⁇ 97 °C to prepare the aqueous solution.
  • the oily solution preparation step (S20) is a step of preparing an oily solution containing horse oil, it is a step of dissolving horse oil in phospholipids while heating 80 ⁇ 100 °C.
  • the horse oil is the most important part in making the phospholipid structure of liposomes with fat-soluble components. Horse oil is very similar to the fatty acid structure of humans, so it is very well suited for the human body. Although commonly used vegetable oils contain a lot of unsaturated fatty acids, there is a limitation of the species of plants, so the skin absorption was not good, but by applying horse oil to liposomes, the phospholipid structure is much more suitable for skin. The horse oil may be used Jeju Island horse oil.
  • the horse oil may be included in the range of 20 to 40% by weight based on the total weight of the mixture of the aqueous solution and the oil solution.
  • the amount of horse oil is less than 20% by weight, there is a problem in forming a liposome phospholipid double layer, and when it exceeds 40% by weight, there is a problem in that it is impossible to manufacture a liposome sphere.
  • the phospholipid may be a natural phospholipid such as egg yolk lecithin, soybean lecithin, sphingomyelin, or synthetic phospholipid such as dipalmitoylphosphatidylcholine, hydrogenated lecithin, and soybean lecithin.
  • the amphiphilic molecular structure of lecithin allows the emulsification of the active ingredient, which is water soluble as an emulsifier.
  • unsaturated lecithin is most preferred as the phospholipid of the present invention because it has excellent skin affinity and penetration, relatively softer and easier to modify.
  • the phospholipid may be included in the range of 1.5 to 3.5% by weight based on the total weight of the mixture of the aqueous solution and the oily solution. If the content of the phospholipid is less than 1.5% by weight, there is a problem that the liposome double layer structure is not formed, and when the content of the phospholipid is greater than 3.5%, the liposome viscosity is increased, so that the liposome formulation is creamed.
  • the oily solution may further include an auxiliary emulsifier.
  • auxiliary emulsifiers may be used anionic surfactants, cationic surfactants or nonionic surfactants.
  • anionic surfactants include alkylacylglutamate, alkylphosphates, alkyllactylates, dialkylphosphates, trialkylphosphates, and the like.
  • nonionic surfactants include alkoxylated alkyl ethers, alkoxylated alkyl esters, alkylpolyglycosides, polyglyceryl esters, sugar esters, and the like. It is preferable to use a natural emulsifier.
  • Natural emulsifiers are commercially available, including OLIVOIL AVENATE EMULSIFIER® (Kalichem), but may be selected and used as appropriate. Auxiliary emulsifier may be included in the range of 0.1 to 5.0% by weight based on the total weight of the mixture of the aqueous solution and the oily solution.
  • the solvent is heated to 80 to 100 ° C. to dissolve, and when heated to less than 80 ° C., the emulsification may not be performed well.
  • the liposome manufacturing step (S30) is a step of forming a nano liposome by mixing and stirring the aqueous solution and the oily solution, the stirring while adding the oily solution to the aqueous solution, and after stirring the temperature is 40 °C or less It is a step of forming a nano liposome by repeating the process using a fluidizer.
  • the liposome manufacturing step (S30) is stirred for 30 minutes to 60 minutes at 2,500 to 3,500rpm using a homomixer while pouring the oil solution to the aqueous solution.
  • the microfluidizer was used to repeatedly process 2 to 5 times at a pressure of 20,000 to 30,000 psi. After centrifugation at 4,500 to 5,500 rpm using a centrifuge for 5 to 15 minutes after the microfluidizer, there is no layer separation between the aqueous solution and the oil solution.
  • the surface structure of nanodiamond maintains a stable structure even in the high temperature and high pressure of microfluidizer, and the functional plant extract bioactive component adsorbed on the surface is also stable.
  • Nanoliposomes prepared according to the present invention penetrates deep into the skin to emit a functional plant extract bioactive component, wherein the functional plant extract bioactive component adsorbed on the surface of the nanodiamond is emitted for a long time. This is because the surface desorption of the physiologically active substance is made over a long period of time in small amounts, so the pharmacological action time is very long, resulting in long-term sustained physiological activity compared to the general nanoliposomes. This results in a much higher pharmacological effect because the drug is continuously made over a long time.
  • Nanoliposomes according to another embodiment of the present invention is prepared by emulsifying the aqueous solution containing the nanodiamond and the oily solution containing horse oil and phospholipid that is bound to the defective part of the functional plant extract bioactive components as As shown in FIG. 1, a water core containing nanodiamond, which is bound to a defective portion of a functional plant extract physiologically active component, and an oily shell composed of phospholipids surrounding the water core.
  • the horse oil component forms bilayer phospholipids by lecithin and coemulsifier inside and outside the liposome sphere, and is also emulsified in O / W form by coemulsifier in the water core.
  • the water core is a spherical structure forming a continuous phase, water is essentially included, and preservatives such as methylparaben may be included in the water core, and butylene glycol for skin moisturizing effect. ) May be additionally included.
  • the functional plant extract physiologically active component is bound to the defective portion of the nanodiamond is preferably contained in 1.0% to 5.0% by weight relative to the total weight of the nanoliposomes.
  • the oily shell is a shell structure that forms a bilayer having a phospholipid structure composed of a hydrophilic head facing the outer core and the nanoliposome and a lipophilic tail facing the oil shell.
  • the particle size of the nanoliposomes according to the present invention is 100 to 600nm.
  • the present invention also provides a composition comprising a nanoliposome contained in the water core as an active ingredient in a state in which the functional plant extract bioactive component is bound to a defective portion of nanodiamonds.
  • the composition may be a pharmaceutical composition or a cosmetic composition.
  • the pharmaceutical composition of the present invention can be classified into any product as long as it conforms to the relevant enforcement regulations at the time of manufacture and distribution in the legal and functional categories.
  • it may be a quasi-drug or drug under the Pharmacist Act or, if it is a drug, it may be a generic or specialized drug.
  • compositions of the present invention may be prepared in oral or parenteral formulations according to the route of administration by conventional methods known in the art, including pharmaceutically acceptable carriers in addition to the active ingredients.
  • pharmaceutically acceptable here means that the subject of application (prescription) is not as toxic as applicable, without inhibiting the activity of the active ingredient.
  • compositions of the present invention are prepared in an oral dosage form
  • powders, granules, tablets, pills, dragees, capsules, solutions, gels, syrups, suspensions, wafers are prepared according to methods known in the art with suitable carriers. It may be prepared in a formulation such as.
  • suitable pharmaceutically acceptable carriers include sugars such as lactose, glucose, sucrose, dextrose, sorbitol, mannitol and xylitol, starch such as corn starch, potato starch, wheat starch, cellulose, methylcellulose, ethylcellulose, Celluloses such as sodium carboxymethyl cellulose and hydroxypropyl methyl cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, magnesium stearate, mineral oil, malt, gelatin, talc, polyol, vegetable Yu etc. can be mentioned.
  • it may be formulated to include diluents and / or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, if necessary.
  • compositions of the present invention When the pharmaceutical compositions of the present invention are prepared in parenteral formulations, they may be formulated in the form of injections, transdermal administrations, nasal inhalants and suppositories with suitable carriers according to methods known in the art.
  • suitable carriers When formulated as an injectable, suitable carriers may be sterile water, ethanol, polyols such as glycerol or propylene glycol, or mixtures thereof, preferably PBS (phosphate buffered saline) containing Ringer's solution, triethanol amine, or injectable sterilization. Water, isotonic solutions such as 5% dextrose, and the like.
  • a transdermal administration When formulated as a transdermal administration, it may be formulated in the form of an ointment, cream, lotion, gel, external solution, pasta, linen, aerosol.
  • Nasal inhalants can be formulated in the form of aerosol sprays using suitable propellants, such as dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, etc. witepsol), tween 61, polyethylene glycols, cacao butter, laurin paper, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearate, sorbitan fatty acid esters, and the like.
  • suitable propellants such as dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, etc. witepsol
  • tween 61 polyethylene glycols, cacao butter, laurin paper, polyoxyethylene sorb
  • composition of this invention can be grasped
  • Cosmetic compositions can take the form of products such as solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, shampoos, soaps, surfactant-containing cleansing, oils, powder foundations, emulsion foundations, wax foundations, sprays, etc. have.
  • it may be a softening lotion, a nourishing lotion, a nourishing cream, a massage cream, an essence, an eye cream, a cleansing cream, a cleansing foam, a cleansing water, a pack, a spray or a powder formulation.
  • the cosmetic composition of the present invention may include, in addition to the active ingredient, components commonly used in the cosmetic composition, for example, conventional adjuvants such as stabilizers, solubilizers, surfactants, vitamins, pigments and pharmaceuticals, and carriers.
  • conventional adjuvants such as stabilizers, solubilizers, surfactants, vitamins, pigments and pharmaceuticals, and carriers.
  • the formulation of the present invention is a paste, cream or gel, animal oils, vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide may be used as carrier components.
  • animal oils, vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide may be used as carrier components.
  • animal oils vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide
  • cellulose derivatives polyethylene glycols
  • silicones bentonites
  • silicas talc or zinc oxide
  • lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used, in particular in the case of a spray, additionally chlorofluorohydrocarbon, propane Propellant such as butane or dimethyl ether.
  • a solvent, solubilizing agent or emulsifying agent is used as the carrier component, specifically water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol, fatty acid ester of sorbitan and the like can be used.
  • liquid carrier diluents such as water, ethanol or propylene glycol
  • suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, polyoxyethylene sorbitan ester, and microcrystals are used as carrier components.
  • Castle cellulose, aluminum metahydroxy, bentonite, agar and the like can be used.
  • the carrier component is an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, an isethionate, an imidazolinium derivative, a methyltaurate, a sarcosinate, a fatty acid amide.
  • Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.
  • the cosmetic composition of the present invention can be prepared according to the manufacturing method of the cosmetic composition usually carried out in the art, except that the active ingredient is included.
  • Centella asiatica extract March extract, burdock extract, calendula extract, lemon extract, leap extract, red pepper extract, sage leaf extract, soap leaf extract, chamomile flower extract, garlic extract, anica flower extract, western pineapple extract, Extract, watercress flower / leaf extract, structure pine leaf extract, and rosemary leaf extract were mixed to prepare a functional plant extract bioactive component.
  • Preparation of the nanoliposomes is a mixture of the aqueous solution of Table 1 below warmed up to 90 ° C., likewise the mixture of the oily solution of Table 1 below warmed up to 90 ° C. and stirred at 3,000 rpm for at least 30 minutes and then at 40 ° C. The following process was repeated three times at a pressure of 25,000 psi with a microfluidizer. After centrifugation at 5,000 rpm for 10 minutes, it was confirmed that a stable liposome was prepared without a layer separation phenomenon of the water-soluble component and the fat-soluble component.
  • Dissolution test conditions are as follows.
  • a cream containing a nanoliposome prepared in the above Example was prepared. All components are shown in Table 4 below. A clinical trial was conducted on the prepared cream.
  • Constellation Light yellow cream density 100% All ingredients Purified water, butylene glycol, hydrogenated polydecene, cyclohexasiloxane, cyclohexasiloxane, cetearyl alcohol, 1,2-hexanediol, panthenol, cetearyl oliveate, sorbitan sulfate, ethylhexyl palmitate , Triethylhexanoin, dimethicone, glyceryl stearate, glycerin, bis-pig-18, methyl ether dimethyl silane, carbomer, adenosine, tromethamine, fragrance, xanthan gum, centella extract, gusset extract, lecithin , Disodium ethane, ethanol, phenoxyethanol, burdock extract, calendula extract, lemon extract, leap extract, red pepper extract, sage leaf extract, soap leaf extract, chamomile flower extract, garlic extract, anica flower extract
  • the subjects were 33 adult women aged 20 to 50 with no grade or chronic diseases including skin diseases, no sensitive skin, and no cosmetic allergies.
  • the subject was changed to a prepared gown and allowed to adjust to the measurement environment by taking skin stability for about 30 minutes in a space of constant temperature and humidity conditions (temperature 20 ⁇ 24 °C, humidity 40 ⁇ 60%).
  • the site of application of the test product was photographed, and the skin reaction was checked by two experts under the same conditions every time.
  • test site For the test site, a flat site such as the back was selected. The test site was marked on the test site for recognition in the next evaluation, and the same site was evaluated for the next evaluation.
  • the induction machine was applied 5 ⁇ l of test substance to the test site 5 times at 3 days intervals for 2 weeks, and the test site was observed after 30 minutes to 1 hour after removing the patch.
  • test substance 20 ⁇ l was applied to the naive site at the end of the resting period for 48 hours, and the test site was observed for 30 minutes, 48 hours, and 96 hours after removing the patch. However, any suspicious findings were observed thereafter.
  • the induction machine is a process for observing skin irritation and cumulative stimulation reactions and is scored according to the following criteria after removing the patch. Judgment criteria are based on the criteria set forth in Table 5 below, based on the guidelines of Frosch & Kligman and The Cosmetic, Toiletry, and Fragrance Association (CTFA).
  • the degree of skin irritation of the test product was determined according to the criteria shown in Table 6 below.
  • Yagi is a process to detect the presence of sensitization.
  • the degree of skin reaction is given according to the ICDRG criteria as shown in Table 7 below.
  • the intensity of the reaction increases from the first observation after the first yawn patch to the second (48, 96 hours after the patch).
  • the survey was conducted to prepare the test subjects for their feelings of tingling, burning, and itching after using the test product.

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Abstract

The present invention relates to a nanoliposome preparation method for forming nanoliposomes by emulsifying horse oil and nanodiamonds by means of lecithin, nanoliposomes in which a biologically active and functional plant-extract substance is bound and comprised in defective parts of the nanodiamonds, and a pharmaceutical or cosmetic composition comprising same. Since the surface detachment of a biologically active material occurs in small amounts over a long period of time, the duration of pharmacological action is very long and thus a liposome composition providing lasting and continuous biological activity can be provided.

Description

마유 및 나노다이아몬드를 이용한 나노리포좀 제조방법 및 이의 조성물Nanoliposome preparation method using horse oil and nanodiamond and composition thereof
본 발명은 마유 및 나노다이아몬드를 이용한 리포좀 제조방법 및 제조된 리포좀을 포함하는 조성물에 관한 것이다.The present invention relates to a liposome preparation method using horse oil and nanodiamonds and to a composition comprising the prepared liposomes.
여기서는, 본 개시에 관한 배경기술이 제공되며, 이들이 반드시 공지기술을 의미하는 것은 아니다.Here, background art is provided with respect to the present disclosure, and these do not necessarily mean known art.
리포좀은 인지질 2중층 구조를 가진 소형 구체로, 양친매성의 인지질이 수상에서 소수성의 힘에 의해 자가배열 되어 있는 구조체이다. 리포좀을 의약이나 화장품 등에 효능물질의 전달체로 활용했을 때 가지는 장점을 열거하면 (a) 인지질이라는 생체 구성성분으로 이루어져 생체 내에서 분해가 가능하고 독성이 없고, (b) 수용성 또는 지용성 성분 모두를 리포좀 내로 포집할 수 있으며, (c) 리포좀의 제조방법, 표면 전하, 지질 조성 등에 따라 크기 및 형태 특성 등을 조절하여 다양하게 만들 수 있고, (d) 포접 물질과 리포좀 사이에 화학적 결합 없이 쉽게 제조가 가능하고, (e) 포접 물질이 약물일 경우 특정 조직에 표적이 가능하여 약물의 치료 효과를 높이고 약물을 거의 모든 투여 경로(경구, 피하, 정맥, 근육 주사 또는 복강 주사)로 투여할 수 있는 등의 많은 이점이 있다.Liposomes are small spheres with a phospholipid bilayer structure in which amphiphilic phospholipids are self-arranged by hydrophobic forces in the water phase. The advantages of using liposomes as drug carriers for medicines and cosmetics are listed: (a) It consists of a biological component called phospholipids, which can be degraded and not toxic in vivo, and (b) Liposomes that contain both water-soluble or fat-soluble components. It can be collected into (c) the size and shape characteristics of the liposomes according to the preparation method, surface charge, lipid composition, etc. can be varied, and (d) easily prepared without chemical bonding between the inclusion material and liposomes. (E) if the inclusion substance is a drug, it can be targeted to specific tissues to enhance the therapeutic effect of the drug and administer the drug by almost any route of administration (oral, subcutaneous, intravenous, intramuscular or intraperitoneal), etc. There are a lot of advantages.
리포좀은 피부 깊숙이 침투하여 포접하고 있던 기능성 성분을 발산하는데, 장시간에 걸쳐 발산되어야 약리 작용시간이 길어져 장시간의 지속적인 생리활성을 제공할 수 있다. Liposomes penetrate deep into the skin and release the functional ingredients that were encapsulated. The liposomes must be released over a long period of time to provide long-term sustained physiological activity.
한편, 마유는 말의 기름으로 예부터 불포화지방산이 풍부해 잔주름이나 노화예방으로 유익한 것으로 알려져 있으며 민간요법으로 피부 미용에 오래전부터 사용되어 왔다. 예를 들어, 마유는 염증을 가라앉게 해주며 열을 제거하는 작용이 있어 화상에 매우 효과적인 것으로 알려져 있으며, 사람의 피부를 보호하는 피지의 주요성분으로 강력한 항균 작용을 하는 팔미톨레산이 다량 함유되어 있어 피부의 천연보호막을 형성시켜 피부의 고보습 효과를 주는 것으로 알려져 있다. 또한 혈액순환을 왕성하게 해주는 비타민 E가 다량 함유되어 있어 기름 그 자체가 훌륭한 화장품 역할을 할 수 있어 피부 미용제에도 사용되고 있다. 뿐만 아니라 마유는 피지에 가장 가까운 성분으로, 지방산의 구성비, 유분, 수분의 밸런스도 거의 같기 때문에 인간의 피부와 친화성이 높으며 불포화지방산이 약 60% 이상 포함되어 있어 피부에 불포화지방산을 공급할 수 있는 물질로 알려져 있다.Horse oil, on the other hand, is rich in unsaturated fatty acids since horse oil has long been known to be beneficial for the prevention of fine lines and aging. It has been used for a long time in skin care as a folk remedy. Horse oil, for example, is known to be very effective for burns because it helps to soothe inflammation and remove heat.It contains a large amount of palmitoleic acid, a powerful antibacterial agent that is an important ingredient in sebum that protects human skin. It is known to form a natural protective film of the skin to give a high moisturizing effect of the skin. In addition, it contains a large amount of vitamin E, which stimulates blood circulation, so that the oil itself can be a great cosmetic product and is also used in skin care products. In addition, horse oil is the closest ingredient to sebum. Since the composition of fatty acids, oil and moisture balance is almost the same, it has high affinity with human skin and contains about 60% of unsaturated fatty acid, which can supply unsaturated fatty acid to skin. Known as a substance.
본 발명은 나노다이아몬드를 활용하여 기능성 물질을 장시간에 걸쳐 발산하여 약리 작용 시간이 현저하게 길어 장시간의 지속적인 생리 활성을 갖는 나노리포좀 및 이의 제조방법을 제공하는 것이다. The present invention is to provide a nano liposome having a long-lasting physiological activity by releasing a functional material over a long period of time using nanodiamonds has a remarkably long pharmacological action and a method for producing the same.
그러나 본 발명의 목적들은 상기에 언급된 목적으로 제한되지 않으며, 언급되지 않은 또 다른 목적들은 아래의 기재로부터 당업자에게 명확하게 이해될 수 있을 것이다.However, the objects of the present invention are not limited to the above-mentioned objects, and other objects not mentioned will be clearly understood by those skilled in the art from the following description.
본 발명은 마유와 나노다이아몬드를 레시틴을 통해 유화시켜 나노리포좀을 형성하는 나노리포좀 제조방법으로서, 나노다이아몬드와 기능성 성분을 포함하는 수상용액을 제조하는 단계인 수상용액 제조단계; 마유와 인지질을 포함하는 유상용액을 제조하는 단계인 유상용액 제조단계; 및 상기 수상용액과 상기 유상용액을 혼합 교반하여 나노리포좀을 형성하는 단계인 리포좀 제조단계;를 포함하는 나노리포좀 제조방법을 제공한다.The present invention provides a method for preparing a nanoliposome by emulsifying horse oil and nanodiamonds through lecithin to form nanoliposomes, wherein the aqueous phase preparation step comprises preparing an aqueous solution containing nanodiamonds and a functional component; An oil phase preparation step of preparing an oil phase solution containing horse oil and phospholipids; And a liposome preparation step of mixing and stirring the aqueous solution and the oily solution to form nanoliposomes.
또한 상기 수상용액 제조단계는 기능성 식물 추출 생리 활성 성분을 나노다이아몬드와 함께 정제수에 첨가하고 80~100℃ 으로 가온하며 용해시키는 단계인 것을 특징으로 한다.In addition, the aqueous solution preparation step is characterized in that the functional plant extract physiologically active ingredient is added to the purified water together with the nanodiamond and warmed to 80 ~ 100 ℃ and dissolved.
또한 상기 나노다이아몬드는 탄소의 폭발법에 의해 만들어진 결함이 있는 그래핀 구조를 갖는 1~100nm 크기의 분말인 것을 특징으로 한다.In addition, the nanodiamond is characterized in that the powder of 1 ~ 100nm size having a defective graphene structure made by the explosion method of carbon.
또한 상기 수상용액 제조단계는 상기 나노다이아몬드 1 내지 5 ppm 수용액을 상기 수상용액과 유상용액의 혼합물 총 중량에 대해 10 내지 50 중량%의 범위로 포함하여 수상용액을 제조하는 단계인 것을 특징으로 한다.In addition, the aqueous phase manufacturing step is characterized in that the step of preparing a water phase solution containing the nanodiamond 1 to 5 ppm aqueous solution in the range of 10 to 50% by weight based on the total weight of the mixture of the aqueous phase solution and the oil phase solution.
또한 상기 유상용액 제조단계는 마유를 80~100℃ 가온하면서 인지질에 용해시키는 단계인 것을 특징으로 한다.In addition, the oil phase manufacturing step is characterized in that the step of dissolving horse oil in phospholipids while heating 80 ~ 100 ℃.
또한 상기 유상용액 제조단계는 상기 마유를 상기 수상용액과 유상용액의 혼합물 총 중량에 대해 20 내지 40 중량%의 범위로 포함하고, 상기 인지질을 상기 수상용액과 유상용액의 혼합물 총 중량에 대해 1.5 내지 3.5 중량%의 범위로 포함하여 유상용액을 제조하는 단계인 것을 특징으로 한다.In addition, the oil phase preparation step may include the horse oil in the range of 20 to 40% by weight based on the total weight of the mixture of the aqueous solution and the oil solution, and the phospholipid 1.5 to 1.5 based on the total weight of the mixture of the aqueous solution and the oil solution Including the range of 3.5% by weight characterized in that the step of producing an oil solution.
또한 상기 리포좀 제조단계는 상기 수상용액에 상기 유상용액을 첨가하면서 교반하고, 교반 후 온도가 40℃ 이하가 되었을 때 마이크로플루다이저를 이용하여 반복 가공함으로써 나노리포좀을 형성하는 단계인 것을 특징으로 한다.In addition, the liposome manufacturing step is characterized in that the step of forming a nano liposome by stirring while adding the oily solution to the aqueous solution, and repeatedly processing using a microfluidizer when the temperature after the stirring is 40 ℃ or less. .
또한 상기 리포좀 제조단계는 상기 수상용액에 상기 유상용액을 부어가면서 30분 내지 60분 동안 교반하고, 온도 40℃ 이하가 되었을 때 마이크로플루다이저를 이용하여 20,000 내지 30,000psi 압력으로 2회 내지 5회 반복 가공함으로써 나노리포좀을 형성하는 단계인 것을 특징으로 한다.In addition, the liposome manufacturing step is stirred for 30 minutes to 60 minutes while pouring the oily solution to the aqueous solution, when the temperature is 40 ℃ or less using a microfluidizer 2 to 5 times at 20,000 to 30,000psi pressure It is characterized by the step of forming a nano-liposomes by repeated processing.
또한 본 발명은 결함이 있는 나노다이아몬드가 포함된 수상용액과 마유 및 인지질이 포함된 유상용액을 유화시켜 제조된 나노리포좀이며, 기능성 식물 추출 생리 활성 성분이 상기 나노다이아몬드의 결함이 있는 부분에 결착되어 포함된 나노리포좀을 제공한다. In another aspect, the present invention is a nanoliposome prepared by emulsifying the aqueous solution containing the defective nanodiamond and the oily solution containing horse oil and phospholipid, the functional plant extract bioactive component is bound to the defective portion of the nanodiamond It provides nanoliposomes included.
또한 상기 나노리포좀은 상기 기능성 식물 추출 생리 활성 성분이 결함이 있는 부분에 결착되어 있는 나노다이아몬드가 포함된 수상코어, 상기 수상코어를 둘러싼 인지질로 구성된 유상쉘을 포함하여 구성된 것을 특징으로 한다.In addition, the nanoliposome is characterized in that it comprises an oil phase shell consisting of a phospholipid surrounding the water core, including the nanodiamond is bound to a defective portion of the functional plant extract bioactive components.
또한 본 발명은 기능성 식물 추출 생리 활성 성분이 나노다이아몬드의 결함이 있는 부분에 결착된 상태로 수상코어에 포함된 나노리포좀을 유효성분으로 포함하는 약제학적 조성물을 제공한다. In another aspect, the present invention provides a pharmaceutical composition comprising a nanoliposome contained in the water core as an active ingredient in a state in which the functional plant extract physiologically active component is bound to a defective portion of the nanodiamond.
또한 본 발명은 기능성 식물 추출 생리 활성 성분이 나노다이아몬드의 결함이 있는 부분에 결착된 상태로 수상코어에 포함된 나노리포좀을 유효성분으로 포함하는 화장료 조성물을 제공한다. In another aspect, the present invention provides a cosmetic composition comprising a nanoliposome contained in the water core as an active ingredient in a state in which the functional plant extract physiologically active component is bound to a defective portion of nanodiamonds.
본 발명은 마유와 나노다이아몬드를 식물성 레시틴을 통해 유화시킨 후 마이크로플루다이저를 활용하여 나노 리포좀을 제조함으로써 생리활성 물질의 표면 탈착이 소량씩 장시간에 걸쳐서 이루어지므로 약리 작용 시간이 매우 길어져 장시간의 지속적인 생리활성을 제공할 수 있는 리포좀 조성물을 제공할 수 있다.The present invention emulsifies horse oil and nanodiamonds through vegetable lecithin, and then prepares nano liposomes using a microfluidizer, so that the surface desorption of physiologically active substances is made in small amounts over a long time. It is possible to provide a liposome composition that can provide physiological activity.
도 1은 본 발명의 일 실시예에 따른 나노리포좀의 구성을 나타낸 것이다. Figure 1 shows the configuration of the nano liposomes according to an embodiment of the present invention.
이하에 본 발명을 상세하게 설명하기에 앞서, 본 명세서에 사용된 용어는 특정의 실시예를 기술하기 위한 것일 뿐 첨부하는 특허청구의 범위에 의해서만 한정되는 본 발명의 범위를 한정하려는 것은 아님을 이해하여야 한다. 본 명세서에 사용되는 모든 기술용어 및 과학용어는 다른 언급이 없는 한은 기술적으로 통상의 기술을 가진 자에게 일반적으로 이해되는 것과 동일한 의미를 가진다.Prior to describing the present invention in detail below, it is understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the invention, which is limited only by the scope of the appended claims. shall. All technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art unless otherwise indicated.
본 명세서 및 청구범위의 전반에 걸쳐, 다른 언급이 없는 한 포함(comprise, comprises, comprising)이라는 용어는 언급된 물건, 단계 또는 일군의 물건, 및 단계를 포함하는 것을 의미하고, 임의의 어떤 다른 물건, 단계 또는 일군의 물건 또는 일군의 단계를 배제하는 의미로 사용된 것은 아니다.Throughout this specification and claims, unless otherwise indicated, the termcomprise, comprises, and configure means to include the referenced article, step, or group of articles, and step, and any other article It is not meant to exclude a stage or group of things or a group of stages.
한편, 본 발명의 여러 가지 실시예들은 명확한 반대의 지적이 없는 한 그 외의 어떤 다른 실시예들과 결합될 수 있다. 특히 바람직하거나 유리하다고 지시하는 어떤 특징도 바람직하거나 유리하다고 지시한 그 외의 어떤 특징 및 특징들과 결합될 수 있다. 이하, 첨부된 도면을 참조하여 본 발명의 실시예 및 이에 따른 효과를 설명하기로 한다.On the other hand, various embodiments of the present invention can be combined with any other embodiment unless clearly indicated to the contrary. Any feature indicated as particularly preferred or advantageous may be combined with any other feature and features indicated as preferred or advantageous. Hereinafter, with reference to the accompanying drawings will be described an embodiment of the present invention and the effects thereof.
본 발명의 일실시예에 따른 나노리포좀의 제조방법은 마유와 나노다이아몬드를 식물성 레시틴을 통해 유화시킨 후 마이크로플루다이저를 활용하여 나노 리포좀을 제조하는 방법으로서, 더욱 구체적으로 나노다이아몬드와 기능성 성분을 포함하는 수상용액을 제조하는 단계인 수상용액 제조단계(S10), 마유를 포함하는 유상용액을 제조하는 단계인 유상용액 제조단계(S20) 및 상기 수상용액과 유상용액을 혼합 교반하여 나노리포좀을 형성하는 단계인 리포좀 제조단계(S30)를 포함한다.The method for preparing nanoliposomes according to an embodiment of the present invention is a method for preparing nanoliposomes using a microfluidizer after emulsifying horse oil and nanodiamonds with vegetable lecithin, and more specifically, nanodiamonds and functional components. Formation of the aqueous solution containing a water phase solution manufacturing step (S10), the step of manufacturing an oil phase solution containing horse oil solution step (S20) and mixing and stirring the water solution and the oil phase solution to form a nano liposomes It comprises a step of preparing a liposome (S30).
상기 수상용액 제조단계(S10)는 나노다이아몬드와 기능성 성분을 포함하는 수상용액을 제조하는 단계로서, 기능성 식물 추출 생리 활성 성분을 나노다이아몬드와 함께 정제수에 첨가하고 80~100℃ 으로 가온하며 용해시키는 단계이다. The aqueous phase preparation step (S10) is a step of preparing an aqueous phase solution containing nanodiamonds and functional components, adding a functional plant extract physiologically active component to the purified water with nanodiamonds and warming and dissolving at 80 ~ 100 ℃ to be.
상기 수상용액은 상기 나노리포좀을 만드는 데 있어 연속상을 형성하는 부분으로, 물이 필수적으로 포함되어 있으며, 메틸파라벤(methylparaben)과 같은 방부제도 상기 수상용액에 포함되어질 수 있다. 이때 물은 수상용액과 유상용액의 혼합물총 중량에 대해 30~80 중량% 범위로 포함될 수 있다. 물의 함량이 30 중량% 미만일 경우 유화가 잘 되지 않을 수 있고, 80 중량% 초과시에는 입자 밀도가 저하될 수 있다.The aqueous solution is a part that forms a continuous phase in making the nanoliposomes, water is essentially included, and preservatives such as methylparaben may be included in the aqueous solution. At this time, the water may be included in the range of 30 to 80% by weight based on the total weight of the mixture of the aqueous solution and the oil solution. If the content of water is less than 30% by weight may not be good emulsification, when more than 80% by weight may lower the particle density.
상기 기능성 식물 추출 생리 활성 성분은 단독으로 목적하는 생리 활성을 나타내거나 또는 그 자체는 활성이 없는 담체와 함께 생리 활성을 나타낼 수 있는 기능성 성분으로서 식물로부터 추출된 성분을 의미한다. The functional plant extract physiologically active ingredient alone means a component extracted from a plant as a functional ingredient capable of exhibiting a desired physiological activity or itself in combination with a carrier having no activity.
상기 나노다이아몬드는 탄소의 폭발법에 의해 만들어진 결함이 있는 그래핀 구조를 갖는 1~100nm 크기의 분말로서, 나노성 입자들이 서로 응집된 그레인 집합체 형태이며 내마모성, 내열성, 내약품성 및 물질 흡착성질을 가지고 있다. 또한 나노다이아몬드는 마이크로플루다이저의 고온 고압의 상황에서도 안정적인 구조를 가지고 있다. The nanodiamond is a powder of 1 ~ 100nm size having a defective graphene structure made by the explosion method of carbon, in the form of grain aggregate in which nanoparticles are agglomerated with each other, and have abrasion resistance, heat resistance, chemical resistance and substance adsorption properties. have. In addition, the nanodiamond has a stable structure even under the high temperature and high pressure conditions of the microfluidizer.
상기 나노다이아몬드는 탄소성분이 비정형 탄소와 다이아몬드 및 다이아몬드 표면에 결합된 구성체로 80% 이상 포함되고, 산소성분이 결합기의 형태로 5% 이상 포함된다. 또한 Si, S, Cu 및 Fe와 같은 불순물을 10% 이하로 포함한다. 상기 비정형 탄소 성분은 고온으로 가열하면 제거되기 때문에 후술할 단계에서 마이크로플루다이저를 이용하여 고온, 고압 처리함으로써 제거할 수 있고 주 구성체가 다이아몬드로 구성될 수 있다. The nanodiamond contains at least 80% as a constituent in which carbon is bonded to amorphous carbon, diamond, and diamond, and at least 5% in the form of an oxygen bonder. It also contains up to 10% impurities such as Si, S, Cu and Fe. Since the amorphous carbon component is removed by heating to a high temperature, it can be removed by high temperature and high pressure treatment using a microfluidizer in a step to be described later, and the main component may be composed of diamond.
상기 나노다이아몬드의 결함은 30 ∼ 300 Å의 범위의 크기를 갖고 평균 크기는 100 내지 150 Å이다. 이와 같은 결함은 내부가 아닌 나노입자들의 집합체에 의해 구성된 외부 표면에 주로 분포한다. 나노다이아몬드의 비표면적은 500~600m2/g 인 것을 사용하는 것이 좋다. The defects of the nanodiamonds have a size in the range of 30 to 300 mm 3 and the average size is 100 to 150 mm 3. Such defects are mainly distributed on the outer surface constituted by a collection of nanoparticles rather than the inside. The specific surface area of nanodiamonds is recommended to use 500 ~ 600m 2 / g.
상기 기능성 식물 추출 생리 활성 성분을 정제수에 용해 교반하면서 나노다이아몬드를 첨가하면 기능성 식물 추출 생리활성 성분이 나노다이아몬드의 표면 결함 구조에 흡착된다. 일반적으로 고온 고압에 강한 식물 추출 성분이 아니라면 마이크로플루다이저를 활용한 리포좀 제조단계에서 모두 파괴되는 단점이 있으나 본 발명은 나노다이아몬드를 사용함으로써 고온 고압에 취약한 식물 추출 생리활성 성분도 나노리포좀을 제조할 수 있게 된 것이다.When the nanodiamond is added while the functional plant extract bioactive component is dissolved in purified water and stirred, the functional plant extract bioactive component is adsorbed to the surface defect structure of the nanodiamond. In general, if the plant extraction component is not resistant to high temperature and high pressure, all of the liposomes are destroyed at the manufacturing stage using a microfluidizer. However, the present invention uses nanodiamonds to produce nanoliposomes that are susceptible to high temperature and high pressure. It is possible.
상기 나노다이아몬드는 나노다이아몬드 1∼5 ppm수용액을 수상용액과 유상용액의 혼합물 총 중량에 대해 10 내지 50 중량%의 범위로 포함될 수 있다. 바람직하게는 나노다이아몬드 2~3 ppm 수용액을 20 내지 30 중량% 의 범위로 포함되는 것이 좋다. The nanodiamond may be included in the range of 10 to 50% by weight of the nanodiamond 1-5 ppm aqueous solution based on the total weight of the mixture of the aqueous solution and the oil solution. Preferably, the nanodiamond 2 to 3 ppm aqueous solution is preferably included in the range of 20 to 30% by weight.
또한 수상용액은 피부 보습 효과를 위해서 1.3 부틸렌글리콜(1.3 butylene glycol)을 추가적으로 포함할 수 있다. In addition, the aqueous solution may further contain 1.3 butylene glycol (1.3 butylene glycol) for the skin moisturizing effect.
상기 수상용액을 제조하기 위하여 80~100℃ 으로 가온하며 용해시키는데, 80℃ 미만으로 가온하는 경우 레시틴이나 첨가한 수상용액들이 완전 용해되지 않기 때문에 유화가 잘 되지 않을 수 있고, 100℃ 초과하여 가온하는 경우 수상용액 속의 수분 증발이 많아지기 때문에 리포좀 형성에 문제가 있다. 바람직하게는 90~97℃로 가온하여 수상용액을 제조하는 것이 좋다.In order to prepare the aqueous solution, it is heated and dissolved at 80 to 100 ° C., but when heated to less than 80 ° C., the lecithin or added aqueous solution may not be completely dissolved, and may not be easily emulsified. In this case, there is a problem in forming liposomes because the water evaporates in the aqueous solution. Preferably heated to 90 ~ 97 ℃ to prepare the aqueous solution.
상기 유상용액 제조단계(S20)는 마유를 포함하는 유상용액을 제조하는 단계로서, 마유를 80~100℃ 가온하면서 인지질에 용해시키는 단계이다. The oily solution preparation step (S20) is a step of preparing an oily solution containing horse oil, it is a step of dissolving horse oil in phospholipids while heating 80 ~ 100 ℃.
상기 마유는 지용성 성분으로 리포좀의 인지질 구조를 만드는데 가장 중요한 부분이다. 마유는 인간의 지방산 구조와 매우 유사하기 때문에 인체의 적합성이 매우 뛰어나다. 일반적으로 사용하는 식물성 오일은 많은 불포화지방산이 함유되어 있음에도 불구하고 식물이라는 종의 한계가 있어 피부 흡수력이 좋지 않았지만 마유를 리포좀에 활용함으로써 훨씬 더 피부에 적합도가 높은 인지질 구조를 가지게 된다. 상기 마유는 제주도 마유를 사용하는 것이 좋다. The horse oil is the most important part in making the phospholipid structure of liposomes with fat-soluble components. Horse oil is very similar to the fatty acid structure of humans, so it is very well suited for the human body. Although commonly used vegetable oils contain a lot of unsaturated fatty acids, there is a limitation of the species of plants, so the skin absorption was not good, but by applying horse oil to liposomes, the phospholipid structure is much more suitable for skin. The horse oil may be used Jeju Island horse oil.
상기 마유는 수상용액과 유상용액의 혼합물 총 중량에 대해 20 내지 40 중량% 범위로 포함될 수 있다. 마유의 함량이 20 중량% 미만일 경우 리포좀 인지질 2중층 형성에 문제점이 있고, 40 중량% 초과시에는 점도가 높아져서 리포좀 구체 제조가 불가능한 문제점이 있다.The horse oil may be included in the range of 20 to 40% by weight based on the total weight of the mixture of the aqueous solution and the oil solution. When the amount of horse oil is less than 20% by weight, there is a problem in forming a liposome phospholipid double layer, and when it exceeds 40% by weight, there is a problem in that it is impossible to manufacture a liposome sphere.
상기 인지질은 난황 레시틴, 대두 레시틴, 스핑고마이엘린과 같은 천연 인지질이나, 디팔미토일포스타티딜콜린, 수첨 레시틴과 같은 합성 인지질 등이 사용될 수 있으며, 대두 레시틴이 바람직하다. 레시틴의 친양쪽성 분자구조로 인해 유화제로서 수용성인 활성 성분을 유화시킬 수 있다. 특히, 불포화 레시틴은 피부 친화력과 침투력이 우수하고, 상대적으로 더 유연하고 변형이 용이하므로, 본 발명의 인지질로서 가장 바람직하다. The phospholipid may be a natural phospholipid such as egg yolk lecithin, soybean lecithin, sphingomyelin, or synthetic phospholipid such as dipalmitoylphosphatidylcholine, hydrogenated lecithin, and soybean lecithin. The amphiphilic molecular structure of lecithin allows the emulsification of the active ingredient, which is water soluble as an emulsifier. In particular, unsaturated lecithin is most preferred as the phospholipid of the present invention because it has excellent skin affinity and penetration, relatively softer and easier to modify.
상기 인지질은 수상용액과 유상용액의 혼합물 총 중량에 대해 1.5 내지 3.5 중량% 범위로 포함될 수 있다. 인지질의 함량이 1.5 중량% 미만일 경우 리포좀 2중층 구조가 미 형성될 문제점이 있고, 3.5 중량% 초과시에는 리포좀 점도가 높아져서 리포좀 제형이 크림화 되는 문제점이 있다.The phospholipid may be included in the range of 1.5 to 3.5% by weight based on the total weight of the mixture of the aqueous solution and the oily solution. If the content of the phospholipid is less than 1.5% by weight, there is a problem that the liposome double layer structure is not formed, and when the content of the phospholipid is greater than 3.5%, the liposome viscosity is increased, so that the liposome formulation is creamed.
또한 상기 유상용액에는 보조 유화제를 추가로 포함할 수 있다. 보조 유화제는 음이온성 계면활성제, 양이온성 계면활성제 또는 비이온성 계면활성제가 사용될 수 있다. 음이온성 계면활성제의 구체적인 예는 알킬아실글루타메이트, 알킬포스페이트, 알킬락틸레이트, 디알킬포스페이트 및 트리알킬포스페이트 등을 포함한다. 비이온성 계면활성제의 구체적인 예는 알콕시레이티드알킬에테르, 알콕시레이티드알킬에스테르, 알킬폴리글리코사이드, 폴리글리세릴에스테르 및 슈가에스테르 등을 포함한다. 바람직하게는 천연 유화제를 사용하는 경우이다. 천연 유화제는 OLIVOIL AVENATE EMULSIFIER　(Kalichem)를 포함하여 다양한 것이 시중에 시판되고 있으나 시판되는 적절한 것을 선택하여 사용할 수 있다. 보조 유화제는 수상용액과 유상용액의 혼합물 총 중량에 대해 0.1∼5.0 중량%의 범위로 포함될 수 있다.In addition, the oily solution may further include an auxiliary emulsifier. Auxiliary emulsifiers may be used anionic surfactants, cationic surfactants or nonionic surfactants. Specific examples of anionic surfactants include alkylacylglutamate, alkylphosphates, alkyllactylates, dialkylphosphates, trialkylphosphates, and the like. Specific examples of nonionic surfactants include alkoxylated alkyl ethers, alkoxylated alkyl esters, alkylpolyglycosides, polyglyceryl esters, sugar esters, and the like. It is preferable to use a natural emulsifier. Natural emulsifiers are commercially available, including OLIVOIL AVENATE EMULSIFIER® (Kalichem), but may be selected and used as appropriate. Auxiliary emulsifier may be included in the range of 0.1 to 5.0% by weight based on the total weight of the mixture of the aqueous solution and the oily solution.
상기 유상용액을 제조하기 위하여 80~100℃으로 가온하며 용해시키는데, 80℃ 미만으로 가온하는 경우 유화가 잘 되지 않을 수 있고, 100℃ 초과하여 가온하는 경우 보조유화제가 타거나 산폐되는 문제점이 있다. 바람직하게는 90~97℃로 가온하여 유상용액을 제조하는 것이 좋다.In order to prepare the oily solution, the solvent is heated to 80 to 100 ° C. to dissolve, and when heated to less than 80 ° C., the emulsification may not be performed well. Preferably heated to 90 ~ 97 ℃ to prepare an oil solution.
상기 리포좀 제조단계(S30)는 상기 수상용액과 유상용액을 혼합 교반하여 나노리포좀을 형성하는 단계로서, 상기 수상용액에 상기 유상용액을 첨가하면서 교반하고, 교반 후 온도가 40℃ 이하가 되었을 때 마이크로플루다이저를 이용하여 반복 가공함으로써 나노리포좀을 형성하는 단계이다. The liposome manufacturing step (S30) is a step of forming a nano liposome by mixing and stirring the aqueous solution and the oily solution, the stirring while adding the oily solution to the aqueous solution, and after stirring the temperature is 40 ℃ or less It is a step of forming a nano liposome by repeating the process using a fluidizer.
더욱 구체적으로, 상기 리포좀 제조단계(S30)는 수상용액에 유상용액을 부어가면서 호모믹서를 이용하여 2,500 내지 3,500rpm으로 30분 내지 60분 동안 교반한다. 교반 후 온도 40℃ 이하가 되었을 때 마이크로플루다이저를 이용하여 20,000 내지 30,000psi 압력으로 2회 내지 5회 반복 가공한다. 마이크로플루다이저 이후 원심분리기를 이용하여 4,500 내지 5,500rpm으로 5 내지 15분간 원심분리 후 수상용액과 유상용액의 층분리 현상이 없다면 안정적인 리포좀이 제조된 것으로 보고 단계를 종료한다.More specifically, the liposome manufacturing step (S30) is stirred for 30 minutes to 60 minutes at 2,500 to 3,500rpm using a homomixer while pouring the oil solution to the aqueous solution. After stirring, when the temperature reached 40 ° C. or less, the microfluidizer was used to repeatedly process 2 to 5 times at a pressure of 20,000 to 30,000 psi. After centrifugation at 4,500 to 5,500 rpm using a centrifuge for 5 to 15 minutes after the microfluidizer, there is no layer separation between the aqueous solution and the oil solution.
마이크로플루다이저의 고온 고압의 혹한 상황에서도 나노다이아몬드의 표면 구조는 안정적인 구조를 유지하고 그 표면에 흡착되어 있는 기능성 식물 추출 생리활성 성분 또한 안정적으로 유지된다.The surface structure of nanodiamond maintains a stable structure even in the high temperature and high pressure of microfluidizer, and the functional plant extract bioactive component adsorbed on the surface is also stable.
본 발명에 따라 제조된 나노리포좀은 피부 깊숙이 침투하여 기능성 식물 추출 생리활성 성분을 발산하는데, 이때 나노다이아몬드의 표면에 흡착되어 있는 기능성 식물 추출 생리활성 성분은 장시간에 걸쳐 발산된다. 이는 생리활성 물질의 표면 탈착이 소량씩 장시간에 걸쳐서 이루어지므로 약리 작용 시간이 매우 길어져 일반적인 나노리포좀에 비해서 장시간의 지속적인 생리 활성을 가져온다. 이는 약효가 지속적으로 장시간에 걸쳐 이뤄지기 때문에 훨씬 높은 약리 효능을 가져오게 된다. Nanoliposomes prepared according to the present invention penetrates deep into the skin to emit a functional plant extract bioactive component, wherein the functional plant extract bioactive component adsorbed on the surface of the nanodiamond is emitted for a long time. This is because the surface desorption of the physiologically active substance is made over a long period of time in small amounts, so the pharmacological action time is very long, resulting in long-term sustained physiological activity compared to the general nanoliposomes. This results in a much higher pharmacological effect because the drug is continuously made over a long time.
본 발명의 또 다른 일 실시예에 따른 나노리포좀은 기능성 식물 추출 생리 활성 성분이 결함이 있는 부분에 결착되어 있는 나노다이아몬드가 포함된 수상용액과 마유 및 인지질이 포함된 유상용액을 유화시켜 제조된 것으로서, 도 1에 나타낸 것과 같이 기능성 식물 추출 생리 활성 성분이 결함이 있는 부분에 결착되어 있는 나노다이아몬드가 포함된 수상코어, 상기 수상코어를 둘러싼 인지질로 구성된 유상쉘로 구성된다.Nanoliposomes according to another embodiment of the present invention is prepared by emulsifying the aqueous solution containing the nanodiamond and the oily solution containing horse oil and phospholipid that is bound to the defective part of the functional plant extract bioactive components as As shown in FIG. 1, a water core containing nanodiamond, which is bound to a defective portion of a functional plant extract physiologically active component, and an oily shell composed of phospholipids surrounding the water core.
마유 성분은 리포좀 구체 내부와 외부에 레시틴과 보조유화제에 의해 2중층 인지질을 형성하고 있으며 수상코어에도 보조유화제에 의해서 O/W 형태로 유화되어 존재한다. The horse oil component forms bilayer phospholipids by lecithin and coemulsifier inside and outside the liposome sphere, and is also emulsified in O / W form by coemulsifier in the water core.
상기 수상코어는 연속상을 형성하는 구형 구조로, 물이 필수적으로 포함되어 있으며, 메틸파라벤(methylparaben)과 같은 방부제도 상기 수상코어에 포함되어질 수 있으며, 피부 보습 효과를 위해서 부틸렌글리콜(butylene glycol)이 추가적으로 포함될 수 있다. The water core is a spherical structure forming a continuous phase, water is essentially included, and preservatives such as methylparaben may be included in the water core, and butylene glycol for skin moisturizing effect. ) May be additionally included.
상기 기능성 식물 추출 생리 활성 성분은 상기 나노다이아몬드의 결함이 있는 부분에 결착되는 것으로 나노리포좀 전체 중량에 대하여 1.0 중량% 내지 5.0 중량%로 포함되는 것이 바람직하다. The functional plant extract physiologically active component is bound to the defective portion of the nanodiamond is preferably contained in 1.0% to 5.0% by weight relative to the total weight of the nanoliposomes.
상기 유상쉘은 수상코어와 나노리포좀 외부를 향한 친수성 머리 및 유상쉘 내부를 향한 친유성 꼬리로 구성되는 인지질 구조를 갖는 이중층을 형성하는 쉘 구조이다. The oily shell is a shell structure that forms a bilayer having a phospholipid structure composed of a hydrophilic head facing the outer core and the nanoliposome and a lipophilic tail facing the oil shell.
본 발명에 따른 나노리포좀의 입도는 100 내지 600nm 이다. The particle size of the nanoliposomes according to the present invention is 100 to 600nm.
또한 본 발명은 상기 기능성 식물 추출 생리 활성 성분이 나노다이아몬드의 결함이 있는 부분에 결착된 상태로 수상코어에 포함된 나노리포좀을 유효성분으로 포함하는 조성물을 제공한다. 상기 조성물은 약제학적 조성물이거나 화장료 조성물일 수 있다. The present invention also provides a composition comprising a nanoliposome contained in the water core as an active ingredient in a state in which the functional plant extract bioactive component is bound to a defective portion of nanodiamonds. The composition may be a pharmaceutical composition or a cosmetic composition.
본 발명의 약제학적 조성물은 법률상·기능상의 구분에 있어서 제조·유통 시점의 관련 시행 법규에 부합하는 한 임의의 제품 구분을 띨 수 있다. 예컨대 약사법에 따른 의약외품 또는 의약품이거나 의약품일 경우 일반의약품 또는 전문의약품일 수 있다. The pharmaceutical composition of the present invention can be classified into any product as long as it conforms to the relevant enforcement regulations at the time of manufacture and distribution in the legal and functional categories. For example, it may be a quasi-drug or drug under the Pharmacist Act or, if it is a drug, it may be a generic or specialized drug.
본 발명의 약제학적 조성물은 그 유효성분 이외에 약제학적으로 허용되는 담체를 포함하여 당업계에 공지된 통상의 방법으로 투여 경로에 따라 경구용 제형 또는 비경구용 제형으로 제조될 수 있다. 여기서 "약제학적으로 허용되는" 의미는 유효성분의 활성을 억제하지 않으면서 적용(처방) 대상이 적응 가능한 이상의 독성을 지니지 않는다는 의미이다.The pharmaceutical compositions of the present invention may be prepared in oral or parenteral formulations according to the route of administration by conventional methods known in the art, including pharmaceutically acceptable carriers in addition to the active ingredients. "Pharmaceutically acceptable" here means that the subject of application (prescription) is not as toxic as applicable, without inhibiting the activity of the active ingredient.
본 발명의 약제학적 조성물이 경구용 제형으로 제조될 경우, 적합한 담체와 함께 당업계에 공지된 방법에 따라 분말, 과립, 정제, 환제, 당의정제, 캡슐제, 액제, 겔제, 시럽제, 현탁액, 웨이퍼 등의 제형으로 제조될 수 있다. 이때 약제학적으로 허용되는 적합한 담체의 예로서는 락토스, 글루코스, 슈크로스, 덱스트로스, 솔비톨, 만니톨, 자일리톨 등의 당류, 옥수수 전분, 감자 전분, 밀 전분 등의 전분류, 셀룰로오스, 메틸셀룰로오스, 에틸셀룰로오스, 나트륨 카르복시메틸셀룰로오스, 하이드록시프로필메틸셀룰로오스 등의 셀룰로오스류, 폴리비닐 피롤리돈, 물, 메틸히드록시벤조에이트, 프로필히드록시벤조에이트, 마그네슘 스테아레이트, 광물유, 맥아, 젤라틴, 탈크, 폴리올, 식물성유 등을 들 수 있다. 제제화활 경우 필요에 따라 충진제, 증량제, 결합제, 습윤제, 붕해제, 계면활성제 등의 희석제 및/또는 부형제를 포함하여 제제화할 수 있다.When the pharmaceutical composition of the present invention is prepared in an oral dosage form, powders, granules, tablets, pills, dragees, capsules, solutions, gels, syrups, suspensions, wafers are prepared according to methods known in the art with suitable carriers. It may be prepared in a formulation such as. Examples of suitable pharmaceutically acceptable carriers include sugars such as lactose, glucose, sucrose, dextrose, sorbitol, mannitol and xylitol, starch such as corn starch, potato starch, wheat starch, cellulose, methylcellulose, ethylcellulose, Celluloses such as sodium carboxymethyl cellulose and hydroxypropyl methyl cellulose, polyvinyl pyrrolidone, water, methyl hydroxybenzoate, propyl hydroxybenzoate, magnesium stearate, mineral oil, malt, gelatin, talc, polyol, vegetable Yu etc. can be mentioned. In the case of formulation, it may be formulated to include diluents and / or excipients such as fillers, extenders, binders, wetting agents, disintegrating agents, surfactants, if necessary.
본 발명의 약제학적 조성물이 비경구용 제형으로 제조될 경우, 적합한 담체와 함께 당업계에 공지된 방법에 따라 주사제, 경피 투여제, 비강 흡입제 및 좌제의 형태로 제제화될 수 있다. 주사제로 제제화할 경우 적합한 담체로서는 멸균수, 에탄올, 글리세롤이나 프로필렌 글리콜 등의 폴리올 또는 이들의 혼합물을 사용할 수 있으며, 바람직하게는 링거 용액, 트리에탄올 아민이 함유된 PBS(phosphate buffered saline)나 주사용 멸균수, 5% 덱스트로스 같은 등장 용액 등을 사용할 수 있다. 경피 투여제로 제제화할 경우 연고제, 크림제, 로션제, 겔제, 외용액제, 파스타제, 리니멘트제, 에어롤제 등의 형태로 제제화할 수 있다. 비강 흡입제의 경우 디클로로플루오로메탄, 트리클로로플루오로메탄, 디클로로테트라플루오로에탄, 이산화탄소 등의 적합한 추진제를 사용하여 에어로졸 스프레이 형태로 제제화할 수 있으며, 좌제로 제제화할 경우 그 기제로는 위텝솔(witepsol), 트윈(tween) 61, 폴리에틸렌글리콜류, 카카오지, 라우린지, 폴리옥시에틸렌 소르비탄 지방산 에스테르류, 폴리옥시에틸렌 스테아레이트류, 소르비탄 지방산 에스테르류 등을 사용할 수 있다.When the pharmaceutical compositions of the present invention are prepared in parenteral formulations, they may be formulated in the form of injections, transdermal administrations, nasal inhalants and suppositories with suitable carriers according to methods known in the art. When formulated as an injectable, suitable carriers may be sterile water, ethanol, polyols such as glycerol or propylene glycol, or mixtures thereof, preferably PBS (phosphate buffered saline) containing Ringer's solution, triethanol amine, or injectable sterilization. Water, isotonic solutions such as 5% dextrose, and the like. When formulated as a transdermal administration, it may be formulated in the form of an ointment, cream, lotion, gel, external solution, pasta, linen, aerosol. Nasal inhalants can be formulated in the form of aerosol sprays using suitable propellants, such as dichlorofluoromethane, trichlorofluoromethane, dichlorotetrafluoroethane, carbon dioxide, etc. witepsol), tween 61, polyethylene glycols, cacao butter, laurin paper, polyoxyethylene sorbitan fatty acid esters, polyoxyethylene stearate, sorbitan fatty acid esters, and the like.
약제학적 조성물의 제제화와 관련하여서는 당업계에 공지되어 있으며, 구체적으로 문헌[Remington's Pharmaceutical Sciences(19th ed., 1995)] 등을 참조할 수 있다. 상기 문헌은 본 명세서의 일부로서 간주 된다.Regarding the formulation of pharmaceutical compositions, it is known in the art and specific reference may be made to Remington's Pharmaceutical Sciences (19th ed., 1995) and the like. The document is considered part of this specification.
본 발명의 조성물은 또 다른 구체적인 양태에 있어서, 화장료 조성물로 파악할 수 있다.The composition of this invention can be grasped | ascertained as a cosmetic composition in another specific aspect.
화장료 조성물은 용액, 현탁액, 유탁액, 페이스트, 젤, 크림, 로션, 파우더, 샴푸, 비누, 계면활성제-함유 클렌징, 오일, 분말 파운데이션, 유탁액 파운데이션, 왁스 파운데이션, 스프레이 등의 제품 형태를 띨 수 있다. 구체적인 제품 형태에 있어서는 유연 화장수, 영양 화장수, 영양 크림, 마사지 크림, 에센스, 아이 크림, 클렌징 크림, 클렌징 포옴, 클렌징 워터, 팩, 스프레이 또는 파우더의 제형 등일 수 있다.Cosmetic compositions can take the form of products such as solutions, suspensions, emulsions, pastes, gels, creams, lotions, powders, shampoos, soaps, surfactant-containing cleansing, oils, powder foundations, emulsion foundations, wax foundations, sprays, etc. have. In the specific product form, it may be a softening lotion, a nourishing lotion, a nourishing cream, a massage cream, an essence, an eye cream, a cleansing cream, a cleansing foam, a cleansing water, a pack, a spray or a powder formulation.
본 발명의 화장료 조성물은 그 유효성분 이외에 화장료 조성물에 통상적으로 이용되는 성분들, 예컨대, 안정화제, 용해화제, 계면활성제, 비타민, 색소 및 항료와 같은 통상적인 보조제, 및 담체를 포함할 수 있다. The cosmetic composition of the present invention may include, in addition to the active ingredient, components commonly used in the cosmetic composition, for example, conventional adjuvants such as stabilizers, solubilizers, surfactants, vitamins, pigments and pharmaceuticals, and carriers.
본 발명의 제형이 페이스트, 크림 또는 젤인 경우에는 담체 성분으로서 동물성유, 식물성유, 왁스, 파라핀, 전분, 트라칸트, 셀룰로오스 유도체, 폴리에틸렌 글리콜, 실리콘, 벤토나이트, 실리카, 탈크 또는 산화아연 등이 이용될 수 있다.When the formulation of the present invention is a paste, cream or gel, animal oils, vegetable oils, waxes, paraffins, starches, trachants, cellulose derivatives, polyethylene glycols, silicones, bentonites, silicas, talc or zinc oxide may be used as carrier components. Can be.
본 발명의 제형이 파우더 또는 스프레이인 경우에는 담체 성분으로서 락토스, 탈크, 실리카, 알루미늄 히드록시드, 칼슘 실리케이트 또는 폴리아미드 파우더가 이용될 수 있고, 특히 스프레이인 경우에는 추가적으로 클로로플루오로히드로카본, 프로판/부탄 또는 디메틸 에테르와 같은 추진체를 포함할 수 있다.When the formulation of the present invention is a powder or a spray, lactose, talc, silica, aluminum hydroxide, calcium silicate or polyamide powder may be used, in particular in the case of a spray, additionally chlorofluorohydrocarbon, propane Propellant such as butane or dimethyl ether.
본 발명의 제형이 용액 또는 유탁액인 경우에는 담체 성분으로서 용매, 용해화제 또는 유탁화제가 이용되는데, 구체적으로 물, 에탄올, 이소프로판올, 에틸 카보네이트, 에틸 아세테이트, 벤질 알코올, 벤질 벤조에이트, 프로필렌 글리콜, 1,3-부틸글리콜 오일, 글리세롤 지방족 에스테르, 폴리에틸렌 글리콜, 소르비탄의 지방산 에스테르 등이 이용될 수 있다. 본 발명의 제형이 현탁액인 경우에는 담체 성분으로서 물, 에탄올 또는 프로필렌 글리콜과 같은 액상의 희석제, 에톡실화 이소스테아릴 알코올, 폴리옥시에틸렌 소르비톨 에스테르, 폴리옥시에틸렌 소르비탄 에스테르와 같은 현탁제, 미소결정성 셀룰로오스, 알루미늄 메타히드록시드, 벤토나이트, 아가 등이 이용될 수 있다.When the formulation of the present invention is a solution or emulsion, a solvent, solubilizing agent or emulsifying agent is used as the carrier component, specifically water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylglycol oil, glycerol aliphatic ester, polyethylene glycol, fatty acid ester of sorbitan and the like can be used. When the formulation of the present invention is a suspension, liquid carrier diluents such as water, ethanol or propylene glycol, suspending agents such as ethoxylated isostearyl alcohol, polyoxyethylene sorbitol ester, polyoxyethylene sorbitan ester, and microcrystals are used as carrier components. Castle cellulose, aluminum metahydroxy, bentonite, agar and the like can be used.
본 발명의 제형이 계면-활성제 함유 클렌징인 경우에는 담체 성분으로서 지방족 알코올 설페이트, 지방족 알코올 에테르 설페이트, 설포숙신산 모노에스테르, 이세티오네이트, 이미다졸리늄 유도체, 메틸타우레이트, 사르코시네이트, 지방산 아미드 에테르 설페이트, 알킬아미도베타인, 지방족 알코올, 지방산 글리세리드, 지방산 디에탄올아미드, 식물성 유, 라놀린 유도체 또는 에톡실화 글리세롤 지방산 에스테르 등이 이용될 수 있다.When the formulation of the present invention is a surfactant-containing cleansing, the carrier component is an aliphatic alcohol sulfate, an aliphatic alcohol ether sulfate, a sulfosuccinic acid monoester, an isethionate, an imidazolinium derivative, a methyltaurate, a sarcosinate, a fatty acid amide. Ether sulfates, alkylamidobetaines, aliphatic alcohols, fatty acid glycerides, fatty acid diethanolamides, vegetable oils, lanolin derivatives or ethoxylated glycerol fatty acid esters and the like can be used.
본 발명의 화장료 조성물은 그 유효성분을 포함하는 것을 제외하고는 당업계에 통상적으로 행하여지는 화장료 조성물의 제조방법에 따라 제조할 수 있다.The cosmetic composition of the present invention can be prepared according to the manufacturing method of the cosmetic composition usually carried out in the art, except that the active ingredient is included.
이하, 실시예를 통하여 본 발명을 더욱 상세히 설명하고자 한다. 이들 실시예는 오로지 본 발명을 예시하기 위한 것으로서, 본 발명의 범위가 이들 실시예에 의해 제한되는 것으로 해석되지는 않는 것은 이 기술분야에서 통상의 지식을 가진 자에게 있어서 자명할 것이다.Hereinafter, the present invention will be described in more detail with reference to Examples. These examples are only for illustrating the present invention, it will be apparent to those skilled in the art that the scope of the present invention is not to be construed as being limited by these examples.
<실시예> 시료의 준비EXAMPLES Preparation of Sample
(1) 기능성 식물 추출 생리 활성 성분 : 피부 주름, 피부 미백, 피부 항산화, 피부 항염, 피부 항균, 피부탄력 그리고 피부 장벽 개선에 효능을 가지고 있으나 본 임상실험은 주름기능성에 대한 본 조성물 함유 여부에 따른 대조임상을 실시하였습니다.(1) Functional plant extract physiologically active ingredients: skin wrinkles, skin whitening, skin antioxidants, skin anti-inflammatory, skin antibacterial, skin elasticity and skin barrier improvement, but this clinical trial is based on the presence of the composition for wrinkle function A controlled clinical trial was conducted.
병풀추출물, 마치현추출물, 우엉추출물, 카렌듈라추출물, 레몬추출물, 도약추출물, 서양고추나물추출물, 세이지잎추출물, 비누풀잎추출물, 캐모마일꽃추출물, 마늘추출물, 아니카플라워추출물, 서양송악추출물, 왜광대수염꽃추출물, 물냉이꽃/잎추출물, 구조소나무잎추출물 및 로즈마리잎추출물을 혼합하여 기능성 식물 추출 생리 활성 성분으로 준비하였다. Centella asiatica extract, March extract, burdock extract, calendula extract, lemon extract, leap extract, red pepper extract, sage leaf extract, soap leaf extract, chamomile flower extract, garlic extract, anica flower extract, western pineapple extract, Extract, watercress flower / leaf extract, structure pine leaf extract, and rosemary leaf extract were mixed to prepare a functional plant extract bioactive component.
(2) 나노리포좀의 제조(2) Preparation of Nanoliposomes
나노리포좀의 제조는 90℃까지 가온된 아래 표 1의 수상 용액의 혼합물에, 마찬가지로 90℃까지 가온된 아래 표 1의 유상 용액의 혼합물을 혼합하고 3,000rpm에서 30분 이상 교반한 후 온도가 40℃이하가 되었을 때 고압유화기(microfluidizer)로 25,000 psi 압력으로 3회 반복 가공하였다. 이후 5,000rpm으로 10분간 원심분리 후 수용성 성분과 지용성 성분의 층분리 현상이 없이 안정적인 리포좀이 제조된 것을 확인하였다. Preparation of the nanoliposomes is a mixture of the aqueous solution of Table 1 below warmed up to 90 ° C., likewise the mixture of the oily solution of Table 1 below warmed up to 90 ° C. and stirred at 3,000 rpm for at least 30 minutes and then at 40 ° C. The following process was repeated three times at a pressure of 25,000 psi with a microfluidizer. After centrifugation at 5,000 rpm for 10 minutes, it was confirmed that a stable liposome was prepared without a layer separation phenomenon of the water-soluble component and the fat-soluble component.
구분division 성분명Ingredient Name 실시예Example 비교예 1Comparative Example 1 비교예 2Comparative Example 2
수상용액Water solution 정제수Purified water 20.020.0 20.020.0 20.020.0
기능성 식물 추출 생리 활성 성분Functional Plant Extract Bioactive Ingredients 2.52.5 2.52.5 2.52.5
나노다이아몬드 수용액Nano Diamond Solution 25.025.0 -- 25.025.0
1,3 부틸렌 글리콜1,3 butylene glycol 20.020.0 20.020.0 20.020.0
유상용액Oil solution 마유Horse oil 25.025.0 25.025.0 --
대두 레시틴Soy Lecithin 2.52.5 2.52.5 2.52.5
천연 보조 유화제Natural auxiliary emulsifiers 1.51.5 1.51.5 1.51.5
토코페릴아세테이트Tocopheryl Acetate 3.03.0 3.03.0 3.03.0
* 천연 유화제는 OLIVOIL AVENATE EMULSIFIER(Kalichem)* 나노 다이아몬드 분말은 입자 크기가 100nm 이하의 것을 시중에서 구입하여 정제수에 넣어 2.5ppm 수용액으로 사용하였음.* 토코페릴아세테이트는 항산화제로서 사용되었음.* Natural emulsifier OLIVOIL AVENATE EMULSIFIER (Kalichem) * Nano diamond powder was purchased on the market with a particle size of 100 nm or less in purified water and used as a 2.5 ppm aqueous solution. * Tocopheryl acetate was used as an antioxidant.
<실험예 1> 용출 특성Experimental Example 1 Dissolution Characteristics
용출시간(min)에 따른 용출량(%) 및 90% 이상 용출되는데 걸린 시간(min)을 확인하였다. 용출시험 조건은 다음과 같다. The elution amount (%) according to the elution time (min) and the time taken to elute 90% or more (min) was confirmed. Dissolution test conditions are as follows.
- 용출시험장치: Electrolab TDT-08L-Dissolution test equipment: Electrolab TDT-08L
- 용출액: 1) 아세트산·아세트산나트륨완충액, pH 6.8 500 mLEluent: 1) acetic acid, sodium acetate buffer, pH 6.8 500 mL
2) 정제수 500 mL2) 500 mL of purified water
- 용출액의 온도: 37 ± 0.5 ℃Eluent temperature: 37 ± 0.5 ° C
- 회전속도: 50 ± 2 rpmRotational speed: 50 ± 2 rpm
그 결과 표 2(용출액 1) 및 표 3(용출액 2)와 같이 모든 용출액에서 대조군인 비교예보다 실시예의 나노리포좀이 느린 용출 속도률 나타내었다. 상기 결과로부터 기능성 식물 추출 생리활성 성분이 장시간에 걸쳐 발산되는 것을 알 수 있다. 이는 생리활성 물질의 나노다이아몬드의 결함부분으로부터의 탈착이 소량씩 장시간에 걸쳐서 이루어지므로 약리 작용 시간이 매우 길어져 일반적인 나노리포좀에 비해서 장시간의 지속적인 생리 활성을 가져오는 것을 알 수 있다. As a result, as shown in Table 2 (eluate 1) and Table 3 (eluate 2), the elution rate of the nanoliposomes of the Example was slower than that of the comparative example in all eluates. From the above results, it can be seen that the functional plant extract physiologically active component is emitted for a long time. This is because the desorption from the defective portion of the nanodiamond of the bioactive material is made in small amounts over a long time, the pharmacological action time is very long, it can be seen that the long-term sustained physiological activity compared to the general nanoliposomes.
용출액 1Eluent 1 실시예Example 비교예 1Comparative Example 1 비교예 2Comparative Example 2
용출량(%)Dissolution amount (%) 30min30min 1010 1515 2525
60min60min 2020 4040 4040
90min90min 3030 6060 5555
120min120 min 3535 7575 6060
90% 이상 용출 시간(min)Elution time over 90% (min) 210210 140140 170170
용출액 2Eluent 2 실시예Example 비교예 1Comparative Example 1 비교예 2Comparative Example 2
용출량(%)Dissolution amount (%) 30min30min 1010 2020 2525
60min60min 2525 3030 3535
90min90min 4040 5555 5050
120min120 min 4545 8080 7575
90% 이상 용출 시간(min)Elution time over 90% (min) 200200 130130 150150
<실험예 2> 임상 특성Experimental Example 2 Clinical Characteristics
상기 실시예에서 제조된 나노리포좀을 포함하는 크림을 제조하였다. 전성분은 하기 표 4와 같다. 상기 제조된 크림에 대하여 임상시험을 진행하였다. A cream containing a nanoliposome prepared in the above Example was prepared. All components are shown in Table 4 below. A clinical trial was conducted on the prepared cream.
성상Constellation 미황색 크림상Light yellow cream
농도density 100%100%
전성분All ingredients 정제수, 부틸렌글라이콜, 하이드로제네이티드폴리데센, 사이클로헥사실록산, 사이클로헥사실록산, 세테아릴알코올, 1,2-헥산디올, 판테놀, 세테아릴올리베이트, 소르비탄올리베이트, 에틸헥실팔미테이트, 트라이에틸헥사노인, 디메치콘, 글리세릴스테아레이트, 글리세린, 비스-피이지-18, 메칠에텔디메칠실란, 카보머, 아데노신, 트로메타민, 향료, 잔탄검, 병풀추출물, 마치현추출물, 레시틴, 디소듐이디티에이, 에탄올, 페녹시에탄올, 우엉추출물, 카렌듈라추출물, 레몬추출물, 도약추출물, 서양고추나물추출물, 세이지잎추출물, 비누풀잎추출물, 캐모마일꽃추출물, 마늘추출물, 아니카플라워추출물, 서양송악추출물, 왜광대수염꽃추출물, 물냉이꽃/잎추출물, 구조소나무잎추출물, 로즈마리잎추출물, 마유, 토코페놀, 포타슘올리보일하이드롤라이즈드귀리단백질, 글리세릴올리에이트, 포타슘솔베이트, 소듐벤조에이트, 벤질알코올, 나노다이아몬드Purified water, butylene glycol, hydrogenated polydecene, cyclohexasiloxane, cyclohexasiloxane, cetearyl alcohol, 1,2-hexanediol, panthenol, cetearyl oliveate, sorbitan sulfate, ethylhexyl palmitate , Triethylhexanoin, dimethicone, glyceryl stearate, glycerin, bis-pig-18, methyl ether dimethyl silane, carbomer, adenosine, tromethamine, fragrance, xanthan gum, centella extract, gusset extract, lecithin , Disodium ethane, ethanol, phenoxyethanol, burdock extract, calendula extract, lemon extract, leap extract, red pepper extract, sage leaf extract, soap leaf extract, chamomile flower extract, garlic extract, anica flower extract, western extract Songak Extract, Dwarf Radish Flower Extract, Watercress Flower / Leave Extract, Structured Pine Leaf Extract, Rosemary Leaf Extract, Horse Oil, Tocophenol, Potassium Oligohydrolide Lee protein, glyceryl oleate, potassium niobate Sol, sodium benzoate, benzyl alcohol, NCD
(1) 시험대상자 (1) Subject
시험대상자는 피부질환을 포함하는 급, 만성 질환이 없고, 민감한 피부가 아니며 화장품 알레르기가 없는 만 20~50세의 성인 여성 33명을 대상으로 실시하였다.The subjects were 33 adult women aged 20 to 50 with no grade or chronic diseases including skin diseases, no sensitive skin, and no cosmetic allergies.
(2) 시험 방법 및 절차(2) test methods and procedures
피부 상태 확인을 위해 시험대상자는 준비된 가운으로 상의를 갈아입은 후 항온항습 조건 (온도20~24℃, 습도40~60%)의 공간에서 약 30분간 피부 안정을 취해 측정 환경에 적응하도록 하였다. 시험제품 적용 부위를 촬영하였고, 매번 같은 조건에서 전문가 2명에 의해 피부 반응 확인이 진행되었다.In order to check the skin condition, the subject was changed to a prepared gown and allowed to adjust to the measurement environment by taking skin stability for about 30 minutes in a space of constant temperature and humidity conditions (temperature 20 ~ 24 ℃, humidity 40 ~ 60%). The site of application of the test product was photographed, and the skin reaction was checked by two experts under the same conditions every time.
(3) 시험제품 적용 부위(3) Application area of test product
시험 부위는 등의 평평한 부위를 선정하였다. 시험 부위를 다음 평가할 때 인식하기 위해 시험 부위에 표시하여 다름 평가 때 동일한 부위를 가지고 평가하도록 하였다.For the test site, a flat site such as the back was selected. The test site was marked on the test site for recognition in the next evaluation, and the same site was evaluated for the next evaluation.
(4) 시험 방법(4) test method
1) 유도기(Induction phase)1) Induction phase
유도기는 2주간 3일 간격으로 시험부위에 시험물질 20㎕를 5회 첩포 하였으며 첩포를 제거한 후 30분 ~ 1시간 후 시험 부위를 관찰하였다.The induction machine was applied 5 μl of test substance to the test site 5 times at 3 days intervals for 2 weeks, and the test site was observed after 30 minutes to 1 hour after removing the patch.
2) 휴지기(Resting period)2) Resting period
유도기에서 5회 첩포가 끝난 후부터 2주간이며, 이 기간 동안은 시험 부위에 아무런 처치를 하지 않았다.Two weeks from the end of the five patches in the induction phase, no treatment was done to the test site during this period.
3) 야기기(Challenge phase)3) Challenge phase
휴지기가 끝나고 아무런 처치를 하지 않았던 부위(naive site)에 시험물질 20㎕를 48시간 동안 1회 첩포하며, 첩포를 제거한 후 30분, 48시간, 96시간까지 시험 부위를 관찰하였다. 단, 의심 소견이 있을 경우는 그 후에도 관찰하였다.20 μl of the test substance was applied to the naive site at the end of the resting period for 48 hours, and the test site was observed for 30 minutes, 48 hours, and 96 hours after removing the patch. However, any suspicious findings were observed thereafter.
(5) 평가 방법 및 판정 기준 (5) Evaluation method and judgment standard
1) 피부 누적 자극 평가 1) skin cumulative stimulation evaluation
유도기는 피부의 자극반응 및 누적자극 반응을 관찰하기 위한 과정으로 첩포 제거 후 다음과 같은 기준에 따라 점수를 부여하고, 제품의 자극성 및 누적 자극성은 반응의 경향과 강도로서 판단한다. 판단 기준은 Frosch & Kligman와 The Cosmetic, Toiletry, and Fragrance Association (CTFA)의 guideline의 기준을 근거로 하여 아래의 표 5에 나타낸 기준에 따라 판단한다. The induction machine is a process for observing skin irritation and cumulative stimulation reactions and is scored according to the following criteria after removing the patch. Judgment criteria are based on the criteria set forth in Table 5 below, based on the guidelines of Frosch & Kligman and The Cosmetic, Toiletry, and Fragrance Association (CTFA).
Grade Grade Characteristics Characteristics
0 0 No reaction No reaction
1 One Slight erythema, spotty or diffuse Slight erythema, spotty or diffuse
2 2 Moderate uniform erythema Moderate uniform erythema
3 3 Intense erythema with edema Intense erythema with edema
4 4 Intense erythema with edema and vesicle Intense erythema with edema and vesicle
예를 들어, 다음과 같은 경우는 점수를 부여한다. For example, the following cases are given a score.
- 시험과정 중 1 주일 이상(3 회 이상) 무반응이면서 검사에 참여하지 못한 경우는 그 전의 점수를 부여한다. -If a student is not responding for more than 1 week (3 or more times) during the course of the test and fails to participate in the test, the previous score will be given.
- 자극 정도가 grade 3 이상의 경우는 첩포를 중단하고 유도기 동안 3 점을 부여 한다. 그러나 첩포를 중단한 상태에서도 반응이 강해지는 경우에는 4 점까지 -If the degree of stimulation is higher than grade 3, stop the patch and give 3 points during the induction period. However, if the reaction is strong even with the patch stopped, up to 4 points
점수를 부여한다. 단, 1 회 이상 첩포를 하지 않거나 기타 이유로 중단한 경우는 제외한다. Give a score. However, if the patch is not applied more than once or discontinued for other reasons.
2) 피부 자극 지수 계산 및 판정 기준 2) Skin irritation index calculation and judgment criteria
피부 반응도 및 피부 자극 지수는 아래의 수식에 따라 구하였다. Skin reactivity and skin irritation index were calculated according to the following formula.
Figure PCTKR2018016045-appb-I000001
Figure PCTKR2018016045-appb-I000001
시험제품의 피부 자극 정도는 아래의 표 6에 나타낸 기준에 따라 판정하였다. The degree of skin irritation of the test product was determined according to the criteria shown in Table 6 below.
피부 자극 지수 Skin irritation index 구분 division
0.00 - 0.25 0.00-0.25 비자극성 Non-irritant
0.26 - 1.00 0.26-1.00 약한 자극성 Mild irritant
1.01 - 2.50 1.01-2.50 중등도 자극성 Moderate irritant
2.51 - 4.00 2.51-4.00 강한 자극성 Strong irritant
3) 피부 감작성 평가 3) skin sensitization evaluation
야기기는 감작성 유무를 검색하기 위한 과정으로 피부 반응 정도는 아래의 표 7에 나타낸 것과 같은 ICDRG 기준에 따라 점수를 부여한다. Yagi is a process to detect the presence of sensitization. The degree of skin reaction is given according to the ICDRG criteria as shown in Table 7 below.
Grade Grade Characteristics Characteristics
1(+?) 1 (+?) Doubtful reaction; faint erythema only Doubtful reaction; faint erythema only
2(+) 2 (+) Weak positive reaction; erythema, infiltration, possibly papules Weak positive reaction; erythema, infiltration, possibly papules
3(++) 3 (++) Strong positive reaction; erythema, infiltration, papules, vesicles Strong positive reaction; erythema, infiltration, papules, vesicles
4(+++) 4 (+++) Extreme positive reaction; intense erythema and infiltration and coalescing vesicles Extreme positive reaction; intense erythema and infiltration and coalescing vesicles
예를 들어, 다음과 같은 경우는 피부 감작성이 있다고 판정한다. For example, in the following cases, it is determined that there is skin sensitization.
- 홍반(erythema), 부종(oedema), 구진(papules), 수포(vesicles)를 동반하는 임상형을 가질 경우(3 (++) 이상)-With clinical forms accompanied by erythema, oedema, papules, and vesicles (3 (++) and above)
- 1차 야기 첩포 후 첫 번째 관찰에서 두 번째 관찰(첩포 후 48, 96시간)까지 반응의 강도가 증가되는 경우The intensity of the reaction increases from the first observation after the first yawn patch to the second (48, 96 hours after the patch).
- 해부학적으로 다른 부위에 두 번째 야기 첩포를 했을 때 유사한 반응이 나타날 경우A similar reaction occurs when a second causal patch is placed anatomically on another site
4) 시험대상자 주관적 반응 평가 4) Subject's subjective response evaluation
설문조사를 시행하여 시험대상자는 시험제품 사용 후 느끼는 따끔거림, 화끈거림, 가려움의 정도에 대하여 직접 설문평가를 작성하도록 하였다. The survey was conducted to prepare the test subjects for their feelings of tingling, burning, and itching after using the test product.
(6) 피부 누적 자극 평가 결과 (6) skin cumulative irritation evaluation results
하기 표 8에 나타낸 것과 같이 유도기 동안 1st에서 1+ Grade 2명, 4st에서 1+ Grade 1명 관찰되었다. 관찰된 피부 반응 중 2회 반응이 나타난 시험대상자는 1명 있었으나 어떤 경향성이나 특이성은 관찰되지 않았고, 피부 자극 지수는 0.02로 판정기준에 따라 비자극 제품으로 판단되었다. As shown in Table 8, two 1+ grades were observed at 1st and one 1+ grades at 4st during the induction phase. There was one subject who showed two reactions among the observed skin reactions, but no tendency or specificity was observed, and skin irritation index was 0.02.
1st1st 1+1+ 22
2+2+ --
3+3+ --
4+4+ --
2st2st 1+1+ --
2+2+ --
3+3+ --
4+4+ --
3st3st 1+1+ --
2+2+ --
3+3+ --
4+4+ --
4st4st 1+1+ 1One
2+2+ --
3+3+ --
4+4+ --
5st5st 1+1+ --
2+2+ --
3+3+ --
4+4+ --
(7) 피부 감작성 평가 결과(7) skin sensitization evaluation result
하기 표 9에 나타낸 것과 같이 야기기 동안 첩포 제거 30분 후 1명에게서 1(+?)grade의 피부 반응이 관찰되었고, 첩포 제거 48시간 경과 후 1명에게서 1(+?)grade의 피부 반응이 관찰되었다. As shown in Table 9, 1 (+?) Grade skin reaction was observed in one patient after 30 minutes of patch removal during induction, and 1 (+?) Grade skin reaction was observed in one patient after 48 hours of patch removal. Was observed.
Challenge phaseChallenge phase 0.5hrs0.5hrs 1(+?)1 (+?) 1One
2(+)2 (+) --
3(++)3 (++) --
4(+++)4 (+++) --
48hrs48hrs 1(+?)1 (+?) 1One
2(+)2 (+) --
3(++)3 (++) --
4(+++)4 (+++) --
96hrs96hrs 1(+?)1 (+?) --
2(+)2 (+) --
3(++)3 (++) --
4(+++)4 (+++) --
(8) 피부 자극에 대한 시험대상자의 주관적 평가 결과 (8) Subject's subjective evaluation result on skin irritation
시험대상자의 주관적 피부 자극 정도에 대한 평가를 하기 표 10에 나타내었다. Evaluation of the subject's subjective skin irritation degree is shown in Table 10 below.
첩포 제거 후After removing patch 인원personnel
1One 22 33
따끔함Tingling 0.5hrs0.5hrs 1One -- --
48hrs48hrs -- -- --
96hrs96hrs 1One -- --
화끈거림Burning 0.5hrs0.5hrs 1One -- --
48hrs48hrs -- -- --
96hrs96hrs -- -- --
가려움itch 0.5hrs0.5hrs 1One 44 --
48hrs48hrs 1One -- --
96hrs96hrs -- -- --
*단계: 1(약함), 2(보통), 3(강함)* Steps: 1 (weak), 2 (medium), 3 (strong)
전술한 각 실시예에서 예시된 특징, 구조, 효과 등은 실시예들이 속하는 분야의 통상의 지식을 가지는 자에 의하여 다른 실시예들에 대해서도 조합 또는 변형되어 실시 가능하다. 따라서 이러한 조합과 변형에 관계된 내용들은 본 발명의 범위에 포함되는 것으로 해석되어야 할 것이다.The features, structures, effects, and the like illustrated in the above-described embodiments may be combined or modified with respect to other embodiments by those skilled in the art to which the embodiments belong. Therefore, it should be interpreted that the contents related to such a combination and modification are included in the scope of the present invention.

Claims (13)

  1. 마유와 나노다이아몬드를 레시틴을 통해 유화시켜 나노리포좀을 형성하는 나노리포좀 제조방법.Nanoliposome manufacturing method of emulsifying horse oil and nanodiamonds through lecithin to form nanoliposomes.
  2. 나노다이아몬드와 기능성 성분을 포함하는 수상용액을 제조하는 단계인 수상용액 제조단계; A water phase solution preparation step of preparing a water phase solution containing nanodiamonds and a functional component;
    마유와 인지질을 포함하는 유상용액을 제조하는 단계인 유상용액 제조단계; 및 An oil phase preparation step of preparing an oil phase solution containing horse oil and phospholipids; And
    상기 수상용액과 상기 유상용액을 혼합 교반하여 나노리포좀을 형성하는 단계인 리포좀 제조단계;를 포함하는 나노리포좀 제조방법. And a liposome manufacturing step of mixing and stirring the aqueous solution and the oily solution to form nanoliposomes.
  3. 제2항에 있어서,The method of claim 2,
    상기 수상용액 제조단계는 기능성 식물 추출 생리 활성 성분을 나노다이아몬드와 함께 정제수에 첨가하고 80~100℃ 으로 가온하며 용해시키는 단계인 것을 특징으로 하는 나노리포좀 제조방법.Said aqueous solution manufacturing step is a nano liposome manufacturing method characterized in that the functional plant extract physiologically active ingredient is added to the purified water together with the nanodiamond and warmed to 80 ~ 100 ℃.
  4. 제2항에 있어서,The method of claim 2,
    상기 나노다이아몬드는 탄소의 폭발법에 의해 만들어진 결함이 있는 그래핀 구조를 갖는 1~100nm 크기의 분말인 것을 특징으로 하는 나노리포좀 제조방법.The nanodiamond is a nano liposome manufacturing method characterized in that the powder of 1 ~ 100nm size having a defective graphene structure made by the explosion method of carbon.
  5. 제2항에 있어서,The method of claim 2,
    상기 수상용액 제조단계는 상기 나노다이아몬드 1 내지 5 ppm 수용액을 상기 수상용액과 유상용액의 혼합물 총 중량에 대해 10 내지 50 중량%의 범위로 포함하여 수상용액을 제조하는 단계인 것을 특징으로 하는 나노리포좀 제조방법.The aqueous phase preparation step is a nanoliposome comprising the nanodiamond 1 to 5 ppm aqueous solution in a range of 10 to 50% by weight based on the total weight of the mixture of the aqueous phase solution and the oil phase solution Manufacturing method.
  6. 제2항에 있어서,The method of claim 2,
    상기 유상용액 제조단계는 마유를 80~100℃ 가온하면서 인지질에 용해시키는 단계인 것을 특징으로 하는 나노리포좀 제조방법.The oil phase manufacturing step is a nano liposome manufacturing method characterized in that the step of dissolving horse oil in phospholipids while heating 80 ~ 100 ℃.
  7. 제6항에 있어서,The method of claim 6,
    상기 유상용액 제조단계는 상기 마유를 상기 수상용액과 유상용액의 혼합물 총 중량에 대해 20 내지 40 중량%의 범위로 포함하고, 상기 인지질을 상기 수상용액과 유상용액의 혼합물 총 중량에 대해 1.5 내지 3.5 중량%의 범위로 포함하여 유상용액을 제조하는 단계인 것을 특징으로 하는 나노리포좀 제조방법.The oil phase preparation step includes the horse oil in the range of 20 to 40% by weight based on the total weight of the mixture of the aqueous solution and the oil solution, and the phospholipid 1.5 to 3.5 with respect to the total weight of the mixture of the aqueous solution and the oil solution Nanoliposome production method characterized in that it comprises the step of preparing an oily solution in a range of weight%.
  8. 제2항에 있어서,The method of claim 2,
    상기 리포좀 제조단계는 상기 수상용액에 상기 유상용액을 첨가하면서 교반하고, 교반 후 온도가 40℃ 이하가 되었을 때 마이크로플루다이저를 이용하여 반복 가공함으로써 나노리포좀을 형성하는 단계인 것을 특징으로 하는 나노리포좀 제조방법.The liposome manufacturing step is a step of forming a nano liposome by stirring by adding the oily solution to the aqueous solution, and repeatedly processing using a microfluidizer when the temperature after the stirring is 40 ℃ or less Liposome preparation method.
  9. 제2항에 있어서,The method of claim 2,
    상기 리포좀 제조단계는 상기 수상용액에 상기 유상용액을 부어가면서 30분 내지 60분 동안 교반하고, 온도 40℃ 이하가 되었을 때 마이크로플루다이저를 이용하여 20,000 내지 30,000psi 압력으로 2회 내지 5회 반복 가공함으로써 나노리포좀을 형성하는 단계인 것을 특징으로 하는 나노리포좀 제조방법.The liposome preparation step is stirred for 30 minutes to 60 minutes while pouring the oily solution to the aqueous solution, and repeated 2 to 5 times at a pressure of 20,000 to 30,000psi using a microfluidizer when the temperature is 40 ℃ or less Nano liposome manufacturing method characterized in that the step of forming a nano liposome by processing.
  10. 결함이 있는 나노다이아몬드가 포함된 수상용액과 마유 및 인지질이 포함된 유상용액을 유화시켜 제조된 나노리포좀이며,It is a nano liposome prepared by emulsifying an aqueous solution containing a defective nanodiamond and an oil solution containing horse oil and phospholipids,
    기능성 식물 추출 생리 활성 성분이 상기 나노다이아몬드의 결함이 있는 부분에 결착되어 포함된 나노리포좀.A nanoliposome containing a functional plant extract bioactive component bound to a defective portion of the nanodiamond.
  11. 제10항에 있어서,The method of claim 10,
    상기 나노리포좀은 상기 기능성 식물 추출 생리 활성 성분이 결함이 있는 부분에 결착되어 있는 나노다이아몬드가 포함된 수상코어, 상기 수상코어를 둘러싼 인지질로 구성된 유상쉘을 포함하여 구성된 것을 특징으로 하는 나노리포좀.The nanoliposomes are nanoliposomes, characterized in that the functional plant extract physiologically active component is composed of an aqueous core containing nanodiamonds bound to a defective portion, an oil shell consisting of a phospholipid surrounding the water core.
  12. 기능성 식물 추출 생리 활성 성분이 나노다이아몬드의 결함이 있는 부분에 결착된 상태로 수상코어에 포함된 나노리포좀을 유효성분으로 포함하는 약제학적 조성물.A pharmaceutical composition comprising a nanoliposome contained in a water core as an active ingredient in a state in which a functional plant extract bioactive component is bound to a defective portion of nanodiamonds.
  13. 기능성 식물 추출 생리 활성 성분이 나노다이아몬드의 결함이 있는 부분에 결착된 상태로 수상코어에 포함된 나노리포좀을 유효성분으로 포함하는 화장료 조성물.A cosmetic composition comprising a nanoliposome contained in a water core as an active ingredient in a state in which a functional plant extract bioactive component is bound to a defective portion of nanodiamonds.
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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20090040144A (en) * 2007-10-19 2009-04-23 한국생산기술연구원 Nanoemulsion composition comprising vitamin-c derivative and method for preparing thereof
KR20100104144A (en) * 2009-03-16 2010-09-29 주식회사 제마유 Skin whitening composition comprising horse fats and horse placenta extracts encapsulated in water soluble nanoliposome
KR101621194B1 (en) * 2014-06-27 2016-05-13 제주대학교 산학협력단 Liposome included horse oil, the method preparing thereof and composition for treating burn or uv-cut containing the same
KR20160132296A (en) * 2015-05-08 2016-11-17 나노리소스 주식회사 Dermal delivery method of physiologically active ingredient using nanodiamond
KR20160132295A (en) * 2015-05-08 2016-11-17 나노리소스 주식회사 Physiologically active ingredient-nanodiamond hybrid, and composition comprising the same

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20090040144A (en) * 2007-10-19 2009-04-23 한국생산기술연구원 Nanoemulsion composition comprising vitamin-c derivative and method for preparing thereof
KR20100104144A (en) * 2009-03-16 2010-09-29 주식회사 제마유 Skin whitening composition comprising horse fats and horse placenta extracts encapsulated in water soluble nanoliposome
KR101621194B1 (en) * 2014-06-27 2016-05-13 제주대학교 산학협력단 Liposome included horse oil, the method preparing thereof and composition for treating burn or uv-cut containing the same
KR20160132296A (en) * 2015-05-08 2016-11-17 나노리소스 주식회사 Dermal delivery method of physiologically active ingredient using nanodiamond
KR20160132295A (en) * 2015-05-08 2016-11-17 나노리소스 주식회사 Physiologically active ingredient-nanodiamond hybrid, and composition comprising the same

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