KR20230000400A - Oxygen gas sustained released nano-emulsion composition and method for producing the same - Google Patents

Abstract

The present invention relates to an oxygen gas sustained-release nanoemulsion composition and a preparation method thereof and, more specifically, to an oxygen gas sustained-release nanoemulsion composition and a preparation method thereof, wherein the composition contains: a water phase portion comprising water; and an oil phase portion composed of nanoparticles dispersed in the water phase portion and containing a perfluorocarbon compound. The oil phase portion contains oxygen gas, and the oxygen gas is released in a sustained release. In the present invention, the hair loss can be prevented and hair growth can be promoted by increasing the amount and release time of oxygen gas supplied to hair bulbs.

Description

Oxygen gas sustained released nano-emulsion composition and method for producing the same

In the present specification, the water phase containing water; and an oil phase portion comprising nanoparticles dispersed in the aqueous phase portion and containing a perfluorocarbon compound, wherein the oil phase portion contains oxygen gas and the oxygen gas is released in a sustained release form. A manufacturing method thereof is disclosed.

Most animals lose their hair at once according to the season and shed new hair, but humans lose about 100 hairs out of a total of about 100,000 hairs every day, and about 100 new hairs are born, always maintaining a similar number. Hair is not an important organ for maintaining life, but it is an important part of the body that determines the appearance and measures the state of health. Therefore, although hair loss is considered a natural physical activity for ordinary people with a lot of hair, the mental well-being and quality of life of people with hair loss can be seriously affected due to depression, shame, social isolation, etc.

The cycle of hair can be largely divided into three cycles: the growth phase, the regression phase, and the telogen phase. Among them, the anagen phase is a period in which active cell division occurs in the dermal papilla to promote the growth of new hair, and hair grows only in this period. Each hair has a growth period of about 3 to 5 years for men and 4 to 6 years for women, so when viewed as a whole, about 80 to 85% of hair corresponds to the growth period. The catagen phase is a period in which cell division gradually stops, and is about 3 to 4 weeks. Finally, the telogen period is about 3 months when the hair papilla atrophy and the hair is separated from the capillaries and simply embedded in the scalp, and the hair in the telogen phase usually falls out easily due to physical stimulation.

Korean Patent Publication No. 10-2010-0116882 discloses that a composition containing a natural extract can be applied to prevent hair loss or promote hair growth. However, according to the process of baldness (hair loss) of the scalp, a phenomenon in which microvessels connected to hair roots become thin, and this occurs due to insufficient oxygen supply through the microvessels. As a basis for hair loss due to a lack of oxygen, it has been reported that lactate, which occurs when oxygen metabolism is insufficient, accumulates, and when treated with an enzyme that decomposes such lactate (Lactate dehydrogenase), hair stem cells There have been reports of increased activity again. In summary, oxygen is the most important factor to promote or maintain the growth of dermal papilla cells, which are located in the center of the hair follicle and are the basis for new hair production (Non-Patent Document 1).

Since oxygen for activating the metabolism of dermal papilla cells is a gas, it cannot permeate through the skin in a general way. Accordingly, research and development on a composition capable of preventing hair loss or promoting hair growth by increasing the amount of oxygen supplied to the hair bulb is further required.

Republic of Korea Patent Publication No. 10-2010-0116882

Aimee et al. “Lactate dehydrogenase activity drives hair follicle stem cell activation”, nature cell biology 19, pp 1017-1026 (2017)

The present disclosure has been made to solve the above problems, and an object of the present disclosure is to provide a composition capable of preventing hair loss or promoting hair growth by increasing the amount and release time of oxygen gas supplied to hair follicles and a method for producing the same. is to do

In order to achieve the above object of the present disclosure, the present disclosure includes a water phase portion containing water; and an oil phase portion comprising nanoparticles dispersed in the aqueous phase portion and containing a perfluorocarbon compound, wherein the oil phase portion contains oxygen gas, and the oxygen gas is released in a sustained release form. And it provides a manufacturing method thereof.

According to the present disclosure, there is an advantage in that it is possible to prevent hair loss or promote hair growth by increasing the amount and release time of oxygen gas supplied to hair bulbs.

1 is a graph showing the size of nanoemulsion according to the type and content ratio of surfactants and auxiliary surfactants.
Figure 2 is a graph showing the oxygen encapsulation rate of the nanoemulsion according to the content of the perfluorocarbon compound.
Figure 3 is a graph showing the oxygen release of the nanoemulsion according to the content of the perfluorocarbon compound.
Figure 4 is a graph showing the results of cytotoxicity evaluation.
Figure 5 is a graph showing the change in oxygen level by the nano-emulsion.
Figure 6 is an image showing the cell growth evaluation results.
Figure 7 is a graph showing the quantification of cell growth evaluation results.
Figure 8 is an image showing the hair follicle growth evaluation results.
Figure 9 is a graph showing the quantification of hair follicle growth evaluation results.
10 and 11 are graphs showing the results of evaluation of the size and polydispersity index of nanoemulsion.
12 is a graph showing the size evaluation results of nanoemulsion according to temperature and time.
13 is a graph showing the oxygen encapsulation rate evaluation results of the nanoemulsion composition.
14 is a graph showing the oxygen encapsulation rate evaluation results of the nanoemulsion composition over time.
15 and 16 are graphs showing the results of evaluation of the particle size and polydispersity index of the nanoemulsion composition according to the content of the main surfactant and the auxiliary surfactant.
17 is a graph showing the results of evaluation of particle size and polydispersity index of nanoemulsion compositions according to temperature and time.
18 to 20 are graphs showing the results of evaluation of the particle size and polydispersity index of the nanoemulsion composition according to the content of the main surfactant and the auxiliary surfactant.
21 is a graph showing the oxygen encapsulation rate evaluation results of the nanoemulsion composition.
22 is a graph showing the oxygen release rate evaluation results of the nanoemulsion composition.

The terms used in this specification have been selected from general terms that are currently widely used as much as possible while considering the functions in the present disclosure, but they may vary according to the intention of a person skilled in the art, precedent, or the emergence of new technologies. In addition, in a specific case, there is also a term arbitrarily selected by the applicant, and in this case, the meaning will be described in detail in the description of the invention. Therefore, terms used in the present disclosure should be defined based on the meaning of the term and the general content of the present disclosure, not simply the name of the term.

Unless defined otherwise, all terms used herein, including technical or scientific terms, have the same meaning as commonly understood by one of ordinary skill in the art to which the present invention belongs. Generally understood terms should be interpreted as having the same meaning as they have in the context of the related art, and unless explicitly defined in the present disclosure, they are not to be interpreted in an ideal or overly formal sense.

Numeric ranges are inclusive of the numbers defined in this disclosure. Every maximum numerical limitation given throughout this specification includes every lower numerical limitation, as if such lower numerical limitations were expressly written. Every minimum numerical limitation given throughout this specification includes every higher numerical limitation, as if such higher numerical limitations were expressly written. Every numerical limitation given throughout this specification will include every better numerical range within the broader numerical range, as if the narrower numerical limitations were expressly written.

As used herein, the words “comprising”, “having”, “including” are inclusive or open-ended and do not exclude additional unrecited elements or method steps. As used herein, the term “or combinations thereof” refers to all permutations and combinations of the items listed prior to the term. For example, “A, B, C, or combinations thereof” could mean A, B, C, AB, AC, BC, or ABC, and where order is important in a particular context, BA, CA, CB, CBA, BCA , ACB, BAC or CAB. Along with this example, combinations containing repetitions of one or more items or terms are expressly included, such as BB, AAA, MB, BBC, AAABCCCC, CBBAAA, CABABB, and the like. Those skilled in the art will understand that there is typically no limit to the number of items or terms in any combination, unless the context clearly dictates otherwise.

Hereinafter, the present disclosure will be described in detail with reference to examples and drawings. However, it is apparent that the present invention is not limited by the following examples and drawings.

In one aspect, the present disclosure provides an aqueous phase comprising water; And an oil phase portion dispersed in the water phase portion and composed of nanoparticles containing a perfluorocarbon compound, wherein the oil phase portion contains oxygen gas, and the oxygen gas is released in a sustained release form. A nanoemulsion composition is provided.

Unlike the microemulsion, the nanoemulsion is only kinetically stable, and since there is no aggregation or coalescence between particles, it is stable for a long time even under low viscosity conditions. The reason why the nanoemulsion is used as a useful formulation is that (1) the particles are very small and are not affected by gravity due to the Brownian motion of the particles, so they are free from sedimentation or creaming, (2) aggregation into small particles (3) Small particles have little deformation of particles, which prevents coalescence, (4) Small particles have a wide interface membrane to improve skin penetration of active ingredients. and (5) that it can be prepared with significantly less surfactant than microemulsion. The nanoemulsion may be an oil-in-water (O/W) emulsion.

The "oxygen gas" may be naturally occurring oxygen or synthetically produced oxygen. Generally, it is known that the oxygen concentration in the atmosphere is at a level of 20 to 22%, and an oxygen condition of about 20% is called a normal oxygen condition. Oxygen conditions of 1% to 5% are called hypoxia conditions, and oxygen conditions of 1% or less are called extreme hypoxia or anoxia conditions. Since hair follicles can grow in an oxygen condition of 0.1% to 0.8%, it is necessary to maintain the oxygen condition in order to prevent hair loss or promote hair growth.

In the present disclosure, the term "immediate release type" means a formulation in which the active ingredient is immediately released, and is a formulation that releases most of the active ingredient within a few seconds. In contrast, the term “sustained-release type” refers to a formulation that slowly releases an active ingredient for several tens of seconds to several hours, and is designed to maintain an effective amount of the active ingredient over a relatively long period of time. Because of the characteristics of the “sustained-release” dosage form, which lasts for a certain amount of time after reaching the therapeutic blood concentration, it means a dosage form with fewer side effects due to less frequent administration than normal preparations and uniform biological response. The nanoemulsion composition of the present disclosure exhibits an “oxygen gas sustained release” profile, and thus may release oxygen for a period of at least 10 seconds or maintain oxygen conditions favorable for preventing hair loss or promoting hair growth.

According to one embodiment of the present disclosure, the average diameter of the nanoparticles may be 100 nm to 300 nm. More specifically, 100 nm or more, 110 nm or more, 120 nm or more, 130 nm or more, 140 nm or more, 150 nm or more, 160 nm or more, 170 nm or more, 180 nm or more, 190 nm or more, 200 nm or more; 300 nm or less, 290 nm or less, 280 nm or less, 270 nm or less, 260 nm or less, 250 nm or less, 240 nm or less, 230 nm or less, 220 nm or less, 210 nm or less, 200 nm or less, but is not limited thereto no.

According to one embodiment of the present disclosure, the oxygen gas may be captured in an amount of 1 ppm (v/w) to 35 ppm (v/w) based on the total weight of the nanoemulsion composition. More specifically, 1 ppm (v/w) or more, 5 ppm (v/w) or more, 10 ppm (v/w) or more, 15 ppm (v/w) or more, 20 ppm (v/w) or more, 21 22 ppm (v/w) or more, 23 ppm (v/w) or more, 24 ppm (v/w) or more, 25 ppm (v/w) or more, 26 ppm (v/w) or more ) or more, 27 ppm (v/w) or more, 27.1 ppm (v/w) or more; 35 ppm (v/w) or less, 34 ppm (v/w) or less, 33 ppm (v/w) or less, 32 ppm (v/w) or less, 31 ppm (v/w) or less, 30 ppm (v/w) or less w) or less, 29 ppm (v/w) or less, 28 ppm (v/w) or less, or 27.1 ppm (v/w) or less, but is not limited thereto.

The perfluorocarbon compound is a completely fluorine-substituted hydrocarbon compound, and the completely fluorine-substituted hydrocarbon compound refers to a hydrocarbon compound in which all hydrogen atoms are substituted with fluorine atoms. The perfluorocarbon compound has very low viscosity, low surface tension, excellent spreadability, high fluidity, low dielectric constant, high vapor pressure, high compressibility and high gas solubility. is a substance with

Examples of the perfluorocarbon compound include cyclic or non-cyclic fluorinated hydrocarbons, and include perfluorinated aliphatic hydrocarbons and fluorinated aromatic hydrocarbons. Preferably, examples of the perfluorocarbon compound include chain fluorinated aliphatic hydrocarbons having 1 to 12 carbon atoms, and cyclic fluorinated aliphatic hydrocarbons having 3 to 12 carbon atoms having one or two rings. hydrocarbons.

Examples of chain-like fluorinated aliphatic hydrocarbons having 1 to 12 carbon atoms include perfluorohexane, perfluoroheptane, perfluorooctane, perfluorononane, perfluorodecane, perfluoroundecane and perfluorodo Decane can be mentioned.

Examples of cyclic fluorinated aliphatic hydrocarbons having 1 or 2 rings and having 3 to 12 carbon atoms include perfluorocyclohexane, perfluorodimethylcyclohexane, perfluoroisopropylcyclohexane, perfluorodecalin, perfluoromethyldecalin, and compounds structurally similar to these compounds.

According to one embodiment of the present disclosure, the perfluorocarbon compound may be a perfluoroalkyl halide. The perfluoroalkyl halide refers to a compound having a non-fluorine substituent, and examples thereof include perfluoroalkyl chloride, perfluoroalkyl bromide, and perfluoroalkyl iodide. The alkyl group of the perfluoroalkyl halide may have 1 to 12 carbon atoms. According to one embodiment of the present disclosure, the perfluorocarbon compound may be perfluorooctylbromide (PFOB).

According to one embodiment of the present disclosure, the perfluorocarbon compound is a chain fluorinated aliphatic hydrocarbon having 1 to 12 carbon atoms and a cyclic fluorinated aliphatic hydrocarbon having 3 to 12 carbon atoms having one or two rings. is one or more hydrocarbons. According to one embodiment of the present disclosure, the perfluorocarbon compound is a chain fluorinated aliphatic hydrocarbon having 1 to 12 carbon atoms and a cyclic fluorinated aliphatic hydrocarbon having 3 to 12 carbon atoms having one or two rings. It is a combination of hydrocarbons.

According to one embodiment of the present disclosure, the perfluorocarbon compound is at least one of perfluorodecalin (PFD) and perfluorohexane (PFH). According to one embodiment of the present disclosure, the perfluorocarbon compound is a combination of perfluorodecalin (PFD) and perfluorohexane (PFH).

According to one embodiment of the present disclosure, the perfluorocarbon compound is a combination of perfluorodecalin (PFD) and perfluorohexane (PFH), and the perfluorodecalin (PFD) and perfluorohexane ( The content ratio of PFH) is 6: 1 to 1: 3 by weight. more specifically 6:1 or higher, 5.5:1 or higher, 5:1 or higher, 4.5:1 or higher, 4:1 or higher, 3.5:1 or higher, 3:1 or higher; 1: 3 or less, 1: 2.5 or less, 1: 2 or less, 1: 1.5 or less, 1: 1 or less, 1.5: 1 or less, 2: 1 or less, 2.5: 1 or less, 3: 1 or less, but is limited thereto It is not. According to one embodiment of the present disclosure, the content ratio of perfluorodecalin (PFD) and perfluorohexane (PFH) is 3:1 based on weight.

According to one embodiment of the present disclosure, the content of the perfluorocarbon compound may be 5 to 80% by weight based on the total weight of the nanoemulsion composition. More specifically, 5% by weight or more, 10% by weight or more, 15% by weight or more, 20% by weight or more, 25% by weight or more, 30% by weight or more, 35% by weight or more, 40% by weight or more, 45% by weight or more, 50% by weight or more greater than or equal to 55%, greater than or equal to 60% by weight; 80 wt% or less, 75 wt% or less, 70 wt% or less, 65 wt% or less, or 60 wt% or less, but is not limited thereto.

According to one embodiment of the present disclosure, the oil phase part further includes at least one of phospholipids, polyglycerin stearic acid esters, and fatty acid esters of sorbitan as a main surfactant, and the nanoemulsion composition contains cholesterol and glyceryl as auxiliary surfactants. diesters, inulin fatty acid esters, polyglycerin lauric acid esters, carboxylate salts of glutamic acid, and fatty acid esters of ethoxylated sorbitan.

In the present disclosure, when different surfactants are used, a surfactant having a relatively high emulsifying power (surfactant activity) is referred to as a "main surfactant". Compared to the case of using one type of surfactant, when mixed with the auxiliary surfactant, a synergistic effect of distributing the surfactant faster, denser, and more in the inner phase is exhibited.

According to one embodiment of the present disclosure, the total content of the auxiliary surfactant may be 0.1 to 10% by weight based on the total weight of the nanoemulsion composition. More specifically, 0.1% by weight or more, 0.2% by weight or more, 0.3% by weight or more, 0.4% by weight or more, 0.5% by weight or more, 0.6% by weight or more, 0.7% by weight or more, 0.8% by weight or more, 0.9% by weight or more, 1 1.5% or more, 2% or more, 2.5% or more, 3% or more, 3.5% or more, 4% or more, 4.5% or more, 5% or more; 10 wt% or less, 9 wt% or less, 8 wt% or less, 7 wt% or less, 6 wt% or less, 5 wt% or less, but is not limited thereto.

According to one embodiment of the present disclosure, the content ratio of the main surfactant and the auxiliary surfactant may be 10:1 to 1:3 based on weight. More specifically, 10:1 or higher, 9.5:1 or higher, 9:1 or higher, 8.5:1 or higher, 8:1 or higher, 7.5:1 or higher, 7:1 or higher, 6.5:1 or higher, 6:1 or higher, 5.5:1 or higher 1 or more, 5:1 or more, 4.5:1 or more, 4:1 or more; 1:3 or less, 1:2.5 or less, 1:2 or less, 1:1.5 or less, 1:1 or less, 1.5:1 or less, 2:1 or less, 2.5:1 or less, 3:1 or less, 3.5:1 or less, It may be 4: 1 or less, but is not limited thereto.

Examples of the phospholipid include lecithin, hydrogenated lecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol. According to one embodiment of the present disclosure, the phospholipid is at least one selected from the group consisting of lecithin, hydrogenated lecithin, and phosphatidylcholine. The phosphatidylcholine may be a naturally derived phosphatidylcholine or a synthetic or highly purified phosphatidylcholine. According to one embodiment of the present disclosure, the phospholipid may be egg phosphatidylcholine and/or soy phosphatidylcholine.

According to one embodiment of the present disclosure, the polyglycerin stearic acid ester is polyglyceryl-10 stearate, polyglyceryl-10 isostearate, polyglyceryl-10 diisostearate and polyglyceryl-10 distearate. It is at least one selected from the group consisting of rates. According to one embodiment of the present disclosure, the polyglycerin stearic acid ester is polyglyceryl-10 stearate.

According to one embodiment of the present disclosure, the fatty acid ester of sorbitan is sorbitan monolaurate (Span 20), sorbitan monopalmitate (Span 40), sorbitan monostearate (Span 60), sorbitan monooli It may be at least one selected from the group consisting of ate (Span 80) and sorbitan isostearate (Span 120).

According to one embodiment of the present disclosure, the glyceryl diester (= diglyceride, diacylglycerol) is glyceryl dilaurate, glyceryl diarachidate, glyceryl dibehenate, glyceryl dielucate, glyceryl Dihydroxystearate, Glyceryl Diisopalmitate, Glyceryl Diisostearate, Glyceryl Dilinoleate, Glyceryl Dimyristate, Glyceryl Dioleate, Glyceryl Diricinoleate, Glyceryl Dipalmitate , Glyceryl dipalmitoleate, glyceryl distearate, glyceryl palmitate lactate, glyceryl stearate citrate, glyceryl stearate lactate and glyceryl stearate succinate is at least one selected from the group consisting of . According to one embodiment of the present disclosure, the glyceryl diester is glyceryl stearate citrate.

According to one embodiment of the present disclosure, the inulin fatty acid ester is inulin octanoate, inulin decanoate, inulin laurate, inulin myristate, inulin lauryl carbamate, inulin palmitate, inulin stearate, inulin arachidate , Inulin behenate, inulin oleate, inulin 2-ethylhexanoate, inulin isomiristate, inulin isopalmitate, inulin isostearate and inulin isooleate. According to one embodiment of the present disclosure, the inulin fatty acid ester is inulin lauryl carbamate.

According to one embodiment of the present disclosure, the polyglycerol lauric acid ester is at least one selected from the group consisting of polyglyceryl-2 laurate and polyglyceryl-10 laurate. According to one embodiment of the present disclosure, the polyglycerin lauric acid ester is polyglyceryl-10 laurate.

According to one embodiment of the present disclosure, the carboxylate salt of glutamic acid is sodium cocoyl glutamate, sodium lauroyl glutamate, sodium myristoyl glutamate, sodium palmitoyl glutamate, sodium stearoyl glutamate, disodium cocoyl glutamate, and at least one selected from the group consisting of disodium stearoyl glutamate, potassium cocoyl glutamate, potassium lauroyl glutamate, and potassium myristoyl glutamate. According to one embodiment of the present disclosure, the carboxylate salt of glutamic acid is sodium stearoyl glutamate.

According to one embodiment of the present disclosure, examples of the fatty acid ester of the ethoxylated sorbitan include PEG-20 sorbitan monolaurate (Tween 20), PEG-4 sorbitan monolaurate (Tween 21), PEG-20 Sorbitan monopalmitate (Tween 40), PEG-20 sorbitan monostearate (Tween 60), PEG-4 sorbitan monostearate (Tween 61), PEG-20 sorbitan monooleate (Tween 80) can According to one embodiment of the present disclosure, the nonionic surfactant may be Tween 80.

According to one embodiment of the present disclosure, the composition has an oxygen gas concentration at the time of 10 seconds or more after the start of dissolution (for example, when the composition is in contact with the atmospheric layer, the system may be the atmospheric layer) and equilibrium (equilibrium). ) can be reached. Therefore, oxygen gas can be released for 10 seconds or longer until equilibrium is reached. More specifically, 10 seconds or more, 20 seconds or more, 30 seconds or more, 40 seconds or more, 50 seconds or more, 1 minute or more, 3 minutes or more, 5 minutes or more, 10 minutes or more, 30 minutes or more, 1 hour or more, 2 hours or more more than 3 hours, more than 4 hours, more than 5 hours, more than 6 hours, more than 7 hours, more than 8 hours, more than 9 hours, more than 10 hours, more than 20 hours, more than 30 hours, more than 32 hours, more than 34 hours, 36+ hours, 38+ hours, 40+ hours, 42+ hours, 44+ hours, 46+ hours, 48+ hours, 50+ hours, 60+ hours, 70+ hours, 80+ hours, 90+ hours, 100+ hours It may be more than 110 hours, more than 120 hours, more than 130 hours, more than 140 hours, but is not limited thereto.

The term “equilibrium” means a state in which the rate of oxygen gas transfer between the composition of the present disclosure and the cage in contact with the composition is the same, so that the amount of oxygen gas in the composition is maintained at a constant level. As the oxygen gas is released in a sustained release form from the nanoemulsion of the present disclosure, the oxygen gas concentration of the composition reaches equilibrium with the system or after reaching equilibrium, the time for continuously releasing oxygen gas into the system is a relatively long time, such as 1 minute or more. can

According to one embodiment of the present disclosure, the composition may be a composition for preventing hair loss or promoting hair growth.

The “hair loss” may refer to a state in which there is no hair in an area where hair is normally present, and may mean, for example, that hair on the scalp is lost. In addition, the “hair growth promotion” may mean not only promotion of new hair growth but also healthy growth of existing hair.

The prevention of hair loss or promotion of hair growth may be due to the proliferation of hair follicle cells or the growth of hair. Specifically, the proliferation of the hair follicle cells means the proliferation of dermal papilla cells or hair cells. The “dermal papilla cells” may refer to cells that play an important role in hair growth as skin cells surrounding hair follicles. The "hair cells" refer to cells that produce hair while being in the dermal papilla tissue. Specifically, the growth of the hair means that the hair papilla, supplied with nutrients and oxygen from the capillaries, transfers nutrients, various growth factors, and growth signals to the hair cells, while the hair cells divide. Therefore, in preventing hair loss or promoting hair growth, supply of nutrients and oxygen to dermal papilla cells and/or hair cells is an important factor. The present disclosure has been derived from the above matters, and an object of the present disclosure is to provide a composition capable of preventing hair loss or promoting hair growth by increasing the amount of oxygen supplied to hair bulbs.

According to one embodiment of the present disclosure, the composition may further include an additional hair loss prevention or hair growth promoting active ingredient. The active ingredient is prostaglandin E2 (PGE2), which can prevent hair loss or promote hair growth, such as an activity inhibitory effect on 5 alpha-reductase known as the main cause of hair loss, and hair loss caused by scalp inflammation. As long as it is a component capable of exhibiting an activity inhibitory effect, the type is not limited.

According to one embodiment of the present disclosure, the composition may be an external preparation for skin. The term "skin" means a tissue covering the body surface of an animal, and is a concept in the broadest sense that includes not only tissues covering the body surface such as the face or body, but also the scalp and hair.

According to one embodiment of the present disclosure, the composition may be a cosmetic, pharmaceutical or food composition.

Specifically, in the cosmetic composition, the formulation is not particularly limited, and according to one embodiment of the present disclosure, the composition may be formulated by a conventional method. In formulation, reference may be made to the contents disclosed in the International Cosmetic Ingredient Dictionary (INCI) published by The Cosmetic, Toiletry and Fragrance Association.

Specifically, the composition is a hair rinse, shampoo, hair conditioner, hair pack, hair oil, hair treatment, hair cream, hair lotion, hair gel, hair essence, hair spray, hair serum, hair ampoule, emulsion, cream, essence etc. can be formulated. The formulation may be of a rinse-off type or a wash-off type, meaning that the formulation is rinsed after application to the hair; Alternatively, it may be of a leave-on or leave-in type, meaning that the formulation remains on the hair after application.

The composition may include fatty substances, organic solvents, solubilizers, thickeners, gelling agents, softeners, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, Surfactants, preservatives, pH adjusters, water, ionic or nonionic emulsifiers, fillers, sequestering agents, chelating agents, preservatives, barrier agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic actives, cosmetics Adjuvants commonly used in the field of cosmetology or dermatology, such as any other commonly used ingredients, may additionally be contained as necessary.

When the formulation of the cosmetic composition is a solution or emulsion, a solvent, solubilizing agent or emulsifying agent is used as a carrier component, such as water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, 1,3-butylglycol oil, fatty acid esters of glycerol, polyethylene glycol or sorbitan.

When the formulation of the cosmetic composition is a suspension, as a carrier component, a liquid diluent such as water, ethanol or propylene glycol, an ethoxylated isostearyl alcohol, a suspension agent such as polyoxyethylene sorbitol ester and polyoxyethylene sorbitan ester, Crystalline cellulose, aluminum metahydroxide, bentonite, agar or tracanth and the like may be used.

When the formulation of the cosmetic composition is a paste, cream or gel, animal oil, vegetable oil, wax, paraffin, starch, tracanth, cellulose derivative, polyethylene glycol, silicone, bentonite, silica, talc or zinc oxide are used as carrier components It can be.

The cosmetic composition may additionally contain a thickening agent. The thickener included in the cosmetic composition is methyl cellulose, carboxy methyl cellulose, carboxy methyl hydroxyguanine, hydroxy methyl cellulose, hydroxy ethyl cellulose, carboxy vinyl polymer, polyquaternium, cetearyl alcohol, stearic acid, Carrageenan and the like may be used, preferably at least one of carboxy methyl cellulose, carboxy vinyl polymer, and polyquaternium, and most preferably carboxy vinyl polymer.

The cosmetic composition may contain various appropriate bases and additives as needed, and the types and amounts of these components can be easily selected by the inventor. Acceptable additives may be included as needed, and for example, components such as preservatives, pigments, and additives common in the art may be further included. The preservative may specifically be phenoxyethanol or 1,2-hexanediol, and the flavor may be artificial flavor.

The cosmetic composition may include a composition selected from the group consisting of water-soluble vitamins, oil-soluble vitamins, high-molecular peptides, high-molecular polysaccharides, sphingolipids, and seaweed extracts. Other ingredients that may be added include fats and oils, humectants, emollients, surfactants, organic and inorganic pigments, organic powders, ultraviolet absorbers, preservatives, bactericides, antioxidants, plant extracts, pH adjusters, alcohols, pigments, fragrances, A blood circulation accelerator, a cooling agent, an antiperspirant, purified water, etc. are mentioned. In addition, the blending components that may be added other than these are not limited thereto, and any of the above components can be blended within a range not impairing the objects and effects of the present invention.

In the pharmaceutical composition, the pharmaceutical composition may be in various oral or parenteral dosage forms. When formulated, it is prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants. Solid preparations for oral administration include tablets, pills, powders, granules, soft or hard capsules, etc. These solid preparations contain at least one excipient such as starch, calcium carbonate, and sucrose in one or more compounds. Alternatively, it is prepared by mixing lactose and gelatin. In addition to simple excipients, lubricants such as magnesium stearate and talc are also used. Liquid preparations for oral administration include suspensions, solutions for oral administration, emulsions, syrups, etc. In addition to water and liquid paraffin, which are commonly used simple diluents, various excipients such as wetting agents, sweeteners, aromatics, and preservatives may be included. there is. Formulations for parenteral administration include sterilized aqueous solutions, non-aqueous solvents, suspensions, emulsions, freeze-dried formulations, and suppositories. Propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable esters such as ethyl oleate may be used as non-aqueous solvents and suspending agents. As a base for suppositories, witepsol, macrogol, Tween 61, cacao butter, laurin paper, glycerogelatin, and the like may be used.

The pharmaceutical dosage form of the pharmaceutical composition may be used alone or in combination with other pharmaceutically active compounds as well as in a suitable set. The salt is not particularly limited as long as it is pharmaceutically acceptable, and examples thereof include hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrofluoric acid, hydrobromic acid, formic acid, tartaric acid, lactic acid, citric acid, fumaric acid, maleic acid, succinic acid, and methanesulfonic acid. , benzenesulfonic acid, toluenesulfonic acid, naphthalenesulfonic acid and the like can be used.

The pharmaceutical composition may be administered parenterally or orally as desired, and may be administered in one to several divided doses to be administered in an amount of 0.1 to 500 mg, preferably 1 to 100 mg per 1 kg of body weight per day. . The dosage for a specific patient may vary depending on the patient's weight, age, sex, health condition, diet, administration time, administration method, excretion rate, severity of the disease, and the like.

The pharmaceutical composition may be formulated according to conventional methods, such as oral formulations such as powders, granules, tablets, soft or hard capsules, suspensions, emulsions, syrups and aerosols, external preparations for the skin such as ointments and creams, suppositories, injections and sterile injections. It may be formulated and used in any form suitable for pharmaceutical preparations, including solutions, etc., and may be preferably formulated and used in the form of injections or external preparations for the skin.

The pharmaceutical composition may be administered to mammals such as rats, mice, livestock, and humans through various routes such as parenteral and oral, and all modes of administration may be expected, for example, oral and transdermal ), can be administered by intravenous, intramuscular or subcutaneous injection. The pharmaceutical composition may be administered through various routes that can be easily applied by those skilled in the art. In particular, the pharmaceutical composition may be administered through a route applied to the skin surface as an external preparation for skin.

In the food composition, the food composition may be a health functional food composition. The formulation of the food composition is not particularly limited, but may be formulated into, for example, tablets, granules, powders, liquids such as drinks, caramels, gels, bars, and the like. The food composition of each formulation can be selected and blended without difficulty by those skilled in the art according to the formulation or purpose of use other than the active ingredient, and synergistic effects can occur when applied simultaneously with other ingredients.

In the food composition, the dosage determination of the active ingredient is within the level of a person skilled in the art, and its daily dosage is, for example, 0.1 mg/kg/day to 5000 mg/kg/day, more specifically 50 mg/kg. /day to 500 mg/kg/day, but is not limited thereto, and may vary depending on various factors such as the age, health condition, and complications of the subject to be administered.

The food composition may be, for example, various foods such as chewing gum, caramel products, candies, frozen confectionery, and confectionery, beverage products such as soft drinks, mineral water, and alcoholic beverages, and health functional foods including vitamins and minerals.

The food composition includes various nutrients, vitamins, minerals (electrolytes), flavors such as synthetic flavors and natural flavors, colorants and enhancers (cheese, chocolate, etc.), pectic acid and its salts, alginic acid and its salts, organic acids, protective colloidal thickeners, pH adjusters, stabilizers, preservatives, glycerin, alcohol, carbonating agents used in carbonated beverages, and the like. The functional food compositions may include natural fruit juice and fruit flesh for preparing fruit juice beverages and vegetable beverages. These components may be used independently or in combination. The ratio of these additives is not so critical, but in one aspect of the present invention, it is generally included in the range of 0 to about 20 parts by weight per 100 parts by weight of the composition.

In another aspect, the present disclosure provides water; oil; at least one of phospholipids and fatty acid esters of sorbitan; and preparing a first mixture by mixing a nonionic surfactant; preparing a second mixture by adding a perfluorocarbon compound to the first mixture; homogenizing the second mixture to prepare a crude emulsion; and bubbling oxygen into the crude emulsion.

A buffer solution may be further mixed in the step of preparing the first mixture. Examples of the buffer solution include HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid, 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), MES (2-(N-morpholino)ethanesulfonic acid) acid, 2-(N-morpholino)ethanesulfonic acid), PBS (Phosphated buffered saline), THAM (Tris(2-Amino-2 hydroxymethyl propane-1,3-diol), Tris(2- Amino-2-hydroxymethyl-propane-1,3-diol)), PB (Phosphate buffer), MOPS (3-(N-morpholino)propanesulfonic acid, 3-(N-morpholino)propanesul phonic acid).

The “homogenization” may include fluidization. The homogenization may include ultrasonic homogenization and high-pressure homogenization. The high-pressure homogenization may be performed under a pressure of 500 to 2500 bar.

Components mentioned in the preparation method may be applied with the same contents as those for the composition.

As another aspect, the present disclosure provides a water phase part containing water in preparing a nanoemulsion composition for preventing hair loss or promoting hair growth; and the use of an oil phase part comprising nanoparticles dispersed in the water phase part and containing a perfluorocarbon compound, wherein the oil phase part contains oxygen gas, and the oxygen gas is released in a sustained release form.

As another aspect, the present disclosure includes an aqueous phase containing water; And a step of applying a nanoemulsion composition comprising an oily phase dispersed in the aqueous phase and comprising nanoparticles containing a perfluorocarbon compound to a subject in need thereof, providing a method for preventing hair loss or promoting hair growth, The oil phase part contains oxygen gas, and the oxygen gas is released in a sustained release form.

As another aspect, the present disclosure provides an aqueous phase comprising water for use in preventing hair loss or promoting hair growth; and an oil phase part comprising nanoparticles dispersed in the water phase part and containing a perfluorocarbon compound, wherein the oil phase part contains oxygen gas, and the oxygen gas is released in a sustained release form.

{Example}

Hereinafter, the present disclosure will be described in detail by examples. However, the following examples are only examples for helping the overall understanding of the present disclosure, and the content of the present disclosure is not limited to the following examples.

<Preparation Example 1> Preparation of sustained-release oxygen nanoparticles

water; oleyl polyoxyl-6 glyceride and propylene glycol monocaprylate (Gatefosse, Saint-Priest, France); egg phosphatidylcholine or soy phosphatidylcholine (Lipoid, Ludwigshafen, Germany); and Tween 80 or Poloxamer 188 (Merck, Darmstadt, Germany) were dissolved in PBS (pH 7.4) and stirred at room temperature for 30 minutes using a magnetic stirrer. PFOB (Sinquest Laboratories, Florida, USA) was then added to the mixture and stirred for 30 minutes. The mixture was homogenized at 8100 rpm for 30 seconds in a high-speed homogenizer (HG-15A; Daehan Science, Wonju, Korea) to obtain a crude emulsion, and then in a LV1-30K microfluidizer (Microfluidics, Westwood, Massachusetts, USA). It was treated for 5 cycles at 15,000 psi (about 1034 bar). Next, oxygen was bubbled into the crude emulsion at a rate of 1 mL/min to prepare a nanoemulsion containing oxygen gas.

<Test Example 1> Evaluation of size of nanoemulsion according to type and content ratio of main surfactant and auxiliary surfactant

1. Material preparation

A nanoemulsion composition was prepared according to the composition of Table 1 below. The content of each component is expressed as a relative content ratio, and the unit is % by weight.

division PFOB egg phosphatidylcholine Span 80 Tween 80 Poloxamer 188 water Example 1 10 5 - - - to 100 Example 2 10 3.75 - - 1.25 to 100 Example 3 10 2.5 - - 2.5 to 100 Example 4 10 1.25 - - 3.75 to 100 Example 5 10 - - - 5 to 100 Example 6 10 5 - - - to 100 Example 7 10 3.75 - 1.25 - to 100 Example 8 10 2.5 - 2.5 - to 100 Example 9 10 1.25 - 3.75 - to 100 Example 10 10 - - 5 - to 100 Example 11 10 - 5 - - to 100 Example 12 10 - 3.75 - 1.25 to 100 Example 13 10 - 2.5 - 2.5 to 100 Example 14 10 - 1.25 - 3.75 to 100 Example 15 10 - - - 5 to 100 Example 16 10 - 5 - - to 100 Example 17 10 - 3.75 1.25 - to 100 Example 18 10 - 2.5 2.5 - to 100 Example 19 10 - 1.25 3.75 - to 100 Example 20 10 - - 5 - to 100

2. Size evaluation method of nanoemulsion

The particle size and surface charge of the prepared nanoemulsion were measured using a zeta potential/particle size analyzer (ELSZ-2000 series, Otsuka Electronics, Japan). The measurement was measured by diluting the nanoemulsion sample for evaluation using Phosphate Buffered Saline (PBS; Corning, USA) and then introducing it into the analyzer. The results are shown in Figure 1 (unit: nm).

3. Size evaluation result of nanoemulsion

Regarding the types of the main surfactant and auxiliary surfactant, it was confirmed from FIG. 1 that when Poloxamer 188 was used as the auxiliary surfactant, a non-nano emulsion with a diameter exceeding 1000 nm was produced. Therefore, it can be seen that it is particularly preferable to use Tween 80 as an auxiliary surfactant.

<Test Example 2> Evaluation of the particle size of the nanoemulsion composition according to the content ratio of the main surfactant and the auxiliary surfactant

The following test was performed to evaluate the change in particle size of the nanoemulsion composition according to the content of PFOB.

1. Material preparation

A nanoemulsion composition was prepared according to the composition shown in Table 2 below. The content of each component is expressed as a relative content ratio, and the unit is % by weight.

division PFOB soy phosphatidylcholine Span 80 Tween 80 water Example 21 40 1.88 - 0.63 to 100 Example 22 40 - 1.88 0.63 to 100 Example 23 40 3.75 - 1.25 to 100 Example 24 40 - 3.75 1.25 to 100 Example 25 50 1.88 - 0.63 to 100 Example 26 50 - 1.88 0.63 to 100 Example 27 50 3.75 - 1.25 to 100 Example 28 50 - 3.75 1.25 to 100 Example 29 60 1.88 - 0.63 to 100 Example 30 60 - 1.88 0.63 to 100 Example 31 60 3.75 - 1.25 to 100 Example 32 60 - 3.75 1.25 to 100 Example 33 7.5 3.75 - 1.25 to 100 Example 34 15 3.75 - 1.25 to 100 Example 35 30 3.75 - 1.25 to 100

2. Particle Size Evaluation Method of Nanoemulsion Composition

The particle size and surface charge of the prepared nanoemulsion were measured using a zeta potential/particle size analyzer (ELSZ-2000 series, Otsuka Electronics, Japan). The measurement was measured by diluting the nanoemulsion sample for evaluation using Phosphate Buffered Saline (PBS; Corning, USA) and then introducing it into the analyzer. The results are shown in Table 3 (unit: nm).

division average particle diameter Example 21 179.61±9.30 Example 22 209.92±7.09 Example 23 165.82±8.88 Example 24 139.92±7.09 Example 25 210.43±5.82 Example 26 204.12±11.65 Example 27 182.40±9.77 Example 28 144.12±11.65 Example 29 251.6±2.96 Example 30 195.28±8.08 Example 31 200.64±4.26 Example 32 135.28±8.08 Example 33 200.64±4.26 Example 34 200.64±4.26 Example 35 200.64±4.26

3. Particle Size Evaluation Results of Nanoemulsion Compositions

From Table 3, it was confirmed that even when PFOB was included at a relatively high content of 60% (w/v), a nanoemulsion having a desirable size was produced. On the other hand, when using soy phosphatidylcholine as the main surfactant, it was confirmed that the size of the nanoemulsion decreased as the content of PFOB increased. When using Span 80 as the main surfactant, it was confirmed that the size of the nanoemulsion increased as the content of PFOB increased.

<Test Example 3> Evaluation of the oxygen encapsulation rate of the nanoemulsion composition according to the content of the perfluorocarbon compound

1. Material preparation

The nanoemulsion compositions of Example 31 and Example 33 to Example 35 were prepared by adjusting the content of PFOB to 60% by weight, 7.5% by weight, 15% by weight, and 30% by weight, respectively.

2. Oxygen encapsulation rate evaluation method of nanoemulsion composition

Oxygen concentration in the nanoemulsion was evaluated using Fospor-R oxygen sensor (Ocean Optics, USA). The Fospor-R oxygen sensor probe was put into the container containing the nanoemulsion solution to measure the oxygen concentration in real time. The results are shown in Figure 2 (unit: ppm (v / w)).

3. Oxygen encapsulation rate evaluation result of nano emulsion

From FIG. 2, it was confirmed that 30 ppm (v/w) or more of oxygen was encapsulated in all of the nanoemulsions of Examples 31 and 33 to 35.

<Test Example 4> Evaluation of the oxygen release rate of the nanoemulsion composition according to the content of the perfluorocarbon compound

1. Material preparation

The nanoemulsion compositions of Examples 31 and 33 to 35 used in Test Example 3 were used.

2. Method for Evaluating Oxygen Release Rate of Nanoemulsion Composition

The oxygen-encapsulated nanoemulsion was stored in a cell culture medium fixed at 37 ° C, and the oxygen concentration was measured in real time using a Fospor-R oxygen sensor (Ocean Optics, USA) according to a predetermined time interval. The results are shown in Figure 3 (unit: ppm (v / w)).

3. Oxygen release rate evaluation result of nanoemulsion

In water used in general industrial or household boilers, about 8 ppm of oxygen is dissolved at a temperature of 20 °C. 3, the nanoemulsion compositions of Examples 31 and 33 to 35 all continued to release oxygen until about 40 hours to reach an equilibrium state. It was confirmed that there is an ability to maintain an oxygen concentration exceeding 8 ppm, which is the equilibrium state of.

<Reference Example 1> Culture of dermal papilla cells

DMEM (Dulbecco's Modified Eagle's Medium) Human Follicle Dermal Papilla Cells (HFDPC ), cat # C-12071; Promo Cell, USA) was cultured for 1 day in a 5% carbon dioxide incubator at 37° C., and then cultured again for two days by exchanging the medium. Thereafter, the cells were cultured while exchanging with a fresh medium every two days.

<Test Example 5> Cytotoxicity test

1. Cytotoxicity evaluation method

After culturing the dermal papilla cells cultured in Reference Example 1 for one day in a new 96-well dish, the oxygen-captured Example 31 and the oxygen-captured Example 1 nanoemulsion composition as a control were each at a concentration of 0 ppm to 2000 ppm. processed. After culturing for 24 hours and 72 hours, cell viability was confirmed by measuring absorbance at 450 nm using QuantiMax WST-8 Cell viability assay kit. The results are shown in Figure 4 (Unit: %).

2. Cytotoxicity evaluation results

From FIG. 4, like the control group in which oxygen was not captured, the treatment with the nanoemulsion composition of Example 31 in which oxygen was captured did not have any effect on the cells, from which the nanoemulsion composition of Example 31 It was confirmed that it was safe and had no toxicity.

<Test Example 6> Evaluation of oxygen level change by nanoemulsion

1. How to evaluate changes in oxygen levels

After removing the medium from the dermal papilla cells cultured in Reference Example 1, under conditions of extreme hypoxia, the oxygen-captured Example 31 and the oxygen-captured Example 31 nanoemulsion composition were each treated as a control. While culturing for 24 hours, the oxygen concentration in the medium was measured using a NeoFox fluorometer equipped with a Fospor-R oxygen sensor (Ocean Optics, Dunedin, Florida, USA). The results are shown in Figure 5 (Unit: %).

2. Cytotoxicity evaluation results

From FIG. 5, it was confirmed that the oxygen concentration of the control group in which oxygen was not captured was 0.227%, whereas when the nanoemulsion composition of Example 31 in which oxygen was captured was treated, the oxygen concentration increased to 0.492%. From this, it can be seen that when the nanoemulsion composition of Example 31 is treated, it can be converted from an extreme-hypoxia condition to a condition in which a certain level or more of oxygen is supplied.

<Test Example 7> Evaluation of cell growth

1. Cell growth evaluation method

After removing the medium from the dermal papilla cells cultured in Reference Example 1, under the conditions and treatment shown in Table 4 below, the oxygen-captured Example 1 and the oxygen-captured nanoemulsion composition were treated as a control, respectively. Cells were treated with the oxygen-scavenged nanoemulsion composition of Example 31 at concentrations of 100 ppm and 200 ppm, respectively.

division condition Serum (10%) added or not Treated Nano Emulsion Experimental Example 1 Extreme hypoxia ○ control group Experimental Example 2 Extreme hypoxia × control group Experimental Example 3 Extreme hypoxia ○ Oxygen Nano Emulsion 100ppm Experimental Example 4 Extreme hypoxia × Oxygen Nano Emulsion 100ppm Experimental Example 5 Extreme hypoxia ○ Oxygen Nano Emulsion 200ppm Experimental Example 6 Extreme hypoxia × Oxygen Nano Emulsion 200ppm Experimental Example 7 hypoxia ○ control group Experimental Example 8 hypoxia × control group Experimental Example 9 normoxia ○ control group Experimental Example 10 normoxia × control group

The degree of growth of dermal papilla cells was confirmed using an optical microscope (Nikon Eclipse T100, Japan). The image is shown in FIG. 6, and a graph showing the quantification of the number of cells is shown in FIG. 7 (unit: %).

2. Cell growth evaluation results

From Figures 6 and 7, it can be seen that it is effective to precede the supply of oxygen compared to the presence or absence of serum in the growth of dermal papilla cells. In addition, compared to the nanoemulsion composition in which oxygen was captured in a concentration of 200ppm, when the nanoemulsion composition in which oxygen was captured in a concentration of 100ppm was treated, it could be confirmed that a better cell growth ability was exhibited.

<Test Example 8> Hair follicle growth evaluation

1. Hair follicle growth evaluation method

A hair follicle sample was isolated from the human body for experimental application. The isolated hair follicle sample was placed in a 24-well plate (Nunc, Wiesbaden, Germany) containing 2 mM L-glutamine (PAA, Coelbe, Germany), 10 μg/ml insulin, and 10 ng/ml hydrocortisone (Sigma, St Louis, MO). , Penicillin / streptomycin (Gibco, NY, USA) 100u / ml DMEM (Gibco, NY, USA) containing 500ul of 3 to 5 pieces per well were cultured.

Under extreme hypoxia conditions, the 24-well plate was treated with a nanoemulsion containing oxygen at a concentration of 100 ppm and a nanoemulsion composition containing no oxygen as a control, respectively. A sample without any treatment was used as a negative control. Medium was changed every 2-3 days. The hair follicles were photographed using a stereomicroscope (Olympus SZX16, Japan), and the hair growth length was measured using the Image J program. 9 (unit: μm).

2. Hair follicle growth evaluation results

From FIGS. 8 and 9 , it can be seen that when the nanoemulsion composition in which oxygen is captured at a concentration of 100 ppm is treated, the hair follicle length growth ability is statistically significant.

<Preparation Example 2> Preparation of sustained-release oxygen nanoparticles

water; oleyl polyoxyl-6 glyceride and propylene glycol monocaprylate (Gatefosse, Saint-Priest, France); soy phosphatidylcholine (Lipoid, Ludwigshafen, Germany); and Tween 80 (Merck, Darmstadt, Germany) were dissolved in PBS (pH 7.4) and stirred at room temperature for 30 minutes using a magnetic stirrer.

followed by PFOB (Sinquest Laboratories, Florida, USA), BB61 (70-95% perfluorohexane, 1-20% perfluorodecalin and 1-15% pentafluoropropane; fiflow® ^BB61 ; Innovation Company, DeHue, France) or BTX (60-75% perfluorohexane, 15-20% perfluoroperhydrophenanthrene, 10-15% perfluorodecalin and 1-5% perfluorodimethylcyclohexane ; fiflow ^® BTX; Innovation Company, DeHue, France) was added to the mixture and stirred for 30 minutes. The mixture was homogenized at 8100 rpm for 30 seconds in a high-speed homogenizer (HG-15A; Daehan Science, Wonju, Korea) to obtain a crude emulsion, and then in a LV1-30K microfluidizer (Microfluidics, Westwood, Massachusetts, USA). It was treated for 5 cycles at 15,000 psi (about 1034 bar). Next, oxygen was bubbled into the crude emulsion at a rate of 1 mL/min to prepare a nanoemulsion containing oxygen gas.

<Test Example 9> Evaluation of nanoemulsion size and polydispersity index

1. Material preparation

A nanoemulsion composition was prepared according to the composition of Table 5 below. The content of each component is expressed as a relative content ratio, and the unit is % by weight.

division PFOB BB61 BTX soy phosphatidylcholine Tween 80 water Example 36 60 - - 1.875 0.625 to 100 Comparative Example 1 - 60 - 1.875 0.625 to 100 Example 37 - - 60 1.875 0.625 to 100

2. Evaluation method of size and polydispersity index of nanoemulsion

The particle size, surface charge, and polydispersity index (PDI) of the prepared nanoemulsion were measured using a zeta potential/particle size analyzer (ELSZ-2000 series, Otsuka Electronics, Japan). The measurement was measured by diluting the nanoemulsion sample for evaluation using Phosphate Buffered Saline (PBS; Corning, USA) and then introducing it into the analyzer. The results are shown in FIG. 10 (particle size unit: nm).

3. Results of nanoemulsion size and polydispersity index evaluation

10, it can be seen that the nanoemulsion of Comparative Example 1 has a large particle size and a polydispersity distribution. On the other hand, in the case of the nanoemulsion of Comparative Example 1, a lot of bubbles were formed during preparation, and in particular, the nanoemulsion of Comparative Example 1 generated bubbles to the extent that it was impossible to prepare.

<Preparation Example 3> Preparation of sustained-release oxygen nanoparticles

water; oleyl polyoxyl-6 glyceride and propylene glycol monocaprylate (Gatefosse, Saint-Priest, France); Soy phosphatidylcholine (Lipoid, Ludwigshafen, Germany), hydrogenated lecithin (Lipoid P100-3, Lipoid GmbH) or polyglyceryl-10 stearate (Nikkol deaglyn 1-sv, Nikko Chemicals Co., Ltd.); and Tween 80 (Merck, Darmstadt, Germany), inulin lauryl carbamate (Inutec SL1, Creachem), polyglyceryl-10 laurate (Sunsoft Q-12Y-C, Taiyo Chemical), glyceryl stearate Citrate (Dracorin CE, Symrise) or sodium stearoyl glutamate (Eumulgin SG, BASF) was dissolved in PBS (pH 7.4) and stirred at room temperature for 30 minutes using a magnetic stirrer.

PFOB (Sinquest Laboratories, Florida, USA), perfluorodecalin (PFD, Sigma, St Louis, MO) and/or perfluorohexane (PFH, Sigma, St Louis, MO) were then mixed was added and stirred for 30 minutes. The mixture was homogenized at 8100 rpm for 30 seconds in a high-speed homogenizer (HG-15A; Daehan Science, Wonju, Korea) to obtain a crude emulsion, and then in a LV1-30K microfluidizer (Microfluidics, Westwood, Massachusetts, USA). It was treated for 5 cycles at 15,000 psi (about 1034 bar). Next, oxygen was bubbled into the crude emulsion at a rate of 1 mL/min to prepare a nanoemulsion containing oxygen gas.

<Preparation Example 4> Preparation of nanoemulsion composition

Nanoemulsion compositions were prepared according to the compositions of Tables 6 to 12 below. The content of each component is expressed as a relative content ratio, and the unit is % by weight.

division PFOB PFD PFH soy phosphatidylcholine Tween 80 water Example 36 60 - - 1.875 0.625 to 100 Example 38 - 60 - 1.875 0.625 to 100 Example 39 - 45 45 1.875 0.625 to 100 Example 40 - 30 30 1.875 0.625 to 100 Example 41 - 45 45 1.875 0.625 to 100 Example 42 - - 60 1.875 0.625 to 100

division PFD PFH Hydrogenated Lecithin inulin lauryl carbamate water Example 43 37.5 12.5 3.75 1.25 to 100 Example 44 37.5 12.5 3 One to 100 Example 45 37.5 12.5 2.25 0.75 to 100 Example 46 37.5 12.5 1.5 0.5 to 100 Example 47 37.5 12.5 0.75 0.25 to 100 Example 48 37.5 12.5 4 One to 100 Example 49 37.5 12.5 3.2 0.8 to 100 Example 50 37.5 12.5 2.4 0.6 to 100 Example 51 37.5 12.5 1.6 0.4 to 100 Example 52 37.5 12.5 0.8 0.2 to 100

division PFD PFH Hydrogenated Lecithin Polyglyceryl-10 Laurate water Example 53 37.5 12.5 3.75 1.25 to 100 Example 54 37.5 12.5 3 One to 100 Example 55 37.5 12.5 2.25 0.75 to 100 Example 56 37.5 12.5 1.5 0.5 to 100 Example 57 37.5 12.5 0.75 0.25 to 100 Example 58 37.5 12.5 4 One to 100 Example 59 37.5 12.5 3.2 0.8 to 100 Example 60 37.5 12.5 2.4 0.6 to 100 Example 61 37.5 12.5 1.6 0.4 to 100 Example 62 37.5 12.5 0.8 0.2 to 100

division PFD PFH Polyglyceryl-10 Stearate Glyceryl Stearate Citrate water Example 63 37.5 12.5 4 One to 100 Example 64 37.5 12.5 3.2 0.8 to 100 Example 65 37.5 12.5 2.4 0.6 to 100 Example 66 37.5 12.5 1.6 0.4 to 100 Example 67 37.5 12.5 0.8 0.2 to 100

division PFD PFH Polyglyceryl-10 Stearate inulin lauryl carbamate water Example 68 37.5 12.5 4 One to 100 Example 69 37.5 12.5 3.2 0.8 to 100 Example 70 37.5 12.5 2.4 0.6 to 100 Example 71 37.5 12.5 1.6 0.4 to 100 Example 72 37.5 12.5 0.8 0.2 to 100

division PFD PFH Polyglyceryl-10 Stearate Sodium Stearoyl Glutamate water Example 73 37.5 12.5 4 One to 100 Example 74 37.5 12.5 3.2 0.8 to 100 Example 75 37.5 12.5 2.4 0.6 to 100 Example 76 37.5 12.5 1.6 0.4 to 100 Example 77 37.5 12.5 0.8 0.2 to 100

division PFD PFH Hydrogenated Lecithin cholesterol water Example 78 37.5 12.5 3.75 1.25 to 100 Example 79 37.5 12.5 3 One to 100 Example 80 37.5 12.5 2.25 0.75 to 100 Example 81 37.5 12.5 1.5 0.5 to 100 Example 82 37.5 12.5 0.75 0.25 to 100 Example 83 37.5 12.5 4 One to 100 Example 84 37.5 12.5 3.2 0.8 to 100 Example 85 37.5 12.5 2.4 0.6 to 100 Example 86 37.5 12.5 1.6 0.4 to 100 Example 87 37.5 12.5 0.8 0.2 to 100

<Test Example 10> Evaluation of particle size and polydispersity index of nanoemulsion

1. Material preparation

The nanoemulsion compositions of Examples 22 and 24 to 28 were used.

2. Evaluation method of particle size and polydispersity index of nanoemulsion

The particle size, surface charge, and polydispersity index (PDI) of the prepared nanoemulsion were measured using a zeta potential/particle size analyzer (ELSZ-2000 series, Otsuka Electronics, Japan). The measurement was measured by diluting the nanoemulsion sample for evaluation using Phosphate Buffered Saline (PBS; Corning, USA) and then introducing it into the analyzer. The results are shown in FIG. 11 (particle size unit: nm).

3. Evaluation results of particle size and polydispersity index of nanoemulsion

From FIG. 11, it can be seen that the nanoemulsions of Examples 36 and 38 to 42 are nanoemulsions with excellent properties having a particle size of 200 nm or less.

<Test Example 11> Size evaluation of nanoemulsion according to temperature and time

1. Material preparation

The nanoemulsion compositions of Examples 36 and 38 to 42 were used.

2. Particle size evaluation method of nanoemulsion

The same evaluation method as in Test Example 10 was performed. The measurement result at a temperature of 4° C. is shown in FIG. 12A and the measurement result at a temperature of 37° C. is shown in FIG. 12B (particle size unit: nm).

3. Results of particle size evaluation of nanoemulsion

From FIG. 12a , when stored at 4° C., the particle size of the nanoemulsion increased with time, and this tendency was somewhat different depending on the concentration of PFH. More specifically, the particle size of the nanoemulsion increased as the concentration of PFH increased. In particular, in the case of the nanoemulsion of Example 38 without PFH, there was no significant change in particle size for 28 days, and in the case of the nanoemulsion of Example 42 without PFD, the particle size increased by about 40% for 28 days. Therefore, it can be expected that PFH affects the particle stability of the nanoemulsion. From FIG. 12b , when stored at 37° C., after 28 days, the particle size of the nanoemulsion tended to increase by about 200 to 530% compared to the initial size in all groups.

<Test Example 12> Evaluation of oxygen encapsulation rate of nanoemulsion composition

1. Material preparation

The nanoemulsion compositions of Examples 36 and 38 to 42 were used.

2. Oxygen encapsulation rate evaluation method of nanoemulsion composition

Oxygen concentration in the nanoemulsion was evaluated using Fospor-R oxygen sensor (Ocean Optics, USA). The Fospor-R oxygen sensor probe was put into the container containing the nanoemulsion solution to measure the oxygen concentration in real time. The results are shown in FIG. 13 (unit: ppm (v/w)).

3. Oxygen encapsulation rate evaluation result of nano emulsion

From FIG. 13, it was confirmed that 20 ppm (v/w) or more of oxygen was encapsulated in all of the nanoemulsions of Examples 36 and 38 to 42. More specifically, about 27 ppm of the PFOB nanoemulsion of Example 36 and 20 to 25 ppm of oxygen were found to be encapsulated in the PFD/PFH nanoemulsion of Examples 38 to 42 depending on the mixing ratio. From this, it can be seen that the oxygen encapsulation concentration decreases as the concentration of PFH increases in the PFD/PFH nanoemulsions of Examples 38 to 42.

<Test Example 13> Evaluation of oxygen encapsulation rate of nanoemulsion composition over time

1. Material preparation

The nanoemulsion compositions of Examples 36 and 38 to 42 were used.

2. Oxygen encapsulation rate evaluation method of nanoemulsion composition

Oxygen concentration in the nanoemulsion was evaluated using Fospor-R oxygen sensor (Ocean Optics, USA). The Fospor-R oxygen sensor probe was put into the container containing the nanoemulsion solution to measure the oxygen concentration in real time. The results are shown in Figure 14a (unit: ppm (v / w)). The normalized results based on the initial concentration are shown in FIG. 14B.

3. Oxygen encapsulation rate evaluation result of nano emulsion

From FIGS. 14a and 14b, the oxygen concentration remaining in the PFOB nanoemulsion of Example 36 was high until 1 hour after the start of the evaluation, but over time, after that, the PFD / PFH of Examples 38 to 42 It was found that the concentration of oxygen remaining in the nanoemulsion was high. In particular, the higher the concentration of PFH, the higher the concentration of residual oxygen. From this, it can be seen that the release of oxygen into the atmosphere is controlled by PFH.

<Test Example 14> Evaluation of particle size and polydispersity index of nanoemulsion composition according to content of main surfactant and auxiliary surfactant

1. Material preparation

The nanoemulsion compositions of Examples 43 to 52 were used.

2. Evaluation method of particle size and polydispersity index of nanoemulsion composition

The same evaluation method as in Test Example 10 was performed. The results are shown in FIG. 15 (particle size unit: nm).

3. Evaluation results of particle size and polydispersity index of nanoemulsion composition

15, it can be seen that the size of the particles increases as the total content of the surfactant increases. However, as the total content of the surfactant increased, the viscosity and latherability of the nanoemulsion tended to increase proportionally.

<Test Example 15> Evaluation of particle size and polydispersity index of nanoemulsion composition according to content of main surfactant and auxiliary surfactant

1. Material preparation

The nanoemulsion compositions of Examples 53 to 62 were used.

2. Evaluation method of particle size and polydispersity index of nanoemulsion composition

The same evaluation method as in Test Example 10 was performed. The results are shown in FIG. 16 (particle size unit: nm).

3. Evaluation results of particle size and polydispersity index of nanoemulsion composition

16, it can be seen that in Examples 53 to 57 in which the content ratio of the main surfactant and the auxiliary surfactant is 3:1, the size of the particles increases as the total content of the surfactant increases. However, in the case of Examples 58 to 62 in which the content ratio of the main surfactant and the auxiliary surfactant was 4:1, the size of the particles decreased as the total content of the surfactant increased. In particular, Example 59 formed the smallest particle size (203.99 nm).

<Test Example 16> Evaluation of particle size and polydispersity index of nanoemulsion composition according to temperature and time

1. Material preparation

The nanoemulsion compositions of Examples 58 to 62 were used.

2. Evaluation method of size and polydispersity index of nanoemulsion

The same evaluation method as in Test Example 10 was performed. The results measured at 4° C. and room temperature (RT) are shown in FIG. 17 (particle size unit: nm).

3. Evaluation results of particle size and polydispersity index of nanoemulsion composition

From FIG. 17, it can be seen that the nanoemulsion particle size increases after 7 days both at 4° C. and room temperature (RT). In addition, the degree of particle size increase was different depending on the storage temperature conditions, and it can be seen that the refrigeration storage conditions promoted the particle size increase.

<Test Example 17> Evaluation of particle size and polydispersity index of nanoemulsion composition according to content of main surfactant and auxiliary surfactant

1. Material preparation

The nanoemulsion compositions of Examples 63 to 67 were used.

2. Evaluation method of particle size and polydispersity index of nanoemulsion composition

The same evaluation method as in Test Example 10 was performed. The results measured at 4° C. and room temperature (RT) are shown in FIG. 18 (particle size unit: nm).

3. Evaluation results of particle size and polydispersity index of nanoemulsion composition

From FIG. 18, it can be seen that all nanoemulsion compositions immediately after preparation were formed with a particle size of less than 300 nm. In particular, Example 63 formed the smallest particle size (203.99 nm). In addition, it can be seen that the size of the nanoemulsion particles increases after 7 days in both the case of a temperature of 4 ° C. and room temperature (RT). Compared to room temperature (RT), the increase in particle size was relatively suppressed at a temperature of 4 °C. Examples 63 and 64 showed a good increase in particle size after 7 days.

<Test Example 18> Evaluation of particle size and polydispersity index of nanoemulsion composition according to content of main surfactant and auxiliary surfactant

1. Material preparation

The nanoemulsion compositions of Examples 68 to 72 were used.

2. Evaluation method of particle size and polydispersity index of nanoemulsion composition

The same evaluation method as in Test Example 10 was performed. The results measured at 4° C. and room temperature (RT) are shown in FIG. 19 (particle size unit: nm).

3. Evaluation results of particle size and polydispersity index of nanoemulsion composition

From FIG. 19 , it can be seen that the size of the particles decreases as the total content of the surfactant increases both at 4° C. and at room temperature (RT). In particular, Example 68 formed the smallest particle size (220 nm). The viscosity was not high enough to affect the manufacturing, and the latherability was weak. It can be seen that the nanoemulsion particle size increases after 7 days in both the case of a temperature of 4 ° C. and room temperature (RT). Compared to room temperature (RT), the increase in particle size was relatively suppressed at a temperature of 4 °C.

<Test Example 19> Evaluation of particle size and polydispersity index of nanoemulsion composition according to content of main surfactant and auxiliary surfactant

1. Material preparation

The nanoemulsion compositions of Examples 73 to 77 were used.

2. Evaluation method of particle size and polydispersity index of nanoemulsion composition

The same evaluation method as in Test Example 10 was performed. The results measured at 4° C. and room temperature (RT) are shown in FIG. 20 (particle size unit: nm).

3. Evaluation results of particle size and polydispersity index of nanoemulsion composition

From FIG. 20, it can be seen that all nanoemulsion compositions immediately after preparation formed similar particle sizes without being greatly affected by the total content of the surfactant. When stored at a temperature of 4 ° C., it can be seen that the total content of the surfactant affects the stability of the nanoemulsion after 7 days. In the case of both the temperature of 4 ° C and room temperature (RT), the particle size increase tendency of the formulation decreased as the total content of the surfactant increased.

<Test Example 20> Oxygen of nanoemulsion composition Enclosure rate evaluation

1. Material preparation

The nanoemulsion compositions of Examples 63, 68 and 73 were used. Also using a composition containing PFOB and containing polyglyceryl-10 stearate as a primary surfactant, and glyceryl stearate citrate, inulin lauryl carbamate, and sodium stearoyl glutamate as auxiliary surfactants did

2. Oxygen encapsulation rate evaluation method of nanoemulsion composition

The same evaluation method as in Test Example 3 was performed. The oxygen concentration of each formulation was measured before oxygen purging, and the oxygen concentration of each formulation after oxygen purging was measured. The results are shown in FIG. 21 (unit: ppm (v/w)).

3. Oxygen encapsulation rate evaluation result of nano emulsion

From FIG. 21, it was confirmed that 20 ppm (v/w) or more of oxygen was encapsulated in all of the nanoemulsions of Examples 63, 68, and 73. After oxygen purging, the formulation of Example 63 was loaded with oxygen at 28.9 ppm (v/w), which was higher than the oxygen concentration of 27.1 ppm (v/w) in the composition containing PFOB.

<Test Example 21> Evaluation of oxygen release rate of nanoemulsion composition

1. Material preparation

The nanoemulsion compositions of Examples 63, 68 and 73 were used. Also using a composition containing PFOB and containing polyglyceryl-10 stearate as a primary surfactant, and glyceryl stearate citrate, inulin lauryl carbamate, and sodium stearoyl glutamate as auxiliary surfactants did

2. Method for Evaluating Oxygen Release Rate of Nanoemulsion Composition

The same evaluation method as in Test Example 3 was performed. The oxygen concentration of each formulation was measured before oxygen purging, and the oxygen concentration of each formulation after oxygen purging was measured. The results are shown in Figure 22a (unit: ppm (v / w)). The normalized results based on the initial concentration are shown in FIG. 22B.

3. Oxygen Release Rate Evaluation Results of Nanoemulsion Compositions

From FIG. 22a, the composition containing PFOB released all oxygen at 36 hours, but all of the nanoemulsions of Examples 63, 68, and 73 continued to release oxygen until the 72nd time point, and 5 to 11 ppm (v/w) of oxygen. 22b, it can be seen that the oxygen concentration of 30-42% compared to the initial encapsulation amount was maintained for up to 72 hours.

Formulation examples of the composition according to one aspect of the present invention will be described below, but can also be applied to various other formulations, which are only intended to be specifically described and not intended to limit the present invention.

[Formulation Example 1] Shampoo

Shampoo was prepared by a conventional method according to the composition shown in Table 13 below.

ingredient Content (% by weight) Perfluorooctyl bromide (PFOB) 10.0 soybean phosphatidylcholine 2.5 Tween 80 2.5 Ammonium Laureth Sulfate 10.0 Glycol Distearate 2.0 cetyl alcohol 0.6 Cocamide MEA 0.5 Ammonium Lauryl Sulfate 6.0 Guar Hydroxypropyltrimonium Chloride 0.15 Polyquaternium-10 0.1 silicon 0.5 distearyldimethylammonium chloride 0.2 Sodium Cocoamphoacetate 4.0 Spices 1.0 antiseptic 0.03 citric acid Appropriate amount Purified water balance

[Formulation Example 2] Rinse

A rinse was prepared in a conventional manner according to the composition shown in Table 14 below.

ingredient Content (% by weight) Perfluorooctyl bromide (PFOB) 10.0 soybean phosphatidylcholine 2.5 Tween 80 2.5 cetyl alcohol 3.0 Glycerin Monostearate 1.0 Hydroxyethyl Cellulose 1.0 propylene glycol 4.0 Methyl parahydroxybenzoate 0.2 Stearyldimethylbenzylammonium chloride 25% 10.0 Spices Appropriate amount pigment Appropriate amount citric acid Appropriate amount Purified water balance

[Formulation Example 3] Ointment

An ointment was prepared in a conventional manner according to the composition shown in Table 15 below.

ingredient Content (% by weight) Perfluorooctyl bromide (PFOB) 10.0 soybean phosphatidylcholine 2.5 Tween 80 2.5 Butylene Glycol 4.0 liquid paraffin 15.0 beta glucan 7.0 carbomer 0.1 Caprylic/Capric Triglyceride 3.0 squalane 1.0 Cetearyl Glucoside 1.5 Sorbitan Stearate 0.4 cetearyl alcohol 1.0 beeswax 4.0 glycerin 8.0 Preservatives, Colors, Flavors Appropriate amount Purified water balance

[Formulation Example 4] Massage Cream

Massage cream was prepared in a conventional manner according to the composition shown in Table 16 below.

ingredient Content (% by weight) Perfluorooctyl bromide (PFOB) 10.0 soybean phosphatidylcholine 2.5 Tween 80 2.5 glycerin 8.0 Butylene Glycol 4.0 liquid paraffin 45.0 beta glucan 7.0 carbomer 0.1 Caprylic/Capric Triglyceride 3.0 beeswax 4.0 Cetearyl Glucoside 1.5 Sesquioleate Sorbitan 0.9 Vaseline 3.0 paraffin 1.5 Preservatives, Colors, Flavors Appropriate amount Purified water balance

[Formulation Example 5] Hair pack

According to the composition shown in Table 17 below, a hair pack was prepared by a conventional method.

ingredient Content (% by weight) Perfluorooctyl bromide (PFOB) 10.0 soybean phosphatidylcholine 2.5 Tween 80 2.5 glycerin 4.0 polyvinyl alcohol 15.0 hyaluronic acid extract 5.0 beta glucan 7.0 allantoin 0.1 nonyl phenyl ether 0.4 Polysorbate 60 1.2 ethanol preservative 6.0 Preservatives, Colors, Flavors Appropriate amount Purified water balance

[Formulation Example 6] Soft capsule

9 mg of vitamin E, 9 mg of vitamin C, 2 mg of palm oil, 8 mg of hydrogenated vegetable oil, 4 mg of yellow wax, and 9 mg of lecithin were mixed with the nanoemulsion composition of Example 2, and mixed according to a conventional method to prepare a soft capsule filling solution. Soft capsules are prepared by filling 400 mg per capsule. Separately from the above, soft capsule sheets containing 400 mg of the composition were prepared by preparing a soft capsule sheet in a ratio of 66 parts by weight of gelatin, 24 parts by weight of glycerin, and 10 parts by weight of sorbitol solution, and filling the filling solution.

[Formulation Example 7] Tablets

9 mg of vitamin E, 9 mg of vitamin C, 200 mg of galacto-oligosaccharide, 60 mg of lactose, and 140 mg of maltose were mixed with the nanoemulsion composition of Example 2 and granulated using a fluidized bed dryer, followed by 6 mg of sugar ester. Add. Tablets were prepared by compressing 500 mg of these compositions in a conventional manner.

[Formulation Example 8] Injection

Injections were prepared by a conventional method according to the compositions shown in Table 18 below.

ingredient Content (mg) Nanoemulsion composition of Example 2 10.0 Sterile Distilled Water for Injection Appropriate amount pH adjuster Appropriate amount

[Formulation Example 9] Health drink

According to the composition shown in Table 19 below, a health drink was prepared by a conventional method.

ingredient Content (mg) Nanoemulsion composition of Example 2 100 Citric acid/oligosaccharide/taurine Appropriate amount

[Formulation Example 10] Shampoo

Shampoo was prepared by a conventional method according to the composition shown in Table 20 below.

ingredient Content (% by weight) Perfluorodecalin (PFD) 37.5 Perfluorohexane (PFH) 12.5 Polyglyceryl-10 Stearate 4 inulin lauryl carbamate One Ammonium Laureth Sulfate 10.0 Glycol Distearate 2.0 cetyl alcohol 0.6 Cocamide MEA 0.5 Ammonium Lauryl Sulfate 6.0 Guar Hydroxypropyltrimonium Chloride 0.15 Polyquaternium-10 0.1 silicon 0.5 distearyldimethylammonium chloride 0.2 Sodium Cocoamphoacetate 4.0 Spices 1.0 antiseptic 0.03 citric acid Appropriate amount Purified water balance

[Formulation Example 11] Rinse

A rinse was prepared by a conventional method according to the composition shown in Table 21 below.

ingredient Content (% by weight) Perfluorodecalin (PFD) 37.5 Perfluorohexane (PFH) 12.5 Polyglyceryl-10 Stearate 4 inulin lauryl carbamate One cetyl alcohol 3.0 Glycerin Monostearate 1.0 Hydroxyethyl Cellulose 1.0 propylene glycol 4.0 Methyl parahydroxybenzoate 0.2 Stearyldimethylbenzylammonium chloride 25% 10.0 Spices Appropriate amount pigment Appropriate amount citric acid Appropriate amount Purified water balance

[Formulation Example 12] Ointment

An ointment was prepared in a conventional manner according to the composition shown in Table 22 below.

ingredient Content (% by weight) Perfluorodecalin (PFD) 37.5 Perfluorohexane (PFH) 12.5 Polyglyceryl-10 Stearate 4 inulin lauryl carbamate 4 Butylene Glycol 4.0 liquid paraffin 15.0 beta glucan 7.0 carbomer 0.1 Caprylic/Capric Triglyceride 3.0 squalane 1.0 Cetearyl Glucoside 1.5 Sorbitan Stearate 0.4 cetearyl alcohol 1.0 beeswax 4.0 glycerin 8.0 Preservatives, Colors, Flavors Appropriate amount Purified water balance

[Formulation Example 13] Massage Cream

A massage cream was prepared in a conventional manner according to the composition shown in Table 23 below.

ingredient Content (% by weight) Perfluorodecalin (PFD) 37.5 Perfluorohexane (PFH) 12.5 Polyglyceryl-10 Stearate 4 inulin lauryl carbamate One glycerin 8.0 Butylene Glycol 4.0 liquid paraffin 45.0 beta glucan 7.0 carbomer 0.1 Caprylic/Capric Triglyceride 3.0 beeswax 4.0 Cetearyl Glucoside 1.5 Sesquioleate Sorbitan 0.9 Vaseline 3.0 paraffin 1.5 Preservatives, Colors, Flavors Appropriate amount Purified water balance

[Formulation Example 14] Hair pack

According to the composition shown in Table 24 below, a hair pack was prepared in a conventional manner.

ingredient Content (% by weight) Perfluorodecalin (PFD) 37.5 Perfluorohexane (PFH) 12.5 Polyglyceryl-10 Stearate 4 inulin lauryl carbamate One glycerin 4.0 polyvinyl alcohol 15.0 hyaluronic acid extract 5.0 beta glucan 7.0 allantoin 0.1 nonyl phenyl ether 0.4 Polysorbate 60 1.2 ethanol preservative 6.0 Preservatives, Colors, Flavors Appropriate amount Purified water balance

[Formulation Example 15] Soft Capsule

9 mg of vitamin E, 9 mg of vitamin C, 2 mg of palm oil, 8 mg of hydrogenated vegetable oil, 4 mg of yellow wax, and 9 mg of lecithin were mixed with the nanoemulsion composition of Example 51, and mixed according to a conventional method to prepare a soft capsule filling solution. Soft capsules are prepared by filling 400 mg per capsule. Separately from the above, soft capsule sheets containing 400 mg of the composition were prepared by preparing a soft capsule sheet in a ratio of 66 parts by weight of gelatin, 24 parts by weight of glycerin, and 10 parts by weight of sorbitol solution, and filling the filling solution.

[Formulation Example 16] Tablets

9 mg of vitamin E, 9 mg of vitamin C, 200 mg of galacto-oligosaccharide, 60 mg of lactose, and 140 mg of maltose were mixed with the nanoemulsion composition of Example 51 and granulated using a fluidized bed dryer, followed by 6 mg of sugar ester. Add. Tablets were prepared by compressing 500 mg of these compositions in a conventional manner.

[Formulation Example 17] Injection

Injections were prepared by a conventional method according to the composition shown in Table 25 below.

ingredient Content (mg) The nanoemulsion composition of Example 51 10.0 Sterile Distilled Water for Injection Appropriate amount pH adjuster Appropriate amount

[Formulation Example 18] Health drink

According to the composition shown in Table 26 below, a health drink was prepared by a conventional method.

ingredient Content (mg) The nanoemulsion composition of Example 51 100 Citric acid/oligosaccharide/taurine Appropriate amount

In various aspects, the present disclosure is directed to, and includes at least the following aspects.

[Aspect 1] An aqueous phase containing water; and an oil phase portion comprising nanoparticles dispersed in the aqueous phase portion and containing a perfluorocarbon compound, wherein the oil phase portion contains oxygen gas, and the oxygen gas is released in a sustained release form. .

[Aspect 2] The composition according to aspect 1, wherein the nanoparticles have an average diameter of 100 nm to 300 nm.

[Aspect 3] The composition according to aspect 1 or aspect 2, wherein the oxygen gas is captured in an amount of 1 ppm (v/w) to 35 ppm (v/w) based on the total weight of the nanoemulsion composition.

[Aspect 4] The composition according to any one of aspects 1 to 3, wherein the perfluorocarbon compound is a perfluoroalkyl halide.

[Aspect 5] The composition according to any one of aspects 1 to 4, wherein the perfluorocarbon compound is perfluorooctyl bromide (PFOB).

[Aspect 6] In any one of aspects 1 to 5, the perfluorocarbon compound is a chain-like fluorinated aliphatic hydrocarbon having 1 to 12 carbon atoms and 3 carbon atoms having 1 or 2 rings. to at least one of 12 cyclic fluorinated aliphatic hydrocarbons.

[Aspect 7] In the aspect of any one of aspects 1 to 6, the perfluorocarbon compound is a chain-like fluorinated aliphatic hydrocarbon having 1 to 12 carbon atoms and 3 carbon atoms having 1 or 2 rings. to 12 cyclic fluorinated aliphatic hydrocarbons.

[Aspect 8] The composition according to any one of aspects 1 to 7, wherein the perfluorocarbon compound is at least one of perfluorodecalin (PFD) and perfluorohexane (PFH).

[Aspect 9] In one aspect of aspect 1 to aspect 8, the perfluorocarbon compound is a combination of perfluorodecalin (PFD) and perfluorohexane (PFH), and the perfluorodecalin (PFD) ) And the content ratio of perfluorohexane (PFH) is 6: 1 to 1: 3 based on weight, the composition.

[Aspect 10] The composition according to any one of aspects 1 to 9, wherein the content of the perfluorocarbon compound is 5 to 80% by weight based on the total weight of the nanoemulsion composition.

[Aspect 11] The method of any one of aspects 1 to 10, wherein the nanoemulsion composition further comprises at least one of phospholipids, polyglycerin stearic acid esters, and fatty acid esters of sorbitan as a main surfactant, and the nanoemulsion composition The composition further comprises at least one of cholesterol, glyceryl diester, inulin fatty acid ester, polyglycerin lauric acid ester, carboxylate salt of glutamic acid, and fatty acid ester of ethoxylated sorbitan as a silver co-surfactant.

[Aspect 12] The composition according to any one of aspects 1 to 11, wherein a total content of the main surfactant and the auxiliary surfactant is 0.1 to 10% by weight based on the total weight of the nanoemulsion composition.

[Aspect 13] The composition according to any one of aspects 1 to 12, wherein a content ratio of the main surfactant and the auxiliary surfactant is 10:1 to 1:3 by weight.

[Mode 14] In one embodiment of any one of modes 1 to 13, the phospholipid is at least one selected from the group consisting of hydrogenated lecithin and phosphatidylcholine, and the polyglycerin stearic acid ester is polyglyceryl-10 stearate. The composition, wherein the fatty acid ester of sorbitan is sorbitan monooleate (Span 80).

[Mode 15] The method of any one of modes 1 to 14, wherein the glyceryl diester is glyceryl stearate citrate, the inulin fatty acid ester is inulin lauryl carbamate, and the polyglycerin lauric acid ester is polyglyceryl-10 laurate, the carboxylate salt of glutamic acid is sodium stearoyl glutamate, and the fatty acid ester of ethoxylated sorbitan is PEG-20 sorbitan monooleate (Tween 80).

[Aspect 16] The composition according to any one of aspects 1 to 15, wherein the concentration of oxygen gas reaches equilibrium at a time of 10 seconds or more after the start of elution.

[Aspect 17] The composition according to one of aspects 1 to 16, wherein the composition is a composition for preventing hair loss or promoting hair growth.

[Aspect 18] The composition according to any one of aspects 1 to 17, further comprising an additional hair loss prevention or hair growth promoting active ingredient.

[Aspect 19] The composition according to any one of aspects 1 to 18, wherein the composition is an external preparation for skin.

[Aspect 20] The composition according to any one of aspects 1 to 19, wherein the composition is a cosmetic, pharmaceutical or food composition.

[Aspect 21] Water; oil; at least one of phospholipids, polyglycerin stearic acid esters and fatty acid esters of sorbitan as a main surfactant; preparing a first mixture by mixing at least one of a glyceryl diester, an inulin fatty acid ester, a polyglycerin lauric acid ester, a carboxylate salt of glutamic acid, and a fatty acid ester of ethoxylated sorbitan as an auxiliary surfactant; preparing a second mixture by adding a perfluorocarbon compound to the first mixture; homogenizing the second mixture to prepare a crude emulsion; and bubbling oxygen into the crude emulsion.

Although the present invention has been described with respect to the preferred embodiments mentioned above, various modifications and variations are possible without departing from the spirit and scope of the invention. Accordingly, the appended claims are intended to include such modifications and variations insofar as they fall within the scope of the present invention.

Claims (21)

Water phase containing water; and
And an oil phase portion made of nanoparticles dispersed in the water phase portion and containing a perfluorocarbon compound,
The oil phase part contains oxygen gas,
The oxygen gas is released in a sustained release, oxygen gas sustained release nanoemulsion composition. According to claim 1,
The average diameter of the nanoparticles is 100 nm to 300 nm, the composition. According to claim 1,
Wherein the oxygen gas is captured in an amount of 1 ppm (v / w) to 35 ppm (v / w) based on the total weight of the nanoemulsion composition. According to claim 1,
Wherein the perfluorocarbon compound is a perfluoroalkyl halide. According to claim 4,
Wherein the perfluorocarbon compound is perfluorooctyl bromide (PFOB). According to claim 1,
Wherein the perfluorocarbon compound is at least one of a chain fluorinated aliphatic hydrocarbon having 1 to 12 carbon atoms and a cyclic fluorinated aliphatic hydrocarbon having 3 to 12 carbon atoms having 1 or 2 rings. According to claim 6,
Wherein the perfluorocarbon compound is a combination of a chain-like fluorinated aliphatic hydrocarbon having 1 to 12 carbon atoms and a cyclic fluorinated aliphatic hydrocarbon having 3 to 12 carbon atoms and having 1 or 2 rings. According to claim 6,
Wherein the perfluorocarbon compound is at least one of perfluorodecalin (PFD) and perfluorohexane (PFH). According to claim 7,
The perfluorocarbon compound is a combination of perfluorodecalin (PFD) and perfluorohexane (PFH),
The content ratio of the perfluorodecalin (PFD) and perfluorohexane (PFH) is 6: 1 to 1: 3 based on weight, the composition. According to claim 1,
The content of the perfluorocarbon compound is 5 to 80% by weight based on the total weight of the nanoemulsion composition, the composition. According to claim 1,
The nanoemulsion composition further includes at least one of phospholipids, polyglycerin stearic acid esters, and fatty acid esters of sorbitan as a main surfactant,
The nanoemulsion composition further comprises at least one of cholesterol, glyceryl diester, inulin fatty acid ester, polyglycerin lauric acid ester, carboxylate salt of glutamic acid, and fatty acid ester of ethoxylated sorbitan as an auxiliary surfactant, composition. According to claim 11,
The total content of the main surfactant and the auxiliary surfactant is 0.1 to 10% by weight based on the total weight of the nanoemulsion composition, composition. According to claim 11,
The content ratio of the main surfactant and the auxiliary surfactant is 10: 1 to 1: 3 by weight, the composition. According to claim 11,
The phospholipid is at least one selected from the group consisting of hydrogenated lecithin and phosphatidylcholine,
The polyglycerin stearic acid ester is polyglyceryl-10 stearate,
Wherein the fatty acid ester of sorbitan is sorbitan monooleate (Span 80). According to claim 11,
The glyceryl diester is glyceryl stearate citrate,
The inulin fatty acid ester is inulin lauryl carbamate,
The polyglycerol lauric acid ester is polyglyceryl-10 laurate,
The carboxylate salt of glutamic acid is sodium stearoyl glutamate;
Wherein the fatty acid ester of the ethoxylated sorbitan is PEG-20 sorbitan monooleate (Tween 80). According to claim 1,
The composition, in which the oxygen gas concentration reaches equilibrium at the time of 10 seconds or more after the start of elution. According to any one of claims 1 to 16,
The composition is a composition for preventing hair loss or promoting hair growth. According to claim 17,
A composition further comprising an additional hair loss prevention or hair growth promoting active ingredient. According to any one of claims 1 to 16,
The composition is a composition for external application to the skin. According to any one of claims 1 to 16,
Wherein the composition is a cosmetic, pharmaceutical or food composition. water; oil; at least one of phospholipids, polyglycerin stearic acid esters and fatty acid esters of sorbitan as a main surfactant; and at least one of cholesterol, glyceryl diester, inulin fatty acid ester, polyglycerin lauric acid ester, carboxylate salt of glutamic acid, and fatty acid ester of ethoxylated sorbitan as an auxiliary surfactant to prepare a first mixture. step;
preparing a second mixture by adding a perfluorocarbon compound to the first mixture;
homogenizing the second mixture to prepare a crude emulsion; and
bubbling oxygen into the crude emulsion,
A method for preparing the composition of any one of claims 1 to 16.

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