Patent Description:
Most animals shed and regrow hair seasonally, but humans shed about <NUM> strands of hair out of about <NUM>,<NUM> strands and about <NUM> strands regrow every day, thus always maintaining a similar number. Although hair is not an organ critical in sustaining life, it is an indicator of health state and an important part of the body in terms of appearance. Whereas hair loss is considered a normal physiological event for those with a lot of hair, those who suffer from severe hair loss can be badly affected in terms of mental well-being and quality of life due to depression, sense of shame, social isolation, etc..

The hair growth cycle consists of anagen, catagen and telogen phases. During the anagen phase, hair growth is promoted as cell division occurs actively in the hair dermal papilla, and hair grows only in this stage. Considering that the anagen is about <NUM> to <NUM> years for men and about <NUM> to <NUM> years for women, about <NUM> to <NUM> % of hair is in the anagen phase. In the catagen phase, which lasts about <NUM> to <NUM> weeks, the cell division declines gradually. Lastly, in the telogen phase, the hair dermal papilla is withdrawn and the hair separated from the capillary vessel and simply stuck in the scalp. This lasts about <NUM> months and the hair in the telogen phase is easily lost upon physical stimulation.

<CIT> discloses that a composition containing a natural extract can be applied to prevent hair loss or promote hair growth. However, according to the process (hair loss) of the scalp becoming bald, the microvessels connected to the hair roots are thinned, which results in insufficient oxygen supply through the microvessels. As the basis for hair loss scalp due to insufficient oxygen, there has been a report that lactate, which occurs when oxygen metabolism is insufficient, is accumulated. There has been a report that the activity of hair stem cells is increased again when an enzyme (lactate dehydrogenase) that degrades the lactate is treated. To summarize, oxygen is the most important element in promoting or maintaining the growth of dermal papilla cells, which are located in the center of the hair follicle and are the basis of new hair generation (Non-Patent Document <NUM>).

Oxygen for activating the metabolism of dermal papilla cells is a gas, so it cannot penetrate the skin in a general way. Accordingly, there is a need for 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.

<CIT> discloses the use of oxygen carriers such as phytohemoglobins and/or perfluorocarbon compounds (PFCs), emulsified with lecithin and further lipids, to improve oxygen supply and energy metabolism of the hair follicle. This enables improvement of hair growth.

<CIT> discloses a composition for restoring hair, comprising a hair restorer compound such as minoxidil, whereby an optional ingredient is an oxygen carrier such as perfluorodecalin. <CIT> discloses a perfluorocarbon emulsion which is useful among other indications to provide oxygen to the hair in hair loss products. The emulsion comprises egg yolk phospholipid as emulsifier and has a particle size in the nanometre range.

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

In order to achieve the object of the present disclosure described above, the present disclosure provides a nanoemulsion composition of oxygen gas sustained release and method for preparing the same, including a water phase part containing water; and an oil phase part dispersed in the water phase part and made of nanoparticle containing a perfluorocarbon compound, wherein the oil phase part contains oxygen gas, and the oxygen gas is released in sustained release.

According to the present disclosure, there is an advantage of preventing hair loss or promoting hair growth by increasing the amount of oxygen gas supplied to the hair bulb and the oxygen release time from the hair bulb.

The terms used in this specification have been selected as currently widely used general terms as possible while considering the functions in the present disclosure, which may vary depending on the intention, precedent, or emergence of new technology of those skilled in the art. In addition, in a specific case, there is a term arbitrarily selected by the applicant, and in this case, the meaning will be described in detail in the description of the corresponding invention. Therefore, the terms used in the present disclosure should be defined based on the meaning of the term and the contents of the present disclosure, rather than the simple name of the term.

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

Numerical ranges are inclusive of the numerical values defined in this disclosure. Every maximum numerical limitation given throughout this specification includes all lower numerical limitations as if the lower numerical limitation were expressly written. Every minimum numerical limitation given throughout this specification includes all higher numerical limitations as if the higher numerical limitation were expressly written. Any numerical limitation given throughout this specification shall include all numerical ranges within the broader numerical range, as if the narrower numerical limitation were expressly written.

As used herein, the words "comprising," "having," "containing," are inclusive or openended 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 items listed prior to the term. For example, "A, B, C, or a combination thereof" means A, B, C, AB, AC, BC or ABC, and it is intended to include at least one of BA, CA, CB, CBA, BCA, ACB, BAC or CAB where order is important in a particular context. 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. One of ordinary skill in the art will understand that there is typically no limit to the number of items or terms in any combination, unless the context makes it clear otherwise.

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

In one aspect, the present disclosure provides a nanoemulsion composition of oxygen gas sustained release including a water phase part containing water; and an oil phase part dispersed in the water phase part and made of nanoparticle containing a perfluorocarbon compound, wherein the oil phase part contains oxygen gas, and the oxygen gas is released in sustained release.

Unlike microemulsion, nanoemulsion is a kinetically stable emulsion, and since there is no aggregation or coalescence between particles, it is stable for a long period of time even under low viscosity conditions. The reason why the nanoemulsion is used as a useful formulation is that (<NUM>) the particles are very small, so they are not affected by gravity due to the Brownian motion of the particles, so they are free from precipitation or creaming, (<NUM>) that there is no aggregation phenomenon with small particles, so the possibility of emulsion separation is low, (<NUM>) that small particles can prevent coalescence due to less deformation of the particles, (<NUM>) that it can improve skin penetration of active ingredients by retaining a wide interfacial membrane with small particles, and (<NUM>) that it can be prepared with significantly less amount of surfactant compared to microemulsions. The nanoemulsion may be an oil-in-water (O/W) emulsion.

The "oxygen gas" may be naturally occurring oxygen or synthetically produced oxygen. In general, it is known that the oxygen concentration in the atmosphere is at a level of <NUM> to <NUM> %, and an oxygen condition of about <NUM> % is called a normoxia condition. An oxygen condition of <NUM> to <NUM> % is called a hypoxia condition, and an oxygen condition of <NUM> % or less is called an extreme hypoxia (or anoxia) condition. Since hair follicles can grow in an oxygen condition of <NUM> to <NUM> %, 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" refers to a drug in which active ingredients are released immediately, and is a formulation that releases most of the active ingredients within a few seconds. In contrast, the term "sustained release" refers to a formulation that releases active ingredients slowly for several tens of seconds to several hours, and is designed to maintain an effective amount of the active ingredients over a relatively long period of time. It refers to a formulation with fewer side effects because the number of administrations is less than that of a general drug and the bioreaction is uniform because of the characteristic of a "sustained release" formulation that lasts for a certain period of time after reaching a therapeutic blood concentration. The nanoemulsion composition of the present disclosure exhibits a "oxygen gas sustained release" profile, thereby releasing oxygen for a period of at least <NUM> seconds or maintaining an oxygen condition favorable for preventing hair loss or promoting hair growth.

The average diameter of the nanoparticles is <NUM> to <NUM>. More specifically, the average diameter of the nanoparticles may be <NUM> or more, <NUM> or more, <NUM> or more, <NUM> or more, <NUM> or more, <NUM> or more, <NUM> or more, <NUM> or more, <NUM> or more, <NUM> or more, <NUM> or more; <NUM> or less, <NUM> or less, <NUM> or less, <NUM> or less, <NUM> or less, <NUM> or less, <NUM> or less, <NUM> or less, <NUM> or less, <NUM> or less, <NUM> or less not, but is not limited thereto.

According to one embodiment of the present disclosure, the oxygen gas may be collected in an amount of <NUM> ppm (v/w) to <NUM> ppm (v/w) based on the total weight of the nanoemulsion composition. More specifically, the oxygen gas may be collected in an amount of <NUM> ppm (v/w) or more, <NUM> ppm (v/w) or more, <NUM> ppm (v/w) or more, <NUM> ppm (v/w) or more, <NUM> ppm (v/w) or more, <NUM> ppm (v/w) or more, <NUM> ppm (v/w) or more, <NUM> ppm (v/w) or more, <NUM> ppm (v/w) or more, <NUM> ppm (v/w) or more, <NUM> ppm (v/w) or more, <NUM> ppm (v/w) or more, <NUM> ppm (v/w) or more; <NUM> ppm (v/w) or less, <NUM> ppm (v/w) or less, <NUM> ppm (v/w) or less, <NUM> ppm (v/w) or less, <NUM> ppm (v/w) or less, <NUM> ppm (v/w) or less, <NUM> ppm (v/w) or less, <NUM> ppm (v/w) or less, or <NUM> ppm (v/w) or less, based on the total weight of the nanoemulsion composition, but is not limited thereto.

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

Examples of the perfluorocarbon compound may include cyclic or acyclic perfluorinated hydrocarbon, and perfluorinated aliphatic hydrocarbon or perfluorinated aromatic hydrocarbon may be included as the example. Preferably, examples of the perfluorocarbon compound may include chain fluorinated aliphatic hydrocarbon of <NUM> to <NUM> carbon atoms, and cyclic perfluorinated aliphatic hydrocarbons of <NUM> to <NUM> carbon atoms having <NUM> or <NUM> rings.

Examples of chain perfluorinated aliphatic hydrocarbon of <NUM> to <NUM> carbon atoms may include perfluorohexane, perfluoroheptane, perfluorooctane, perfluorononane, perfluorodecane, perfluoroundecane and perfluorododecane.

Examples of cyclic perfluorinated aliphatic hydrocarbon of <NUM> to <NUM> carbon atoms having <NUM> or <NUM> rings may 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 <NUM> to <NUM> 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 one or more of a chain perfluorinated aliphatic hydrocarbon of <NUM> to <NUM> carbon atoms and a cyclic perfluorinated aliphatic hydrocarbon of <NUM> to <NUM> carbon atoms having <NUM> or <NUM> rings. According to one embodiment of the present disclosure, the perfluorocarbon compound is a combination of a chain perfluorinated aliphatic hydrocarbon of <NUM> to <NUM> carbon atoms and a cyclic perfluorinated aliphatic hydrocarbon of <NUM> to <NUM> carbon atoms having <NUM> or <NUM> rings.

According to one embodiment of the present disclosure, the perfluorocarbon compound is one or more 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 content ratio of the perfluorodecalin (PFD) and perfluorohexane (PFH) is <NUM> : <NUM> to <NUM> : <NUM> by weight. More specifically the content ratio of the perfluorodecalin (PFD) and perfluorohexane (PFH) is <NUM> : <NUM> or more, <NUM> : <NUM> or more, <NUM> : <NUM> or more, <NUM> : <NUM> or more, <NUM> : <NUM> or more, <NUM> : <NUM> or more, <NUM> : <NUM> or more; <NUM> : <NUM> or less, <NUM> : <NUM> or less, <NUM> : <NUM> or less, <NUM> : <NUM> or less, <NUM> : <NUM> or less, <NUM> : <NUM> or less, <NUM> : <NUM> or less, <NUM> : <NUM> or less, <NUM> : <NUM> or less by weight, but is not limited thereto. According to one embodiment of the present disclosure, the content ratio of perfluorodecalin (PFD) and perfluorohexane (PFH) is <NUM> : <NUM> by weight.

According to one embodiment of the present disclosure, the content of the perfluorocarbon compound may be <NUM> % to <NUM> % by weight based on the total weight of the nanoemulsion composition. More specifically, the content of the perfluorocarbon compound may be <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more; <NUM> % by weight or less, <NUM> % by weight or less, <NUM> % by weight or less, <NUM> % by weight or less, <NUM> % by weight or less, based on the total weight of the nanoemulsion composition, but is not limited thereto.

The oil phase part further contains one or more of phospholipid, polyglycerin stearic acid ester, and fatty acid ester of sorbitan as a main surfactant, and one or more 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.

In the present disclosure, a surfactant having a relatively high emulsifying power (interfacial 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 is exhibited in that the surfactant is distributed faster and more densely in the inner phase.

According to one embodiment of the present disclosure, the total content of the auxiliary surfactant may be <NUM> to <NUM> % by weight based on the total weight of the nanoemulsion composition. More specifically, the total content of the auxiliary surfactant may be <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more, <NUM> % by weight or more ; <NUM> % by weight or less, <NUM> % by weight or less, <NUM> % by weight or less, <NUM> % by weight or less, <NUM> % by weight or less, <NUM> % by weight or less based on the total weight of the nanoemulsion composition, but is not limited thereto.

The content ratio of the main surfactant and the auxiliary surfactant is <NUM> : <NUM> to <NUM> : <NUM>.

Examples of the phospholipid may include lecithin, hydrogenated lecithin, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, and phosphatidylinositol. According to one embodiment of the present disclosure, the phospholipid is one or more 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 one or more selected from the group consisting of polyglyceryl-<NUM> stearate, polyglyceryl-<NUM> isostearate, polyglyceryl-<NUM> diisostearate, and polyglyceryl-<NUM> distearate. According to one embodiment of the present disclosure, the polyglycerin stearic acid ester is polyglyceryl-<NUM> stearate.

According to one embodiment of the present disclosure, the fatty acid ester of sorbitan is one or more selected from the group consisting of sorbitan monolaurate (Span <NUM>), sorbitan monopalmitate (Span <NUM>), sorbitan monostearate (Span <NUM>), sorbitan monooleate (Span <NUM>), sorbitan isostearate (Span <NUM>).

According to one embodiment of the present disclosure, the glyceryl diester (= diglyceride, diacylglycerol) is one or more selected from the group consisting of glyceryl dilaurate, glyceryl diarachidate, glyceryl dibehenate, glyceryl dieleucate, glyceryl dihydroxystearate, glyceryl diisopalmitate, glyceryl diisostearate, glyceryl dilinoleate, glyceryl dimyristate, glyceryl dioleate, glyceryl diricinoleate, glyceryl dipalmitate, glyceryl dipalmitoliate, glyceryl distearate, glyceryl palmitate lactate, glyceryl stearate citrate, glyceryl stearate lactate and glyceryl stearate succinate. 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 one or more selected from the group consisting of inulin octanoate, inulin decanoate, inulin laurate, inulin myristate, inulin lauryl carbamate, inulin palmitate, inulin stearate, inulin arachidate, inulin behenate, inulin oleate, inulin <NUM>-ethylhexanoate, inulin isomyristate, 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 polyglycerin lauric acid ester is one or more selected from the group consisting of polyglyceryl-<NUM> laurate and polyglyceryl-<NUM> laurate. According to one embodiment of the present disclosure, the polyglycerin lauric acid ester is polyglyceryl-<NUM> laurate.

According to one embodiment of the present disclosure, the carboxylate salt of glutamic acid is one or more selected from the group consisting of sodium cocoyl glutamate, sodium lauroyl glutamate, sodium myristoyl glutamate, sodium palmitoyl glutamate, sodium stearoyl glutamate, disodium cocoyl glutamate, 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 ethoxylated sorbitan may include PEG-<NUM> sorbitan monolaurate (Tween <NUM>), PEG-<NUM> sorbitan monolaurate (Tween <NUM>), PEG-<NUM> sorbitan monopalmitate (Tween <NUM>), PEG-<NUM> sorbitan monostearate (Tween <NUM>), PEG-<NUM> sorbitan monostearate (Tween <NUM>), PEG-<NUM> sorbitan monooleate (Tween <NUM>). According to one embodiment of the present disclosure, the nonionic surfactant may be Tween <NUM>.

According to one embodiment of the present disclosure, at a time point at least <NUM> seconds after the start of dissolution of the composition, the oxygen gas concentration may reach equilibrium with the system (e.g., when the composition is in contact with the atmospheric layer, the system may be the atmospheric layer). Therefore, oxygen gas can be released for more than <NUM> seconds until equilibrium is reached. More specifically, oxygen gas can be released for <NUM> seconds or more, <NUM> seconds or more, <NUM> seconds or more, <NUM> seconds or more, <NUM> seconds or more, <NUM> minute or more, <NUM> minutes or more, <NUM> minutes or more, <NUM> minutes or more, <NUM> minutes or more, <NUM> hour or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, <NUM> hours or more, but is not limited thereto.

The term "equilibrium" refers to a state in which the oxygen gas transfer rate between the composition of the present disclosure and the system in contact with the composition is the same, so that the amount of oxygen gas in the composition is maintained at a constant level. In order for the oxygen gas concentration of the composition to reach equilibrium with the system, or even after it is reached, the time for continuously releasing oxygen gas into the system may be <NUM> minute or more by the sustained release of oxygen gas from the nanoemulsion of the present disclosure.

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

The term "hair loss" may refer to absence of hair on the part where hair is normally present, for example, it may mean depilation of hair from the scalp. In addition, the term "promoting hair growth" may refer to the healthy growth of existing hair as well as the promotion of growth of new hair.

The hair loss prevention or hair growth promotion may be due to the proliferation of hair follicle cells or hair growth. Specifically, the proliferation of the hair follicle cells means the proliferation of dermal papilla cells or hair germinal matrix cells. The "dermal papilla cells" are skin cells surrounding the hair follicle and may refer to cells that play an important role in hair growth. The "hair germinal matrix cells" refers to cells existing in the dermal papilla tissue and capable of producing hair. Specifically, the hair growth means that the dermal papilla, which is supplied with nutrients and oxygen from the capillaries, delivers nutrients and various growth factors, growth signals, etc. to the hair germinal matrix cells, while the hair germinal matrix cells divide. Therefore, in preventing hair loss or promoting hair growth, the supply of nutrition and oxygen to the dermal papilla cells and/or hair germinal matrix cells is an important factor. The present disclosure has been devised from the above, 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 the hair bulb.

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

According to one embodiment of the present disclosure, the composition may be a formulation for external application to skin. The term "skin" refers to a tissue covering the body surface of an animal, and is the broadest concept including not only tissues covering body surfaces such as the face or body, but also 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 commonly used method. For formulation, reference may be made to the contents disclosed in the <NPL>.

Specifically, the composition may be formulated as a hair rinse, a shampoo, a hair conditioner, a hair pack, a hair oil, a hair treatment, a hair cream, a hair lotion, a hair gel, a hair essence, a hair spray, a hair serum, a hair ampoule, an emulsion, cream, an essence, etc. 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 can be of a leave-on or leave-in type, meaning that the formulation remains on the hair after application.

The composition may additionally contain fatty substances, organic solvents, solubilizers, thickening agents, gelling agents, emollients, antioxidants, suspending agents, stabilizers, foaming agents, fragrances, surfactants, antiseptics, pH controllers, water, ionic or nonionic emulsifiers, fillers, sequestering agents, chelating agents, preservatives, blocking agents, wetting agents, essential oils, dyes, pigments, hydrophilic or lipophilic active agents, adjuvants commonly used in the field of cosmetology or dermatology, such as any other ingredients commonly used in cosmetics, as needed.

When the formulation of the cosmetic composition is a solution or emulsion, a solvent, solubilizer or emulsifier is used as a carrier component. As examples, there are water, ethanol, isopropanol, ethyl carbonate, ethyl acetate, benzyl alcohol, benzyl benzoate, propylene glycol, <NUM>,<NUM>-butylglycol oil, glycerol fatty ester, polyethylene glycol or fatty acid ester of sorbitan.

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

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

The cosmetic composition may additionally contain a thickening agent. As the thickening agent included in the cosmetic composition, methyl cellulose, carboxy methyl cellulose, carboxy methyl hydroxy guanine, hydroxy methyl cellulose, hydroxy ethyl cellulose, carboxy vinyl polymer, polyquaternium, cetearyl alcohol, stearic acid, carrageenan and the like may be used, and preferably, one or more of carboxymethyl cellulose, carboxyvinyl polymer, and polyquaternium may be used, and most preferably, carboxyvinyl polymer may be used.

The cosmetic composition may contain various suitable bases and additives as needed, and the types and amounts of these components can be easily selected by the inventor. If necessary, it may contain acceptable additives, for example, may further include components such as preservatives, pigments, and additives commonly used in the art. Specifically, the preservative may be phenoxyethanol or <NUM>,<NUM>-hexanediol, and the fragrance may be an artificial fragrance.

The cosmetic composition may include a composition selected from the group consisting of water-soluble vitamin, oil-soluble vitamin, high-molecular peptide, high-molecular polysaccharide, sphingolipid, and seaweed extract. As other ingredients that may be added, there may be an oil and fat, a moisturizer, an emollient, a surfactant, an organic and inorganic pigment, an organic powder, an UV absorber, an antiseptic, a bactericide, antioxidant, a plant extract, a pH controller, an alcohol, a colorant, a fragrance, a blood circulation stimulant, a cooling agent, an antiperspirant, purified water, etc. In addition, the ingredients that may be contained in the cosmetic composition are not limited thereto and, the amount of the ingredients may be determined within a range not negatively affecting the purpose and effect of the present disclosure.

The pharmaceutical composition may be administered parenterally or orally depending on purposes and the pharmaceutical composition may be administered once or several times a day such that a daily dosage is to be <NUM> to <NUM>, specifically <NUM> to <NUM>, per kg body weight. The administration dosage for a particular patient may vary depending on the body weight, age, sex, health status, and diet of a patient, administration time, administration method, excretion rate, severity of disease, etc..

The pharmaceutical composition may be prepared into any formulation suitable for a pharmaceutical composition, including an oral formulation such as a powder, a granule, a tablet, a soft or hard capsule, a suspension, an emulsion, a syrup, an aerosol, etc., a formulation for external application to skin such as an ointment, a cream, etc., a suppository, an injection, a sterile injectable solution, etc., according to a commonly used method. Specifically, it may be prepared into an injection or a formulation for external application to skin.

The pharmaceutical composition may be administered to a mammal such as rat, mouse, livestock, human, etc. through various routes including parenteral and oral routes. Any mode of administration may be expected. For example, it may be administered orally, transdermally, intravenously, intramuscularly or subcutaneously. The pharmaceutical composition may be administered through various routes that can be easily adopted by those skilled in the art. In particular, the pharmaceutical composition may be administered as a formulation for external application to skin by applying onto the skin surface.

In the food composition, the food composition may be a health functional food composition. The formulation of the food composition is not particularly limited. For example, it may be formulated into a tablet, a granule, a powder, a liquid formulation such as a drink, a caramel, a gel, a bar, etc. The food composition of each formulation may contain, in addition to the active ingredient, various ingredients that are commonly used in the related art and can be appropriately selected by those skilled in the art without difficulty depending on the formulation or purpose of use. A synergistic effect may occur when applied simultaneously with other raw materials.

In the food composition, the determination of the administration dose of the active ingredient is within the level of those skilled in the art. A daily dose may be, for example, <NUM>/kg/day to <NUM>/kg/day, more specifically <NUM>/kg to <NUM>/kg/day, but is not limited thereto. The administration dose will vary depending on various factors such as age, health status, and complications of the subject to be administered.

The food composition, for example, may be various foods such as a chewing gum, a caramel product, a candy, a frozen dessert, confectionery, etc., drink products such as a soft drink, mineral water, an alcoholic beverage, etc. or health functional foods including a vitamin and a mineral.

The food composition may contain various nutrients, vitamins, minerals (electrolytes), flavoring agents including synthetic and natural flavoring agents, colorants, extenders (cheese, chocolate, etc.), pectic acid and salts thereof, alginic acid and salts thereof, organic acids, protective colloidal thickeners, pH controllers, stabilizers, preservatives, glycerin, alcohols, carbonating agents used in soft drinks, etc. The functional food composition may contain a pulp for preparing a natural fruit juice, a fruit drink or a vegetable drink. These ingredients may be used either independently or in combination. The mixing ratio of the additives is of no significant importance. In an aspect of the present disclosure, the additives may be contained in an amount of about <NUM> to <NUM> parts by weight based on <NUM> parts by weight of the composition.

In another aspect, the present disclosure provides a method for preparing the composition including the steps of preparing a first mixture by mixing water; oil; one or more of phospholipid and fatty acid ester of sorbitan; and a nonionic surfactant; preparing a second mixture by adding a perfluorocarbon compound to the first mixture; preparing a crude emulsion by homogenizing the second mixture; and bubbling oxygen in the crude emulsion.

A buffer solution may be further mixed in the step of preparing the first mixture. Examples of the buffer may include <NUM>-(<NUM>-hydroxyethyl)-<NUM>-piperazineethanesulfonic acid (HEPES), <NUM>-(N-morpholino)ethanesulfonic acid (MES), phosphated buffered saline (PBS), tris(<NUM>-amino-<NUM> hydroxymethyl propane-<NUM>,<NUM>-diol (THAM), phosphate buffer (PB), <NUM>-(N-morpholino)propanesulfonic acid (MOPS).

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 <NUM> to <NUM> bar.

For the components mentioned in the preparation method, the same contents as those related to the composition may be applied.

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

As another aspect, the present disclosure provides a method for preventing hair loss or promoting hair growth, including the steps of applying to an individual in need thereof a nanoemulsion composition including a water phase part containing water and an oil phase part dispersed in the water phase part and made of nanoparticle containing a perfluorocarbon compound. The oil phase part contains oxygen gas, and the oxygen gas is released in sustained release.

As another aspect, the present disclosure provides a water phase part containing water and an oil phase part dispersed in the water phase part and made of nanoparticle containing a perfluorocarbon compound, which are used in preventing hair loss or promoting hair growth. The oil phase part contains oxygen gas, and the oxygen gas is released in sustained release.

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

Water; oleyl polyoxyl-<NUM> glyceride and propylene glycol monocaprylate (Gatefosse, Saint-Priest, France); egg phosphatidylcholine or soy phosphatidylcholine (Lipoid, Ludwigshafen, Germany); and Tween <NUM> or Poloxamer <NUM> (Merck, Darmstadt, Germany) were dissolved in PBS (pH <NUM>) and stirred at room temperature for <NUM> minutes using a magnetic stirrer. PFOB (Sinquest Laboratories, FL, USA) was then added to the mixture and stirred for <NUM> minutes. The mixture was homogenized at <NUM> rpm for <NUM> seconds in a high-speed homogenizer (HG-15A; Daehan Science, Wonju, Korea) to obtain a crude emulsion, and then treated in an LV1-<NUM> microfluidics (Microfluidics, Westwood, Massachusetts, USA) at <NUM>,<NUM> psi (about <NUM> bar) for <NUM> cycles. Next, oxygen was bubbled into the crude emulsion at a rate of <NUM>/min to prepare a nanoemulsion containing oxygen gas.

A nanoemulsion composition was prepared according to the composition of Table <NUM> below. The content of each ingredient was expressed as a relative content ratio, and the unit was weight %.

The particle size and surface charge of the prepared nanoemulsion were measured and evaluated using a zeta potential/particle size analyzer (ELSZ-<NUM> series, Otsuka Electronics, Japan). The measurement was performed by diluting the nanoemulsion sample for evaluation with phosphate buffered saline (PBS; Corning, USA) and then putting the diluted nanoemulsion sample into the analyzer. The result was shown in <FIG> (unit: nm).

With respect to the types of the main surfactant and the auxiliary surfactant, when Poloxamer <NUM> was used as the auxiliary surfactant, it was confirmed from <FIG> that an emulsion having a diameter exceeding <NUM>, not in nano units, was produced. Thus, it can be seen that the use of Tween <NUM> as the auxiliary surfactant is particularly preferred.

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

The particle size and surface charge of the prepared nanoemulsion were measured and evaluated using a zeta potential/particle size analyzer (ELSZ-<NUM> series, Otsuka Electronics, Japan). The measurement was performed by diluting the nanoemulsion sample for evaluation with phosphate buffered saline (PBS; Corning, USA) and then putting the diluted nanoemulsion sample into the analyzer. The result was shown in Table <NUM> (unit: nm).

It was confirmed from Table <NUM> that even when PFOB was contained in a relatively high content of <NUM> % (w/v), the nanoemulsion of a desirable size was produced. On the other hand, when soy phosphatidylcholine was used as the main surfactant, it was confirmed that the size of the nanoemulsion was reduced as the content of PFOB was increased. When Span <NUM> was used as the main surfactant, it was confirmed that the size of the nanoemulsion increased as the content of PFOB increased.

The nanoemulsion compositions of Examples <NUM> and <NUM> to <NUM> were prepared as the content of PFOB was <NUM> % by weight, <NUM> % by weight, <NUM> % by weight, and <NUM> % by weight, respectively.

The oxygen concentration in the nanoemulsion was evaluated using a Fospor-R oxygen sensor (Ocean Optics, USA). A Fospor-R oxygen sensor probe was placed in a container containing the nanoemulsion solution to measure the oxygen concentration in real time. The result was shown in <FIG> (unit: ppm (v/w)).

It was confirmed from <FIG> that oxygen of <NUM> ppm (v/w) or more was encapsulated in all of the nanoemulsions of Example <NUM> and Examples <NUM> to <NUM>.

The nanoemulsion compositions of Example <NUM> and Examples <NUM> to <NUM> used in Test Example <NUM> were used.

The oxygen-encapsulated nanoemulsion was stored in a cell incubator fixed at <NUM>, and the oxygen concentration was measured in real time using a Fospor-R oxygen sensor (Ocean Optics, USA) at a set time interval. The result was shown in <FIG> (unit: ppm (v/w)).

In water used in a general industrial or home boiler, about <NUM> ppm of oxygen was dissolved at a temperature of <NUM>. It was confirmed from <FIG> that the nanoemulsion compositions of Examples <NUM> and <NUM> to <NUM> all continued to release oxygen until about <NUM> hours to reach an equilibrium state, and from thereafter, until <NUM> hours which was the measurement time, maintained an oxygen concentration exceeding <NUM> ppm, which was the equilibrium state of the amount of dissolved oxygen.

Using a medium containing <NUM> % fetal bovine serum (Gibco, USA) and <NUM> % penicillin/streptomycin (Invitrogen, USA) in DMEM (Dulbecco's Modified Eagle's Medium) as a culture medium, human follicle dermal papilla cells (HFDPC, cat #C-<NUM>; Promo Cell, USA) were cultured in a <NUM> % carbon dioxide incubator at <NUM> for <NUM> day, then the medium was exchanged and cultured again for two days. Thereafter, the cells were cultured while exchanging with a new medium every two days.

After the dermal papilla cells cultured in Reference Example <NUM> were newly cultured in a <NUM> well dish for one day, the cultured cells were treated with the nanoemulsion composition of Example <NUM> in which oxygen was captured at a concentration of <NUM> ppm to <NUM> ppm and Example <NUM> in which oxygen was not captured as a control at a concentration of <NUM> ppm to <NUM> ppm, respectively. After incubation for <NUM> hours and <NUM> hours, cell viability was confirmed by measuring absorbance at <NUM> using the QuantiMax WST-<NUM> Cell viability assay kit. The result was shown in <FIG> (unit: %).

Like the control in which oxygen was not captured, even when the nanoemulsion composition of Example <NUM> in which oxygen was collected was treated, it did not have any effect on the cells as shown in <FIG>. From this, it was confirmed that the nanoemulsion composition of Example <NUM> had no toxicity to cells and was safe.

After removing the medium from the dermal papilla cells cultured in Reference Example <NUM>, under extreme hypoxia conditions, the cells were treated with Example <NUM> in which oxygen was captured and the nanoemulsion composition of Example <NUM> in which oxygen was not captured as a control, respectively. The oxygen concentration in the medium was measured using a NeoFox fluorometer (Ocean Optics, Dunedin, Florida, USA) equipped with a Fospor-R oxygen sensor while culturing for <NUM> hours. The result was shown in <FIG> (unit: %).

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

After removing the medium from the dermal papilla cells cultured in Reference Example <NUM>, under the conditions and treatments of Table <NUM> below, the cells were treated with Example <NUM> in which oxygen was captured and the nanoemulsion composition in which oxygen was not captured as a control, respectively. Cells were treated with the nanoemulsion composition of Example <NUM> in which oxygen was captured at concentrations of <NUM> ppm and <NUM> ppm, respectively.

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

It was confirmed from <FIG> and <FIG> that for the growth of dermal papilla cells, it was more effective to supply oxygen rather than the presence of serum. In addition, it was confirmed that compared to the treatment with the nanoemulsion composition in which oxygen was captured at a concentration of <NUM> ppm, when the nanoemulsion composition in which oxygen was captured at a concentration of <NUM> ppm was treated, better cell growth ability was exhibited.

Hair follicle samples to be applied to the experiment were isolated from humans. The isolated hair follicle samples were placed in a <NUM>-well plate (Nunc, Wiesbaden, Germany) and cultured in DMEM medium containing <NUM> L-glutamine (PAA, Coelbe, Germany), <NUM>µg/ml insulin, <NUM> ng/ml hydrocortisone (Sigma, St Louis, MO), 100u/ml Penicillin / streptomycin (Gibco, NY, USA) at <NUM> to <NUM> samples per well.

Under extreme hypoxia conditions, the nanoemulsion in which oxygen was captured at a concentration of <NUM> ppm and the nanoemulsion composition in which oxygen was not captured as a control were treated in the <NUM>-well plate, respectively. A sample without any treatment was used as a negative control. The medium was changed every <NUM> to <NUM> days. The hair follicles were photographed using a stereo microscope (Olympus SZX16, Japan), and the hair growth length was measured using the Image J program, and the image was shown in <FIG>. A graph showing the quantification of hair growth length was shown in <FIG> (unit: µm).

It was confirmed from <FIG> and <FIG> that when the nanoemulsion composition in which oxygen was captured at a concentration of <NUM> ppm was treated, the hair follicle length growth ability was statistically significant.

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

Then, PFOB (Sinquest Laboratories, FL, USA), BB61 (<NUM>-<NUM>% perfluorohexane, <NUM>-<NUM>% perfluorodecalin and <NUM>-<NUM>% pentafluoropropane; fiflow® BB61; Innovation Company, De Hue, France) or BTX (<NUM>-<NUM>% perfluorohexane, <NUM>-<NUM>% perfluoroperhydrophenanthrene, <NUM>-<NUM>% perfluorodecalin and <NUM>-<NUM>% perfluorodimethylcyclohexane; fiflow® BTX; Innovation Company, De Hue, France) was added to the mixture and stirred for <NUM> minutes. The mixture was homogenized at <NUM> rpm for <NUM> seconds in a high-speed homogenizer (HG-15A; Daehan Science, Wonju, Korea) to obtain a crude emulsion, and then treated in an LV1-<NUM> microfluidics (Microfluidics, Westwood, Massachusetts, USA) at <NUM>,<NUM> psi (about <NUM> bar) for <NUM> cycles. Next, oxygen was bubbled into the crude emulsion at a rate of <NUM>/min to prepare a nanoemulsion containing oxygen gas.

The particle size, surface charge, and polydispersity index (PDI) of the prepared nanoemulsion were measured and evaluated using a zeta potential/particle size analyzer (ELSZ-<NUM> series, Otsuka Electronics, Japan). The measurement was performed by diluting the nanoemulsion sample for evaluation with phosphate buffered saline (PBS; Corning, USA) and then putting the diluted nanoemulsion sample into the analyzer. The result was shown in <FIG> (particle size unit: nm).

It was confirmed from <FIG> that the nanoemulsion of Comparative Example <NUM> had a large particle size and a polydisperse distribution. On the other hand, in the case of the nanoemulsion of Comparative Example <NUM>, a lot of bubbles were formed during production, and in particular, the nanoemulsion of Comparative Example <NUM> produced bubbles to the extent that it was impossible to manufacture.

Water; oleyl polyoxyl-<NUM> glyceride and propylene glycol monocaprylate (Gatefosse, Saint-Priest, France); soy phosphatidylcholine (Lipoid, Ludwigshafen, Germany), hydrogenated lecithin (Lipoid P100-<NUM>, Lipoid GmbH) or polyglyceryl-<NUM> stearate (Nikkol decaglyn <NUM>-sv, Nikko Chemicals Co. ); and Tween <NUM> (Merck, Darmstadt, Germany), inulin lauryl carbamate (Inutec SL1, Creachem), polyglyceryl-<NUM> 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 <NUM>) and stirred at room temperature for <NUM> minutes using a magnetic stirrer.

PFOB (Sinquest Laboratories, FL, USA), perfluorodecalin (PFD, Sigma, St Louis, MO) and/or perfluorohexane (PFH, Sigma, St Louis, MO) was then added to the mixture and stirred for <NUM> minutes. The mixture was homogenized at <NUM> rpm for <NUM> seconds in a high-speed homogenizer (HG-15A; Daehan Science, Wonju, Korea) to obtain a crude emulsion, and then treated in an LV1-<NUM> microfluidics (Microfluidics, Westwood, Massachusetts, USA) at <NUM>,<NUM> psi (about <NUM> bar) for <NUM> cycles. Next, oxygen was bubbled into the crude emulsion at a rate of <NUM>/min to prepare a nanoemulsion containing oxygen gas.

Nanoemulsion compositions were prepared according to the compositions of Tables <NUM> to <NUM> below. The content of each ingredient was expressed as a relative content ratio, and the unit was weight %.

The nanoemulsion compositions of Example <NUM>, Examples <NUM>-<NUM> were used.

The particle size, surface charge, and polydispersity index (PDI) of the prepared nanoemulsion were measured using a zeta potential/particle size analyzer (ELSZ-<NUM> series, Otsuka Electronics, Japan). The measurement was performed by diluting the nanoemulsion sample for evaluation with phosphate buffered saline (PBS; Corning, USA) and then putting the diluted nanoemulsion sample into the analyzer. The result was shown in <FIG> (particle size unit: nm).

It was confirmed from <FIG> that all the nanoemulsions of Examples <NUM> and <NUM> to <NUM> had excellent properties with the particle size of <NUM> or less.

The nanoemulsion compositions of Examples <NUM> and <NUM> to <NUM> were used.

The same method as the evaluation method in Test Example <NUM> was performed. The measurement result at a temperature of <NUM> was shown in <FIG>, and the measurement result at a temperature of <NUM> was shown in <FIG> (particle size unit: nm).

When stored at <NUM>, the particle size of the nanoemulsion increased with time as shown in <FIG>, and this trend was slightly different depending on the concentration of PFH. More specifically, as the concentration of PFH increased, the particle size of the nanoemulsion further increased. In particular, in the case of the nanoemulsion of Example <NUM> without PFH, there was no significant change in particle size for <NUM> days, and in the case of the nanoemulsion of Example <NUM> without PFD, the particle size increased by about <NUM> % for <NUM> days. Therefore, it can be expected that PFH affects the particle stability of the nanoemulsion. As shown in <FIG>, when stored at <NUM>, the nanoemulsion showed a tendency to increase in particle size by about <NUM> to <NUM> % compared to the initial size in all groups after <NUM> days.

It was confirmed from <FIG> that <NUM> ppm (v/w) or more of oxygen was encapsulated in all of the nanoemulsions of Examples <NUM> and <NUM> to <NUM>. More specifically, the PFOB nanoemulsion of Example <NUM> contained about <NUM> ppm, and the PFD/PFH nanoemulsions of Examples <NUM> to <NUM> contained <NUM> to <NUM> ppm of oxygen depending on the mixing ratio. Through this, it can be seen that the oxygen encapsulation concentration decreases as the concentration of PFH increases in the PFD/PFH nanoemulsions of Examples <NUM> to <NUM>.

The oxygen concentration in the nanoemulsion was evaluated using a Fospor-R oxygen sensor (Ocean Optics, USA). A Fospor-R oxygen sensor probe was placed in a container containing the nanoemulsion solution to measure the oxygen concentration in real time. The result was shown in <FIG> (unit: ppm (v/w)). The result of normalization based on the initial concentration was shown in <FIG>.

As shown in <FIG> and <FIG>, the oxygen concentration remaining in the PFOB nanoemulsion of Example <NUM> was high until <NUM> hour after the start of the evaluation, but after that, the oxygen concentration remaining in the PFD/PFH nanoemulsions of Examples <NUM> to <NUM> was high with lapse of time. In particular, the higher the concentration of PFH, the higher the concentration of residual oxygen, and from this, it can be seen that the release of oxygen into the atmosphere is controlled by PFH.

The nanoemulsion compositions of Examples <NUM> to <NUM> were used.

The same method as the evaluation method in Test Example <NUM> was performed. The result was shown in <FIG> (particle size unit: nm).

It was confirmed from <FIG> that the size of the particles increased as the total content of the surfactant increased. However, as the total content of the surfactant increased, the viscosity and foaming degree of the nanoemulsion showed a tendency to increase proportionally.

As shown in <FIG>, in the case of Examples <NUM> to <NUM> in which the content ratio of the main surfactant and the auxiliary surfactant was <NUM> : <NUM>, it was found that the particle size increased as the total content of the surfactant increased. However, in the case of Examples <NUM> to <NUM> in which the content ratio of the main surfactant and the auxiliary surfactant was <NUM> : <NUM>, it was found that the particle size decreased as the total content of the surfactant increased. In particular, Example <NUM> formed the smallest particle size (<NUM>).

The same method as the evaluation method in Test Example <NUM> was performed. The results respectively measured at a temperature of <NUM> and at room temperature (RT) were shown in <FIG> (particle size unit: nm).

It was confirmed from <FIG> that the nanoemulsion particle size increased at both <NUM> and room temperature (RT) when <NUM> days had elapsed. In addition, it was found that the degree of particle size increase was different according to the storage temperature condition, and the refrigerated storage condition promoted the particle size increase.

The same method as the evaluation method in Test Example <NUM> was performed. The results respectively measured at <NUM> and room temperature (RT) were shown in <FIG> (particle size unit: nm).

It was confirmed from <FIG> that all the nanoemulsion compositions immediately after preparation were formed with a particle size of less than <NUM>. In particular, Example <NUM> formed the smallest particle size (<NUM>). In addition, it was found that the nanoemulsion particle size increased at both <NUM> and room temperature (RT) when <NUM> days had elapsed. Compared to the case of room temperature (RT), the increase in particle size was relatively suppressed at a temperature of <NUM>. Examples <NUM> and <NUM> showed good increase in particle size after <NUM> days.

It was confirmed from <FIG> that the size of the particles decreased as the total content of the surfactant increased both at a temperature of <NUM> and at room temperature (RT). In particular, Example <NUM> formed the smallest particle size (<NUM>). The viscosity was not high enough to affect the preparation and the degree of foam formation was also weak. It could be seen that the particle size of the nanoemulsion increased at a time point of <NUM> days in both the temperature of <NUM> and the room temperature (RT). Compared to the case of room temperature (RT), the increase in particle size was relatively suppressed at a temperature of <NUM>.

It was confirmed from <FIG> that all nanoemulsion compositions immediately after preparation were not significantly affected by the total content of surfactant and formed similar particle sizes. When stored at a temperature of <NUM>, it could be seen that the total content of the surfactant affected the stability of the nanoemulsion at the time of <NUM> days. For both the temperature of <NUM> and the room temperature (RT), the tendency of the particle size increase of the formulation decreased as the total content of the surfactant increased.

The nanoemulsion compositions of Examples <NUM>, <NUM> and <NUM> were used. Also, a composition containing PFOB, polyglyceryl-<NUM> stearate as the main surfactant, and glyceryl stearate citrate, inulin lauryl carbamate, sodium stearoyl glutamate as the auxiliary surfactants was used.

The same method as the evaluation method in Test Example <NUM> 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 result was shown in <FIG> (unit: ppm (v/w)).

It was confirmed from <FIG> that oxygen of <NUM> ppm (v/w) or more was encapsulated in all of the nanoemulsions of Examples <NUM>, <NUM> and <NUM>. After oxygen purge, the formulation of Example <NUM> had an oxygen encapsulation concentration of <NUM> ppm (v/w), which was higher than that of the composition containing PFOB having an oxygen concentration of <NUM> ppm (v/w).

The same method as the evaluation method in Test Example <NUM> 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 result was shown in <FIG> (unit: ppm (v/w)). The result of normalization based on the initial concentration was shown in <FIG>.

As shown in <FIG>, the composition containing PFOB released all oxygen within <NUM> hours, but all of the nanoemulsions of Examples <NUM>, <NUM>, and <NUM> continued to release oxygen until <NUM> hours had elapsed, and contained the oxygen of <NUM> to <NUM> ppm (v/w). It could be seen from <FIG> that the oxygen concentration of <NUM> to <NUM> % compared to the initial encapsulation amount was maintained for up to <NUM> hours.

Formulation examples of the composition according to one aspect of the present invention will be described below, but other various formulations are also applicable, which is not intended to limit the present invention, but merely to describe it in detail.

A shampoo was prepared in a commonly used method according to the composition shown in Table <NUM> below.

A rinse was prepared in a commonly used method according to the composition shown in Table <NUM> below.

An ointment was prepared in a commonly used method according to the composition shown in Table <NUM> below.

A massage cream was prepared in a commonly used method according to the composition shown in Table <NUM> below.

A hair pack was prepared in a commonly used method according to the composition shown in Table <NUM> below.

<NUM> of vitamin E, <NUM> of vitamin C, <NUM> of palm oil, <NUM> of hydrogenated vegetable oil, <NUM> of yellow wax and <NUM> of lecithin were mixed to the nanoemulsion composition of Example <NUM>, and mixed according to a commonly used method to prepare a soft capsule filling solution. Soft capsules were prepared by filling <NUM> of the solution per capsule. In addition, a soft capsule sheet was prepared in a ratio of <NUM> parts by weight of gelatin, <NUM> parts by weight of glycerin, and <NUM> parts by weight of sorbitol solution, separately from the above, and the filling solution was filled to prepare a soft capsule containing <NUM> of the composition.

<NUM> of vitamin E, <NUM> of vitamin C, <NUM> of galactooligosaccharide, <NUM> of lactose, and <NUM> of maltose were mixed to the nanoemulsion composition of Example <NUM>, granulated using a fluidized bed dryer, and <NUM> of sugar ester was added thereto. <NUM> of these compositions were compressed in a commonly used method to prepare tablets.

Injection was prepared in a commonly used method according to the composition shown in Table <NUM> below.

A health drink was prepared in a commonly used method according to the composition shown in Table <NUM> below.

Claim 1:
A nanoemulsion composition of oxygen gas sustained release, comprising:
a water phase part containing water; and
an oil phase part dispersed in the water phase part and made of nanoparticle containing a perfluorocarbon compound,
wherein the oil phase part contains oxygen gas, and the oxygen gas is released in sustained release,
wherein the oxygen gas sustained release means that the composition releases the oxygen gas for a period of at least <NUM> seconds,
wherein an average diameter of the nanoparticle is <NUM> to <NUM>,
wherein the nanoemulsion composition further comprises one or more of phospholipid, polyglycerin stearic acid ester and fatty acid ester of sorbitan as a main surfactant, and the nanoemulsion composition further comprises one or more 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 auxiliary surfactant, and
wherein a content ratio of the main surfactant and the auxiliary surfactant is <NUM> : <NUM> to <NUM> : <NUM> by weight.