Complex composition for prevention or alleviating hair loss

Abstract

The present invention relates to a composition for preventing or alleviating hair loss, comprising: a first nanoparticle in which a first ingredient having an anti-hair loss effect is encapsulated; and a second nanoparticle in which a second ingredient and a third ingredient having anti-hair loss effects are encapsulated, wherein the first nanoparticles include the first component, a lipophilic surfactant as a first solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)], and the second nanoparticles include the second component, the third component, a hydrophilic surfactant as a second solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)], whereby the composition exhibits excellent effects in preventing or alleviating hair loss and has superior stability.

Description

Complex composition for preventing or improving hair loss

[0001] The present invention is a complex composition for preventing or improving hair loss, and the composition of the present invention is a composition that is effective for preventing hair loss, promoting hair growth, anti-inflammation, anti-oxidation, and / or balancing the scalp.

[0002]

[0003] The human body has approximately 100,000 to 150,000 hairs, and each hair goes through a different cycle of growth, regression, and resting phases before growing and falling out. In a healthy person, this cycle usually repeats itself over a period of 3 to 6 years, resulting in an average of 60 to 100 hairs falling out per day. On the other hand, in patients with alopecia, the proportion of hair in the growth phase is low, while the proportion of hair in the regression and resting phases increases, resulting in an abnormal increase in hair loss.

[0004] The known causes of hair loss include excessive male hormones, excessive sebum secretion, decreased scalp function due to dandruff bacteria and other bacteria, genetic factors, aging, and stress. These factors work in combination to cause various scalp and hair abnormalities in addition to hair loss, such as decreased hair growth effect that promotes hair growth, decreased hair growth effect that thickens and strengthens thin and weak hair, excessive sebum production, proliferation of dandruff bacteria, itching, and dryness of the scalp and hair. In particular, itching and dandruff on the scalp not only worsen hair loss symptoms, but also cause inflammation and clog the hair roots.

[0005] Recently, due to social, environmental, and stressful circumstances, the number of people suffering from scalp and hair problems such as the above-mentioned is increasing. The average age of these people is also decreasing, and the number of women experiencing hair loss is also increasing. Accordingly, research has been conducted on compositions that can prevent various scalp and hair problems, including hair loss, and improve scalp and hair condition.

[0006] Recent research has highlighted dihydrotestosterone, a reduced form of the male hormone androgen, as a major factor in hair loss. Testosterone, a male hormone, is converted to dihydrotestosterone by the enzyme 5α-reductase. Hair follicles in patients with hair loss have high levels of 5α-reductase activity, which is known to contribute to hair loss.

[0007] Additionally, for some hair loss patients, unbearable itching occurs due to internal and external factors. If left untreated or scratched, it can lead to the formation of dead skin cells. If this persists for a long time, the scalp may become red and blotchy, and repeated scratching can lead to wounds, pus, scabs, and pimples. In such scalps, an inflammatory reaction may occur, which can lower the overall balance of the scalp and further accelerate hair loss.

[0008] In order to cure the cause of hair loss, research has been conducted using substances such as terpenes, flavones, isoflavones, and vitamins that inhibit the action of 5α-reductase. However, although efforts were made to create emulsion products in various formulations, there were disadvantages such as very low solubility and insufficient stability within the formulation, and the large particle size prevented absorption to the area needed for the 5α-reductase inhibition action. In addition, when the above-mentioned insoluble ingredients are dissolved through various emulsification products, the cause of hair loss is solved by blocking or making the hair follicles of the scalp oily, but in some cases, the scalp may be affected, such as inflammation in the hair follicles of the scalp, even though the cause of hair loss is prevented.

[0009] Substances that do not affect these hair follicles, prevent inflammatory reactions in the scalp, and maintain scalp balance have also been studied, but those that are effective have the disadvantage of having low solubility and being unstable.

[0010] Oleanolic acid, a type of triterpene compound, is a saponin derivative and is known to be effective in preventing hair loss or promoting hair growth (Korean Patent Publication No. 2016-0028801).

[0011] Apigenin is a type of flavonoid compound and is known to be effective in improving blood circulation and preventing hair loss.

[0012] Korean Patent Publication No. 10-2023-0154334 discloses an anti-hair loss emulsion composition comprising a first anti-hair loss ingredient comprising oleanolic acid, a second anti-hair loss ingredient comprising apigenin, and glabridin, which is known to be effective in preventing hair loss.

[0013] Meanwhile, equol is the main metabolite of daidzein, a type of isoflavone, and is known to have a hair loss prevention effect by inhibiting the function of dihydrotertosterone (DHT), a male hormone that causes hair loss.

[0014] Accordingly, the inventors of the present invention developed an emulsified formulation containing as active ingredients a triteprene compound such as oleanolic acid, which is known to be effective in preventing hair loss, a flavonoid compound such as apigenin, which is known to be effective in improving blood circulation and preventing hair loss, and an isoflavone compound such as equol, which is known to be effective in preventing hair loss instead of glabridin. The composition of the novel emulsified formulation according to the present invention exhibits a synergistic effect between the components, and thus has excellent long-term stability while effectively penetrating into the skin, thereby confirming that it is more effective in preventing hair loss, promoting hair growth, anti-inflammation, antioxidant activity, and maintaining scalp balance, and thus completing the present invention.

[0015]

[0016] The present invention aims to provide a novel emulsifying composition comprising a triterpene compound, a flavonoid compound and an isoflavone compound.

[0017]

[0018] The means to achieve the above objectives are as follows.

[0019] In one aspect, the present invention

[0020] First nanoparticles encapsulating a first ingredient having an anti-hair loss effect;

[0021] It includes a second nanoparticle encapsulating a second component and a third component having an anti-hair loss effect,

[0022] The first nanoparticle comprises a first component, a lipophilic surfactant as a first solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)],

[0023] The second nanoparticle provides a cosmetic composition for preventing or improving hair loss, comprising a second component, a third component, a hydrophilic surfactant as a second solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)].

[0024] In another aspect, the present invention

[0025] First nanoparticles encapsulating a first ingredient having an anti-hair loss effect;

[0026] It includes a second nanoparticle encapsulating a second component and a third component having an anti-hair loss effect,

[0027] The first nanoparticle comprises a first component, a lipophilic surfactant as a first solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)],

[0028] The second nanoparticle provides a pharmaceutical composition for preventing or treating hair loss, comprising a second component, a third component, a hydrophilic surfactant as a second solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)].

[0029] In another aspect, the present invention

[0030] First nanoparticles encapsulating a first ingredient having an anti-hair loss effect;

[0031] It includes a second nanoparticle encapsulating a second component and a third component having an anti-hair loss effect,

[0032] The first nanoparticle comprises a first component, a lipophilic surfactant as a first solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)],

[0033] The second nanoparticle provides a health functional food composition for preventing or improving hair loss, comprising a second component, a third component, a hydrophilic surfactant as a second solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)].

[0034] The present invention, in another aspect,

[0035] First nanoparticles encapsulating a first ingredient having an anti-hair loss effect;

[0036] It includes a second nanoparticle encapsulating a second component and a third component having an anti-hair loss effect,

[0037] The first nanoparticle comprises a first component, a lipophilic surfactant as a first solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)],

[0038] The second nanoparticle comprises a second component, a third component, a hydrophilic surfactant as a second solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)].

[0039] An emulsion composition for preventing or improving hair loss is provided, wherein the first nanoparticle and the second nanoparticle are dispersed in water.

[0040] A step of mixing a first component effective in preventing hair loss, a lipophilic surfactant as a first solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)] and dispersing them in water to form first nanoparticles in which the first component is encapsulated; and

[0041] A method for producing an emulsion composition for preventing or improving hair loss is provided, comprising the step of mixing a second component effective in preventing hair loss, a third component, a hydrophilic surfactant as a second solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)], and dispersing the mixture in water to form second nanoparticles in which the second component is encapsulated.

[0042]

[0043] The composition according to the present invention comprises:

[0044] It solves the problem of low solubility in water of effective substances that are effective in preventing or improving hair loss, and can be usefully used in preventing or improving hair loss by showing effects such as improving hair loss, hair count, hair thickness, scalp redness, scalp keratin, scalp oil, scalp moisturizing, and hair anti-aging.

[0045]

[0046] Figure 1 is a diagram showing the results of cytotoxicity evaluation of compositions according to the control group, comparative example 2, comparative example 1, and example 1.

[0047] Figure 2 shows the results of a comparative evaluation of changes in the number of hair loss when a control group using a control product and a test group using a composition according to one embodiment were applied to a human body.

[0048] Figure 3 shows the results of a comparative evaluation of changes in the number of hairs when a control group using a control product and a test group using a composition according to one embodiment were applied to a human body.

[0049] Figure 4 shows the results of a comparative evaluation of changes in hair thickness when a control group using a control product and a test group using a composition according to one embodiment were applied to a human body.

[0050] Figure 5 shows the results of a comparative evaluation of changes in the degree of scalp redness when a control group using a control product and a test group using a composition according to one embodiment were applied to a human body.

[0051] Figure 6 shows the results of a comparative evaluation of changes in the level of scalp keratin when a control group using a control product and a test group using a composition according to one embodiment were applied to a human body.

[0052] Figure 7 shows the results of a comparative evaluation of changes in scalp oiliness when a control group using a control product and a test group using a composition according to one embodiment were applied to a human body.

[0053] Figure 8 shows the results of a comparative evaluation of changes in scalp moisturizing levels when a control group using a control product and a test group using a composition according to one embodiment were applied to a human body.

[0054] Figure 9 shows the results of a comparative evaluation of changes in hair gloss when a control group using a control product and a test group using a composition according to one embodiment were applied to the human body.

[0055] Figure 10 shows the results of a comparative evaluation of changes in hair tensile strength when a control group using a control product and a test group using a composition according to one embodiment were applied to the human body.

[0056] Figure 11 shows the results of a comparative evaluation of changes in hair roughness when a control group using a control product and a test group using a composition according to one embodiment were applied to the human body.

[0057] Figure 12 shows the results of a comparative evaluation of changes in the degree of hair distribution when a control group using a control product and a test group using a composition according to one embodiment were applied to the human body.

[0058] Figure 13 shows the appearance of the scalp over time when a control group using a control product and a test group using a composition according to one embodiment were applied to the human body.

[0059]

[0060] The present invention is described in detail below.

[0061] Meanwhile, the embodiments of the present invention may be modified into various other forms, and the scope of the present invention is not limited to the embodiments described below. Furthermore, the embodiments of the present invention are provided to more fully explain the present invention to those with average knowledge in the relevant technical field.

[0062] Furthermore, reference to an element "including" throughout the specification does not exclude other elements, but rather includes other elements, unless specifically stated otherwise.

[0063] Explains the terms used in this specification.

[0064] “Nanoparticle” means a nano-sized particle, having a particle size in the range of 1 to 1000 nm, and generally a spherical particle.

[0065] First, the above cosmetic composition, pharmaceutical composition, health functional food composition and emulsion composition will be described.

[0066] The following applies to all forms of compositions unless otherwise stated.

[0067]

[0068] First, let's explain about the first nanoparticle.

[0069] The above first component is a substance having an anti-hair loss effect, and is an effective substance for preventing hair loss and / or promoting hair growth, and may be a 5-ring triterpene compound, or may be oleanolic acid, asiatic acid, ursolic acid, madecassic acid, betulinic acid, boswellic acid, geraniol, menthol, alpha-pinene, santonin, saponin, abietic acid, beta-carotene, etc., and in the present invention, oleanolic acid is used as an example.

[0070] The above first dissolving agent is preferably a lipophilic surfactant capable of dissolving a pentacyclic triterpene compound that is poorly soluble in water, and may have an HLB value of 10 or less, 9 or less, or 8 or less as an upper limit, and may be a lipophilic surfactant having an HLB value of 1 or more, 2 or more, or 3 or more as a lower limit.

[0071] The first dissolving agent is a lipophilic surfactant, which is a fatty acid ester of a glycol such as fatty acid, ethylene glycol, propylene glycol or glycerol, which may be a monoester, diester or triester, and the fatty acid may be a saturated or unsaturated fatty acid of C6-C30, C6-C20, C6-C12 or C6-C10.

[0072] It may be any one or a combination thereof selected from the group consisting of commercially available Maisine 35-1 (glyceryl monolinoleate), Miglyol 812 (Capric Triglyceride), Labrafil M 1933 CS (Oleoyl polyoxyl-6 glycerides), Capryol 90 (Propylene glycol monocaprylate (type II)), Triacetin (Glycerol triacetate), Labacfac CC (Capric Triglyceride), and Labrasol (Caprylocaproyl polyoxyl-8 glyceride), and in the present invention, Capryol 90 is used as an example. The HLB of Capryol 90 is known to be approximately 5-6.

[0073] The content of the first dissolving agent can be used in an appropriate amount to sufficiently dissolve the first component, and can be selected and used within the range of 50 to 200 parts by weight, 70 to 150 parts by weight, 80 to 120 parts by weight, and 90 to 110 parts by weight for 2.5 parts by weight of the first component. The content of the first dissolving agent can be used in a slightly excessive amount as long as it sufficiently dissolves the first component, but if it is used in too excessive amount, the content of the first component contained in the nanoparticles may be too low, and the concentration of the first component may not reach an effective concentration to achieve the purpose of preventing, improving, or treating hair loss.

[0074] The triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)] plays a role in forming micelles, and poloxamer 184, poloxamer 185, poloxamer 188, poloxamer 124, poloxamer 237, poloxamer 338, poloxamer 407, etc. can be used. Here, the triblock copolymer can be used in an amount of 100 to 1000 parts by weight, 200 to 500 parts by weight, or 250 to 450 parts by weight based on 2.5 parts by weight of the first component. If the content of the triblock copolymer is low, stable micelle formation is not achieved, which causes a problem in that the first component precipitates, and if too much is used, the particle size increases, which causes a problem in that stability is reduced.

[0075]

[0076] Let's talk about the second nanoparticle.

[0077] The second component is a substance having an anti-hair loss effect, and is an effective substance for blood circulation and anti-hair loss, and a flavonoid compound can be used, and more specifically, apigenin, luteolin, baicalein, cyanidin, delphinidin, malvidin, pelargonidin, peoridin, eriodicytyol, hesperetin, or naringenin can be used.

[0078] There is no reason why the ratio of the first component and the second component should be particularly limited, and as a specific example, the first component may be selected and used within the range of 0.1 to 100 parts by weight, 0.5 to 50 parts by weight, 1 to 10 parts by weight, or 1 to 5 parts by weight for 1 part by weight of the second component.

[0079] The third component is a substance having an anti-hair loss effect, and is an effective substance for preventing hair loss and antioxidant activity. An isoflavone compound may be used, and more specifically, daidzein, dihydrodaidzein, tetrahydrodaidzein, equol, or O-desmethylangolensin may be used.

[0080] There is no reason why the ratio of the first component and the third component is particularly limited, and as a specific example, the third component may be used in an amount of 1 to 100 parts by weight, 5 to 50 parts by weight, 7 to 40 parts by weight, 10 to 50 parts by weight, or 10 to 20 parts by weight relative to 2.5 parts by weight of the first component.

[0081] The third component can be used in an amount of 1 to 100 parts by weight, 5 to 50 parts by weight, 7 to 40 parts by weight, 10 to 50 parts by weight, or 10 to 20 parts by weight relative to 1 part by weight of the second component.

[0082] The above hydrophilic surfactant may have a lower limit of HLB value of 10 or more, 11 or more, or 12 or more, and an upper limit of HLB value of 30 or less, 25 or less, 22 or less, or 20 or less.

[0083] Specific examples include hydrophilic surfactants such as glycols, polyethylene glycols, polypropylene glycol, polyethylene glycol sorbate, and polyoxyl-castor oil.

[0084] Polyethylene glycols can be PEG-200, PEG-400, PEG-600, PEG-800. Polyethylene glycol sorbate is commercialized under the name Tween and can be Tween-20, Tween-400, Tween-60, Tween-80, etc. Polyoxyl-castor oil is a polyoxyl (PEG) esterified form of castor oil commercialized under the name Cremophor or Kolliphor, including Cremophor RH40 (Macrofolclycerol hydroxystearate), Pluronic L62 (polyoxyethylene-polyoxypropylene block copolymer), Cremophor RH60 (Ethoxylated hydrogenated caster oil), Cremophor CO40 (PEG-40 Hydrogenated caster oil), Cremophor ELP (Polyoxyl 35 hydrogenated caster oil), Span 80 (Sorbitan monooleate), etc.

[0085] The above hydrophilic surfactant may be used alone or in combination of two or more. When using different types of hydrophilic surfactants in combination, hydrophilic surfactants having different HLB values ​​may be mixed and used. The hydrophilic surfactant includes a first hydrophilic surfactant such as polyethylene glycol, and may further include a second hydrophilic surfactant of the Tween series. In terms of HLB, the first hydrophilic surfactant is 15 to 30 or 15 to 25, and the second hydrophilic surfactant is 13 to 18, and the HLB of the first hydrophilic surfactant may be higher than that of the second hydrophilic surfactant. In a specific embodiment of the present invention, the second component was dissolved using Tween-20 in PEG-400. PEG-400 belongs to a hydrophilic surfactant known to have an HLB value of approximately 20. The HLB of Tween 20 is known to be approximately 16.7. By using Tween 20 together, the solubility can be further increased.

[0086] If necessary, a third hydrophilic surfactant may be further included as an auxiliary surfactant, and examples thereof include Cremophor RH40 (Macrofolclycerol hydroxystearate), Pluronic L62 (polyoxyethylene-polyoxypropylene block copolymer), Cremophor RH60 (Ethoxylated hydrogenated caster oil), Cremophor CO40 (PEG-40 hydrogenated caster oil), Cremophor ELP (Polyoxyl 35 hydrogenated caster oil), and Span 80 (Sorbitan monooleate). Cremophor ELP (Kolliphor EL, HLB = approximately 13.5) can be used as an example.

[0087] A third hydrophilic surfactant may be preferably used to stabilize the second nanoparticles and increase skin permeability.

[0088] The hydrophilic surfactant can be used in an amount of 500 to 2000 parts by weight, 600 to 1800 parts by weight, 700 to 1600 parts by weight, 800 to 1800 parts by weight, 900 to 1600 parts by weight, or 900 to 1500 parts by weight, based on 1 part by weight of the second component.

[0089] The hydrophilic surfactant can be selected and used in the range of 1 to 1000 parts by weight, 10 to 500 parts by weight, 40 to 300 parts by weight, 50 to 250 parts by weight, 80 to 180 parts by weight, and 100 to 150 parts by weight, relative to 1 part by weight of the third component.

[0090] The ratio of the first hydrophilic surfactant to the second hydrophilic surfactant is not limited, but can be used in a weight ratio of, for example, 2:2 to 5, 2:3 to 4.

[0091] The third hydrophilic surfactant may not be used, but if used, it may be used in a ratio of 0.1 to 10 parts by weight, 0.4 to 5 parts by weight, or 0.6 to 2 parts by weight per 1 part by weight of the first hydrophilic surfactant.

[0092] The second nanoparticles may further include a fourth ingredient that is effective in maintaining scalp balance. The fourth ingredient may include coenzyme Q10, vitamin C, ononin, ascorbic acid, vitamin A, caffeine, etc., and in the present invention, as a specific example, retinol 50C was used.

[0093] When the second nanoparticle further includes a fourth component effective in maintaining scalp balance, the fourth component may be used in an amount of 1 to 20 parts by weight, 2 to 10 parts by weight, or 3 to 5 parts by weight relative to 1 part by weight of the sum of the second component and the third component.

[0094] The second nanoparticles may further include anti-inflammatory and antioxidant substances, such as glabridin, genistein, daidzein, glycitein, and vitamin E. In the present invention, vitamin E is used as a specific example.

[0095] The above anti-inflammatory and antioxidant substances may be selected within the range of 1 to 50 parts by weight, 5 to 30 parts by weight, 8 to 20 parts by weight, or 8 to 15 parts by weight relative to 1 part by weight of the sum of the second component and the third component.

[0096] The triblock copolymer for forming the second nanoparticles is of the same type as the triblock copolymer for forming the first nanoparticles, but does not need to be a poloxamer of the same number. The content may be 20 to 200 parts by weight, 40 to 100 parts by weight, or 50 to 80 parts by weight based on 1 part by weight of the sum of the second component and the third component. If the content of the triblock copolymer is low, stable micelle formation is not achieved, resulting in a problem of precipitation of the second component and / or the third component. If too much is used, the particle size increases, resulting in a problem of reduced stability.

[0097] The composition according to the present invention may further include 1 to 10, or 1 to 5 parts by weight of an antioxidant per 1 part by weight of the fourth component to effectively prevent oxidation over time of the first to fourth components in the nanoparticles, particularly the fourth component such as vitamin A, and may include α-lipoic acid, glutathione, butylated hydroxy anisole, butylated hydroxy toluene, propyl gallate, epigallocatechin gallate, gallocatechin gallate, silybin, diosmetin, epicatechin, galangin, tocopherol acetate, etc.

[0098]

[0099] Hereinafter, a method for manufacturing a composition comprising first nanoparticles and second nanoparticles according to the present invention will be described. The composition herein refers to all pharmaceutical compositions, health functional food compositions, cosmetic compositions, and emulsion compositions.

[0100]

[0101] The steps for manufacturing the first nanoparticle of the present invention are described.

[0102] The first component, the first solvent, and the triblock copolymer are mixed and dispersed in water to form the first nanoparticles.

[0103] The first component, the first solubilizer, the triblock copolymer, and the first nanoparticles are as described above.

[0104] When mixed, the triblock copolymer is provided as a solid, and heating may be involved during stirring for mixing and dissolution.

[0105] At this time, the heating temperature may be 20 to 100°C, 40 to 90°C, or 60 to 80°C. If the temperature is too low, sufficient mixing and dissolution may not occur, and thus the first nanoparticles may not be stably maintained.

[0106] The stirring time should be in the range of approximately 10 minutes to 2 hours, or 20 minutes to 60 minutes, to ensure sufficient mixing and dissolution.

[0107] Once sufficient mixing and dissolution are determined, emulsification is performed by continuously stirring while adding water. When stirring for emulsification, heating may be applied as needed, and stirring may be performed at 20 to 100°C, 20 to 40°C, or, for example, at room temperature. The stirring time is performed until nanoparticles are sufficiently formed, and can be appropriately selected within the range of 10 to 120 minutes.

[0108]

[0109] In the step of forming the second nanoparticles, the second component, the third component, and the second dissolving agent are mixed to dissolve the second and third components in the second dissolving agent. The mixture is stirred for dissolution, and the stirring temperature may be 20 to 80°C, and is performed in the range of 30 to 70°C or 50 to 70°C.

[0110] When the hydrophilic surfactant includes the first and second hydrophilic surfactants, it is mixed with the second component and the third component, for example, and then stirred.

[0111] Meanwhile, when adding the fourth component, it can be added together with the second and third components, but it can also be added separately if necessary. In particular, when adding vitamin A, since vitamin A is weak to heat, after dissolving the second and third components, it is cooled to room temperature, and then the fourth component is added and then dissolved. The mixing of the fourth component is performed at approximately 20 to 40°C, and after that, after adding the triblock copolymer, stirring is additionally performed while heating at 30 to 80°C and 40 to 70°C to form the second nanoparticles. Since the triblock copolymer is a solid, heating is preferable for sufficient dissolution. The heating time is approximately 5 to 60 minutes and 10 to 30 minutes.

[0112] Once sufficient mixing is achieved, water is added to perform emulsification to form second nanoparticles.

[0113] If more of the third hydrophilic surfactant is to be added, the third hydrophilic surfactant may be added before adding water.

[0114] If you add anti-inflammatory / antioxidant substances or antioxidants, you can add them before or when adding the fourth ingredient.

[0115]

[0116] The composition according to the present invention,

[0117] First nanoparticles encapsulating a first ingredient having an anti-hair loss effect;

[0118] It includes a second nanoparticle encapsulating a second component and a third component having an anti-hair loss effect,

[0119] The first nanoparticle comprises 80 to 120 parts by weight of a lipophilic surfactant as a first solubilizer and 250 to 450 parts by weight of a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)], relative to 2.5 parts by weight of the first component.

[0120] The second nanoparticle may include 100 to 150 parts by weight of a hydrophilic surfactant as a second dissolving agent and 50 to 80 parts by weight of a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)], based on 1 part by weight of the sum of the second component and the third component.

[0121] When the second nanoparticle further includes a fourth component, it may further include 5 to 15 parts by weight of the fourth component per 1 part by weight of the sum of the second component and the third component.

[0122]

[0123] The composition according to the present invention can prevent, improve or treat hair loss by activating the β-catenin signaling pathway (Wnt / β-catenin signaling pathway).

[0124] Activation of β-catenin signaling activates hair follicle stem cells, transitioning them from the telogen to the anagen phase, thereby enabling new hair growth. Furthermore, because the β-catenin pathway plays a central role in hair follicle formation and regeneration, it may help inhibit hair follicle degeneration and repair damaged hair follicles. Furthermore, it is involved in inducing and extending the anagen phase of the hair growth cycle, allowing hair to grow longer and thicker. Furthermore, restoring Wnt / β-catenin signaling, which is suppressed by DHT, may help improve androgenetic alopecia (AGA).

[0125]

[0126] In relation to the medicinal use of the composition according to the present invention,

[0127] One specific example relates to a method for preventing or treating hair loss, comprising administering the composition in a therapeutically effective amount to a subject in need thereof.

[0128] Another specific example relates to the use or use of the composition in preventing, improving or treating hair loss.

[0129] Another specific example relates to the use of the composition in the manufacture of a medicament for preventing, improving or treating hair loss.

[0130]

[0131] Hereinafter, the present invention will be described in detail through examples and experimental examples.

[0132] However, the following examples and experimental examples are merely illustrative of the present invention, and the content of the present invention is not limited by the examples and experimental examples.

[0133]

[0134] <Example 1> Preparation of composition

[0135] 1. Manufacturing of the first nanoparticle

[0136] 0.5 g of capryol 90, a dissolving agent, was added to 0.0125 g of oleanolic acid and dissolved at a temperature of 90°C. Then, 1.75 g of poloxamer 407, a triblock copolymer, was added and dissolved by stirring at a temperature of 65 to 70°C. Then, 45.2795 g of distilled water was added and stirred at room temperature to prepare an emulsion composition in which the first nanoparticles were dispersed.

[0137]

[0138] 2. Manufacturing of second nanoparticles

[0139] Apigenin (0.005 g), equol (0.05 g), biotin (0.011 g), polyethylene glycol 400 (2 g), and Tween 20 (3.5 g) were weighed and mixed by stirring at 70°C. After everything was mixed transparently and uniformly, it was cooled to room temperature, and then 0.167 g of vitamin A (retinol 50C) and 0.5 g of vitamin E were added to the mixture and mixed at 30-40°C. After everything was mixed, 3.5 g of poloxamer 407, a triblock copolymer, was added, melted at 50-60°C, stirred, and mixed, and then 1.5 g of Cremophor ELP was added and further stirred and mixed at 50-60°C.

[0140] After sufficient mixing, 41.0 g of distilled water was added and stirred at room temperature to prepare an emulsion composition in which the second nanoparticles were dispersed.

[0141]

[0142] 3. Mixing of the first and second nanoparticles

[0143] An emulsion composition according to the present invention was prepared by mixing the compositions in which the first nanoparticles and the second nanoparticles prepared above were dispersed.

[0144] The components included in the production of the first nanoparticle and the second nanoparticle are as follows.

[0145] Emulsion composition containing first nanoparticles Emulsion composition containing second nanoparticles Oleanolic acid 0.0125g Apigenin 0.00498g Equol 0.0502g Vitamin A 0.167g Biotin 0.011g Vitamin E 0.5g Capryol 90 0.5g Polyethylene glycol 400 1.998g Tween 20 3.528g Cremophor ELP 1.601g Poloxamer 407 1.75g ​​Poloxamer 407 3.467g Distilled water 45.2795g Distilled water 41.0g

[0146]

[0147] <Comparative Example 1> Preparation of composition

[0148] An emulsion composition containing the ingredients listed in Table 2 below was prepared in the same manner as in Example 1, using glabridin instead of equol.

[0149] Emulsion composition containing first nanoparticles Emulsion composition containing second nanoparticles Oleanolic acid 0.0125g Apigenin 0.00498g Glabridin 0.0502g Vitamin A 0.167g Biotin 0.011g Vitamin E 0.5g Capryol 90 0.5g Polyethylene glycol 400 1.998g Tween 20 3.528g Cremophor ELP 1.601g Poloxamer 407 1.75g ​​Poloxamer 407 3.467g Distilled water 45.2795g Distilled water 41.0g

[0150]

[0151] <Comparative Example 2> Preparation of composition

[0152] An emulsion composition containing the components listed in Table 3 below was prepared in the same manner as the second nanoparticle preparation in Example 1.

[0153] Emulsion composition containing nanoparticles Equol 0.0502g Polyethylene glycol 400 1.998g Tween 20 3.528g Cremophor ELP 1.601g Poloxamer 407 3.467g Distilled water 41.0g

[0154]

[0155] <Experimental Example 1> Cytotoxicity Evaluation (MTT Assay)

[0156] Human Follicel Dermal Papilla Cells were purchased from PromoCell GmbH and cultured in a CO2 incubator (37°C, 5% CO2) using Follicle Dermal Papilla Cell Growth Medium as the basic medium. The compositions prepared in the examples and comparative examples were diluted to a concentration appropriate for the cell medium.

[0157] The cell lines were cultured in a 48-well plate at a density of 2-5 x 10 using DMEM medium supplemented with 10% FBS. 4 Cells were seeded at a concentration of 10 cells / ㎖ and cultured in a 5% CO2 incubator for 24 hours. The medium was removed, the sample was added to a medium without FBS, and cultured for 24 hours. The medium was then removed, and MTT solution was added at a concentration of 1 ㎍ / ㎖ and reacted at 37℃ for 3 hours. The unreacted MTT solution was removed, 100 ㎕ of DMSO was added to dissolve the formed reactant, and the cell proliferation of the sample was confirmed by measuring the absorbance at 540 nm.

[0158] As a result, as shown in Fig. 1, Comparative Example 2 showed a cell viability of 93.52% at a treatment concentration of 0.001 μg / ml, 40.52% at a treatment concentration of 1 μg / ml, and 17.36% at a treatment concentration of 10 μg / ml compared to the control group. According to the internal standard that determines cytotoxicity when it is less than 80% compared to the control group, Comparative Example 2 can be determined to be cytotoxic at a treatment concentration of 1 μg / ml or more. Comparative Example 2 showed a cell viability of 16.31% at a treatment concentration of 10 μg / ml compared to the control group, and thus can be determined to be cytotoxic at a treatment concentration of 10 μg / ml. Example 1 showed a cell viability of 46.84% at a treatment concentration of 1 μg / ml and 15.20% at a treatment concentration of 10 μg / ml compared to the control group, so it can be judged that there is cytotoxicity at a treatment concentration of 1 μg / ml or higher.

[0159]

[0160] <Experimental Example 2> Analysis of β-catenin signaling pathway activity

[0161] The Wnt / β-catenin signaling pathway plays a key role in the growth and regeneration of hair follicles, and increased activity of this pathway has a very important effect on preventing hair loss and promoting hair growth. Accordingly, the β-catenin signaling pathway activity of the compositions prepared in Example 1, Comparative Examples 1, and Comparative Examples 2 was confirmed.

[0162] Specifically, when the intracellular β-catenin signaling pathway is activated, the TCF / LEF transcription factor binds to a specific DNA sequence, resulting in transcription. Therefore, the TOPflash reporter, which fuses the luciferase gene to the promoter sequence to which the TCF / LEF transcription factor binds, is the most common experimental method for confirming the activation of the intracellular β-catenin signaling pathway. Therefore, the activity of the β-catenin signaling pathway was measured using a recombinant adenovirus containing the TOPflash reporter and a luminometer.

[0163] Human Follicel Dermal Papilla Cells were purchased from PromoCell GmbH and cultured in Follicle Dermal Papilla Cell Growth Medium in a CO2 incubator (37°C, 5% CO2). The compositions prepared in the examples and comparative examples were diluted to an appropriate concentration in the cell medium. The control group is an untreated group. To measure β-catenin pathway activity, human dermal papilla cells were treated with adenovirus at a multiplicity of infection (MOI) of 1 and cultured for one day, after which they were subcultured into 24-well plates. The cells were treated with test substances and cultured for another day. The cells were disrupted and luciferase activity was measured using a luminometer.

[0164]

[0165] *N1 means test number 1, N2 means test number 2, and N3 means test number 3.

[0166]

[0167] As a result, when the TOPflash activity of the control group was converted to 100% as shown in Table 4, Comparative Example 2 showed a TOPflash activity of 230.6% at a treatment concentration of 0.1 μg / ml. Comparative Example 1 showed a TOPflash activity of 244.9% at a treatment concentration of 0.01 μg / ml, 301.1% at a treatment concentration of 0.1 μg / ml, and 295.5% at a treatment concentration of 1 μg / ml. Example 1 showed a TOPflash activity of 286.7% at a treatment concentration of 0.001 μg / ml, 308.2% at a treatment concentration of 0.01 μg / ml, and 407.1% at a treatment concentration of 0.1 μg / ml.

[0168] Although no significant results were obtained compared to the control group at the 0.001 μg / ml treatment concentration of Comparative Examples 1 and 2, it was confirmed that the 0.001 μg / ml and 0.01 μg / ml treatment concentrations of Example 1 showed activity more than twice as excellent as the control group, and it was also confirmed that a synergistic increase in activity was shown compared to Comparative Examples 1 and 2. Through this, it can be seen that the composition according to the present invention shows a superior hair loss prevention and hair growth promotion effect than the compositions of Comparative Examples 1 and 2.

[0169]

[0170] <Experimental Example 3> Clinical trial for hair loss relief

[0171] To determine whether the anti-hair loss functional cosmetic material according to Example 1 improves hair loss, a human application test was conducted on 60 subjects who agreed to a 24-week trial. Subjects who used the anti-hair loss functional cosmetic material visited the clinical trial institution before use, after 8 weeks of use, after 16 weeks of use, and after 24 weeks of use, and hair changes were observed through visual and instrumental evaluations.

[0172] The subjects were divided into a control group (30 subjects treated with the control product) and a test group (30 subjects treated with the test product corresponding to Example 1). A commercially available shampoo was used as the control product, and a shampoo that does not show any hair loss prevention effect was used.

[0173] In order to measure improvement in hair count and hair thickness, hair was cut from a fixed area (1 cm wide × 1 cm long) of the scalp and photographed once at each visit, and a phototrichogram was performed. In order to measure improvement in scalp redness, improvement in scalp keratin, improvement in scalp oil, improvement in scalp moisture, and hair anti-aging (shine), a fixed area of ​​the scalp on the vertex was photographed and measured using a measuring device. In addition, to measure hair anti-aging (tensile strength (breakage)) and hair anti-aging improvement (roughness), a fixed amount of hair was cut from the left temporal region and measured using a measuring device.

[0174] The evaluation method included primary efficacy evaluation, secondary efficacy evaluation, and adverse reactions and side effects. The primary efficacy evaluation confirmed the change in the number of hair loss through visual evaluation, and the total number of hairs (ea / 100mm) was evaluated using phototrichogram. 2) was evaluated, and after taking pictures of a certain area of ​​the scalp using Folliscope, changes in the number of hairs were confirmed, scalp redness was confirmed using SkinColorCatch (SCC, Delfin), scalp keratin was confirmed using Visioscan Corneofix F 20, scalp oil was confirmed using Sebumeter (SM820, C&K electronic), and scalp moisture was confirmed using Corneometer CM 825. In addition, hair gloss was confirmed using GlossyMeter GL 200, hair tensile strength was confirmed using a tensile compression tester (MCT-2150), and hair roughness was observed using a scanning electron microscope (SEM).

[0175] Secondary validity assessment was conducted by visual assessment by experts, using the scales shown in Table 5 below to assess intra-class correlation agreement. Two experienced experts scored the items in increments of 0.5, and after confirming that the intra-class correlation agreement demonstrated a score of 0.8 or higher, the average of the scores from the two experts was used for the evaluation.

[0176] How does the subject's hair distribution compare to before the test? Grade 1 Grade 2 Grade 3 Grade 4 Grade 5 Grade 6 Grade 7 Very worse Worse Slightly worse No change Slightly better Better Very better +1+2+3+4+5+6+7

[0177]

[0178] In addition, a survey was conducted on the evaluation contents listed in Table 6 below as a questionnaire evaluation of the test subjects.

[0179]

[0180] Adverse reactions were evaluated to check for skin damage before and after use, and in case of side effects, symptoms were checked, appropriate treatment and compensation were taken in accordance with the compensation regulations, and participation in the trial was decided.

[0181]

[0182] The results of the first efficacy evaluation are shown in Figs. 2 to 13. The test subjects were divided into a control group and a test group, and each product was used on the hair and scalp for 24 weeks. As a result of checking the change in the total number of hair loss (ea), the number of hair loss in the control group increased after 8, 16, and 24 weeks of product use compared to before using the product, whereas in the test group, the number of hair loss statistically significantly decreased after 8, 16, and 24 weeks of product use compared to before using the product (Fig. 2). As a result of checking the change in the number of hairs (ea), the number of hairs in the control group decreased after 8 and 16 weeks of product use compared to before using the product, but showed a tendency to increase after 24 weeks, whereas in the test group, the number of hairs statistically significantly increased after 8, 16, and 24 weeks of product use compared to before using the product (Fig. 3). As a result of checking the change in hair thickness (mm), in the control group, hair thickness decreased after 8 weeks of product use compared to before product use, but showed a tendency to increase after 16 and 24 weeks, whereas in the test group, hair thickness increased statistically significantly after 8, 16, and 24 weeks of product use compared to before product use (Fig. 4).

[0183] In addition, as a result of checking the change in Redness (scalp redness, a*) after using each product on the scalp for 24 weeks, the scalp redness was statistically significantly reduced after 8, 16, and 24 weeks of product use in both the control and test groups compared to before using the product (Fig. 5). As a result of checking the change in Scale Area (scalp keratin, %), in the control group, the scalp keratin decreased after 8 and 16 weeks of product use compared to before using the product, but did not reach significance, and statistically significantly decreased after 24 weeks, whereas in the test group, the scalp keratin was statistically significantly reduced after 8, 16, and 24 weeks of product use compared to before using the product (Fig. 6). As a result of checking the change in Sebum (scalp oil, ㎍ / ㎠), the scalp oil was statistically significantly reduced after 8, 16, and 24 weeks of product use in both the control and test groups compared to before using the product (Fig. 7). As a result of confirming the change in hydration (scalp moisture, AU), in both the control group and the test group, scalp moisture increased statistically significantly after 8, 16, and 24 weeks of product use compared to before product use (Fig. 8).

[0184] In addition, as a result of checking the change in Gloss (GU) after using each product on the hair area for 24 weeks, hair gloss statistically significantly increased after 8, 16, and 24 weeks of product use in both the control and test groups compared to before using the product, and in particular, it was confirmed that hair gloss increased by more than 50% after 16 weeks in the test group (Fig. 9). As a result of checking the change in tensile strength (MPa), it was confirmed that the tensile strength statistically significantly increased after 24 weeks of product use in both the control and test groups compared to before using the product, and in particular, it was confirmed that the tensile strength increased by more than 40% after 24 weeks in the test group (Fig. 10). As a result of checking the change in hair roughness (△, pixel), hair roughness increased in the control group compared to before using the product, whereas hair roughness statistically significantly decreased in the test group compared to before using the product after 24 weeks of product use (Fig. 11).

[0185] The results of the secondary validity evaluation are shown in Figs. 12 and 13. The front and crown of the head of the test subjects were photographed under the same conditions, composition, and position at each evaluation time point and visually evaluated (Fig. 13). The hair distribution of the control group and the test group was confirmed through an intra-class correlation agreement evaluation, and a high level of agreement was shown, indicating that there was no change in the test subjects. The results of the visual evaluation of the hair distribution using the average value of the scores evaluated by two experts showed that the average difference in all time points in the test group was statistically significantly increased compared to the control group (Fig. 12).

[0186] In addition, as a result of evaluating product satisfaction and usability of 30 subjects who used the test product for 24 weeks, 100% of the test subjects gave a yes or higher rating for the following items: improvement in number of hair loss, improvement in crown hair, improvement in hairline hair, improvement in hair thickness, improvement in scalp soothing, improvement in hair damage, improvement in scalp keratin, improvement in scalp oil, improvement in dandruff / itchiness, and product satisfaction.

[0187] As a result of the human application test as described above, it was confirmed that the hair loss prevention functional cosmetic material according to the present invention can be used for hair loss prevention and improvement by helping to improve hair loss, hair count, hair thickness, scalp redness, scalp keratin, scalp oil, scalp moisturizing, and hair anti-aging (shine, tensile strength (breakage), roughness).

Claims

1. First nanoparticles encapsulating a first ingredient having an anti-hair loss effect; It includes a second nanoparticle encapsulating a second component and a third component having an anti-hair loss effect, The first nanoparticle comprises a first component, a lipophilic surfactant as a first solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)], A cosmetic composition for preventing or improving hair loss, comprising a second nanoparticle, a second component, a third component, a hydrophilic surfactant as a second solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)].

2. In paragraph 1, The above first component is, A cosmetic composition comprising at least one selected from the group consisting of oleanolic acid, asiatic acid, ursolic acid, madecassic acid, betulinic acid, boswellic acid, geraniol, menthol, alpha-pinene, santonin, saponin, abietic acid, and beta-carotene.

3. In paragraph 1, The second component is, A cosmetic composition comprising at least one selected from apigenin, luteolin, baicalein, cyanidin, delphinidin, malvidin, pelargonidin, peoridin, eriodicytyol, hesperetin, and naringenin.

4. In paragraph 1, A cosmetic composition wherein the third ingredient is equol.

5. In paragraph 1, A cosmetic composition wherein the lipophilic surfactant has an HLB value of 1 or more and 10 or less.

6. In paragraph 1, A cosmetic composition wherein the hydrophilic surfactant has an HLB of 10 or more and 30 or less.

7. In paragraph 1, A cosmetic composition, wherein the triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)] is at least one selected from the group consisting of poloxamer 184, poloxamer 185, poloxamer 188, poloxamer 124, poloxamer 237, poloxamer 338, and poloxamer 407.

8. In paragraph 1, A cosmetic composition wherein the second nanoparticle further comprises a fourth ingredient effective in maintaining scalp balance selected from coenzyme Q10, vitamin C, ononin, ascorbic acid, vitamin A, and caffeine.

9. In paragraph 1, A cosmetic composition wherein the second nanoparticle further comprises at least one anti-inflammatory and antioxidant substance selected from the group consisting of glabridin, genistein, daidzein, glycitein, formonontin, and vitamin E.

10. First nanoparticles encapsulating a first ingredient having an anti-hair loss effect; It includes a second nanoparticle encapsulating a second component and a third component having an anti-hair loss effect, The first nanoparticle comprises a first component, a lipophilic surfactant as a first solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)], A pharmaceutical composition for preventing or treating hair loss, wherein the second nanoparticle comprises a second component, a third component, a hydrophilic surfactant as a second solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)].

11. First nanoparticles encapsulating a first ingredient having an anti-hair loss effect; It includes a second nanoparticle encapsulating a second component and a third component having an anti-hair loss effect, The first nanoparticle comprises a first component, a lipophilic surfactant as a first solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)], A health functional food composition for preventing or improving hair loss, comprising a second nanoparticle, a second component, a third component, a hydrophilic surfactant as a second solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)].

12. First nanoparticles encapsulating a first ingredient having an anti-hair loss effect; It includes a second nanoparticle encapsulating a second component and a third component having an anti-hair loss effect, The first nanoparticle comprises a first component, a lipophilic surfactant as a first solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)], The second nanoparticle comprises a second component, a third component, a hydrophilic surfactant as a second solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)]. An emulsion composition for preventing or improving hair loss, wherein the first nanoparticles and the second nanoparticles are dispersed in water.

13. A step of mixing a first component effective in preventing hair loss, a lipophilic surfactant as a first solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)] and dispersing the mixture in water to form a first nanoparticle in which the first component is encapsulated; and A method for producing an emulsion composition for preventing or improving hair loss, comprising the step of mixing a second component effective in preventing hair loss, a third component, a hydrophilic surfactant as a second solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)], and dispersing the mixture in water to form second nanoparticles in which the second component is encapsulated.

14. First nanoparticles encapsulating a first ingredient having an anti-hair loss effect; It includes a second nanoparticle encapsulating a second component and a third component having an anti-hair loss effect, The first nanoparticle comprises a first component, a lipophilic surfactant as a first solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)], A method for preventing or treating hair loss, comprising administering to a subject in need thereof a therapeutically effective amount of a composition comprising a second component, a third component, a hydrophilic surfactant as a second solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)].

15. First nanoparticles encapsulating a first ingredient having an anti-hair loss effect; It includes a second nanoparticle encapsulating a second component and a third component having an anti-hair loss effect, The first nanoparticle comprises a first component, a lipophilic surfactant as a first solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)], The second nanoparticle is used for the preparation of a medicament for preventing or treating hair loss, comprising a second component, a third component, a hydrophilic surfactant as a second solubilizer, and a triblock copolymer in the form of [polyethylene oxide (PEO)-polypropylene oxide (PPO)-polyethylene oxide (PEO)].

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