Composition for facial contour improvement, retinacula cutis repair, dermal fiber structure enhancement and / or Anti-aging after high-intensity focused ultrasound treatment and / or after treatment with radiofrequency skin tightening device

Abstract

To provide a novel composition having effects of improving the facial contour, repairing the retinacula cutis, enhancing dermal fiber structure, and / or anti-aging, after high-intensity focused ultrasound treatment and / or after treatment with a radiofrequency skin tightening device.SOLUTION: The composition comprises, as an active ingredient, a compound represented by the general formula (1) in the figure. [In the formula, R1 represents a linear or branched alkyl group having 1 to 4 carbon atoms substituted with a carboxyl group, or a linear or branched alkyl group having 1 to 4 carbon atoms substituted with a carboxylic acid ester group having an alkyl chain having 1 to 4 carbon atoms; and R2 and R3 each independently represent a linear or branched alkyl group having 1 to 4 carbon atoms.]SELECTED DRAWING: None

Description

Technical Field

[0001] The present invention relates to a composition for improving facial shape, improving skin ligaments, improving dermal fiber structure, and / or anti-aging after high-intensity focused ultrasound (HIFU) treatment and / or after treatment with a high-frequency relaxation therapy device.

Background Art

[0002] With the recent progress of medical technology, the interest in aesthetic medicine has been increasing. As aesthetic medicine, high-intensity focused ultrasound (HIFU) treatment and treatment with a high-frequency relaxation therapy device have attracted attention in recent years.

[0003] By the way, conventionally, a topical skin composition for aftercare after laser treatment containing Prunus mume extract as an active ingredient for the skin after aesthetic medical treatment has been known (Patent Document 1).

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] In view of the above prior art, the present inventor has conducted intensive research to find a novel composition that exhibits an effect of improving facial shape, an effect of improving skin ligaments, an effect of improving dermal fiber structure, and / or an anti-aging effect after high-intensity focused ultrasound (HIFU) treatment and / or after treatment with a high-frequency relaxation therapy device. As a result, it has been found that the compound represented by the following general formula (1), its isomers and / or their pharmacologically acceptable salts have a remarkable facial shape improving effect, skin ligament improving effect, dermal fiber structure improving effect, and / or anti-aging effect on the skin after high-intensity focused ultrasound (HIFU) treatment and / or after treatment with a high-frequency relaxation therapy device.

[0006] That is, an object of the present invention is to provide a novel composition having a facial shape improving effect, skin ligament improving effect, dermal fiber structure improving effect, and / or anti-aging effect after high-intensity focused ultrasound (HIFU) treatment and / or after treatment with a high-frequency relaxation therapy device.

Means for Solving the Problems

[0007] [1] The present invention for solving the above problems is a composition for improving facial shape, improving skin ligaments, improving dermal fiber structure, and / or anti-aging after high-intensity focused ultrasound (HIFU) treatment and / or after treatment with a high-frequency relaxation therapy device, containing a compound represented by the following general formula (1), its isomers and / or their pharmacologically acceptable salts as an active ingredient.

[0008]

Chemical formula

[0009] [In the formula, R1 represents a linear or branched alkyl group having 1 to 4 carbon atoms substituted by a carboxyl group, or a linear or branched alkyl group having 1 to 4 carbon atoms substituted by a carboxylic acid ester group having an alkyl chain of 1 to 4 carbon atoms, and R2 and R3 each independently represent a linear or branched alkyl group having 1 to 4 carbon atoms.]

[0010] According to the present invention, it is possible to improve the skin condition after High Intensity Focused Ultrasound treatment and / or after treatment with a high-frequency lifting device.

[0011] [2] A preferred embodiment of the present invention is that the composition for improving facial shape, improving skin retinaculum, improving dermal fiber structure, and / or anti-aging is for suppressing the excessive inflammatory response of the skin after High Intensity Focused Ultrasound treatment and / or after treatment with a high-frequency lifting device, and is the composition for improving facial shape, improving skin retinaculum, improving dermal fiber structure, and / or anti-aging described in [1].

[0012] [3] A preferred embodiment of the present invention is that the composition for improving facial shape, improving skin retinaculum, improving dermal fiber structure, and / or anti-aging is for suppressing the excessive induction of neutrophil elastase and / or neutrophil extracellular traps, and / or for improving the skin retinaculum (Retinacula Cutis), and is the composition for improving facial shape, improving skin retinaculum, improving dermal fiber structure, and / or anti-aging described in [1] or [2].

[0013] [4] A preferred embodiment of the present invention is for one or more selected from improving the sustainability of the lifting effect, the early perception effect of the lifting effect, improving sagging, improving elasticity, improving the smoothness of the skin, and suppressing side effects, and is the composition for improving facial shape, improving skin retinaculum, improving dermal fiber structure, and / or anti-aging described in any one of [1] to [3].

[0014] [5] A preferred embodiment of the present invention is by suppressing the excessive induction of neutrophil elastase and / or neutrophil extracellular traps, and / or by improving the skin retinaculum (Retinacula Cutis). It is for one or more selected from the group consisting of improvement in the persistence of the lifting effect, early perception of the lifting effect, improvement in dullness, improvement in elasticity, improvement in skin smoothness, and suppression of side effects, and is a composition for improving facial shape, improving skin support, improving dermal fiber structure, and / or anti-aging according to any one of [1] to [4].

[0015] [6] A preferred embodiment of the present invention is a composition for improving facial shape, improving skin support, improving dermal fiber structure, and / or anti-aging according to any one of [1] to [5], which is applied to the skin thermally stimulated by the high-intensity focused ultrasound treatment.

[0016] [7] A preferred embodiment of the present invention is also applied to the skin within 1 hour after the high-intensity focused ultrasound (High Intensity Focused Ultrasound) treatment and / or after the treatment with a high-frequency relaxation treatment device, and is a composition for improving facial shape, improving skin support, improving dermal fiber structure, and / or anti-aging according to any one of [1] to [6].

[0017] [8] A preferred embodiment of the present invention is a composition for improving facial shape, improving skin support, improving dermal fiber structure, and / or anti-aging according to any one of [1] to [7], wherein the active ingredient is sodium isopropyl oxopropyl aminocarbonyl pyrrolidine carbonyl methylpropyl aminocarbonyl benzoyl aminoacetate.

[0018] [9] A preferred embodiment of the present invention is a composition for improving facial shape, improving skin support, improving dermal fiber structure, and / or anti-aging according to any one of [1] to [8], which contains 0.01% by mass or more and 10% by mass or less of the compound represented by the general formula (1), its isomers, and / or their pharmacologically acceptable salts as an active ingredient.

[0019]

[10] A preferred embodiment of the present invention is a composition for improving facial shape, improving skin support, improving dermal fiber structure, and / or anti-aging according to any one of [1] to [9], which is characterized by being a topical skin preparation.

[0020] The present invention is also an agent for improving facial shape, improving skin support, improving dermal fiber structure, and / or anti-aging after high-intensity focused ultrasound (HIFU) treatment and / or after treatment with a high-frequency lifting device, which contains the compound represented by the general formula (1) above, its isomers and / or their pharmacologically acceptable salts as active ingredients.

[0021]

Chemical formula

[0022] [In the formula, R1 represents a linear or branched alkyl group having 1 to 4 carbon atoms substituted by a carboxyl group, or a linear or branched alkyl group having 1 to 4 carbon atoms substituted by a carboxylic acid ester group having an alkyl chain of 1 to 4 carbon atoms, and R2 and R3 each independently represent a linear or branched alkyl group having 1 to 4 carbon atoms.]

[0023] The present invention is also a method for improving facial shape, improving skin support, improving dermal fiber structure, and / or anti-aging (excluding medical acts) after high-intensity focused ultrasound (HIFU) treatment and / or after treatment with a high-frequency lifting device, which is characterized by applying a composition for improving skin containing the compound represented by the general formula (1) above, its isomers and / or their pharmacologically acceptable salts as active ingredients to the skin after high-intensity focused ultrasound (HIFU) treatment and / or after treatment with a high-frequency lifting device.

[0024] [Chemical formula]

[0025] [In the formula, R1 represents a linear or branched alkyl group having 1 to 4 carbon atoms substituted by a carboxyl group, or a linear or branched alkyl group having 1 to 4 carbon atoms substituted by a carboxylic acid ester group having an alkyl chain of 1 to 4 carbon atoms, and R2 and R3 each independently represent a linear or branched alkyl group having 1 to 4 carbon atoms.] [Advantages of the Invention]

[0026] According to the present invention, it is possible to provide a novel composition that improves the skin condition after high-intensity focused ultrasound (HIFU) treatment and / or after treatment with a high-frequency lifting device. [Brief Description of the Drawings]

[0027]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

[0028] [Composition for improving facial shape, improving skin ligaments, improving dermal fiber structure, and / or anti-aging after high-intensity focused ultrasound (HIFU) treatment and / or after treatment with a high-frequency lifting device> Hereinafter, a composition for improving facial shape, improving skin ligaments, improving dermal fiber structure, and / or anti-aging after high-intensity focused ultrasound (HIFU) treatment and / or after treatment with a high-frequency relaxation therapy device of the present invention will be described in detail.

[0029] (i) Active ingredient The composition for improving facial shape, improving skin ligaments, improving dermal fiber structure, and / or anti-aging after high-intensity focused ultrasound (HIFU) treatment and / or after treatment with a high-frequency relaxation therapy device of the present invention contains, as an active ingredient, a compound represented by the following general formula (1), its isomers, and / or their pharmacologically acceptable salts.

[0030] [Chemical formula]

[0031] [In the formula, R1 represents a linear or branched alkyl group having 1 to 4 carbon atoms substituted by a carboxyl group, or a linear or branched alkyl group having 1 to 4 carbon atoms substituted by a carboxylic acid ester group having an alkyl chain of 1 to 4 carbon atoms, and R2 and R3 each independently represent a linear or branched alkyl group having 1 to 4 carbon atoms.]

[0032] The compound represented by the general formula (1), its isomers, and / or their pharmacologically acceptable salts can be produced, for example, by the method described in JP-A-04-297446. Since the compound represented by the general formula (1) is an optically active compound having a plurality of asymmetric carbon atoms in its molecular structure, enantiomers and diastereomers exist as its isomers. Further, as the compound represented by the general formula (1) of the present invention, there exist racemates, enantiomers, diastereomers, and furthermore, compounds in which the above isomers are mixed in an arbitrary ratio.

[0033] Regarding the compound represented by the general formula (1) of the present invention, in the formula, R1 represents a linear or branched alkyl group having 1 to 4 carbon atoms substituted by a carboxyl group or a linear or branched alkyl group having 1 to 4 carbon atoms substituted by a carboxylic acid ester group having an alkyl chain of 1 to 4 carbon atoms, and R2 and R3 each independently represent a linear or branched alkyl group having 1 to 4 carbon atoms. Specific examples of preferred ones for R1 are carboxymethyl group, carboxyethyl group, carboxypropyl group, carboxybutyl group, methoxycarbonylmethyl group, methoxycarbonylethyl group, methoxycarbonylpropyl group, methoxycarbonylbutyl group, ethoxycarbonylmethyl group, ethoxycarbonylethyl group, ethoxycarbonylpropyl group, ethoxycarbonylbutyl group, propyloxycarbonylmethyl group, propyloxycarbonylethyl group, propyloxycarbonylpropyl group, propyloxycarbonylbutyl group, butyloxycarbonylmethyl group, butyloxycarbonylethyl group, butyloxycarbonylpropyl group, butyloxycarbonylbutyl group, etc., and more preferably, a carboxymethyl group can be exemplified. Regarding R2 and R3, specific examples of preferred ones are methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, isobutyl group, sec-butyl group, tert-butyl group, etc., and more preferably, an isopropyl group can be preferably exemplified.

[0034] The compound represented by the general formula (1) has human leukocyte elastase inhibitory activity and is expected to have a therapeutic effect on cerebral ischemic diseases including cerebral infarction. Also, for example, as described in WO 1999 / 43352 pamphlet, it has a preventive or therapeutic effect on skin aging. Further, the compound represented by the general formula (1) of the present invention has actions such as the regeneration of elastic fibers in the dermal papilla, the regeneration of fine collagen fibers in the dermal site directly under the epidermis, and the increase in epidermal thickness, and exerts a preventive or improving effect on wrinkle formation by such actions.

[0035] The compound represented by the general formula (1) is preferably a compound represented by the following general formula (2).

[0036]

Chemical formula

[0037] Regarding the compound represented by the general formula (2) of the present invention, in the formula, R4 represents a linear or branched alkyl group having 1 to 4 carbon atoms substituted by a carboxyl group, and R5 and R6 each independently represent a linear or branched alkyl group having 1 to 4 carbon atoms. The above R4 represents a linear or branched alkyl group having 1 to 4 carbon atoms substituted by a carboxyl group. Specific preferred examples of the above R4 include a carboxymethyl group, a 1-carboxyethyl group, a 2-carboxyethyl group, a 1-carboxypropyl group, a 2-carboxypropyl group, a 3-carboxypropyl group, a 1-carboxybutyl group, a 2-carboxybutyl group, a 3-carboxybutyl group, a 4-carboxybutyl group, etc., and more preferably, a carboxymethyl group can be preferably exemplified.

[0038] R5 and R6 each independently represent a linear or branched alkyl group having 1 to 4 carbon atoms. Specific preferred examples of R5 and R6 include a methyl group, an ethyl group, an n-propyl group, an isopropyl group, an n-butyl group, an isobutyl group, a sec-butyl group, a tert-butyl group, etc. More preferably, an isopropyl group can be preferably exemplified. Further, examples of the compound represented by the general formula (2) include 3-[[4-(carboxymethylaminocarbonyl)phenylcarbonyl]-valyl-prolyl]amino-1,1,1-trifluoro-4-methyl-2-oxopentane, N-[4-[[(carboxymethyl)amino]carbonyl]benzoyl]-L-alanyl-N-[3,3,3-trifluoro-1-(1-methyl)-2-oxopropyl]-L-prolinamide, N-[4-[[(carboxyethyl)amino]carbonyl]benzoyl]-L-alanyl-N-[3,3,3-trifluoro-1-(1-methyl)-2-oxopropyl]-L-prolinamide, N-[4-[[(carboxypropyl)amino]carbonyl]benzoyl]-L-alanyl-N-[3,3,3-trifluoro-1-(1-methyl)-2-oxopropyl]-L-prolinamide, N-[4-[[(carboxybutyl)amino]carbonyl]benzoyl]-L-alanyl-N-[3,3,3-trifluoro-1-(1-methyl)-2-oxopropyl]-L-prolinamide, N-[4-[[(carboxymethyl)amino]carbonyl]benzoyl]-L-alanyl-N-[3,3,3-trifluoro-1-(1-ethyl)-2-oxopropyl]-L-prolinamide, N-[4-[[(carboxyethyl)amino]carbonyl]benzoyl]-L-alanyl-N-[3,3,3-trifluoro-1-(1-ethyl)-2-oxopropyl]-L-prolinamide, N-[4-[[(carboxypropyl)amino]carbonyl]benzoyl]-L-alanyl-N-[3,3,3-trifluoro-1-(1-ethyl)-2-oxopropyl]-L-prolinamide, N-[4-[[(carboxybutyl)amino]carbonyl]benzoyl]-L-alanyl-N-[3,3,3-Trifluoro-1-(1-ethyl)-2-oxopropyl]-L-prolinamide, N-[4-[[(carboxymethyl)amino]carbonyl]benzoyl]-L-alanyl-N-[3,3,3-trifluoro-1-(1-methylethyl)-2-oxopropyl]-L-prolinamide, N-[4-[[(carboxyethyl)amino]carbonyl]benzoyl]-L-alanyl-N-[3,3,3-trifluoro-1-(1-methylethyl)-2-oxopropyl]-L-prolinamide, N-[4-[[(carboxypropyl)amino]carbonyl]benzoyl]-L-alanyl-N-[3,3,3-trifluoro-1-(1-methylethyl)-2-oxopropyl]-L-prolinamide, N-[4-[[(carboxybutyl)amino]carbonyl]benzoyl]-L-alanyl-N-[3,3,3-trifluoro-1-(1-methylethyl)-2-oxopropyl]-L-prolinamide, N-[4-[[(carboxymethyl)amino]carbonyl]benzoyl]-L-valyl-N-[3,3,3-trifluoro-1-(1-methyl)-2-oxopropyl]-L-prolinamide, N-[4-[[(carboxyethyl)amino]carbonyl]benzoyl]-L-valyl-N-[3,3,3-trifluoro-1-(1-methyl)-2-oxopropyl]-L-prolinamide, N-[4-[[(carboxypropyl)amino]carbonyl]benzoyl]-L-valyl-N-[3,3,3-trifluoro-1-(1-methyl)-2-oxopropyl]-L-prolinamide, N-[4-[[(carboxybutyl)amino]carbonyl]benzoyl]-L-valyl-N-[3,3,3-trifluoro-1-(1-methyl)-2-oxopropyl]-L-prolinamide, N-[4-[[(carboxymethyl)amino]carbonyl]benzoyl]-L-valyl-N-[3,3,3-trifluoro-1-(1-ethyl)-2-oxopropyl]-L-prolinamide, N-[4-[[(carboxyethyl)amino]carbonyl]benzoyl]-L-valyl-N-[3,3,3-trifluoro-1-(1-ethyl)-2-oxopropyl]-L-prolinamide, N-[4-[[(carboxypropyl)amino]carbonyl]benzoyl]-L-valyl-N-[3,3,3-Trifluoro-1-(1-ethyl)-2-oxopropyl]-L-prolinamide, N-[4-[[(carboxybutyl)amino]carbonyl]benzoyl]-L-valyl-N-[3,3,3-trifluoro-1-(1-ethyl)-2-oxopropyl]-L-prolinamide, N-[4-[[(carboxymethyl)amino]carbonyl]benzoyl]-L-valyl-N-[3,3,3-trifluoro-1-(1-methylethyl)-2-oxopropyl]-L-prolinamide (3(RS)-N-[4-[[(carboxymethyl)amino]carbonyl]benzoyl]-L-valyl-N-[3,3,3-trifluoro-1-(1-methylethyl)-2-oxopropyl]-L-prolinamide), N-[4-[[(carboxyethyl)amino]carbonyl]benzoyl]-L-valyl-N-[3,3,3-trifluoro-1-(1-methylethyl)-2-oxopropyl]-L-prolinamide, N-[4-[[(carboxypropyl)amino]carbonyl]benzoyl]-L-valyl-N-[3,3,3-trifluoro-1-(1-methylethyl)-2-oxopropyl]-L-prolinamide, N-[4-[[(carboxybutyl)amino]carbonyl]benzoyl]-L-valyl-N-[3,3,3-trifluoro-1-(1-methylethyl)-2-oxopropyl]-L-prolinamide can be preferably exemplified.,

[0039] Among the compounds represented by the general formula (2), 3-[[4-(carboxymethylaminocarbonyl)phenylcarbonyl]-valyl-prolyl]amino-1,1,1-trifluoro-4-methyl-2-oxopentane is more preferably mentioned, and more preferably 3(RS)-[[4-(carboxymethylaminocarbonyl)phenylcarbonyl]-L-valyl-L-prolyl]amino-1,1,1-trifluoro-4-methyl-2-oxopentane represented by the following formula (3). And as the compound to be contained in the composition of the present invention, the sodium salt of the above 3(RS)-[[4-(carboxymethylaminocarbonyl)phenylcarbonyl]-L-valyl-L-prolyl]amino-1,1,1-trifluoro-4-methyl-2-oxopentane (hereinafter also referred to as "KSK32") is particularly preferred., Incidentally, KSK32 is also denoted as N-[4-[[(carboxymethyl)amino]carbonyl]benzoyl]-L-valyl-N-[(RS)-3,3,3-trifluoro-1-(1-methylethyl)-2-oxopropyl]-L-prolinamide in another nomenclature, and it is the same compound.

[0040] [Chemical formula]

[0041] In the present invention, the compound represented by the general formula (1) can be directly contained in the composition, but it can also be treated with a pharmacologically acceptable acid or base and converted into a salt form for use as a salt. For example, inorganic acid salts such as hydrochloride, sulfate, nitrate, phosphate, carbonate; organic acid salts such as maleate, fumarate, oxalate, citrate, lactate, tartrate, methanesulfonate, paratoluenesulfonate, benzenesulfonate; alkali metal salts such as sodium salt, potassium salt, alkaline earth metal salts such as calcium salt, magnesium salt; organic amine salts such as triethylamine salt, triethanolamine salt, ammonium salt, monoethanolamine salt, piperidine salt, basic amino acid salts such as lysine salt, arginine salt; and the like. In addition, the composition of the present invention can contain one or more selected from the compound represented by the general formula (1), its isomers and / or their pharmacologically acceptable salts.

[0042] In the present invention, the compound represented by the general formula (1), its isomers and / or their pharmacologically acceptable salts are preferably sodium trifluoroisopropyloxopropylaminocarbonylpyrrolidinecarbonylmethylpropylaminocarbonylbenzoylaminoacetate.

[0043] (ii) Use The compound represented by the general formula (1) above, its isomers and / or their pharmacologically acceptable salts have a remarkable effect of improving the skin condition after High Intensity Focused Ultrasound treatment and / or after treatment with a high-frequency lifting device, as shown in the examples described below. More specifically, the skin condition can be improved by applying the active ingredient of the present invention after High Intensity Focused Ultrasound treatment and / or after treatment with a high-frequency lifting device.

[0044] In addition, according to the present invention, by applying the active ingredient after High Intensity Focused Ultrasound treatment and / or after treatment with a high-frequency lifting device, the utility of the High Intensity Focused Ultrasound treatment and / or the treatment with a high-frequency lifting device itself can be made more excellent.

[0045] As shown in the examples described below, the active ingredient has an excellent anti-aging effect on the skin after High Intensity Focused Ultrasound treatment and / or after treatment with a high-frequency lifting device. In addition, as shown in the examples described below, the active ingredient has an excellent facial shape improving effect on the skin after High Intensity Focused Ultrasound treatment and / or after treatment with a high-frequency lifting device.

[0046] In addition, as shown in the examples described below, the active ingredient has an effect of improving skin support bands under conditions where neutrophil infiltration occurs. Here, the condition of neutrophil infiltration is a state in which inflammation is induced inside the skin by the heat action caused by High Intensity Focused Ultrasound treatment, and neutrophil infiltration associated with the inflammation occurs. In addition, the skin retinaculum improvement effect in this specification includes, for example, an effect of improving the state of the skin retinaculum by suppressing the decomposition of the skin retinaculum (Retinacula cutis).

[0047] The active ingredient exerts an effect of improving the dermal fiber structure under the condition where neutrophil infiltration occurs. Here, the condition of neutrophil infiltration is a state in which inflammation is induced inside the skin by the heat action caused by the treatment with a high-frequency relaxation treatment device, and neutrophil infiltration associated with the inflammation occurs. In addition, the dermal fiber structure improvement effect in this specification includes, for example, an effect of remodeling the fiber structure by suppressing excessive decomposition of collagen fibers in the dermis and promoting neogenesis.

[0048] That is, the present invention can be in the form of a composition for improving facial shape, improving skin retinaculum, improving dermal fiber structure, and / or anti-aging after treatment with high-intensity focused ultrasound (HIFU) and / or after treatment with a high-frequency relaxation treatment device, containing the above-mentioned active ingredient.

[0049] Furthermore, the facial shape improvement use preferably includes, more specifically, an improvement use for the skin sagging state and an improvement use for the dermal and / or subcutaneous tissue structure. That is, the present invention can be in the form of a composition for improving facial shape for the skin sagging state, dermal and / or subcutaneous tissue structure after treatment with high-intensity focused ultrasound (HIFU) and / or after treatment with a high-frequency relaxation treatment device, containing the above-mentioned active ingredient.

[0050] In addition, as shown in the examples described later, the active ingredient exerts effects related to improving the persistence of the lifting effect, the early perception of the lifting effect, improving turgor, improving elasticity, and improving the smoothness of the skin. That is, the present invention can be in the form of a composition for improving facial shape, improving skin ligaments, improving dermal fiber structure, and / or anti-aging after high-intensity focused ultrasound (HIFU) treatment and / or after treatment with a high-frequency wrinkle treatment device for one or more selected from improving the sustainability of the lifting effect, the early perception of the lifting effect, improving sagging, improving elasticity, and improving skin smoothness.

[0051] In addition, the active ingredient has an effect of suppressing the over-induction of neutrophil elastase and / or neutrophil extracellular traps. In addition, as shown in the examples described later, the active ingredient has an effect of improving the skin retinacula.

[0052] That is, the present invention can be in the form of a composition for improving facial shape, improving skin ligaments, improving dermal fiber structure, and / or anti-aging after high-intensity focused ultrasound (HIFU) treatment and / or after treatment with a high-frequency wrinkle treatment device for suppressing the over-induction of neutrophil elastase and / or neutrophil extracellular traps and / or for improving the skin retinacula.

[0053] Here, the present invention is for one or more selected from improving the sustainability of the lifting effect, the early perception of the lifting effect, improving sagging, improving elasticity, improving skin smoothness, and suppressing side effects by suppressing the over-induction of neutrophil elastase and / or neutrophil extracellular traps and / or by improving the skin retinacula. Here, as shown in the examples described later, the active ingredient has an effect of suppressing side effects after high-intensity focused ultrasound (HIFU) treatment and / or after treatment with a high-frequency wrinkle treatment device.

[0054] ​More specifically, the active ingredient exhibits an excessive inflammation inhibitory effect, a skin tissue regeneration effect after inflammation, a scar formation inhibitory effect, and an excessive inflammation inhibitory effect in the dermis and subcutaneous tissue. That is, the present invention can be in the form of a composition for improving facial shape, improving skin ligaments, improving dermal fiber structure, and / or anti-aging after high-intensity focused ultrasound (HIFU) treatment and / or after treatment with a high-frequency relaxation device for one or more selected from the excessive inflammation inhibitory effect, skin tissue regeneration effect after inflammation, scar formation inhibitory effect, and excessive inflammation inhibitory effect in the dermis and subcutaneous tissue, containing the above active ingredient.

[0055] For the irradiation of high-intensity focused ultrasound (HIFU), known high-intensity focused ultrasound (HIFU) treatment devices can be used. Examples of high-intensity focused ultrasound (HIFU) treatment devices include, for example, Ultraformer MPT (CLASSYS), Ultraformer III (CLASSYS), Ultrashape Zi (Jeisys), Ultrashape Q+ (Jeisys), Sofwave (C-edge, Inc.), and the like.

[0056] Here, the skin undergoes a thermal effect by high-intensity focused ultrasound (HIFU) treatment. The active ingredient of the present invention is preferably applied to the skin thermally stimulated by high-intensity focused ultrasound (HIFU) treatment.

[0057] In addition, scar formation and excessive inflammation can occur in the skin by high-intensity focused ultrasound (HIFU) treatment. As described above, the active ingredient has an effect of suppressing side reactions. Thus, it is preferably applied to the skin after High Intensity Focused Ultrasound treatment and / or after treatment with a high-frequency relaxation treatment device, preferably within 48 hours, more preferably within 24 hours, more preferably within 12 hours, more preferably within 8 hours, more preferably within 4 hours, and even more preferably within 1 hour.

[0058] Hereinafter, when the application target of the active ingredient of the present invention is the skin after High Intensity Focused Ultrasound treatment, the preferred conditions of High Intensity Focused Ultrasound treatment will be described in detail.

[0059] In the present specification, the treatment with a high-frequency relaxation treatment device refers to the treatment with a high-frequency relaxation treatment device for cosmetic purposes.

[0060] The High Intensity Focused Ultrasound treatment is preferably performed using a terminal (probe) having a focal depth from the deep subcutaneous SMAS (Superficial Musculo-Aponeurotic System), the deep dermis, to the superficial dermis.

[0061] Here, the High Intensity Focused Ultrasound treatment is preferably performed in the following steps.

[0062] Step 1: Using a terminal having a predetermined focal depth, irradiate from the cheek to the submandibular area at a predetermined pitch interval. Here, the terminal used in Step 1 preferably has a focal depth of 4 mm to 5 mm, particularly preferably 4.5 mm. Also, the irradiation can be based on 0.5 J or more and 0.7 J or less. Also, the pitch interval can be set with a reference of 1.0 mm or more and 1.5 mm or less.

[0063] Step 2: Using a terminal with a predetermined focal depth, irradiate from the cheek to the submandibular region at a predetermined pitch interval. Here, the terminal used in Step 2 preferably has a shorter focal depth than the terminal used in Step 1. More specifically, the terminal used in Step 2 preferably has a focal depth of 2.5 mm to 3.5 mm, particularly preferably 3 mm. Also, the irradiation in Step 2 preferably has a lower heat quantity than the irradiation in Step 1. More specifically, the irradiation in Step 2 can be set with a reference of 0.4 J or more and 0.5 J or less. Also, the pitch interval can be set with a reference of 1.0 mm or more and 1.5 mm or less.

[0064] Step 3: Using a terminal with a predetermined focal depth, irradiate the cheek, the eyelids, the area around the eyes, and the forehead at a predetermined pitch interval. Here, the terminal used in Step 3 preferably has a shorter focal depth than the terminal used in Step 2. More specifically, the terminal used in Step 3 preferably has a focal depth of 1.5 mm to 2.5, particularly preferably 2 mm. Also, the irradiation in Step 3 preferably has a lower heat quantity than the irradiation in Step 2. More specifically, the irradiation in Step 2 can be set with a reference of 0.2 J or more and 0.3 J or less. Also, the pitch interval can be set with a reference of 1.0 mm or more and 1.5 mm or less.

[0065] Note that the irradiation output can be adjusted while checking the degree of pain and redness of the treatment area.

[0066] Here, for the treatment with a high-frequency relaxation therapy device, a known treatment device by a high-frequency relaxation therapy device can be used. Examples of the treatment device using a high-frequency wrinkle treatment device include, for example, Bole Nuoma (CLASSYS), Thermacool (Thermage), Potenza (Jeisys), Vivace (Motomitech Inc), and the like.

[0067] Hereinafter, when the application target of the active ingredient of the present invention is the skin after treatment with a high-frequency wrinkle treatment device, the preferable conditions for the treatment with the high-frequency wrinkle treatment device will be described in detail.

[0068] The treatment with a high-frequency wrinkle treatment device is a treatment that irradiates high-frequency (radio waves) from the skin surface or from the tip of a needle inserted into the dermis to apply heat to the main body of the dermis, thereby promoting the contraction and regeneration of dermal collagen fibers.

[0069] Here, the treatment with a high-frequency wrinkle treatment device is preferably in a form implemented by the following steps.

[0070] Step 1: Shoot high-frequency waves on the cheek using a terminal of a predetermined area. Here, the terminal used in Step 1 is preferably one having an area of 2 cm 2 ~4 cm 2 , particularly preferably 3 cm 2 . Also, the conditions for shooting can be based on 6 J / cm 2 or more and 22 J / cm 2 or less. Also, it is preferable to use 6.72 M for the shooting conditions. Also, the number of shots can be based on 100 - 180 shots / half face (200 - 360 shots / both cheeks).

[0071] Step 2: Shoot high-frequency waves 50 times on the forehead using a terminal. Here, the terminal used in Step 2 is preferably one having an area of 2 cm 2 ~4 cm 2 , particularly preferably 3 cm 2 . In addition, the shot conditions can be based on 6 J / cm 2 or more and 22 J / cm 2 or less. In addition, it is preferable to use 6.72 M for the shot conditions. In addition, the number of shots can be based on 25 - 75 shots / half face (50 - 150 shots / both cheeks), particularly preferably 50 shots / half face (100 shots / both cheeks).

[0072] Step 3: Around the eyelids, using a terminal, apply high frequency at 100 shots / half face (200 shots / around both eyelids) Here, the terminal used in Step 3 has an area of 0.12 cm 2 to 0.38 cm 2 , particularly preferably 0.25 cm 2 and is preferably one with such an area. In addition, the shot conditions can be based on 6 J / cm 2 or more and 15 J / cm 2 or less. In addition, it is preferable to use 6.72 M for the shot conditions. In addition, the number of shots can be based on 75 - 125 shots / around both eyelids (150 - 250 shots / around both eyelids), particularly preferably 100 shots / around both eyelids (200 shots / around both eyelids).

[0073] Note that the irradiation output can be adjusted while checking the degree of pain and redness of the treatment area.

[0074] (iii) Dosage and administration For improving facial shape, improving skin support bands, improving dermal fiber structure, and / or for anti - aging after the treatment with high - density focused ultrasound (High Intensity Focused Ultrasound) of the present invention and / or after the treatment with a high - frequency wrinkle treatment device, the content of the compound represented by the general formula (1), its isomers and / or their pharmacologically acceptable salts in the composition is 0.01% by mass or more in total, more preferably 0.1% by mass or more, and even more preferably 1% by mass or more. In addition, in the composition for improving facial shape, improving skin ligaments, improving dermal fiber structure, and / or anti-aging after the treatment with high-intensity focused ultrasound (HIFU) of the present invention and / or after the treatment with a high-frequency wrinkle treatment device, the content of the compound represented by the general formula (1), its isomers and / or their pharmacologically acceptable salts is 10% by mass or less in total, more preferably 7% by mass or less, and even more preferably 5% by mass or less.

[0075] In addition, the composition for improving facial shape, improving skin ligaments, improving dermal fiber structure, and / or anti-aging of the present invention is preferably used continuously for 2 weeks or more, more preferably 4 weeks or more, and particularly preferably 12 weeks or more.

[0076] Here, the composition for improving facial shape, improving skin ligaments, improving dermal fiber structure, and / or anti-aging of the present invention is preferably in a form in which the compound represented by the general formula (1), its isomers and / or their pharmacologically acceptable salts are used in combination with an introduction cosmetic liquid. By combining the compound represented by the general formula (1), its isomers and / or their pharmacologically acceptable salts with the introduction cosmetic liquid, the improvement of facial shape, the improvement of skin ligaments, and / or the anti-aging effect can be exerted more efficiently.

[0077] Here, the introduction cosmetic liquid refers to a cosmetic liquid having an action of enhancing the penetration power of other components into the skin. The introduction cosmetic liquid is not particularly limited in type as long as it is an aqueous preparation for assisting the dissolution of the above active ingredients. Here, the introduction cosmetic liquid preferably contains an anti-inflammatory agent.

[0078] Suitable examples of the topical skin composition include cosmetics, quasi-drugs, pharmaceuticals, and the like.

[0079] The agent according to the present invention is preferably in the form of a topical skin composition. The topical skin composition can be produced using appropriately known methods and equipment.

[0080] Preferable forms of the topical skin composition include forms such as lotions, emulsions, gels, creams, ointments, packs, sprays, tapes, and patches. Specifically, preferable forms of the topical skin composition can preferably include dosage forms selected from emulsions, pastes, gels, lotions, creams, moisturizing oils, powders, surfactant-containing cleansings, and oils.

[0081] When the present invention is in the form of a topical skin composition, within a range that does not impair the facial shape improvement effect, skin support improvement effect, dermal fiber structure improvement effect, and / or anti-aging effect after high-intensity focused ultrasound (HIFU) treatment and / or treatment with a high-frequency relaxation device, whitening components, wrinkle improvement components, anti-inflammatory components, extracts derived from animals and plants other than rice bran, and components commonly used in cosmetics other than active ingredients may be blended as optional components. These optional components may be obtained and blended from commercially available products, or those synthesized by known methods may be blended. Further, each optional component may have two or more effects (for example, a whitening effect and a wrinkle improvement effect).

[0082] When provided in the form of a composition for external use on the skin, the composition is not particularly limited, and can also contain any components that are commonly used, as long as the effects of the present invention are not impaired. Such optional components include, for example, oils and waxes such as macadamia nut oil, avocado oil, corn oil, olive oil, rapeseed oil, sesame oil, castor oil, safflower oil, cottonseed oil, jojoba oil, coconut oil, palm oil, liquid lanolin, hydrogenated coconut oil, hydrogenated oil, beeswax, hydrogenated castor oil, beeswax, candelilla wax, carnauba wax, spermaceti wax, lanolin, reduced lanolin, hard lanolin, jojoba wax, etc.; hydrocarbons such as liquid paraffin, squalane, pristane, ozokerite, paraffin, ceresin, petrolatum, microcrystalline wax, etc.; higher fatty acids such as oleic acid, isostearic acid, lauric acid, myristic acid, palmitic acid, stearic acid, behenic acid, undecylenic acid, etc.; higher alcohols such as cetyl alcohol, stearyl alcohol, isostearyl alcohol, behenyl alcohol, octyldodecanol, myristyl alcohol, cetostearyl alcohol, etc.; oil agents such as synthetic ester oils such as cetyl isooctanoate, isopropyl myristate, hexadecyl isostearate, diisopropyl adipate, di-2-ethylhexyl sebacate, cetyl lactate, distearyl malate, ethylene glycol di-2-ethylhexanoate, neopentyl glycol dicaprate, glycerin di-2-heptylundecanoate, glycerin tri-2-ethylhexanoate, trimethylolpropane tri-2-ethylhexanoate, trimethylolpropane triisostearate, pentaerythritol tetra-2-ethylhexanoate, etc.; anionic surfactants such as fatty acid soaps (sodium laurate, sodium palmitate, etc.), potassium lauryl sulfate, alkyl sulfate triethanolamine ether, etc.; cationic surfactants such as stearyltrimethylammonium chloride, benzalkonium chloride, laurylamine oxide, etc.; amphoteric surfactants such as imidazoline-based amphoteric surfactants (2-cocoyl-2-imidazolinium hydroxide-1-carboxyethyloxy 2 sodium salt, etc.), betaine-based surfactants (alkyl betaine, amide betaine, sulfobetaine, etc.), acylmethyl taurine, etc.;Sorbitan fatty acid esters (such as sorbitan monostearate and sorbitan sesquioleate), glycerin fatty acids (such as glycerin monostearate), propylene glycol fatty acid esters (such as propylene glycol monostearate), hydrogenated castor oil derivatives, glycerin alkyl ethers, POE sorbitan fatty acid esters (such as POE sorbitan monooleate and polyoxyethylene sorbitan monostearate), POE sorbit fatty acid esters (such as POE-sorbitan monolaurate), POE glycerin fatty acid esters (such as POE-glycerin monoisostearate), POE fatty acid esters (such as polyethylene glycol monooleate and POE distearate), POE alkyl ethers (such as POE2-octyldodecyl ether), POE alkyl phenyl ethers (such as POE nonyl phenyl ether), pluronic (registered trademark) types, POE·POP alkyl ethers (such as POE·POP2-decyltetradecyl ether), tetronic types, POE castor oil·hydrogenated castor oil derivatives (such as POE castor oil and POE hydrogenated castor oil), sucrose fatty acid esters, nonionic surfactants such as alkyl glucoside; polyhydric alcohols such as polyethylene glycol, glycerin, erythritol, sorbitol, maltitol, propylene glycol, and 2,4-hexanediol; moisturizing components such as sodium pyrrolidone carboxylate, lactic acid, and sodium lactate; para-aminobenzoic acid-based ultraviolet absorbers; anthranilic acid-based ultraviolet absorbers; salicylic acid-based ultraviolet absorbers; cinnamic acid-based ultraviolet absorbers; benzophenone-based ultraviolet absorbers; sugar-based ultraviolet absorbers; ultraviolet absorbers such as 2-(2'-hydroxy-5'-t-octylphenyl)benzotriazole and 4-methoxy-4'-t-butyldibenzoylmethane can be preferably exemplified.;

[0083] Further, when the present invention is made into a composition for external use on the skin, it is also preferable that the present invention is in a form with a label indicating "for improving facial shape, improving skin support, improving dermal fiber structure, and / or anti-aging after treatment with High Intensity Focused Ultrasound and / or after treatment with a high-frequency lifting device".

[0084] The "display" includes all displays having the function of informing the consumer of the use. That is, any display that can evoke or analogize the use, regardless of the purpose of the display, the content of the display, the object or medium to be displayed, etc., falls within the scope of the "display". In addition, "being provided with the display" means that there is a display act for making the display and a composition for external use on the skin (product), etc. recognized in association with each other.

[0085] Preferably, the display act enables the consumer to directly recognize the use. Specifically, examples thereof include the act of describing the use on the product or the packaging of the product according to the present invention, advertisements regarding the product, price lists, or transaction documents (including those provided by electromagnetic methods) to which the use is described.

[0086] When it is an oral composition, it can also be a food composition containing the active ingredient of the present invention. Specifically, it can be in the form of a supplement having a dosage form such as general food, tablets, granules, drink agents, etc.

[0087] Here, regarding the content of the compound represented by the general formula (1) in the oral composition, its isomers and / or their pharmacologically acceptable salts, the description of the aforementioned preferred embodiments can be applied mutatis mutandis.

[0088] In addition, when it is an oral composition, optional components may be appropriately blended within a range that does not impair the effects of the present invention.

[0089] <Agent for improving facial shape, improving skin support, improving dermal fiber structure, and / or anti-aging after high-intensity focused ultrasound (HIFU) treatment and / or treatment with a high-frequency relaxation therapy device> Furthermore, the present invention is also an agent for improving facial shape, improving skin ligaments, improving dermal fiber structure, and / or anti-aging, which comprises the compound represented by the general formula (1) above, its isomers and / or their pharmacologically acceptable salts, after high-intensity focused ultrasound (HIFU) treatment and / or after treatment with a high-frequency relaxation therapy device.

[0090] In addition, the preferred embodiments of the agent for improving facial shape, improving skin ligaments, improving dermal fiber structure, and / or anti-aging according to the present invention can apply the above-described content.

[0091] <Beauty method> Furthermore, the present invention can also be a method for improving facial shape, improving skin ligaments, improving dermal fiber structure, and / or anti-aging, which is characterized by applying the compound represented by the general formula (1) above, its isomers and / or their pharmacologically acceptable salts to the skin. According to the present invention, by applying the compound represented by the general formula (1) above, its isomers and / or their pharmacologically acceptable salts to the skin, it is possible to relieve the symptoms and / or prevent recurrence of the skin condition.

[0092] In addition, after high-intensity focused ultrasound (HIFU) treatment and / or after treatment with a high-frequency relaxation therapy device, a composition for improving facial shape, improving skin ligaments, improving dermal fiber structure, and / or anti-aging, which contains 4-alkylresorcinol as an active ingredient, is applied to the skin after high-intensity focused ultrasound (HIFU) treatment and / or after treatment with a high-frequency relaxation therapy device. A beauty method for improving the skin condition symptoms after high-intensity focused ultrasound (HIFU) treatment and / or after treatment with a high-frequency relaxation therapy device can be provided.

[0093] The method according to the present invention can be carried out by a seller of a topical skin composition according to the present invention, a makeup artist, a beauty staff, a counselor or an esthetician, a general user (a subject undergoing high-intensity focused ultrasound treatment and / or treatment with a high-frequency wrinkle treatment device), and the like.

[0094] Here, the method for improving facial shape, improving skin support, improving dermal fiber structure, and / or anti-aging according to the present invention is preferably in a form of using the compound represented by the general formula (1) above, its isomers and / or their pharmacologically acceptable salts, and an introduction beauty liquid in combination.

[0095] Here, the beauty method for improving facial shape, improving skin support, improving dermal fiber structure, and / or anti-aging according to the present invention does not include medical acts. More specifically, the beauty method for improving facial shape, improving skin support, improving dermal fiber structure, and / or anti-aging according to the present invention is a non-therapeutic method.

[0096] In addition, the preferred embodiments in the method of the present invention can apply the above-described content.

Example

[0097] Examples are given below to explain the present invention in more detail, but it goes without saying that the present invention is not limited only to the examples according to the present invention.

[0098] <1> Verification of the effect of applying an active ingredient to skin under specific conditions <Test conditions>

[0099] (1) Test content Twenty-three subjects complaining of facial sagging were given the following high-intensity focused ultrasound (HIFU) treatment (hereinafter also simply referred to as HIFU).

[0100] Then, 23 subjects were each applied with the test preparation of (3) below on one half of the face, and on the other half of the face, a preparation obtained by excluding only the active ingredient from the test preparation (hereinafter referred to as placebo preparation) was applied.

[0101] (2) Conditions for HIFU treatment Equipment used: Ultraformer MPT (manufactured by CLASSYS) HIFU treatment timing: At the start of the test Usage conditions:

[0102]

Table 1

[0103] (3) Test preparation / Application of test preparation (i) Test preparation A preparation containing sodium isopropyl oxopropyl aminocarbonyl pyrrolidine carbonyl methylpropyl aminocarbonyl benzoyl aminoacetate as an active ingredient was used as the test preparation.

[0104] (ii) Application conditions Twice a day, in the morning and evening, each subject applied 0.4 - 0.5 g of the test preparation or placebo preparation in a sufficient amount to one half of the face including the area around the eyes to the cheek area.

[0105] The test was conducted under the above conditions, and the following measurements / evaluations were performed on the subjects.

[0106] <Example 1> Visual evaluation of the change in appearance of the entire area around the cheeks · Method In this example, 3D face images at the initial value and 1 month after the treatment were obtained using VECTRA Face (Canfield Scientific). The two images were overlaid using the analysis software Mirror, and the change in the three-dimensional shape with respect to the initial value was compared three-dimensionally. The change in the appearance of the entire face was visualized using a heat map.

[0107] · Results Typical examples of the results are shown in Figures 1 and 2. As a result of this example, the same tendency as the results shown in Fig. 1 was also shown for other subjects. Fig. 2 is the same drawing as Fig. 1 and shows the three-dimensional position variation results.

[0108] One month after the treatment, an increase in volume above the face line was confirmed in both the half faces of the group combining HIFU treatment and the test preparation and the group combining the placebo preparation, and it was confirmed that both the HIFU treatment itself and the test preparation were effective in lifting the face. Here, since a decrease in volume was also confirmed at the lower part of the face line in the group combining the test preparation, it was found that the combined use of HIFU treatment and the test preparation has an effect of improving the sagging at the lower part of the face line. Therefore, it became clear that the combined use of HIFU treatment and the test preparation (containing the active ingredient) brings about an early and high improvement effect as compared with the group combining the placebo preparation. Further effects can be expected by continuous use. It was also found that further effects can be expected by continuously using the test preparation together with the HIFU treatment.

[0109] <Example 2> IGA (Investigator Global Assessment) Evaluation · Method In this example, the initial value and the face images one month after the treatment were acquired using VISIA Evolution (Canfield Scientific). Comparing the face images with the photos at the 0-week time point, a doctor who did not know the breakdown of the test subject group of the subject scored the degree of improvement of the face shape in 5 grades (significant improvement, improvement, slight improvement, unchanged, deterioration) by IGA (Investigator Global Assessment).

[0110] · Results The results are shown in Fig. 3. One month after the treatment, slight improvements were observed in some subjects in both the half faces of the group treated with HIFU and the test agent, and the group treated with the placebo agent. Thus, it was confirmed that both the HIFU treatment itself and the test agent were effective in improving the facial shape. Here, in the group treated with the test agent, the number of subjects showing improvements beyond slight improvement and the proportion of subjects showing improvements beyond slight improvement were twice as high. Therefore, it became clear that combining the HIFU treatment and the test agent (containing the active ingredient) brings about an early and high improvement effect as compared with the group treated with the placebo agent. It was also found that further effects can be expected by continuously using the test agent together with the HIFU treatment.

[0111] <Example 3> Evaluation of Skin Sagging due to Facial Sagging · Method In this example, three-dimensional facial images at the initial value and one month after the treatment were acquired using VECTRA Face (Canfield Scientific). The two images were superimposed using the analysis software Mirror, and after unifying the facial angles, they were extracted as two-dimensional images. In the extracted two-dimensional images, as an index of skin sagging due to facial sagging, the straight-line distance from the lowest point of the nasal column through the corner of the mouth to the point where it touches the contour was calculated, and a correction value was calculated by dividing it by the straight-line distance between the inner canthi, which is less likely to vary between measurement times. The measured value one month after the treatment with respect to the initial value was calculated with the measured value at the initial value of each subject taken as 100%.

[0112] · Results The results are shown in Table 2.

[0113]

Table 2

[0114] One month after the treatment, a decrease in the length from the lowest point of the nasal column to the facial contour was confirmed in both the half-faces of the group treated with HIFU combined with the test preparation and the group treated with the placebo preparation. It was confirmed that both the HIFU treatment itself and the test preparation were effective in improving the facial shape. Here, in the group treated with the test preparation, the length from the lowest point of the nasal column to the facial contour was significantly decreased. Therefore, it was revealed that combining the test preparation (active ingredient) brings about an early and high improvement effect as compared with the group treated with the placebo preparation. Also, it was revealed that combining the HIFU treatment with the test preparation (containing the active ingredient) brings about an early and high improvement effect. Moreover, it was also found that further effects can be expected by continuously using the test preparation together with the HIFU treatment.

[0115] <Example 4> Evaluation of Skin Viscoelasticity · Method In this example, the skin viscoelasticity of the cheek was measured for each half-face using Cutometer CM580 (Courage+Khazaka). Specifically, using Cutometer CM580, the viscoelasticity was evaluated by measuring the displacement of the skin suction height over time by suction and release of the skin by applying negative pressure. R5 (instantaneous return Ur after release of negative pressure / instantaneous deformation Ue during suction) calculated by the attached software was used as an index.

[0116] · Results The results are shown in Table 3.

[0117]

Table 3

[0118] At the initial value, no significant difference was observed among the groups. One month after the treatment, an increase in the R5 value of skin viscoelasticity was observed in both the half faces of the group treated with HIFU combined with the test preparation and the group treated with the placebo preparation. Therefore, it was confirmed that any of the interventions was effective in improving the facial shape. Also, in the group treated with the test preparation, the R5 value increased significantly. Thus, it was revealed that combining the test preparation (containing the active ingredient) brought about an early and high improvement effect as compared with the group treated with the placebo preparation. It was also found that further effects could be expected by continuously using the test preparation together with the HIFU treatment.

[0119] <Example 5> Evaluation of Skin Barrier Function · Method In this example, the skin surface moisture content of the cheek was evaluated for each half face using a Corneometer CM825 (Courage + Khazaka).

[0120] · Results The results are shown in Table 4.

[0121]

Table 4

[0122] At the initial value, no significant difference was observed among the groups. One month after the treatment, a slight decrease in the skin surface moisture content was observed in the group treated with the placebo preparation, while an increase in the skin surface moisture content was confirmed in the group treated with the test preparation. From the above results, it was confirmed that by combining the HIFU treatment and the test preparation, the deterioration of the skin barrier function was suppressed by suppressing excessive inflammation. Thus, it was revealed that combining the HIFU treatment and the test preparation (containing the active ingredient) brought about an effect of suppressing excessive inflammation as compared with the group treated with the placebo preparation.

[0123] <Conclusion> According to the results of this example, the compound represented by the above general formula (1), its isomers and / or their pharmacologically acceptable salts have been found to exhibit remarkable effects as a composition for improving facial shape and / or anti-aging after high-intensity focused ultrasound (HIFU) treatment and / or after treatment with a high-frequency relaxation therapy device. Moreover, according to the results of this example, the compound represented by the above general formula (1), its isomers and / or their pharmacologically acceptable salts have been found to be components that can be used without side effects as a composition for improving facial shape and / or anti-aging after high-intensity focused ultrasound (HIFU) treatment and / or after treatment with a high-frequency relaxation therapy device.

[0124] <2> Verification of the inhibitory effect of applying the active ingredient on the retinacula cutis (RC) and dermal fiber structure under specific conditions

[0125] (1) Test conditions A skin thin section (12 μm thick) prepared from frozen skin tissue was added with a neutrophil elastase solution (50 μg / mL) and a solution containing sodium 3-(isopropylcarbonyloxy)-3-(propylaminocarbonyl)pyrrolidin-1-ylcarbonylmethylpropylaminocarbonylbenzoylaminoacetate (hereinafter simply referred to as the active ingredient) (active ingredient addition group). In addition, as a control group, an active ingredient-free non-addition group was prepared.

[0126] After reacting the active ingredient addition group and the non-addition group in an incubator for 4 hours, the degraded collagen in the retinacula cutis (RC) site and the dermal fiber structure site was stained with Collagen Hybridizing Peptide (CHP, manufactured by Triple Helix). For the stained skin thin sections, bright-field images and fluorescence images were obtained using BZ X800 (manufactured by Keyence) (see Figure 4). The luminance value of the CHP-positive region in the RC site was quantified using ImageJ, and the average value was calculated (see Figure 5).

[0127] (2) Results / Examination The results are shown in Figs. 4 and 5. As shown in the figures, CHP fluorescence was not confirmed in the active ingredient addition group. Also, the average luminance value of CHP staining at the RC site was significantly lower in the active ingredient addition group. On the other hand, in the non-active ingredient addition group, fluorescence of CHP, which is a marker for degraded collagen, was significantly detected at the subcutaneous tissue RC site and the dermal fiber structure site.

[0128] As described above, it was found that the active ingredient exhibits a skin fascia improvement effect and a dermal fiber structure improvement effect under conditions where neutrophil infiltration occurs. Here, the conditions of neutrophil infiltration are a state in which inflammation is induced inside the skin by the heat action caused by high-intensity focused ultrasound (HIFU) treatment and / or radiofrequency laxity treatment, and neutrophil infiltration associated with the inflammation occurs. Looking at it, from the above results, it was found that sodium isopropyl 3-fluoropropionate aminocarbonylpyrrolidine carbonylmethylpropylaminocarbonylbenzoylaminoacetate exhibits a neutrophil elastase inhibitory effect and is effective in suppressing the degradation of subcutaneous tissue RC and dermal fiber structure against inflammation inside the skin after high-intensity focused ultrasound (HIFU) treatment and / or radiofrequency laxity treatment.

Industrial Applicability

[0129] According to the present invention, it is possible to provide a composition capable of improving the skin condition after high-intensity focused ultrasound (HIFU) treatment and / or treatment with a radiofrequency laxity treatment device.

Claims

1. A composition for improving facial shape, improving skin retinaculum, improving dermal fiber structure, and / or anti-aging after treatment with High Intensity Focused Ultrasound and / or treatment with a high frequency sagging treatment device, comprising a compound represented by the following general formula (1), an isomer thereof, and / or a pharmacologically acceptable salt thereof as an active ingredient: 【Chemistry 1】 [In the formula, R1 represents a linear or branched alkyl group having 1 to 4 carbon atoms substituted with a carboxyl group, or a linear or branched alkyl group having 1 to 4 carbon atoms substituted with a carboxylate group having an alkyl chain having 1 to 4 carbon atoms, and R2 and R3 each independently represent a linear or branched alkyl group having 1 to 4 carbon atoms.]

2. The composition for improving facial shape, improving retinaculum, improving dermal fiber structure, and / or anti-aging according to claim 1, which is for suppressing inflammatory response of the skin after high intensity focused ultrasound treatment and / or treatment with a high frequency sagging treatment device.

3. The composition for improving facial shape, improving retinaculum, improving dermal fibrous structure, and / or anti-aging according to claim 1 or 2, wherein the composition for improving facial shape, improving retinaculum, improving dermal fibrous structure, and / or anti-aging is for suppressing excessive induction of neutrophil elastase and / or neutrophil extracellular traps and / or for improving retinaculum cutis after treatment with high intensity focused ultrasound and / or treatment with a high frequency sagging treatment device.

4. The composition for improving facial shape, improving skin retinaculum, improving dermal fiber structure, and / or anti-aging according to claim 1 or 2, which is for one or more of the following purposes: improving the durability of a lift-up effect, quickly realizing a lift-up effect, improving sagging, improving elasticity, improving skin smoothness, and suppressing side effects. The composition for improving facial shape, improving skin retinaculum, improving dermal fiber structure, and / or anti-aging after a high-intensity focused ultrasound treatment and / or a high-frequency sagging treatment device treatment.

5. By inhibiting excessive induction of neutrophil elastase and / or neutrophil extracellular traps, and / or by improving the retinacula cutis, 3. The composition for improving facial shape, improving skin retinaculum, improving dermal fiber structure, and / or anti-aging after treatment with High Intensity Focused Ultrasound and / or treatment with a high frequency sagging treatment device according to claim 1 or 2, which is for one or more of the following purposes: improving the durability of the lift-up effect, quickly realizing the lift-up effect, improving sagging, improving elasticity, improving skin smoothness, and suppressing side effects.

6. The composition for improving facial shape, improving skin retinaculum, improving dermal fiber structure, and / or anti-aging after a high-intensity focused ultrasound treatment and / or a high-frequency sagging treatment device according to claim 1 or 2, which is applied to skin that has been thermally stimulated by a high-intensity focused ultrasound treatment.

7. The composition for improving facial shape, improving skin retinaculum, improving dermal fiber structure, and / or anti-aging after a high intensity focused ultrasound treatment and / or a high frequency sagging treatment device according to claim 1 or 2, which is also applied to skin within one hour after a high intensity focused ultrasound treatment and / or a high frequency sagging treatment device.

8. 3. The composition for improving facial shape, improving skin retinaculum, improving dermal fiber structure, and / or anti-aging after treatment with High Intensity Focused Ultrasound and / or treatment with a high frequency sagging treatment device according to claim 1 or 2, wherein the active ingredient is sodium trifluoroisopropyloxopropylaminocarbonylpyrrolidinecarbonylmethylpropylaminocarbonylbenzoylaminoacetate.

9. The composition according to claim 1 or 2, which contains 0.01% by mass or more and 10% by mass or less of the compound represented by the general formula (1), its isomer and / or a pharmacologically acceptable salt thereof as an active ingredient, for improving facial shape, improving skin retinaculum, improving dermal fiber structure, and / or anti-aging after treatment with High Intensity Focused Ultrasound and / or treatment with a high frequency sagging treatment device.

10. The composition according to claim 1 or 2, which is an external preparation for the skin, is used to improve facial shape, improve skin retinaculum, improve dermal fiber structure, and / or for anti-aging after treatment with high intensity focused ultrasound and / or treatment with a high frequency sagging treatment device.

11. An agent for improving facial shape, improving skin retinaculum, improving dermal fiber structure, and / or anti-aging after treatment with High Intensity Focused Ultrasound and / or treatment with a high frequency sagging treatment device, comprising a compound represented by the following general formula (1), an isomer thereof, and / or a pharmacologically acceptable salt thereof as an active ingredient. 【Chemistry 2】 [In the formula, R1 represents a linear or branched alkyl group having 1 to 4 carbon atoms substituted with a carboxyl group, or a linear or branched alkyl group having 1 to 4 carbon atoms substituted with a carboxylate group having an alkyl chain having 1 to 4 carbon atoms, and R2 and R3 each independently represent a linear or branched alkyl group having 1 to 4 carbon atoms.]

12. A composition for improving facial shape, improving retinaculum, improving dermal fiber structure, and / or for anti-aging, which comprises a compound represented by the following general formula (1), an isomer thereof, and / or a pharmacologically acceptable salt thereof as an active ingredient, is applied to the skin after a high intensity focused ultrasound treatment and / or a high frequency sagging treatment device, the composition being characterized in that the composition is applied to the skin after a high intensity focused ultrasound treatment and / or a high frequency sagging treatment device. Facial shape improvement, skin retinaculum improvement, dermal fiber structure improvement, and / or anti-aging method after treatment with a high-frequency ultrasound treatment device (excluding medical procedures). 【Chemistry 3】 [In the formula, R1 represents a linear or branched alkyl group having 1 to 4 carbon atoms substituted with a carboxyl group, or a linear or branched alkyl group having 1 to 4 carbon atoms substituted with a carboxylate group having an alkyl chain having 1 to 4 carbon atoms, and R2 and R3 each independently represent a linear or branched alkyl group having 1 to 4 carbon atoms.]

Images