HK1197582B - Keratotic plug regrowth inhibition agent, keratotic plug regrowth inhibition method, and keratotic plug regrowth inhibition kit - Google Patents

Description

Keratotic plug regeneration inhibitor, keratotic plug regeneration inhibition method, and keratotic plug regeneration inhibition kit

Technical Field

The present invention relates to an keratotic plug regeneration inhibitor, a keratotic plug regeneration inhibition method, and a keratotic plug regeneration inhibition kit. More specifically, the present invention relates to a keratotic plug regeneration inhibitor, a method for inhibiting keratotic plug regeneration, and a kit for inhibiting keratotic plug regeneration, which can effectively inhibit the regeneration of keratotic plugs without causing skin roughness.

Background

The annoyance of the keratotic plug is the item that is in front of the female's skin annoyance. The keratotic plug is formed by blocking pores (pores) with a mixture of sebum, exfoliated cuticle and the like (see non-patent document 1), and as it grows, the pores become a blocked white small pimple, or if further contains sweat hair and dirt, the pores become a blocked black small pimple, and both the skin and skin are in a striking pimple state, and it is not preferable because both the appearance and the touch are not good. It is also said to cause skin irritation if left untreated. As a countermeasure against such a corner plug which has been formed, it is usually removed with a cleanser, a mask (pack), or the like, and a large number of products are commercially available. There are also many prior art documents relating to removal of corner plugs, and examples thereof include: examples of the surfactant include a substance containing an N-acylamino acid salt (patent document 1), a substance containing lauroyl sarcosine or the like (patent document 2), a combination of a liquid oil at room temperature with N, N' -tetrakis (2-hydroxypropyl) ethylenediamine, a nonionic surfactant or the like (patent document 3), a combination of a diester of a dimer acid and a monoglyceride of fatty acids (patent document 4), a combination of a diester of a dimer acid and a monoglyceride of polyoxyethylene fatty acids (patent document 5), and a diester of a dibasic acid having 6 to 20 carbon atoms (patent document 6). However, the removal efficiency is not high, and even if the skin is removed, the skin is regenerated in about 1 week, and the skin is often rough by repeating the treatment with the mask.

Heretofore, it has been known that organic acids such as tannic acid, lactic acid, citric acid, tartaric acid, glutamic acid, and salts thereof are effective for the regeneration inhibition of keratotic plugs (see patent documents 7 to 8). However, it is actually difficult to actually feel the effect, and there are commercial products which are claimed to constrict pores such as astringent lotion, but there are no commercial products which are claimed to make regeneration of keratotic plug difficult. In addition, the use of organic acids alone causes skin roughness and sensory irritation, and is generally difficult to use as cosmetics.

Documents of the prior art

Patent document

Patent document 1: japanese patent No. 3857182

Patent document 2: japanese patent No. 4058399

Patent document 3: japanese patent No. 4285699

Patent document 4: japanese laid-open patent publication No. 2007-119393

Patent document 5: japanese patent laid-open publication No. 2007-119394

Patent document 6: japanese patent laid-open publication No. 2007-230929

Patent document 7: japanese laid-open patent publication No. 4-360834

Patent document 8: japanese laid-open patent publication No. 4-360830

Non-patent document

Nonpatent document 1, tailgating, フレグランスジャーナル, No.8 month of 2008, pages 28 to 32

Disclosure of Invention

Problems to be solved by the invention

The present invention has been made in view of the above circumstances, and an object thereof is to provide an agent for inhibiting regeneration of keratotic plug, a method for inhibiting regeneration of keratotic plug, and a kit for inhibiting regeneration of keratotic plug, which can effectively inhibit regeneration of keratotic plug without causing skin roughness.

Means for solving the problems

As a result of extensive studies to solve the above problems, the present inventors have found that the combination of a specific organic acid, a specific surfactant and a specific anti-skin-roughness component can effectively inhibit the regeneration of keratotic plugs without causing skin roughness, thereby completing the regeneration inhibitor for keratotic plugs of the present invention.

The present inventors have also found that the use of a specific skin cleanser and a specific keratotic plug regeneration inhibitor can greatly improve the regeneration-inhibiting effect of keratotic plugs without causing skin roughness, and thus completed the method for inhibiting keratotic plug regeneration and the kit for inhibiting keratotic plug regeneration of the present invention.

That is, the present invention relates to a keratotic plug regeneration inhibitor, which comprises: (a) one or more selected from lactic acid, succinic acid, citric acid, malic acid, salicylic acid, pyrrolidone carboxylic acid, glycolic acid and their salts; (b) one or more surfactants selected from fatty acid alkali, higher alkyl sulfate, N-acyl glutamate, N-acyl lower alkyl taurate, betaine surfactant and polyoxyalkylene phytosterol; (c) one or more selected from polyoxyethylene polyoxypropylene dimethyl ether, tranexamic acid, panthenol ethyl ether, fructus Rhodomyrti, serine, trimethylglycine, alanine, glycylglycine, vitamin E acetate, vitamin E nicotinate, 1-piperidine propionic acid and their salts.

The present invention also relates to a method for inhibiting keratotic plug regeneration, which comprises applying a skin cleansing agent comprising a polyoxyethylene fatty acid ester to the skin and then applying to the skin a keratotic plug regeneration inhibitor comprising one or more members selected from the group consisting of lactic acid, succinic acid, citric acid, malic acid, salicylic acid, pyrrolidone carboxylic acid, glycolic acid, and salts thereof.

In the method for suppressing the regeneration of keratotic plug, the keratotic plug regeneration-suppressing agent further contains one or more surfactants selected from the group consisting of fatty acid bases, higher alkyl sulfate salts, N-acyl glutamates, N-acyl lower alkyl taurates, betaine surfactants, and polyoxyalkylene phytosterols. In addition, an anti-skin-roughening agent may be further contained.

In addition, the present invention relates to a keratotic plug regeneration inhibition kit, comprising: a skin cleanser containing polyoxyethylene fatty acid ester and keratotic plug regeneration inhibitor containing one or more selected from lactic acid, succinic acid, citric acid, malic acid, salicylic acid, pyrrolidone carboxylic acid, glycolic acid and their salts are provided.

ADVANTAGEOUS EFFECTS OF INVENTION

The present invention provides a keratotic plug regeneration inhibitor, a keratotic plug regeneration inhibition method, and a keratotic plug regeneration inhibition kit, which can effectively inhibit keratotic plug regeneration without causing skin roughness.

Drawings

FIG. 1 is a graph showing the effect of coating with formulation 3 continuously on moisture content of stratum corneum in example 2.

Detailed Description

Hereinafter, the present invention will be described in detail. Hereinafter, POE represents polyoxyethylene, POP represents polyoxypropylene, and PEG represents polyethylene glycol.

A. Keratotic plug regeneration inhibitor:

the keratotic plug regeneration inhibitor according to an embodiment of the present invention contains the following components (a) to (c).

[ (a) component ]

The component (a) used in the present invention is an organic acid selected from lactic acid, succinic acid, citric acid, malic acid, salicylic acid, pyrrolidone carboxylic acid, and glycolic acid, or a salt thereof. The salt is not particularly limited as long as it is a substance that can be generally used in cosmetics, and examples thereof include: alkali metal salts (sodium salt, potassium salt, lithium salt, etc.), alkaline earth metal salts (calcium salt, magnesium salt, etc.), ammonium salts, organic amine salts (monoethanolamine salt, diethanolamine salt, triethanolamine salt, etc.), and the like. Among them, lactic acid, succinic acid, salicylic acid, pyrrolidone carboxylic acid, or salts thereof are preferable. (a) One or more of the components may be used.

In the keratotic plug regeneration inhibitor of the present invention, the amount of component (a) is preferably 0.001 to 20% by mass, more preferably 0.05 to 5% by mass. When the amount is less than 0.001% by mass, the effect as the component (a) cannot be sufficiently exhibited, while when it exceeds 20% by mass, the effect is not expected to be increased in accordance with the amount to be blended.

[ (b) component ]

(b) The component (A) is one or more surfactants selected from fatty acid base, higher alkyl sulfate, N-acyl glutamate, N-acyl lower alkyl taurate, betaine surfactant and polyoxyalkylene phytosterol.

As fatty acid bases, there may be mentioned: sodium laurate, potassium laurate, sodium palmitate, potassium palmitate, and the like.

Examples of the higher alkyl sulfate salt include sodium lauryl sulfate and potassium lauryl sulfate.

Examples of the N-acyl glutamate include: sodium N-lauroyl glutamate, potassium N-lauroyl glutamate, disodium N-cocoyl glutamate, dipotassium N-cocoyl glutamate, sodium N-myristoyl-L-glutamate, monopotassium N-myristoyl-L-glutamate, and the like.

As N-acyl lower alkyl taurates, N-acyl methyltaurates are particularly preferred; specific examples thereof include: sodium N-cocofatty acid-N-methyltaurate, triethanolamine N-cocofatty acid-N-methyltaurate, magnesium N-cocofatty acid-N-methyltaurate, and the like.

Examples of the betaine-type surfactant include: 2-heptadecyl-N-carboxymethyl-N-hydroxyethyl imidazoline betaine, lauryl dimethyl amino butyric acid betaine, alkyl betaine (for example, lauryl betaine, etc.), amide betaine, sulfobetaine, etc. Their salts may also be mentioned. Examples of the salt include, but are not limited to, sodium salts and potassium salts.

As the polyoxyalkylene phytosterol, polyoxyethylene phytosterol is preferably used. Particularly preferred are polyoxyethylene phytosterols to which 5 to 50 moles, more preferably 20 to 50 moles, of oxyethylene groups are added. Specifically, there may be mentioned: POE (5) phytosterol, POE (10) phytosterol, POE (20) phytosterol, POE (30) phytosterol, and the like, commercially available products include: NIKKOLBPS-5, NIKKOLBPS-10, NIKKOLBPS-20, and NIKKOLBPS-30 (all of which are manufactured by Nihon SurfactantKogyoK. K).

The component (b) is particularly preferably POE phytosterol, potassium laurate, lauryl betaine, or the like.

In the keratotic plug regeneration inhibitor of the present invention, the amount of component (b) is preferably 0.001 to 20% by mass, more preferably 0.05 to 5% by mass. When the amount is less than 0.001% by mass, the effect as the component (b) cannot be sufficiently exhibited, while when it exceeds 20% by mass, the effect is not expected to be increased in accordance with the amount to be blended.

[ (c) component ]

(c) The ingredient is an ingredient having an anti-skin-roughening effect which can be generally applied to an external preparation for skin, and examples thereof include: tranexamic acid derivatives such as tranexamic acid and tranexamic acid formamide; vitamin E derivatives such as 1-piperidinepropionic acid, vitamin E acetate, and vitamin E nicotinate; erythritol, polyoxyethylene polyoxypropylene dimethyl ether (═ POE — POP dimethyl ether), panthenol ethyl ether, serine, trimethylglycine, alanine, glycylglycine, and the like. (c) The component (c) may be used in the form of a salt (sodium salt, potassium salt, etc.). In addition to the above, there may be mentioned: extracts of Hypericum perforatum, Matricaria chamomilla, Sophora flavescens, peony and other plants.

In the present invention, POE POP dimethyl ether, tranexamic acid, panthenyl ethyl ether, hypericum, serine, trimethylglycine, alanine, glycylglycine, vitamin E acetate, vitamin E nicotinate, 1-piperidinepropionic acid, and salts thereof are preferably used.

It is preferable to use POE-POP dimethyl ether in which the molar ratio of POE to POP is 1: 2-5: about 1 POE-POP dimethyl ether. In addition, the addition mole number of the ethylene oxide is preferably 1 to 70, and more preferably 2 to 20; the addition mole number of the propylene oxide is preferably 1 to 70, and more preferably 2 to 20. (c) One or more of the components may be used.

In the keratotic plug regeneration inhibitor of the present invention, the amount of component (c) is preferably 0.001 to 20% by mass, more preferably 0.05 to 5% by mass. When the amount is less than 0.001% by mass, the effect as the component (c) cannot be sufficiently exhibited, while when it exceeds 20% by mass, the effect is not expected to be increased in accordance with the amount to be blended.

The keratotic plug regeneration inhibitor of the present invention comprising the combination of the components (a) to (c) does not cause skin roughness and is excellent in the regeneration-inhibiting effect and feeling of effect of keratotic plug. The term "suppression of the regeneration of keratotic plugs" means to suppress the formation of keratotic plugs again in the pores after removing the keratotic plugs from the pores once.

The keratotic plug regeneration inhibitor of the present invention may be appropriately blended with other optional additives that are generally used in external preparations for skin such as cosmetics and drugs, if necessary, within a range that does not impair the effects of the present invention, for example: oils and fats, waxes, hydrocarbon oils, higher fatty acids, higher alcohols, synthetic ester oils, silicone oils, water-soluble polymers, chelating agents, lower alcohols, polyhydric alcohols, pH regulators, antioxidants, powdery components, perfumes, water, and the like. But is not limited to these examples.

The formulation of the keratotic plug regeneration inhibitor of the present invention is not particularly limited, and it may be used in the form of a liquid preparation, a gel preparation, a cream, a sheet-dipped preparation, or the like, and a liquid preparation is particularly preferable. The pH of the keratotic plug regeneration inhibitor of the present invention is preferably about 3.0 to 8.0.

B. Keratotic plug regeneration inhibition method and keratotic plug regeneration inhibition kit:

another aspect of the present invention provides a method for suppressing regeneration of a corner plug, including: the method for treating keratotic skin comprises a step of applying a specific skin cleanser shown below to the skin and a step of applying a specific keratotic regeneration inhibitor shown below to the skin after the step.

In addition, another embodiment of the present invention provides a kit for inhibiting keratotic plug regeneration, which comprises a specific skin cleansing agent and a specific keratotic plug regeneration inhibitor.

< skin cleanser >

The skin cleanser used in the method for inhibiting the regeneration of keratotic plug of the present invention contains a polyoxyethylene fatty acid ester as an active ingredient. Examples of POE fatty acid esters include: POE sorbitan fatty acid esters, POE glycerin fatty acid esters, POE propylene glycol fatty acid esters, POE hydrogenated castor oil surfactants, sorbitan surfactants, and the like, each having one or more fatty acid residues selected from an oleic acid residue, an isostearic acid residue, and a lauric acid residue. But is not limited to these examples. One or more kinds of POE fatty acid esters can be used.

The amount of POE fatty acid ester blended in the skin cleanser is preferably 1 to 60 mass%, more preferably 5 to 40 mass%. By setting the blending amount within the above range, an extremely excellent effect of suppressing the regeneration of the keratoplug can be obtained when the composition is used in combination with a keratoplug regeneration-suppressing agent. When the amount is less than 1% by mass, the effect as a component cannot be sufficiently exhibited, and when it exceeds 60% by mass, the effect corresponding to the amount to be added is not expected to be increased.

The skin cleansing agent may be any base agent such as oil type, foam type, and liquid type. In the present invention, particularly, oil-type liquid preparations (cleansing oil and the like) are preferably used. In the case of an oil-type detergent (oil-based detergent), an oil component that is liquid at room temperature is blended as a main component in addition to the above essential components. Examples of such liquid oil include: hydrocarbon oils such as liquid paraffin (mineral oil), squalane, olefin oligomers, and light isoparaffins; ester oils such as triglyceride 2-ethylhexanoate, cetyl 2-ethylhexanoate, pentaerythritol 2-ethylhexanoate, trimethylolpropane 2-ethylhexanoate, 2-ethylhexyl palmitate, isocetyl isononanoate, and isopropyl myristate; jojoba oil, olive oil, macadamia nut oil, cottonseed oil, tea tree seed oil, safflower oil, rice bran oil, and other natural plant oils; silicone oils such as decamethylcyclopentasiloxane, octamethylcyclotetrasiloxane, dimethylsiloxane, and methylphenylsiloxane.

When the liquid oil component is blended, it is preferably blended in the skin cleanser in a range of 50 to 95% by mass, more preferably 60 to 80% by mass. When the amount is 50% by mass, the effect as a component cannot be sufficiently exhibited, while when the amount exceeds 95% by mass, the effect is not expected to be increased in accordance with the amount to be added.

As other components that can be blended in addition to these liquid oil components, various components that are generally blended in the fields of cosmetics and pharmaceuticals may be added within a range that does not impair the effects of the present invention. Examples of such components include: lower alcohols such as ethanol and isopropanol; polyhydric alcohols such as glycerin, 1, 3-butanediol (butyleneglycol), isoprene glycol (isoprenediol), 1, 3-butanediol (butyldiol), dipropylene glycol, and propylene glycol; anionic surfactants, amphoteric surfactants such as N-alkyl-N, N-dimethylaminoacetic acid betaine and alkyldimethylamine oxides, cationic surfactants, nonionic surfactants, bactericides, ultraviolet absorbers, antioxidants, perfumes, and water.

< inhibitor of regeneration of keratotic plug >

[ organic acids ]

The keratotic plug regeneration inhibitor used in the method for inhibiting keratotic plug regeneration of the present invention includes organic acids, and examples of these organic acids include the same components as the component (a) in the above-mentioned "inhibitor for keratotic plug regeneration". The same applies to the preferred embodiments. One or two or more of these organic acids may be used.

In the keratotic plug regeneration inhibitor used in the present invention, the amount of the organic acid is preferably 0.001 to 20% by mass, and more preferably 0.05 to 5% by mass. When the amount is less than 0.001% by mass, the effect as the component (a) cannot be sufficiently exhibited, while when it exceeds 20% by mass, the effect is not expected to be increased in accordance with the amount to be blended.

[ surfactant ]

The agent for suppressing regeneration of keratotic plug to be used in the method for suppressing regeneration of keratotic plug of the present invention preferably contains, in addition to the above-mentioned organic acids, a surfactant selected from fatty acid bases, higher alkyl sulfate ester salts, N-acyl glutamates, N-acyl lower alkyl taurates, betaine-based surfactants and polyoxyalkylene phytosterols. Specific examples and preferable examples of these surfactants include the same components as the component (b) in the above-mentioned "inhibitor for regeneration of a. keratotic plug". One or two or more surfactants may be used.

The amount of these surfactants to be blended is preferably 0.001 to 20% by mass, more preferably 0.05 to 5% by mass, in the keratotic plug regeneration inhibitor. When the amount is less than 0.001% by mass, the effect as a blending component cannot be sufficiently exhibited, while when the amount exceeds 20% by mass, the effect corresponding to the blending amount is not expected to be increased.

[ anti-skin-roughening agent ]

The keratotic plug regeneration inhibitor used in the method for inhibiting keratotic plug regeneration of the present invention is preferably further formulated with an anti-skin-roughening agent. Specific examples and preferable examples of these anti-skin-roughening agents include the same components as the component (c) in the above-mentioned "inhibitor of regeneration of keratotic plug". The anti-skin-roughening agent may be used singly or in combination.

The amount of the anti-skin-roughening agent to be added is preferably 0.001 to 20% by mass, more preferably 0.05 to 5% by mass, to the keratotic plug regeneration inhibitor. When the amount is less than 0.001% by mass, the effect as an anti-skin-roughening ingredient cannot be sufficiently exhibited, while when the amount exceeds 20% by mass, the effect is not expected to be increased in accordance with the amount to be blended.

In the inhibition of regeneration of keratotic plug to be used in the method for inhibiting regeneration of keratotic plug of the present invention, other optional additives to be used in general external preparations for skin such as cosmetics and drugs may be appropriately added as necessary within the range not to impair the effects of the present invention, for example: oils and fats, waxes, hydrocarbon oils, higher fatty acids, higher alcohols, synthetic ester oils, silicone oils, water-soluble polymers, chelating agents, lower alcohols, polyhydric alcohols, pH regulators, antioxidants, powdery components, perfumes, water, and the like. But is not limited to these examples.

The formulation of the keratotic plug regeneration-suppressing agent to be used in the method for suppressing keratotic plug regeneration of the present invention is not particularly limited, and the agent may be used in the form of a liquid preparation, a gel preparation, a cream, a sheet-dipped preparation, or the like, and a liquid preparation is particularly preferable. The pH of the keratotic plug regeneration inhibitor is preferably about 3.0 to 8.0.

< method for suppressing regeneration of keratotic plug and kit of the present invention >

In the present invention, by applying the keratotic plug regeneration inhibitor to the skin after washing the skin with the skin cleanser, keratotic plug regeneration can be inhibited very effectively. The method of applying the composition to the skin may be suitably performed depending on the form of the composition, such as by coating the composition by allowing the composition to permeate into cotton or the like, or by spraying the composition with a spray or the like.

Further, the cosmetic kit provided with the detergent and the keratotic plug regeneration inhibitor can be sold and used more easily.

Examples

The present invention will be described in more detail with reference to the following examples, but the present invention is not limited to these examples. The amounts to be blended are not particularly limited and are in% by mass.

A. Keratotic plug regeneration inhibitor:

example 1 comparison of the Effect of inhibiting regeneration of keratotic plugs by human body test

1. Test specimen

Formulations 1 and 2 shown below were used. Formulation 1 is a comparative formulation containing component (a) and component (c). Formulation 2 is a sample obtained by adding POE (30) phytosterol to formulation 1, and is the inventive product formulation containing component (a), component (b), and component (c).

(formulation 1: comparative formulation. pH4.1)

2. Evaluation test method

The regeneration inhibition test of keratotic plugs was performed on 4 males who were awake by keratotic plugs between 30 and 50 years old. A frame paper was attached to an appropriate area of the tip of the nose, and the corneal embolism was observed with a video microscope (VMS, (videoscope), "KEYENCEVHX-100"). After a few drops of an adhesive ("aron alpha a"; tricot) were dropped on a glass slide (MATSUNAMI, with APS coating, s8444), the adhesive-coated surface side was brought into close contact with the above-mentioned region. After 10 minutes, the slides were slowly peeled away, removing the corner plugs. Again by VMS observations, it was determined that keratotic plug-removed pores were completely removed, for these determined pores, and then the process of keratotic plug regeneration was observed. Here, the procedure of regeneration of the keratoplug in the state where the preparation was not used (control) was compared with the procedure of regeneration of the keratoplug when the preparation (preparations 1 and 2) was continuously used for coating.

Preparation 1: the whole face was coated with 2mL of cotton (Zishengtang cotton) for 1 day and 2 times, and the whole face was used for 3 weeks.

Preparation 2: the same test subjects were subjected to the coating test in the same manner as in the case of the preparation 1. Formulation 2 was applied to the half face including the nasal tip as the observation site of VMS for 3 weeks.

The growth of keratotic plugs in the same pores was compared with time, and the growth of keratotic plugs (i.e., clogging of pores) when the formulation was applied was slower than that when the formulation was not used (control), and the growth of keratotic plugs when the control and the formulation were applied were almost the same was regarded as "flat"; the result was "negative" indicating that the growth of keratotic plugs (i.e., clogging of pores) was more rapid when the preparation was applied than when the preparation was not applied (control), and 4 of the formulations were compared. The results are shown in Table 1.

[ Table 1]

Since the number of pores from which keratotic plugs were completely removed (i.e., the number of pores to be evaluated in the test) was different in each evaluation test, the number of pores evaluated in formulation 1 was different from that of formulation 2. Based on 4 total subjects, the test subjects were 12 wins, 8 defeats and 9 peaces in the test using preparation 1, and 16 wins, 2 defeats and 7 peaces in the test using preparation 2. The results of calculating only the "win" ratio are shown in table 2 below, and the "win" ratio was significantly increased in the test using formulation 2. That is, it was confirmed that the effect of suppressing keratotic regeneration was higher in formulation 2 containing component (b) added to formulation 1 than in formulation 1 containing component (a) and component (c).

[ Table 2]

Example 2 Effect of keratotic plug regeneration inhibitor on skin Condition

1. Test specimen

Formulation 3 shown below (formulation in which panthenyl ethyl ether was added to formulation 2) was used.

(formulation 3: inventive preparation. pH4.1)

2. Evaluation test method

The nasal ala and facial eggs were coated on the half face side for 3 weeks with 5 male subjects as subjects, and compared with the change in skin condition on the uncoated side, using the above preparation 3 continuously. The amount of sebum before and after 3 weeks of continuous use was measured by a multi-probe MP5(Courage + khazaka corporation) for the coated side and the uncoated side of the nasal wings, and compared with the water content of the horny layer. The results of the amount of sebum are shown in Table 3, and the results of the water content of the horny layer are shown in FIG. 1. In FIG. 1, the vertical axis represents the Corneometer value (unit: AU).

[ Table 3]

From the results shown in table 3, although the amount of sebum tends to increase on the coated side, the increase tends to be suppressed as compared with the non-coated side, and even if there is an individual difference, 4 out of 5 cases were confirmed to have such a tendency.

As shown in the results of fig. 1, the water content of the stratum corneum increased in a large range on the average on the application side, and 3 out of 5 were good on the application side even though there was an individual difference. Thus, it was confirmed that the skin condition was good when the preparation 3 was continuously applied.

Example 4 comparison of the Effect of inhibiting regeneration of keratotic plugs by human body test

1. Test specimen

Formulation 2 described in example 1 (inventive preparation) and formulations 4 and 5 described below were used.

Formulation 4 was prepared by removing tranexamic acid and POE (14) · POP (7) dimethyl ether from formulation 2, adding glycerol and potassium hydroxide in an increased amount, and adding xylitol thereto, and was a comparative formulation containing component (a) and component (b).

Formulation 5 is a formulation obtained by removing tranexamic acid from formulation 2, adding potassium hydroxide in an increased amount, and adding L-serine, trimethylglycine, and hypericum extract, and is a formulation of the present invention comprising component (a), component (b), and component (c).

(formulation 4: comparative formulation. pH4.2)

2. Evaluation test method

The regeneration inhibition test of keratotic plugs was performed on 4 males who were awake by keratotic plugs between 30 and 50 years old. Of the 4 specimens, 3 specimens which are common to example 1 were used (specimen Nos. 1,3 and 4 are given the same reference numerals as in example 1). The remaining 1 (specimen No.5) was the first evaluation test conducted this time. The evaluation test of example 4 was performed on a different date from the evaluation test of example 1.

The corner pins were observed in the same manner as in example 1. That is, a frame paper is pasted on an appropriate area of the nose tip, and VMS observation is performed. After a few drops of an adhesive ("aron alpha a"; tricot) were dropped on a glass slide (MATSUNAMI, with APS coating, s8444), the adhesive-coated surface side was brought into close contact with the above-mentioned region. After 10 minutes, the slides were slowly peeled away, removing the corner plugs. Again by VMS observations, it was determined that keratotic plug-removed pores were completely removed, for these determined pores, and then the process of keratotic plug regeneration was observed. Here, the procedure for regenerating keratotic plugs in the state where no formulation was used (control) was compared with the procedure for regenerating keratotic plugs when coating was performed continuously using a formulation (only one formulation in the tests of formulations 2, 4, and 5.1). Each preparation was applied 2mL each time 1 day 2 times, and the whole face was coated with cotton, using the side of the nose including the nose tip of the VMS observation site and facial eggs as the center, and used continuously for 3 weeks. All the tests were carried out by using 4 patients in total.

The growth of keratotic plugs in the same pores was compared with time, and the growth of keratotic plugs (i.e., clogging of pores) when the formulation was applied was slower than that when the formulation was not used (control), and the growth of keratotic plugs when the control and the formulation were applied were almost the same was regarded as "flat"; the result was "negative" indicating that the growth of keratotic plugs (i.e., clogging of pores) was more rapid when the formulation was applied than when the formulation was not used (control), and 4 of the formulations were compared. The results are shown in Table 4.

[ Table 4]

The number of pores from which keratotic plugs could be completely removed (i.e., the number of pores to be evaluated in the test) varied among the evaluation tests, and therefore the number of pores evaluated in formulations 2, 4, and 5 varied among the tests. The results of calculating only the ratio of "win" are shown in table 5 below.

[ Table 5]

From the results shown in table 5, it is understood that sample No.3 exhibited a higher effect of inhibiting keratotic regeneration than preparations 2 and 5, and as a result of combining the results of table 4, the ratio of "negative" to the number of hair holes to be evaluated in the test was 0% in preparation 2 and 8.7% in preparation 5, while the ratio of "negative" in preparation 4 was also increased to 28.6%. In Table 5, the other subjects (3 subjects) showed higher keratotic regeneration-inhibiting effects than the formulation 4 in formulations 2 and 5. In the total of 4 subjects, the ratio of "win" in the application of the preparation 4 was reduced as compared with the preparation 2, and the test of the preparation 5 was almost equal to that of the preparation 2. That is, it was confirmed that preparations 2 and 5 containing all of the components (a), (b), and (c) had a higher effect of inhibiting keratotic thrombosis regeneration than preparation 4 containing only the components (a) and (b).

Example 6 screening of inhibitors of regeneration of keratotic plugs

The keratotic plugs obtained according to the method described in example 1 were used, and the regeneration inhibitory effects of the keratotic plugs were screened using the evaluation formula shown in table 6 below.

That is, after a few drops of an adhesive ("Aron alpha A"; three in three) were dropped onto the slide glass, the adhesive-applied surface side was brought into close contact with a partial region of the nasal tip of the examinee. After 10 minutes, the slides were slowly peeled off to obtain corner plugs.

The corner pin on the slide glass thus obtained is cut from the adhesive surface with a blade or the like, and is adhered to the upper surface of the double-sided tape applied to the cover glass. This was added to a 5mL petri dish, and an aqueous solution (1% aqueous solution) containing the evaluation formula shown in table 4 was added. Changes over time of the angle plug were observed by a solid microscope and SEM, and the form of the angle plug was evaluated on the basis of the degree of disintegration of the angle plug according to the following 4-degree scale. The evaluation was performed by a comprehensive evaluation using a solid microscope method and an SEM method.

(evaluation criteria)

Level 0: no change (no change was confirmed at all on the surface of the corner bolt)

Level 1: slight change was confirmed (slight change was confirmed, for example, the surface of the corner bolt became slightly unclear)

And 2, stage: there was a change (obvious change was confirmed on the surface of the angle pin)

And 3, level: has considerable change (the surface of the angle bolt is disintegrated, and the like, the concave-convex change is obvious)

(evaluation solution)

As the evaluation solution, an aqueous solution (containing a 1 mass% aqueous solution) containing the evaluation formulae shown in table 6 was used.

[ Table 6]

The following further shows formulation examples of the present invention.

(formulation example 1: emulsion)

(preparation method)

(10) (phase A) is dissolved in a part of (16). To the remaining (16) were added (7), (8), (9), (11), (14) and (15), and the mixture was dissolved by heating and kept at 70 ℃ (aqueous phase). On the other hand, the components (1) to (6), (12) and (13) were mixed and dissolved by heating and kept at 70 ℃ (oil phase). Adding oil phase into water phase for pre-emulsification, adding phase A, emulsifying uniformly with homogenizing mixer, stirring and cooling to 30 deg.C to obtain emulsion.

(formulation example 2 emulsion)

(preparation method)

To (17) were added (8) to (14), and the mixture was heated and maintained at 70 ℃ C (aqueous phase). On the other hand, the components (1) to (7), (15) and (16) were mixed and dissolved by heating and kept at 70 ℃ (oil phase). The aqueous phase was slowly added while mixing the oil phase with stirring, and after uniformly emulsifying with a homomixer, the mixture was cooled to 30 ℃ while well mixing with stirring to obtain an emulsion.

(formulation example 3 emulsion (W/O emulsion type))

(preparation method)

The emulsion is obtained by dissolving (1) to (9) by heating (oil phase), dissolving (10) to (16) (water phase), adding water phase to the oil phase, and emulsifying.

(formulation example 4 gel)

(preparation method)

The A phase and the C phase are uniformly dissolved, and the A phase is added to the C phase for solubilization. And then filling after adding the phase B to obtain the jelly.

(formulation example 5O/W cream)

(preparation method)

Heating A (oil phase) and B (water phase) to 70 deg.C respectively, and dissolving completely. Subsequently, a was added to B and emulsified by an emulsifier. Further, the emulsion was cooled using a heat exchanger to obtain a cream.

(formulation example 6: W/O cream)

(preparation method)

Heating (2), (3), (4) and (6) to 50 ℃, adding (5) to completely dissolve to form an oil phase, and adding (1) to the oil phase part to uniformly disperse; the aqueous phase portion in which (7) to (12) were dissolved in (13) was heated to 50 ℃ and added to the oil phase, and the mixture was uniformly dispersed with HM and then cooled to room temperature to obtain W/O cream.

(formulation example 7: turbid white lotion)

(preparation method)

Heating (1) - (8) to 70 deg.C, dissolving, stirring, mixing, maintaining the temperature at 70 deg.C, stirring, and slowly adding (23) to emulsify to obtain oil-in-water type emulsified composition. The obtained oil-in-water emulsion composition is further added to the aqueous formulation containing (9) to (22), and uniformly dispersed by stirring to obtain a cloudy cosmetic water.

(formulation example 8: toner)

(preparation method)

Dissolving (4) in (3) and heating the dissolved (12). Further, (1), (2), (5) to (11) were dissolved in (13), and the two were mixed to obtain a cosmetic lotion.

B. Keratotic plug regeneration inhibition method and keratotic plug regeneration inhibition kit:

example 7 synergistic Effect of skin cleanser and keratotic plug regeneration inhibitor Using human test)

1. Test specimen

The skin cleanser and keratotic plug regeneration inhibitor used in this example were as follows.

< skin cleanser (cleansing oil) >

(mass%)

< inhibitor of the regeneration of keratotic plug ("formulation 6"). pH4.1>

(mass%)

2. Evaluation test method

[ test (1): use of formulation 6 only

The regeneration inhibition test of keratotic plugs was performed on 4 males who were awake by keratotic plugs between 30 and 40 years old. A frame paper was attached to an appropriate area of the tip of the nose, and the corneal embolism was observed with a video microscope (VMS, videoscope, "KEYENCEVHX-100"). After a few drops of an adhesive ("aron alpha a"; tricot) were dropped on a glass slide (MATSUNAMI, with APS coating, s8444), the adhesive-coated surface side was brought into close contact with the above-mentioned region. After 10 minutes, the slides were slowly peeled away, removing the corner plugs. Again by VMS observations, it was determined that keratotic plug-removed pores were completely removed, for these determined pores, and then the process of keratotic plug regeneration was observed. Here, the procedure of regeneration of the kerato plug in a state where the preparation was not used (control) was compared with the procedure of regeneration of the kerato plug when the preparation was continuously used for coating.

Preparation 6: the half face is coated with cotton (Zishengtang cosmetic cotton) 2mL each time for 1 day and 2 times, and the half face is coated with the nasal wing and facial egg of nose tip part including VMS observation part for 3 weeks.

[ test (2): use of skin cleanser in combination with preparation 6

In the test (2) in which the preparation 6 was combined with a skin cleansing agent, the same application test as in the test (1) was carried out on 4 subjects to be examined. After thoroughly wiping off the ingredients of the skin cleanser, formulation (1) was applied.

In addition, only continuous coating was performed for 1 out of 4 without observation of VMS.

< evaluation >

The growth of keratotic plugs in the same pores was compared with time, and when the growth of keratotic plugs in the state (control) in which the formulation 6 was not used (the same applies in test (2), the growth of keratotic plugs (i.e., clogging of pores) was slow when the formulation was applied was regarded as "win", and when the growth of keratotic plugs in the control and the formulation 6 were applied was regarded as "flat"; the result was negative when the growth of keratotic plugs (i.e., clogging of pores) was more rapid when the formulation 6 was applied than when the formulation 6 was not used (control), and 4 of the results were compared. The results are shown in Table 7.

[ Table 7]

Since the number of pores that can be completely removed and compared at first varies depending on the test, the number of pores evaluated in the test (1) and the test (2) differs. Based on 4 total subjects, the test (1) showed 22 wins, 3 losses and 8 balances, and the test (2) showed 43 wins, 4 losses and 8 balances by combining with the wash oil. Table 8 shows the results of calculating only the ratio of wins, but the ratio was increased from 66.7% to 78.2%, and the results were particularly improved in young subjects such as No.7 and No. 8.

[ Table 8]

In addition, in the results of the examination (counting 5) including 1 subject who was observed by VMS without keratotic plug, the number of people who were able to clearly feel the alleviation of keratotic plug clogging after 3 weeks, and only 1 of 5 subjects was observed when the preparation 6 was applied. On the other hand, by combining with a detergent, the effect was remarkably improved in 5 patients who had 2 patients after 1 week, 3 patients after 2 weeks, and 4 patients after 3 weeks. The skin condition was evaluated as smooth and clear on the side of the nose and the facial egg coated with the facial mask, and the skin condition was also good.

Example 8 screening of inhibitors of regeneration of keratotic plug

In the invention of "b-type method for inhibiting regeneration of keratotic plug and kit for inhibiting regeneration of keratotic plug", the keratotic plug obtained by the method described in the above-mentioned example 6 was used, and the effect of inhibiting regeneration of keratotic plug was screened by the method and the evaluation criteria shown in the above-mentioned table 6 using the evaluation formula shown in the above-mentioned table 6, and as a result, the same results as the evaluation results shown in table 6 were obtained.

The following further shows formulation examples of the present invention.

< skin cleanser (formulation example 9-10) >)

(formulation example 9: skin cleanser)

(formulation example 10: skin cleanser)

(preparation method)

After the normal-temperature liquid oil component and the surfactant were uniformly mixed and stirred at room temperature, the aqueous component was added and uniformly mixed and stirred to prepare a sample.

< inhibitor for regeneration of keratotic plug (formulation examples 11-19) >)

(formulation example 11: toner)

(preparation method)

Adding the alcohol phase of A into the water phase of B for solubilization to obtain cosmetic water. (formulation example 12 emulsion)

(preparation method)

Adding the dissolved phase (A) to the dissolved phase (B), emulsifying, and neutralizing with phase (C) to obtain an emulsion.

(formulation example 13) to (formulation example 19)

Examples of the formulation include those similar to formulation examples 1 to 7 described in the section "a. keratotic regeneration inhibitor".

Industrial applicability

The present invention provides a keratotic plug regeneration inhibitor, a keratotic plug regeneration inhibition method, and a keratotic plug regeneration inhibition kit, which can effectively inhibit keratotic plug regeneration without causing skin roughness.

Claims (3)

1. An agent for inhibiting the regeneration of keratotic plugs, which comprises the following components (a), (b) and (c) as an active ingredient for inhibiting the regeneration of keratotic plugs, and which comprises: (a) 0.001-20% by mass of the component (a), (b) 0.001-20% by mass of the component (b), and (c) 0.001-20% by mass of the component (c):

(a) one or more selected from lactic acid, succinic acid, citric acid, salicylic acid, pyrrolidone carboxylic acid, glycolic acid and their salts;

(b) one or more surfactants selected from fatty acid alkali, N-acyl glutamate, betaine surfactant and polyoxyalkylene phytosterol, wherein the betaine surfactant is one or more selected from 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazoline betaine, alkyl betaine and salt thereof; and

(c) one or more selected from polyoxyethylene and polyoxypropylene dimethyl ether, tranexamic acid, panthenol ethyl ether, Hypericum perforatum extract, serine, trimethylglycine, alanine, glycylglycine, glycine and their salts.

2. A cosmetic method for inhibiting the regeneration of keratotic plugs, characterized in that after a skin cleanser containing polyoxyethylene fatty acid ester is applied to the skin, the skin cleanser is applied to the skin, and the effective components of the keratotic plugs comprise the following components (a) to (c): (a) 0.001 to 20% by mass of component (a), 0.001 to 20% by mass of component (b), and 0.001 to 20% by mass of component (c):

(a) one or more organic acids selected from lactic acid, succinic acid, citric acid, salicylic acid, pyrrolidone carboxylic acid, glycolic acid, and their salts;

(b) one or more surfactants selected from fatty acid alkali, N-acyl glutamate, betaine surfactant and polyoxyalkylene phytosterol, wherein the betaine surfactant is one or more selected from 2-alkyl-N-carboxymethyl-N-hydroxyethyl imidazoline betaine, alkyl betaine and salt thereof; and

(c) one or more anti-skin roughness agents selected from polyoxyethylene/polyoxypropylene/dimethyl ether, tranexamic acid and panthenyl ethyl ether.

3. A keratotic plug regeneration-inhibiting kit comprising: the skin cleanser and keratotic plug regeneration inhibitor for use in the cosmetic method for keratotic plug regeneration inhibition according to claim 2.