WO2016159184A1 - Topical composition for amelioration of acne vulgaris - Google Patents
Topical composition for amelioration of acne vulgaris Download PDFInfo
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- WO2016159184A1 WO2016159184A1 PCT/JP2016/060561 JP2016060561W WO2016159184A1 WO 2016159184 A1 WO2016159184 A1 WO 2016159184A1 JP 2016060561 W JP2016060561 W JP 2016060561W WO 2016159184 A1 WO2016159184 A1 WO 2016159184A1
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- WIPO (PCT)
- Prior art keywords
- allantoin
- composition
- salicylic acid
- external
- acne vulgaris
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/60—Salicylic acid; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
Definitions
- the present invention relates to an external composition for improving acne vulgaris.
- Salicylic acid is known to have a keratolytic action (Patent Document 1), and is generally used for the treatment of acne vulgaris for the purpose of softening hardened keratin and clogging pores, for example. Has been. Allantoin has an anti-inflammatory effect and is used for skin diseases because of its anti-inflammatory effect. However, salicylic acid is hardly soluble in water and its formulation is limited (Non-patent Document 1), and allantoin is hardly soluble in water and extremely insoluble in ethanol (Non-patent Document 2).
- acne vulgaris is a well-known skin disease, and is a disease found in a wide range of ages including adolescence. For this reason, many preparations for the treatment of acne vulgaris have been marketed so far (Patent Documents 1 to 5), but they are more useful due to the discomfort caused by the appearance and pain of the affected area. There is a need for formulations.
- Patent Document 1 discloses that salicylic acid can be used as a keratolytic agent, and that an anti-acne agent may be further added to an external preparation for skin containing an NF ⁇ B activation inhibitor.
- Patent Document 2 discloses a composition for beautifying skin, which contains a specific compound as an active ingredient, and acts effectively on the prevention and improvement of acne and the like.
- salicylic acid and allantoin are listed.
- Patent Document 3 discloses an acne skin external preparation containing a specific amount of a singlet oxygen scavenger, and further discloses that a component such as salicylic acid may be contained.
- Patent Document 4 discloses an acne-preventing skin external preparation containing alanine as an active ingredient
- Patent Document 5 discloses an acne-preventing skin external preparation containing serine as an active ingredient. It is disclosed that the skin external preparation for prevention can contain various other components.
- an object of the present invention is to provide a composition for external use that is useful for improving acne vulgaris while using both salicylic acid and allantoin.
- a composition for external use that is useful for improving acne vulgaris while using both salicylic acid and allantoin.
- salicylic acid and allantoin are precipitated, they are not re-dissolved even when the temperature is returned to room temperature. Therefore, an object of the present invention is to provide a composition for external use that is more excellent in stability and is suppressed in precipitation even at low temperatures.
- precipitation of salicylic acid and allantoin can be suppressed even at a low temperature.
- the composition for external use for acne vulgaris improvement by which stability was improved more can be provided.
- composition for external use for improving acne vulgaris comprises (a) salicylic acid, (b) allantoin, a derivative thereof, and at least one selected from the group thereof, (c) ethanol, and (d) Contains polyhydric alcohol.
- Salicylic acid is a conventionally known substance, and a commercially available product may be used.
- the content of the component (a) is not limited as long as the effect of the present invention is obtained.
- the component (a) is 0.001 to 10% by weight, preferably 0.01 to 5% by weight, More preferred is 0.1 to 1% by weight.
- allantoin is also known as 5-ureidohydantoin or glyoxydiureido.
- allantoin derivatives, allantoin or allantoin derivatives salts are not limited as long as they are pharmaceutically or cosmetically acceptable derivatives and salts, respectively.
- Allantoin acetyl-DL-methionine, allantoin polygalacturonic acid, allantoin Examples thereof include ⁇ -glycyrrhetinic acid, allantoin DL-pantothenyl alcohol, allantoinchlorohydroxyaluminum, allantoindihydroxyaluminum, allantoin pyrophosphoric acid sodium carboxylate and the like.
- the component (b) is preferably allantoin, allantoinchlorohydroxyaluminum, allantoindihydroxyaluminum, more preferably allantoin. These may be used alone or in combination of two or more.
- the content of the component (b) is not limited as long as the effects of the present invention can be obtained, but in the composition for external use, the component (b) is 0.001 to 10% by weight in terms of allantoin, preferably 0.00. Examples are 01 to 5% by weight, more preferably 0.05 to 1% by weight.
- (C) Ethanol is conventionally known and is not limited as long as it is a pharmaceutically or cosmetically acceptable grade.
- the content of the component (c) is not limited as long as the effect of the present invention is obtained, but in the composition for external use, the component (c) is 1 to 23% by weight, preferably 10 to 23% by weight, more preferably 18%. Illustrated is ⁇ 23 wt%, particularly preferably 20 to 22 wt%.
- (D) As polyhydric alcohol, 1,3-butylene glycol, dipropylene glycol, propylene glycol, 1,2-pentanediol, 1,2-hexanediol, glycerin, diglycerin, polyglycerin, polyethylene glycol, polypropylene glycol, Examples include macrogol and sorbitol.
- the component (d) is preferably 1,3-butylene glycol, dipropylene glycol, propylene glycol, glycerin, polyethylene glycol, macrogol, sorbitol, more preferably 1,3-butylene glycol, dipropylene glycol, propylene glycol. And glycerin. These may be used alone or in combination of two or more.
- the component (d) is not limited as long as it is used, but from the viewpoint of improving the familiarity and / or irritation to the skin, particularly the familiarity and / or irritation of acne vulgaris, Two or more polyhydric alcohols are preferably used.
- the content of the component (d) is not limited as long as the effects of the present invention are obtained.
- the component (d) is 1 to 30% by weight, preferably 5 to 30% by weight, more preferably 10%. ⁇ 25% by weight is exemplified.
- the external composition of the present invention may further contain any pharmaceutically or cosmetically acceptable component as necessary.
- Such optional ingredients include water, surfactants, fragrances, colorants, preservatives, antioxidants, emulsifiers, oils, thickeners, metal sequestering agents, bactericides, deodorants, pH adjusters, and cooling. , Cell activator, anti-aging agent, moisturizer, blood circulation promoter, vitamins, plant extract, collagen, skin astringent, anti-inflammatory agent, whitening agent, antioxidant, etc.
- Examples of publicly known ingredients used in external compositions applied to the skin such as external quasi drugs and cosmetics. These may be used individually by 1 type, may be used in combination of 2 or more type, and should just select and use arbitrary things suitably.
- distilled water, tap water, ion exchange water, pure water, and ultrapure water are exemplified as water.
- the water content is not limited as long as the effects of the present invention are not hindered. However, when water is contained, it is 26 to 99% by weight, more preferably 46 to 90% by weight, and still more preferably 59% in the composition for external use of the present invention. Examples are -80% by weight, particularly preferably 60-70% by weight.
- the form of the composition for external use of the present invention is not particularly limited as long as it can be applied externally, and preferable examples include forms applicable to the skin including face, neck, chest, back and scalp. Examples of such forms include liquids, emulsions, creams, gels, pastes, and mousses at room temperature (25 ° C.). Although it does not restrict
- the composition for external use of the present invention can be used as a pharmaceutical, a quasi-drug, and a cosmetic.
- composition for external use of the present invention is excellent in stability because precipitation is suppressed, it can also be used for sprays in which clogging of the injection port due to the precipitate is a problem.
- Suitable for storing in a spray container The material of the spray container is not particularly limited, and a plastic container such as polyethylene or polypropylene is preferably exemplified.
- the composition for external use of the present invention is not limited as long as the effects of the present invention can be obtained, but usually, pH 2 to 9 is exemplified at room temperature (25 ° C.), and it is hypoallergenic to the skin including acne vulgaris. From the viewpoint of usability, the pH is preferably 2 to 7, and more preferably pH 2.2 to 6.
- composition for external use of the present invention can be produced by mixing the components (a) to (d) and, if necessary, optional components according to a conventional method corresponding to various forms.
- the composition for external use of this invention can be manufactured.
- composition for external use of the present invention may be applied to the skin, particularly acne vulgaris, the amount used may be appropriately set according to the degree of acne vulgaris, etc. What is necessary is just to set, and what is necessary is just to use an appropriate amount / time or an appropriate frequency / day for the acne vulgaris part of skin.
- an external composition of the present invention precipitation of the component (a) and the component (b) can be suppressed even at a low temperature. For this reason, according to the present invention, it is possible to provide an external composition for improving acne vulgaris with improved stability, and therefore, acne vulgaris can be improved more effectively.
- the present invention further provides the external composition containing the components (a) and (b), wherein the components (c) and (d) are used in combination. It can also be said that it provides a method for suppressing precipitation of the component (b).
- the components (a) to (d), the content of the components, and the like are described in the same manner as described above.
- the composition for external use contains the components (a) and (b), it can be preferably used for the improvement of acne vulgaris, and the composition for external use contains the above-mentioned optional components as necessary. You may contain.
- the form of the composition for external use and the like will be described in the same manner as described above. According to this method, precipitation of the components (a) and (b) can be suppressed even at low temperatures.
- Test example 1 Preparation of composition for external use for improving acne vulgaris (Examples 1 to 11) According to the following Table 1, acne vulgaris containing salicylic acid, allantoin, ethanol, dipropylene glycol, 1,3-butylene glycol and / or water External compositions for improving acne (Examples 1 to 11) were prepared. Specifically, according to Table 1, salicylic acid was added to ethanol and stirred to dissolve the salicylic acid (mixture 1).
- allantoin was added to an appropriate amount of purified water and stirred to dissolve allantoin, and then dipropylene glycol or 1,3-butylene glycol was added and stirred to dissolve (mixture 2).
- the obtained mixtures 1 and 2 were mixed and stirred well, and then the total weight was adjusted to 100 g with purified water.
- the value is% by weight. Moreover, pH was measured at room temperature (about 25 degreeC) using the pH meter.
- compositions for external use (Examples 1 to 6 and Example 10) containing salicylic acid, allantoin, ethanol and dipropylene glycol, and containing salicylic acid, allantoin, ethanol and 1,3-butylene glycol
- salicylic acid and allantoin were sufficiently dissolved immediately after production, and no precipitation was observed even after storage.
- the tested pH was a condition in which precipitation was likely to occur, it was found that, despite this, precipitation can be significantly suppressed, and thus a highly stable external composition can be obtained.
- action which each component of salicylic acid, allantoin, and ethanol has is acquired.
- Test example 2 Preparation of external composition for improving acne vulgaris (Examples 12 to 16) According to the following Table 3, salicylic acid, allantoin, ethanol, 1,3-butylene glycol, dipropylene glycol, propylene glycol, glycerin and / or water were added. The composition for external use for improving acne vulgaris (Examples 12 to 16) was prepared. Specifically, according to Table 3, salicylic acid was added to ethanol and stirred to dissolve the salicylic acid (mixture 1).
- allantoin was added to an appropriate amount of purified water and stirred to dissolve allantoin, and then 1,3-butylene glycol, dipropylene glycol, propylene glycol and glycerin were appropriately added and stirred to dissolve (mixture 2 ).
- the obtained mixtures 1 and 2 were mixed and stirred well, and then the total weight was adjusted to 100 g with purified water.
- Comparative Example 9 a comparative external composition (Comparative Example 9) was prepared according to Table 3.
- the lowest score was 0 point and the highest score was 10 points, and each subject was evaluated for the degree of skin familiarity. Larger numbers indicate better skin familiarity.
- the average value of the obtained values is obtained, and the average value is less than 4 points “x”, 4 points to less than 6 points “ ⁇ ”, 6 points to less than 8 points “ ⁇ ”, 8 points to 10 points.
- the results are shown in Table 3 as “ ⁇ ”.
- Sense of irritation was evaluated with each subject evaluating the degree of irritation, with 0 being the lowest score and 10 being the highest score. A smaller value indicates less irritation.
- the average of the obtained values is obtained, and the average value is less than 4 points “ ⁇ ”, 4 points to less than 6 points “ ⁇ ”, 6 points to less than 8 points “ ⁇ ”, 8 points to 10 points.
- Results Table 3 shows the evaluation results of the external composition for improving acne vulgaris (Examples 12 to 16) and the comparative external composition (Comparative Example 9).
- Comparative Example 9 when only salicylic acid, allantoin, and ethanol were used (Comparative Example 9), although salicylic acid and allantoin were sufficiently dissolved immediately after production, precipitation of these components was observed after storage. Further, the external composition of Comparative Example 9 was not a desirable external composition because the skin was not well-fitted and the irritation was strong.
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Abstract
[Problem] The purpose of the present invention is to provide a topical composition that comprises both salicylic acid and allantoin, and is useful for the amelioration of acne vulgaris. [Solution] A topical composition for the amelioration of acne vulgaris, said topical composition including: (a) salicylic acid; (b) at least one substance selected from the group consisting of allantoin, derivatives thereof, and salts of allantoin and the derivatives; (c) ethanol; and (d) a polyhydric alcohol.
Description
本発明は、尋常性ざ瘡改善用外用組成物に関する。
The present invention relates to an external composition for improving acne vulgaris.
サリチル酸は角質溶解作用を有することが知られており（特許文献１）、例えば、硬くなった角質を柔らかくして毛穴のつまりをとる目的で尋常性ざ瘡（にきび）の治療に一般的に使用されている。また、アラントインは抗炎症作用を有し、その消炎作用から皮膚疾患に使用されている。しかしながら、サリチル酸は水に溶けにくく、その製剤化には制限があり（非特許文献１）、また、アラントインは水に溶けにくく、エタノールには極めて溶けにくい（非特許文献２）。
Salicylic acid is known to have a keratolytic action (Patent Document 1), and is generally used for the treatment of acne vulgaris for the purpose of softening hardened keratin and clogging pores, for example. Has been. Allantoin has an anti-inflammatory effect and is used for skin diseases because of its anti-inflammatory effect. However, salicylic acid is hardly soluble in water and its formulation is limited (Non-patent Document 1), and allantoin is hardly soluble in water and extremely insoluble in ethanol (Non-patent Document 2).
一方、尋常性ざ瘡は広く知られている皮膚疾患であり、思春期をはじめ幅広い年齢層に認められる疾患である。このため、尋常性ざ瘡の治療を目的とする製剤はこれまでにも数多く市販されているが（特許文献１～５）、その患部の外観や痛み等に起因する不快感から、より有用な製剤が求められている。
On the other hand, acne vulgaris is a well-known skin disease, and is a disease found in a wide range of ages including adolescence. For this reason, many preparations for the treatment of acne vulgaris have been marketed so far (Patent Documents 1 to 5), but they are more useful due to the discomfort caused by the appearance and pain of the affected area. There is a need for formulations.
例えば特許文献１には、角質溶解剤としてサリチル酸を使用できることが開示されており、また、ＮＦκＢ活性化抑制物質を含有する皮膚外用剤に更に抗にきび剤を添加してもよいことが開示されている。また、特許文献２には、特定の化合物を有効成分とする、にきび等の予防や改善に対して有用に作用する美肌用組成物が開示されており、該美肌用組成物にはその他の様々な成分を含有可能であることが開示されており、その一例としてサリチル酸やアラントインが列挙されている。また、特許文献３には特定量の一重項酸素除去剤を含有するにきび用皮膚外用剤が開示されており、更にサリチル酸等の成分を含有してもよいことが開示されている。また、例えば特許文献４にはアラニンを有効成分として含有するにきび防止用皮膚外用剤が、特許文献５にはセリンを有効成分として含有するにきび防止用皮膚外用剤が開示されており、これらのにきび防止用皮膚外用剤にはその他の様々な成分を含有可能であることが開示されている。
For example, Patent Document 1 discloses that salicylic acid can be used as a keratolytic agent, and that an anti-acne agent may be further added to an external preparation for skin containing an NFκB activation inhibitor. Yes. Further, Patent Document 2 discloses a composition for beautifying skin, which contains a specific compound as an active ingredient, and acts effectively on the prevention and improvement of acne and the like. As an example, salicylic acid and allantoin are listed. Patent Document 3 discloses an acne skin external preparation containing a specific amount of a singlet oxygen scavenger, and further discloses that a component such as salicylic acid may be contained. For example, Patent Document 4 discloses an acne-preventing skin external preparation containing alanine as an active ingredient, and Patent Document 5 discloses an acne-preventing skin external preparation containing serine as an active ingredient. It is disclosed that the skin external preparation for prevention can contain various other components.
しかしながら、これらはいずれもサリチル酸やアラントインの析出の問題は開示していない。
However, none of these disclose the problem of precipitation of salicylic acid or allantoin.
そこで、本発明は、サリチル酸とアラントインとを共に用いながらも、尋常性ざ瘡の改善に有用な外用組成物を提供することを目的とする。特に、サリチル酸とアラントインはいったん析出すると室温に戻しても再溶解しないことから、低温であっても析出が抑制された、安定性が一層優れた外用組成物を提供することを目的とする。
Therefore, an object of the present invention is to provide a composition for external use that is useful for improving acne vulgaris while using both salicylic acid and allantoin. In particular, once salicylic acid and allantoin are precipitated, they are not re-dissolved even when the temperature is returned to room temperature. Therefore, an object of the present invention is to provide a composition for external use that is more excellent in stability and is suppressed in precipitation even at low temperatures.
本発明者らは、前記課題を解決するために鋭意検討を重ねていたところ、サリチル酸とアラントインに、エタノールと多価アルコールを併用することにより、低温であってもサリチル酸とアラントインの析出が抑制された外用組成物が得られることを見出した。本発明は該知見に基づき更に検討を重ねた結果完成されたものであり、次に掲げるものである。
項１．（ａ）サリチル酸、（ｂ）アラントイン、その誘導体及びこれらの塩からなる群より選択される少なくとも１種、（ｃ）エタノール、ならびに（ｄ）多価アルコールを含有する、尋常性ざ瘡改善用外用組成物。
項２．（ｃ）エタノールの含有量が１～２３重量％である、項１に記載の外用組成物。
項３．（ｄ）多価アルコールの含有量が１～３０重量％である、項１または２に記載の外用組成物。
項４．２種以上の多価アルコールを含有する、項１～３のいずれかに記載の外用組成物。 The inventors of the present invention have made extensive studies in order to solve the above problems. By using ethanol and polyhydric alcohol in combination with salicylic acid and allantoin, precipitation of salicylic acid and allantoin is suppressed even at low temperatures. It was found that a composition for external use was obtained. The present invention has been completed as a result of further studies based on this finding, and is as follows.
Item 1. (A) Salicylic acid, (b) Allantoin, a derivative thereof, and at least one selected from the group consisting of these salts, (c) ethanol, and (d) a polyhydric alcohol, for external use for improving acne vulgaris Composition.
Item 2. (C) The external composition according to Item 1, wherein the ethanol content is 1 to 23% by weight.
Item 3. (D) The composition for external use according to Item 1 or 2, wherein the content of the polyhydric alcohol is 1 to 30% by weight.
Item 4. The composition for external use according to any one of Items 1 to 3, comprising two or more polyhydric alcohols.
項１．（ａ）サリチル酸、（ｂ）アラントイン、その誘導体及びこれらの塩からなる群より選択される少なくとも１種、（ｃ）エタノール、ならびに（ｄ）多価アルコールを含有する、尋常性ざ瘡改善用外用組成物。
項２．（ｃ）エタノールの含有量が１～２３重量％である、項１に記載の外用組成物。
項３．（ｄ）多価アルコールの含有量が１～３０重量％である、項１または２に記載の外用組成物。
項４．２種以上の多価アルコールを含有する、項１～３のいずれかに記載の外用組成物。 The inventors of the present invention have made extensive studies in order to solve the above problems. By using ethanol and polyhydric alcohol in combination with salicylic acid and allantoin, precipitation of salicylic acid and allantoin is suppressed even at low temperatures. It was found that a composition for external use was obtained. The present invention has been completed as a result of further studies based on this finding, and is as follows.
Item 1. (A) Salicylic acid, (b) Allantoin, a derivative thereof, and at least one selected from the group consisting of these salts, (c) ethanol, and (d) a polyhydric alcohol, for external use for improving acne vulgaris Composition.
Item 2. (C) The external composition according to Item 1, wherein the ethanol content is 1 to 23% by weight.
Item 3. (D) The composition for external use according to Item 1 or 2, wherein the content of the polyhydric alcohol is 1 to 30% by weight.
Item 4. The composition for external use according to any one of Items 1 to 3, comprising two or more polyhydric alcohols.
本発明によれば、低温であってもサリチル酸とアラントインの析出を抑制することができる。このため、本発明によれば、より安定性が高められた尋常性ざ瘡改善用の外用組成物を提供できる。
According to the present invention, precipitation of salicylic acid and allantoin can be suppressed even at a low temperature. For this reason, according to this invention, the composition for external use for acne vulgaris improvement by which stability was improved more can be provided.
以下、本発明の尋常性ざ瘡改善用外用組成物をより詳細に説明する。
Hereinafter, the external composition for improving acne vulgaris according to the present invention will be described in more detail.
本発明の尋常性ざ瘡改善用外用組成物は、（ａ）サリチル酸、（ｂ）アラントイン、その誘導体及びこれらの塩からなる群より選択される少なくとも１種、（ｃ）エタノール、ならびに（ｄ）多価アルコールを含有する。
The composition for external use for improving acne vulgaris according to the present invention comprises (a) salicylic acid, (b) allantoin, a derivative thereof, and at least one selected from the group thereof, (c) ethanol, and (d) Contains polyhydric alcohol.
（ａ）サリチル酸は従来公知の物質であり、市販品を用いても良い。
(A) Salicylic acid is a conventionally known substance, and a commercially available product may be used.
（ａ）成分の含有量は、本発明の効果が得られる限り制限されないが、該外用組成物中、（ａ）成分は０．００１～１０重量％、好ましくは０．０１～５重量％、更に好ましくは０．１～１重量％が例示される。
The content of the component (a) is not limited as long as the effect of the present invention is obtained. In the composition for external use, the component (a) is 0.001 to 10% by weight, preferably 0.01 to 5% by weight, More preferred is 0.1 to 1% by weight.
（ｂ）アラントイン、その誘導体及びこれらの塩からなる群より選択される少なくとも１種のうち、アラントインは別名５－ウレイドヒダントイン、グリオキシジウレイドとして知られている。また、アラントインの誘導体、アラントインまたはアラントインの誘導体の塩は、それぞれ薬学的または香粧学的に許容される誘導体、塩であれば制限されず、アラントインアセチル－ＤＬ－メチオニン、アラントインポリガラクツロン酸、アラントインβ－グリチルレチン酸、アラントインＤＬ－パントテニルアルコール、アラントインクロルヒドロキシアルミニウム、アラントインジヒドロキシアルミニウム、アラントインピロリドン酸カルボン酸ナトリウム等が例示される。（ｂ）成分として好ましくはアラントイン、アラントインクロルヒドロキシアルミニウム、アラントインジヒドロキシアルミニウム、より好ましくはアラントインが例示される。これらは１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。
(B) Of at least one selected from the group consisting of allantoin, derivatives thereof and salts thereof, allantoin is also known as 5-ureidohydantoin or glyoxydiureido. In addition, allantoin derivatives, allantoin or allantoin derivatives salts are not limited as long as they are pharmaceutically or cosmetically acceptable derivatives and salts, respectively. Allantoin acetyl-DL-methionine, allantoin polygalacturonic acid, allantoin Examples thereof include β-glycyrrhetinic acid, allantoin DL-pantothenyl alcohol, allantoinchlorohydroxyaluminum, allantoindihydroxyaluminum, allantoin pyrophosphoric acid sodium carboxylate and the like. The component (b) is preferably allantoin, allantoinchlorohydroxyaluminum, allantoindihydroxyaluminum, more preferably allantoin. These may be used alone or in combination of two or more.
（ｂ）成分の含有量は、本発明の効果が得られる限り制限されないが、該外用組成物中、（ｂ）成分は、アラントインに換算して０．００１～１０重量％、好ましくは０．０１～５重量％、更に好ましくは０．０５～１重量％が例示される。
The content of the component (b) is not limited as long as the effects of the present invention can be obtained, but in the composition for external use, the component (b) is 0.001 to 10% by weight in terms of allantoin, preferably 0.00. Examples are 01 to 5% by weight, more preferably 0.05 to 1% by weight.
（ｃ）エタノールは従来公知であり、薬学的または香粧学的に許容されるグレードであれば制限されない。
(C) Ethanol is conventionally known and is not limited as long as it is a pharmaceutically or cosmetically acceptable grade.
（ｃ）成分の含有量は、本発明の効果が得られる限り制限されないが、該外用組成物中、（ｃ）成分は１～２３重量％、好ましくは１０～２３重量％、更に好ましくは１８～２３重量％、特に好ましくは２０～２２重量％が例示される。
The content of the component (c) is not limited as long as the effect of the present invention is obtained, but in the composition for external use, the component (c) is 1 to 23% by weight, preferably 10 to 23% by weight, more preferably 18%. Illustrated is ˜23 wt%, particularly preferably 20 to 22 wt%.
（ｄ）多価アルコールとして、１，３－ブチレングリコール、ジプロピレングリコール、プロピレングリコール、１，２－ペンタンジオール、１，２－ヘキサンジオール、グリセリン、ジグリセリン、ポリグリセリン、ポリエチレングリコール、ポリプロピレングリコール、マクロゴール、ソルビトール等が例示される。（ｄ）成分として好ましくは１，３－ブチレングリコール、ジプロピレングリコール、プロピレングリコール、グリセリン、ポリエチレングリコール、マクロゴール、ソルビトールが例示され、より好ましくは１，３－ブチレングリコール、ジプロピレングリコール、プロピレングリコール、グリセリンが例示される。これらは１種単独で使用してもよく、２種以上を組み合わせて使用してもよい。
(D) As polyhydric alcohol, 1,3-butylene glycol, dipropylene glycol, propylene glycol, 1,2-pentanediol, 1,2-hexanediol, glycerin, diglycerin, polyglycerin, polyethylene glycol, polypropylene glycol, Examples include macrogol and sorbitol. The component (d) is preferably 1,3-butylene glycol, dipropylene glycol, propylene glycol, glycerin, polyethylene glycol, macrogol, sorbitol, more preferably 1,3-butylene glycol, dipropylene glycol, propylene glycol. And glycerin. These may be used alone or in combination of two or more.
（ｄ）成分はこの限りにおいて制限されないが、肌へのなじみ及び／または刺激感、特に尋常性ざ瘡（にきび）部位への肌なじみ及び／または刺激感をより良好なものとする観点から、２種以上の多価アルコールを用いることが好ましい。
The component (d) is not limited as long as it is used, but from the viewpoint of improving the familiarity and / or irritation to the skin, particularly the familiarity and / or irritation of acne vulgaris, Two or more polyhydric alcohols are preferably used.
（ｄ）成分の含有量は、本発明の効果が得られる限り制限されないが、該外用組成物中、（ｄ）成分は１～３０重量％、好ましくは５～３０重量％、更に好ましくは１０～２５重量％が例示される。
The content of the component (d) is not limited as long as the effects of the present invention are obtained. In the composition for external use, the component (d) is 1 to 30% by weight, preferably 5 to 30% by weight, more preferably 10%. ˜25% by weight is exemplified.
本発明の外用組成物には、薬学的または香粧学的に許容される任意の成分を必要に応じて更に含有してもよい。このような任意の成分として、水、界面活性剤、香料、着色料、防腐剤、酸化防止剤、乳化剤、油分、増粘剤、金属封鎖剤、殺菌剤、防臭剤、ｐＨ調整剤、清涼化剤、細胞賦活剤、老化防止剤、保湿剤、血行促進剤、ビタミン類、植物エキス、コラーゲン、皮膚収斂剤、抗炎症剤、美白剤、抗酸化剤等の公知の各種成分、特に外用の医薬品、外用の医薬部外品、化粧料等の皮膚に適用される外用組成物に用いられる公知の成分が例示される。これらは１種単独で使用してもよく２種以上を組み合わせて使用してもよく、任意のものを適宜選択し使用すればよい。
The external composition of the present invention may further contain any pharmaceutically or cosmetically acceptable component as necessary. Such optional ingredients include water, surfactants, fragrances, colorants, preservatives, antioxidants, emulsifiers, oils, thickeners, metal sequestering agents, bactericides, deodorants, pH adjusters, and cooling. , Cell activator, anti-aging agent, moisturizer, blood circulation promoter, vitamins, plant extract, collagen, skin astringent, anti-inflammatory agent, whitening agent, antioxidant, etc. Examples of publicly known ingredients used in external compositions applied to the skin, such as external quasi drugs and cosmetics. These may be used individually by 1 type, may be used in combination of 2 or more type, and should just select and use arbitrary things suitably.
例えば水として蒸留水、水道水、イオン交換水、純水、超純水が例示される。水の含有量も本発明の効果を妨げない限り制限されないが、水を含有する場合、本発明の外用組成物中、２６～９９重量％、より好ましくは４６～９０重量％、更に好ましくは５９～８０重量％、特に好ましくは６０～７０重量％が例示される。
For example, distilled water, tap water, ion exchange water, pure water, and ultrapure water are exemplified as water. The water content is not limited as long as the effects of the present invention are not hindered. However, when water is contained, it is 26 to 99% by weight, more preferably 46 to 90% by weight, and still more preferably 59% in the composition for external use of the present invention. Examples are -80% by weight, particularly preferably 60-70% by weight.
本発明の外用組成物の形態は、外用できるものであれは特に制限されず、好ましくは顔、首、胸元、背中、頭皮をはじめとする皮膚に適用可能な形態が例示される。このような形態として、室温（２５℃）で液剤、乳液剤、クリーム剤、ゲル剤、ペースト状、ムース状等が例示される。本発明を制限するものではないが、本発明の外用組成物の形態として好ましくは液剤が例示される。本発明の外用組成物は医薬品、医薬部外品、化粧料として使用できる。本発明の外用組成物は析出が抑制され安定性に優れているので、析出物による噴射口の目詰まりが問題となるスプレー剤にも使用することが出来、特に、外用組成物のうち、液剤をスプレー容器に収納する場合に適している。スプレー容器の材質は特に制限されず、ポリエチレン製、ポリプロピレン製等のプラスチック製容器が好ましく例示される。
The form of the composition for external use of the present invention is not particularly limited as long as it can be applied externally, and preferable examples include forms applicable to the skin including face, neck, chest, back and scalp. Examples of such forms include liquids, emulsions, creams, gels, pastes, and mousses at room temperature (25 ° C.). Although it does not restrict | limit this invention, Preferably a liquid agent is illustrated as a form of the composition for external use of this invention. The composition for external use of the present invention can be used as a pharmaceutical, a quasi-drug, and a cosmetic. Since the composition for external use of the present invention is excellent in stability because precipitation is suppressed, it can also be used for sprays in which clogging of the injection port due to the precipitate is a problem. Suitable for storing in a spray container. The material of the spray container is not particularly limited, and a plastic container such as polyethylene or polypropylene is preferably exemplified.
本発明の外用組成物は、本発明の効果が得られる限り制限されないが、通常、室温（２５℃）でｐＨ２～９が例示され、尋常性ざ瘡部位をはじめとする皮膚に対する低刺激性や使用感の観点から、好ましくはｐＨ２～７、より好ましくはｐＨ２．２～６が例示される。
The composition for external use of the present invention is not limited as long as the effects of the present invention can be obtained, but usually, pH 2 to 9 is exemplified at room temperature (25 ° C.), and it is hypoallergenic to the skin including acne vulgaris. From the viewpoint of usability, the pH is preferably 2 to 7, and more preferably pH 2.2 to 6.
本発明の外用組成物は、各種形態に応じた常法により、前記（ａ）～（ｄ）成分、また、必要に応じて任意の成分を混合することにより製造することができる。例えば後述の実施例に従って、本発明の外用組成物を製造することができる。
The composition for external use of the present invention can be produced by mixing the components (a) to (d) and, if necessary, optional components according to a conventional method corresponding to various forms. For example, according to the below-mentioned Example, the composition for external use of this invention can be manufactured.
本発明の外用組成物は皮膚、特に尋常性ざ瘡部位に適用すればよく、その使用量は尋常性ざ瘡の症状の程度等に応じて適宜設定すればよく、また使用回数も同様に適宜設定すればよく、適当量／回または適当回数／日を皮膚の尋常性ざ瘡部位に使用すればよい。
The composition for external use of the present invention may be applied to the skin, particularly acne vulgaris, the amount used may be appropriately set according to the degree of acne vulgaris, etc. What is necessary is just to set, and what is necessary is just to use an appropriate amount / time or an appropriate frequency / day for the acne vulgaris part of skin.
このような本発明の外用組成物によれば、低温であっても前記（ａ）成分と前記（ｂ）成分の析出を抑制することができる。このため、本発明によれば、より安定性が高められた尋常性ざ瘡改善用の外用組成物を提供することができ、従って、より効果的に尋常性ざ瘡を改善可能となる。
According to such an external composition of the present invention, precipitation of the component (a) and the component (b) can be suppressed even at a low temperature. For this reason, according to the present invention, it is possible to provide an external composition for improving acne vulgaris with improved stability, and therefore, acne vulgaris can be improved more effectively.
このことから、本発明は更に、前記（ａ）及び（ｂ）成分を含有する外用組成物において、前記（ｃ）及び（ｄ）成分を併用することを特徴とする、低温における前記（ａ）及び（ｂ）成分の析出抑制方法を提供するものともいえる。該（ａ）～（ｄ）成分や該成分の含有量等は前述と同様に説明される。また、該外用組成物は前記（ａ）及び（ｂ）成分を含有していることから尋常性ざ瘡の改善に好ましく使用でき、また、該外用組成物は必要に応じて前記任意の成分を含有していてもよい。このほか、該外用組成物の形態等も前述と同様に説明される。該方法によれば、低温であっても前記（ａ）及び（ｂ）成分の析出抑制できる。
Accordingly, the present invention further provides the external composition containing the components (a) and (b), wherein the components (c) and (d) are used in combination. It can also be said that it provides a method for suppressing precipitation of the component (b). The components (a) to (d), the content of the components, and the like are described in the same manner as described above. Further, since the composition for external use contains the components (a) and (b), it can be preferably used for the improvement of acne vulgaris, and the composition for external use contains the above-mentioned optional components as necessary. You may contain. In addition, the form of the composition for external use and the like will be described in the same manner as described above. According to this method, precipitation of the components (a) and (b) can be suppressed even at low temperatures.
以下に実施例及び処方例を示して本発明をより詳細に説明するが、本発明はこれらに限定されない。
試験例１
１．尋常性ざ瘡改善用外用組成物（実施例１～１１）の作製
次の表１に従って、サリチル酸、アラントイン、エタノール、ジプロピレングリコール、１，３－ブチレングリコール及び／または水を含有する尋常性ざ瘡改善用外用組成物（実施例１～１１）を作製した。具体的には、表１に従って、サリチル酸をエタノールに添加して攪拌し、サリチル酸を溶解させた（混合物１）。別途、適量の精製水にアラントインを添加して攪拌し、アラントインを溶解させ、次いでジプロピレングリコールまたは１，３－ブチレングリコール添加して攪拌し、溶解させた（混合物２）。得られた混合物１及び２を混合し、よく攪拌し、その後、精製水で合計重量を１００ｇとした。 Hereinafter, the present invention will be described in more detail with reference to examples and formulation examples, but the present invention is not limited thereto.
Test example 1
1. Preparation of composition for external use for improving acne vulgaris (Examples 1 to 11) According to the following Table 1, acne vulgaris containing salicylic acid, allantoin, ethanol, dipropylene glycol, 1,3-butylene glycol and / or water External compositions for improving acne (Examples 1 to 11) were prepared. Specifically, according to Table 1, salicylic acid was added to ethanol and stirred to dissolve the salicylic acid (mixture 1). Separately, allantoin was added to an appropriate amount of purified water and stirred to dissolve allantoin, and then dipropylene glycol or 1,3-butylene glycol was added and stirred to dissolve (mixture 2). The obtained mixtures 1 and 2 were mixed and stirred well, and then the total weight was adjusted to 100 g with purified water.
試験例１
１．尋常性ざ瘡改善用外用組成物（実施例１～１１）の作製
次の表１に従って、サリチル酸、アラントイン、エタノール、ジプロピレングリコール、１，３－ブチレングリコール及び／または水を含有する尋常性ざ瘡改善用外用組成物（実施例１～１１）を作製した。具体的には、表１に従って、サリチル酸をエタノールに添加して攪拌し、サリチル酸を溶解させた（混合物１）。別途、適量の精製水にアラントインを添加して攪拌し、アラントインを溶解させ、次いでジプロピレングリコールまたは１，３－ブチレングリコール添加して攪拌し、溶解させた（混合物２）。得られた混合物１及び２を混合し、よく攪拌し、その後、精製水で合計重量を１００ｇとした。 Hereinafter, the present invention will be described in more detail with reference to examples and formulation examples, but the present invention is not limited thereto.
Test example 1
1. Preparation of composition for external use for improving acne vulgaris (Examples 1 to 11) According to the following Table 1, acne vulgaris containing salicylic acid, allantoin, ethanol, dipropylene glycol, 1,3-butylene glycol and / or water External compositions for improving acne (Examples 1 to 11) were prepared. Specifically, according to Table 1, salicylic acid was added to ethanol and stirred to dissolve the salicylic acid (mixture 1). Separately, allantoin was added to an appropriate amount of purified water and stirred to dissolve allantoin, and then dipropylene glycol or 1,3-butylene glycol was added and stirred to dissolve (mixture 2). The obtained mixtures 1 and 2 were mixed and stirred well, and then the total weight was adjusted to 100 g with purified water.
また、表２に従って、同様にして比較外用組成物（比較例１～８）を作製した。
Further, according to Table 2, comparative external compositions (Comparative Examples 1 to 8) were produced in the same manner.
表中、値は重量％である。また、ｐＨは、ｐＨメーターを用いて室温（約２５℃）で測定した。
In the table, the value is% by weight. Moreover, pH was measured at room temperature (about 25 degreeC) using the pH meter.
２．尋常性ざ瘡改善用外用組成物の安定性評価
得られた各外用組成物について、作製直後のサリチル酸とアラントインの溶解の程度及び低温（４℃）で１週間静置保存した後のサリチル酸とアラントインの析出の程度を評価した。具体的には、作製直後の外用組成物については、外用組成物の攪拌後の外観を目視で観察し、溶解している「◎」、やや溶解している「○」、溶解しにくい「△」、溶解しない「×」との判断基準によって評価した。保存後の外用組成物については、外用組成物の外観を目視で観察し、析出なし「○」、若干の析出あり「△」、多量の析出あり「×」との判断基準にて評価した。 2. Stability evaluation of external composition for improving acne vulgaris About each obtained external composition, the degree of dissolution of salicylic acid and allantoin immediately after preparation and salicylic acid and allantoin after standing at low temperature (4 ° C) for 1 week The degree of precipitation was evaluated. Specifically, for the external composition immediately after preparation, the appearance after stirring of the external composition is visually observed, dissolved “◎”, slightly dissolved “◯”, difficult to dissolve “Δ” ”And evaluation was made according to the judgment standard of“ x ”not dissolving. About the composition for external use after a preservation | save, the external appearance of the composition for external use was observed visually, and it evaluated by the judgment criteria of "(circle)" with no precipitation, "(triangle | delta)" with some precipitation, and "x" with many precipitation.
得られた各外用組成物について、作製直後のサリチル酸とアラントインの溶解の程度及び低温（４℃）で１週間静置保存した後のサリチル酸とアラントインの析出の程度を評価した。具体的には、作製直後の外用組成物については、外用組成物の攪拌後の外観を目視で観察し、溶解している「◎」、やや溶解している「○」、溶解しにくい「△」、溶解しない「×」との判断基準によって評価した。保存後の外用組成物については、外用組成物の外観を目視で観察し、析出なし「○」、若干の析出あり「△」、多量の析出あり「×」との判断基準にて評価した。 2. Stability evaluation of external composition for improving acne vulgaris About each obtained external composition, the degree of dissolution of salicylic acid and allantoin immediately after preparation and salicylic acid and allantoin after standing at low temperature (4 ° C) for 1 week The degree of precipitation was evaluated. Specifically, for the external composition immediately after preparation, the appearance after stirring of the external composition is visually observed, dissolved “◎”, slightly dissolved “◯”, difficult to dissolve “Δ” ”And evaluation was made according to the judgment standard of“ x ”not dissolving. About the composition for external use after a preservation | save, the external appearance of the composition for external use was observed visually, and it evaluated by the judgment criteria of "(circle)" with no precipitation, "(triangle | delta)" with some precipitation, and "x" with many precipitation.
３．結果
尋常性ざ瘡改善用外用組成物（実施例１～１１）の結果を表１に、比較外用組成物（比較例１～８）の評価結果を表２に示す。 3. Results The results of the external compositions for improving acne vulgaris (Examples 1 to 11) are shown in Table 1, and the evaluation results of the comparative external compositions (Comparative Examples 1 to 8) are shown in Table 2.
尋常性ざ瘡改善用外用組成物（実施例１～１１）の結果を表１に、比較外用組成物（比較例１～８）の評価結果を表２に示す。 3. Results The results of the external compositions for improving acne vulgaris (Examples 1 to 11) are shown in Table 1, and the evaluation results of the comparative external compositions (Comparative Examples 1 to 8) are shown in Table 2.
これに対して、表２から明らかなように、エタノールや多価アルコールを用いていない場合（比較例１）には、作製直後であってもサリチル酸やアラントインは溶解しておらず、また、保存後であっても多量の析出が認められた。サリチル酸、アラントイン、エタノールの組み合わせでは（比較例２～６）、エタノールの含有量依存的にサリチル酸とアラントインが溶解しやすくなった。しかしながら、にきび治療を目的とする一般用医薬品において、有効成分の内、殺菌剤としてエタノール（日局エタノール：１５℃でエタノール（Ｃ２Ｈ６Ｏ）９５．１～９６．９ｖｏｌ％を含む）の含有量は通常２２．８４重量％より多くしてはならず、表２から明らかなように、日局エタノールを２５重量％とした場合には保存後であっても析出は認められなかったが、日局エタノールを２３重量％とした場合には保存後に析出が認められた。該結果から、にきび治療薬の一般用医薬品として望ましい実用を考慮すると、エタノールを組み合わせただけでは、サリチル酸とアラントインの溶解安定性を十分に達成できないことが分かった。また、サリチル酸とアラントインと多価アルコールの組み合わせでは（比較例７及び８）、比較例１と同様に、作製直後であってもサリチル酸やアラントインは溶解しておらず、また、保存後であっても多量の析出が認められた。
On the other hand, as is apparent from Table 2, when ethanol or polyhydric alcohol is not used (Comparative Example 1), salicylic acid and allantoin are not dissolved even immediately after the preparation, and storage is also possible. Even after that, a large amount of precipitation was observed. In the combination of salicylic acid, allantoin, and ethanol (Comparative Examples 2 to 6), salicylic acid and allantoin were easily dissolved depending on the ethanol content. However, in over-the-counter medicines for the treatment of acne, among the active ingredients, ethanol (Japanese ethanol: ethanol (C 2 H 6 O) at 15 ° C. containing 95.1 to 96.9 vol%) as a fungicide The content should normally not be more than 22.84% by weight. As is apparent from Table 2, when JP ethanol was 25% by weight, no precipitation was observed even after storage. When the JP ethanol was 23% by weight, precipitation was observed after storage. From the results, it was found that the solubility stability of salicylic acid and allantoin cannot be sufficiently achieved only by combining ethanol in consideration of desirable practical use as an over-the-counter medicine for treating acne. Further, in the combination of salicylic acid, allantoin, and polyhydric alcohol (Comparative Examples 7 and 8), as in Comparative Example 1, salicylic acid and allantoin are not dissolved even immediately after production, and after storage. A large amount of precipitation was also observed.
このことから、サリチル酸、アラントイン、エタノール及び多価アルコールを組み合わせて用いることにより、作製直後であってもサリチル酸とアラントインとを十分に溶解でき、また、保存後であってもサリチル酸とアラントインの析出を抑制できることが分かった。特に、これらの成分を組み合わせて用いた場合には、エタノールの含有量を過度に高めることなく、作製直後であってもサリチル酸とアラントインとを十分に溶解でき、且つ、保存後であってもサリチル酸とアラントインの析出を抑制でき、安定性の高い外用組成物とできることが分かった。更に、試験したｐＨは析出が生じやすい条件であったが、これにもかかわらず有意に析出を抑制でき、従って、安定性の高い外用組成物とできることが分かった。また、該外用組成物によれば、サリチル酸、アラントイン、エタノールの各成分の有する作用に起因する尋常性ざ瘡改善効果が得られる。
From this, by using a combination of salicylic acid, allantoin, ethanol and polyhydric alcohol, it is possible to sufficiently dissolve salicylic acid and allantoin even immediately after production, and also precipitate salicylic acid and allantoin even after storage. It turned out that it can suppress. In particular, when these components are used in combination, salicylic acid and allantoin can be sufficiently dissolved even immediately after production without excessively increasing the ethanol content, and salicylic acid even after storage. It was found that precipitation of allantoin can be suppressed and a highly stable external composition can be obtained. Furthermore, although the tested pH was a condition in which precipitation was likely to occur, it was found that, despite this, precipitation can be significantly suppressed, and thus a highly stable external composition can be obtained. Moreover, according to this composition for external use, the acne vulgaris improvement effect resulting from the effect | action which each component of salicylic acid, allantoin, and ethanol has is acquired.
試験例２
１．尋常性ざ瘡改善用外用組成物（実施例１２～１６）の作製
次の表３に従って、サリチル酸、アラントイン、エタノール、１，３－ブチレングリコール、ジプロピレングリコール、プロピレングリコール、グリセリン及び／または水を含有する尋常性ざ瘡改善用外用組成物（実施例１２～１６）を作製した。具体的には、表３に従って、サリチル酸をエタノールに添加して攪拌し、サリチル酸を溶解させた（混合物１）。別途、適量の精製水にアラントインを添加して攪拌し、アラントインを溶解させ、次いで１，３－ブチレングリコール、ジプロピレングリコール、プロピレングリコール、グリセリンを適宜添加して攪拌し、溶解させた（混合物２）。得られた混合物１及び２を混合し、よく攪拌し、その後、精製水で合計重量を１００ｇとした。 Test example 2
1. Preparation of external composition for improving acne vulgaris (Examples 12 to 16) According to the following Table 3, salicylic acid, allantoin, ethanol, 1,3-butylene glycol, dipropylene glycol, propylene glycol, glycerin and / or water were added. The composition for external use for improving acne vulgaris (Examples 12 to 16) was prepared. Specifically, according to Table 3, salicylic acid was added to ethanol and stirred to dissolve the salicylic acid (mixture 1). Separately, allantoin was added to an appropriate amount of purified water and stirred to dissolve allantoin, and then 1,3-butylene glycol, dipropylene glycol, propylene glycol and glycerin were appropriately added and stirred to dissolve (mixture 2 ). The obtained mixtures 1 and 2 were mixed and stirred well, and then the total weight was adjusted to 100 g with purified water.
１．尋常性ざ瘡改善用外用組成物（実施例１２～１６）の作製
次の表３に従って、サリチル酸、アラントイン、エタノール、１，３－ブチレングリコール、ジプロピレングリコール、プロピレングリコール、グリセリン及び／または水を含有する尋常性ざ瘡改善用外用組成物（実施例１２～１６）を作製した。具体的には、表３に従って、サリチル酸をエタノールに添加して攪拌し、サリチル酸を溶解させた（混合物１）。別途、適量の精製水にアラントインを添加して攪拌し、アラントインを溶解させ、次いで１，３－ブチレングリコール、ジプロピレングリコール、プロピレングリコール、グリセリンを適宜添加して攪拌し、溶解させた（混合物２）。得られた混合物１及び２を混合し、よく攪拌し、その後、精製水で合計重量を１００ｇとした。 Test example 2
1. Preparation of external composition for improving acne vulgaris (Examples 12 to 16) According to the following Table 3, salicylic acid, allantoin, ethanol, 1,3-butylene glycol, dipropylene glycol, propylene glycol, glycerin and / or water were added. The composition for external use for improving acne vulgaris (Examples 12 to 16) was prepared. Specifically, according to Table 3, salicylic acid was added to ethanol and stirred to dissolve the salicylic acid (mixture 1). Separately, allantoin was added to an appropriate amount of purified water and stirred to dissolve allantoin, and then 1,3-butylene glycol, dipropylene glycol, propylene glycol and glycerin were appropriately added and stirred to dissolve (mixture 2 ). The obtained mixtures 1 and 2 were mixed and stirred well, and then the total weight was adjusted to 100 g with purified water.
また、表３に従って比較外用組成物（比較例９）を作製した。
Further, a comparative external composition (Comparative Example 9) was prepared according to Table 3.
表中、値は重量％である。また、ｐＨは前述と同様に測定した。
In the table, the value is% by weight. The pH was measured in the same manner as described above.
２．尋常性ざ瘡改善用外用組成物の安定性評価
得られた各外用組成物について、作製直後のサリチル酸とアラントインの溶解の程度、ならびに４℃で２日間静置保存後及び４℃で１週間静置保存後のサリチル酸とアラントインの析出の程度を、それぞれ前述と同様に評価した。 2. Stability evaluation of external composition for improving acne vulgaris About each of the obtained external compositions, the degree of dissolution of salicylic acid and allantoin just after preparation and after standing still at 4 ° C. for 2 days and still at 4 ° C. for 1 week The degree of precipitation of salicylic acid and allantoin after storage was evaluated in the same manner as described above.
得られた各外用組成物について、作製直後のサリチル酸とアラントインの溶解の程度、ならびに４℃で２日間静置保存後及び４℃で１週間静置保存後のサリチル酸とアラントインの析出の程度を、それぞれ前述と同様に評価した。 2. Stability evaluation of external composition for improving acne vulgaris About each of the obtained external compositions, the degree of dissolution of salicylic acid and allantoin just after preparation and after standing still at 4 ° C. for 2 days and still at 4 ° C. for 1 week The degree of precipitation of salicylic acid and allantoin after storage was evaluated in the same manner as described above.
３．肌なじみ及び刺激感評価
にきびのある被験者を用いて、得られた外用組成物の肌なじみ及び刺激感を評価した。具体的には、得られた外用組成物を各被験者のにきび部位に塗布し、各被験者が次の判断基準に従って評価した。 3. Skin familiarity and irritation feeling evaluation Using subjects with acne, skin familiarity and irritation feeling of the obtained external composition were evaluated. Specifically, the obtained external composition was applied to the acne site of each subject, and each subject was evaluated according to the following criteria.
にきびのある被験者を用いて、得られた外用組成物の肌なじみ及び刺激感を評価した。具体的には、得られた外用組成物を各被験者のにきび部位に塗布し、各被験者が次の判断基準に従って評価した。 3. Skin familiarity and irritation feeling evaluation Using subjects with acne, skin familiarity and irritation feeling of the obtained external composition were evaluated. Specifically, the obtained external composition was applied to the acne site of each subject, and each subject was evaluated according to the following criteria.
肌なじみは、最低点を０点、最高点を１０点として、各被験者に肌なじみの程度を評価させた。数値が大きいほど肌なじみが良いことを示す。得られた値の平均値を求め、平均値で、４点未満を「×」、４点以上６点未満を「○」、６点以上８点未満を「◎」、８点以上１０点を「◎◎」として、結果を表３に示した。
For skin familiarity, the lowest score was 0 point and the highest score was 10 points, and each subject was evaluated for the degree of skin familiarity. Larger numbers indicate better skin familiarity. The average value of the obtained values is obtained, and the average value is less than 4 points “x”, 4 points to less than 6 points “◯”, 6 points to less than 8 points “◎”, 8 points to 10 points. The results are shown in Table 3 as “◎”.
刺激感は、最低点を０点、最高点を１０点として、各被験者に刺激感の程度を評価させた。数値が小さいほど刺激感が少ないことを示す。得られた値の平均値を求め、平均値で、４点未満を「◎◎」、４点以上６点未満を「◎」、６点以上８点未満を「○」、８点以上１０点を「×」として、結果を表３に示した。
Sense of irritation was evaluated with each subject evaluating the degree of irritation, with 0 being the lowest score and 10 being the highest score. A smaller value indicates less irritation. The average of the obtained values is obtained, and the average value is less than 4 points “◎◎”, 4 points to less than 6 points “◎”, 6 points to less than 8 points “◯”, 8 points to 10 points The results are shown in Table 3.
なお、肌なじみ、刺激感の両評価において、精製水をにきび部位に塗布した場合を５点として評価させた。
In addition, in both skin familiarity and irritation, the case where purified water was applied to acne sites was evaluated as 5 points.
４．結果
尋常性ざ瘡改善用外用組成物（実施例１２～１６）及び比較外用組成物（比較例９）の評価結果を表３に示す。 4). Results Table 3 shows the evaluation results of the external composition for improving acne vulgaris (Examples 12 to 16) and the comparative external composition (Comparative Example 9).
尋常性ざ瘡改善用外用組成物（実施例１２～１６）及び比較外用組成物（比較例９）の評価結果を表３に示す。 4). Results Table 3 shows the evaluation results of the external composition for improving acne vulgaris (Examples 12 to 16) and the comparative external composition (Comparative Example 9).
一方、サリチル酸、アラントイン、エタノールのみを用いた場合には（比較例９）、作製直後はサリチル酸とアラントインが十分に溶解していたものの、保存後はこれらの成分の析出が認められた。また、比較例９の外用組成物では、肌なじみが悪く、刺激感も強く、望ましい外用組成物ではなかった。
On the other hand, when only salicylic acid, allantoin, and ethanol were used (Comparative Example 9), although salicylic acid and allantoin were sufficiently dissolved immediately after production, precipitation of these components was observed after storage. Further, the external composition of Comparative Example 9 was not a desirable external composition because the skin was not well-fitted and the irritation was strong.
このように、サリチル酸、アラントイン、エタノール及び多価アルコールを組み合わせて用いることにより、良好な尋常性ざ瘡改善用外用組成物が得られることが分かった。これらの外用組成物においてもサリチル酸、アラントイン、エタノールの各成分の有する作用に起因する尋常性ざ瘡改善効果が得られる。更に表３から、２種以上の多価アルコールを用いた場合には、肌なじみが一層向上され、且つ、刺激感が一層低減された尋常性ざ瘡改善用外用組成物を得られることが分かった。
Thus, it was found that by using a combination of salicylic acid, allantoin, ethanol and polyhydric alcohol, a good external composition for improving acne vulgaris can be obtained. Also in these external compositions, the acne vulgaris improvement effect resulting from the action of each component of salicylic acid, allantoin, and ethanol is obtained. Furthermore, it can be seen from Table 3 that when two or more kinds of polyhydric alcohols are used, an external composition for improving acne vulgaris with further improved skin familiarity and further reduced irritation feeling can be obtained. It was.
処方例
次の表４及び５に従い前述と同様にして、処方例１～１８の尋常性ざ瘡改善用外用組成物を作製した。いずれもサリチル酸、アラントインの析出は認められず、また、サリチル酸、アラントイン、エタノールに起因する尋常性ざ瘡改善効果が得られる。 Formulation Examples External compositions for improving acne vulgaris according to Formulation Examples 1 to 18 were prepared in the same manner as described above according to Tables 4 and 5 below. In either case, precipitation of salicylic acid and allantoin is not observed, and the effect of improving acne vulgaris due to salicylic acid, allantoin and ethanol is obtained.
次の表４及び５に従い前述と同様にして、処方例１～１８の尋常性ざ瘡改善用外用組成物を作製した。いずれもサリチル酸、アラントインの析出は認められず、また、サリチル酸、アラントイン、エタノールに起因する尋常性ざ瘡改善効果が得られる。 Formulation Examples External compositions for improving acne vulgaris according to Formulation Examples 1 to 18 were prepared in the same manner as described above according to Tables 4 and 5 below. In either case, precipitation of salicylic acid and allantoin is not observed, and the effect of improving acne vulgaris due to salicylic acid, allantoin and ethanol is obtained.
Claims (4)
- （ａ）サリチル酸、（ｂ）アラントイン、その誘導体及びこれらの塩からなる群より選択される少なくとも１種、（ｃ）エタノール、ならびに（ｄ）多価アルコールを含有する、尋常性ざ瘡改善用外用組成物。 (A) Salicylic acid, (b) Allantoin, a derivative thereof, and at least one selected from the group consisting of these salts, (c) ethanol, and (d) a polyhydric alcohol, for external use for improving acne vulgaris Composition.
- （ｃ）エタノールの含有量が１～２３重量％である、請求項１に記載の外用組成物。 The composition for external use according to claim 1, wherein the content of (c) ethanol is 1 to 23% by weight.
- （ｄ）多価アルコールの含有量が１～３０重量％である、請求項１または２に記載の外用組成物。 The composition for external use according to claim 1 or 2, wherein the content of the (d) polyhydric alcohol is 1 to 30% by weight.
- ２種以上の多価アルコールを含有する、請求項１～３のいずれかに記載の外用組成物。 The external composition according to any one of claims 1 to 3, comprising two or more polyhydric alcohols.
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| WO2001080827A2 (en) * | 2000-04-21 | 2001-11-01 | Nature's Cure | Salicylic acid acne spray formulations and methods for treating acne with same |
| JP2008110993A (en) * | 2008-01-29 | 2008-05-15 | Mandom Corp | Antibacterial composition and skin care preparation |
| JP2009035488A (en) * | 2007-07-31 | 2009-02-19 | Pias Arise Kk | External preparation for acne and method for using external preparation for acne |
| CN102232913A (en) * | 2010-04-26 | 2011-11-09 | 王洪 | Medical mask for eliminating acnes |
| JP2011231082A (en) * | 2010-04-30 | 2011-11-17 | Lion Corp | External preparation composition for pimple |
| WO2012147861A1 (en) * | 2011-04-27 | 2012-11-01 | ロート製薬株式会社 | Composition for inhibiting endoserine-1 production and composition for promoting cell proliferation |
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| WO2001080827A2 (en) * | 2000-04-21 | 2001-11-01 | Nature's Cure | Salicylic acid acne spray formulations and methods for treating acne with same |
| JP2009035488A (en) * | 2007-07-31 | 2009-02-19 | Pias Arise Kk | External preparation for acne and method for using external preparation for acne |
| JP2008110993A (en) * | 2008-01-29 | 2008-05-15 | Mandom Corp | Antibacterial composition and skin care preparation |
| CN102232913A (en) * | 2010-04-26 | 2011-11-09 | 王洪 | Medical mask for eliminating acnes |
| JP2011231082A (en) * | 2010-04-30 | 2011-11-17 | Lion Corp | External preparation composition for pimple |
| WO2012147861A1 (en) * | 2011-04-27 | 2012-11-01 | ロート製薬株式会社 | Composition for inhibiting endoserine-1 production and composition for promoting cell proliferation |
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