JP2021004184A - Method of stabilizing allantoin and/or derivative thereof - Google Patents
Method of stabilizing allantoin and/or derivative thereof Download PDFInfo
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- POJWUDADGALRAB-UHFFFAOYSA-N allantoin Chemical compound NC(=O)NC1NC(=O)NC1=O POJWUDADGALRAB-UHFFFAOYSA-N 0.000 title claims abstract description 130
- 229960000458 allantoin Drugs 0.000 title claims abstract description 64
- POJWUDADGALRAB-PVQJCKRUSA-N Allantoin Natural products NC(=O)N[C@@H]1NC(=O)NC1=O POJWUDADGALRAB-PVQJCKRUSA-N 0.000 title claims abstract description 63
- 238000000034 method Methods 0.000 title claims abstract description 47
- 230000000087 stabilizing effect Effects 0.000 title claims description 7
- 239000000203 mixture Substances 0.000 claims abstract description 77
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 48
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims abstract description 38
- 239000004202 carbamide Substances 0.000 claims abstract description 26
- 239000004471 Glycine Substances 0.000 claims abstract description 19
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 claims abstract description 18
- 235000004279 alanine Nutrition 0.000 claims abstract description 18
- 230000006641 stabilisation Effects 0.000 claims description 37
- 238000011105 stabilization Methods 0.000 claims description 37
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- 238000003860 storage Methods 0.000 abstract description 22
- 238000000354 decomposition reaction Methods 0.000 abstract description 13
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- LNAZSHAWQACDHT-XIYTZBAFSA-N (2r,3r,4s,5r,6s)-4,5-dimethoxy-2-(methoxymethyl)-3-[(2s,3r,4s,5r,6r)-3,4,5-trimethoxy-6-(methoxymethyl)oxan-2-yl]oxy-6-[(2r,3r,4s,5r,6r)-4,5,6-trimethoxy-2-(methoxymethyl)oxan-3-yl]oxyoxane Chemical compound CO[C@@H]1[C@@H](OC)[C@H](OC)[C@@H](COC)O[C@H]1O[C@H]1[C@H](OC)[C@@H](OC)[C@H](O[C@H]2[C@@H]([C@@H](OC)[C@H](OC)O[C@@H]2COC)OC)O[C@@H]1COC LNAZSHAWQACDHT-XIYTZBAFSA-N 0.000 description 1
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 1
- XPFCZYUVICHKDS-UHFFFAOYSA-N 3-methylbutane-1,3-diol Chemical compound CC(C)(O)CCO XPFCZYUVICHKDS-UHFFFAOYSA-N 0.000 description 1
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- HDSBZMRLPLPFLQ-UHFFFAOYSA-N Propylene glycol alginate Chemical compound OC1C(O)C(OC)OC(C(O)=O)C1OC1C(O)C(O)C(C)C(C(=O)OCC(C)O)O1 HDSBZMRLPLPFLQ-UHFFFAOYSA-N 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
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- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
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- 229940125715 antihistaminic agent Drugs 0.000 description 1
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- 239000002585 base Substances 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
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- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 description 1
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- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 1
- 230000001969 hypertrophic effect Effects 0.000 description 1
- FZWBNHMXJMCXLU-BLAUPYHCSA-N isomaltotriose Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H](OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C=O)O1 FZWBNHMXJMCXLU-BLAUPYHCSA-N 0.000 description 1
- 210000001117 keloid Anatomy 0.000 description 1
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- 239000003589 local anesthetic agent Substances 0.000 description 1
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- 235000010420 locust bean gum Nutrition 0.000 description 1
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- 229920000609 methyl cellulose Polymers 0.000 description 1
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- 239000006072 paste Substances 0.000 description 1
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- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 description 1
- 229920002432 poly(vinyl methyl ether) polymer Polymers 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
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- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
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- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
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- Medicinal Preparation (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
Description
本発明は、アラントイン及び／又はその誘導体、並びに尿素を含む外用組成物において、アラントイン及び／又はその誘導体の分解を抑制して、保存安定性を向上させる方法に関する。 The present invention relates to a method for improving storage stability by suppressing decomposition of allantoin and / or its derivative in an external composition containing allantoin and / or a derivative thereof and urea.
アラントインには、組織修復賦活作用、抗炎症作用、鎮痒作用等があり、外用組成物に使用されている。また、尿素には、角質中での水分保持、細胞賦活作用、抗菌作用、鎮痒作用等があり、皮膚外用医薬品や化粧料等の外用組成物に使用されている。 Allantoin has a tissue repair activating effect, an anti-inflammatory effect, an antipruritic effect, and the like, and is used in external compositions. In addition, urea has a water retention effect in the keratin, a cell activation effect, an antibacterial effect, an antipruritic effect, and the like, and is used in external compositions such as external skin medicines and cosmetics.
近年、外用組成物に対する機能性の向上が強く求められるようになっており、アラントイン及び／又はその誘導体、並びに尿素の機能性に着目し、これらの成分を併用することにより機能性を向上させた外用組成物についても提案されている。例えば、特許文献１には、所定量のアラントイン、尿素、１，３−ブチレングリコール、ポリグリセリン、及び海洋深層水を含む外用組成物が、アトピー性皮膚炎の予防や治療などに有効であることが開示されている。 In recent years, there has been a strong demand for improvement in functionality for external compositions, and attention has been paid to the functionality of allantoin and / or its derivatives, and urea, and the functionality has been improved by using these components in combination. Topical compositions have also been proposed. For example, in Patent Document 1, an external composition containing a predetermined amount of allantoin, urea, 1,3-butylene glycol, polyglycerin, and deep sea water is effective for prevention and treatment of atopic dermatitis. Is disclosed.
一方、アラントインはｐＨ６以上になると分解され易いという欠点がある。また、尿素は、僅かでも分解するとアルカリ性を呈し、アラントインを分解させ易くするという特性がある。そのため、アラントイン及び／又はその誘導体、並びに尿素を含む外用組成物では、アラントインの分解を抑制し、保存安定性を高める製剤技術が要求されるが、従来、このような製剤技術については十分な検討がなされていない。 On the other hand, allantoin has a drawback that it is easily decomposed when the pH is 6 or higher. In addition, urea becomes alkaline when decomposed even slightly, and has the property of facilitating the decomposition of allantoin. Therefore, in an external composition containing allantoin and / or a derivative thereof, and urea, a formulation technique that suppresses the decomposition of allantoin and enhances storage stability is required, but conventionally, such formulation techniques have been sufficiently studied. Has not been done.
本発明者は、アラントイン及び／又はその誘導体、並びに尿素を含む外用組成物を開発すべく種々検討を行ったところ、アラントイン及び／又はその誘導体、並びに尿素を含む外用組成物では、保存によりｐＨが上昇してアラントインが分解されるため、保存安定性が著しく悪いという知見を得た。 The present inventor has conducted various studies to develop an external composition containing allantoin and / or a derivative thereof and urea. As a result, the pH of the external composition containing allantoin and / or a derivative thereof and urea is increased by storage. It was found that the storage stability is extremely poor because allantoin rises and decomposes allantoin.
そこで、本発明の目的は、アラントイン及び／又はその誘導体、並びに尿素を含む外用組成物において、アラントイン及び／又はその誘導体の分解を抑制でき、保存安定性を向上させる製剤技術を提供することである。 Therefore, an object of the present invention is to provide a formulation technique capable of suppressing decomposition of allantoin and / or its derivative and improving storage stability in an external composition containing allantoin and / or its derivative and urea. ..
本発明者は、前記課題を解決すべく鋭意検討を行ったところ、アラントイン及び／又はその誘導体、並びに尿素を含む外用組成物に、グリシン及び／又はアラニンを含有させることにより、アラントイン及び／又はその誘導体の分解を抑制でき、アラントイン及び／又はその誘導体の保存安定性が向上することを見出した。本発明は、かかる知見に基づいて更に検討を重ねることにより完成したものである。 As a result of diligent studies to solve the above problems, the present inventor has found that allantoin and / or its derivatives and / or its derivatives are contained in an external composition containing allantoin and / or alanine to contain glycine and / or alanine. It has been found that the decomposition of the derivative can be suppressed and the storage stability of allantoin and / or the derivative thereof is improved. The present invention has been completed by further studies based on such findings.
即ち、本発明は、下記に掲げる態様の発明を提供する。
項１． アラントイン及び／又はその誘導体、並びに尿素を含む外用組成物におけるアラントイン及び／又はその誘導体の安定化方法であって、
外用組成物中に、(A)アラントイン及び／又はその誘導体、並びに(B)尿素と共に、(C)グリシン及び／又はアラニンを含有させる、安定化方法。
項２． 前記(C)成分として、グリシン及びアラニンを含む、項１に記載の安定化方法。
項３． 前記(A)成分がアラントインである、項１又は２に記載の安定化方法。
項４． 外用組成物に、更に水を含有させる、項１〜３のいずれかに記載の安定化方法。
That is, the present invention provides the inventions of the following aspects.
Item 1. A method for stabilizing allantoin and / or its derivative in an external composition containing allantoin and / or its derivative, and urea.
A stabilization method in which (C) glycine and / or alanine is contained together with (A) allantoin and / or a derivative thereof, and (B) urea in the external composition.
Item 2. Item 2. The stabilization method according to Item 1, which comprises glycine and alanine as the component (C).
Item 3. Item 2. The stabilization method according to Item 1 or 2, wherein the component (A) is allantoin.
Item 4. Item 3. The stabilization method according to any one of Items 1 to 3, wherein the external composition further contains water.
本発明によれば、アラントイン及び／又はその誘導体、並びに尿素を含む外用組成物において、アラントイン及び／又はその誘導体の分解を抑制でき、優れた保存安定性を備えさせることができる。 According to the present invention, in an external composition containing allantoin and / or a derivative thereof, and urea, decomposition of allantoin and / or a derivative thereof can be suppressed, and excellent storage stability can be provided.
本発明の安定化方法は、アラントイン及び／又はその誘導体、並びに尿素を含む外用組成物におけるアラントイン及び／又はその誘導体の安定化方法であって、外用組成物中に、(A)アラントイン及び／又はその誘導体、並びに(B)尿素と共に、(C)グリシン及び／又はアラニンを含有させることを特徴とする。以下、本発明の安定化方法について詳述する。 The stabilizing method of the present invention is a method for stabilizing allantoin and / or a derivative thereof in an external composition containing allantoin and / or a derivative thereof, and (A) allantoin and / or a derivative thereof in the external composition. It is characterized by containing (C) glycine and / or alanine together with the derivative and (B) urea. Hereinafter, the stabilization method of the present invention will be described in detail.
(A)アラントイン及び／又はその誘導体
本発明の安定化方法において、外用組成物には、保存安定化の対象成分として、アラントインを含有させる。アラントインは、５−ウレイドヒダントインとも称される化合物であり、組織修復賦活作用、抗炎症作用、鎮痒作用等を有することが知られている公知の成分である。
(A) Allantoin and / or its derivative In the stabilization method of the present invention, the external composition contains allantoin as a target component for storage stabilization. Allantoin is a compound also called 5-ureidohydantoin, and is a known component known to have a tissue repair activating effect, an anti-inflammatory effect, an antipruritic effect and the like.
アラントインの誘導体としては、薬学的又は香粧学的に許容できることを限度として特に制限されないが、具体的には、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、アラントインクロルヒドロキシアルミニウム等が挙げられる。これらのアラントインの誘導体は、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。 The derivative of allantoin is not particularly limited as long as it is pharmaceutically or cosmetically acceptable, and specific examples thereof include allantoin chlorohydroxyaluminum, allantoinhydroxyaluminum, allantoindihydroxyaluminum, and allantoinchlorohydroxyaluminum. .. These allantoin derivatives may be used alone or in combination of two or more.
本発明の安定化方法では、(A)成分として、アラントイン又はその誘導体のいずれか一方のみを使用してもよく、またこれらを組み合わせて使用してもよい。(A)成分の中でも、その安定化効果をより一層向上させるという観点から、好ましくはアラントインが挙げられる。 In the stabilization method of the present invention, only one of allantoin or a derivative thereof may be used as the component (A), or these may be used in combination. Among the components (A), allantoin is preferably mentioned from the viewpoint of further improving its stabilizing effect.
本発明の安定化方法において、外用組成物に含有させる(A)成分の量については、特に制限されず、外用組成物に対して付与すべき薬効、外用組成物の形態等に応じて適宜設定されるが、例えば０．０５〜２重量％、好ましくは０．１〜２重量％、更に好ましくは０．２〜１．５重量％が挙げられる。 In the stabilization method of the present invention, the amount of the component (A) contained in the external composition is not particularly limited, and is appropriately set according to the medicinal effect to be imparted to the external composition, the form of the external composition, and the like. However, for example, 0.05 to 2% by weight, preferably 0.1 to 2% by weight, and more preferably 0.2 to 1.5% by weight can be mentioned.
［（B)尿素］
本発明の安定化方法において、外用組成物には尿素を含有させる。尿素は、保湿作用、細胞賦活作用、抗菌作用、鎮痒作用等を有することが知られている公知の成分である。
[(B) Urea]
In the stabilization method of the present invention, the external composition contains urea. Urea is a known component known to have a moisturizing effect, a cell activating effect, an antibacterial effect, an antipruritic effect and the like.
本発明の安定化方法において、外用組成物に含有させる(B)成分の量については、外用組成物に対して付与すべき薬効、外用組成物の形態等に応じて適宜設定されるが、例えば１〜３０重量％、好ましくは２．５〜２５重量％、更に好ましくは５〜２０重量％が挙げられる。 In the stabilization method of the present invention, the amount of the component (B) contained in the external composition is appropriately set according to the medicinal effect to be imparted to the external composition, the form of the external composition, and the like. 1 to 30% by weight, preferably 2.5 to 25% by weight, and more preferably 5 to 20% by weight.
本発明の安定化方法において、外用組成物に含有させる(A)成分に対する(B)成分の比率については、これらの成分の各含有量に応じて定まるが、例えば、(A)成分１重量部当たり、(B)成分が０．５〜６００重量部、好ましくは１．５〜２５０重量部、更に好ましくは５〜２００重量部が挙げられる。 In the stabilization method of the present invention, the ratio of the component (B) to the component (A) contained in the external composition is determined according to the content of each of these components. For example, 1 part by weight of the component (A) is determined. The component (B) is 0.5 to 600 parts by weight, preferably 1.5 to 250 parts by weight, and more preferably 5 to 200 parts by weight.
［(C)グリシン及び／又はアラニン］
本発明の安定化方法において、外用組成物には、グリシン及び／又はアラニンを含有させる。アラントイン又はその誘導体、並びに尿素を含む外用組成物では、保存によりアラントイン及び／又はその誘導体の分解が生じ、保存安定性が悪くなるが、本発明の安定化方法では、外用組成物において、これらの成分に加えてグリシン及び／又はアラニンを含有させることにより、アラントイン及び／又はその誘導体の分解を抑制でき、保存安定性を向上させることが可能なる。グリシン及びアラニンは、アミノ酸として公知の成分である。
[(C) Glycine and / or alanine]
In the stabilization method of the present invention, the external composition contains glycine and / or alanine. In an external composition containing allantoin or a derivative thereof and urea, storage causes decomposition of allantoin and / or a derivative thereof, resulting in poor storage stability. However, in the stabilization method of the present invention, these are used in the external composition. By containing glycine and / or alanine in addition to the components, the decomposition of allantoin and / or its derivative can be suppressed, and the storage stability can be improved. Glycine and alanine are known components as amino acids.
本発明の安定化方法において、(C)成分として、グリシン及びアラニンの内、少なくとも一方を使用すればよいが、アラントイン及び／又はその誘導体の分解をより一層効果的に抑制するという観点から、好ましくは、グリシン、又はグリシンとアラニンの組み合わせ、更に好ましくはグリシンとアラニンの組み合わせが挙げられる。 In the stabilization method of the present invention, at least one of glycine and alanine may be used as the component (C), but it is preferable from the viewpoint of more effectively suppressing the decomposition of allantoin and / or its derivative. Is glycine, or a combination of glycine and alanine, more preferably a combination of glycine and alanine.
本発明の安定化方法において、グリシンとアラニンを組み合わせて使用する場合、これらの比率については、特に制限されないが、例えば、グリシン１重量部当たり、アラニンが０．０５〜２０重量部、好ましくは０．１〜２０重量部、更に好ましくは０．５〜１０重量部が挙げられる。 When glycine and alanine are used in combination in the stabilization method of the present invention, the ratio thereof is not particularly limited, but for example, alanine is 0.05 to 20 parts by weight, preferably 0 per part by weight of glycine. .1 to 20 parts by weight, more preferably 0.5 to 10 parts by weight.
本発明の安定化方法において、外用組成物に含有させる(C)成分の量については、外用組成物の形態等に応じて適宜設定されるが、例えば、(C)成分の総量で０．５〜２０重量％、好ましくは１〜１０重量％、更に好ましくは１〜６重量％が挙げられる。 In the stabilization method of the present invention, the amount of the component (C) contained in the external composition is appropriately set according to the form of the external composition and the like. For example, the total amount of the component (C) is 0.5. -20% by weight, preferably 1 to 10% by weight, more preferably 1 to 6% by weight.
また、本発明の安定化方法において、外用組成物に含有させる(A)成分に対する(C)成分の比率については、これらの成分の各含有量に応じて定まるが、例えば、(A)成分１重量部当たり、(C)成分が総量で０．２５〜４００重量部、好ましくは０．５〜２００重量部、更に好ましくは０．５〜１００重量部が挙げられる。 Further, in the stabilization method of the present invention, the ratio of the component (C) to the component (A) contained in the external composition is determined according to the content of each of these components. For example, the component (A) 1 The total amount of the component (C) per part by weight is 0.25 to 400 parts by weight, preferably 0.5 to 200 parts by weight, and more preferably 0.5 to 100 parts by weight.
［水］
本発明の安定化方法では、外用組成物には、基剤等として水を含有させてもよい。アラントイン又はその誘導体、並びに尿素と共に、水を含む外用組成物では、保存によりアラントイン及び／又はその誘導体の分解が顕著になる傾向があるが、本発明の安定化方法において、外用組成物に、基剤等として水を含有させても、アラントイン及び／又はその誘導体の分解を効果的に抑制することができる。
[water]
In the stabilization method of the present invention, the external composition may contain water as a base or the like. In an external composition containing water together with allantoin or a derivative thereof and urea, decomposition of allantoin and / or a derivative thereof tends to be remarkable by storage, but in the stabilization method of the present invention, the external composition is based on the base. Even if water is contained as an agent or the like, the decomposition of allantoin and / or its derivative can be effectively suppressed.
本発明の安定化方法において、外用組成物に水を含有させる場合、その含有量については、外用組成物の形態等に応じて適宜設定されるが、例えば２５〜９８．５重量％、好ましくは３０〜９０重量％、更に好ましくは３５〜８５重量％が挙げられる。 In the stabilization method of the present invention, when water is contained in the external composition, the content thereof is appropriately set according to the form of the external composition and the like, and is, for example, 25 to 98.5% by weight, preferably 25 to 98.5% by weight. 30 to 90% by weight, more preferably 35 to 85% by weight.
［多価アルコール］
本発明の安定化方法では、外用組成物には、保湿作用の増強等を目的として、必要に応じて、多価アルコールを含有させてもよい。
[Multivalent alcohol]
In the stabilization method of the present invention, the external composition may contain a polyhydric alcohol, if necessary, for the purpose of enhancing the moisturizing effect.
多価アルコールとしては、薬学的又は香粧学的に許容されることを限度として特に制限されないが、例えば、１，３−ブチレングリコール、エチレングリコール、プロピレングリコール、イソプレングリコール、ジエチレングリコール、ジプロピレングリコール、グリセリン等が挙げられる。これらの多価アルコールの中でも、好ましくはプロピレングリコール、グリセリンが挙げられる。これらの多価アルコールは、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。 The polyhydric alcohol is not particularly limited as long as it is pharmaceutically or cosmetically acceptable, and for example, 1,3-butylene glycol, ethylene glycol, propylene glycol, isoprene glycol, diethylene glycol, dipropylene glycol, etc. Glycerin and the like can be mentioned. Among these polyhydric alcohols, propylene glycol and glycerin are preferable. These polyhydric alcohols may be used alone or in combination of two or more.
本発明の安定化方法において、外用組成物に多価アルコールを含有させる場合、その含有量については、使用する多価アルコールの種類、外用組成物の形態等に応じて適宜設定すればよいが、例えば１〜２０重量％、好ましくは１．５〜１５重量％、更に好ましくは２〜１０重量％が挙げられる。 In the stabilization method of the present invention, when the external composition contains a polyhydric alcohol, the content thereof may be appropriately set according to the type of the polyhydric alcohol used, the form of the external composition, and the like. For example, 1 to 20% by weight, preferably 1.5 to 15% by weight, and more preferably 2 to 10% by weight.
［増粘剤］
本発明の安定化方法において、外用組成物には前述する成分の他に、粘性の調節等のために、必要に応じて、増粘剤を含有させてもよい。
[Thickener]
In the stabilization method of the present invention, the external composition may contain a thickener, if necessary, in addition to the above-mentioned components for adjusting the viscosity and the like.
増粘剤としては、薬学的又は香粧学的に許容されることを限度として特に制限されないが、例えば、キサンタンガム、グアーガム、ローカストビーンガム、カラギーナン、デキストラン、メチルセルロース、エチルセルロース、カルボキシメチルセルロース、ヒドロキシエチルセルロース、ヒドロキシエチルセルロース、ヒドロキシプロピルセルロース、ヒドロキシプロピルメチルセルロース、アルギン酸ナトリウム、アルギン酸プロピレングリコールエステル、ポリビニルアルコール、ポリビニルピロリドン、ポリビニルメチルエーテル、カルボキシビニルポリマー、アクリル酸メタクリル酸アルキル共重合体、ポリアクリル酸ナトリウムベントナイト、デキストリン脂肪酸エステル、ペクチン等が挙げられる。これらの増粘剤の中でも、好ましくはカルボキシビニルポリマーが挙げられる。これらの増粘剤は１種又は２種以上を組み合わせて使用できる。 The thickener is not particularly limited as long as it is pharmaceutically or cosmetically acceptable, and for example, xanthan gum, guar gum, locust bean gum, carrageenan, dextran, methyl cellulose, ethyl cellulose, carboxymethyl cellulose, hydroxyethyl cellulose, etc. Hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, sodium alginate, propylene glycol alginate, polyvinyl alcohol, polyvinylpyrrolidone, polyvinylmethyl ether, carboxyvinyl polymer, alkyl methacrylate copolymer, sodium polyacrylate, dextrin fatty acid Examples include ester and pectin. Among these thickeners, a carboxyvinyl polymer is preferably mentioned. These thickeners can be used alone or in combination of two or more.
本発明の安定化方法において、外用組成物に増粘剤を含有させる場合、その含有量については、使用する増粘剤の種類、付与すべき粘性、外用組成物の形態等に応じて適宜設定すればよいが、例えば０．０１〜１．５重量％、好ましくは０．０５〜１重量％、更に好ましくは０．１〜１．０重量％が挙げられる。 In the stabilization method of the present invention, when the external composition contains a thickener, the content thereof is appropriately set according to the type of thickener used, the viscosity to be imparted, the form of the external composition, and the like. However, for example, 0.01 to 1.5% by weight, preferably 0.05 to 1% by weight, and more preferably 0.1 to 1.0% by weight can be mentioned.
［キレート剤］
本発明の安定化方法において、外用組成物には前述する成分の他に、必要に応じて、キレート剤を含有させてもよい。
[Chelating agent]
In the stabilization method of the present invention, the external composition may contain a chelating agent in addition to the above-mentioned components, if necessary.
キレート剤としては、薬学的又は香粧学的に許容されることを限度として特に制限されないが、例えば、エデト酸、クエン酸、コハク酸、及びこれら塩等が挙げられる。塩の形態としては、例えば、ナトリウム塩、カリウム塩等のアルカリ金属塩等が挙げられる。これらのキレート剤の中でも、好ましくはエデト酸及びその塩、より好ましくはエデト酸ナトリウムが挙げられる。これらのキレート剤は、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。 The chelating agent is not particularly limited as long as it is pharmaceutically or cosmetically acceptable, and examples thereof include edetonic acid, citric acid, succinic acid, and salts thereof. Examples of the salt form include alkali metal salts such as sodium salt and potassium salt. Among these chelating agents, edetic acid and a salt thereof are preferable, and sodium edetate is more preferable. These chelating agents may be used alone or in combination of two or more.
本発明の安定化方法において、外用組成物にキレート剤を含有させる場合、その含有量については、使用するキレート剤の種類、外用組成物の形態等に応じて適宜設定すればよいが、例えば０．０１〜２重量％、好ましくは０．０１〜１重量％、更に好ましくは０．０２〜０．５重量％が挙げられる。 In the stabilization method of the present invention, when a chelating agent is contained in the external composition, the content thereof may be appropriately set according to the type of the chelating agent used, the form of the external composition, etc., but for example, 0. It is .01 to 2% by weight, preferably 0.01 to 1% by weight, and more preferably 0.02 to 0.5% by weight.
［その他の成分］
本発明の安定化方法において、外用組成物には、前述する成分の他に、必要に応じて、通常使用される他の添加剤を含有させてもよい。このような添加剤としては、例えば、界面活性剤、１価低級アルコール、植物油、動物油、鉱物油、脂肪酸アルキルエステル、脂肪酸、高級アルコール、ｐＨ調節剤、緩衝剤、可溶化剤、防腐剤、保存剤、酸化防止剤、安定化剤、香料、着色料等が挙げられる。外用組成物に、これらの添加剤を含有させる場合、その含有量については、使用する添加剤の種類等に応じて適宜設定すればよい。
[Other ingredients]
In the stabilization method of the present invention, the external composition may contain other commonly used additives, if necessary, in addition to the above-mentioned components. Examples of such additives include surfactants, monohydric lower alcohols, vegetable oils, animal oils, mineral oils, fatty acid alkyl esters, fatty acids, higher alcohols, pH regulators, buffers, solubilizers, preservatives, and storage. Examples include agents, antioxidants, stabilizers, fragrances, colorants and the like. When these additives are contained in the external composition, the content thereof may be appropriately set according to the type of the additive to be used and the like.
本発明の安定化方法において、外用組成物には、前述する成分の他に、薬理成分を含有させてもよい。このような薬理成分としては、例えば、ステロイド剤、抗ヒスタミン剤、局所麻酔剤、アラントイン及びその誘導体以外の抗炎症剤、尿素以外の保湿剤、殺菌剤、抗菌剤、鎮痒剤、皮膚保護剤、血行促進成分、ビタミン類、ムコ多糖類等が挙げられる。これらの薬理成分は、１種単独で使用してもよく、また２種以上を組み合わせて使用してもよい。また、外用組成物に、これらの薬理成分を含有させる場合、その濃度については、使用する薬理成分の種類、期待する効果等に応じて適宜設定すればよい。 In the stabilization method of the present invention, the external composition may contain a pharmacological component in addition to the above-mentioned components. Such pharmacological components include, for example, steroids, antihistamines, local anesthetics, anti-inflammatory agents other than allantoin and its derivatives, moisturizers other than urea, bactericides, antibacterial agents, antipruritic agents, skin protectants, and blood circulation promoting agents. Ingredients, vitamins, mucopolysaccharides and the like can be mentioned. These pharmacological components may be used alone or in combination of two or more. When these pharmacological components are contained in the external composition, the concentration thereof may be appropriately set according to the type of the pharmacological component used, the expected effect, and the like.
［ｐＨ］
本発明の安定化方法において、外用組成物のｐＨとしては、アラントイン及び／又はその誘導体が安定に保持される範囲であればよいが、例えば２〜９、好ましくは３〜８．５、更に好ましくは４〜８．５、調整直後については２〜５．５が挙げられる。
[PH]
In the stabilization method of the present invention, the pH of the external composition may be in the range in which allantoin and / or its derivative is stably maintained, but is, for example, 2 to 9, preferably 3 to 8.5, more preferably. Is 4 to 8.5, and 2 to 5.5 immediately after adjustment.
［剤型・製剤形態］
本発明の安定化方法において、外用組成物の剤型については、経皮適用可能であることを限度として特に制限されず、液状、半固形状（クリーム状、ゲル状、軟膏状、ペースト状）、固形状等のいずれであってもよいが、好ましくは液状又は半固形状が挙げられる。また、外用組成物は、水中油型乳化製剤、油中水型乳化製剤等の乳化製剤であってもよく、また可溶化型製剤、水性軟膏等の非乳化製剤であってもよい。
[Dosage form / formulation form]
In the stabilization method of the present invention, the dosage form of the external composition is not particularly limited as long as it can be applied transdermally, and is liquid or semi-solid (cream, gel, ointment, paste). , Solid state, etc., but liquid or semi-solid state is preferable. Further, the external composition may be an emulsified preparation such as an oil-in-water emulsified preparation or a water-in-oil emulsified preparation, or may be a non-emulsified preparation such as a solubilized preparation or an aqueous ointment.
また、本発明の安定化方法において、外用組成物は、皮膚に適用されるものである限り、皮膚外用医薬品（医薬部外品を含む）、化粧料、皮膚洗浄料等のいずれの製剤形態であってもよい。 Further, in the stabilizing method of the present invention, the external composition is in any form of preparation such as a skin external medicine (including quasi-drugs), a cosmetic, and a skin cleansing agent as long as it is applied to the skin. There may be.
外用組成物の製剤形態として、具体的には、クリーム剤、ローション剤、ジェル剤、乳液剤、液剤、パップ剤、貼付剤、リニメント剤、エアゾール剤、水性軟膏剤、パック剤等の皮膚外用医薬品；水性軟膏、クリーム、乳液、化粧水、ローション、パック、ゲル等の化粧料；ボディーシャンプー、ヘアシャンプー、リンス等の皮膚洗浄料等が挙げられる。これらの中でも、好ましくは皮膚外用医薬品が挙げられる。 Specific examples of the formulation form of the external composition include external preparations for skin such as creams, lotions, gels, emulsions, liquids, paps, patches, liniments, aerosols, aqueous ointments, and packs. Cosmetics such as aqueous ointments, creams, milky lotions, lotions, lotions, packs and gels; skin cleaning agents such as body shampoos, hair shampoos and rinses. Among these, topical skin drugs are preferable.
本発明の安定化方法において、保存安定化がもたらされる外用組成物は、(A)成分に基づいて、組織修復賦活作用、抗炎症作用、鎮痒作用等を発揮でき、更に含有する(B)成分に基づいて、保湿作用、細胞賦活作用、抗菌作用、鎮痒作用等を発揮できるので、保湿、肌荒れ改善、乾燥性皮膚疾患、炎症性皮膚疾患、肥厚性瘢痕、ケロイド等の予防又は治療等の目的で好適に使用される。 In the stabilization method of the present invention, the external composition that brings about storage stabilization can exert a tissue repair activation action, an anti-inflammatory action, an antipruritic action, etc. based on the component (A), and further contains the component (B). Since it can exert moisturizing action, cell activating action, antibacterial action, antipruritic action, etc. based on, the purpose of prevention or treatment of moisturizing, rough skin improvement, dry skin disease, inflammatory skin disease, hypertrophic scar, keloid, etc. Suitable for use in.
以下に実施例を示して本発明をより具体的に説明するが、本発明はこれらに限定されるものではない。 The present invention will be described in more detail with reference to Examples below, but the present invention is not limited thereto.
試験例１
表１に示す成分を配合して外用組成物（液剤）を調製した。得られた外用組成物を、遮光条件下で、５０℃で２週間、又は５０℃で１カ月間保存した。製造直後と保存後の外用組成物について、ｐＨ及びアラントイン含量を測定した。ｐＨの測定はｐＨメーター（「ＨＯＲＩＢＡ」、株式会社堀場製作所）を用いて行った。アラントイン含量は高速液体クロマトグラフィーにて測定した。測定されたアラントイン含量の値から、アラントイン含有率（仕込み量を１００％とした場合の相対値）（％）を算出した。
Test Example 1
The components shown in Table 1 were blended to prepare an external composition (liquid preparation). The obtained external composition was stored at 50 ° C. for 2 weeks or at 50 ° C. for 1 month under light-shielding conditions. The pH and allantoin content of the external composition immediately after production and after storage were measured. The pH was measured using a pH meter (“HORIBA”, HORIBA, Ltd.). Allantoin content was measured by high performance liquid chromatography. From the measured allantoin content value, the allantoin content (relative value when the charged amount was 100%) (%) was calculated.
得られた結果を表１に示す。アラントイン及び尿素を含む場合（比較例１及び２）には、保存によりｐＨの向上とアラントイン残存率の低下が著しかった。これに対して、アラントイン及び尿素に加えてグリシンを配合した場合（実施例１及び２）には、比較例１及び２に比べて、保存後のｐＨの上昇が抑えられ、アラントイン残存率の向上が認められた。更に、アラントイン及び尿素に加えてグリシン及びアラニンを配合した場合（実施例３）には、格段に高いアラントイン残存率が認められた。 The results obtained are shown in Table 1. When allantoin and urea were contained (Comparative Examples 1 and 2), the pH was significantly improved and the residual rate of allantoin was significantly decreased by storage. On the other hand, when glycine was added in addition to allantoin and urea (Examples 1 and 2), the increase in pH after storage was suppressed and the residual rate of allantoin was improved as compared with Comparative Examples 1 and 2. Was recognized. Furthermore, when glycine and alanine were added in addition to allantoin and urea (Example 3), a remarkably high residual rate of allantoin was observed.
処方例
表２及び３に示す組成の外用組成物（処方例１〜６はゲル剤、処方例７は液剤、処方例８は水中油型乳化製剤）を調製した。得られた外用組成物を前記試験例１と同様の方法で保存安定性を評価したところ、いずれも保存後のアラントイン残存率が高く、優れた保存安定性を有していた。
Preparation examples The external compositions having the compositions shown in Tables 2 and 3 (formulation examples 1 to 6 are gel preparations, formulation example 7 is a liquid preparation, and formulation example 8 is an oil-in-water emulsion preparation) were prepared. When the storage stability of the obtained external composition was evaluated by the same method as in Test Example 1, the residual rate of allantoin after storage was high and the storage stability was excellent.
Claims (4)
外用組成物中に、(A)アラントイン及び／又はその誘導体、並びに(B)尿素と共に、(C)グリシン及び／又はアラニンを含有させる、安定化方法。 A method for stabilizing allantoin and / or its derivative in an external composition containing allantoin and / or its derivative, and urea.
A stabilization method in which (C) glycine and / or alanine is contained together with (A) allantoin and / or a derivative thereof, and (B) urea in the external composition.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113425614A (en) * | 2021-06-28 | 2021-09-24 | 广东药科大学 | Application of amino acid or amino acid analogue or salt thereof as additive for improving dissolving property of allantoin |
| WO2022153907A1 (en) | 2021-01-14 | 2022-07-21 | 国立大学法人新潟大学 | Marker for assisting in diagnosis of nephrotic syndrome and use thereof |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5148441A (en) * | 1974-10-22 | 1976-04-26 | Kowa Co | HIFUSHORISOSEIBUTSUNO ANTEIKAHOHO |
| JPS63159317A (en) * | 1986-12-24 | 1988-07-02 | Terumo Corp | Allantoin-containing aqueous preparation |
| JP2014111673A (en) * | 2012-10-31 | 2014-06-19 | Rohto Pharmaceut Co Ltd | External composition for skin |
| JP2014141470A (en) * | 2012-12-25 | 2014-08-07 | Lion Corp | External preparation composition and skin care sheet |
| WO2020251017A1 (en) * | 2019-06-14 | 2020-12-17 | ゼリア新薬工業株式会社 | Composition for external application |
-
2019
- 2019-06-25 JP JP2019117408A patent/JP2021004184A/en active Pending
Patent Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS5148441A (en) * | 1974-10-22 | 1976-04-26 | Kowa Co | HIFUSHORISOSEIBUTSUNO ANTEIKAHOHO |
| JPS63159317A (en) * | 1986-12-24 | 1988-07-02 | Terumo Corp | Allantoin-containing aqueous preparation |
| JP2014111673A (en) * | 2012-10-31 | 2014-06-19 | Rohto Pharmaceut Co Ltd | External composition for skin |
| JP2014111563A (en) * | 2012-10-31 | 2014-06-19 | Rohto Pharmaceut Co Ltd | External composition for skin |
| JP2014133733A (en) * | 2012-10-31 | 2014-07-24 | Rohto Pharmaceut Co Ltd | External composition for skin |
| JP2018111705A (en) * | 2012-10-31 | 2018-07-19 | ロート製薬株式会社 | Topical skin composition |
| JP2014141470A (en) * | 2012-12-25 | 2014-08-07 | Lion Corp | External preparation composition and skin care sheet |
| WO2020251017A1 (en) * | 2019-06-14 | 2020-12-17 | ゼリア新薬工業株式会社 | Composition for external application |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2022153907A1 (en) | 2021-01-14 | 2022-07-21 | 国立大学法人新潟大学 | Marker for assisting in diagnosis of nephrotic syndrome and use thereof |
| CN113425614A (en) * | 2021-06-28 | 2021-09-24 | 广东药科大学 | Application of amino acid or amino acid analogue or salt thereof as additive for improving dissolving property of allantoin |
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