JP2021001137A - External composition - Google Patents
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- JP2021001137A JP2021001137A JP2019115534A JP2019115534A JP2021001137A JP 2021001137 A JP2021001137 A JP 2021001137A JP 2019115534 A JP2019115534 A JP 2019115534A JP 2019115534 A JP2019115534 A JP 2019115534A JP 2021001137 A JP2021001137 A JP 2021001137A
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- external composition
- inositol
- ufenamate
- water
- present
- Prior art date
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- 239000000203 mixture Substances 0.000 title claims abstract description 73
- CDAISMWEOUEBRE-UHFFFAOYSA-N scyllo-inosotol Natural products OC1C(O)C(O)C(O)C(O)C1O CDAISMWEOUEBRE-UHFFFAOYSA-N 0.000 claims abstract description 44
- CDAISMWEOUEBRE-GPIVLXJGSA-N inositol Chemical compound O[C@H]1[C@H](O)[C@@H](O)[C@H](O)[C@H](O)[C@@H]1O CDAISMWEOUEBRE-GPIVLXJGSA-N 0.000 claims abstract description 43
- 229960000367 inositol Drugs 0.000 claims abstract description 43
- SQUHHTBVTRBESD-UHFFFAOYSA-N Hexa-Ac-myo-Inositol Natural products CC(=O)OC1C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C(OC(C)=O)C1OC(C)=O SQUHHTBVTRBESD-UHFFFAOYSA-N 0.000 claims abstract description 41
- JDLSRXWHEBFHNC-UHFFFAOYSA-N Ufenamate Chemical compound CCCCOC(=O)C1=CC=CC=C1NC1=CC=CC(C(F)(F)F)=C1 JDLSRXWHEBFHNC-UHFFFAOYSA-N 0.000 claims abstract description 37
- 229950010121 ufenamate Drugs 0.000 claims abstract description 37
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 36
- 239000002244 precipitate Substances 0.000 claims abstract description 31
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 28
- 239000002562 thickening agent Substances 0.000 claims abstract description 20
- 238000000034 method Methods 0.000 claims abstract description 11
- 230000015572 biosynthetic process Effects 0.000 claims description 23
- 239000007788 liquid Substances 0.000 claims description 6
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 6
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 6
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 6
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 claims description 5
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 claims description 5
- 239000001863 hydroxypropyl cellulose Substances 0.000 claims description 5
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 5
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 5
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 5
- 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 claims description 5
- 239000007787 solid Substances 0.000 claims description 5
- 238000009472 formulation Methods 0.000 abstract description 7
- 238000002360 preparation method Methods 0.000 description 10
- 201000004624 Dermatitis Diseases 0.000 description 5
- 239000012046 mixed solvent Substances 0.000 description 5
- 230000000144 pharmacologic effect Effects 0.000 description 5
- 239000000654 additive Substances 0.000 description 4
- 150000001298 alcohols Chemical class 0.000 description 4
- 239000006210 lotion Substances 0.000 description 4
- 239000002674 ointment Substances 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 3
- 230000003110 anti-inflammatory effect Effects 0.000 description 3
- -1 butyl flufenamic acid Chemical compound 0.000 description 3
- 239000006071 cream Substances 0.000 description 3
- 235000014113 dietary fatty acids Nutrition 0.000 description 3
- 239000002552 dosage form Substances 0.000 description 3
- 239000000194 fatty acid Substances 0.000 description 3
- 229930195729 fatty acid Natural products 0.000 description 3
- 239000000499 gel Substances 0.000 description 3
- 230000007721 medicinal effect Effects 0.000 description 3
- 230000003020 moisturizing effect Effects 0.000 description 3
- 238000001556 precipitation Methods 0.000 description 3
- 239000004375 Dextrin Substances 0.000 description 2
- 229920001353 Dextrin Polymers 0.000 description 2
- 208000010201 Exanthema Diseases 0.000 description 2
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 2
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 2
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- 208000003251 Pruritus Diseases 0.000 description 2
- 229920002678 cellulose Chemical class 0.000 description 2
- 239000001913 cellulose Chemical class 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000002537 cosmetic Substances 0.000 description 2
- 235000019425 dextrin Nutrition 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 201000005884 exanthem Diseases 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 206010037844 rash Diseases 0.000 description 2
- 239000002453 shampoo Substances 0.000 description 2
- 229920001059 synthetic polymer Polymers 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 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
- MUZDXNQOSGWMJJ-UHFFFAOYSA-N 2-methylprop-2-enoic acid;prop-2-enoic acid Chemical compound OC(=O)C=C.CC(=C)C(O)=O MUZDXNQOSGWMJJ-UHFFFAOYSA-N 0.000 description 1
- 229930091051 Arenine Natural products 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- 206010012444 Dermatitis diaper Diseases 0.000 description 1
- 208000003105 Diaper Rash Diseases 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- 229920002683 Glycosaminoglycan Polymers 0.000 description 1
- 229920002907 Guar gum Polymers 0.000 description 1
- 229920000161 Locust bean gum Polymers 0.000 description 1
- 239000004909 Moisturizer Substances 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 229920002125 Sokalan® Polymers 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 239000010775 animal oil Substances 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000003908 antipruritic agent Substances 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 230000003796 beauty Effects 0.000 description 1
- 230000017531 blood circulation Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000001768 carboxy methyl cellulose Substances 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 235000010418 carrageenan Nutrition 0.000 description 1
- 239000000679 carrageenan Substances 0.000 description 1
- 229920001525 carrageenan Polymers 0.000 description 1
- 229940113118 carrageenan Drugs 0.000 description 1
- 239000002738 chelating agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 239000012459 cleaning agent Substances 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 229920001577 copolymer Polymers 0.000 description 1
- 239000003599 detergent Substances 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000001804 emulsifying effect Effects 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 230000003631 expected effect Effects 0.000 description 1
- 150000004665 fatty acids Chemical class 0.000 description 1
- 229960004369 flufenamic acid Drugs 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 235000011187 glycerol Nutrition 0.000 description 1
- 235000010417 guar gum Nutrition 0.000 description 1
- 239000000665 guar gum Substances 0.000 description 1
- 229960002154 guar gum Drugs 0.000 description 1
- 229920003112 high viscosity grade hydroxypropyl cellulose Polymers 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000000865 liniment Substances 0.000 description 1
- 239000003589 local anesthetic agent Substances 0.000 description 1
- 229960005015 local anesthetics Drugs 0.000 description 1
- 235000010420 locust bean gum Nutrition 0.000 description 1
- 239000000711 locust bean gum Substances 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 235000010981 methylcellulose Nutrition 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 239000002480 mineral oil Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000001333 moisturizer Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000006072 paste Substances 0.000 description 1
- 235000010987 pectin Nutrition 0.000 description 1
- 239000001814 pectin Substances 0.000 description 1
- 229920001277 pectin Polymers 0.000 description 1
- 229920001495 poly(sodium acrylate) polymer Polymers 0.000 description 1
- 229920002432 poly(vinyl methyl ether) polymer Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 210000002374 sebum Anatomy 0.000 description 1
- 235000010413 sodium alginate Nutrition 0.000 description 1
- 239000000661 sodium alginate Substances 0.000 description 1
- 229940005550 sodium alginate Drugs 0.000 description 1
- NNMHYFLPFNGQFZ-UHFFFAOYSA-M sodium polyacrylate Chemical compound [Na+].[O-]C(=O)C=C NNMHYFLPFNGQFZ-UHFFFAOYSA-M 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 150000005846 sugar alcohols Polymers 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 230000008719 thickening Effects 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- UHVMMEOXYDMDKI-JKYCWFKZSA-L zinc;1-(5-cyanopyridin-2-yl)-3-[(1s,2s)-2-(6-fluoro-2-hydroxy-3-propanoylphenyl)cyclopropyl]urea;diacetate Chemical compound [Zn+2].CC([O-])=O.CC([O-])=O.CCC(=O)C1=CC=C(F)C([C@H]2[C@H](C2)NC(=O)NC=2N=CC(=CC=2)C#N)=C1O UHVMMEOXYDMDKI-JKYCWFKZSA-L 0.000 description 1
Abstract
Description
本発明は、ウフェナマート、イノシトール、１価低級アルコール、及び水を含み、析出物の生成が抑制されている外用組成物に関する。 The present invention relates to an external composition containing ufenamate, inositol, a monohydric lower alcohol, and water in which the formation of precipitates is suppressed.
ウフェナマートは、非ステロイド抗炎症剤であり、皮膚炎、かゆみ、かぶれの抑制、治療する効果が知られており、抗炎症目的で外用組成物に配合して使用されている（例えば、特許文献１参照）。ウフェナマートは、脂溶性成分であるため、外用組成物に配合する場合には、乳化状態にしたり、１価低級アルコールを使用して可溶化したりすることによって製剤化されている。 Ufenamart is a non-steroidal anti-inflammatory drug, which is known to have an effect of suppressing and treating dermatitis, itch and rash, and is used in combination with an external composition for anti-inflammatory purposes (for example, Patent Document 1). reference). Since ufenamart is a fat-soluble component, when it is blended in an external composition, it is formulated by emulsifying it or solubilizing it with a monohydric lower alcohol.
一方、イノシトールは、保湿作用や皮脂改善作用等が知られており、潤いの付与等の目的で外用組成物に配合して使用されている（例えば、特許文献２参照）。イノシトールは、水溶性成分であるため、外用組成物に配合する場合には、水に溶解させることによって製剤化されている。 On the other hand, inositol is known to have a moisturizing effect, a sebum improving effect, and the like, and is used by blending it in an external composition for the purpose of imparting moisture (see, for example, Patent Document 2). Since inositol is a water-soluble component, it is formulated by dissolving it in water when it is added to an external composition.
近年、外用組成物の機能性の向上に対する消費者の要望と共に消費者の美容意識が高まっており、皮膚炎等の炎症性皮膚疾患をきれいに治したいというニーズが高まっている。このような消費者ニーズに追従するために、ウフェナマートによる抗炎症作用とイノシトールによる保湿作用の双方を発揮できる外用組成物の開発が望まれている。 In recent years, along with consumers' demands for improving the functionality of external compositions, consumers' awareness of beauty has increased, and there is an increasing need to cleanly cure inflammatory skin diseases such as dermatitis. In order to meet such consumer needs, it is desired to develop an external composition capable of exerting both an anti-inflammatory effect of ufenamate and a moisturizing effect of inositol.
ウフェナマート及びイノシトールは、それぞれ外用組成物に配合できることは知られているが、ウフェナマート及びイノシトールを含む外用組成物の安定性等については、これまで検討されていない。ウフェナマートは脂溶性であるのに対して、イノシトールは水溶性であるがエタノールには殆ど溶解せず、ウフェナマートとは相反する特性がある。そこで、本発明者は、ウフェナマート及びイノシトールを含む外用組成物を開発すべく検討を行ったところ、ウフェナマート及びイノシトールは、それぞれ単独で１価低級アルコール及び水の混合溶媒に対して溶解又は可溶化させると、透明な外観を呈するが、これらの双方を一緒に１価低級アルコール及び水の混合溶媒に対して溶解又は可溶化させると、析出物が生成して白濁した状態になることを知見した。即ち、ウフェナマート、イノシトール、１価低級アルコール、及び水を含む外用組成物では、析出物の生成により白濁して透明な外観にならないという特有の課題が存在することが明らかとなった。このような析出物が生成した状態では、外観性状の悪化を招くだけでなく、ウフェナマート及び／又はイノシトールが十分に溶解又は可溶化された状態になっておらず所望の薬効を十分に発現できないことが懸念される。 It is known that ufenamate and inositol can be blended in the external composition, respectively, but the stability of the external composition containing ufenamate and inositol has not been studied so far. While ufenamate is fat-soluble, inositol is water-soluble but hardly soluble in ethanol, which is contrary to ufenamate. Therefore, the present inventor investigated to develop an external composition containing ufenamate and inositol. As a result, ufenamate and inositol were independently dissolved or solubilized in a mixed solvent of monohydric lower alcohol and water, respectively. It was found that when both of them are dissolved or solubilized together in a mixed solvent of monohydric lower alcohol and water, a precipitate is formed and becomes cloudy. That is, it has been clarified that the external composition containing ufenamate, inositol, monohydric lower alcohol, and water has a peculiar problem that it becomes cloudy due to the formation of precipitates and does not have a transparent appearance. In the state where such a precipitate is formed, not only the appearance property is deteriorated, but also ufenamate and / or inositol is not sufficiently dissolved or solubilized, and the desired medicinal effect cannot be sufficiently exhibited. Is a concern.
そこで、本発明の目的は、ウフェナマート、イノシトール、１価低級アルコール、及び水を含む外用組成物において、析出物の生成を抑制できる製剤化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 the formation of precipitates in an external composition containing ufenamate, inositol, a monohydric lower alcohol, and water.
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、外用組成物において、ウフェナマート、イノシトール、１価低級アルコール、及び水に加えて、増粘剤を配合することにより、析出物の生成を抑制できることを見出した。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 a thickener is added to ufenamate, inositol, monohydric lower alcohol, and water in the external composition to obtain a precipitate. It was found that the generation can be suppressed. 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． ウフェナマート、イノシトール、増粘剤、１価低級アルコール、及び水を含有する、外用組成物。
項２． 増粘剤が、ポリビニルピロリドン、ヒドロキシプロピルセルロース、及びヒドロキシプロピルメチルセルロースよりなる群から選択される少なくとも１種である、項１に記載の外用組成物。
項３． 液状又は半固形状である、項１又は２に記載の外用組成物。
項４． ウフェナマート、イノシトール、１価低級アルコール、及び水を含む外用組成物において析出物の生成を抑制する方法であって、
外用組成物中で、ウフェナマート、イノシトール、１価低級アルコール、及び水と共に、増粘剤を共存させる、析出物の生成抑制方法。
That is, the present invention provides the inventions of the following aspects.
Item 1. An external composition containing ufenamate, inositol, a thickener, a monohydric lower alcohol, and water.
Item 2. Item 2. The external composition according to Item 1, wherein the thickener is at least one selected from the group consisting of polyvinylpyrrolidone, hydroxypropyl cellulose, and hydroxypropyl methyl cellulose.
Item 3. Item 2. The external composition according to Item 1 or 2, which is liquid or semi-solid.
Item 4. A method for suppressing the formation of precipitates in an external composition containing ufenamate, inositol, a monohydric lower alcohol, and water.
A method for suppressing the formation of precipitates, in which a thickener is allowed to coexist with ufenamate, inositol, a monohydric lower alcohol, and water in an external composition.
本発明の外用組成物によれば、ウフェナマート、イノシトール、１価低級アルコール、及び水を含んでいながらも、これらの成分の共存状態で生じる析出物の生成を抑制できるので、良好な外観を呈することができる。 According to the external composition of the present invention, although it contains ufenamate, inositol, a monohydric lower alcohol, and water, it is possible to suppress the formation of precipitates generated in the coexistence state of these components, so that a good appearance is exhibited. be able to.
１．外用組成物
本発明の外用組成物は、ウフェナマート、イノシトール、増粘剤、１価低級アルコール、及び水を含有することを特徴とする。以下、本発明の外用組成物について詳述する。
1. 1. External Composition The external composition of the present invention is characterized by containing ufenamate, inositol, a thickener, a monohydric lower alcohol, and water. Hereinafter, the external composition of the present invention will be described in detail.
［ウフェナマート］
本発明の外用組成物は、ウフェナマートを含有する。ウフェナマートは、フルフェナム酸ブチルとも称され、脂溶性の非ステロイド性抗炎症薬として公知の成分である。
[Ufena Mart]
The external composition of the present invention contains ufenamate. Ufenamate, also referred to as butyl flufenamic acid, is a known ingredient as a fat-soluble non-steroidal anti-inflammatory drug.
本発明の外用組成物におけるウフェナマートの含有量については、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０．１〜２０重量％、好ましくは０．２５〜１０重量％、更に好ましくは０．２５〜７重量％が挙げられる。 The content of ufenamate in the external composition of the present invention is appropriately set according to the medicinal effect to be imparted, the form of the external composition, etc., and is, for example, 0.1 to 20% by weight, preferably 0.25 to 10. By weight%, more preferably 0.25 to 7% by weight.
［イノシトール］
本発明の外用組成物は、イノシトールを含有する。イノシトールは、１，２，３，４，５，６−シクロヘキサンヘキサオールとも称され、シクロヘキサンの各炭素上の水素原子が１つずつヒドロキシ基に置換した構造を持ち、ビタミン様作用物質として知られている公知の成分である。イノシトールには、ヒドロキシ基の立体配置の組み合わせにより、９種類の立体異性体が存在しており、本発明では、いずれの立体異性体を使用してもよいが、好ましくはｍｙｏ−イノシトール（シス−１，２，３，５−トランス−４，６−シクロヘキサンヘキサオール）が挙げられる。
[Inositol]
The external composition of the present invention contains inositol. Inositol, also called 1,2,3,4,5,6-cyclohexanehexaol, has a structure in which one hydrogen atom on each carbon of cyclohexane is replaced with a hydroxy group, and is known as a vitamin-like agent. It is a known component. There are nine types of steric isomers in inositol depending on the combination of the configuration of hydroxy groups. In the present invention, any steric isomer may be used, but myo-inositol (cis-) is preferable. 1,2,3,5-trans-4,6-cyclohexanehexaol).
本発明の外用組成物におけるイノシトールの含有量については、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０．０５〜１０重量％、好ましくは０．１〜１０重量％、更に好ましくは０．２５〜７重量％が挙げられる。 The content of inositol in the external composition of the present invention is appropriately set according to the medicinal effect to be imparted, the form of the external composition, etc., and is, for example, 0.05 to 10% by weight, preferably 0.1 to 10%. By weight%, more preferably 0.25 to 7% by weight.
本発明の外用組成物において、ウフェナマートに対するイノシトールの比率については、これらの成分の各含有量に応じて定まるが、例えば、ウフェナマート１重量部当たり、イノシトールが０．００２５〜１００重量部、好ましくは０．０１〜５０重量部、更に好ましくは０．１〜３０重量部が挙げられる。 In the external composition of the present invention, the ratio of inositol to ufenamate is determined according to the content of each of these components. For example, 0.0025 to 100 parts by weight of inositol per part by weight of ufenamate, preferably 0. 0.01 to 50 parts by weight, more preferably 0.1 to 30 parts by weight.
［増粘剤］
本発明の外用組成物は、増粘剤を含有する。ウフェナマート、イノシトール、１価低級アルコール、及び水を含む外用組成物では、析出物が生成して白濁した外観になるが、本発明の外用組成物では、これらの成分に加えて増粘剤を含むことにより、析出物の生成を抑制することが可能になる。
[Thickener]
The external composition of the present invention contains a thickener. In an external composition containing ufenamate, inositol, a monohydric lower alcohol, and water, precipitates are formed to give a cloudy appearance, whereas the external composition of the present invention contains a thickener in addition to these components. This makes it possible to suppress the formation of precipitates.
本発明で使用される増粘剤の種類については、薬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、ポリビニルピロリドン、ポリビニルアルコール、カルボキシビニルポリマー、ポリビニルメチルエーテル、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等の合成系高分子；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、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等のセルロース誘導体；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、アルギン酸ナトリウム、ペクチン等の増粘多糖類等が挙げられる。 The type of thickener used in the present invention is not particularly limited as long as it is pharmaceutically acceptable, but for example, polyvinylpyrrolidone, polyvinyl alcohol, carboxyvinyl polymer, polyvinylmethyl ether, methacrylic acid acrylate. Synthetic polymers such as alkyl copolymers, sodium polyacrylate, dextrin fatty acid esters; cellulose derivatives such as hydroxypropyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, ethyl cellulose, carboxymethyl cellulose, hydroxyethyl cellulose, hydroxyethyl cellulose; xanthan gum, guar gum, Examples thereof include thickening polysaccharides such as locust bean gum, carrageenan, dextrin, sodium alginate, and pectin.
これらの増粘剤は、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。 These thickeners may be used alone or in combination of two or more.
これらの増粘剤の中でも、析出物の生成をより一層効果的に抑制するという観点から、好ましくは合成系高分子、セルロース誘導体；更に好ましくはポリビニルピロリドン、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；特に好ましくはポリビニルピロリドンが挙げられる。 Among these thickeners, from the viewpoint of more effectively suppressing the formation of precipitates, preferably synthetic polymers and cellulose derivatives; more preferably polyvinylpyrrolidone, hydroxypropyl cellulose, hydroxypropyl methyl cellulose; particularly preferably. Examples include polyvinylpyrrolidone.
本発明の外用組成物における増粘剤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０．１〜２重量％、好ましくは０．２５〜１．５重量％、更に好ましくは０．２５〜１．０重量％が挙げられる。 The content of the thickener in the external composition of the present invention is appropriately set according to the form of the external composition and the like, and is, for example, 0.1 to 2% by weight, preferably 0.25 to 1.5% by weight. %, More preferably 0.25 to 1.0% by weight.
本発明の外用組成物において、ウフェナマート及びイノシトールの総量に対する増粘剤の比率については、これらの成分の各含有量に応じて定まるが、例えば、ウフェナマート及びイノシトールの総量（ウフェナマートとイノシトールの合計量）１重量部当たり、増粘剤が０．００３〜１３重量部、好ましくは０．０１〜４．５重量部、更に好ましくは０．１〜４．０重量部が挙げられる。 In the external composition of the present invention, the ratio of the thickener to the total amount of ufenamate and inositol is determined according to the content of each of these components. For example, the total amount of ufenamate and inositol (total amount of ufenamate and inositol). The thickener is 0.003 to 13 parts by weight, preferably 0.01 to 4.5 parts by weight, and more preferably 0.1 to 4.0 parts by weight per 1 part by weight.
［１価低級アルコール及び水］
本発明の外用組成物は、溶媒として１価低級アルコール及び水を含有する。
[Monohydric lower alcohol and water]
The external composition of the present invention contains a monohydric lower alcohol and water as a solvent.
本発明で使用される１価低級アルコールの種類については、特に制限されないが、例えば、炭素数２〜６の１価低級アルコール、より具体的には、エタノール、プロパノール、ブタノール、イソプロパノール等が挙げられる。これらの１価低級アルコールは、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。これらの１価低級アルコールの中でも、析出物の生成をより一層効果的に抑制するという観点から、好ましくはエタノールが挙げられる。 The type of monohydric lower alcohol used in the present invention is not particularly limited, and examples thereof include monohydric lower alcohols having 2 to 6 carbon atoms, and more specifically, ethanol, propanol, butanol, isopropanol and the like. .. These monohydric lower alcohols may be used alone or in combination of two or more. Among these monohydric lower alcohols, ethanol is preferably mentioned from the viewpoint of more effectively suppressing the formation of precipitates.
本発明の外用組成物において、１価低級アルコールと水の比率については、特に制限されないが、例えば、１価低級アルコール１重量部当たり、水が０．１〜１．８重量部、好ましくは０．１〜１．５重量部、更に好ましくは０．１５〜１．０重量部が挙げられる。 In the external composition of the present invention, the ratio of the monohydric lower alcohol to water is not particularly limited, but for example, 0.1 to 1.8 parts by weight of water per 1 part by weight of the monohydric lower alcohol, preferably 0. .1 to 1.5 parts by weight, more preferably 0.15 to 1.0 parts by weight.
本発明の外用組成物における１価低級アルコール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３０〜８９重量％、好ましくは４０〜８９重量％、更に好ましくは５０〜８５重量％が挙げられる。 The content of the monohydric lower alcohol in the external composition of the present invention is appropriately set according to the form of the external composition and the like, and is, for example, 30 to 89% by weight, preferably 40 to 89% by weight, more preferably. 50-85% by weight is mentioned.
また、本発明の外用組成物における水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１０〜５５重量％、好ましくは１０〜５０重量％、更に好ましくは１０〜４５重量％が挙げられる。 The water content in the external composition of the present invention is appropriately set according to the form of the external composition and the like, and is, for example, 10 to 55% by weight, preferably 10 to 50% by weight, more preferably 10. ~ 45% by weight can be mentioned.
［その他の成分］
本発明の外用組成物は、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が含まれていてもよい。このような添加剤としては、例えば、界面活性剤、多価アルコール、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、キレート剤、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。本発明の外用組成物において、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 addition to the above-mentioned components, the external composition of the present invention may contain other commonly used additives, if necessary. Such additives include, for example, surfactants, polyhydric alcohols, vegetable oils, animal oils, mineral oils, fatty acid alkyl esters, fatty acids, higher alcohols, pH regulators, buffers, solubilizers, chelating agents, preservatives. , Preservatives, antioxidants, stabilizers, fragrances, colorants and the like. When these additives are contained in the external composition of the present invention, the content thereof may be appropriately set according to the type of the additive to be used and the like.
本発明の外用組成物は、前述する成分の他に、薬理成分が含まれていてもよい。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、ウフェナマート以外の抗炎症剤、イノシトール以外の保湿剤、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、本発明の外用組成物において、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。 The external composition of the present invention may contain a pharmacological component in addition to the above-mentioned components. Examples of such pharmacological components include steroids, antihistamines, local anesthetics, anti-inflammatory agents other than ufenamate, moisturizers other than inositol, bactericidal agents, antibacterial agents, antipruritic agents, skin protectants, blood circulation promoting components, vitamins. Kind, mucopolysaccharide and the like. These pharmacological components may be used alone or in combination of two or more. In addition, when these pharmacological components are contained in the external composition of the present invention, the concentration thereof may be appropriately set according to the type of the pharmacological component used, the expected effect, and the like.
［剤型・製剤形態］
本発明の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、本発明の外用組成物は、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]
The dosage form of the external composition of the present invention is not particularly limited as long as it can be applied transdermally, and may be liquid, semi-solid (cream, gel, ointment, paste), solid, or the like. Either may be used, but a liquid or semi-solid state is preferable. Further, the external composition of the present invention 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。 In addition, the external composition of the present invention may be in any form of preparation such as an external preparation for skin (including quasi-drugs), a cosmetic, and a skin cleansing agent, as long as it is applied to the skin.
本発明の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 of the present invention include creams, lotions, gels, emulsions, liquids, paps, patches, liniments, aerosols, aqueous ointments, and packs. Topical skin preparations; cosmetics such as aqueous ointments, creams, milky lotions, lotions, lotions, packs, gels; skin cleaning agents such as body shampoos, hair shampoos, and rinses. Among these, topical skin drugs are preferable.
本発明の外用組成物は、ウフェナマートとイノシトールを含み、抗炎症作用と保湿作用を発揮できるので、皮膚炎、かゆみ、湿疹、かぶれ、おむつかぶれ、ただれ等の炎症性の皮膚症状や疾患の治療等に用途に使用できる。 Since the external composition of the present invention contains ufenamate and inositol and can exert anti-inflammatory and moisturizing effects, it can be used to treat inflammatory skin symptoms and diseases such as dermatitis, itch, eczema, rash, diaper rash, and sores. Can be used for various purposes.
２．析出物の生成抑制方法
本発明は、更に、ウフェナマート、イノシトール、１価低級アルコール、及び水を含む外用組成物において析出物の生成を抑制する方法であって、外用組成物中で、ウフェナマート、イノシトール、１価低級アルコール、及び水と共に、増粘剤を共存させることを特徴とする、析出物の生成抑制方法を提供する。
2. 2. Method for Inhibiting Precipitate Formation The present invention further comprises a method for suppressing the formation of a precipitate in an external composition containing ufenamate, inositol, a monohydric lower alcohol, and water. Provided is a method for suppressing the formation of a precipitate, which comprises coexisting a thickener together with a monohydric lower alcohol and water.
当該方法において、使用する成分の種類や含有量、配合される他の成分の種類や含有量、外用組成物の剤型や製剤形態等については、前記「１．外用組成物」の場合と同様である。 In the method, the types and contents of the components used, the types and contents of other components to be blended, the dosage form and the formulation form of the external composition, etc. are the same as in the case of "1. External composition". Is.
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.
なお、以下に示す試験例及び処方例では、イノシトールとして、ｍｙｏ−イノシトールを使用した。また、以下に示す試験例及び処方例において、ヒドロキシプロピルセルロースは商品名「ＨＰＣ−Ｈ」（日本曹達株式会社）、ヒドロキシプロピルメチルセルロースは商品名「サンジェロースＭ」（大同化成工業株式会社）、及びポリビニルピロリドンは商品名「グリーシャスＫ−３０」（第一工業製薬株式会社）を使用した。 In the test examples and prescription examples shown below, myo-inositol was used as inositol. Further, in the test examples and formulation examples shown below, hydroxypropyl cellulose has a trade name of "HPC-H" (Nippon Sotatsu Co., Ltd.), and hydroxypropyl methyl cellulose has a trade name of "Sangelose M" (Daido Kasei Kogyo Co., Ltd.). For polyvinylpyrrolidone, the trade name "Greecious K-30" (Daiichi Kogyo Seiyaku Co., Ltd.) was used.
試験例１
表１に示す所定量の各成分を混合し、外用組成物（液剤）を調製した。調製直後に室温に静置して、外観を目視にて観察し、以下の判定基準に従って、析出物の生成の程度を評点化した。
＜析出物の生成の程度の判定基準＞
１：析出物の著しい生成により完全に白濁して不透明な状態になっている（図１に示す外観例Ａのような状態）。
２：評点１と評点３の中間の状態になっており、析出物の生成によって白濁し、不透明な状態になっている。
３：析出物が少し生じており、半透明な状態になっている（図１に示す外観例Ｂのような状態）
４：評点３と評点４の中間の状態になっており、僅かにだけ析出物が生じているが、十分に透明な状態になっている。
５：析出物が生じておらず、完全に透明な状態になっている（図１に示す外観例Ｃのような状態）
Test Example 1
A predetermined amount of each component shown in Table 1 was mixed to prepare an external composition (liquid preparation). Immediately after the preparation, the mixture was allowed to stand at room temperature, the appearance was visually observed, and the degree of precipitation formation was scored according to the following criteria.
<Criteria for determining the degree of precipitate formation>
1: It is completely cloudy and opaque due to the remarkable formation of precipitates (state as in appearance example A shown in FIG. 1).
2: It is in an intermediate state between the scores 1 and 3, and becomes cloudy and opaque due to the formation of precipitates.
3: A small amount of precipitate is generated and it is in a translucent state (a state like the appearance example B shown in FIG. 1).
4: It is in an intermediate state between the score 3 and the score 4, and although a slight amount of precipitate is formed, it is in a sufficiently transparent state.
5: No precipitates are formed and the state is completely transparent (state as in appearance example C shown in FIG. 1).
得られた結果を表１に示す。エタノール及び水の混合溶媒中に、ウフェナマート又はイノシトールを単独で配合しても、析出物が生じず透明な外観であったが（参考例１及び２参照）、当該混合溶媒中にウフェナマートとイノシトールの双方を配合すると、析出物が著しく生成して白濁した外観になった（比較例１）。また、可溶化剤や溶解補助剤等として知られているプロピレングリコールやグリセリンを配合しても、析出物の生成を抑制することはできなかった（比較例２及び３）。これに対して、エタノール及び水の混合溶媒中に、ウフェナマート及びイノシトールと共に増粘剤を配合すると、析出物の生成が抑制され、半透明又は透明な外観が実現できた（実施例１〜３）。 The results obtained are shown in Table 1. Even if ufenamate or inositol was blended alone in a mixed solvent of ethanol and water, no precipitate was formed and the appearance was transparent (see Reference Examples 1 and 2), but ufenamate and inositol were mixed in the mixed solvent. When both were blended, precipitates were remarkably formed and the appearance became cloudy (Comparative Example 1). Further, even if propylene glycol or glycerin known as a solubilizing agent or a solubilizing agent was added, the formation of precipitates could not be suppressed (Comparative Examples 2 and 3). On the other hand, when a thickener was blended with ufenamate and inositol in a mixed solvent of ethanol and water, the formation of precipitates was suppressed and a translucent or transparent appearance could be realized (Examples 1 to 3). ..
処方例
表２に示す組成の外用組成物を調製した。得られた外用組成物を、前記試験例１と同様の方法で析出物の生成の程度を評価したところ、いずれも、析出物の生成を抑制できていた。
Formulation Example An external composition having the composition shown in Table 2 was prepared. When the degree of precipitation formation was evaluated for the obtained external composition by the same method as in Test Example 1, the formation of precipitates could be suppressed in each case.
Claims (4)
外用組成物中で、ウフェナマート、イノシトール、１価低級アルコール、及び水と共に、増粘剤を共存させる、析出物の生成抑制方法。 A method for suppressing the formation of precipitates in an external composition containing ufenamate, inositol, a monohydric lower alcohol, and water.
A method for suppressing the formation of precipitates, in which a thickener is allowed to coexist with ufenamate, inositol, a monohydric lower alcohol, and water in an external composition.
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Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH1029937A (en) * | 1996-05-15 | 1998-02-03 | Kobayashi Seiyaku Kogyo Kk | Pharmaceutical preparation of mefenamic acid aqueous solution |
| JP2008195712A (en) * | 2007-01-16 | 2008-08-28 | Rohto Pharmaceut Co Ltd | Emulsified skin care preparation for external use |
| JP2009541222A (en) * | 2006-06-16 | 2009-11-26 | アイピー−６ リサーチ インコーポレイテッド | Prevention of nuclear, sunlight, and other radiation-induced tissue damage |
| JP2011219369A (en) * | 2010-04-02 | 2011-11-04 | Shiseido Co Ltd | Emulsified skin care preparation for external use |
| JP2011231052A (en) * | 2010-04-28 | 2011-11-17 | Kracie Home Products Ltd | Skin care external preparation composition |
| JP2012031068A (en) * | 2010-07-28 | 2012-02-16 | Shiseido Co Ltd | Ufenamate-containing skin care preparation |
| JP2012136491A (en) * | 2010-12-28 | 2012-07-19 | Shiseido Co Ltd | Ufenamate-containing skin care preparation |
| JP2016121092A (en) * | 2014-12-25 | 2016-07-07 | ポーラ化成工業株式会社 | Tranexamic acid-containing composition |
| JP2018197203A (en) * | 2017-05-23 | 2018-12-13 | 小林製薬株式会社 | Emulsion composition |
| JP2018197202A (en) * | 2017-05-23 | 2018-12-13 | 小林製薬株式会社 | Emulsion composition |
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Patent Citations (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH1029937A (en) * | 1996-05-15 | 1998-02-03 | Kobayashi Seiyaku Kogyo Kk | Pharmaceutical preparation of mefenamic acid aqueous solution |
| JP2009541222A (en) * | 2006-06-16 | 2009-11-26 | アイピー−６ リサーチ インコーポレイテッド | Prevention of nuclear, sunlight, and other radiation-induced tissue damage |
| JP2008195712A (en) * | 2007-01-16 | 2008-08-28 | Rohto Pharmaceut Co Ltd | Emulsified skin care preparation for external use |
| JP2011219369A (en) * | 2010-04-02 | 2011-11-04 | Shiseido Co Ltd | Emulsified skin care preparation for external use |
| JP2011231052A (en) * | 2010-04-28 | 2011-11-17 | Kracie Home Products Ltd | Skin care external preparation composition |
| JP2012031068A (en) * | 2010-07-28 | 2012-02-16 | Shiseido Co Ltd | Ufenamate-containing skin care preparation |
| JP2012136491A (en) * | 2010-12-28 | 2012-07-19 | Shiseido Co Ltd | Ufenamate-containing skin care preparation |
| JP2016121092A (en) * | 2014-12-25 | 2016-07-07 | ポーラ化成工業株式会社 | Tranexamic acid-containing composition |
| JP2018197203A (en) * | 2017-05-23 | 2018-12-13 | 小林製薬株式会社 | Emulsion composition |
| JP2018197202A (en) * | 2017-05-23 | 2018-12-13 | 小林製薬株式会社 | Emulsion composition |
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